Surgical Oncology

SILVER SPRING, MD. – Pertuzumab is likely to be approved for the neoadjuvant treatment of breast cancer in the preoperative setting, based on the recommendation of a Food and Drug Administration advisory panel.

At a meeting on Sept. 12, the FDA’s Oncologic Drugs Advisory Committee panel voted 13-0, with 1 abstention, that treatment with pertuzumab, a human epidermal growth factor receptor 2 (HER2)-targeted monoclonal antibody, had a favorable benefit-to-risk profile as a neoadjuvant treatment in combination with trastuzumab and docetaxel before surgery in patients with locally-advanced, inflammatory, or early-stage breast cancers greater than 2 cm in diameter. The neoadjuvant approach would be part of a complete early breast cancer treatment regimen containing fluorouracil, epirubicin, and cyclophosphamide or carboplatin.

The drug is being reviewed under the accelerated approval process, a mechanism that makes drugs available to fill an unmet medical need in patients with serious diseases. Historically, the usual sequence of the FDA approvals for breast cancer agents starts with approval for metastatic disease, followed by approval for early-stage disease years later after the results of large studies with long follow-up periods are available. Pertuzumab, marketed as Perjeta by Genentech, was just approved in 2012 as a first-line treatment for metastatic HER2-positive breast cancer in women who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

Accelerated approvals are based on a surrogate endpoint that is considered “reasonably likely” to predict clinical benefit. In this instance, pathologic complete response rate (pCR) was used in the phase II NeoSphere study. For this trial, pertuzumab was added to trastuzumab (Herceptin) – another HER2 receptor antagonist – and docetaxel, and was given before surgery to women with HER-2-positive, locally advanced, inflammatory or early-stage breast cancer. The comparator group was patients treated preoperatively with trastuzumab and docetaxel.

The women who received the three-drug neoadjuvant regimen had an 18% improvement in pCR as compared to women given trastuzumab and docetaxel only.

In addition to the NeoSphere study, the panel also considered the body of data on pertuzumab in metastatic breast cancer, the known biology of the pertuzumab, and the activity of HER-2 targeted therapies in breast cancer.

Should pertuzumab receive the accelerated approval, its full approval will be contingent on the final results of APHINITY, a confirmatory study. If the APHINITY results do not confirm the NeoSphere results, the FDA can withdraw the approval for this indication.

The vote to support the first approval of a drug for the neoadjuvant treatment of breast cancer is “a historic moment,” said the panel chair, Dr. Mikkael A. Sekeres of the Cleveland Clinic. “In so doing, we are supporting the rapid movement of a highly active drug for metastatic breast cancer to the first-line setting with the hope that women with earlier stages of breast cancer will live longer and better.”

However, he added, “all eyes will be on the confirmatory APHINITY trial” and on Genentech, to “verify this initial signal of efficacy and to confirm the bandwidth of safety we have seen so far.” If the results are negative, he and other panelists urged the company to voluntarily remove the drug for this indication, and avoid what happened with another Genentech drug, bevacizumab (Avastin), which was granted an accelerated approval as a first-line treatment in combination with paclitaxel for metastatic breast cancer in 2008. The FDA decided to withdraw approval of this indication after studies failed to confirm the benefit. The company appealed the decision, however, delaying the FDA’s withdrawal of the approval until 2011.

NeoSphere, a randomized study conducted outside of the United States, compared four treatment regimens in 417 women newly diagnosed with locally advanced, inflammatory or operable HER2-positive early breast cancer, with tumors greater than 2 cm, treated for four cycles before surgery. The median tumor size was about 5 cm, and two-thirds were node positive.

Based on the pCR definition used by Genentech (the absence of invasive cancer in the breast), almost 46% of those on the combination of pertuzumab, trastuzumab, and docetaxel reached the primary endpoint, compared with 29% of those on trastuzumab and docetaxel – a statistically significant difference of nearly 17%. Based on the FDA-preferred definition of pCR definition (the absence of invasive cancer in the breast and lymph nodes), the pCR rate was almost 18% higher with the three-drug regimen (39.3% vs. 21.5%).

The FDA considers pCR as “reasonably likely” to predict outcomes in HER2-positive breast cancer.

The treatment has the potential to cure more patients in this high risk population, said Dr. Suparna Wedam, a medical officer in FDA’s Office of Hematology and Oncology Products. Yet, still to be determined are whether the regimen has long-term safety and results in improvements in overall survival, progression-free survival, and other improvements in long-term outcomes.

Genentech also provided results from the TRYPHAENA phase II study that compared three neoadjuvant treatment regimens before surgery; as well as the CLEOPATRA phase III study, the basis of the 2012 approval of trastuzumab. In TRYPHAENA, 225 women with HER2-positive, locally advanced, operable or inflammatory breast cancer, received one of three neoadjuvant treatment regimens. The pCR rates, a secondary endpoint, ranged from about 55% to 64% when pertuzumab was added to trastuzumab and chemotherapy. CLEOPATRA enrolled 808 women with HER2-positive, locally recurrent, unresectable or metastatic breast cancer previously untreated with a biologic or chemotherapy for metastatic disease. In that trial, pertuzumab in combination with trastuzumab and docetaxel resulted in significant improvements in progression-free survival and overall survival.

The most common adverse events with the three-drug regimen in the NeoSphere study were neutropenia, diarrhea, nausea, fatigue, mucosal inflammation, and rash, according to the company. No unexpected safety signals were observed with the addition of pertuzumab. The addition of pertuzumab did not appear to increase symptomatic cardiac toxicity when added to trastuzumab-based neoadjuvant or metastatic treatment regimens.

The FDA reviewers noted, however, that the rate of left ventricular dysfunction (mostly asymptomatic) was higher with neoadjuvant pertuzumab treatment. Cardiac toxicity appeared to be reversible, however.

Panel member Deborah Armstrong of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, said that there were “some hints of increased cardiac toxicity.” She encouraged the company to closely evaluate patients on longer-term pertuzumab in trials for cardiac toxicity. Dr. Armstrong voted in favor of the benefit risk profile, but like other panelists, was concerned about the potential for approval “opening the floodgates” to the use of this drug in treating patients for whom it may not yet be appropriate.

Citing the clear potential benefit in the intended population, Dr. Michael Menefee of the division of hematology and oncology at the Mayo Clinic, Jacksonville, Fla., also shared his concerns about the potential for toxicity and overuse of the drug. “My hope is that the FDA is very clear in the ultimate labeling so practitioners have clear guidance as to how to use this drug best and most safely.”

Genentech has completed enrollment in the confirmatory, phase III APHINITY study, which will compare chemotherapy plus trastuzumab with or without pertuzumab before surgery in about 4,800 patients with HER-2 positive early breast cancer. The patients will be followed for 10 years, and the study will evaluate invasive disease-free survival. Results are expected to be first available in 2016.

Panel members have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

Genentech also markets trastuzumab.

SILVER SPRING, MD. – Pertuzumab is likely to be approved for the neoadjuvant treatment of breast cancer in the preoperative setting, based on the recommendation of a Food and Drug Administration advisory panel.

At a meeting on Sept. 12, the FDA’s Oncologic Drugs Advisory Committee panel voted 13-0, with 1 abstention, that treatment with pertuzumab, a human epidermal growth factor receptor 2 (HER2)-targeted monoclonal antibody, had a favorable benefit-to-risk profile as a neoadjuvant treatment in combination with trastuzumab and docetaxel before surgery in patients with locally-advanced, inflammatory, or early-stage breast cancers greater than 2 cm in diameter. The neoadjuvant approach would be part of a complete early breast cancer treatment regimen containing fluorouracil, epirubicin, and cyclophosphamide or carboplatin.

The drug is being reviewed under the accelerated approval process, a mechanism that makes drugs available to fill an unmet medical need in patients with serious diseases. Historically, the usual sequence of the FDA approvals for breast cancer agents starts with approval for metastatic disease, followed by approval for early-stage disease years later after the results of large studies with long follow-up periods are available. Pertuzumab, marketed as Perjeta by Genentech, was just approved in 2012 as a first-line treatment for metastatic HER2-positive breast cancer in women who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

Accelerated approvals are based on a surrogate endpoint that is considered “reasonably likely” to predict clinical benefit. In this instance, pathologic complete response rate (pCR) was used in the phase II NeoSphere study. For this trial, pertuzumab was added to trastuzumab (Herceptin) – another HER2 receptor antagonist – and docetaxel, and was given before surgery to women with HER-2-positive, locally advanced, inflammatory or early-stage breast cancer. The comparator group was patients treated preoperatively with trastuzumab and docetaxel.

The women who received the three-drug neoadjuvant regimen had an 18% improvement in pCR as compared to women given trastuzumab and docetaxel only.

In addition to the NeoSphere study, the panel also considered the body of data on pertuzumab in metastatic breast cancer, the known biology of the pertuzumab, and the activity of HER-2 targeted therapies in breast cancer.

Should pertuzumab receive the accelerated approval, its full approval will be contingent on the final results of APHINITY, a confirmatory study. If the APHINITY results do not confirm the NeoSphere results, the FDA can withdraw the approval for this indication.

The vote to support the first approval of a drug for the neoadjuvant treatment of breast cancer is “a historic moment,” said the panel chair, Dr. Mikkael A. Sekeres of the Cleveland Clinic. “In so doing, we are supporting the rapid movement of a highly active drug for metastatic breast cancer to the first-line setting with the hope that women with earlier stages of breast cancer will live longer and better.”

However, he added, “all eyes will be on the confirmatory APHINITY trial” and on Genentech, to “verify this initial signal of efficacy and to confirm the bandwidth of safety we have seen so far.” If the results are negative, he and other panelists urged the company to voluntarily remove the drug for this indication, and avoid what happened with another Genentech drug, bevacizumab (Avastin), which was granted an accelerated approval as a first-line treatment in combination with paclitaxel for metastatic breast cancer in 2008. The FDA decided to withdraw approval of this indication after studies failed to confirm the benefit. The company appealed the decision, however, delaying the FDA’s withdrawal of the approval until 2011.

NeoSphere, a randomized study conducted outside of the United States, compared four treatment regimens in 417 women newly diagnosed with locally advanced, inflammatory or operable HER2-positive early breast cancer, with tumors greater than 2 cm, treated for four cycles before surgery. The median tumor size was about 5 cm, and two-thirds were node positive.

Based on the pCR definition used by Genentech (the absence of invasive cancer in the breast), almost 46% of those on the combination of pertuzumab, trastuzumab, and docetaxel reached the primary endpoint, compared with 29% of those on trastuzumab and docetaxel – a statistically significant difference of nearly 17%. Based on the FDA-preferred definition of pCR definition (the absence of invasive cancer in the breast and lymph nodes), the pCR rate was almost 18% higher with the three-drug regimen (39.3% vs. 21.5%).

The FDA considers pCR as “reasonably likely” to predict outcomes in HER2-positive breast cancer.

The treatment has the potential to cure more patients in this high risk population, said Dr. Suparna Wedam, a medical officer in FDA’s Office of Hematology and Oncology Products. Yet, still to be determined are whether the regimen has long-term safety and results in improvements in overall survival, progression-free survival, and other improvements in long-term outcomes.

Genentech also provided results from the TRYPHAENA phase II study that compared three neoadjuvant treatment regimens before surgery; as well as the CLEOPATRA phase III study, the basis of the 2012 approval of trastuzumab. In TRYPHAENA, 225 women with HER2-positive, locally advanced, operable or inflammatory breast cancer, received one of three neoadjuvant treatment regimens. The pCR rates, a secondary endpoint, ranged from about 55% to 64% when pertuzumab was added to trastuzumab and chemotherapy. CLEOPATRA enrolled 808 women with HER2-positive, locally recurrent, unresectable or metastatic breast cancer previously untreated with a biologic or chemotherapy for metastatic disease. In that trial, pertuzumab in combination with trastuzumab and docetaxel resulted in significant improvements in progression-free survival and overall survival.

The most common adverse events with the three-drug regimen in the NeoSphere study were neutropenia, diarrhea, nausea, fatigue, mucosal inflammation, and rash, according to the company. No unexpected safety signals were observed with the addition of pertuzumab. The addition of pertuzumab did not appear to increase symptomatic cardiac toxicity when added to trastuzumab-based neoadjuvant or metastatic treatment regimens.

The FDA reviewers noted, however, that the rate of left ventricular dysfunction (mostly asymptomatic) was higher with neoadjuvant pertuzumab treatment. Cardiac toxicity appeared to be reversible, however.

Panel member Deborah Armstrong of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, said that there were “some hints of increased cardiac toxicity.” She encouraged the company to closely evaluate patients on longer-term pertuzumab in trials for cardiac toxicity. Dr. Armstrong voted in favor of the benefit risk profile, but like other panelists, was concerned about the potential for approval “opening the floodgates” to the use of this drug in treating patients for whom it may not yet be appropriate.

Citing the clear potential benefit in the intended population, Dr. Michael Menefee of the division of hematology and oncology at the Mayo Clinic, Jacksonville, Fla., also shared his concerns about the potential for toxicity and overuse of the drug. “My hope is that the FDA is very clear in the ultimate labeling so practitioners have clear guidance as to how to use this drug best and most safely.”

Genentech has completed enrollment in the confirmatory, phase III APHINITY study, which will compare chemotherapy plus trastuzumab with or without pertuzumab before surgery in about 4,800 patients with HER-2 positive early breast cancer. The patients will be followed for 10 years, and the study will evaluate invasive disease-free survival. Results are expected to be first available in 2016.

Panel members have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

Genentech also markets trastuzumab.

SILVER SPRING, MD. – Pertuzumab is likely to be approved for the neoadjuvant treatment of breast cancer in the preoperative setting, based on the recommendation of a Food and Drug Administration advisory panel.

At a meeting on Sept. 12, the FDA’s Oncologic Drugs Advisory Committee panel voted 13-0, with 1 abstention, that treatment with pertuzumab, a human epidermal growth factor receptor 2 (HER2)-targeted monoclonal antibody, had a favorable benefit-to-risk profile as a neoadjuvant treatment in combination with trastuzumab and docetaxel before surgery in patients with locally-advanced, inflammatory, or early-stage breast cancers greater than 2 cm in diameter. The neoadjuvant approach would be part of a complete early breast cancer treatment regimen containing fluorouracil, epirubicin, and cyclophosphamide or carboplatin.

The drug is being reviewed under the accelerated approval process, a mechanism that makes drugs available to fill an unmet medical need in patients with serious diseases. Historically, the usual sequence of the FDA approvals for breast cancer agents starts with approval for metastatic disease, followed by approval for early-stage disease years later after the results of large studies with long follow-up periods are available. Pertuzumab, marketed as Perjeta by Genentech, was just approved in 2012 as a first-line treatment for metastatic HER2-positive breast cancer in women who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

Accelerated approvals are based on a surrogate endpoint that is considered “reasonably likely” to predict clinical benefit. In this instance, pathologic complete response rate (pCR) was used in the phase II NeoSphere study. For this trial, pertuzumab was added to trastuzumab (Herceptin) – another HER2 receptor antagonist – and docetaxel, and was given before surgery to women with HER-2-positive, locally advanced, inflammatory or early-stage breast cancer. The comparator group was patients treated preoperatively with trastuzumab and docetaxel.

The women who received the three-drug neoadjuvant regimen had an 18% improvement in pCR as compared to women given trastuzumab and docetaxel only.

In addition to the NeoSphere study, the panel also considered the body of data on pertuzumab in metastatic breast cancer, the known biology of the pertuzumab, and the activity of HER-2 targeted therapies in breast cancer.

Should pertuzumab receive the accelerated approval, its full approval will be contingent on the final results of APHINITY, a confirmatory study. If the APHINITY results do not confirm the NeoSphere results, the FDA can withdraw the approval for this indication.

The vote to support the first approval of a drug for the neoadjuvant treatment of breast cancer is “a historic moment,” said the panel chair, Dr. Mikkael A. Sekeres of the Cleveland Clinic. “In so doing, we are supporting the rapid movement of a highly active drug for metastatic breast cancer to the first-line setting with the hope that women with earlier stages of breast cancer will live longer and better.”

However, he added, “all eyes will be on the confirmatory APHINITY trial” and on Genentech, to “verify this initial signal of efficacy and to confirm the bandwidth of safety we have seen so far.” If the results are negative, he and other panelists urged the company to voluntarily remove the drug for this indication, and avoid what happened with another Genentech drug, bevacizumab (Avastin), which was granted an accelerated approval as a first-line treatment in combination with paclitaxel for metastatic breast cancer in 2008. The FDA decided to withdraw approval of this indication after studies failed to confirm the benefit. The company appealed the decision, however, delaying the FDA’s withdrawal of the approval until 2011.

NeoSphere, a randomized study conducted outside of the United States, compared four treatment regimens in 417 women newly diagnosed with locally advanced, inflammatory or operable HER2-positive early breast cancer, with tumors greater than 2 cm, treated for four cycles before surgery. The median tumor size was about 5 cm, and two-thirds were node positive.

Based on the pCR definition used by Genentech (the absence of invasive cancer in the breast), almost 46% of those on the combination of pertuzumab, trastuzumab, and docetaxel reached the primary endpoint, compared with 29% of those on trastuzumab and docetaxel – a statistically significant difference of nearly 17%. Based on the FDA-preferred definition of pCR definition (the absence of invasive cancer in the breast and lymph nodes), the pCR rate was almost 18% higher with the three-drug regimen (39.3% vs. 21.5%).

The FDA considers pCR as “reasonably likely” to predict outcomes in HER2-positive breast cancer.

The treatment has the potential to cure more patients in this high risk population, said Dr. Suparna Wedam, a medical officer in FDA’s Office of Hematology and Oncology Products. Yet, still to be determined are whether the regimen has long-term safety and results in improvements in overall survival, progression-free survival, and other improvements in long-term outcomes.

Genentech also provided results from the TRYPHAENA phase II study that compared three neoadjuvant treatment regimens before surgery; as well as the CLEOPATRA phase III study, the basis of the 2012 approval of trastuzumab. In TRYPHAENA, 225 women with HER2-positive, locally advanced, operable or inflammatory breast cancer, received one of three neoadjuvant treatment regimens. The pCR rates, a secondary endpoint, ranged from about 55% to 64% when pertuzumab was added to trastuzumab and chemotherapy. CLEOPATRA enrolled 808 women with HER2-positive, locally recurrent, unresectable or metastatic breast cancer previously untreated with a biologic or chemotherapy for metastatic disease. In that trial, pertuzumab in combination with trastuzumab and docetaxel resulted in significant improvements in progression-free survival and overall survival.

The most common adverse events with the three-drug regimen in the NeoSphere study were neutropenia, diarrhea, nausea, fatigue, mucosal inflammation, and rash, according to the company. No unexpected safety signals were observed with the addition of pertuzumab. The addition of pertuzumab did not appear to increase symptomatic cardiac toxicity when added to trastuzumab-based neoadjuvant or metastatic treatment regimens.

The FDA reviewers noted, however, that the rate of left ventricular dysfunction (mostly asymptomatic) was higher with neoadjuvant pertuzumab treatment. Cardiac toxicity appeared to be reversible, however.

Panel member Deborah Armstrong of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, said that there were “some hints of increased cardiac toxicity.” She encouraged the company to closely evaluate patients on longer-term pertuzumab in trials for cardiac toxicity. Dr. Armstrong voted in favor of the benefit risk profile, but like other panelists, was concerned about the potential for approval “opening the floodgates” to the use of this drug in treating patients for whom it may not yet be appropriate.

Citing the clear potential benefit in the intended population, Dr. Michael Menefee of the division of hematology and oncology at the Mayo Clinic, Jacksonville, Fla., also shared his concerns about the potential for toxicity and overuse of the drug. “My hope is that the FDA is very clear in the ultimate labeling so practitioners have clear guidance as to how to use this drug best and most safely.”

Genentech has completed enrollment in the confirmatory, phase III APHINITY study, which will compare chemotherapy plus trastuzumab with or without pertuzumab before surgery in about 4,800 patients with HER-2 positive early breast cancer. The patients will be followed for 10 years, and the study will evaluate invasive disease-free survival. Results are expected to be first available in 2016.

Panel members have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

Genentech also markets trastuzumab.

The albumin-bound formulation of paclitaxel has been approved by the Food and Drug Administration as a first-line treatment for metastatic adenocarcinoma of the pancreas, in combination with gemcitabine, the agency announced on Sept. 6.

The expanded indication for Abraxane (paclitaxel protein-bound particles for injectable suspension, albumin-bound), a microtubule inhibitor, is based on a study that found survival and progression-free survival were a median of almost 2 months longer among those treated with Abraxane and gemcitabine, compared with those treated with gemcitabine alone, according to the FDA statement announcing the approval.

When pancreatic cancer is diagnosed in an advanced stage and is inoperable, which is often when pancreatic cancer is diagnosed, "and in situations when the cancer has progressed following surgery, options like Abraxane can help prolong a patient’s life," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

The international study compared Abraxane plus gemcitabine with gemcitabine alone as a first-line treatment in 861 people with metastatic adenocarcinoma of the pancreas. Their median age was 63 years, and almost half had three or more sites of metastasis (84% had liver metastases).

Median overall survival was 8.5 months in those on the combination vs. 6.7 months among those on gemcitabine alone, a highly statistically significant difference. Median progression-free survival was 5.5 months among those on the combination vs. 3.7 months for those on gemcitabine alone, also a highly statistically significant difference. In addition, 23% of those in the combination arm had a confirmed complete or partial overall response, compared with 7% of those on gemcitabine, according to the prescribing information.

The results of the study, IMPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial), have been submitted for publication, according to the Celgene statement announcing the approval, and were presented at the American Society of Clinical Oncology annual meeting this year.

Common adverse events associated with treatment with Abraxane and gemcitabine included neutropenia, thrombocytopenia, peripheral neuropathy, nausea, alopecia, peripheral edema, diarrhea, fever, vomiting, rash, and dehydration. Fever, dehydration, pneumonia, and vomiting were the most common serious adverse events. Other "clinically important" adverse events included sepsis and pneumonitis, according to the FDA.

According to the new prescribing information, for pancreatic cancer, Abraxane (125 mg/m²) is administered intravenously on days 1, 8, and 15 of each 28-day cycle, followed by gemcitabine immediately afterwards. In the United States, pancreatic cancer is the fourth-leading cause of cancer deaths, according to the FDA statement, which cites National Cancer Institute estimates that 45,220 patients will be diagnosed with pancreatic cancer and 38,460 will die from the disease in 2013.

Abraxane, marketed by Celgene, was approved for treating breast cancer in 2005 and non–small cell lung cancer in 2012. Gemcitabine, a nucleoside metabolic inhibitor marketed as Gemzar by Eli Lilly, was approved in 1996 and is also available in generic formulations. Gemcitabine is approved as a single agent to treat pancreatic cancer.

The revised label is available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021660s037lbl.pdf.

[email protected]

The albumin-bound formulation of paclitaxel has been approved by the Food and Drug Administration as a first-line treatment for metastatic adenocarcinoma of the pancreas, in combination with gemcitabine, the agency announced on Sept. 6.

The expanded indication for Abraxane (paclitaxel protein-bound particles for injectable suspension, albumin-bound), a microtubule inhibitor, is based on a study that found survival and progression-free survival were a median of almost 2 months longer among those treated with Abraxane and gemcitabine, compared with those treated with gemcitabine alone, according to the FDA statement announcing the approval.

When pancreatic cancer is diagnosed in an advanced stage and is inoperable, which is often when pancreatic cancer is diagnosed, "and in situations when the cancer has progressed following surgery, options like Abraxane can help prolong a patient’s life," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

The international study compared Abraxane plus gemcitabine with gemcitabine alone as a first-line treatment in 861 people with metastatic adenocarcinoma of the pancreas. Their median age was 63 years, and almost half had three or more sites of metastasis (84% had liver metastases).

Median overall survival was 8.5 months in those on the combination vs. 6.7 months among those on gemcitabine alone, a highly statistically significant difference. Median progression-free survival was 5.5 months among those on the combination vs. 3.7 months for those on gemcitabine alone, also a highly statistically significant difference. In addition, 23% of those in the combination arm had a confirmed complete or partial overall response, compared with 7% of those on gemcitabine, according to the prescribing information.

The results of the study, IMPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial), have been submitted for publication, according to the Celgene statement announcing the approval, and were presented at the American Society of Clinical Oncology annual meeting this year.

Common adverse events associated with treatment with Abraxane and gemcitabine included neutropenia, thrombocytopenia, peripheral neuropathy, nausea, alopecia, peripheral edema, diarrhea, fever, vomiting, rash, and dehydration. Fever, dehydration, pneumonia, and vomiting were the most common serious adverse events. Other "clinically important" adverse events included sepsis and pneumonitis, according to the FDA.

According to the new prescribing information, for pancreatic cancer, Abraxane (125 mg/m²) is administered intravenously on days 1, 8, and 15 of each 28-day cycle, followed by gemcitabine immediately afterwards. In the United States, pancreatic cancer is the fourth-leading cause of cancer deaths, according to the FDA statement, which cites National Cancer Institute estimates that 45,220 patients will be diagnosed with pancreatic cancer and 38,460 will die from the disease in 2013.

Abraxane, marketed by Celgene, was approved for treating breast cancer in 2005 and non–small cell lung cancer in 2012. Gemcitabine, a nucleoside metabolic inhibitor marketed as Gemzar by Eli Lilly, was approved in 1996 and is also available in generic formulations. Gemcitabine is approved as a single agent to treat pancreatic cancer.

The revised label is available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021660s037lbl.pdf.

[email protected]

The albumin-bound formulation of paclitaxel has been approved by the Food and Drug Administration as a first-line treatment for metastatic adenocarcinoma of the pancreas, in combination with gemcitabine, the agency announced on Sept. 6.

The expanded indication for Abraxane (paclitaxel protein-bound particles for injectable suspension, albumin-bound), a microtubule inhibitor, is based on a study that found survival and progression-free survival were a median of almost 2 months longer among those treated with Abraxane and gemcitabine, compared with those treated with gemcitabine alone, according to the FDA statement announcing the approval.

When pancreatic cancer is diagnosed in an advanced stage and is inoperable, which is often when pancreatic cancer is diagnosed, "and in situations when the cancer has progressed following surgery, options like Abraxane can help prolong a patient’s life," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

The international study compared Abraxane plus gemcitabine with gemcitabine alone as a first-line treatment in 861 people with metastatic adenocarcinoma of the pancreas. Their median age was 63 years, and almost half had three or more sites of metastasis (84% had liver metastases).

Median overall survival was 8.5 months in those on the combination vs. 6.7 months among those on gemcitabine alone, a highly statistically significant difference. Median progression-free survival was 5.5 months among those on the combination vs. 3.7 months for those on gemcitabine alone, also a highly statistically significant difference. In addition, 23% of those in the combination arm had a confirmed complete or partial overall response, compared with 7% of those on gemcitabine, according to the prescribing information.

The results of the study, IMPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial), have been submitted for publication, according to the Celgene statement announcing the approval, and were presented at the American Society of Clinical Oncology annual meeting this year.

Common adverse events associated with treatment with Abraxane and gemcitabine included neutropenia, thrombocytopenia, peripheral neuropathy, nausea, alopecia, peripheral edema, diarrhea, fever, vomiting, rash, and dehydration. Fever, dehydration, pneumonia, and vomiting were the most common serious adverse events. Other "clinically important" adverse events included sepsis and pneumonitis, according to the FDA.

According to the new prescribing information, for pancreatic cancer, Abraxane (125 mg/m²) is administered intravenously on days 1, 8, and 15 of each 28-day cycle, followed by gemcitabine immediately afterwards. In the United States, pancreatic cancer is the fourth-leading cause of cancer deaths, according to the FDA statement, which cites National Cancer Institute estimates that 45,220 patients will be diagnosed with pancreatic cancer and 38,460 will die from the disease in 2013.

Abraxane, marketed by Celgene, was approved for treating breast cancer in 2005 and non–small cell lung cancer in 2012. Gemcitabine, a nucleoside metabolic inhibitor marketed as Gemzar by Eli Lilly, was approved in 1996 and is also available in generic formulations. Gemcitabine is approved as a single agent to treat pancreatic cancer.

The revised label is available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021660s037lbl.pdf.

[email protected]

CHICAGO – The multigene PAM50 assay identifies postmenopausal women with node-positive early breast cancer who have a low risk of distant metastases and may be able to skip adjuvant chemotherapy.

The 543 women studied had one to three positive nodes and low- or intermediate-grade tumors; all received adjuvant endocrine therapy but no chemotherapy in a pair of randomized trials: the ABCSG-8 (Austrian Breast Cancer Study Group 8) trial and the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial.

Results showed that three PAM50 parameters – the risk of recurrence (ROR) score, ROR risk group, and intrinsic subtype – significantly added to clinicopathologic factors in predicting the 10-year risk of metastases.

"A significant proportion of early breast cancer patients with only one positive node has a limited long-term risk of metastases, as well as at least some patients with two or three positive nodes," first author Dr. Michael Gnant commented in presenting the findings at the annual meeting of the American Society of Clinical Oncology.

In particular, among patients with only one positive node, those falling into the ROR low-risk group (41% of the one-node subset) and those having the luminal A intrinsic subtype (71% of the one-node subset) had 10-year risks of metastases that were less than 9%.

"Based on their low risk of metastases, these patients could – and I would personally add should – be spared the side effects of adjuvant chemotherapy despite having node-positive early breast cancer," maintained Dr. Gnant, who is a professor of surgery at the Medical University of Vienna, Austria.

"In the adjuvant treatment of hormone receptor–positive breast cancer, we every day face the dilemma of undertreatment versus overtreatment. Assessing an individual patient’s risk of metastasis as accurately as possible is an important goal in early breast cancer, and it directly impacts on treatment decisions," he added. "Still, risk assessment is mainly based on clinicopathological variables, of which nodal status is considered to be most important. As a consequence, most node-positive patients with hormone receptor–positive breast cancer globally still receive adjuvant chemotherapy."

In the study, the researchers assessed the added prognostic value derived from NanoString Technologies’ PAM50, a 50-gene assay designed to identify intrinsic subtypes of breast cancer. The subtypes are combined with a proliferation score and tumor size to yield the ROR score, and scores are used to classify patients into ROR-based risk groups.

The clinical usefulness of the PAM50 assay and other similar molecular assays, such as Genomic Health’s Oncotype DX and Agendia’s MammaPrint, has not been defined in node-positive patients, he noted.

The node-positive patients studied were drawn from the ABCSG-8 and ATAC trials. The former trial assigned women either to tamoxifen for 5 years or to 2 years of tamoxifen followed by 3 years of the aromatase inhibitor anastrozole (Arimidex); the latter assigned patients to 5 years of adjuvant anastrozole alone, tamoxifen alone, or the (subsequently discontinued) combination.

For each patient, the investigators analyzed tumor tissue to determine the PAM50 ROR score, ROR risk group, and intrinsic subtype. In addition, they derived the clinical treatment score, which is an overall integrated measure of clinicopathologic factors.

The median follow-up was 11 years, according to Dr. Gnant. As the ROR score increased from 0 to 100, so did the 10-year risk of metastases.

When added to the clinical treatment score alone, the ROR score significantly improved on the prediction of metastasis (chi-square for the difference in likelihood ratios, 32.45; P less than .0001).

The ROR risk groups also stratified patients well. The risk of metastases was about 30% in the high-risk group, 14% in the intermediate-risk group, and 8% in the low-risk group.

When added to the clinical treatment score, the luminal subtype significantly improved on prediction of metastasis (chi-square for the difference in likelihood ratios, 20.48; P less than .0001).

The estimated 10-year risk of metastasis was 11% in the luminal A group and 31% in the luminal B group.

In a combined analysis, the risk of metastases was less than 10% in several subsets of patients: those with one or two positive nodes in the ROR low-risk group (6.6% and 7.2% risks, respectively) and those with one positive node having the luminal A subtype (8.4% risk).

Finally, each factor – ROR score, ROR risk group, and intrinsic subtype – significantly improved on the prediction of risk above and beyond clinicopathologic factors in patients with one positive node, two positive nodes, and two or three positive nodes individually.

One session attendee asked, "Was there any opportunity to look at the interaction [of PAM50 parameters] with therapy?"

"Given the rather limited overall difference between anastrozole and tamoxifen both in the ATAC trial and in the sequencing study, ABCSG-8 – tamoxifen versus tamoxifen followed by anastrozole – I don’t think that we can reasonably comment on the interaction between these scores and treatment," Dr. Gnant replied.

Another attendee, Dr. Carlos Arteaga of the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., asked, "Until we all start doing these genomic tests, can you tell us whether the Ki-67 had equal power in your study? It’s a simple test, and we are all using 14% as a cutoff for luminal A and B [intrinsic subtypes]. How did that pan out in this cohort?

"We are trying to have central review for Ki-67 and bring it into the multivariate model. Hopefully, later this year we will be able to answer that question," Dr. Gnant replied.

Dr. Gnant disclosed ties to several companies including Sanofi-Aventis, Novartis, and Roche, as well as NanoString Technologies, the maker of the PAM50 assay.

CHICAGO – The multigene PAM50 assay identifies postmenopausal women with node-positive early breast cancer who have a low risk of distant metastases and may be able to skip adjuvant chemotherapy.

The 543 women studied had one to three positive nodes and low- or intermediate-grade tumors; all received adjuvant endocrine therapy but no chemotherapy in a pair of randomized trials: the ABCSG-8 (Austrian Breast Cancer Study Group 8) trial and the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial.

Results showed that three PAM50 parameters – the risk of recurrence (ROR) score, ROR risk group, and intrinsic subtype – significantly added to clinicopathologic factors in predicting the 10-year risk of metastases.

"A significant proportion of early breast cancer patients with only one positive node has a limited long-term risk of metastases, as well as at least some patients with two or three positive nodes," first author Dr. Michael Gnant commented in presenting the findings at the annual meeting of the American Society of Clinical Oncology.

In particular, among patients with only one positive node, those falling into the ROR low-risk group (41% of the one-node subset) and those having the luminal A intrinsic subtype (71% of the one-node subset) had 10-year risks of metastases that were less than 9%.

"Based on their low risk of metastases, these patients could – and I would personally add should – be spared the side effects of adjuvant chemotherapy despite having node-positive early breast cancer," maintained Dr. Gnant, who is a professor of surgery at the Medical University of Vienna, Austria.

"In the adjuvant treatment of hormone receptor–positive breast cancer, we every day face the dilemma of undertreatment versus overtreatment. Assessing an individual patient’s risk of metastasis as accurately as possible is an important goal in early breast cancer, and it directly impacts on treatment decisions," he added. "Still, risk assessment is mainly based on clinicopathological variables, of which nodal status is considered to be most important. As a consequence, most node-positive patients with hormone receptor–positive breast cancer globally still receive adjuvant chemotherapy."

In the study, the researchers assessed the added prognostic value derived from NanoString Technologies’ PAM50, a 50-gene assay designed to identify intrinsic subtypes of breast cancer. The subtypes are combined with a proliferation score and tumor size to yield the ROR score, and scores are used to classify patients into ROR-based risk groups.

The clinical usefulness of the PAM50 assay and other similar molecular assays, such as Genomic Health’s Oncotype DX and Agendia’s MammaPrint, has not been defined in node-positive patients, he noted.

The node-positive patients studied were drawn from the ABCSG-8 and ATAC trials. The former trial assigned women either to tamoxifen for 5 years or to 2 years of tamoxifen followed by 3 years of the aromatase inhibitor anastrozole (Arimidex); the latter assigned patients to 5 years of adjuvant anastrozole alone, tamoxifen alone, or the (subsequently discontinued) combination.

For each patient, the investigators analyzed tumor tissue to determine the PAM50 ROR score, ROR risk group, and intrinsic subtype. In addition, they derived the clinical treatment score, which is an overall integrated measure of clinicopathologic factors.

The median follow-up was 11 years, according to Dr. Gnant. As the ROR score increased from 0 to 100, so did the 10-year risk of metastases.

When added to the clinical treatment score alone, the ROR score significantly improved on the prediction of metastasis (chi-square for the difference in likelihood ratios, 32.45; P less than .0001).

The ROR risk groups also stratified patients well. The risk of metastases was about 30% in the high-risk group, 14% in the intermediate-risk group, and 8% in the low-risk group.

When added to the clinical treatment score, the luminal subtype significantly improved on prediction of metastasis (chi-square for the difference in likelihood ratios, 20.48; P less than .0001).

The estimated 10-year risk of metastasis was 11% in the luminal A group and 31% in the luminal B group.

In a combined analysis, the risk of metastases was less than 10% in several subsets of patients: those with one or two positive nodes in the ROR low-risk group (6.6% and 7.2% risks, respectively) and those with one positive node having the luminal A subtype (8.4% risk).

Finally, each factor – ROR score, ROR risk group, and intrinsic subtype – significantly improved on the prediction of risk above and beyond clinicopathologic factors in patients with one positive node, two positive nodes, and two or three positive nodes individually.

One session attendee asked, "Was there any opportunity to look at the interaction [of PAM50 parameters] with therapy?"

"Given the rather limited overall difference between anastrozole and tamoxifen both in the ATAC trial and in the sequencing study, ABCSG-8 – tamoxifen versus tamoxifen followed by anastrozole – I don’t think that we can reasonably comment on the interaction between these scores and treatment," Dr. Gnant replied.

Another attendee, Dr. Carlos Arteaga of the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., asked, "Until we all start doing these genomic tests, can you tell us whether the Ki-67 had equal power in your study? It’s a simple test, and we are all using 14% as a cutoff for luminal A and B [intrinsic subtypes]. How did that pan out in this cohort?

"We are trying to have central review for Ki-67 and bring it into the multivariate model. Hopefully, later this year we will be able to answer that question," Dr. Gnant replied.

Dr. Gnant disclosed ties to several companies including Sanofi-Aventis, Novartis, and Roche, as well as NanoString Technologies, the maker of the PAM50 assay.

CHICAGO – The multigene PAM50 assay identifies postmenopausal women with node-positive early breast cancer who have a low risk of distant metastases and may be able to skip adjuvant chemotherapy.

The 543 women studied had one to three positive nodes and low- or intermediate-grade tumors; all received adjuvant endocrine therapy but no chemotherapy in a pair of randomized trials: the ABCSG-8 (Austrian Breast Cancer Study Group 8) trial and the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial.

Results showed that three PAM50 parameters – the risk of recurrence (ROR) score, ROR risk group, and intrinsic subtype – significantly added to clinicopathologic factors in predicting the 10-year risk of metastases.

"A significant proportion of early breast cancer patients with only one positive node has a limited long-term risk of metastases, as well as at least some patients with two or three positive nodes," first author Dr. Michael Gnant commented in presenting the findings at the annual meeting of the American Society of Clinical Oncology.

In particular, among patients with only one positive node, those falling into the ROR low-risk group (41% of the one-node subset) and those having the luminal A intrinsic subtype (71% of the one-node subset) had 10-year risks of metastases that were less than 9%.

"Based on their low risk of metastases, these patients could – and I would personally add should – be spared the side effects of adjuvant chemotherapy despite having node-positive early breast cancer," maintained Dr. Gnant, who is a professor of surgery at the Medical University of Vienna, Austria.

"In the adjuvant treatment of hormone receptor–positive breast cancer, we every day face the dilemma of undertreatment versus overtreatment. Assessing an individual patient’s risk of metastasis as accurately as possible is an important goal in early breast cancer, and it directly impacts on treatment decisions," he added. "Still, risk assessment is mainly based on clinicopathological variables, of which nodal status is considered to be most important. As a consequence, most node-positive patients with hormone receptor–positive breast cancer globally still receive adjuvant chemotherapy."

In the study, the researchers assessed the added prognostic value derived from NanoString Technologies’ PAM50, a 50-gene assay designed to identify intrinsic subtypes of breast cancer. The subtypes are combined with a proliferation score and tumor size to yield the ROR score, and scores are used to classify patients into ROR-based risk groups.

The clinical usefulness of the PAM50 assay and other similar molecular assays, such as Genomic Health’s Oncotype DX and Agendia’s MammaPrint, has not been defined in node-positive patients, he noted.

The node-positive patients studied were drawn from the ABCSG-8 and ATAC trials. The former trial assigned women either to tamoxifen for 5 years or to 2 years of tamoxifen followed by 3 years of the aromatase inhibitor anastrozole (Arimidex); the latter assigned patients to 5 years of adjuvant anastrozole alone, tamoxifen alone, or the (subsequently discontinued) combination.

For each patient, the investigators analyzed tumor tissue to determine the PAM50 ROR score, ROR risk group, and intrinsic subtype. In addition, they derived the clinical treatment score, which is an overall integrated measure of clinicopathologic factors.

The median follow-up was 11 years, according to Dr. Gnant. As the ROR score increased from 0 to 100, so did the 10-year risk of metastases.

When added to the clinical treatment score alone, the ROR score significantly improved on the prediction of metastasis (chi-square for the difference in likelihood ratios, 32.45; P less than .0001).

The ROR risk groups also stratified patients well. The risk of metastases was about 30% in the high-risk group, 14% in the intermediate-risk group, and 8% in the low-risk group.

When added to the clinical treatment score, the luminal subtype significantly improved on prediction of metastasis (chi-square for the difference in likelihood ratios, 20.48; P less than .0001).

The estimated 10-year risk of metastasis was 11% in the luminal A group and 31% in the luminal B group.

In a combined analysis, the risk of metastases was less than 10% in several subsets of patients: those with one or two positive nodes in the ROR low-risk group (6.6% and 7.2% risks, respectively) and those with one positive node having the luminal A subtype (8.4% risk).

Finally, each factor – ROR score, ROR risk group, and intrinsic subtype – significantly improved on the prediction of risk above and beyond clinicopathologic factors in patients with one positive node, two positive nodes, and two or three positive nodes individually.

One session attendee asked, "Was there any opportunity to look at the interaction [of PAM50 parameters] with therapy?"

"Given the rather limited overall difference between anastrozole and tamoxifen both in the ATAC trial and in the sequencing study, ABCSG-8 – tamoxifen versus tamoxifen followed by anastrozole – I don’t think that we can reasonably comment on the interaction between these scores and treatment," Dr. Gnant replied.

Another attendee, Dr. Carlos Arteaga of the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., asked, "Until we all start doing these genomic tests, can you tell us whether the Ki-67 had equal power in your study? It’s a simple test, and we are all using 14% as a cutoff for luminal A and B [intrinsic subtypes]. How did that pan out in this cohort?

"We are trying to have central review for Ki-67 and bring it into the multivariate model. Hopefully, later this year we will be able to answer that question," Dr. Gnant replied.

Dr. Gnant disclosed ties to several companies including Sanofi-Aventis, Novartis, and Roche, as well as NanoString Technologies, the maker of the PAM50 assay.

The accuracy of cyst fluid carcinoembryonic antigen in differentiating between benign and malignant pancreatic cysts is poor, and the antigen should not be used as a sole marker for guiding surgical decision making, results from a meta-analysis of available literature on the topic suggests.

"The clinical value of cyst fluid CEA should be limited only to distinguishing mucinous from nonmucinous cystic lesions," Dr. Saowanee Ngamruengphong and her colleagues from the division of gastroenterology and hepatology at Mayo Clinic Florida, Jacksonville, wrote in an article in Digestive and Liver Disease (2013 June 18 [doi: 10.1016/j.dld.2013.05.002]). "Large, multicentric, well-designed trials are needed to further characterize the role of cyst fluid tumor marker and molecular analysis in the evaluation of pancreatic cysts."

Results from two previously published articles in the medical literature showed that a cyst fluid EA level of 192-200 ng/mL had 80% accuracy in differentiating between mucinous and nonmucinous cysts (Gastroenterology 2004;126:1330-6 and Pancreatology 2012;12:183-97).

In an effort to determine the diagnostic accuracy of cyst fluid CEA in discriminating benign from malignant pancreatic cystic neoplasms, the authors of the current study conducted a literature search of Medline and Embase databases for studies published before October 2012. They used the following keywords: "pancreas OR pancreatic cystic lesion," "tumor marker OR carcinoembryonic antigen OR CEA," and "diagnosis." A total of eight published articles involving 504 patients were included in the final analysis. Random-effects models were used to calculate pooled estimates of diagnostic precision.

Dr. Ngamruengphong and her colleagues reported that the CEA cutoff level for determining a malignant cyst ranged from 109.9 to 6,000 mg/mL, and that the pooled sensitivity of cyst fluid CEA in the prediction of malignant pancreatic cysts was 63% while the pooled specificity was 63%. In addition, the positive likelihood ratio was 1.89, the negative likelihood ratio was 0.62, and the diagnostic odds ratio was 3.84.

A subgroup analysis of 227 patients with mucinous cysts revealed similar results: a pooled sensitivity of 65%, a pooled specificity of 66%, and a diagnostic odds ratio of 4.74.

"Our findings support the current guidelines, which do not recommend the use of fluid cyst CEA to diagnose malignant pancreatic cysts," the researchers wrote.

They acknowledged certain limitations of the study, including the fact that there was significant heterogeneity among the studies and that the small sample sizes in the included studies "could potentially be subject to selection bias."

The researchers stated that they had no relevant financial conflicts to disclose.

[email protected]

The accuracy of cyst fluid carcinoembryonic antigen in differentiating between benign and malignant pancreatic cysts is poor, and the antigen should not be used as a sole marker for guiding surgical decision making, results from a meta-analysis of available literature on the topic suggests.

"The clinical value of cyst fluid CEA should be limited only to distinguishing mucinous from nonmucinous cystic lesions," Dr. Saowanee Ngamruengphong and her colleagues from the division of gastroenterology and hepatology at Mayo Clinic Florida, Jacksonville, wrote in an article in Digestive and Liver Disease (2013 June 18 [doi: 10.1016/j.dld.2013.05.002]). "Large, multicentric, well-designed trials are needed to further characterize the role of cyst fluid tumor marker and molecular analysis in the evaluation of pancreatic cysts."

Results from two previously published articles in the medical literature showed that a cyst fluid EA level of 192-200 ng/mL had 80% accuracy in differentiating between mucinous and nonmucinous cysts (Gastroenterology 2004;126:1330-6 and Pancreatology 2012;12:183-97).

In an effort to determine the diagnostic accuracy of cyst fluid CEA in discriminating benign from malignant pancreatic cystic neoplasms, the authors of the current study conducted a literature search of Medline and Embase databases for studies published before October 2012. They used the following keywords: "pancreas OR pancreatic cystic lesion," "tumor marker OR carcinoembryonic antigen OR CEA," and "diagnosis." A total of eight published articles involving 504 patients were included in the final analysis. Random-effects models were used to calculate pooled estimates of diagnostic precision.

Dr. Ngamruengphong and her colleagues reported that the CEA cutoff level for determining a malignant cyst ranged from 109.9 to 6,000 mg/mL, and that the pooled sensitivity of cyst fluid CEA in the prediction of malignant pancreatic cysts was 63% while the pooled specificity was 63%. In addition, the positive likelihood ratio was 1.89, the negative likelihood ratio was 0.62, and the diagnostic odds ratio was 3.84.

A subgroup analysis of 227 patients with mucinous cysts revealed similar results: a pooled sensitivity of 65%, a pooled specificity of 66%, and a diagnostic odds ratio of 4.74.

"Our findings support the current guidelines, which do not recommend the use of fluid cyst CEA to diagnose malignant pancreatic cysts," the researchers wrote.

They acknowledged certain limitations of the study, including the fact that there was significant heterogeneity among the studies and that the small sample sizes in the included studies "could potentially be subject to selection bias."

The researchers stated that they had no relevant financial conflicts to disclose.

[email protected]

The accuracy of cyst fluid carcinoembryonic antigen in differentiating between benign and malignant pancreatic cysts is poor, and the antigen should not be used as a sole marker for guiding surgical decision making, results from a meta-analysis of available literature on the topic suggests.

"The clinical value of cyst fluid CEA should be limited only to distinguishing mucinous from nonmucinous cystic lesions," Dr. Saowanee Ngamruengphong and her colleagues from the division of gastroenterology and hepatology at Mayo Clinic Florida, Jacksonville, wrote in an article in Digestive and Liver Disease (2013 June 18 [doi: 10.1016/j.dld.2013.05.002]). "Large, multicentric, well-designed trials are needed to further characterize the role of cyst fluid tumor marker and molecular analysis in the evaluation of pancreatic cysts."

Results from two previously published articles in the medical literature showed that a cyst fluid EA level of 192-200 ng/mL had 80% accuracy in differentiating between mucinous and nonmucinous cysts (Gastroenterology 2004;126:1330-6 and Pancreatology 2012;12:183-97).

In an effort to determine the diagnostic accuracy of cyst fluid CEA in discriminating benign from malignant pancreatic cystic neoplasms, the authors of the current study conducted a literature search of Medline and Embase databases for studies published before October 2012. They used the following keywords: "pancreas OR pancreatic cystic lesion," "tumor marker OR carcinoembryonic antigen OR CEA," and "diagnosis." A total of eight published articles involving 504 patients were included in the final analysis. Random-effects models were used to calculate pooled estimates of diagnostic precision.

Dr. Ngamruengphong and her colleagues reported that the CEA cutoff level for determining a malignant cyst ranged from 109.9 to 6,000 mg/mL, and that the pooled sensitivity of cyst fluid CEA in the prediction of malignant pancreatic cysts was 63% while the pooled specificity was 63%. In addition, the positive likelihood ratio was 1.89, the negative likelihood ratio was 0.62, and the diagnostic odds ratio was 3.84.

A subgroup analysis of 227 patients with mucinous cysts revealed similar results: a pooled sensitivity of 65%, a pooled specificity of 66%, and a diagnostic odds ratio of 4.74.

"Our findings support the current guidelines, which do not recommend the use of fluid cyst CEA to diagnose malignant pancreatic cysts," the researchers wrote.

They acknowledged certain limitations of the study, including the fact that there was significant heterogeneity among the studies and that the small sample sizes in the included studies "could potentially be subject to selection bias."

The researchers stated that they had no relevant financial conflicts to disclose.

[email protected]

Angelina Jolie caused a social and public media storm recently when she revealed that she carries a mutation in the BRCA1 gene, thus putting her at heightened risk for developing breast cancer and ovarian cancer. She also disclosed her very personal decision to have preventative bilateral mastectomy, at the age of 37, to reduce her risk of breast cancer, which she was informed was 87%.

Jolie was courageous in sharing this personal decision and bringing the conversation of genetics and one’s health to the forefront. It did spark discussion and debate on genetic testing and how to manage the risk associated with having a BRCA mutation. When a star of Jolie’s status makes such an announcement, it provides an opportunity to help educate patients and discuss their management options. It gives them the chance to decide on a risk reduction strategy that is medically sound and their own personal choice.

My clinic did see an influx of patients calling about having BRCA testing. But what was more interesting were the calls from former patients who had tested positive for a BRCA mutation – they were concerned about the actual level of risk (87%) being quoted by the media’s medical correspondents, many of whom were physicians. They were worried about whether "they are doing enough" to manage their risk, given that they had decided on a different strategy involving high-risk breast cancer screening, which consists of an annual breast MRI, an annual mammogram, a clinical breast exam every 6 months (one with a breast specialist), and a self-exam monthly.

These patients’ reactions raise an important point: Physicians need to have an ongoing conversation about the different options for managing risk – specifically, about screening vs. prevention.

While mastectomy is certainly a medically sound option, high-risk screening is, too, if the protocol is followed. There are additional ways to reduce risk, and the conversation cannot be one-sided in favor of surgery.

Many women who choose the option of high-risk breast cancer screening will opt to take tamoxifen preventively. This can reduce breast cancer risk up to 50% and, when combined with high-risk screening, is a medically sound plan. A similar reduction in breast cancer risk is achieved with prophylactic salpingo-oophorectomy, if performed premenopausally, which is necessary to manage the ovarian cancer risk associated with the BRCA genes.

Finally, making a decision on the right risk-reduction strategy to pursue relies on having an appropriate understanding of risk – so one can understand what "reducing risk by 50%" really means. The 87% breast cancer risk that made the media reports is a very high estimate based on early studies in BRCA families. Most genetics professionals would quote lower lifetime estimates (60%-70%) and use age-adjusted data that are more recent.

For example, Dr. Sining Chen and Dr. Giovanni Parmigiani have provided a nice meta-analysis to estimate BRCA1 and BRCA2 mutation carriers’ risks of developing breast cancer or ovarian cancer, broken down by decade, all the way to age 70 years (J. Clin. Oncol. 2007;25:1329-33).

In Angelina Jolie’s case, her BRCA1-associated risk from age 40 to age 70 is approximately 49%. For comparison, the risk for a BRCA2 carrier from age 40 to age 70 is approximately 38%. Granted, the risk remains elevated (average breast cancer risk is 12% lifetime), and there is risk beyond age 70. But the data provide a more informed perspective on actual risk.

This is key to having patients understand their own risk and the timing of that risk. That understanding can help them make an informed decision regarding their strategy to manage BRCA-related cancer risks.

While Jolie’s decision is sound medically, there are sound alternatives. Choosing the right plan requires an in-depth conversation with our patients to make sure they understand their risk and devise a medically sound plan that is personalized to them.

Dr. Hulick is a medical geneticist at NorthShore University HealthSystem, Evanston, Ill., and a clinician educator at the University of Chicago. He reported having no conflicts of interest.

Angelina Jolie caused a social and public media storm recently when she revealed that she carries a mutation in the BRCA1 gene, thus putting her at heightened risk for developing breast cancer and ovarian cancer. She also disclosed her very personal decision to have preventative bilateral mastectomy, at the age of 37, to reduce her risk of breast cancer, which she was informed was 87%.

Jolie was courageous in sharing this personal decision and bringing the conversation of genetics and one’s health to the forefront. It did spark discussion and debate on genetic testing and how to manage the risk associated with having a BRCA mutation. When a star of Jolie’s status makes such an announcement, it provides an opportunity to help educate patients and discuss their management options. It gives them the chance to decide on a risk reduction strategy that is medically sound and their own personal choice.

My clinic did see an influx of patients calling about having BRCA testing. But what was more interesting were the calls from former patients who had tested positive for a BRCA mutation – they were concerned about the actual level of risk (87%) being quoted by the media’s medical correspondents, many of whom were physicians. They were worried about whether "they are doing enough" to manage their risk, given that they had decided on a different strategy involving high-risk breast cancer screening, which consists of an annual breast MRI, an annual mammogram, a clinical breast exam every 6 months (one with a breast specialist), and a self-exam monthly.

These patients’ reactions raise an important point: Physicians need to have an ongoing conversation about the different options for managing risk – specifically, about screening vs. prevention.

While mastectomy is certainly a medically sound option, high-risk screening is, too, if the protocol is followed. There are additional ways to reduce risk, and the conversation cannot be one-sided in favor of surgery.

Many women who choose the option of high-risk breast cancer screening will opt to take tamoxifen preventively. This can reduce breast cancer risk up to 50% and, when combined with high-risk screening, is a medically sound plan. A similar reduction in breast cancer risk is achieved with prophylactic salpingo-oophorectomy, if performed premenopausally, which is necessary to manage the ovarian cancer risk associated with the BRCA genes.

Finally, making a decision on the right risk-reduction strategy to pursue relies on having an appropriate understanding of risk – so one can understand what "reducing risk by 50%" really means. The 87% breast cancer risk that made the media reports is a very high estimate based on early studies in BRCA families. Most genetics professionals would quote lower lifetime estimates (60%-70%) and use age-adjusted data that are more recent.

For example, Dr. Sining Chen and Dr. Giovanni Parmigiani have provided a nice meta-analysis to estimate BRCA1 and BRCA2 mutation carriers’ risks of developing breast cancer or ovarian cancer, broken down by decade, all the way to age 70 years (J. Clin. Oncol. 2007;25:1329-33).

In Angelina Jolie’s case, her BRCA1-associated risk from age 40 to age 70 is approximately 49%. For comparison, the risk for a BRCA2 carrier from age 40 to age 70 is approximately 38%. Granted, the risk remains elevated (average breast cancer risk is 12% lifetime), and there is risk beyond age 70. But the data provide a more informed perspective on actual risk.

This is key to having patients understand their own risk and the timing of that risk. That understanding can help them make an informed decision regarding their strategy to manage BRCA-related cancer risks.

While Jolie’s decision is sound medically, there are sound alternatives. Choosing the right plan requires an in-depth conversation with our patients to make sure they understand their risk and devise a medically sound plan that is personalized to them.

Dr. Hulick is a medical geneticist at NorthShore University HealthSystem, Evanston, Ill., and a clinician educator at the University of Chicago. He reported having no conflicts of interest.

Angelina Jolie caused a social and public media storm recently when she revealed that she carries a mutation in the BRCA1 gene, thus putting her at heightened risk for developing breast cancer and ovarian cancer. She also disclosed her very personal decision to have preventative bilateral mastectomy, at the age of 37, to reduce her risk of breast cancer, which she was informed was 87%.

Jolie was courageous in sharing this personal decision and bringing the conversation of genetics and one’s health to the forefront. It did spark discussion and debate on genetic testing and how to manage the risk associated with having a BRCA mutation. When a star of Jolie’s status makes such an announcement, it provides an opportunity to help educate patients and discuss their management options. It gives them the chance to decide on a risk reduction strategy that is medically sound and their own personal choice.

My clinic did see an influx of patients calling about having BRCA testing. But what was more interesting were the calls from former patients who had tested positive for a BRCA mutation – they were concerned about the actual level of risk (87%) being quoted by the media’s medical correspondents, many of whom were physicians. They were worried about whether "they are doing enough" to manage their risk, given that they had decided on a different strategy involving high-risk breast cancer screening, which consists of an annual breast MRI, an annual mammogram, a clinical breast exam every 6 months (one with a breast specialist), and a self-exam monthly.

These patients’ reactions raise an important point: Physicians need to have an ongoing conversation about the different options for managing risk – specifically, about screening vs. prevention.

While mastectomy is certainly a medically sound option, high-risk screening is, too, if the protocol is followed. There are additional ways to reduce risk, and the conversation cannot be one-sided in favor of surgery.

Many women who choose the option of high-risk breast cancer screening will opt to take tamoxifen preventively. This can reduce breast cancer risk up to 50% and, when combined with high-risk screening, is a medically sound plan. A similar reduction in breast cancer risk is achieved with prophylactic salpingo-oophorectomy, if performed premenopausally, which is necessary to manage the ovarian cancer risk associated with the BRCA genes.

Finally, making a decision on the right risk-reduction strategy to pursue relies on having an appropriate understanding of risk – so one can understand what "reducing risk by 50%" really means. The 87% breast cancer risk that made the media reports is a very high estimate based on early studies in BRCA families. Most genetics professionals would quote lower lifetime estimates (60%-70%) and use age-adjusted data that are more recent.

For example, Dr. Sining Chen and Dr. Giovanni Parmigiani have provided a nice meta-analysis to estimate BRCA1 and BRCA2 mutation carriers’ risks of developing breast cancer or ovarian cancer, broken down by decade, all the way to age 70 years (J. Clin. Oncol. 2007;25:1329-33).

In Angelina Jolie’s case, her BRCA1-associated risk from age 40 to age 70 is approximately 49%. For comparison, the risk for a BRCA2 carrier from age 40 to age 70 is approximately 38%. Granted, the risk remains elevated (average breast cancer risk is 12% lifetime), and there is risk beyond age 70. But the data provide a more informed perspective on actual risk.

This is key to having patients understand their own risk and the timing of that risk. That understanding can help them make an informed decision regarding their strategy to manage BRCA-related cancer risks.

While Jolie’s decision is sound medically, there are sound alternatives. Choosing the right plan requires an in-depth conversation with our patients to make sure they understand their risk and devise a medically sound plan that is personalized to them.

Dr. Hulick is a medical geneticist at NorthShore University HealthSystem, Evanston, Ill., and a clinician educator at the University of Chicago. He reported having no conflicts of interest.

CHICAGO – Long-term intensive blood and computed tomography follow-up offered no significant advantage over minimal follow-up for detecting colorectal cancer recurrences in the phase III FACS trial.

The proportion of patients with recurrence treated surgically with curative intent was 6.7% with intensive carcinoembryonic antigen (CEA) testing, 8% with monthly computed tomography imaging and 6.6% with combination CEA plus CT, compared with 2.3% with minimal follow-up involving a single CT scan.

After adjustment, it was about three times more likely that patients would have a recurrence with CEA (adjusted odds ratio, 2.70; P = .035), monthly CT imaging (OR, 3.45; P = .007) and CEA plus CT (OR, 2.95; P = .021) than with minimal follow-up.

"This result appeared to be quite robust" and was independent of cancer stage, co-primary investigator Dr. David Mant said at the annual meeting of the American Society of Clinical Oncology.

There was virtually no deviation in protocol by patients, however, the desire for unscheduled CT scans by surgeons meant that up to 30% in the minimal follow-up arm had 1 or more additional CTs, he noted. Still, in a per protocol analysis, the absolute differences in recurrence were 3.8- to 5.4-times higher with intensive follow-up. Again, there was no evidence of an additive effect of CEA plus CT.

Guidelines in the United States and Europe stress intensive follow-up including routine history and physical examination, CEA monitoring, yearly colonoscopy and repeated CT scans in those at high risk of recurrence.

The FACS (Follow-Up After Colorectal Surgery) trial looked at whether long-term intensive follow-up was worthwhile. Though commonplace after curative surgery, economic modeling suggests intensive followup may not be cost-effective and claims of a substantial overall survival benefit are inconsistent with the reported frequency and effectiveness of treatment for recurrence, explained Dr. David Mant, emeritus professor of general practice, Oxford University.

"As a long-term family physician, I’d seen many patients being followed-up for cancer and watched their cycle of deep anxiety, followed usually by relief, but sometimes with misery, as they waited for their follow-up appointments," he added. "It seemed to me that it was a very bad idea to carry on with this practice, unless it was to their benefit."

FACS involved 1,202 patients who were disease free on colonoscopy and CT imaging and had a blood CEA level of 10 mcg/L or less (Dukes’ stages A-C) after treatment for primary colorectal cancer. Their median age was 70 years.

Patients were randomly assigned to one of four follow-up regimens: "minimal" follow-up based mainly on symptoms and a single CT scan at 12-18 months; "CEA," which included minimal follow-up, plus 3 monthly blood CEA tests for 2 years then 6 monthly tests in years 3-5; "CT," which included minimal follow-up plus intensive CT imaging involving 6 monthly scans of the chest, abdomen, and pelvis for 2 years, and then annually for another 3 years; and "CEA plus CT," which included the CEA regimen in group 2 and the CT measures in group 3.

If during monitoring, a patient’s CEA level was 7 mcg/L or more above their baseline level at trial entry, the test was repeated as soon as possible. If the second test was also above the threshold, the patient’s physician was asked to refer the patient urgently to the local hospital.

Overall, 6% of patients (71/1,202) developed a recurrence treated surgically with curative intent. There was little difference between patients according to Duke’s staging (stage A, 5.1%; stage B, 6.1%; stage C, 6.2%), reported Dr. Mant and coprincipal investigator Dr. John Primrose of University of Southhampton, U.K.

"You actually do need rigorous initial staging to detect residual disease before you embark on any follow-up," Dr. Mant stressed. "I think both John and I are convinced that the reason why we have a 6% overall recurrence rate is because the people in this trial were appropriately staged. The survival curves don’t suggest they were any less sick than patients in other trials."

At the time of the analysis, 59% of patients with a recurrence treated with curative intent were still alive, but there was no statistical difference in colorectal cancer deaths (P = .66) or total deaths (P = .45) between the minimum and intensive follow-up arms, he said.

In a meta-analysis that integrated the FACS data with that from three previous trials, the overall effect of intensive follow-up was not significant (OR, 0.96; P = .56), Dr. Mant said. The number needed to treat to detect potentially curable recurrence with intensive follow-up is about 20 to 25 and that predicts a number-needed-to-treat of about 40 to 50 for 5-year post-recurrence survival.

Dr. Maughan said the disparity between the current meta-analysis and the Cochrane review may be because the latter included six studies, not three, and that the survival data from FACS may not be fully mature. A further analysis of the FACS data is planned in about 18 months.

Dr. Mant and his coauthors reported having no financial disclosures.

Mant, D., et al. "Effect of 3-5 years of scheduled CED and CT follow-up to detect recurrence of colorectal cancer: FACS randomized controlled trial." Ab. 3500.

[email protected]

CHICAGO – Long-term intensive blood and computed tomography follow-up offered no significant advantage over minimal follow-up for detecting colorectal cancer recurrences in the phase III FACS trial.

The proportion of patients with recurrence treated surgically with curative intent was 6.7% with intensive carcinoembryonic antigen (CEA) testing, 8% with monthly computed tomography imaging and 6.6% with combination CEA plus CT, compared with 2.3% with minimal follow-up involving a single CT scan.

After adjustment, it was about three times more likely that patients would have a recurrence with CEA (adjusted odds ratio, 2.70; P = .035), monthly CT imaging (OR, 3.45; P = .007) and CEA plus CT (OR, 2.95; P = .021) than with minimal follow-up.

"This result appeared to be quite robust" and was independent of cancer stage, co-primary investigator Dr. David Mant said at the annual meeting of the American Society of Clinical Oncology.

There was virtually no deviation in protocol by patients, however, the desire for unscheduled CT scans by surgeons meant that up to 30% in the minimal follow-up arm had 1 or more additional CTs, he noted. Still, in a per protocol analysis, the absolute differences in recurrence were 3.8- to 5.4-times higher with intensive follow-up. Again, there was no evidence of an additive effect of CEA plus CT.

Guidelines in the United States and Europe stress intensive follow-up including routine history and physical examination, CEA monitoring, yearly colonoscopy and repeated CT scans in those at high risk of recurrence.

The FACS (Follow-Up After Colorectal Surgery) trial looked at whether long-term intensive follow-up was worthwhile. Though commonplace after curative surgery, economic modeling suggests intensive followup may not be cost-effective and claims of a substantial overall survival benefit are inconsistent with the reported frequency and effectiveness of treatment for recurrence, explained Dr. David Mant, emeritus professor of general practice, Oxford University.

"As a long-term family physician, I’d seen many patients being followed-up for cancer and watched their cycle of deep anxiety, followed usually by relief, but sometimes with misery, as they waited for their follow-up appointments," he added. "It seemed to me that it was a very bad idea to carry on with this practice, unless it was to their benefit."

FACS involved 1,202 patients who were disease free on colonoscopy and CT imaging and had a blood CEA level of 10 mcg/L or less (Dukes’ stages A-C) after treatment for primary colorectal cancer. Their median age was 70 years.

Patients were randomly assigned to one of four follow-up regimens: "minimal" follow-up based mainly on symptoms and a single CT scan at 12-18 months; "CEA," which included minimal follow-up, plus 3 monthly blood CEA tests for 2 years then 6 monthly tests in years 3-5; "CT," which included minimal follow-up plus intensive CT imaging involving 6 monthly scans of the chest, abdomen, and pelvis for 2 years, and then annually for another 3 years; and "CEA plus CT," which included the CEA regimen in group 2 and the CT measures in group 3.

If during monitoring, a patient’s CEA level was 7 mcg/L or more above their baseline level at trial entry, the test was repeated as soon as possible. If the second test was also above the threshold, the patient’s physician was asked to refer the patient urgently to the local hospital.

Overall, 6% of patients (71/1,202) developed a recurrence treated surgically with curative intent. There was little difference between patients according to Duke’s staging (stage A, 5.1%; stage B, 6.1%; stage C, 6.2%), reported Dr. Mant and coprincipal investigator Dr. John Primrose of University of Southhampton, U.K.

"You actually do need rigorous initial staging to detect residual disease before you embark on any follow-up," Dr. Mant stressed. "I think both John and I are convinced that the reason why we have a 6% overall recurrence rate is because the people in this trial were appropriately staged. The survival curves don’t suggest they were any less sick than patients in other trials."

At the time of the analysis, 59% of patients with a recurrence treated with curative intent were still alive, but there was no statistical difference in colorectal cancer deaths (P = .66) or total deaths (P = .45) between the minimum and intensive follow-up arms, he said.

In a meta-analysis that integrated the FACS data with that from three previous trials, the overall effect of intensive follow-up was not significant (OR, 0.96; P = .56), Dr. Mant said. The number needed to treat to detect potentially curable recurrence with intensive follow-up is about 20 to 25 and that predicts a number-needed-to-treat of about 40 to 50 for 5-year post-recurrence survival.

Dr. Maughan said the disparity between the current meta-analysis and the Cochrane review may be because the latter included six studies, not three, and that the survival data from FACS may not be fully mature. A further analysis of the FACS data is planned in about 18 months.

Dr. Mant and his coauthors reported having no financial disclosures.

Mant, D., et al. "Effect of 3-5 years of scheduled CED and CT follow-up to detect recurrence of colorectal cancer: FACS randomized controlled trial." Ab. 3500.

[email protected]

CHICAGO – Long-term intensive blood and computed tomography follow-up offered no significant advantage over minimal follow-up for detecting colorectal cancer recurrences in the phase III FACS trial.

The proportion of patients with recurrence treated surgically with curative intent was 6.7% with intensive carcinoembryonic antigen (CEA) testing, 8% with monthly computed tomography imaging and 6.6% with combination CEA plus CT, compared with 2.3% with minimal follow-up involving a single CT scan.

After adjustment, it was about three times more likely that patients would have a recurrence with CEA (adjusted odds ratio, 2.70; P = .035), monthly CT imaging (OR, 3.45; P = .007) and CEA plus CT (OR, 2.95; P = .021) than with minimal follow-up.

"This result appeared to be quite robust" and was independent of cancer stage, co-primary investigator Dr. David Mant said at the annual meeting of the American Society of Clinical Oncology.

There was virtually no deviation in protocol by patients, however, the desire for unscheduled CT scans by surgeons meant that up to 30% in the minimal follow-up arm had 1 or more additional CTs, he noted. Still, in a per protocol analysis, the absolute differences in recurrence were 3.8- to 5.4-times higher with intensive follow-up. Again, there was no evidence of an additive effect of CEA plus CT.

Guidelines in the United States and Europe stress intensive follow-up including routine history and physical examination, CEA monitoring, yearly colonoscopy and repeated CT scans in those at high risk of recurrence.

The FACS (Follow-Up After Colorectal Surgery) trial looked at whether long-term intensive follow-up was worthwhile. Though commonplace after curative surgery, economic modeling suggests intensive followup may not be cost-effective and claims of a substantial overall survival benefit are inconsistent with the reported frequency and effectiveness of treatment for recurrence, explained Dr. David Mant, emeritus professor of general practice, Oxford University.

"As a long-term family physician, I’d seen many patients being followed-up for cancer and watched their cycle of deep anxiety, followed usually by relief, but sometimes with misery, as they waited for their follow-up appointments," he added. "It seemed to me that it was a very bad idea to carry on with this practice, unless it was to their benefit."

FACS involved 1,202 patients who were disease free on colonoscopy and CT imaging and had a blood CEA level of 10 mcg/L or less (Dukes’ stages A-C) after treatment for primary colorectal cancer. Their median age was 70 years.

Patients were randomly assigned to one of four follow-up regimens: "minimal" follow-up based mainly on symptoms and a single CT scan at 12-18 months; "CEA," which included minimal follow-up, plus 3 monthly blood CEA tests for 2 years then 6 monthly tests in years 3-5; "CT," which included minimal follow-up plus intensive CT imaging involving 6 monthly scans of the chest, abdomen, and pelvis for 2 years, and then annually for another 3 years; and "CEA plus CT," which included the CEA regimen in group 2 and the CT measures in group 3.

If during monitoring, a patient’s CEA level was 7 mcg/L or more above their baseline level at trial entry, the test was repeated as soon as possible. If the second test was also above the threshold, the patient’s physician was asked to refer the patient urgently to the local hospital.

Overall, 6% of patients (71/1,202) developed a recurrence treated surgically with curative intent. There was little difference between patients according to Duke’s staging (stage A, 5.1%; stage B, 6.1%; stage C, 6.2%), reported Dr. Mant and coprincipal investigator Dr. John Primrose of University of Southhampton, U.K.

"You actually do need rigorous initial staging to detect residual disease before you embark on any follow-up," Dr. Mant stressed. "I think both John and I are convinced that the reason why we have a 6% overall recurrence rate is because the people in this trial were appropriately staged. The survival curves don’t suggest they were any less sick than patients in other trials."

At the time of the analysis, 59% of patients with a recurrence treated with curative intent were still alive, but there was no statistical difference in colorectal cancer deaths (P = .66) or total deaths (P = .45) between the minimum and intensive follow-up arms, he said.

In a meta-analysis that integrated the FACS data with that from three previous trials, the overall effect of intensive follow-up was not significant (OR, 0.96; P = .56), Dr. Mant said. The number needed to treat to detect potentially curable recurrence with intensive follow-up is about 20 to 25 and that predicts a number-needed-to-treat of about 40 to 50 for 5-year post-recurrence survival.

Dr. Maughan said the disparity between the current meta-analysis and the Cochrane review may be because the latter included six studies, not three, and that the survival data from FACS may not be fully mature. A further analysis of the FACS data is planned in about 18 months.

Dr. Mant and his coauthors reported having no financial disclosures.

Mant, D., et al. "Effect of 3-5 years of scheduled CED and CT follow-up to detect recurrence of colorectal cancer: FACS randomized controlled trial." Ab. 3500.

[email protected]

MINNEAPOLIS – Increasing the surgical margin length up to 15 mm during wedge resection of small lung cancer tumors significantly lowered the risk of local recurrence among 474 consecutive patients.

No additional benefit was observed, however, beyond 15 mm, said Dr. Kamran Mohiuddin, a surgical research fellow at Brigham and Women’s Hospital, Boston.

Compared with a margin length of 5 mm, the adjusted risk of local recurrence was estimated to be 45% lower with a margin length of 10 mm (hazard ratio, 0.55), 59% lower with a 15-mm margin (HR, 0.41), and 54% lower with a 20-mm margin (HR, 0.46).

"The downward trend flattens out, indicating diminished benefit of increasing the margin length," he said at the annual meeting of the American Association for Thoracic Surgery.

Patrice Wendling/IMNG Medical Media

Currently, the data are unclear regarding the optimal margin length for wedge resection of small non–small cell lung cancer (NSCLC) tumors of less than 2 cm. Wedge resections are associated with margins less than 1 cm and a high risk for locoregional recurrence (Ann. Surg. Oncol. 2007;14:2400-5), with a multicenter, prospective study suggesting that the optimal margin length should be larger than the maximum tumor diameter (Ann. Thorac. Surg. 2004;77:415-20).

When asked during a discussion of the analysis whether a more aggressive resection or segmentectomy would be performed if margins are found in the operating room to be inadequate based on the current results, senior author Dr. Scott J. Swanson, an ACS Fellow and director of minimally invasive thoracic surgery at the hospital, said they are taking the results forward into practice, but that it’s unclear whether 15 mm is the optimal number to target.

"Is 15 mm the correct margin? I am not sure we know the answer in all cases, but it is a useful number to keep in the surgeon’s head when we are doing resections for tumors that are 2 cm or less," he said in an interview. "A 15-mm margin seems to be a better target to aim for than margin length to tumor diameter ratio of greater than 1, as suggested by other investigators."

The current analysis included data from all patients, aged 21-85 years, who underwent wedge resection for NSCLC 2 cm or less at their institution between January 2001 and August 2011. Margin length, defined as the distance from the tumor to the closest stapled resection margin, was 0.1-0.5 cm in 36%, 0.6-1.0 cm in 25.5%, 1.1-2.0 cm in 28.5%, and greater than 2 cm in 10%.

The mean tumor size was 1.33 cm, the location of the tumor was the right upper lobe in the majority (36%), and video-assisted thoracic surgery (VATS) was used in 57.5%. The patients’ mean forced expiratory volume in 1 second (FEV₁) was 79.8%, and the mean age was 68.5 years.

Perioperative death occurred in 1 patient and at least one major complication in 41 patients, Dr. Mohiuddin said.

The local recurrence rate was 5.8% at 1 year, 11.3% at 2 years, and 16.8% at 3 years. Median follow-up was 3.9 years.

In multivariate regression analysis, increased margin length was significantly associated with a lower risk of local recurrence, with evidence of diminished additional benefit beyond a length of 15 mm (P = .031), he said. The analysis adjusted for FEV₁, chronic obstructive pulmonary disease, smoking, diabetes, tumor size, tumor lobe location, location within the hemothorax, surgeon, whether VATS or open surgery was used, and whether or not nodes were sampled.

Dr. Mohiuddin and his coauthors reported having no financial disclosures.

[email protected]

MINNEAPOLIS – Increasing the surgical margin length up to 15 mm during wedge resection of small lung cancer tumors significantly lowered the risk of local recurrence among 474 consecutive patients.

No additional benefit was observed, however, beyond 15 mm, said Dr. Kamran Mohiuddin, a surgical research fellow at Brigham and Women’s Hospital, Boston.

Compared with a margin length of 5 mm, the adjusted risk of local recurrence was estimated to be 45% lower with a margin length of 10 mm (hazard ratio, 0.55), 59% lower with a 15-mm margin (HR, 0.41), and 54% lower with a 20-mm margin (HR, 0.46).

"The downward trend flattens out, indicating diminished benefit of increasing the margin length," he said at the annual meeting of the American Association for Thoracic Surgery.

Patrice Wendling/IMNG Medical Media

Currently, the data are unclear regarding the optimal margin length for wedge resection of small non–small cell lung cancer (NSCLC) tumors of less than 2 cm. Wedge resections are associated with margins less than 1 cm and a high risk for locoregional recurrence (Ann. Surg. Oncol. 2007;14:2400-5), with a multicenter, prospective study suggesting that the optimal margin length should be larger than the maximum tumor diameter (Ann. Thorac. Surg. 2004;77:415-20).

When asked during a discussion of the analysis whether a more aggressive resection or segmentectomy would be performed if margins are found in the operating room to be inadequate based on the current results, senior author Dr. Scott J. Swanson, an ACS Fellow and director of minimally invasive thoracic surgery at the hospital, said they are taking the results forward into practice, but that it’s unclear whether 15 mm is the optimal number to target.

"Is 15 mm the correct margin? I am not sure we know the answer in all cases, but it is a useful number to keep in the surgeon’s head when we are doing resections for tumors that are 2 cm or less," he said in an interview. "A 15-mm margin seems to be a better target to aim for than margin length to tumor diameter ratio of greater than 1, as suggested by other investigators."

The current analysis included data from all patients, aged 21-85 years, who underwent wedge resection for NSCLC 2 cm or less at their institution between January 2001 and August 2011. Margin length, defined as the distance from the tumor to the closest stapled resection margin, was 0.1-0.5 cm in 36%, 0.6-1.0 cm in 25.5%, 1.1-2.0 cm in 28.5%, and greater than 2 cm in 10%.

The mean tumor size was 1.33 cm, the location of the tumor was the right upper lobe in the majority (36%), and video-assisted thoracic surgery (VATS) was used in 57.5%. The patients’ mean forced expiratory volume in 1 second (FEV₁) was 79.8%, and the mean age was 68.5 years.

Perioperative death occurred in 1 patient and at least one major complication in 41 patients, Dr. Mohiuddin said.

The local recurrence rate was 5.8% at 1 year, 11.3% at 2 years, and 16.8% at 3 years. Median follow-up was 3.9 years.

In multivariate regression analysis, increased margin length was significantly associated with a lower risk of local recurrence, with evidence of diminished additional benefit beyond a length of 15 mm (P = .031), he said. The analysis adjusted for FEV₁, chronic obstructive pulmonary disease, smoking, diabetes, tumor size, tumor lobe location, location within the hemothorax, surgeon, whether VATS or open surgery was used, and whether or not nodes were sampled.

Dr. Mohiuddin and his coauthors reported having no financial disclosures.

[email protected]

MINNEAPOLIS – Increasing the surgical margin length up to 15 mm during wedge resection of small lung cancer tumors significantly lowered the risk of local recurrence among 474 consecutive patients.

No additional benefit was observed, however, beyond 15 mm, said Dr. Kamran Mohiuddin, a surgical research fellow at Brigham and Women’s Hospital, Boston.

Compared with a margin length of 5 mm, the adjusted risk of local recurrence was estimated to be 45% lower with a margin length of 10 mm (hazard ratio, 0.55), 59% lower with a 15-mm margin (HR, 0.41), and 54% lower with a 20-mm margin (HR, 0.46).

"The downward trend flattens out, indicating diminished benefit of increasing the margin length," he said at the annual meeting of the American Association for Thoracic Surgery.

Patrice Wendling/IMNG Medical Media

Currently, the data are unclear regarding the optimal margin length for wedge resection of small non–small cell lung cancer (NSCLC) tumors of less than 2 cm. Wedge resections are associated with margins less than 1 cm and a high risk for locoregional recurrence (Ann. Surg. Oncol. 2007;14:2400-5), with a multicenter, prospective study suggesting that the optimal margin length should be larger than the maximum tumor diameter (Ann. Thorac. Surg. 2004;77:415-20).

When asked during a discussion of the analysis whether a more aggressive resection or segmentectomy would be performed if margins are found in the operating room to be inadequate based on the current results, senior author Dr. Scott J. Swanson, an ACS Fellow and director of minimally invasive thoracic surgery at the hospital, said they are taking the results forward into practice, but that it’s unclear whether 15 mm is the optimal number to target.

"Is 15 mm the correct margin? I am not sure we know the answer in all cases, but it is a useful number to keep in the surgeon’s head when we are doing resections for tumors that are 2 cm or less," he said in an interview. "A 15-mm margin seems to be a better target to aim for than margin length to tumor diameter ratio of greater than 1, as suggested by other investigators."

The current analysis included data from all patients, aged 21-85 years, who underwent wedge resection for NSCLC 2 cm or less at their institution between January 2001 and August 2011. Margin length, defined as the distance from the tumor to the closest stapled resection margin, was 0.1-0.5 cm in 36%, 0.6-1.0 cm in 25.5%, 1.1-2.0 cm in 28.5%, and greater than 2 cm in 10%.

The mean tumor size was 1.33 cm, the location of the tumor was the right upper lobe in the majority (36%), and video-assisted thoracic surgery (VATS) was used in 57.5%. The patients’ mean forced expiratory volume in 1 second (FEV₁) was 79.8%, and the mean age was 68.5 years.

Perioperative death occurred in 1 patient and at least one major complication in 41 patients, Dr. Mohiuddin said.

The local recurrence rate was 5.8% at 1 year, 11.3% at 2 years, and 16.8% at 3 years. Median follow-up was 3.9 years.

In multivariate regression analysis, increased margin length was significantly associated with a lower risk of local recurrence, with evidence of diminished additional benefit beyond a length of 15 mm (P = .031), he said. The analysis adjusted for FEV₁, chronic obstructive pulmonary disease, smoking, diabetes, tumor size, tumor lobe location, location within the hemothorax, surgeon, whether VATS or open surgery was used, and whether or not nodes were sampled.

Dr. Mohiuddin and his coauthors reported having no financial disclosures.

[email protected]

Private companies do not have the right to patent human genes, the U.S. Supreme Court has ruled.

In a unanimous decision issued on June 13, the high court ruled that a naturally occurring DNA segment is a "product of nature" and is not eligible for a patent simply because it has been isolated. But the court also ruled that synthetically created DNA known as complementary DNA (cDNA) can be granted a patent.

In Association for Molecular Pathology et al. v. Myriad Genetics, the high court considered the validity of patents held by Utah-based Myriad Genetics for the BRCA1 and BRCA2 genes, which are associated with an increased risk of breast and ovarian cancer.

Scientists at Myriad Genetics uncovered the location and sequence of the BRCA1 and BRCA2 genes in the mid-1990s. Since then, they have held the exclusive rights to the diagnostic testing for the mutations. But critics say the monopoly on testing held by Myriad is bad for patients because the test is expensive and they have no alternative confirmatory test.

"It is undisputed that Myriad did not create or alter any of the genetic information encoded in the BRCA1 and BRCA2 genes," Justice Clarence Thomas wrote in the court’s opinion. "Myriad’s principal contribution was uncovering the precise location and genetic sequence of the BRCA1 and BRCA2 genes within chromosomes 17 and 13."

The justices concluded that simply isolating genes and the information they encode from the surrounding genetic material is insufficient for a patent. However, cDNA are not naturally occurring so tests using that technology can be patented.

The American Medical Association, which filed an amicus brief in support of invalidating the Myriad patents, praised the Court’s decision.

“Removing the patents on the building blocks of life ensures that scientific discovery and medical care based on insights into human DNA will remain freely accessible and widely disseminated, not hidden behind a vast thicket of exclusive rights,” Dr. Jeremy A. Lazarus, AMA president, said in a statement.

The American Civil Liberties Union, which joined the suit against Myriad, said the decision brings down a major barrier to patient care and medical innovation. "Because of this ruling, patients will have greater access to genetic testing and scientists can engage in research on these genes without fear of being sued," Sandra Park, senior staff attorney with the ACLU Women’s Rights Project, said in a statement.

The Supreme Court’s decision comes too late to have much of a practical impact on BRCA1 and BRCA2 testing, since Myriad’s 20-year exclusivity on the patents in dispute all expire by 2015.

[email protected]

On Twitter @MaryEllenNY

Private companies do not have the right to patent human genes, the U.S. Supreme Court has ruled.

In a unanimous decision issued on June 13, the high court ruled that a naturally occurring DNA segment is a "product of nature" and is not eligible for a patent simply because it has been isolated. But the court also ruled that synthetically created DNA known as complementary DNA (cDNA) can be granted a patent.

In Association for Molecular Pathology et al. v. Myriad Genetics, the high court considered the validity of patents held by Utah-based Myriad Genetics for the BRCA1 and BRCA2 genes, which are associated with an increased risk of breast and ovarian cancer.

Scientists at Myriad Genetics uncovered the location and sequence of the BRCA1 and BRCA2 genes in the mid-1990s. Since then, they have held the exclusive rights to the diagnostic testing for the mutations. But critics say the monopoly on testing held by Myriad is bad for patients because the test is expensive and they have no alternative confirmatory test.

"It is undisputed that Myriad did not create or alter any of the genetic information encoded in the BRCA1 and BRCA2 genes," Justice Clarence Thomas wrote in the court’s opinion. "Myriad’s principal contribution was uncovering the precise location and genetic sequence of the BRCA1 and BRCA2 genes within chromosomes 17 and 13."

The justices concluded that simply isolating genes and the information they encode from the surrounding genetic material is insufficient for a patent. However, cDNA are not naturally occurring so tests using that technology can be patented.

The American Medical Association, which filed an amicus brief in support of invalidating the Myriad patents, praised the Court’s decision.

“Removing the patents on the building blocks of life ensures that scientific discovery and medical care based on insights into human DNA will remain freely accessible and widely disseminated, not hidden behind a vast thicket of exclusive rights,” Dr. Jeremy A. Lazarus, AMA president, said in a statement.

The American Civil Liberties Union, which joined the suit against Myriad, said the decision brings down a major barrier to patient care and medical innovation. "Because of this ruling, patients will have greater access to genetic testing and scientists can engage in research on these genes without fear of being sued," Sandra Park, senior staff attorney with the ACLU Women’s Rights Project, said in a statement.

The Supreme Court’s decision comes too late to have much of a practical impact on BRCA1 and BRCA2 testing, since Myriad’s 20-year exclusivity on the patents in dispute all expire by 2015.

[email protected]

On Twitter @MaryEllenNY

Private companies do not have the right to patent human genes, the U.S. Supreme Court has ruled.

In a unanimous decision issued on June 13, the high court ruled that a naturally occurring DNA segment is a "product of nature" and is not eligible for a patent simply because it has been isolated. But the court also ruled that synthetically created DNA known as complementary DNA (cDNA) can be granted a patent.

In Association for Molecular Pathology et al. v. Myriad Genetics, the high court considered the validity of patents held by Utah-based Myriad Genetics for the BRCA1 and BRCA2 genes, which are associated with an increased risk of breast and ovarian cancer.

Scientists at Myriad Genetics uncovered the location and sequence of the BRCA1 and BRCA2 genes in the mid-1990s. Since then, they have held the exclusive rights to the diagnostic testing for the mutations. But critics say the monopoly on testing held by Myriad is bad for patients because the test is expensive and they have no alternative confirmatory test.

"It is undisputed that Myriad did not create or alter any of the genetic information encoded in the BRCA1 and BRCA2 genes," Justice Clarence Thomas wrote in the court’s opinion. "Myriad’s principal contribution was uncovering the precise location and genetic sequence of the BRCA1 and BRCA2 genes within chromosomes 17 and 13."

The justices concluded that simply isolating genes and the information they encode from the surrounding genetic material is insufficient for a patent. However, cDNA are not naturally occurring so tests using that technology can be patented.

The American Medical Association, which filed an amicus brief in support of invalidating the Myriad patents, praised the Court’s decision.

“Removing the patents on the building blocks of life ensures that scientific discovery and medical care based on insights into human DNA will remain freely accessible and widely disseminated, not hidden behind a vast thicket of exclusive rights,” Dr. Jeremy A. Lazarus, AMA president, said in a statement.

The American Civil Liberties Union, which joined the suit against Myriad, said the decision brings down a major barrier to patient care and medical innovation. "Because of this ruling, patients will have greater access to genetic testing and scientists can engage in research on these genes without fear of being sued," Sandra Park, senior staff attorney with the ACLU Women’s Rights Project, said in a statement.

The Supreme Court’s decision comes too late to have much of a practical impact on BRCA1 and BRCA2 testing, since Myriad’s 20-year exclusivity on the patents in dispute all expire by 2015.

[email protected]

On Twitter @MaryEllenNY

PHOENIX – The longer a laparoscopic colectomy for cancer takes, the less its advantages over an open colectomy in terms of morbidity and mortality, researchers reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

A team led by Dr. Matthew Bailey, a surgery resident at the University of Kentucky in Lexington, queried the National Surgical Quality Improvement Program (NSQIP) database to identify more than 4,000 patients undergoing right colectomy because of colorectal malignancy.

Results showed that compared with their peers having an open operation lasting 3 hours or less, patients having a laparoscopic operation of this duration were less likely to develop complications and to die. However, when the operations lasted more than 3 hours, there was no longer any significant difference.

Within the laparoscopic group, patients were more likely to have a procedure lasting longer than 3 hours if they had recently received radiation therapy, were morbidly obese, or had peripheral vascular disease.

"We recommend that surgeons consider an open approach if the patient has risk factors for an operative duration greater than 3 hours," Dr. Bailey said. "We also recommend surgeons consider conversion to an open approach when it is anticipated that a laparoscopic right colectomy will exceed 3 hours."

Dr. Walter Peters of Columbia (Mo.) Surgical Associates, who comoderated the session, asked, "Were the laparoscopic procedures lasting more than 3 hours concentrated in a few institutions, or were they spread across the entire NSQIP database?"

The investigators did not assess the institutional distribution, and it may not be possible to tease that information out of NSQIP, Dr. Bailey replied.

Session attendee Dr. Eric Haas, of Colorectal Surgical Associates in Houston asked what percentage of patients had a conversion from laparoscopic to open procedures and whether analyses were conducted according to intention to treat.

"NSQIP unfortunately does not allow you to discern that, there’s no CPT [Current Procedural Terminology] code for conversion," Dr. Bailey said. "We can only assume that cases that were converted laparoscopic to open were most likely ultimately coded as open. So there was no way to perform an intent-to-treat analysis."

Dr. Haas also noted that surgeon experience with laparoscopy may have played a role. "In my own experience, certainly at the beginning of the learning curve phase, I would take 3, maybe 4 hours. And the one risk factor that you can’t put [in analyses] is surgeon," he said. "So were these 3-hour cases because of the learning curve, or were they true 3-hour cases because of the patient factors?"

The NSQIP database captures the surgeon who dictates the operative report and the level of training, the highest-level resident involved, and the specialty of the surgeon (although colorectal surgery is not among the options), according to Dr. Bailey. Still, it is generally not possible to determine who did all or most of the operation.

"We did look at operative time, and it was around 138 minutes, plus-minus, for a laparoscopic right colectomy, with the reported literature being around 187 minutes. So I’m not sure if the reported literature is dated or if, in these over 200 hospitals across the nation, this is realistic of current practice trends," he said.

"The study shows that patients are probably going to have increased complications with longer surgery, whether it’s laparoscopic or open," Dr. Timothy Geiger of Vanderbilt University Medical Center, Nashville, Tenn., the session’s other comoderator, said in an interview. "It was a good study, but it needs a little bit more in-depth look, especially at things like redosing of antibiotics, whether that is done in an appropriate manner. But otherwise, it’s a great kind of intro for us to look at this."

Giving some background to the research, Dr. Bailey noted, "The use of laparoscopy in colon cancer has been shown to be equivalent to open surgery in survival and oncologic outcomes. The question of whether operative time negatively impacts laparoscopic outcomes compared to open surgery outcomes requires further investigation if we are to endorse a laparoscopic approach regardless of procedure length. We postulated that there is an operative duration where the benefits of a laparoscopic approach are negated."

The investigators analyzed data from the NSQIP database for the years 2005 through 2010, identifying patients who had a right colectomy for cancer and excluding those treated on an emergent basis, or having secondary procedures other than enterolysis or mobilization of the splenic flexure.

Analyses were based on 2,141 patients in the laparoscopic group and 2,132 patients in the open group. Procedures lasted longer than 3 hours in 18% of the former and 11% of the latter.

Compared with the open group, the laparoscopic group was younger and had lower American Society of Anesthesiologists scores, higher serum albumin levels, and lower prothrombin time and platelet count.

In unadjusted analysis among patients whose operations lasted 3 hours or less, the laparoscopic group fared better than did the open group in terms of 30-day mortality (1.1% vs 2.6%, P less than .001), cardiopulmonary and cerebrovascular complications (5.4% vs. 8.4%, P less than .001), and infectious complications (9.2% vs. 13.3%, P less than .001).

In contrast, among patients whose operations lasted more than 3 hours, differences in these outcomes were not significant. If anything, there was a trend toward a higher rate of infectious complications with laparoscopy.

To assess the role of preoperative risk factors, the investigators looked at NSQIP estimates of morbidity and mortality for all gastrointestinal and abdominal surgery by operative duration and including 37 preoperative risk factors, and found patterns differing from those in the study cohort.

Specifically, these estimates suggested mortality was consistently lower for procedures lasting more then 3 hours, whether laparoscopic or open. And the risk of infectious complications was constant for each type and less for laparoscopy, regardless of the operative duration.

Thus, "there is something other than preoperative risk factors causing an increase in mortality" with longer operative time for laparoscopic procedures in the study cohort, said Dr. Bailey, who disclosed no conflicts of interest related to the research. Also, "the increased infectious complications that we demonstrated are not related to the morbidity risk."

Patients in the laparoscopic group had a significantly higher risk of surgery lasting more than 3 hours if they had recently received radiation therapy (odds ratio, 6.5), were morbidly obese (3.0), or had peripheral vascular disease (2.5).

Hospital length of stay was consistently shorter with the laparoscopic approach, regardless of how long the operation lasted, according to Dr. Bailey.

PHOENIX – The longer a laparoscopic colectomy for cancer takes, the less its advantages over an open colectomy in terms of morbidity and mortality, researchers reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

A team led by Dr. Matthew Bailey, a surgery resident at the University of Kentucky in Lexington, queried the National Surgical Quality Improvement Program (NSQIP) database to identify more than 4,000 patients undergoing right colectomy because of colorectal malignancy.

Results showed that compared with their peers having an open operation lasting 3 hours or less, patients having a laparoscopic operation of this duration were less likely to develop complications and to die. However, when the operations lasted more than 3 hours, there was no longer any significant difference.

Within the laparoscopic group, patients were more likely to have a procedure lasting longer than 3 hours if they had recently received radiation therapy, were morbidly obese, or had peripheral vascular disease.

"We recommend that surgeons consider an open approach if the patient has risk factors for an operative duration greater than 3 hours," Dr. Bailey said. "We also recommend surgeons consider conversion to an open approach when it is anticipated that a laparoscopic right colectomy will exceed 3 hours."

Dr. Walter Peters of Columbia (Mo.) Surgical Associates, who comoderated the session, asked, "Were the laparoscopic procedures lasting more than 3 hours concentrated in a few institutions, or were they spread across the entire NSQIP database?"

The investigators did not assess the institutional distribution, and it may not be possible to tease that information out of NSQIP, Dr. Bailey replied.

Session attendee Dr. Eric Haas, of Colorectal Surgical Associates in Houston asked what percentage of patients had a conversion from laparoscopic to open procedures and whether analyses were conducted according to intention to treat.

"NSQIP unfortunately does not allow you to discern that, there’s no CPT [Current Procedural Terminology] code for conversion," Dr. Bailey said. "We can only assume that cases that were converted laparoscopic to open were most likely ultimately coded as open. So there was no way to perform an intent-to-treat analysis."

Dr. Haas also noted that surgeon experience with laparoscopy may have played a role. "In my own experience, certainly at the beginning of the learning curve phase, I would take 3, maybe 4 hours. And the one risk factor that you can’t put [in analyses] is surgeon," he said. "So were these 3-hour cases because of the learning curve, or were they true 3-hour cases because of the patient factors?"

The NSQIP database captures the surgeon who dictates the operative report and the level of training, the highest-level resident involved, and the specialty of the surgeon (although colorectal surgery is not among the options), according to Dr. Bailey. Still, it is generally not possible to determine who did all or most of the operation.

"We did look at operative time, and it was around 138 minutes, plus-minus, for a laparoscopic right colectomy, with the reported literature being around 187 minutes. So I’m not sure if the reported literature is dated or if, in these over 200 hospitals across the nation, this is realistic of current practice trends," he said.

"The study shows that patients are probably going to have increased complications with longer surgery, whether it’s laparoscopic or open," Dr. Timothy Geiger of Vanderbilt University Medical Center, Nashville, Tenn., the session’s other comoderator, said in an interview. "It was a good study, but it needs a little bit more in-depth look, especially at things like redosing of antibiotics, whether that is done in an appropriate manner. But otherwise, it’s a great kind of intro for us to look at this."

Giving some background to the research, Dr. Bailey noted, "The use of laparoscopy in colon cancer has been shown to be equivalent to open surgery in survival and oncologic outcomes. The question of whether operative time negatively impacts laparoscopic outcomes compared to open surgery outcomes requires further investigation if we are to endorse a laparoscopic approach regardless of procedure length. We postulated that there is an operative duration where the benefits of a laparoscopic approach are negated."

The investigators analyzed data from the NSQIP database for the years 2005 through 2010, identifying patients who had a right colectomy for cancer and excluding those treated on an emergent basis, or having secondary procedures other than enterolysis or mobilization of the splenic flexure.

Analyses were based on 2,141 patients in the laparoscopic group and 2,132 patients in the open group. Procedures lasted longer than 3 hours in 18% of the former and 11% of the latter.

Compared with the open group, the laparoscopic group was younger and had lower American Society of Anesthesiologists scores, higher serum albumin levels, and lower prothrombin time and platelet count.

In unadjusted analysis among patients whose operations lasted 3 hours or less, the laparoscopic group fared better than did the open group in terms of 30-day mortality (1.1% vs 2.6%, P less than .001), cardiopulmonary and cerebrovascular complications (5.4% vs. 8.4%, P less than .001), and infectious complications (9.2% vs. 13.3%, P less than .001).

In contrast, among patients whose operations lasted more than 3 hours, differences in these outcomes were not significant. If anything, there was a trend toward a higher rate of infectious complications with laparoscopy.

To assess the role of preoperative risk factors, the investigators looked at NSQIP estimates of morbidity and mortality for all gastrointestinal and abdominal surgery by operative duration and including 37 preoperative risk factors, and found patterns differing from those in the study cohort.

Specifically, these estimates suggested mortality was consistently lower for procedures lasting more then 3 hours, whether laparoscopic or open. And the risk of infectious complications was constant for each type and less for laparoscopy, regardless of the operative duration.

Thus, "there is something other than preoperative risk factors causing an increase in mortality" with longer operative time for laparoscopic procedures in the study cohort, said Dr. Bailey, who disclosed no conflicts of interest related to the research. Also, "the increased infectious complications that we demonstrated are not related to the morbidity risk."

Patients in the laparoscopic group had a significantly higher risk of surgery lasting more than 3 hours if they had recently received radiation therapy (odds ratio, 6.5), were morbidly obese (3.0), or had peripheral vascular disease (2.5).

Hospital length of stay was consistently shorter with the laparoscopic approach, regardless of how long the operation lasted, according to Dr. Bailey.

PHOENIX – The longer a laparoscopic colectomy for cancer takes, the less its advantages over an open colectomy in terms of morbidity and mortality, researchers reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

A team led by Dr. Matthew Bailey, a surgery resident at the University of Kentucky in Lexington, queried the National Surgical Quality Improvement Program (NSQIP) database to identify more than 4,000 patients undergoing right colectomy because of colorectal malignancy.

Results showed that compared with their peers having an open operation lasting 3 hours or less, patients having a laparoscopic operation of this duration were less likely to develop complications and to die. However, when the operations lasted more than 3 hours, there was no longer any significant difference.

Within the laparoscopic group, patients were more likely to have a procedure lasting longer than 3 hours if they had recently received radiation therapy, were morbidly obese, or had peripheral vascular disease.

"We recommend that surgeons consider an open approach if the patient has risk factors for an operative duration greater than 3 hours," Dr. Bailey said. "We also recommend surgeons consider conversion to an open approach when it is anticipated that a laparoscopic right colectomy will exceed 3 hours."

Dr. Walter Peters of Columbia (Mo.) Surgical Associates, who comoderated the session, asked, "Were the laparoscopic procedures lasting more than 3 hours concentrated in a few institutions, or were they spread across the entire NSQIP database?"

The investigators did not assess the institutional distribution, and it may not be possible to tease that information out of NSQIP, Dr. Bailey replied.

Session attendee Dr. Eric Haas, of Colorectal Surgical Associates in Houston asked what percentage of patients had a conversion from laparoscopic to open procedures and whether analyses were conducted according to intention to treat.

"NSQIP unfortunately does not allow you to discern that, there’s no CPT [Current Procedural Terminology] code for conversion," Dr. Bailey said. "We can only assume that cases that were converted laparoscopic to open were most likely ultimately coded as open. So there was no way to perform an intent-to-treat analysis."

Dr. Haas also noted that surgeon experience with laparoscopy may have played a role. "In my own experience, certainly at the beginning of the learning curve phase, I would take 3, maybe 4 hours. And the one risk factor that you can’t put [in analyses] is surgeon," he said. "So were these 3-hour cases because of the learning curve, or were they true 3-hour cases because of the patient factors?"

The NSQIP database captures the surgeon who dictates the operative report and the level of training, the highest-level resident involved, and the specialty of the surgeon (although colorectal surgery is not among the options), according to Dr. Bailey. Still, it is generally not possible to determine who did all or most of the operation.

"We did look at operative time, and it was around 138 minutes, plus-minus, for a laparoscopic right colectomy, with the reported literature being around 187 minutes. So I’m not sure if the reported literature is dated or if, in these over 200 hospitals across the nation, this is realistic of current practice trends," he said.

"The study shows that patients are probably going to have increased complications with longer surgery, whether it’s laparoscopic or open," Dr. Timothy Geiger of Vanderbilt University Medical Center, Nashville, Tenn., the session’s other comoderator, said in an interview. "It was a good study, but it needs a little bit more in-depth look, especially at things like redosing of antibiotics, whether that is done in an appropriate manner. But otherwise, it’s a great kind of intro for us to look at this."

Giving some background to the research, Dr. Bailey noted, "The use of laparoscopy in colon cancer has been shown to be equivalent to open surgery in survival and oncologic outcomes. The question of whether operative time negatively impacts laparoscopic outcomes compared to open surgery outcomes requires further investigation if we are to endorse a laparoscopic approach regardless of procedure length. We postulated that there is an operative duration where the benefits of a laparoscopic approach are negated."

The investigators analyzed data from the NSQIP database for the years 2005 through 2010, identifying patients who had a right colectomy for cancer and excluding those treated on an emergent basis, or having secondary procedures other than enterolysis or mobilization of the splenic flexure.

Analyses were based on 2,141 patients in the laparoscopic group and 2,132 patients in the open group. Procedures lasted longer than 3 hours in 18% of the former and 11% of the latter.

Compared with the open group, the laparoscopic group was younger and had lower American Society of Anesthesiologists scores, higher serum albumin levels, and lower prothrombin time and platelet count.

In unadjusted analysis among patients whose operations lasted 3 hours or less, the laparoscopic group fared better than did the open group in terms of 30-day mortality (1.1% vs 2.6%, P less than .001), cardiopulmonary and cerebrovascular complications (5.4% vs. 8.4%, P less than .001), and infectious complications (9.2% vs. 13.3%, P less than .001).

In contrast, among patients whose operations lasted more than 3 hours, differences in these outcomes were not significant. If anything, there was a trend toward a higher rate of infectious complications with laparoscopy.

To assess the role of preoperative risk factors, the investigators looked at NSQIP estimates of morbidity and mortality for all gastrointestinal and abdominal surgery by operative duration and including 37 preoperative risk factors, and found patterns differing from those in the study cohort.

Specifically, these estimates suggested mortality was consistently lower for procedures lasting more then 3 hours, whether laparoscopic or open. And the risk of infectious complications was constant for each type and less for laparoscopy, regardless of the operative duration.

Thus, "there is something other than preoperative risk factors causing an increase in mortality" with longer operative time for laparoscopic procedures in the study cohort, said Dr. Bailey, who disclosed no conflicts of interest related to the research. Also, "the increased infectious complications that we demonstrated are not related to the morbidity risk."

Patients in the laparoscopic group had a significantly higher risk of surgery lasting more than 3 hours if they had recently received radiation therapy (odds ratio, 6.5), were morbidly obese (3.0), or had peripheral vascular disease (2.5).

Hospital length of stay was consistently shorter with the laparoscopic approach, regardless of how long the operation lasted, according to Dr. Bailey.

ORLANDO – The rates of adjuvant therapy and the use of surgery for resectable stage I and II pancreatic cancer have remained lower than expected, while nonsurgical therapy for the stage II disease has significantly increased, according to an analysis of a national cancer database.

The analysis showed that more patients with stage I and II resectable disease are receiving chemotherapy in addition to surgery, and fewer are undergoing chemoradiation.

But, "despite all the evidence in favor of adjuvant therapy, its use remains unacceptably low," said Siavash Raigani, a second-year medical student at Case Western Reserve University, Cleveland, who presented the abstract at the annual Digestive Disease Week.

Depending on hospital setting and stage, somewhere between one-third and two-thirds of the patients did not receive adjuvant therapy, Mr. Raigani reported.

The analysis also showed that nonsurgical therapy for the disease continues to be used at a high rate, with 43% of stage I and 60% of stage II pancreatic cancer patients undergoing surgery, "which is lower than expected," said Mr. Raigani.

The analysis reflects what previous studies have shown.

In 2007, Dr. Karl Y. Bilimoria and his colleagues analyzed the National Cancer Data Base (NCDB) for the years between 1995 and 2004 and found "the striking underuse of pancreatectomy in the United States. Of early stage pancreatic cancer patients without any identifiable contraindications, 38.2% failed to undergo surgery." (Ann. Surg. 2007;246:173-80).

"What’s more startling is that there has been no improvement in the years since Dr. Bilimoria brought this to our attention several years ago and the authors should be commended for not letting this issue rest," said Dr. John D. Allendorf of Columbia University Medical Center, New York, who called Mr. Raigani’s analysis "impressive."

Mr. Raigani and his colleagues analyzed the NCDB, selecting 47,000 patients diagnosed with stage I and II pancreatic cancer between 2003 and 2010. They analyzed the database on initial treatment – surgery alone, surgery plus chemotherapy, or surgery plus chemoradiation – and collected data on the hospital setting, community hospital or teaching-research hospital.

Results showed that there was no significant change in surgical resection rates for stage I pancreatic cancer during the study period, but there was a significant different between the two hospital settings, with 53% of patients receiving surgery in teaching hospitals, compared with 32% in community hospitals in 2010.

Similarly, the use of surgery for treatment of stage II disease didn’t change significantly over time, but a significant difference remained between teaching hospitals (60%) and community hospitals (52%) in 2010.

One issue in pancreatic cancer keeps coming up over and over again, said Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa. "We know who is a resectable candidate based on pathologic criteria, but what we don’t know is should they be getting an operation based on associated comorbidities," he said.

The other issue has to do with where patients are getting these operations done. "The teaching hospitals or high-volume hospitals are all going to have lower mortalities. But the opposite side of that coin is if you’re at a smaller hospital, where your predicted mortality is higher, perhaps by not operating on those patient, you’re actually saving lives, because you’re not subjecting them to postoperative mortality just because of that operation," said Dr. Velanovich, who moderated the abstract session.

Meanwhile, the use of chemotherapy plus surgery for treatment of stage I and II disease increased more than twofold at both types of hospital (P less than .0001). In contrast, use of chemoradiation plus surgery decreased by roughly 30% in both types of hospitals (P less than .05), the authors reported.

The analysis showed that in community hospitals, the rate of chemotherapy for patients with stage I disease receiving surgery increased from 5% to 14%, while the chemoradiation rates decreased from 34% to 19% during the study period. For stage II patients, the rate of chemotherapy increased from 9% to 27%, and chemoradiation rates decreased from 53% to 39% (P less than .0001 for all).

In teaching hospitals, the rate of chemotherapy for stage I patients increased from 6% to 16%, while the chemoradiation rate decreased from 30% to 19% between 2003 and 2010. For stage II patients, the rate of chemotherapy increased from 9% to 32%, while chemoradiation rates decreased from 42% to 30% (P less than .0001 for all).

Mr. Raigani said the increase in the use of chemotherapy concurrent with the decrease in the use of chemoradiation in addition to surgery correlates temporally with the publication of more trials examining chemotherapy only. However, the use of adjuvant chemoradiation was still more common in the United States as of 2010. Among stage I patients, 44% received chemotherapy, compared with 56% receiving chemoradiation. In stage II patients, those rates were 47% and 53%, respectively.

Meanwhile, the use of surgery alone as first-course treatment for stage II pancreatic cancer decreased by nearly 25% at both hospital settings (P less than .0001 for both). There was no significant change in rates of surgery alone in stage I disease.

Nonsurgical treatment of stage II disease was "surprisingly high," the authors reported. It increased from 31% to 36% at teaching-research hospitals and from 41% to 43% at community hospitals (P less than .0001). There was no significant change in the use of nonsurgical therapy for stage I cancer at either hospital setting during the analysis period, although the difference based on hospital setting remained significant (44% in teaching hospitals vs. 63% in community hospitals, P less than .0001).

Mr. Raigani said some of the possible factors leading to nonsurgical therapy – in addition to age, race, and insurance type – are lack of referral because of the pessimistic view on pancreatic cancer survival and an evaluation by a surgeon inexperienced in pancreas surgery.

The analysis had several limitations, according to the authors. The NCDB provides data in aggregate form and not at an individual level, which limits the predictive factor analysis. Also, NDCB does not distinguish between adjuvant and neoadjuvant therapy.

Mr. Raigani and Dr. Velanovich had no disclosures. Dr. Allendorf is a consultant for Covidien.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – The rates of adjuvant therapy and the use of surgery for resectable stage I and II pancreatic cancer have remained lower than expected, while nonsurgical therapy for the stage II disease has significantly increased, according to an analysis of a national cancer database.

The analysis showed that more patients with stage I and II resectable disease are receiving chemotherapy in addition to surgery, and fewer are undergoing chemoradiation.

But, "despite all the evidence in favor of adjuvant therapy, its use remains unacceptably low," said Siavash Raigani, a second-year medical student at Case Western Reserve University, Cleveland, who presented the abstract at the annual Digestive Disease Week.

Depending on hospital setting and stage, somewhere between one-third and two-thirds of the patients did not receive adjuvant therapy, Mr. Raigani reported.

The analysis also showed that nonsurgical therapy for the disease continues to be used at a high rate, with 43% of stage I and 60% of stage II pancreatic cancer patients undergoing surgery, "which is lower than expected," said Mr. Raigani.

The analysis reflects what previous studies have shown.

In 2007, Dr. Karl Y. Bilimoria and his colleagues analyzed the National Cancer Data Base (NCDB) for the years between 1995 and 2004 and found "the striking underuse of pancreatectomy in the United States. Of early stage pancreatic cancer patients without any identifiable contraindications, 38.2% failed to undergo surgery." (Ann. Surg. 2007;246:173-80).

"What’s more startling is that there has been no improvement in the years since Dr. Bilimoria brought this to our attention several years ago and the authors should be commended for not letting this issue rest," said Dr. John D. Allendorf of Columbia University Medical Center, New York, who called Mr. Raigani’s analysis "impressive."

Mr. Raigani and his colleagues analyzed the NCDB, selecting 47,000 patients diagnosed with stage I and II pancreatic cancer between 2003 and 2010. They analyzed the database on initial treatment – surgery alone, surgery plus chemotherapy, or surgery plus chemoradiation – and collected data on the hospital setting, community hospital or teaching-research hospital.

Results showed that there was no significant change in surgical resection rates for stage I pancreatic cancer during the study period, but there was a significant different between the two hospital settings, with 53% of patients receiving surgery in teaching hospitals, compared with 32% in community hospitals in 2010.

Similarly, the use of surgery for treatment of stage II disease didn’t change significantly over time, but a significant difference remained between teaching hospitals (60%) and community hospitals (52%) in 2010.

One issue in pancreatic cancer keeps coming up over and over again, said Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa. "We know who is a resectable candidate based on pathologic criteria, but what we don’t know is should they be getting an operation based on associated comorbidities," he said.

The other issue has to do with where patients are getting these operations done. "The teaching hospitals or high-volume hospitals are all going to have lower mortalities. But the opposite side of that coin is if you’re at a smaller hospital, where your predicted mortality is higher, perhaps by not operating on those patient, you’re actually saving lives, because you’re not subjecting them to postoperative mortality just because of that operation," said Dr. Velanovich, who moderated the abstract session.

Meanwhile, the use of chemotherapy plus surgery for treatment of stage I and II disease increased more than twofold at both types of hospital (P less than .0001). In contrast, use of chemoradiation plus surgery decreased by roughly 30% in both types of hospitals (P less than .05), the authors reported.

The analysis showed that in community hospitals, the rate of chemotherapy for patients with stage I disease receiving surgery increased from 5% to 14%, while the chemoradiation rates decreased from 34% to 19% during the study period. For stage II patients, the rate of chemotherapy increased from 9% to 27%, and chemoradiation rates decreased from 53% to 39% (P less than .0001 for all).

In teaching hospitals, the rate of chemotherapy for stage I patients increased from 6% to 16%, while the chemoradiation rate decreased from 30% to 19% between 2003 and 2010. For stage II patients, the rate of chemotherapy increased from 9% to 32%, while chemoradiation rates decreased from 42% to 30% (P less than .0001 for all).

Mr. Raigani said the increase in the use of chemotherapy concurrent with the decrease in the use of chemoradiation in addition to surgery correlates temporally with the publication of more trials examining chemotherapy only. However, the use of adjuvant chemoradiation was still more common in the United States as of 2010. Among stage I patients, 44% received chemotherapy, compared with 56% receiving chemoradiation. In stage II patients, those rates were 47% and 53%, respectively.

Meanwhile, the use of surgery alone as first-course treatment for stage II pancreatic cancer decreased by nearly 25% at both hospital settings (P less than .0001 for both). There was no significant change in rates of surgery alone in stage I disease.

Nonsurgical treatment of stage II disease was "surprisingly high," the authors reported. It increased from 31% to 36% at teaching-research hospitals and from 41% to 43% at community hospitals (P less than .0001). There was no significant change in the use of nonsurgical therapy for stage I cancer at either hospital setting during the analysis period, although the difference based on hospital setting remained significant (44% in teaching hospitals vs. 63% in community hospitals, P less than .0001).

Mr. Raigani said some of the possible factors leading to nonsurgical therapy – in addition to age, race, and insurance type – are lack of referral because of the pessimistic view on pancreatic cancer survival and an evaluation by a surgeon inexperienced in pancreas surgery.

The analysis had several limitations, according to the authors. The NCDB provides data in aggregate form and not at an individual level, which limits the predictive factor analysis. Also, NDCB does not distinguish between adjuvant and neoadjuvant therapy.

Mr. Raigani and Dr. Velanovich had no disclosures. Dr. Allendorf is a consultant for Covidien.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – The rates of adjuvant therapy and the use of surgery for resectable stage I and II pancreatic cancer have remained lower than expected, while nonsurgical therapy for the stage II disease has significantly increased, according to an analysis of a national cancer database.

The analysis showed that more patients with stage I and II resectable disease are receiving chemotherapy in addition to surgery, and fewer are undergoing chemoradiation.

But, "despite all the evidence in favor of adjuvant therapy, its use remains unacceptably low," said Siavash Raigani, a second-year medical student at Case Western Reserve University, Cleveland, who presented the abstract at the annual Digestive Disease Week.

Depending on hospital setting and stage, somewhere between one-third and two-thirds of the patients did not receive adjuvant therapy, Mr. Raigani reported.

The analysis also showed that nonsurgical therapy for the disease continues to be used at a high rate, with 43% of stage I and 60% of stage II pancreatic cancer patients undergoing surgery, "which is lower than expected," said Mr. Raigani.

The analysis reflects what previous studies have shown.

In 2007, Dr. Karl Y. Bilimoria and his colleagues analyzed the National Cancer Data Base (NCDB) for the years between 1995 and 2004 and found "the striking underuse of pancreatectomy in the United States. Of early stage pancreatic cancer patients without any identifiable contraindications, 38.2% failed to undergo surgery." (Ann. Surg. 2007;246:173-80).

"What’s more startling is that there has been no improvement in the years since Dr. Bilimoria brought this to our attention several years ago and the authors should be commended for not letting this issue rest," said Dr. John D. Allendorf of Columbia University Medical Center, New York, who called Mr. Raigani’s analysis "impressive."

Mr. Raigani and his colleagues analyzed the NCDB, selecting 47,000 patients diagnosed with stage I and II pancreatic cancer between 2003 and 2010. They analyzed the database on initial treatment – surgery alone, surgery plus chemotherapy, or surgery plus chemoradiation – and collected data on the hospital setting, community hospital or teaching-research hospital.

Results showed that there was no significant change in surgical resection rates for stage I pancreatic cancer during the study period, but there was a significant different between the two hospital settings, with 53% of patients receiving surgery in teaching hospitals, compared with 32% in community hospitals in 2010.

Similarly, the use of surgery for treatment of stage II disease didn’t change significantly over time, but a significant difference remained between teaching hospitals (60%) and community hospitals (52%) in 2010.

One issue in pancreatic cancer keeps coming up over and over again, said Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa. "We know who is a resectable candidate based on pathologic criteria, but what we don’t know is should they be getting an operation based on associated comorbidities," he said.

The other issue has to do with where patients are getting these operations done. "The teaching hospitals or high-volume hospitals are all going to have lower mortalities. But the opposite side of that coin is if you’re at a smaller hospital, where your predicted mortality is higher, perhaps by not operating on those patient, you’re actually saving lives, because you’re not subjecting them to postoperative mortality just because of that operation," said Dr. Velanovich, who moderated the abstract session.

Meanwhile, the use of chemotherapy plus surgery for treatment of stage I and II disease increased more than twofold at both types of hospital (P less than .0001). In contrast, use of chemoradiation plus surgery decreased by roughly 30% in both types of hospitals (P less than .05), the authors reported.

The analysis showed that in community hospitals, the rate of chemotherapy for patients with stage I disease receiving surgery increased from 5% to 14%, while the chemoradiation rates decreased from 34% to 19% during the study period. For stage II patients, the rate of chemotherapy increased from 9% to 27%, and chemoradiation rates decreased from 53% to 39% (P less than .0001 for all).

In teaching hospitals, the rate of chemotherapy for stage I patients increased from 6% to 16%, while the chemoradiation rate decreased from 30% to 19% between 2003 and 2010. For stage II patients, the rate of chemotherapy increased from 9% to 32%, while chemoradiation rates decreased from 42% to 30% (P less than .0001 for all).

Mr. Raigani said the increase in the use of chemotherapy concurrent with the decrease in the use of chemoradiation in addition to surgery correlates temporally with the publication of more trials examining chemotherapy only. However, the use of adjuvant chemoradiation was still more common in the United States as of 2010. Among stage I patients, 44% received chemotherapy, compared with 56% receiving chemoradiation. In stage II patients, those rates were 47% and 53%, respectively.

Meanwhile, the use of surgery alone as first-course treatment for stage II pancreatic cancer decreased by nearly 25% at both hospital settings (P less than .0001 for both). There was no significant change in rates of surgery alone in stage I disease.

Nonsurgical treatment of stage II disease was "surprisingly high," the authors reported. It increased from 31% to 36% at teaching-research hospitals and from 41% to 43% at community hospitals (P less than .0001). There was no significant change in the use of nonsurgical therapy for stage I cancer at either hospital setting during the analysis period, although the difference based on hospital setting remained significant (44% in teaching hospitals vs. 63% in community hospitals, P less than .0001).

Mr. Raigani said some of the possible factors leading to nonsurgical therapy – in addition to age, race, and insurance type – are lack of referral because of the pessimistic view on pancreatic cancer survival and an evaluation by a surgeon inexperienced in pancreas surgery.

The analysis had several limitations, according to the authors. The NCDB provides data in aggregate form and not at an individual level, which limits the predictive factor analysis. Also, NDCB does not distinguish between adjuvant and neoadjuvant therapy.

Mr. Raigani and Dr. Velanovich had no disclosures. Dr. Allendorf is a consultant for Covidien.

[email protected]

On Twitter @NaseemSMiller