Surgical Oncology

SAN FRANCISCO – Patients with triple-negative breast cancer had no higher risk for metastases in the lymph nodes as compared with patients whose breast cancer was not triple-negative, a review of 2,957 cases found.

The study included patients with invasive breast cancer treated surgically between January 2000 and May 2012. Immunohistochemical identification of markers showed that 2,201 (74%) had luminal A subtype breast cancer (estrogen receptor– and progesterone receptor–positive and HER2 negative), 344 (12%) had luminal B subtype (all three markers positive), 144 (5%) were HER2 positive but estrogen and progesterone receptors–negative, and 278 (9%) were negative for all three markers (the triple-negative group). The study excluded men, patients treated with neoadjuvant therapy, patients with distant metastases, and those who did not undergo nodal sampling.

At least one positive lymph node was found in 35% of patients, and four or more positive nodes were found in 10% of patients.

Patients in the triple-negative group were significantly younger at diagnosis and significantly more likely to have higher-grade tumors, compared with patients with other subtypes of breast cancer. Grade 3 cancer was seen in 87% of the triple-negative group and in 27% of the luminal A group, 51% of the luminal B group, and 80% of the HER2-positive group, Dr. Alexandra Gangi and her associates reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

In multivariant analyses, younger age, higher tumor grade, larger tumor size, and lymphovascular invasion predicted increased likelihood of lymph node metastases. The triple-negative phenotype predicted neither a higher risk for lymph node positivity nor a greater likelihood of having four or more positive lymph nodes, which was found in 9% of the triple-negative group, 9% of the luminal A group, 14% of the luminal B group, and 19% of the HER2-positive group, reported Dr. Gangi of Cedars-Sinai Hospital, Los Angeles.

The likelihood of lymph node metastases was 50% higher in patients younger than 50 years as compared with older patients, 70% higher with grade 2 cancer as compared with grade 1 cancer, and 90% higher with grade 3 cancer as compared with grade 1 cancer. Lymphovascular invasion increased the likelihood of lymph node involvement four-fold. The risk of lymph node metastases was three times higher in patients with stage T2 breast cancer and 11 times higher in patients with stage T3 disease as compared with those with stage T1 breast cancer. All of these differences were statistically significant.

The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Dr. Gangi reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Patients with triple-negative breast cancer had no higher risk for metastases in the lymph nodes as compared with patients whose breast cancer was not triple-negative, a review of 2,957 cases found.

The study included patients with invasive breast cancer treated surgically between January 2000 and May 2012. Immunohistochemical identification of markers showed that 2,201 (74%) had luminal A subtype breast cancer (estrogen receptor– and progesterone receptor–positive and HER2 negative), 344 (12%) had luminal B subtype (all three markers positive), 144 (5%) were HER2 positive but estrogen and progesterone receptors–negative, and 278 (9%) were negative for all three markers (the triple-negative group). The study excluded men, patients treated with neoadjuvant therapy, patients with distant metastases, and those who did not undergo nodal sampling.

At least one positive lymph node was found in 35% of patients, and four or more positive nodes were found in 10% of patients.

Patients in the triple-negative group were significantly younger at diagnosis and significantly more likely to have higher-grade tumors, compared with patients with other subtypes of breast cancer. Grade 3 cancer was seen in 87% of the triple-negative group and in 27% of the luminal A group, 51% of the luminal B group, and 80% of the HER2-positive group, Dr. Alexandra Gangi and her associates reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

In multivariant analyses, younger age, higher tumor grade, larger tumor size, and lymphovascular invasion predicted increased likelihood of lymph node metastases. The triple-negative phenotype predicted neither a higher risk for lymph node positivity nor a greater likelihood of having four or more positive lymph nodes, which was found in 9% of the triple-negative group, 9% of the luminal A group, 14% of the luminal B group, and 19% of the HER2-positive group, reported Dr. Gangi of Cedars-Sinai Hospital, Los Angeles.

The likelihood of lymph node metastases was 50% higher in patients younger than 50 years as compared with older patients, 70% higher with grade 2 cancer as compared with grade 1 cancer, and 90% higher with grade 3 cancer as compared with grade 1 cancer. Lymphovascular invasion increased the likelihood of lymph node involvement four-fold. The risk of lymph node metastases was three times higher in patients with stage T2 breast cancer and 11 times higher in patients with stage T3 disease as compared with those with stage T1 breast cancer. All of these differences were statistically significant.

The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Dr. Gangi reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Patients with triple-negative breast cancer had no higher risk for metastases in the lymph nodes as compared with patients whose breast cancer was not triple-negative, a review of 2,957 cases found.

The study included patients with invasive breast cancer treated surgically between January 2000 and May 2012. Immunohistochemical identification of markers showed that 2,201 (74%) had luminal A subtype breast cancer (estrogen receptor– and progesterone receptor–positive and HER2 negative), 344 (12%) had luminal B subtype (all three markers positive), 144 (5%) were HER2 positive but estrogen and progesterone receptors–negative, and 278 (9%) were negative for all three markers (the triple-negative group). The study excluded men, patients treated with neoadjuvant therapy, patients with distant metastases, and those who did not undergo nodal sampling.

At least one positive lymph node was found in 35% of patients, and four or more positive nodes were found in 10% of patients.

Patients in the triple-negative group were significantly younger at diagnosis and significantly more likely to have higher-grade tumors, compared with patients with other subtypes of breast cancer. Grade 3 cancer was seen in 87% of the triple-negative group and in 27% of the luminal A group, 51% of the luminal B group, and 80% of the HER2-positive group, Dr. Alexandra Gangi and her associates reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

In multivariant analyses, younger age, higher tumor grade, larger tumor size, and lymphovascular invasion predicted increased likelihood of lymph node metastases. The triple-negative phenotype predicted neither a higher risk for lymph node positivity nor a greater likelihood of having four or more positive lymph nodes, which was found in 9% of the triple-negative group, 9% of the luminal A group, 14% of the luminal B group, and 19% of the HER2-positive group, reported Dr. Gangi of Cedars-Sinai Hospital, Los Angeles.

The likelihood of lymph node metastases was 50% higher in patients younger than 50 years as compared with older patients, 70% higher with grade 2 cancer as compared with grade 1 cancer, and 90% higher with grade 3 cancer as compared with grade 1 cancer. Lymphovascular invasion increased the likelihood of lymph node involvement four-fold. The risk of lymph node metastases was three times higher in patients with stage T2 breast cancer and 11 times higher in patients with stage T3 disease as compared with those with stage T1 breast cancer. All of these differences were statistically significant.

The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.

Dr. Gangi reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Fear and a desire for control over breast cancer may drive women to choose mastectomy over less aggressive management, a qualitative study of 30 patients has shown.

She interviewed 15 women who were candidates for breast-conserving surgery but chose unilateral mastectomy and 15 average-risk women who were candidates for surgery in one breast but also chose prophylactic contralateral mastectomy.

Fear led patients to overestimate their risk of local recurrence and contralateral cancer and to misunderstand their odds of dying of breast cancer. The fear combined with wanting to eliminate and control the risk of cancer resulted in the patient choosing mastectomy or bilateral mastectomy, factors that probably are contributing to increasing rates of mastectomy for early-stage breast cancer, Dr. Andrea M. Covelli reported in a poster at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

When deciding on treatment, the women sought out multiple sources of information but gave greatest weight to the experiences of people they’d known with breast cancer and information from breast cancer survivors. It was the patients, not clinicians, who raised the topic of contralateral prophylactic mastectomy, which some patients chose in an attempt to eliminate any risk of contralateral breast cancer.

"More surgery is seen as more control," reported Dr. Covelli of the University of Toronto. A better understanding of patients’ decision process may help physicians be better able to discuss issues important to their patients in making treatment decisions.

Dr. Covelli conducted semistructured one-on-one interviews with patients with early-stage breast cancer chosen from five hospitals in the greater Toronto area to represent a variety of ages and ethnicities. Twelve were treated at academic cancer centers, 6 were treated at academic noncancer centers, and 12 were treated at community medical centers.

She identified several themes in the results. The diagnosis brought shock and fear. Patients discussed both breast-conserving surgery and unilateral mastectomy during their surgical consultation, during which the physician discouraged contralateral prophylactic mastectomy. Patients relied on multiple sources of information in their decision making, but the greatest impact came from the experiences of others with breast cancer, she reported.

Women who chose unilateral mastectomy did so most often out of fear of recurrence and the misguided notion that it would give them a survival advantage. Occasionally, they chose unilateral mastectomy to avoid radiation therapy.

Women who also chose contralateral prophylactic mastectomy initiated discussions about it, which their surgeons then discouraged. These patients chose it anyway because they overestimated the risk of contralateral cancer and mistakenly believed it would improve their chance of survival. Occasionally they added contralateral prophylactic mastectomy for body symmetry.

In essence, patients chose these more aggressive surgeries because they were actively trying to control their cancer outcomes and ensure that they "never have to go through this again," Dr. Covelli said.

The study cohort had a mean age of 55 years, with ages ranging from 36 to 84 years.

Dr. Covelli has received funding from Roche Canada and the Canadian Breast Cancer Foundation Physician Fellowship Award.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Fear and a desire for control over breast cancer may drive women to choose mastectomy over less aggressive management, a qualitative study of 30 patients has shown.

She interviewed 15 women who were candidates for breast-conserving surgery but chose unilateral mastectomy and 15 average-risk women who were candidates for surgery in one breast but also chose prophylactic contralateral mastectomy.

Fear led patients to overestimate their risk of local recurrence and contralateral cancer and to misunderstand their odds of dying of breast cancer. The fear combined with wanting to eliminate and control the risk of cancer resulted in the patient choosing mastectomy or bilateral mastectomy, factors that probably are contributing to increasing rates of mastectomy for early-stage breast cancer, Dr. Andrea M. Covelli reported in a poster at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

When deciding on treatment, the women sought out multiple sources of information but gave greatest weight to the experiences of people they’d known with breast cancer and information from breast cancer survivors. It was the patients, not clinicians, who raised the topic of contralateral prophylactic mastectomy, which some patients chose in an attempt to eliminate any risk of contralateral breast cancer.

"More surgery is seen as more control," reported Dr. Covelli of the University of Toronto. A better understanding of patients’ decision process may help physicians be better able to discuss issues important to their patients in making treatment decisions.

Dr. Covelli conducted semistructured one-on-one interviews with patients with early-stage breast cancer chosen from five hospitals in the greater Toronto area to represent a variety of ages and ethnicities. Twelve were treated at academic cancer centers, 6 were treated at academic noncancer centers, and 12 were treated at community medical centers.

She identified several themes in the results. The diagnosis brought shock and fear. Patients discussed both breast-conserving surgery and unilateral mastectomy during their surgical consultation, during which the physician discouraged contralateral prophylactic mastectomy. Patients relied on multiple sources of information in their decision making, but the greatest impact came from the experiences of others with breast cancer, she reported.

Women who chose unilateral mastectomy did so most often out of fear of recurrence and the misguided notion that it would give them a survival advantage. Occasionally, they chose unilateral mastectomy to avoid radiation therapy.

Women who also chose contralateral prophylactic mastectomy initiated discussions about it, which their surgeons then discouraged. These patients chose it anyway because they overestimated the risk of contralateral cancer and mistakenly believed it would improve their chance of survival. Occasionally they added contralateral prophylactic mastectomy for body symmetry.

In essence, patients chose these more aggressive surgeries because they were actively trying to control their cancer outcomes and ensure that they "never have to go through this again," Dr. Covelli said.

The study cohort had a mean age of 55 years, with ages ranging from 36 to 84 years.

Dr. Covelli has received funding from Roche Canada and the Canadian Breast Cancer Foundation Physician Fellowship Award.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Fear and a desire for control over breast cancer may drive women to choose mastectomy over less aggressive management, a qualitative study of 30 patients has shown.

She interviewed 15 women who were candidates for breast-conserving surgery but chose unilateral mastectomy and 15 average-risk women who were candidates for surgery in one breast but also chose prophylactic contralateral mastectomy.

Fear led patients to overestimate their risk of local recurrence and contralateral cancer and to misunderstand their odds of dying of breast cancer. The fear combined with wanting to eliminate and control the risk of cancer resulted in the patient choosing mastectomy or bilateral mastectomy, factors that probably are contributing to increasing rates of mastectomy for early-stage breast cancer, Dr. Andrea M. Covelli reported in a poster at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

When deciding on treatment, the women sought out multiple sources of information but gave greatest weight to the experiences of people they’d known with breast cancer and information from breast cancer survivors. It was the patients, not clinicians, who raised the topic of contralateral prophylactic mastectomy, which some patients chose in an attempt to eliminate any risk of contralateral breast cancer.

"More surgery is seen as more control," reported Dr. Covelli of the University of Toronto. A better understanding of patients’ decision process may help physicians be better able to discuss issues important to their patients in making treatment decisions.

Dr. Covelli conducted semistructured one-on-one interviews with patients with early-stage breast cancer chosen from five hospitals in the greater Toronto area to represent a variety of ages and ethnicities. Twelve were treated at academic cancer centers, 6 were treated at academic noncancer centers, and 12 were treated at community medical centers.

She identified several themes in the results. The diagnosis brought shock and fear. Patients discussed both breast-conserving surgery and unilateral mastectomy during their surgical consultation, during which the physician discouraged contralateral prophylactic mastectomy. Patients relied on multiple sources of information in their decision making, but the greatest impact came from the experiences of others with breast cancer, she reported.

Women who chose unilateral mastectomy did so most often out of fear of recurrence and the misguided notion that it would give them a survival advantage. Occasionally, they chose unilateral mastectomy to avoid radiation therapy.

Women who also chose contralateral prophylactic mastectomy initiated discussions about it, which their surgeons then discouraged. These patients chose it anyway because they overestimated the risk of contralateral cancer and mistakenly believed it would improve their chance of survival. Occasionally they added contralateral prophylactic mastectomy for body symmetry.

In essence, patients chose these more aggressive surgeries because they were actively trying to control their cancer outcomes and ensure that they "never have to go through this again," Dr. Covelli said.

The study cohort had a mean age of 55 years, with ages ranging from 36 to 84 years.

Dr. Covelli has received funding from Roche Canada and the Canadian Breast Cancer Foundation Physician Fellowship Award.

[email protected]

On Twitter @sherryboschert

AMSTERDAM – Despite finding no overall survival benefit by adding bevacizumab to standard chemotherapy for newly diagnosed or platinum-resistant advanced ovarian cancer, the results of two phase III clinical trials remain "practice changing," according to a commentator Dr. Rebecca Kristeleit at the the multidisciplinary European cancer congresses.

Final overall survival results from the ICON7 trial showed that, in more than 1,500 women with newly diagnosed advanced ovarian cancer, there was a nonstatistical (P =.85) difference in overall survival of about 0.9 months using the restricted mean when all patients were considered.

Sara Freeman/IMNG Medical Media

In the AURELIA trial, conducted in 361 women with platinum-resistant disease, the hazard ratio for overall survival was 0.85, in favor of the addition of bevacizumab to chemotherapy, although this was not statistically significant (P = .174). The median overall survival was 16.6 months vs. 13.3 months in the control arm.

"The message I take from ICON7 is that there is a significant overall survival benefit in the high-risk group," said Dr. Kristeleit. "It’s an important clinical improvement, and it’s most important in the poor-prognosis patients, the ones who are inoperable, and the ones who are stage IV."

Regarding AURELIA, Dr. Kristeleit, a senior lecturer and consultant medical oncologist at University College London, said, "The study has shown a significant progression-free survival benefit, and we need to remember that it has doubled this in this really hard to treat group of ovarian cancer patients where there is significant clinical need."

ICON7: Bevacizumab in front-line treatment

The ICON7 (International Collaboration on Ovarian Neoplasms) study investigated the safety and efficacy of adding bevacizumab (7.5 mg/kg every 3 weeks) to standard chemotherapy in women with newly diagnosed ovarian cancer who were recruited and treated at 253 centers. The mean age of patients in the trial was 57 years.

The primary efficacy findings from the study were reported 3 years ago at the annual Congress of the European Society for Medical Oncology and published in the New England Journal of Medicine (2011;365:2484-96). These findings showed a clear benefit of adding the targeted agent to carboplatin (AUC 5 or 6) and paclitaxel (175 mg/m²) given every 3 weeks for six cycles vs. chemotherapy alone, with median progression-free survival times of 19.0 vs. 17.3 months (HR, 0.81; P = .0041), respectively.

Sara Freeman/IMNG Medical Media

Now, with a median follow-up of 49 months, "it’s reassuring to see the progression-free survival is essentially the same [19.9 vs. 17.5 months]," observed study investigator Dr. Amit Oza of the Princess Margaret Cancer Centre at the University of Toronto.

Dr. Oza noted that 502 (33%) women met prespecified criteria for having a "poor prognosis," including women with suboptimally debulked stage III disease, those with stage IV disease, and those who could not have surgery, potentially putting them at high risk of progression. In those women, bevacizumab improved progression-free survival by a median of 5.5 months (HR, 0.73, P =.001), or 4.1 months using the restricted mean as the data were found to be non-proportional.

Final overall survival in these high-risk women was improved by a median of 9.4 months by the additional use of bevacizumab (HR, 0.78, P = .03), or 4.8 months using the restricted mean, from 34.5 months with chemotherapy alone to 39.3 months by the addition of the targeted agent.

"The overall survival difference in the high-risk subgroup is clinically meaningful," Dr. Oza said.

AURELIA: Bevacizumab in platinum-resistant disease

AURELIA was an open-label, randomized trial involving women who had progressive ovarian cancer within 6 months of receiving platinum-based chemotherapy. Women were randomized to receive chemotherapy alone (n = 182) or to chemotherapy plus bevacizumab (n = 179). The choice of chemotherapy was at the investigators’ discretion from a choice of weekly paclitaxel (80 mg/m² on days 1, 8, 15, and 22), topotecan (4 mg/m² on days 1, 8, and 15), or pegylated liposomal doxorubicin (PLD, 40 mg/m² on day 1). Bevacizumab was given at a dose of 15 mg/kg every 3 weeks.

The primary endpoint was progression-free survival, with secondary endpoints of overall survival, quality of life, and, of course, safety and tolerability. The primary endpoint findings were presented last year at the annual meeting American Society of Clinical Oncology (J. Clin. Oncol. 2012;30 Suppl:LBA5002) and showed that the addition of bevacizumab almost doubled progression-free survival from 3.4 months with chemotherapy alone to 6.7 months when bevacizumab was added (HR, 0.48, P less than .001).

"The study was not powered to detect a significant difference in overall survival," said Dr. Petronella O. Witteveen, who was one of the AURELIA study investigators. Dr. Witteveen of the University Medical Center Utrecht in the Netherlands commented that overall survival was a key secondary endpoint for the trial and that interpretation of these data were complicated by the high percentage (40%) of patients in the chemotherapy arm that were allowed to crossover to additional treatment with bevacizumab.

Sara Freeman/IMNG Medical Media

Although no difference between the treatment arms could be seen in the final overall survival analysis, exploratory findings hinted that patients who received bevacizumab in combination with weekly paclitaxel might have had a survival advantage. The median overall survival in the cohort of patients who received bevacizumab in addition to weekly paclitaxel (n = 60) was 22.4 months vs. 13.2 months in the patients who received the chemotherapy alone (n = 55; HR, 0.65). Overall survival in the topotecan and PLD cohorts did not show any benefit of the addition of bevacizumab, with median overall survival times of just over 13-14 months whether or not bevacizumab was added to chemotherapy.

Updated safety findings showed no undue concerns or new side effects, with a higher percentage of patients experiencing hypertension if treated with bevacizumab rather than chemotherapy alone (7.8% vs. 1.1%). "There were strict instructions to try to reduce the number of gastrointestinal perforations," Dr. Witteveen noted. This resulted in a low rate (1.1% vs. 0%) of this adverse event, she observed

"Practice-changing trials"

"I think these are practice-changing trials," Dr. Kristeleit commented, stating that bevacizumab is clearly an active drug in advanced bulky ovarian cancer.

Based on the ICON7 findings, "first-line bevacizumab and 3-weekly chemotherapy should be considered a standard of care in high risk ovarian cancer," she said.

Meanwhile AURELIA shows, "Bevacizumab with weekly paclitaxel should be considered a new paradigm in platinum-resistant ovarian cancer."

Bevacizumab (Avastin) was recently approved for use in combination with chemotherapy in the first- and second-line treatment of advanced ovarian cancer in Europe. In the second-line setting, it is indicated in platinum-sensitive disease and not platinum-resistant disease as tested in the AURELIA trial. Bevacizumab is not currently licensed for ovarian cancer treatment in the United States.

Roche sponsored the AURELIA study. Dr. Witteveen had no conflicts of interest; some of her coinvestigators disclosed ties with Roche, GlaxoSmithKline, and Novartis. ICON-7 was funded by Roche and the National Institute for Health Research through the National Cancer Research Network in the United Kingdom. Dr. Oza disclosed ties with Roche. Dr. Kristeleit disclosed ties with Roche, Clovis, Janssen, Lytix, and Novartis.

AMSTERDAM – Despite finding no overall survival benefit by adding bevacizumab to standard chemotherapy for newly diagnosed or platinum-resistant advanced ovarian cancer, the results of two phase III clinical trials remain "practice changing," according to a commentator Dr. Rebecca Kristeleit at the the multidisciplinary European cancer congresses.

Final overall survival results from the ICON7 trial showed that, in more than 1,500 women with newly diagnosed advanced ovarian cancer, there was a nonstatistical (P =.85) difference in overall survival of about 0.9 months using the restricted mean when all patients were considered.

Sara Freeman/IMNG Medical Media

In the AURELIA trial, conducted in 361 women with platinum-resistant disease, the hazard ratio for overall survival was 0.85, in favor of the addition of bevacizumab to chemotherapy, although this was not statistically significant (P = .174). The median overall survival was 16.6 months vs. 13.3 months in the control arm.

"The message I take from ICON7 is that there is a significant overall survival benefit in the high-risk group," said Dr. Kristeleit. "It’s an important clinical improvement, and it’s most important in the poor-prognosis patients, the ones who are inoperable, and the ones who are stage IV."

Regarding AURELIA, Dr. Kristeleit, a senior lecturer and consultant medical oncologist at University College London, said, "The study has shown a significant progression-free survival benefit, and we need to remember that it has doubled this in this really hard to treat group of ovarian cancer patients where there is significant clinical need."

ICON7: Bevacizumab in front-line treatment

The ICON7 (International Collaboration on Ovarian Neoplasms) study investigated the safety and efficacy of adding bevacizumab (7.5 mg/kg every 3 weeks) to standard chemotherapy in women with newly diagnosed ovarian cancer who were recruited and treated at 253 centers. The mean age of patients in the trial was 57 years.

The primary efficacy findings from the study were reported 3 years ago at the annual Congress of the European Society for Medical Oncology and published in the New England Journal of Medicine (2011;365:2484-96). These findings showed a clear benefit of adding the targeted agent to carboplatin (AUC 5 or 6) and paclitaxel (175 mg/m²) given every 3 weeks for six cycles vs. chemotherapy alone, with median progression-free survival times of 19.0 vs. 17.3 months (HR, 0.81; P = .0041), respectively.

Sara Freeman/IMNG Medical Media

Now, with a median follow-up of 49 months, "it’s reassuring to see the progression-free survival is essentially the same [19.9 vs. 17.5 months]," observed study investigator Dr. Amit Oza of the Princess Margaret Cancer Centre at the University of Toronto.

Dr. Oza noted that 502 (33%) women met prespecified criteria for having a "poor prognosis," including women with suboptimally debulked stage III disease, those with stage IV disease, and those who could not have surgery, potentially putting them at high risk of progression. In those women, bevacizumab improved progression-free survival by a median of 5.5 months (HR, 0.73, P =.001), or 4.1 months using the restricted mean as the data were found to be non-proportional.

Final overall survival in these high-risk women was improved by a median of 9.4 months by the additional use of bevacizumab (HR, 0.78, P = .03), or 4.8 months using the restricted mean, from 34.5 months with chemotherapy alone to 39.3 months by the addition of the targeted agent.

"The overall survival difference in the high-risk subgroup is clinically meaningful," Dr. Oza said.

AURELIA: Bevacizumab in platinum-resistant disease

AURELIA was an open-label, randomized trial involving women who had progressive ovarian cancer within 6 months of receiving platinum-based chemotherapy. Women were randomized to receive chemotherapy alone (n = 182) or to chemotherapy plus bevacizumab (n = 179). The choice of chemotherapy was at the investigators’ discretion from a choice of weekly paclitaxel (80 mg/m² on days 1, 8, 15, and 22), topotecan (4 mg/m² on days 1, 8, and 15), or pegylated liposomal doxorubicin (PLD, 40 mg/m² on day 1). Bevacizumab was given at a dose of 15 mg/kg every 3 weeks.

The primary endpoint was progression-free survival, with secondary endpoints of overall survival, quality of life, and, of course, safety and tolerability. The primary endpoint findings were presented last year at the annual meeting American Society of Clinical Oncology (J. Clin. Oncol. 2012;30 Suppl:LBA5002) and showed that the addition of bevacizumab almost doubled progression-free survival from 3.4 months with chemotherapy alone to 6.7 months when bevacizumab was added (HR, 0.48, P less than .001).

"The study was not powered to detect a significant difference in overall survival," said Dr. Petronella O. Witteveen, who was one of the AURELIA study investigators. Dr. Witteveen of the University Medical Center Utrecht in the Netherlands commented that overall survival was a key secondary endpoint for the trial and that interpretation of these data were complicated by the high percentage (40%) of patients in the chemotherapy arm that were allowed to crossover to additional treatment with bevacizumab.

Sara Freeman/IMNG Medical Media

Although no difference between the treatment arms could be seen in the final overall survival analysis, exploratory findings hinted that patients who received bevacizumab in combination with weekly paclitaxel might have had a survival advantage. The median overall survival in the cohort of patients who received bevacizumab in addition to weekly paclitaxel (n = 60) was 22.4 months vs. 13.2 months in the patients who received the chemotherapy alone (n = 55; HR, 0.65). Overall survival in the topotecan and PLD cohorts did not show any benefit of the addition of bevacizumab, with median overall survival times of just over 13-14 months whether or not bevacizumab was added to chemotherapy.

Updated safety findings showed no undue concerns or new side effects, with a higher percentage of patients experiencing hypertension if treated with bevacizumab rather than chemotherapy alone (7.8% vs. 1.1%). "There were strict instructions to try to reduce the number of gastrointestinal perforations," Dr. Witteveen noted. This resulted in a low rate (1.1% vs. 0%) of this adverse event, she observed

"Practice-changing trials"

"I think these are practice-changing trials," Dr. Kristeleit commented, stating that bevacizumab is clearly an active drug in advanced bulky ovarian cancer.

Based on the ICON7 findings, "first-line bevacizumab and 3-weekly chemotherapy should be considered a standard of care in high risk ovarian cancer," she said.

Meanwhile AURELIA shows, "Bevacizumab with weekly paclitaxel should be considered a new paradigm in platinum-resistant ovarian cancer."

Bevacizumab (Avastin) was recently approved for use in combination with chemotherapy in the first- and second-line treatment of advanced ovarian cancer in Europe. In the second-line setting, it is indicated in platinum-sensitive disease and not platinum-resistant disease as tested in the AURELIA trial. Bevacizumab is not currently licensed for ovarian cancer treatment in the United States.

Roche sponsored the AURELIA study. Dr. Witteveen had no conflicts of interest; some of her coinvestigators disclosed ties with Roche, GlaxoSmithKline, and Novartis. ICON-7 was funded by Roche and the National Institute for Health Research through the National Cancer Research Network in the United Kingdom. Dr. Oza disclosed ties with Roche. Dr. Kristeleit disclosed ties with Roche, Clovis, Janssen, Lytix, and Novartis.

AMSTERDAM – Despite finding no overall survival benefit by adding bevacizumab to standard chemotherapy for newly diagnosed or platinum-resistant advanced ovarian cancer, the results of two phase III clinical trials remain "practice changing," according to a commentator Dr. Rebecca Kristeleit at the the multidisciplinary European cancer congresses.

Final overall survival results from the ICON7 trial showed that, in more than 1,500 women with newly diagnosed advanced ovarian cancer, there was a nonstatistical (P =.85) difference in overall survival of about 0.9 months using the restricted mean when all patients were considered.

Sara Freeman/IMNG Medical Media

In the AURELIA trial, conducted in 361 women with platinum-resistant disease, the hazard ratio for overall survival was 0.85, in favor of the addition of bevacizumab to chemotherapy, although this was not statistically significant (P = .174). The median overall survival was 16.6 months vs. 13.3 months in the control arm.

"The message I take from ICON7 is that there is a significant overall survival benefit in the high-risk group," said Dr. Kristeleit. "It’s an important clinical improvement, and it’s most important in the poor-prognosis patients, the ones who are inoperable, and the ones who are stage IV."

Regarding AURELIA, Dr. Kristeleit, a senior lecturer and consultant medical oncologist at University College London, said, "The study has shown a significant progression-free survival benefit, and we need to remember that it has doubled this in this really hard to treat group of ovarian cancer patients where there is significant clinical need."

ICON7: Bevacizumab in front-line treatment

The ICON7 (International Collaboration on Ovarian Neoplasms) study investigated the safety and efficacy of adding bevacizumab (7.5 mg/kg every 3 weeks) to standard chemotherapy in women with newly diagnosed ovarian cancer who were recruited and treated at 253 centers. The mean age of patients in the trial was 57 years.

The primary efficacy findings from the study were reported 3 years ago at the annual Congress of the European Society for Medical Oncology and published in the New England Journal of Medicine (2011;365:2484-96). These findings showed a clear benefit of adding the targeted agent to carboplatin (AUC 5 or 6) and paclitaxel (175 mg/m²) given every 3 weeks for six cycles vs. chemotherapy alone, with median progression-free survival times of 19.0 vs. 17.3 months (HR, 0.81; P = .0041), respectively.

Sara Freeman/IMNG Medical Media

Now, with a median follow-up of 49 months, "it’s reassuring to see the progression-free survival is essentially the same [19.9 vs. 17.5 months]," observed study investigator Dr. Amit Oza of the Princess Margaret Cancer Centre at the University of Toronto.

Dr. Oza noted that 502 (33%) women met prespecified criteria for having a "poor prognosis," including women with suboptimally debulked stage III disease, those with stage IV disease, and those who could not have surgery, potentially putting them at high risk of progression. In those women, bevacizumab improved progression-free survival by a median of 5.5 months (HR, 0.73, P =.001), or 4.1 months using the restricted mean as the data were found to be non-proportional.

Final overall survival in these high-risk women was improved by a median of 9.4 months by the additional use of bevacizumab (HR, 0.78, P = .03), or 4.8 months using the restricted mean, from 34.5 months with chemotherapy alone to 39.3 months by the addition of the targeted agent.

"The overall survival difference in the high-risk subgroup is clinically meaningful," Dr. Oza said.

AURELIA: Bevacizumab in platinum-resistant disease

AURELIA was an open-label, randomized trial involving women who had progressive ovarian cancer within 6 months of receiving platinum-based chemotherapy. Women were randomized to receive chemotherapy alone (n = 182) or to chemotherapy plus bevacizumab (n = 179). The choice of chemotherapy was at the investigators’ discretion from a choice of weekly paclitaxel (80 mg/m² on days 1, 8, 15, and 22), topotecan (4 mg/m² on days 1, 8, and 15), or pegylated liposomal doxorubicin (PLD, 40 mg/m² on day 1). Bevacizumab was given at a dose of 15 mg/kg every 3 weeks.

The primary endpoint was progression-free survival, with secondary endpoints of overall survival, quality of life, and, of course, safety and tolerability. The primary endpoint findings were presented last year at the annual meeting American Society of Clinical Oncology (J. Clin. Oncol. 2012;30 Suppl:LBA5002) and showed that the addition of bevacizumab almost doubled progression-free survival from 3.4 months with chemotherapy alone to 6.7 months when bevacizumab was added (HR, 0.48, P less than .001).

"The study was not powered to detect a significant difference in overall survival," said Dr. Petronella O. Witteveen, who was one of the AURELIA study investigators. Dr. Witteveen of the University Medical Center Utrecht in the Netherlands commented that overall survival was a key secondary endpoint for the trial and that interpretation of these data were complicated by the high percentage (40%) of patients in the chemotherapy arm that were allowed to crossover to additional treatment with bevacizumab.

Sara Freeman/IMNG Medical Media

Although no difference between the treatment arms could be seen in the final overall survival analysis, exploratory findings hinted that patients who received bevacizumab in combination with weekly paclitaxel might have had a survival advantage. The median overall survival in the cohort of patients who received bevacizumab in addition to weekly paclitaxel (n = 60) was 22.4 months vs. 13.2 months in the patients who received the chemotherapy alone (n = 55; HR, 0.65). Overall survival in the topotecan and PLD cohorts did not show any benefit of the addition of bevacizumab, with median overall survival times of just over 13-14 months whether or not bevacizumab was added to chemotherapy.

Updated safety findings showed no undue concerns or new side effects, with a higher percentage of patients experiencing hypertension if treated with bevacizumab rather than chemotherapy alone (7.8% vs. 1.1%). "There were strict instructions to try to reduce the number of gastrointestinal perforations," Dr. Witteveen noted. This resulted in a low rate (1.1% vs. 0%) of this adverse event, she observed

"Practice-changing trials"

"I think these are practice-changing trials," Dr. Kristeleit commented, stating that bevacizumab is clearly an active drug in advanced bulky ovarian cancer.

Based on the ICON7 findings, "first-line bevacizumab and 3-weekly chemotherapy should be considered a standard of care in high risk ovarian cancer," she said.

Meanwhile AURELIA shows, "Bevacizumab with weekly paclitaxel should be considered a new paradigm in platinum-resistant ovarian cancer."

Bevacizumab (Avastin) was recently approved for use in combination with chemotherapy in the first- and second-line treatment of advanced ovarian cancer in Europe. In the second-line setting, it is indicated in platinum-sensitive disease and not platinum-resistant disease as tested in the AURELIA trial. Bevacizumab is not currently licensed for ovarian cancer treatment in the United States.

Roche sponsored the AURELIA study. Dr. Witteveen had no conflicts of interest; some of her coinvestigators disclosed ties with Roche, GlaxoSmithKline, and Novartis. ICON-7 was funded by Roche and the National Institute for Health Research through the National Cancer Research Network in the United Kingdom. Dr. Oza disclosed ties with Roche. Dr. Kristeleit disclosed ties with Roche, Clovis, Janssen, Lytix, and Novartis.

ATLANTA – A decade after treatment for early-stage breast cancer, women who underwent surgery and radiation had higher survival rates than women who had surgery alone, with no increase in radiation-related cardiac or secondary cancer deaths, investigators reported at the annual meeting of the American Society for Radiation Oncology.

An analysis of Surveillance, Epidemiology and End Results (SEER) data on women treated for stage TIA N0 breast cancer in their mid to late 50s showed that after a median follow-up of 14 years, 10-year overall survival among the 2,397 women who received lumpectomy or mastectomy and radiation was 91.6%, compared with 87% for 2,988 women who had lumpectomy or mastectomy only (P less than .001).

Ten-year cardiac cause–specific survival was 96.7% vs. 92.7% (P less than .001), respectively. Breast cancer–specific survival was also higher among women who had undergone radiation, at 97% vs. 95.7% (P = .01), reported Dr. Jason C. Ye, a resident in radiation oncology at Weill Cornell Medical College, New York.

The data also suggest that breast irradiation does not increase the risk of lung cancer death, which occurred in 6 patients (1.9%) who underwent lumpectomy and radiation, and in 48 (1.6%) of those who had lumpectomies only, a difference that was not significant.

Dr. Ye noted, however, that between-group differences may begin to show up with longer follow-up.

"Although 14 years is a long time, studies have found increases in cardiac mortality and secondary cancers at 20 and 30 years after radiation. Also, there might have been a selection bias by physicians treating at the time, based on patients’ comorbidities and the patient’s health status. This might explain why the overall survival and the cardiac cause–specific survival were different between the two groups, with the no-radiation arm doing worse," he said at a media briefing.

In addition, changes in techniques introduced since the 1990s, such as three-dimensional conformal radiation, prone irradiation, hypofractionation, and intensity-modulated radiation therapy, may have effects on cardiac-specific and overall survival rates in the future, Dr. Ye said.

Dr. Ye and his colleagues reviewed SEER records on 5,385 women treated for early breast cancer during 1990-1997, and stratified them according to treatment with external-beam radiation or no radiation.

They included only patients with stage TIA N0 breast cancer identified as their first malignancy.

The authors used cause-of-death codes to identify cardiac deaths (either from cardiac disease or from atherosclerosis, breast cancer mortality, and deaths from second cancers in the chest area).

Radiation was associated with significantly lower overall mortality (relative risk, 0.69; P less than .001), breast cancer mortality (RR, 0.75; P = .02), and cardiac mortality (RR, 0.53; P less than .001).

Women with tumors in the left breast, whose hearts would presumably receive a larger dose of radiation than women with right breast tumors, were not at increased risk for cardiac-specific death. Deaths from second cancers included lung cancer in 2%; lymphomas and leukemias, each in 0.4%; soft-tissue malignancies (including the heart) in 0.06%; and cancer of the esophagus in 0.04%.

There were no significant differences between the radiation and no-radiation groups in incidence of death from second cancers.

The study was supported by the National Cancer Institute. Dr. Ye reported having no relevant disclosures.

ATLANTA – A decade after treatment for early-stage breast cancer, women who underwent surgery and radiation had higher survival rates than women who had surgery alone, with no increase in radiation-related cardiac or secondary cancer deaths, investigators reported at the annual meeting of the American Society for Radiation Oncology.

An analysis of Surveillance, Epidemiology and End Results (SEER) data on women treated for stage TIA N0 breast cancer in their mid to late 50s showed that after a median follow-up of 14 years, 10-year overall survival among the 2,397 women who received lumpectomy or mastectomy and radiation was 91.6%, compared with 87% for 2,988 women who had lumpectomy or mastectomy only (P less than .001).

Ten-year cardiac cause–specific survival was 96.7% vs. 92.7% (P less than .001), respectively. Breast cancer–specific survival was also higher among women who had undergone radiation, at 97% vs. 95.7% (P = .01), reported Dr. Jason C. Ye, a resident in radiation oncology at Weill Cornell Medical College, New York.

The data also suggest that breast irradiation does not increase the risk of lung cancer death, which occurred in 6 patients (1.9%) who underwent lumpectomy and radiation, and in 48 (1.6%) of those who had lumpectomies only, a difference that was not significant.

Dr. Ye noted, however, that between-group differences may begin to show up with longer follow-up.

"Although 14 years is a long time, studies have found increases in cardiac mortality and secondary cancers at 20 and 30 years after radiation. Also, there might have been a selection bias by physicians treating at the time, based on patients’ comorbidities and the patient’s health status. This might explain why the overall survival and the cardiac cause–specific survival were different between the two groups, with the no-radiation arm doing worse," he said at a media briefing.

In addition, changes in techniques introduced since the 1990s, such as three-dimensional conformal radiation, prone irradiation, hypofractionation, and intensity-modulated radiation therapy, may have effects on cardiac-specific and overall survival rates in the future, Dr. Ye said.

Dr. Ye and his colleagues reviewed SEER records on 5,385 women treated for early breast cancer during 1990-1997, and stratified them according to treatment with external-beam radiation or no radiation.

They included only patients with stage TIA N0 breast cancer identified as their first malignancy.

The authors used cause-of-death codes to identify cardiac deaths (either from cardiac disease or from atherosclerosis, breast cancer mortality, and deaths from second cancers in the chest area).

Radiation was associated with significantly lower overall mortality (relative risk, 0.69; P less than .001), breast cancer mortality (RR, 0.75; P = .02), and cardiac mortality (RR, 0.53; P less than .001).

Women with tumors in the left breast, whose hearts would presumably receive a larger dose of radiation than women with right breast tumors, were not at increased risk for cardiac-specific death. Deaths from second cancers included lung cancer in 2%; lymphomas and leukemias, each in 0.4%; soft-tissue malignancies (including the heart) in 0.06%; and cancer of the esophagus in 0.04%.

There were no significant differences between the radiation and no-radiation groups in incidence of death from second cancers.

The study was supported by the National Cancer Institute. Dr. Ye reported having no relevant disclosures.

ATLANTA – A decade after treatment for early-stage breast cancer, women who underwent surgery and radiation had higher survival rates than women who had surgery alone, with no increase in radiation-related cardiac or secondary cancer deaths, investigators reported at the annual meeting of the American Society for Radiation Oncology.

An analysis of Surveillance, Epidemiology and End Results (SEER) data on women treated for stage TIA N0 breast cancer in their mid to late 50s showed that after a median follow-up of 14 years, 10-year overall survival among the 2,397 women who received lumpectomy or mastectomy and radiation was 91.6%, compared with 87% for 2,988 women who had lumpectomy or mastectomy only (P less than .001).

Ten-year cardiac cause–specific survival was 96.7% vs. 92.7% (P less than .001), respectively. Breast cancer–specific survival was also higher among women who had undergone radiation, at 97% vs. 95.7% (P = .01), reported Dr. Jason C. Ye, a resident in radiation oncology at Weill Cornell Medical College, New York.

The data also suggest that breast irradiation does not increase the risk of lung cancer death, which occurred in 6 patients (1.9%) who underwent lumpectomy and radiation, and in 48 (1.6%) of those who had lumpectomies only, a difference that was not significant.

Dr. Ye noted, however, that between-group differences may begin to show up with longer follow-up.

"Although 14 years is a long time, studies have found increases in cardiac mortality and secondary cancers at 20 and 30 years after radiation. Also, there might have been a selection bias by physicians treating at the time, based on patients’ comorbidities and the patient’s health status. This might explain why the overall survival and the cardiac cause–specific survival were different between the two groups, with the no-radiation arm doing worse," he said at a media briefing.

In addition, changes in techniques introduced since the 1990s, such as three-dimensional conformal radiation, prone irradiation, hypofractionation, and intensity-modulated radiation therapy, may have effects on cardiac-specific and overall survival rates in the future, Dr. Ye said.

Dr. Ye and his colleagues reviewed SEER records on 5,385 women treated for early breast cancer during 1990-1997, and stratified them according to treatment with external-beam radiation or no radiation.

They included only patients with stage TIA N0 breast cancer identified as their first malignancy.

The authors used cause-of-death codes to identify cardiac deaths (either from cardiac disease or from atherosclerosis, breast cancer mortality, and deaths from second cancers in the chest area).

Radiation was associated with significantly lower overall mortality (relative risk, 0.69; P less than .001), breast cancer mortality (RR, 0.75; P = .02), and cardiac mortality (RR, 0.53; P less than .001).

Women with tumors in the left breast, whose hearts would presumably receive a larger dose of radiation than women with right breast tumors, were not at increased risk for cardiac-specific death. Deaths from second cancers included lung cancer in 2%; lymphomas and leukemias, each in 0.4%; soft-tissue malignancies (including the heart) in 0.06%; and cancer of the esophagus in 0.04%.

There were no significant differences between the radiation and no-radiation groups in incidence of death from second cancers.

The study was supported by the National Cancer Institute. Dr. Ye reported having no relevant disclosures.

CHICAGO – One in three patients sent to surgery for a suspicious lung nodule by their community pulmonologist did not have cancer in a retrospective analysis of 385 patients.

In addition, half of patients with benign disease underwent an invasive procedure, Dr. Nichole Tanner said at the annual meeting of the American College of Chest Physicians (ACCP).

Physician judgment plays a key role in the newly updated ACCP lung cancer guidelines (Chest 2013;143:e93S-e120S). They recommend that clinicians estimate the pretest probability of malignancy for indeterminate nodules larger than 8 mm either qualitatively by using their clinical judgment and/or quantitatively with a validated risk model.

Patients in the study, conducted at 16 sites across the country, had 8- to 20-mm nodules, and were mostly former (45%) or current smokers (27.5%), white (86%), and covered by private insurance (55.3%) or Medicare (38.2%). Their average age was 64.5 years.

Invasive procedures included anything outside of simple imaging for monitoring. Computed tomography (CT)- and bronchoscopic-guided biopsy were considered minor invasive procedures, while major invasive procedures included any surgical procedure such as mediastinoscopy, thoracotomy, and video-assisted thorascopic surgery (VATS).

Monitoring only was used for 184 patients, and ran the gamut from one to a "shocking seven" CT or positron-emission tomography (PET) scans in 2 years, said Dr. Tanner, with the Medical University of South Carolina, Charleston. None of these nodules were malignant.

Of the 124 nodules biopsied, 35% were malignant, 56% were diagnosed as benign, and 8% were benign based on stability.

Of the 77 nodules surgically removed, 64% were malignant and 36% were benign, she said.

While a reassuring 76% of nodules seen by community pulmonologists were benign, the results highlight the complexity involved in managing a patient population that is surely on the rise as lung cancer screening spreads nationally.

During a rousing debate that followed the presentation, audience members expressed concern over the 36% of patients taken to surgery for benign disease, highlighting a 3% death rate associated with thoracotomy and the potential for reduced lung function after surgery.

Others, including a thoracic surgeon, countered that removal of a suspicious nodule can catch lung disease at an earlier stage, eliminates the need for repeat CT/PET imaging exposure, and is requested by some patients for their peace of mind or even to pass a pre-employment physical.

Session comoderator and interventional respirologist Dr. Anne Gonzalez, with McGill University Health Center, Montreal, said in an interview, "I was perhaps shocked there were so many [patients] that went directly to surgery, but on the other hand, the guidelines do recommend that if the suspicion of lung cancer is high enough – 65% – patients should go to surgery."

Dr. Gonzalez also echoed comments from the floor that, importantly, the study failed to detail whether patients’ nodules were identified as incidental findings or were the result of symptom-driven screening.

In a multivariate analysis, current smoking (odds ratio, 3.28) and larger nodule size (12-15 mm: OR, 3.30; 16-20 mm: OR, 4.97) influenced who underwent invasive procedures, Dr. Tanner said. Geographic region of the country did not pan out as a predictor.

Cancer was present in 39% of 16- to 20-mm nodules and 31% of 12- to 15-mm nodules, compared with 12% of 8- to 11-mm nodules.

One attendee commented that the number of patients undergoing surgery for benign disease at his institution has dramatically declined with the establishment of a 45-member multidisciplinary tumor board to review and manage patients with lung nodules.

This approach is helpful in that patients won’t be lost to follow-up and can be presented with a plan that has the support of multiple physicians, but "I don’t see this as a feasible way with which to manage every pulmonary nodule," Dr. Tanner said in an interview. "In the lung cancer screening program we’re implementing at our Veterans Affairs hospital in the very near future, we will have a nodule tracking system to ensure that no patients are lost to follow-up and will make treatment and diagnostic decisions based on the Fleischner criteria for radiographic follow-up of lung nodules, as well as the ACCP guidelines."

Dr. Tanner reported consulting for the study sponsor, Integrated Diagnostics.

[email protected]

CHICAGO – One in three patients sent to surgery for a suspicious lung nodule by their community pulmonologist did not have cancer in a retrospective analysis of 385 patients.

In addition, half of patients with benign disease underwent an invasive procedure, Dr. Nichole Tanner said at the annual meeting of the American College of Chest Physicians (ACCP).

Physician judgment plays a key role in the newly updated ACCP lung cancer guidelines (Chest 2013;143:e93S-e120S). They recommend that clinicians estimate the pretest probability of malignancy for indeterminate nodules larger than 8 mm either qualitatively by using their clinical judgment and/or quantitatively with a validated risk model.

Patients in the study, conducted at 16 sites across the country, had 8- to 20-mm nodules, and were mostly former (45%) or current smokers (27.5%), white (86%), and covered by private insurance (55.3%) or Medicare (38.2%). Their average age was 64.5 years.

Invasive procedures included anything outside of simple imaging for monitoring. Computed tomography (CT)- and bronchoscopic-guided biopsy were considered minor invasive procedures, while major invasive procedures included any surgical procedure such as mediastinoscopy, thoracotomy, and video-assisted thorascopic surgery (VATS).

Monitoring only was used for 184 patients, and ran the gamut from one to a "shocking seven" CT or positron-emission tomography (PET) scans in 2 years, said Dr. Tanner, with the Medical University of South Carolina, Charleston. None of these nodules were malignant.

Of the 124 nodules biopsied, 35% were malignant, 56% were diagnosed as benign, and 8% were benign based on stability.

Of the 77 nodules surgically removed, 64% were malignant and 36% were benign, she said.

While a reassuring 76% of nodules seen by community pulmonologists were benign, the results highlight the complexity involved in managing a patient population that is surely on the rise as lung cancer screening spreads nationally.

During a rousing debate that followed the presentation, audience members expressed concern over the 36% of patients taken to surgery for benign disease, highlighting a 3% death rate associated with thoracotomy and the potential for reduced lung function after surgery.

Others, including a thoracic surgeon, countered that removal of a suspicious nodule can catch lung disease at an earlier stage, eliminates the need for repeat CT/PET imaging exposure, and is requested by some patients for their peace of mind or even to pass a pre-employment physical.

Session comoderator and interventional respirologist Dr. Anne Gonzalez, with McGill University Health Center, Montreal, said in an interview, "I was perhaps shocked there were so many [patients] that went directly to surgery, but on the other hand, the guidelines do recommend that if the suspicion of lung cancer is high enough – 65% – patients should go to surgery."

Dr. Gonzalez also echoed comments from the floor that, importantly, the study failed to detail whether patients’ nodules were identified as incidental findings or were the result of symptom-driven screening.

In a multivariate analysis, current smoking (odds ratio, 3.28) and larger nodule size (12-15 mm: OR, 3.30; 16-20 mm: OR, 4.97) influenced who underwent invasive procedures, Dr. Tanner said. Geographic region of the country did not pan out as a predictor.

Cancer was present in 39% of 16- to 20-mm nodules and 31% of 12- to 15-mm nodules, compared with 12% of 8- to 11-mm nodules.

One attendee commented that the number of patients undergoing surgery for benign disease at his institution has dramatically declined with the establishment of a 45-member multidisciplinary tumor board to review and manage patients with lung nodules.

This approach is helpful in that patients won’t be lost to follow-up and can be presented with a plan that has the support of multiple physicians, but "I don’t see this as a feasible way with which to manage every pulmonary nodule," Dr. Tanner said in an interview. "In the lung cancer screening program we’re implementing at our Veterans Affairs hospital in the very near future, we will have a nodule tracking system to ensure that no patients are lost to follow-up and will make treatment and diagnostic decisions based on the Fleischner criteria for radiographic follow-up of lung nodules, as well as the ACCP guidelines."

Dr. Tanner reported consulting for the study sponsor, Integrated Diagnostics.

[email protected]

CHICAGO – One in three patients sent to surgery for a suspicious lung nodule by their community pulmonologist did not have cancer in a retrospective analysis of 385 patients.

In addition, half of patients with benign disease underwent an invasive procedure, Dr. Nichole Tanner said at the annual meeting of the American College of Chest Physicians (ACCP).

Physician judgment plays a key role in the newly updated ACCP lung cancer guidelines (Chest 2013;143:e93S-e120S). They recommend that clinicians estimate the pretest probability of malignancy for indeterminate nodules larger than 8 mm either qualitatively by using their clinical judgment and/or quantitatively with a validated risk model.

Patients in the study, conducted at 16 sites across the country, had 8- to 20-mm nodules, and were mostly former (45%) or current smokers (27.5%), white (86%), and covered by private insurance (55.3%) or Medicare (38.2%). Their average age was 64.5 years.

Invasive procedures included anything outside of simple imaging for monitoring. Computed tomography (CT)- and bronchoscopic-guided biopsy were considered minor invasive procedures, while major invasive procedures included any surgical procedure such as mediastinoscopy, thoracotomy, and video-assisted thorascopic surgery (VATS).

Monitoring only was used for 184 patients, and ran the gamut from one to a "shocking seven" CT or positron-emission tomography (PET) scans in 2 years, said Dr. Tanner, with the Medical University of South Carolina, Charleston. None of these nodules were malignant.

Of the 124 nodules biopsied, 35% were malignant, 56% were diagnosed as benign, and 8% were benign based on stability.

Of the 77 nodules surgically removed, 64% were malignant and 36% were benign, she said.

While a reassuring 76% of nodules seen by community pulmonologists were benign, the results highlight the complexity involved in managing a patient population that is surely on the rise as lung cancer screening spreads nationally.

During a rousing debate that followed the presentation, audience members expressed concern over the 36% of patients taken to surgery for benign disease, highlighting a 3% death rate associated with thoracotomy and the potential for reduced lung function after surgery.

Others, including a thoracic surgeon, countered that removal of a suspicious nodule can catch lung disease at an earlier stage, eliminates the need for repeat CT/PET imaging exposure, and is requested by some patients for their peace of mind or even to pass a pre-employment physical.

Session comoderator and interventional respirologist Dr. Anne Gonzalez, with McGill University Health Center, Montreal, said in an interview, "I was perhaps shocked there were so many [patients] that went directly to surgery, but on the other hand, the guidelines do recommend that if the suspicion of lung cancer is high enough – 65% – patients should go to surgery."

Dr. Gonzalez also echoed comments from the floor that, importantly, the study failed to detail whether patients’ nodules were identified as incidental findings or were the result of symptom-driven screening.

In a multivariate analysis, current smoking (odds ratio, 3.28) and larger nodule size (12-15 mm: OR, 3.30; 16-20 mm: OR, 4.97) influenced who underwent invasive procedures, Dr. Tanner said. Geographic region of the country did not pan out as a predictor.

Cancer was present in 39% of 16- to 20-mm nodules and 31% of 12- to 15-mm nodules, compared with 12% of 8- to 11-mm nodules.

One attendee commented that the number of patients undergoing surgery for benign disease at his institution has dramatically declined with the establishment of a 45-member multidisciplinary tumor board to review and manage patients with lung nodules.

This approach is helpful in that patients won’t be lost to follow-up and can be presented with a plan that has the support of multiple physicians, but "I don’t see this as a feasible way with which to manage every pulmonary nodule," Dr. Tanner said in an interview. "In the lung cancer screening program we’re implementing at our Veterans Affairs hospital in the very near future, we will have a nodule tracking system to ensure that no patients are lost to follow-up and will make treatment and diagnostic decisions based on the Fleischner criteria for radiographic follow-up of lung nodules, as well as the ACCP guidelines."

Dr. Tanner reported consulting for the study sponsor, Integrated Diagnostics.

[email protected]

SYDNEY – Stereotactic lung radiotherapy for centrally located non–small cell lung carcinomas can result in overall survival outcomes that are similar to those for peripheral tumors, but with an increased risk of local failure and pneumonitis, based on the results of an analysis of a large international data set.

Overall survival at 3 years was similar for 100 centrally located non–small cell lung cancers – defined as being located within 2 cm of the proximal bronchial tree – and for 869 peripheral tumors treated with stereotactic body radiotherapy (50% vs. 51%; P = .70), based on data presented by Dr. Maria Werner-Wasik at a world conference on lung cancer, sponsored by the International Association for the Study of Lung Cancer.

Also, the two groups did not significantly differ in the incidence of chest wall pain and myositis, rib fracture, and dermatitis. Patients with central tumors had a significantly higher incidence of grade 2 or above pneumonitis (8% vs. 1% in those with peripheral tumors; P less than .001). The incidence of grade 3 pneumonitis was similar between the two groups.

Central tumors were associated with a lower rate of cause-specific survival than were peripheral tumors (75% vs. 88%; P less than .001) and higher local failure rates at 3 years (16.2% vs. 5.9%; P less than .001) and 5 years (20.4% vs. 8.3%; P less than .001).

Dr. Werner-Wasik said central tumors had fallen into a "no-fly zone" for stereotactic body radiotherapy since an earlier trial showed unacceptable levels of toxicities from treating centrally located lung tumors. Thereafter, prospective trials examined only peripheral tumors.

"If you have a central tumor you have to do something. You can always treat with standard fractionation, but that’s not the idea. We want to give those patients (with centrally located tumors) the benefit of a short, effective regimen," said Dr. Werner-Wasik, professor and director of clinical research at the department of radiation oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia.

The data from the Elekta Lung Research Groupshowed a higher rate of local failure. Dr. Werner-Wasik said this was still "respectable," especially as the centrally located tumors did receive slightly less radiation than the peripheral tumors did and were significantly larger at baseline (3.1 vs. 2.4 cm; P less than .001).

"The local control was worse for central tumors versus peripheral tumors, presumably because we treated them with lower biologically effective doses," said Dr. Werner-Wasik in an interview. "But also, these tumors were slightly different ... as illustrated by higher values on PET scans."

Results from the upcoming RTOG 0813 study may shed more light on the question of how to deliver stereotactic body radiotherapy to centrally located tumors, she said. "We have to find an effective central dose radiation fractionation and total dose so these patients do not suffer complications and yet are assured local control."

The research was partly supported by a grant from Elekta, makers of stereotactic body radiation technology products. Dr. Werner-Wasik said she had no relevant financial disclosures. The Elekta Lung Research Group includes participants from William Beaumont Hospital in Royal Oak, Mich.; Princess Margaret Cancer Centre, Toronto; Thomas Jefferson University, Philadelphia; Julius Maximilian University of Würzburg (Germany); and the Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital in Amsterdam.

SYDNEY – Stereotactic lung radiotherapy for centrally located non–small cell lung carcinomas can result in overall survival outcomes that are similar to those for peripheral tumors, but with an increased risk of local failure and pneumonitis, based on the results of an analysis of a large international data set.

Overall survival at 3 years was similar for 100 centrally located non–small cell lung cancers – defined as being located within 2 cm of the proximal bronchial tree – and for 869 peripheral tumors treated with stereotactic body radiotherapy (50% vs. 51%; P = .70), based on data presented by Dr. Maria Werner-Wasik at a world conference on lung cancer, sponsored by the International Association for the Study of Lung Cancer.

Also, the two groups did not significantly differ in the incidence of chest wall pain and myositis, rib fracture, and dermatitis. Patients with central tumors had a significantly higher incidence of grade 2 or above pneumonitis (8% vs. 1% in those with peripheral tumors; P less than .001). The incidence of grade 3 pneumonitis was similar between the two groups.

Central tumors were associated with a lower rate of cause-specific survival than were peripheral tumors (75% vs. 88%; P less than .001) and higher local failure rates at 3 years (16.2% vs. 5.9%; P less than .001) and 5 years (20.4% vs. 8.3%; P less than .001).

Dr. Werner-Wasik said central tumors had fallen into a "no-fly zone" for stereotactic body radiotherapy since an earlier trial showed unacceptable levels of toxicities from treating centrally located lung tumors. Thereafter, prospective trials examined only peripheral tumors.

"If you have a central tumor you have to do something. You can always treat with standard fractionation, but that’s not the idea. We want to give those patients (with centrally located tumors) the benefit of a short, effective regimen," said Dr. Werner-Wasik, professor and director of clinical research at the department of radiation oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia.

The data from the Elekta Lung Research Groupshowed a higher rate of local failure. Dr. Werner-Wasik said this was still "respectable," especially as the centrally located tumors did receive slightly less radiation than the peripheral tumors did and were significantly larger at baseline (3.1 vs. 2.4 cm; P less than .001).

"The local control was worse for central tumors versus peripheral tumors, presumably because we treated them with lower biologically effective doses," said Dr. Werner-Wasik in an interview. "But also, these tumors were slightly different ... as illustrated by higher values on PET scans."

Results from the upcoming RTOG 0813 study may shed more light on the question of how to deliver stereotactic body radiotherapy to centrally located tumors, she said. "We have to find an effective central dose radiation fractionation and total dose so these patients do not suffer complications and yet are assured local control."

The research was partly supported by a grant from Elekta, makers of stereotactic body radiation technology products. Dr. Werner-Wasik said she had no relevant financial disclosures. The Elekta Lung Research Group includes participants from William Beaumont Hospital in Royal Oak, Mich.; Princess Margaret Cancer Centre, Toronto; Thomas Jefferson University, Philadelphia; Julius Maximilian University of Würzburg (Germany); and the Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital in Amsterdam.

SYDNEY – Stereotactic lung radiotherapy for centrally located non–small cell lung carcinomas can result in overall survival outcomes that are similar to those for peripheral tumors, but with an increased risk of local failure and pneumonitis, based on the results of an analysis of a large international data set.

Overall survival at 3 years was similar for 100 centrally located non–small cell lung cancers – defined as being located within 2 cm of the proximal bronchial tree – and for 869 peripheral tumors treated with stereotactic body radiotherapy (50% vs. 51%; P = .70), based on data presented by Dr. Maria Werner-Wasik at a world conference on lung cancer, sponsored by the International Association for the Study of Lung Cancer.

Also, the two groups did not significantly differ in the incidence of chest wall pain and myositis, rib fracture, and dermatitis. Patients with central tumors had a significantly higher incidence of grade 2 or above pneumonitis (8% vs. 1% in those with peripheral tumors; P less than .001). The incidence of grade 3 pneumonitis was similar between the two groups.

Central tumors were associated with a lower rate of cause-specific survival than were peripheral tumors (75% vs. 88%; P less than .001) and higher local failure rates at 3 years (16.2% vs. 5.9%; P less than .001) and 5 years (20.4% vs. 8.3%; P less than .001).

Dr. Werner-Wasik said central tumors had fallen into a "no-fly zone" for stereotactic body radiotherapy since an earlier trial showed unacceptable levels of toxicities from treating centrally located lung tumors. Thereafter, prospective trials examined only peripheral tumors.

"If you have a central tumor you have to do something. You can always treat with standard fractionation, but that’s not the idea. We want to give those patients (with centrally located tumors) the benefit of a short, effective regimen," said Dr. Werner-Wasik, professor and director of clinical research at the department of radiation oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia.

The data from the Elekta Lung Research Groupshowed a higher rate of local failure. Dr. Werner-Wasik said this was still "respectable," especially as the centrally located tumors did receive slightly less radiation than the peripheral tumors did and were significantly larger at baseline (3.1 vs. 2.4 cm; P less than .001).

"The local control was worse for central tumors versus peripheral tumors, presumably because we treated them with lower biologically effective doses," said Dr. Werner-Wasik in an interview. "But also, these tumors were slightly different ... as illustrated by higher values on PET scans."

Results from the upcoming RTOG 0813 study may shed more light on the question of how to deliver stereotactic body radiotherapy to centrally located tumors, she said. "We have to find an effective central dose radiation fractionation and total dose so these patients do not suffer complications and yet are assured local control."

The research was partly supported by a grant from Elekta, makers of stereotactic body radiation technology products. Dr. Werner-Wasik said she had no relevant financial disclosures. The Elekta Lung Research Group includes participants from William Beaumont Hospital in Royal Oak, Mich.; Princess Margaret Cancer Centre, Toronto; Thomas Jefferson University, Philadelphia; Julius Maximilian University of Würzburg (Germany); and the Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital in Amsterdam.

AMSTERDAM – Two-fifths of patients with refractory recurrent or metastatic cancers were successfully matched to an appropriate targeted treatment using molecular profiling, according to research presented at the multidisciplinary European cancer congresses.

Feasibility findings from the phase II, proof-of-concept SHIVA study showed that a molecular abnormality leading to targeted treatment was present in 40% patients.

This is the first randomized trial to consider treating patients purely on the basis of their molecular profile rather than the type of tumor that they have. It is also the first trial designed to determine what the outcome of such an approach will be, with the primary endpoint being progression-free survival.

Currently, the prescription of approved molecularly targeted agents relies on the primary tumor location and histological subtype. For example, a woman with breast cancer overexpressing HER2 may be treated with a HER2-targeting agent such as trastuzumab or lapatinib, or with endocrine therapies such as tamoxifen and letrozole, if there is overexpression of the estrogen or progestogen receptor (ER/PR).

However, it is not clear if this is the best means of using these therapies, as their molecular targets may not be specific to a single tumor type. Indeed, HER2 is overexpressed in several tumor types other than breast cancer, including ovarian, gastric, colorectal, pancreatic, and endometrial cancers.

The idea of giving patients treatment based on their molecular profiles rather than their tumor types represents a new paradigm and requires prospective validation before being implemented in clinical practice, Dr. Christophe Le Tourneau of Institut Curie, Paris, said in an interview.

The SHIVA trial was therefore initiated to compare molecularly targeted therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer (Target Oncol. 2012;7:253-65). Although two previous studies have suggested that this approach is possible and could improve patient outcomes (J. Clin. Oncol. 2010;4877-83; Clin. Cancer Res. 2012;18:6373-83), these studies were not randomized against the standard of care and so the conclusions that can be drawn from their results are not robust.

Patients are eligible for inclusion in the ongoing SHIVA trial if they have recurrent or metastatic disease despite standard treatment, an ECOG performance status of 0 or 1, adequate organ function, and measurable disease that can be biopsied not involving the bone or brain.

After recruitment, all patients will have a biopsy taken of one metastasis that is then assessed for gene mutations and amplifications, and for the expression of hormone (estrogen, progestogen and androgen) receptors. If a molecular abnormality is identified for which an approved targeted agent is available, then patients are randomized to receive either the matching targeted therapy or the conventional therapy that they would have received had they not be identified as having a possible molecular target. At progression, patients in the conventional treatment arm may crossover to targeted therapy.

Patients are only randomized if they have a molecular target that is not already known for their disease. So a patient with breast cancer found to have amplified HER2 or a patient with non–small-cell lung cancer and overexpression of EGFR would not be included, Dr. Le Tourneau said.

The SHIVA investigators have developed an algorithm or Molecular Biology Board (MBB) to help guide treatment in the experimental arm. The following targeted agents may be used if an appropriate molecular target is found: KIT or ABL for imatinib; PTEN or mTOR, among others, for everolimus; BRAF for vemurafenib; PDGFRA/B or FLT-3 for sorafenib; EGFR for erlotinib; HER2 for lapatinib in combination with trastuzumab; SRC, and others, for dasatinib; ER and PR for tamoxifen or letrozole; and the androgen receptor for abiraterone.

The trial is using high throughput sequencing, so processing the biopsies involves only two assays – one for gene mutation analysis and one for gene copy number alterations – "so we look at everything at the same time," Dr. Le Tourneau said.

As of September 2013, 350 patients had been included in the study and feasibility of the molecular profiling approach was tested in the first 95 patients. Of these, a complete molecular profile could be obtained in 61%. The median time to obtaining the biopsy sample and performing the MBB was 26 days, ranging from 2 weeks to 42 days. Mutations could be assessed in two-thirds of samples, with gene copy alterations analyzed in 68%, and immunohistochemistry for hormone receptors possible in 92%.

In the experimental arm, 14 patients (15%) with a variety of tumor types are now being treated with abiraterone, 13 (14%) with everolimus, nine (9%) with endocrine treatment, and two (2%) with anti-HER2 treatment or sorafenib.

The primary efficacy analysis for progression-free survival will be performed once 100 patients have been randomized into each study arm. Other analyses will determine the overall response rate (ORR) and overall survival, among other key endpoints.

The SHIVA trial is planned to run for 3 years, and as it is already a year in, "within 2 years the study will be finished," Dr. Le Tourneau said.

The SHIVA trial is funded by Institut Curie. Dr. Le Tourneau had no conflicts of interest.

AMSTERDAM – Two-fifths of patients with refractory recurrent or metastatic cancers were successfully matched to an appropriate targeted treatment using molecular profiling, according to research presented at the multidisciplinary European cancer congresses.

Feasibility findings from the phase II, proof-of-concept SHIVA study showed that a molecular abnormality leading to targeted treatment was present in 40% patients.

This is the first randomized trial to consider treating patients purely on the basis of their molecular profile rather than the type of tumor that they have. It is also the first trial designed to determine what the outcome of such an approach will be, with the primary endpoint being progression-free survival.

Currently, the prescription of approved molecularly targeted agents relies on the primary tumor location and histological subtype. For example, a woman with breast cancer overexpressing HER2 may be treated with a HER2-targeting agent such as trastuzumab or lapatinib, or with endocrine therapies such as tamoxifen and letrozole, if there is overexpression of the estrogen or progestogen receptor (ER/PR).

However, it is not clear if this is the best means of using these therapies, as their molecular targets may not be specific to a single tumor type. Indeed, HER2 is overexpressed in several tumor types other than breast cancer, including ovarian, gastric, colorectal, pancreatic, and endometrial cancers.

The idea of giving patients treatment based on their molecular profiles rather than their tumor types represents a new paradigm and requires prospective validation before being implemented in clinical practice, Dr. Christophe Le Tourneau of Institut Curie, Paris, said in an interview.

The SHIVA trial was therefore initiated to compare molecularly targeted therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer (Target Oncol. 2012;7:253-65). Although two previous studies have suggested that this approach is possible and could improve patient outcomes (J. Clin. Oncol. 2010;4877-83; Clin. Cancer Res. 2012;18:6373-83), these studies were not randomized against the standard of care and so the conclusions that can be drawn from their results are not robust.

Patients are eligible for inclusion in the ongoing SHIVA trial if they have recurrent or metastatic disease despite standard treatment, an ECOG performance status of 0 or 1, adequate organ function, and measurable disease that can be biopsied not involving the bone or brain.

After recruitment, all patients will have a biopsy taken of one metastasis that is then assessed for gene mutations and amplifications, and for the expression of hormone (estrogen, progestogen and androgen) receptors. If a molecular abnormality is identified for which an approved targeted agent is available, then patients are randomized to receive either the matching targeted therapy or the conventional therapy that they would have received had they not be identified as having a possible molecular target. At progression, patients in the conventional treatment arm may crossover to targeted therapy.

Patients are only randomized if they have a molecular target that is not already known for their disease. So a patient with breast cancer found to have amplified HER2 or a patient with non–small-cell lung cancer and overexpression of EGFR would not be included, Dr. Le Tourneau said.

The SHIVA investigators have developed an algorithm or Molecular Biology Board (MBB) to help guide treatment in the experimental arm. The following targeted agents may be used if an appropriate molecular target is found: KIT or ABL for imatinib; PTEN or mTOR, among others, for everolimus; BRAF for vemurafenib; PDGFRA/B or FLT-3 for sorafenib; EGFR for erlotinib; HER2 for lapatinib in combination with trastuzumab; SRC, and others, for dasatinib; ER and PR for tamoxifen or letrozole; and the androgen receptor for abiraterone.

The trial is using high throughput sequencing, so processing the biopsies involves only two assays – one for gene mutation analysis and one for gene copy number alterations – "so we look at everything at the same time," Dr. Le Tourneau said.

As of September 2013, 350 patients had been included in the study and feasibility of the molecular profiling approach was tested in the first 95 patients. Of these, a complete molecular profile could be obtained in 61%. The median time to obtaining the biopsy sample and performing the MBB was 26 days, ranging from 2 weeks to 42 days. Mutations could be assessed in two-thirds of samples, with gene copy alterations analyzed in 68%, and immunohistochemistry for hormone receptors possible in 92%.

In the experimental arm, 14 patients (15%) with a variety of tumor types are now being treated with abiraterone, 13 (14%) with everolimus, nine (9%) with endocrine treatment, and two (2%) with anti-HER2 treatment or sorafenib.

The primary efficacy analysis for progression-free survival will be performed once 100 patients have been randomized into each study arm. Other analyses will determine the overall response rate (ORR) and overall survival, among other key endpoints.

The SHIVA trial is planned to run for 3 years, and as it is already a year in, "within 2 years the study will be finished," Dr. Le Tourneau said.

The SHIVA trial is funded by Institut Curie. Dr. Le Tourneau had no conflicts of interest.

AMSTERDAM – Two-fifths of patients with refractory recurrent or metastatic cancers were successfully matched to an appropriate targeted treatment using molecular profiling, according to research presented at the multidisciplinary European cancer congresses.

Feasibility findings from the phase II, proof-of-concept SHIVA study showed that a molecular abnormality leading to targeted treatment was present in 40% patients.

This is the first randomized trial to consider treating patients purely on the basis of their molecular profile rather than the type of tumor that they have. It is also the first trial designed to determine what the outcome of such an approach will be, with the primary endpoint being progression-free survival.

Currently, the prescription of approved molecularly targeted agents relies on the primary tumor location and histological subtype. For example, a woman with breast cancer overexpressing HER2 may be treated with a HER2-targeting agent such as trastuzumab or lapatinib, or with endocrine therapies such as tamoxifen and letrozole, if there is overexpression of the estrogen or progestogen receptor (ER/PR).

However, it is not clear if this is the best means of using these therapies, as their molecular targets may not be specific to a single tumor type. Indeed, HER2 is overexpressed in several tumor types other than breast cancer, including ovarian, gastric, colorectal, pancreatic, and endometrial cancers.

The idea of giving patients treatment based on their molecular profiles rather than their tumor types represents a new paradigm and requires prospective validation before being implemented in clinical practice, Dr. Christophe Le Tourneau of Institut Curie, Paris, said in an interview.

The SHIVA trial was therefore initiated to compare molecularly targeted therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer (Target Oncol. 2012;7:253-65). Although two previous studies have suggested that this approach is possible and could improve patient outcomes (J. Clin. Oncol. 2010;4877-83; Clin. Cancer Res. 2012;18:6373-83), these studies were not randomized against the standard of care and so the conclusions that can be drawn from their results are not robust.

Patients are eligible for inclusion in the ongoing SHIVA trial if they have recurrent or metastatic disease despite standard treatment, an ECOG performance status of 0 or 1, adequate organ function, and measurable disease that can be biopsied not involving the bone or brain.

After recruitment, all patients will have a biopsy taken of one metastasis that is then assessed for gene mutations and amplifications, and for the expression of hormone (estrogen, progestogen and androgen) receptors. If a molecular abnormality is identified for which an approved targeted agent is available, then patients are randomized to receive either the matching targeted therapy or the conventional therapy that they would have received had they not be identified as having a possible molecular target. At progression, patients in the conventional treatment arm may crossover to targeted therapy.

Patients are only randomized if they have a molecular target that is not already known for their disease. So a patient with breast cancer found to have amplified HER2 or a patient with non–small-cell lung cancer and overexpression of EGFR would not be included, Dr. Le Tourneau said.

The SHIVA investigators have developed an algorithm or Molecular Biology Board (MBB) to help guide treatment in the experimental arm. The following targeted agents may be used if an appropriate molecular target is found: KIT or ABL for imatinib; PTEN or mTOR, among others, for everolimus; BRAF for vemurafenib; PDGFRA/B or FLT-3 for sorafenib; EGFR for erlotinib; HER2 for lapatinib in combination with trastuzumab; SRC, and others, for dasatinib; ER and PR for tamoxifen or letrozole; and the androgen receptor for abiraterone.

The trial is using high throughput sequencing, so processing the biopsies involves only two assays – one for gene mutation analysis and one for gene copy number alterations – "so we look at everything at the same time," Dr. Le Tourneau said.

As of September 2013, 350 patients had been included in the study and feasibility of the molecular profiling approach was tested in the first 95 patients. Of these, a complete molecular profile could be obtained in 61%. The median time to obtaining the biopsy sample and performing the MBB was 26 days, ranging from 2 weeks to 42 days. Mutations could be assessed in two-thirds of samples, with gene copy alterations analyzed in 68%, and immunohistochemistry for hormone receptors possible in 92%.

In the experimental arm, 14 patients (15%) with a variety of tumor types are now being treated with abiraterone, 13 (14%) with everolimus, nine (9%) with endocrine treatment, and two (2%) with anti-HER2 treatment or sorafenib.

The primary efficacy analysis for progression-free survival will be performed once 100 patients have been randomized into each study arm. Other analyses will determine the overall response rate (ORR) and overall survival, among other key endpoints.

The SHIVA trial is planned to run for 3 years, and as it is already a year in, "within 2 years the study will be finished," Dr. Le Tourneau said.

The SHIVA trial is funded by Institut Curie. Dr. Le Tourneau had no conflicts of interest.

WASHINGTON – Elderly patients who undergo laparoscopic colon surgery are significantly more likely to be discharged back to their homes than to a long-term care facility.

In a retrospective study of almost 10,000 elderly patients, 12.5% of those who had a laparoscopic procedure went to a nursing home, compared with 20% of those who had open surgery. In a multivariate analysis, laparoscopic surgery was associated with a significant, 39% decrease in the risk of being discharged to a nursing home, Dr. Richard Liu said at the annual clinical congress of the American College of Surgeons.

"For patients in their early 70s who do not have advanced disease or significant comorbidities, laparoscopic colon cancer resection is an option not only to prolong survival but also to preserve quality of life," said Dr. Liu, a surgical resident at Dalhousie University, Halifax, N.S.

The study highlights some important differences in the ways surgeons and patients perceive surgical outcomes. Surgeons and researchers often focus on 5-year survival rates and short-term morbidity and mortality, Dr. Liu said. But prior research done by his group found that immediate quality of life was at least as important to elderly patients – and sometimes more so.

"We have looked at elderly patients in our emergency services and followed up with them several times after admission," he said in an interview. "A common theme that came up was quality of life after hospitalization. Some were actually refusing to have operations for fear of what might become of them afterward."

Dr. Liu’s study comprised 9,416 patients from the U.S. National Inpatient Sample database. All were older than 70 years (mean age 79) and all were living independently at home. They underwent elective colon surgery during 2009-2010 for either cancer or a resection. The primary outcome was discharge back to home or to a long-term care facility. None of the patients were discharged to home health care or to hospice.

Most of the group (61%) had open surgery; the remainder had laparoscopy. Of those who had open surgery, 20% were discharged to a nursing facility, compared with 12.5% of the laparoscopy group – a significant difference.

Laparoscopy significantly decreased the chance of a nursing home admission by 39% in a multivariate analysis that controlled for age, sex, race, comorbidity score, cancer stage, income and insurance, and hospital size.

Factors significantly associated with nursing home discharge included advancing age and cancer stage.

Generally speaking, open surgery is physically more trying for elderly patients. A difficult recovery could be just enough to tip them over the edge from independent living, Dr. Liu said.

Dr. Liu had no financial disclosures.

[email protected]

WASHINGTON – Elderly patients who undergo laparoscopic colon surgery are significantly more likely to be discharged back to their homes than to a long-term care facility.

In a retrospective study of almost 10,000 elderly patients, 12.5% of those who had a laparoscopic procedure went to a nursing home, compared with 20% of those who had open surgery. In a multivariate analysis, laparoscopic surgery was associated with a significant, 39% decrease in the risk of being discharged to a nursing home, Dr. Richard Liu said at the annual clinical congress of the American College of Surgeons.

"For patients in their early 70s who do not have advanced disease or significant comorbidities, laparoscopic colon cancer resection is an option not only to prolong survival but also to preserve quality of life," said Dr. Liu, a surgical resident at Dalhousie University, Halifax, N.S.

The study highlights some important differences in the ways surgeons and patients perceive surgical outcomes. Surgeons and researchers often focus on 5-year survival rates and short-term morbidity and mortality, Dr. Liu said. But prior research done by his group found that immediate quality of life was at least as important to elderly patients – and sometimes more so.

"We have looked at elderly patients in our emergency services and followed up with them several times after admission," he said in an interview. "A common theme that came up was quality of life after hospitalization. Some were actually refusing to have operations for fear of what might become of them afterward."

Dr. Liu’s study comprised 9,416 patients from the U.S. National Inpatient Sample database. All were older than 70 years (mean age 79) and all were living independently at home. They underwent elective colon surgery during 2009-2010 for either cancer or a resection. The primary outcome was discharge back to home or to a long-term care facility. None of the patients were discharged to home health care or to hospice.

Most of the group (61%) had open surgery; the remainder had laparoscopy. Of those who had open surgery, 20% were discharged to a nursing facility, compared with 12.5% of the laparoscopy group – a significant difference.

Laparoscopy significantly decreased the chance of a nursing home admission by 39% in a multivariate analysis that controlled for age, sex, race, comorbidity score, cancer stage, income and insurance, and hospital size.

Factors significantly associated with nursing home discharge included advancing age and cancer stage.

Generally speaking, open surgery is physically more trying for elderly patients. A difficult recovery could be just enough to tip them over the edge from independent living, Dr. Liu said.

Dr. Liu had no financial disclosures.

[email protected]

WASHINGTON – Elderly patients who undergo laparoscopic colon surgery are significantly more likely to be discharged back to their homes than to a long-term care facility.

In a retrospective study of almost 10,000 elderly patients, 12.5% of those who had a laparoscopic procedure went to a nursing home, compared with 20% of those who had open surgery. In a multivariate analysis, laparoscopic surgery was associated with a significant, 39% decrease in the risk of being discharged to a nursing home, Dr. Richard Liu said at the annual clinical congress of the American College of Surgeons.

"For patients in their early 70s who do not have advanced disease or significant comorbidities, laparoscopic colon cancer resection is an option not only to prolong survival but also to preserve quality of life," said Dr. Liu, a surgical resident at Dalhousie University, Halifax, N.S.

The study highlights some important differences in the ways surgeons and patients perceive surgical outcomes. Surgeons and researchers often focus on 5-year survival rates and short-term morbidity and mortality, Dr. Liu said. But prior research done by his group found that immediate quality of life was at least as important to elderly patients – and sometimes more so.

"We have looked at elderly patients in our emergency services and followed up with them several times after admission," he said in an interview. "A common theme that came up was quality of life after hospitalization. Some were actually refusing to have operations for fear of what might become of them afterward."

Dr. Liu’s study comprised 9,416 patients from the U.S. National Inpatient Sample database. All were older than 70 years (mean age 79) and all were living independently at home. They underwent elective colon surgery during 2009-2010 for either cancer or a resection. The primary outcome was discharge back to home or to a long-term care facility. None of the patients were discharged to home health care or to hospice.

Most of the group (61%) had open surgery; the remainder had laparoscopy. Of those who had open surgery, 20% were discharged to a nursing facility, compared with 12.5% of the laparoscopy group – a significant difference.

Laparoscopy significantly decreased the chance of a nursing home admission by 39% in a multivariate analysis that controlled for age, sex, race, comorbidity score, cancer stage, income and insurance, and hospital size.

Factors significantly associated with nursing home discharge included advancing age and cancer stage.

Generally speaking, open surgery is physically more trying for elderly patients. A difficult recovery could be just enough to tip them over the edge from independent living, Dr. Liu said.

Dr. Liu had no financial disclosures.

[email protected]

WASHINGTON – Colon cancer screening with sigmoidoscopy alone could miss up to 50% of colon polyps in older patients.

As people age, polyps seem to develop more and more proximally, Dr. Victor Tsirline said at the annual clinical congress of the American College of Surgeons. His review of more than 120,000 colonoscopies found that a flexible sigmoidoscopy alone could miss 44% of polyps in patients aged 60-69 years and 50% in those aged 70-79 years.

"We found that proximal colon polyps are more frequent with advanced age than previously considered," said Dr. Tsirline of Carolinas Medical Center, Charlotte, N.C. "So if this is true, what happens if we use sigmoidoscopy instead of colonoscopy? If we had, we would have missed 22,800 polyps, and 16,800 of those would have been adenomatous. In [patients 59 and younger] 32%-36% would be missed and in the older patients, 45%-50%."

Dr. Tsirline obtained his data from the Provation MD endoscopy transcription system. He obtained information on 120,365 colonoscopies that were performed from 2003 to 2011.

He cross-referenced this with CoPathPlus, a pathology reporting system. This allowed him to cross-reference polyp pathology (adenoma vs. hyperplasia) by computer algorithm. There was complete information available on 43,833 polyps.

Because of the large sample size, he set his level of statistical significance at P = less than 0.01.

The patients in the study were aged 20-90 years. Of the entire group of procedures, 53,492 colonoscopies (44%) identified polyps. Most studies (64%) found a single polyp; 25% found two, and 11% found three or more. A subset of the colonoscopies was only for average risk screening (44,806). Of these, 46% identified polyps.

Overall, 48% of polyps were adenomatous; 37% were hyperplastic. Pathology was not available for the remainder.

The polyps were fairly evenly distributed throughout the colon: rectum, 18%; sigmoid, 26%; descending, 14%; transverse, 16%; ascending, 15%; cecum, 11%.

However, when broken down by patient age, the distribution changed significantly. With every advancing decade of life, patients were:

• 22% less likely to have polyps in the rectum or sigmoid.

• 7% more likely to have polyps in the descending colon.

• 19% more likely to have polyps in the transverse colon.

• 30% more likely to have polyps in the ascending colon.

• 22% more likely to have polyps in the cecum.

All of these risks were statistically significant, and they held for both adenomatous and hyperplastic polyps.

The findings led Dr. Tsirline to conclude that flexible sigmoidoscopy should not be relied upon as an effective colon cancer screening method in patients older than 60 years. The U.S. Preventive Services Task Force states that sigmoidoscopy every 5 years combined with high-sensitivity fecal occult blood testing every 3 years is an adequate screening alternative.

"From this study, it’s pretty apparent that sigmoidoscopy should not be used for colon cancer screening in older patients," he said.

During a discussion, Dr. Tsirline fielded a question about screening the very elderly – patients in their 80s and 90s. The study group did include a small number of these patients, he said.

"I think the argument for not screening older individuals is based on the question of whether finding a colon cancer would change anything. Most people think the risks of screening and treatment would outweigh the benefits. Yes, you may find anything, but what are you going to do about it?"

Dr. Tsirline had no financial disclosures.

[email protected]

WASHINGTON – Colon cancer screening with sigmoidoscopy alone could miss up to 50% of colon polyps in older patients.

As people age, polyps seem to develop more and more proximally, Dr. Victor Tsirline said at the annual clinical congress of the American College of Surgeons. His review of more than 120,000 colonoscopies found that a flexible sigmoidoscopy alone could miss 44% of polyps in patients aged 60-69 years and 50% in those aged 70-79 years.

"We found that proximal colon polyps are more frequent with advanced age than previously considered," said Dr. Tsirline of Carolinas Medical Center, Charlotte, N.C. "So if this is true, what happens if we use sigmoidoscopy instead of colonoscopy? If we had, we would have missed 22,800 polyps, and 16,800 of those would have been adenomatous. In [patients 59 and younger] 32%-36% would be missed and in the older patients, 45%-50%."

Dr. Tsirline obtained his data from the Provation MD endoscopy transcription system. He obtained information on 120,365 colonoscopies that were performed from 2003 to 2011.

He cross-referenced this with CoPathPlus, a pathology reporting system. This allowed him to cross-reference polyp pathology (adenoma vs. hyperplasia) by computer algorithm. There was complete information available on 43,833 polyps.

Because of the large sample size, he set his level of statistical significance at P = less than 0.01.

The patients in the study were aged 20-90 years. Of the entire group of procedures, 53,492 colonoscopies (44%) identified polyps. Most studies (64%) found a single polyp; 25% found two, and 11% found three or more. A subset of the colonoscopies was only for average risk screening (44,806). Of these, 46% identified polyps.

Overall, 48% of polyps were adenomatous; 37% were hyperplastic. Pathology was not available for the remainder.

The polyps were fairly evenly distributed throughout the colon: rectum, 18%; sigmoid, 26%; descending, 14%; transverse, 16%; ascending, 15%; cecum, 11%.

However, when broken down by patient age, the distribution changed significantly. With every advancing decade of life, patients were:

• 22% less likely to have polyps in the rectum or sigmoid.

• 7% more likely to have polyps in the descending colon.

• 19% more likely to have polyps in the transverse colon.

• 30% more likely to have polyps in the ascending colon.

• 22% more likely to have polyps in the cecum.

All of these risks were statistically significant, and they held for both adenomatous and hyperplastic polyps.

The findings led Dr. Tsirline to conclude that flexible sigmoidoscopy should not be relied upon as an effective colon cancer screening method in patients older than 60 years. The U.S. Preventive Services Task Force states that sigmoidoscopy every 5 years combined with high-sensitivity fecal occult blood testing every 3 years is an adequate screening alternative.

"From this study, it’s pretty apparent that sigmoidoscopy should not be used for colon cancer screening in older patients," he said.

During a discussion, Dr. Tsirline fielded a question about screening the very elderly – patients in their 80s and 90s. The study group did include a small number of these patients, he said.

"I think the argument for not screening older individuals is based on the question of whether finding a colon cancer would change anything. Most people think the risks of screening and treatment would outweigh the benefits. Yes, you may find anything, but what are you going to do about it?"

Dr. Tsirline had no financial disclosures.

[email protected]

WASHINGTON – Colon cancer screening with sigmoidoscopy alone could miss up to 50% of colon polyps in older patients.

As people age, polyps seem to develop more and more proximally, Dr. Victor Tsirline said at the annual clinical congress of the American College of Surgeons. His review of more than 120,000 colonoscopies found that a flexible sigmoidoscopy alone could miss 44% of polyps in patients aged 60-69 years and 50% in those aged 70-79 years.

"We found that proximal colon polyps are more frequent with advanced age than previously considered," said Dr. Tsirline of Carolinas Medical Center, Charlotte, N.C. "So if this is true, what happens if we use sigmoidoscopy instead of colonoscopy? If we had, we would have missed 22,800 polyps, and 16,800 of those would have been adenomatous. In [patients 59 and younger] 32%-36% would be missed and in the older patients, 45%-50%."

Dr. Tsirline obtained his data from the Provation MD endoscopy transcription system. He obtained information on 120,365 colonoscopies that were performed from 2003 to 2011.

He cross-referenced this with CoPathPlus, a pathology reporting system. This allowed him to cross-reference polyp pathology (adenoma vs. hyperplasia) by computer algorithm. There was complete information available on 43,833 polyps.

Because of the large sample size, he set his level of statistical significance at P = less than 0.01.

The patients in the study were aged 20-90 years. Of the entire group of procedures, 53,492 colonoscopies (44%) identified polyps. Most studies (64%) found a single polyp; 25% found two, and 11% found three or more. A subset of the colonoscopies was only for average risk screening (44,806). Of these, 46% identified polyps.

Overall, 48% of polyps were adenomatous; 37% were hyperplastic. Pathology was not available for the remainder.

The polyps were fairly evenly distributed throughout the colon: rectum, 18%; sigmoid, 26%; descending, 14%; transverse, 16%; ascending, 15%; cecum, 11%.

However, when broken down by patient age, the distribution changed significantly. With every advancing decade of life, patients were:

• 22% less likely to have polyps in the rectum or sigmoid.

• 7% more likely to have polyps in the descending colon.

• 19% more likely to have polyps in the transverse colon.

• 30% more likely to have polyps in the ascending colon.

• 22% more likely to have polyps in the cecum.

All of these risks were statistically significant, and they held for both adenomatous and hyperplastic polyps.

The findings led Dr. Tsirline to conclude that flexible sigmoidoscopy should not be relied upon as an effective colon cancer screening method in patients older than 60 years. The U.S. Preventive Services Task Force states that sigmoidoscopy every 5 years combined with high-sensitivity fecal occult blood testing every 3 years is an adequate screening alternative.

"From this study, it’s pretty apparent that sigmoidoscopy should not be used for colon cancer screening in older patients," he said.

During a discussion, Dr. Tsirline fielded a question about screening the very elderly – patients in their 80s and 90s. The study group did include a small number of these patients, he said.

"I think the argument for not screening older individuals is based on the question of whether finding a colon cancer would change anything. Most people think the risks of screening and treatment would outweigh the benefits. Yes, you may find anything, but what are you going to do about it?"

Dr. Tsirline had no financial disclosures.

[email protected]

WASHINGTON – Delays in esophageal cancer surgery after a course of neoadjuvant chemotherapy and radiation were associated with more surgical complications and worse survival, based on the results of a retrospective study presented at the annual clinical congress of the American College of Surgeons.

Clinicians should focus on "prehabilitating" their patients, completing their neoadjuvant therapy and recommending esophagectomy as soon as clinically feasible, Dr. Nicholas Teman said.

Dr. Teman and his colleagues at the University of Michigan, Ann Arbor, reviewed prospectively collected data from the period of 1999-2010 on 457 patients treated at a single site. All patients underwent neoadjuvant chemotherapy and radiation with a subsequent esophagectomy; patients who underwent salvage esophagectomies were excluded from the analysis.

Outcome measures included postoperative pulmonary adverse events, anastomotic leaks, pathologic response, and mortality.

The mean time to surgery after chemotherapy and radiation was 50 days, ranging between 10 and 523 days. The most common reasons for surgical delays were patient deconditioning, noncompliance, seeking a second opinion, and complications stemming from neoadjuvant therapies.

When the time from completion of neoadjuvant therapy to surgery was analyzed as a continuous variable, there were no differences in postoperative complications and mortality. Similarly, postoperative staging and pathologic response were not significantly different.

Additionally, outcomes did not significantly differ for those who had surgery within 8 weeks of completing chemotherapy and radiation and those who had surgery after 8 weeks.

However, when time to surgery was used to place patients into quintiles of 8 weeks or less (n = 345), 9-12 weeks (n = 58), 13-16 weeks (n = 27), 17-26 weeks (n = 19), and 27 or more weeks (n = 8), there were significant differences in pulmonary complications (P = .05) and anastomotic leaks (P = .02), and a trend toward worse mortality between the quintiles (P = .09). No significant differences in pathologic response were noted in the quintiles.

Predictors of higher long-term mortality were lower pretreatment weight (P = .04), tobacco use (P = .05), higher pretreatment stage (P = .004), and failure to complete neoadjuvant treatment (P = .003).

One limitation of the study was that the neoadjuvant therapies were not standardized. A shorter time to surgery was predicted if chemotherapy included cisplatin (P = .04) or taxol (P = .001), and if there were increasing chemotherapy cycles. Chemotherapy that included 5-flourouracil was associated with longer times to surgery (P less than .001).

Dr. Teman and his associates reported no relevant disclosures.

[email protected]

WASHINGTON – Delays in esophageal cancer surgery after a course of neoadjuvant chemotherapy and radiation were associated with more surgical complications and worse survival, based on the results of a retrospective study presented at the annual clinical congress of the American College of Surgeons.

Clinicians should focus on "prehabilitating" their patients, completing their neoadjuvant therapy and recommending esophagectomy as soon as clinically feasible, Dr. Nicholas Teman said.

Dr. Teman and his colleagues at the University of Michigan, Ann Arbor, reviewed prospectively collected data from the period of 1999-2010 on 457 patients treated at a single site. All patients underwent neoadjuvant chemotherapy and radiation with a subsequent esophagectomy; patients who underwent salvage esophagectomies were excluded from the analysis.

Outcome measures included postoperative pulmonary adverse events, anastomotic leaks, pathologic response, and mortality.

The mean time to surgery after chemotherapy and radiation was 50 days, ranging between 10 and 523 days. The most common reasons for surgical delays were patient deconditioning, noncompliance, seeking a second opinion, and complications stemming from neoadjuvant therapies.

When the time from completion of neoadjuvant therapy to surgery was analyzed as a continuous variable, there were no differences in postoperative complications and mortality. Similarly, postoperative staging and pathologic response were not significantly different.

Additionally, outcomes did not significantly differ for those who had surgery within 8 weeks of completing chemotherapy and radiation and those who had surgery after 8 weeks.

However, when time to surgery was used to place patients into quintiles of 8 weeks or less (n = 345), 9-12 weeks (n = 58), 13-16 weeks (n = 27), 17-26 weeks (n = 19), and 27 or more weeks (n = 8), there were significant differences in pulmonary complications (P = .05) and anastomotic leaks (P = .02), and a trend toward worse mortality between the quintiles (P = .09). No significant differences in pathologic response were noted in the quintiles.

Predictors of higher long-term mortality were lower pretreatment weight (P = .04), tobacco use (P = .05), higher pretreatment stage (P = .004), and failure to complete neoadjuvant treatment (P = .003).

One limitation of the study was that the neoadjuvant therapies were not standardized. A shorter time to surgery was predicted if chemotherapy included cisplatin (P = .04) or taxol (P = .001), and if there were increasing chemotherapy cycles. Chemotherapy that included 5-flourouracil was associated with longer times to surgery (P less than .001).

Dr. Teman and his associates reported no relevant disclosures.

[email protected]

WASHINGTON – Delays in esophageal cancer surgery after a course of neoadjuvant chemotherapy and radiation were associated with more surgical complications and worse survival, based on the results of a retrospective study presented at the annual clinical congress of the American College of Surgeons.

Clinicians should focus on "prehabilitating" their patients, completing their neoadjuvant therapy and recommending esophagectomy as soon as clinically feasible, Dr. Nicholas Teman said.

Dr. Teman and his colleagues at the University of Michigan, Ann Arbor, reviewed prospectively collected data from the period of 1999-2010 on 457 patients treated at a single site. All patients underwent neoadjuvant chemotherapy and radiation with a subsequent esophagectomy; patients who underwent salvage esophagectomies were excluded from the analysis.

Outcome measures included postoperative pulmonary adverse events, anastomotic leaks, pathologic response, and mortality.

The mean time to surgery after chemotherapy and radiation was 50 days, ranging between 10 and 523 days. The most common reasons for surgical delays were patient deconditioning, noncompliance, seeking a second opinion, and complications stemming from neoadjuvant therapies.

When the time from completion of neoadjuvant therapy to surgery was analyzed as a continuous variable, there were no differences in postoperative complications and mortality. Similarly, postoperative staging and pathologic response were not significantly different.

Additionally, outcomes did not significantly differ for those who had surgery within 8 weeks of completing chemotherapy and radiation and those who had surgery after 8 weeks.

However, when time to surgery was used to place patients into quintiles of 8 weeks or less (n = 345), 9-12 weeks (n = 58), 13-16 weeks (n = 27), 17-26 weeks (n = 19), and 27 or more weeks (n = 8), there were significant differences in pulmonary complications (P = .05) and anastomotic leaks (P = .02), and a trend toward worse mortality between the quintiles (P = .09). No significant differences in pathologic response were noted in the quintiles.

Predictors of higher long-term mortality were lower pretreatment weight (P = .04), tobacco use (P = .05), higher pretreatment stage (P = .004), and failure to complete neoadjuvant treatment (P = .003).

One limitation of the study was that the neoadjuvant therapies were not standardized. A shorter time to surgery was predicted if chemotherapy included cisplatin (P = .04) or taxol (P = .001), and if there were increasing chemotherapy cycles. Chemotherapy that included 5-flourouracil was associated with longer times to surgery (P less than .001).

Dr. Teman and his associates reported no relevant disclosures.

[email protected]