Head & Neck/Thyroid Cancers

Anemia drugs sold under the brand names of Procrit, Aranesp, and Epogen come under new and scathing scrutiny in an exclusive report published July 20 in the Washington Post.

The investigative article by Peter Whoriskey alleges that pharmaceutical giants Amgen and Johnson & Johnson "wildly overstated" benefits while understating potentially lethal side effects of these erythropoiesis-stimulating agents (ESAs).

While safety trials required by the Food and Drug Administration lagged for more than a decade, the companies successfully lobbied for a payment system that rewarded physicians for giving large doses of their high-priced drugs, according to the report.

Use of the drugs declined in recent years after studies showed higher mortality rates in patients given ESAs. Epoetin-alfa (Procrit and Epogen) and darbepoetin alfa (Aranesp) are used to treat anemia in patients undergoing cancer chemotherapy or dialysis for chronic kidney disease.

Anemia drugs sold under the brand names of Procrit, Aranesp, and Epogen come under new and scathing scrutiny in an exclusive report published July 20 in the Washington Post.

The investigative article by Peter Whoriskey alleges that pharmaceutical giants Amgen and Johnson & Johnson "wildly overstated" benefits while understating potentially lethal side effects of these erythropoiesis-stimulating agents (ESAs).

While safety trials required by the Food and Drug Administration lagged for more than a decade, the companies successfully lobbied for a payment system that rewarded physicians for giving large doses of their high-priced drugs, according to the report.

Use of the drugs declined in recent years after studies showed higher mortality rates in patients given ESAs. Epoetin-alfa (Procrit and Epogen) and darbepoetin alfa (Aranesp) are used to treat anemia in patients undergoing cancer chemotherapy or dialysis for chronic kidney disease.

Anemia drugs sold under the brand names of Procrit, Aranesp, and Epogen come under new and scathing scrutiny in an exclusive report published July 20 in the Washington Post.

The investigative article by Peter Whoriskey alleges that pharmaceutical giants Amgen and Johnson & Johnson "wildly overstated" benefits while understating potentially lethal side effects of these erythropoiesis-stimulating agents (ESAs).

While safety trials required by the Food and Drug Administration lagged for more than a decade, the companies successfully lobbied for a payment system that rewarded physicians for giving large doses of their high-priced drugs, according to the report.

Use of the drugs declined in recent years after studies showed higher mortality rates in patients given ESAs. Epoetin-alfa (Procrit and Epogen) and darbepoetin alfa (Aranesp) are used to treat anemia in patients undergoing cancer chemotherapy or dialysis for chronic kidney disease.

A risk evaluation and mitigation strategy for extended-release and long-acting opioid medications has received Food and Drug Administration approval.

The move has been anticipated as an important element in an attempt to stem the swelling tide of abuse, misuse, and overdose of these prescription drugs while assuring continued access to the highly potent analgesics for patients with moderate to severe persistent pain, Dr. Margaret A. Hamburg said in a media briefing.

The new safety measures, which pertain to approximately 30 currently available medications, will require the manufacturers of the drugs to make FDA-approved education materials available to prescribers no later than March 1, 2013, via development grants to continuing education providers who will develop and deliver the training, said Dr. Hamburg, commissioner of the FDA. In addition, the risk evaluation and mitigation strategy (REMS) will include the distribution of a patient counseling leaflet to prescribers regarding the safe and effective use of the drugs; an updated, single-page medication guide for consumers, an implementation plan, and periodic assessments to evaluate the impact of the program on the safe use of these products, which the FDA will review and use to tweak the program as needed, she said.

"It is important to note that we are focusing on extended-release and long-acting opioid medications ... because these have very specific safety problems that have to be addressed very carefully," according to Dr. John Jenkins, director of the Office of New Drugs within the FDA’s Center for Drug Evaluation and Research. These drugs, including hydromorphone, oxycodone, morphine, oxymorphone, methadone, transdermal fentanyl, and transdermal buprenorphine, "can cause problems even when prescribed appropriately."

The prescriber education component of the REMS will include information regarding the risks and benefits of opioid therapy for individual patients, choosing patients appropriately, patient management and monitoring, and patient counseling, Dr. Jenkins explained. It will also include guidance on the potential for misuse, abuse, and addition, as well as recognizing evidence for these outcomes. The updated medication guide and patient counseling document will include information on how to safely use, store, and dispose of these analgesics, specific instructions for recognizing the signs of potential overdose and advice for preventing accidental exposure to family and household visitors, he said.

With respect to the assessment and auditing component of the program, the FDA has established goals, which the manufacturers are expected to achieve, for the percentage of prescribers who complete the training and for assessing prescribers’ understanding of the risk information. Participation in the educational programs is not mandatory for prescribers, Dr. Hamburg stated. The assessments are also required to evaluate whether the [REMS] adversely affect patient access to these drugs, she said. "Patients in pain must have continued assess to medications they need," she added.

The new REMS program is one component of a multiagency, national strategy unveiled by the White House in 2011 to address prescription drug abuse, "which is this country’s fastest-growing drug problem," said Dr. Hamburg, noting that opioid overdoses in particular were the cause of approximately 15,000 deaths among Americans in 2008 and nearly 16,000 in 2009. Called Epidemic: Responding to America's Prescription Drug Abuse Crisis, the national plan suggests expansion of state-based prescription drug-monitoring programs; seeks creation of recommendations for convenient and environmentally responsible ways to dispose of unused medications; and calls for legislative action to reduce "doctor shopping" and "pill mills."

In the absence of the legislative changes needed to fulfill the comprehensive White House plan, the REMS "is an important and timely step by FDA to supplement prescriber training and consumer information," R. Gil Kerlikowske, director of the White House Office of National Drug Control Policy, said during the telebriefing.

A risk evaluation and mitigation strategy for extended-release and long-acting opioid medications has received Food and Drug Administration approval.

The move has been anticipated as an important element in an attempt to stem the swelling tide of abuse, misuse, and overdose of these prescription drugs while assuring continued access to the highly potent analgesics for patients with moderate to severe persistent pain, Dr. Margaret A. Hamburg said in a media briefing.

The new safety measures, which pertain to approximately 30 currently available medications, will require the manufacturers of the drugs to make FDA-approved education materials available to prescribers no later than March 1, 2013, via development grants to continuing education providers who will develop and deliver the training, said Dr. Hamburg, commissioner of the FDA. In addition, the risk evaluation and mitigation strategy (REMS) will include the distribution of a patient counseling leaflet to prescribers regarding the safe and effective use of the drugs; an updated, single-page medication guide for consumers, an implementation plan, and periodic assessments to evaluate the impact of the program on the safe use of these products, which the FDA will review and use to tweak the program as needed, she said.

"It is important to note that we are focusing on extended-release and long-acting opioid medications ... because these have very specific safety problems that have to be addressed very carefully," according to Dr. John Jenkins, director of the Office of New Drugs within the FDA’s Center for Drug Evaluation and Research. These drugs, including hydromorphone, oxycodone, morphine, oxymorphone, methadone, transdermal fentanyl, and transdermal buprenorphine, "can cause problems even when prescribed appropriately."

The prescriber education component of the REMS will include information regarding the risks and benefits of opioid therapy for individual patients, choosing patients appropriately, patient management and monitoring, and patient counseling, Dr. Jenkins explained. It will also include guidance on the potential for misuse, abuse, and addition, as well as recognizing evidence for these outcomes. The updated medication guide and patient counseling document will include information on how to safely use, store, and dispose of these analgesics, specific instructions for recognizing the signs of potential overdose and advice for preventing accidental exposure to family and household visitors, he said.

With respect to the assessment and auditing component of the program, the FDA has established goals, which the manufacturers are expected to achieve, for the percentage of prescribers who complete the training and for assessing prescribers’ understanding of the risk information. Participation in the educational programs is not mandatory for prescribers, Dr. Hamburg stated. The assessments are also required to evaluate whether the [REMS] adversely affect patient access to these drugs, she said. "Patients in pain must have continued assess to medications they need," she added.

The new REMS program is one component of a multiagency, national strategy unveiled by the White House in 2011 to address prescription drug abuse, "which is this country’s fastest-growing drug problem," said Dr. Hamburg, noting that opioid overdoses in particular were the cause of approximately 15,000 deaths among Americans in 2008 and nearly 16,000 in 2009. Called Epidemic: Responding to America's Prescription Drug Abuse Crisis, the national plan suggests expansion of state-based prescription drug-monitoring programs; seeks creation of recommendations for convenient and environmentally responsible ways to dispose of unused medications; and calls for legislative action to reduce "doctor shopping" and "pill mills."

In the absence of the legislative changes needed to fulfill the comprehensive White House plan, the REMS "is an important and timely step by FDA to supplement prescriber training and consumer information," R. Gil Kerlikowske, director of the White House Office of National Drug Control Policy, said during the telebriefing.

A risk evaluation and mitigation strategy for extended-release and long-acting opioid medications has received Food and Drug Administration approval.

The move has been anticipated as an important element in an attempt to stem the swelling tide of abuse, misuse, and overdose of these prescription drugs while assuring continued access to the highly potent analgesics for patients with moderate to severe persistent pain, Dr. Margaret A. Hamburg said in a media briefing.

The new safety measures, which pertain to approximately 30 currently available medications, will require the manufacturers of the drugs to make FDA-approved education materials available to prescribers no later than March 1, 2013, via development grants to continuing education providers who will develop and deliver the training, said Dr. Hamburg, commissioner of the FDA. In addition, the risk evaluation and mitigation strategy (REMS) will include the distribution of a patient counseling leaflet to prescribers regarding the safe and effective use of the drugs; an updated, single-page medication guide for consumers, an implementation plan, and periodic assessments to evaluate the impact of the program on the safe use of these products, which the FDA will review and use to tweak the program as needed, she said.

"It is important to note that we are focusing on extended-release and long-acting opioid medications ... because these have very specific safety problems that have to be addressed very carefully," according to Dr. John Jenkins, director of the Office of New Drugs within the FDA’s Center for Drug Evaluation and Research. These drugs, including hydromorphone, oxycodone, morphine, oxymorphone, methadone, transdermal fentanyl, and transdermal buprenorphine, "can cause problems even when prescribed appropriately."

The prescriber education component of the REMS will include information regarding the risks and benefits of opioid therapy for individual patients, choosing patients appropriately, patient management and monitoring, and patient counseling, Dr. Jenkins explained. It will also include guidance on the potential for misuse, abuse, and addition, as well as recognizing evidence for these outcomes. The updated medication guide and patient counseling document will include information on how to safely use, store, and dispose of these analgesics, specific instructions for recognizing the signs of potential overdose and advice for preventing accidental exposure to family and household visitors, he said.

With respect to the assessment and auditing component of the program, the FDA has established goals, which the manufacturers are expected to achieve, for the percentage of prescribers who complete the training and for assessing prescribers’ understanding of the risk information. Participation in the educational programs is not mandatory for prescribers, Dr. Hamburg stated. The assessments are also required to evaluate whether the [REMS] adversely affect patient access to these drugs, she said. "Patients in pain must have continued assess to medications they need," she added.

The new REMS program is one component of a multiagency, national strategy unveiled by the White House in 2011 to address prescription drug abuse, "which is this country’s fastest-growing drug problem," said Dr. Hamburg, noting that opioid overdoses in particular were the cause of approximately 15,000 deaths among Americans in 2008 and nearly 16,000 in 2009. Called Epidemic: Responding to America's Prescription Drug Abuse Crisis, the national plan suggests expansion of state-based prescription drug-monitoring programs; seeks creation of recommendations for convenient and environmentally responsible ways to dispose of unused medications; and calls for legislative action to reduce "doctor shopping" and "pill mills."

In the absence of the legislative changes needed to fulfill the comprehensive White House plan, the REMS "is an important and timely step by FDA to supplement prescriber training and consumer information," R. Gil Kerlikowske, director of the White House Office of National Drug Control Policy, said during the telebriefing.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

HOUSTON – A novel gene expression test could eliminate the need for a third of operations done for cytologically indeterminate thyroid nodules by winnowing out low-risk nodules, a large, prospective, double-blind, multicenter study suggests.

The study included fine-needle aspirates of thyroid nodules 1 cm or larger that were classified as indeterminate on cytology and that had corresponding histopathological specimens from excised lesions. A test that measures the expression of 167 genes was applied to 265 cytologically indeterminate nodules, with the patients, physicians, and pathology laboratories blinded to the results of the Afirma gene expression classifier test during management.

In general, cytologically indeterminate thyroid aspirates get classified one of three ways. The negative predictive value of results from the Afirma gene expression classifier test was 95% for the subset cytologically classified as "atypia (or follicular lesion) of undetermined clinical significance," 94% for "follicular neoplasm or lesion suspicious for follicular neoplasm," and 85% for "suspicious cytologic findings," Dr. Erik K. Alexander and his associates reported in a press briefing at the annual meeting of the Endocrine Society.

The Afirma test correctly identified as "suspicious" 78 of the 85 nodules that ultimately were found to be malignant, for a sensitivity of 92% and a specificity of 52%, he said.

A closer look at the seven aspirates that had false negative results from Afirma testing found that six samples lacked a sufficient quantity of thyroid follicular cells to be considered a sufficient sampling of the nodule, said Dr. Alexander of Brigham and Women’s Hospital and Harvard University, Boston.

The results are good enough that clinicians could take a conservative approach to managing most patients whose thyroid nodules are cytologically indeterminate on fine-needle aspiration but benign on the gene expression classifier test, he said.

The New England Journal of Medicine published the study online on June 25 (doi: 10.1056/NEJMoa1203208).

The new gene expression test could eliminate the need for 25,000 of the 75,000 surgeries each year in patients with cytologically indeterminate thyroid aspirates, but at the risk of likely malignancy in 5%-10% of nodules classified as benign, particularly nodules that are cytologically indeterminate but suggestive of cancer, Dr. J. Larry Jameson said in an editorial published simultaneously online by the journal (doi: 10.1056/NEJMe1205893).

In this high-risk group, repeating the fine-needle aspiration biopsy or performing a diagnostic hemithyroidectomy might be reasonable even when the gene expression classifier suggests a benign nodule, said Dr. Jameson of the University of Pennsylvania, Philadelphia.

For patients with indeterminate aspirates and negative Afirma test results who are monitored rather than sent to surgery, clinicians should have a low threshold for repeating fine-needle aspiration if ultrasound tests show rapid nodule growth or characteristics suggestive of cancer, he suggested.

Dr. Jameson called the new gene expression classifier test a "welcome addition" to tools for managing thyroid nodules that could substantially reduce costs by avoiding operations, even when considering the added cost of the test.

One of the strengths of the 49-site study was that 80% of participants came from community-based sites and 20% from academic medical sites, representing a real-world sample, coinvestigator Dr. Bryan R. Haugen said at the press briefing.

He described recent use of the Afirma test at his institution on aspirates from 126 patients with indeterminate cytology results from January 2011 to April 2012. The gene expression classifier results said 56% were benign, 41% were suspicious, and 3% could not produce a result. Seventy patients avoided surgery. Among patients who underwent surgery, 52% of nodes were malignant, said Dr. Haugen, head of endocrinology, metabolism, and diabetes at the University of Colorado, Denver.

Dr. Haugen and Dr. Alexander emphasized that the Afirma test should only be used for aspirates with indeterminate cytology, not for biopsies classified as cytologically benign, because of the 70% specificity when used on benign lesions.

Thyroid nodules are common and can be found in 25%-50% of adults. When fine-needle aspiration biopsy produces indeterminate cytological results, most patients have undergone hemithyroidectomy or total thyroidectomy for diagnosis and treatment.

Veracyte, which makes the gene expression classifier, funded the study and tested the samples in its laboratory. Veracyte employees helped design and supervise the study, conducted the statistical analysis, and made up 6 of the 18 investigators. Dr. Alexander disclosed financial associations with Veracyte, Asuragen, Genzyme, and the Boston Clinical Research Institute. His coinvestigators disclosed financial associations with Veracyte and multiple other companies. Dr. Jameson disclosed financial associations with Quest Diagnostics, Novartis, and Ferring, and said that he knows some of the investigators professionally.

HOUSTON – A novel gene expression test could eliminate the need for a third of operations done for cytologically indeterminate thyroid nodules by winnowing out low-risk nodules, a large, prospective, double-blind, multicenter study suggests.

The study included fine-needle aspirates of thyroid nodules 1 cm or larger that were classified as indeterminate on cytology and that had corresponding histopathological specimens from excised lesions. A test that measures the expression of 167 genes was applied to 265 cytologically indeterminate nodules, with the patients, physicians, and pathology laboratories blinded to the results of the Afirma gene expression classifier test during management.

In general, cytologically indeterminate thyroid aspirates get classified one of three ways. The negative predictive value of results from the Afirma gene expression classifier test was 95% for the subset cytologically classified as "atypia (or follicular lesion) of undetermined clinical significance," 94% for "follicular neoplasm or lesion suspicious for follicular neoplasm," and 85% for "suspicious cytologic findings," Dr. Erik K. Alexander and his associates reported in a press briefing at the annual meeting of the Endocrine Society.

The Afirma test correctly identified as "suspicious" 78 of the 85 nodules that ultimately were found to be malignant, for a sensitivity of 92% and a specificity of 52%, he said.

A closer look at the seven aspirates that had false negative results from Afirma testing found that six samples lacked a sufficient quantity of thyroid follicular cells to be considered a sufficient sampling of the nodule, said Dr. Alexander of Brigham and Women’s Hospital and Harvard University, Boston.

The results are good enough that clinicians could take a conservative approach to managing most patients whose thyroid nodules are cytologically indeterminate on fine-needle aspiration but benign on the gene expression classifier test, he said.

The New England Journal of Medicine published the study online on June 25 (doi: 10.1056/NEJMoa1203208).

The new gene expression test could eliminate the need for 25,000 of the 75,000 surgeries each year in patients with cytologically indeterminate thyroid aspirates, but at the risk of likely malignancy in 5%-10% of nodules classified as benign, particularly nodules that are cytologically indeterminate but suggestive of cancer, Dr. J. Larry Jameson said in an editorial published simultaneously online by the journal (doi: 10.1056/NEJMe1205893).

In this high-risk group, repeating the fine-needle aspiration biopsy or performing a diagnostic hemithyroidectomy might be reasonable even when the gene expression classifier suggests a benign nodule, said Dr. Jameson of the University of Pennsylvania, Philadelphia.

For patients with indeterminate aspirates and negative Afirma test results who are monitored rather than sent to surgery, clinicians should have a low threshold for repeating fine-needle aspiration if ultrasound tests show rapid nodule growth or characteristics suggestive of cancer, he suggested.

Dr. Jameson called the new gene expression classifier test a "welcome addition" to tools for managing thyroid nodules that could substantially reduce costs by avoiding operations, even when considering the added cost of the test.

One of the strengths of the 49-site study was that 80% of participants came from community-based sites and 20% from academic medical sites, representing a real-world sample, coinvestigator Dr. Bryan R. Haugen said at the press briefing.

He described recent use of the Afirma test at his institution on aspirates from 126 patients with indeterminate cytology results from January 2011 to April 2012. The gene expression classifier results said 56% were benign, 41% were suspicious, and 3% could not produce a result. Seventy patients avoided surgery. Among patients who underwent surgery, 52% of nodes were malignant, said Dr. Haugen, head of endocrinology, metabolism, and diabetes at the University of Colorado, Denver.

Dr. Haugen and Dr. Alexander emphasized that the Afirma test should only be used for aspirates with indeterminate cytology, not for biopsies classified as cytologically benign, because of the 70% specificity when used on benign lesions.

Thyroid nodules are common and can be found in 25%-50% of adults. When fine-needle aspiration biopsy produces indeterminate cytological results, most patients have undergone hemithyroidectomy or total thyroidectomy for diagnosis and treatment.

Veracyte, which makes the gene expression classifier, funded the study and tested the samples in its laboratory. Veracyte employees helped design and supervise the study, conducted the statistical analysis, and made up 6 of the 18 investigators. Dr. Alexander disclosed financial associations with Veracyte, Asuragen, Genzyme, and the Boston Clinical Research Institute. His coinvestigators disclosed financial associations with Veracyte and multiple other companies. Dr. Jameson disclosed financial associations with Quest Diagnostics, Novartis, and Ferring, and said that he knows some of the investigators professionally.

HOUSTON – A novel gene expression test could eliminate the need for a third of operations done for cytologically indeterminate thyroid nodules by winnowing out low-risk nodules, a large, prospective, double-blind, multicenter study suggests.

The study included fine-needle aspirates of thyroid nodules 1 cm or larger that were classified as indeterminate on cytology and that had corresponding histopathological specimens from excised lesions. A test that measures the expression of 167 genes was applied to 265 cytologically indeterminate nodules, with the patients, physicians, and pathology laboratories blinded to the results of the Afirma gene expression classifier test during management.

In general, cytologically indeterminate thyroid aspirates get classified one of three ways. The negative predictive value of results from the Afirma gene expression classifier test was 95% for the subset cytologically classified as "atypia (or follicular lesion) of undetermined clinical significance," 94% for "follicular neoplasm or lesion suspicious for follicular neoplasm," and 85% for "suspicious cytologic findings," Dr. Erik K. Alexander and his associates reported in a press briefing at the annual meeting of the Endocrine Society.

The Afirma test correctly identified as "suspicious" 78 of the 85 nodules that ultimately were found to be malignant, for a sensitivity of 92% and a specificity of 52%, he said.

A closer look at the seven aspirates that had false negative results from Afirma testing found that six samples lacked a sufficient quantity of thyroid follicular cells to be considered a sufficient sampling of the nodule, said Dr. Alexander of Brigham and Women’s Hospital and Harvard University, Boston.

The results are good enough that clinicians could take a conservative approach to managing most patients whose thyroid nodules are cytologically indeterminate on fine-needle aspiration but benign on the gene expression classifier test, he said.

The New England Journal of Medicine published the study online on June 25 (doi: 10.1056/NEJMoa1203208).

The new gene expression test could eliminate the need for 25,000 of the 75,000 surgeries each year in patients with cytologically indeterminate thyroid aspirates, but at the risk of likely malignancy in 5%-10% of nodules classified as benign, particularly nodules that are cytologically indeterminate but suggestive of cancer, Dr. J. Larry Jameson said in an editorial published simultaneously online by the journal (doi: 10.1056/NEJMe1205893).

In this high-risk group, repeating the fine-needle aspiration biopsy or performing a diagnostic hemithyroidectomy might be reasonable even when the gene expression classifier suggests a benign nodule, said Dr. Jameson of the University of Pennsylvania, Philadelphia.

For patients with indeterminate aspirates and negative Afirma test results who are monitored rather than sent to surgery, clinicians should have a low threshold for repeating fine-needle aspiration if ultrasound tests show rapid nodule growth or characteristics suggestive of cancer, he suggested.

Dr. Jameson called the new gene expression classifier test a "welcome addition" to tools for managing thyroid nodules that could substantially reduce costs by avoiding operations, even when considering the added cost of the test.

One of the strengths of the 49-site study was that 80% of participants came from community-based sites and 20% from academic medical sites, representing a real-world sample, coinvestigator Dr. Bryan R. Haugen said at the press briefing.

He described recent use of the Afirma test at his institution on aspirates from 126 patients with indeterminate cytology results from January 2011 to April 2012. The gene expression classifier results said 56% were benign, 41% were suspicious, and 3% could not produce a result. Seventy patients avoided surgery. Among patients who underwent surgery, 52% of nodes were malignant, said Dr. Haugen, head of endocrinology, metabolism, and diabetes at the University of Colorado, Denver.

Dr. Haugen and Dr. Alexander emphasized that the Afirma test should only be used for aspirates with indeterminate cytology, not for biopsies classified as cytologically benign, because of the 70% specificity when used on benign lesions.

Thyroid nodules are common and can be found in 25%-50% of adults. When fine-needle aspiration biopsy produces indeterminate cytological results, most patients have undergone hemithyroidectomy or total thyroidectomy for diagnosis and treatment.

Veracyte, which makes the gene expression classifier, funded the study and tested the samples in its laboratory. Veracyte employees helped design and supervise the study, conducted the statistical analysis, and made up 6 of the 18 investigators. Dr. Alexander disclosed financial associations with Veracyte, Asuragen, Genzyme, and the Boston Clinical Research Institute. His coinvestigators disclosed financial associations with Veracyte and multiple other companies. Dr. Jameson disclosed financial associations with Quest Diagnostics, Novartis, and Ferring, and said that he knows some of the investigators professionally.

As the use of CT scans in children – especially multiple scans – is increasing, so is concern about the long-term risks of CT radiation exposure.

There are approximately 7 million CT studies performed in children every year in the United States, and the number is increasing approximately 10% per year, according to the Alliance for Radiation Safety in Pediatric Imaging, a consortium of 63 professional societies representing the fields of radiology, pediatrics, and medical physics and radiation safety.  

In a 2012 British study of children from birth to age 21 years who underwent multiple CT scans in 1985-2002, the researchers found a small increased risk of leukemia and brain tumors a decade after the first scan. They estimated that for every 10,000 head CT scans performed on children 10 years of age or younger, one case of leukemia and one brain tumor would occur in the decade following the first CT beyond what would have been expected if the children had no CT scans.

But the physicians involved in this study and others are quick to emphasize the benefits of CT scans: that these scans are extremely important in early diagnosis, clinical decision-making, and for saving lives. But much needs to be done to make sure all CT scans are justified and to reduce the doses of radiation associated with them.

The Food and Drug Administration is working to reduce unnecessary radiation exposure for children on several fronts, through recommending manufacturers design new X-ray imaging devices – including CT scanners – to address pediatric safety issues or by writing new safety training materials that emphasize dose reduction for children on existing equipment.

Read a news article in the Washington Post.

As the use of CT scans in children – especially multiple scans – is increasing, so is concern about the long-term risks of CT radiation exposure.

There are approximately 7 million CT studies performed in children every year in the United States, and the number is increasing approximately 10% per year, according to the Alliance for Radiation Safety in Pediatric Imaging, a consortium of 63 professional societies representing the fields of radiology, pediatrics, and medical physics and radiation safety.  

In a 2012 British study of children from birth to age 21 years who underwent multiple CT scans in 1985-2002, the researchers found a small increased risk of leukemia and brain tumors a decade after the first scan. They estimated that for every 10,000 head CT scans performed on children 10 years of age or younger, one case of leukemia and one brain tumor would occur in the decade following the first CT beyond what would have been expected if the children had no CT scans.

But the physicians involved in this study and others are quick to emphasize the benefits of CT scans: that these scans are extremely important in early diagnosis, clinical decision-making, and for saving lives. But much needs to be done to make sure all CT scans are justified and to reduce the doses of radiation associated with them.

The Food and Drug Administration is working to reduce unnecessary radiation exposure for children on several fronts, through recommending manufacturers design new X-ray imaging devices – including CT scanners – to address pediatric safety issues or by writing new safety training materials that emphasize dose reduction for children on existing equipment.

Read a news article in the Washington Post.

As the use of CT scans in children – especially multiple scans – is increasing, so is concern about the long-term risks of CT radiation exposure.

There are approximately 7 million CT studies performed in children every year in the United States, and the number is increasing approximately 10% per year, according to the Alliance for Radiation Safety in Pediatric Imaging, a consortium of 63 professional societies representing the fields of radiology, pediatrics, and medical physics and radiation safety.  

In a 2012 British study of children from birth to age 21 years who underwent multiple CT scans in 1985-2002, the researchers found a small increased risk of leukemia and brain tumors a decade after the first scan. They estimated that for every 10,000 head CT scans performed on children 10 years of age or younger, one case of leukemia and one brain tumor would occur in the decade following the first CT beyond what would have been expected if the children had no CT scans.

But the physicians involved in this study and others are quick to emphasize the benefits of CT scans: that these scans are extremely important in early diagnosis, clinical decision-making, and for saving lives. But much needs to be done to make sure all CT scans are justified and to reduce the doses of radiation associated with them.

The Food and Drug Administration is working to reduce unnecessary radiation exposure for children on several fronts, through recommending manufacturers design new X-ray imaging devices – including CT scanners – to address pediatric safety issues or by writing new safety training materials that emphasize dose reduction for children on existing equipment.

Read a news article in the Washington Post.

Patients who are obese are more likely than are normal-weight patients to present with advanced papillary thyroid cancer and to have an aggressive subtype of the malignancy, according to a report published online May 21 in the Archives of Surgery.

The reasons for these adverse findings are not yet certain, but the findings are enough to warrant more careful screening for thyroid cancer among obese patients, said Dr. Avital Harari of the section of endocrine surgery, University of California, Los Angeles, and her associates.

Increased body mass index has been linked to an increased incidence of thyroid cancer in several study populations. Higher BMI also has been associated with a more advanced stage of disease at diagnosis in several other types of cancer, including breast and prostate cancers.

To assess a possible relationship between obesity and thyroid cancer, Dr. Harari and her colleagues reviewed the medical records of 443 adults who underwent total thyroidectomy as first-line treatment for papillary thyroid cancer and its variants at their institution during 2004-2011.

The study subjects were categorized as normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg), obese (30-39.9 kg), or morbidly obese (at least 40 kg). The age range was 18-93 years, with a mean age of 48 years.

Obese and morbidly obese patients were significantly more likely than were thinner patients to have stage III or IV disease at diagnosis. In addition, for the study cohort as a whole, higher BMI was a significant predictor of presenting with stage III or IV disease, with an odds ratio (OR) of 1.94 for overweight subjects, an OR of 2.11 for obese subjects, and an OR of 3.67 for morbidly obese patients, compared with normal-weight patients.

Subgroup analysis showed that the percentages of the most-aggressive subtypes of papillary thyroid cancer were higher among patients in the obese and morbidly obese categories than they were among those in the normal-weight and overweight categories, the investigators said (Arch. Surg. 2012 [doi:10.1001/archsurg.2012.713]).

It was noteworthy that patients with higher BMI did not have higher complication rates than did thinner patients. Rates of wound infection, excessive bleeding, hypocalcemia, respiratory problems, and reintubations were similar across all BMI categories. "However, the number of patients was underpowered to detect a less than 3% complication rate," Dr. Harari and her associates noted.

Obese and morbidly obese patients were significantly more likely to have laryngeal nerve dysfunction after thyroidectomy – a rate of 12%, compared with a 2.6% rate in overweight patients and a 2.0% rate in normal-weight patients. But that was because the obese and morbidly obese patients already had vocal cord dysfunction at presentation, concordant with their more advanced local disease.

"We believe that the cause of [the] increase in aggressive papillary thyroid cancer in the overweight and obese population could be multifactorial," the researchers said.

One such factor may be that diagnosis is delayed in patients with higher BMI because it is more difficult to palpate thyroid nodules in the obese neck, so tumors are more advanced when they are finally detected. Another possibility is that certain biomarkers common in obesity, such as high leptin levels, are associated with cancer development and progression.

It is also likely that obesity and thyroid cancer are both linked to third biological factor, such as diabetes. A recent study of diet and health in older Americans found an increased risk of papillary thyroid cancer among women with diabetes, Dr. Harari and her colleagues said.

"Given our findings, we believe that obese patients are at a higher risk of developing aggressive thyroid cancers and thus should be screened ... by sonography, which has been shown to be more sensitive in detecting thyroid cancer than physical examination alone," they said.

No potential financial conflicts of interest were reported.

Patients who are obese are more likely than are normal-weight patients to present with advanced papillary thyroid cancer and to have an aggressive subtype of the malignancy, according to a report published online May 21 in the Archives of Surgery.

The reasons for these adverse findings are not yet certain, but the findings are enough to warrant more careful screening for thyroid cancer among obese patients, said Dr. Avital Harari of the section of endocrine surgery, University of California, Los Angeles, and her associates.

Increased body mass index has been linked to an increased incidence of thyroid cancer in several study populations. Higher BMI also has been associated with a more advanced stage of disease at diagnosis in several other types of cancer, including breast and prostate cancers.

To assess a possible relationship between obesity and thyroid cancer, Dr. Harari and her colleagues reviewed the medical records of 443 adults who underwent total thyroidectomy as first-line treatment for papillary thyroid cancer and its variants at their institution during 2004-2011.

The study subjects were categorized as normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg), obese (30-39.9 kg), or morbidly obese (at least 40 kg). The age range was 18-93 years, with a mean age of 48 years.

Obese and morbidly obese patients were significantly more likely than were thinner patients to have stage III or IV disease at diagnosis. In addition, for the study cohort as a whole, higher BMI was a significant predictor of presenting with stage III or IV disease, with an odds ratio (OR) of 1.94 for overweight subjects, an OR of 2.11 for obese subjects, and an OR of 3.67 for morbidly obese patients, compared with normal-weight patients.

Subgroup analysis showed that the percentages of the most-aggressive subtypes of papillary thyroid cancer were higher among patients in the obese and morbidly obese categories than they were among those in the normal-weight and overweight categories, the investigators said (Arch. Surg. 2012 [doi:10.1001/archsurg.2012.713]).

It was noteworthy that patients with higher BMI did not have higher complication rates than did thinner patients. Rates of wound infection, excessive bleeding, hypocalcemia, respiratory problems, and reintubations were similar across all BMI categories. "However, the number of patients was underpowered to detect a less than 3% complication rate," Dr. Harari and her associates noted.

Obese and morbidly obese patients were significantly more likely to have laryngeal nerve dysfunction after thyroidectomy – a rate of 12%, compared with a 2.6% rate in overweight patients and a 2.0% rate in normal-weight patients. But that was because the obese and morbidly obese patients already had vocal cord dysfunction at presentation, concordant with their more advanced local disease.

"We believe that the cause of [the] increase in aggressive papillary thyroid cancer in the overweight and obese population could be multifactorial," the researchers said.

One such factor may be that diagnosis is delayed in patients with higher BMI because it is more difficult to palpate thyroid nodules in the obese neck, so tumors are more advanced when they are finally detected. Another possibility is that certain biomarkers common in obesity, such as high leptin levels, are associated with cancer development and progression.

It is also likely that obesity and thyroid cancer are both linked to third biological factor, such as diabetes. A recent study of diet and health in older Americans found an increased risk of papillary thyroid cancer among women with diabetes, Dr. Harari and her colleagues said.

"Given our findings, we believe that obese patients are at a higher risk of developing aggressive thyroid cancers and thus should be screened ... by sonography, which has been shown to be more sensitive in detecting thyroid cancer than physical examination alone," they said.

No potential financial conflicts of interest were reported.

Patients who are obese are more likely than are normal-weight patients to present with advanced papillary thyroid cancer and to have an aggressive subtype of the malignancy, according to a report published online May 21 in the Archives of Surgery.

The reasons for these adverse findings are not yet certain, but the findings are enough to warrant more careful screening for thyroid cancer among obese patients, said Dr. Avital Harari of the section of endocrine surgery, University of California, Los Angeles, and her associates.

Increased body mass index has been linked to an increased incidence of thyroid cancer in several study populations. Higher BMI also has been associated with a more advanced stage of disease at diagnosis in several other types of cancer, including breast and prostate cancers.

To assess a possible relationship between obesity and thyroid cancer, Dr. Harari and her colleagues reviewed the medical records of 443 adults who underwent total thyroidectomy as first-line treatment for papillary thyroid cancer and its variants at their institution during 2004-2011.

The study subjects were categorized as normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg), obese (30-39.9 kg), or morbidly obese (at least 40 kg). The age range was 18-93 years, with a mean age of 48 years.

Obese and morbidly obese patients were significantly more likely than were thinner patients to have stage III or IV disease at diagnosis. In addition, for the study cohort as a whole, higher BMI was a significant predictor of presenting with stage III or IV disease, with an odds ratio (OR) of 1.94 for overweight subjects, an OR of 2.11 for obese subjects, and an OR of 3.67 for morbidly obese patients, compared with normal-weight patients.

Subgroup analysis showed that the percentages of the most-aggressive subtypes of papillary thyroid cancer were higher among patients in the obese and morbidly obese categories than they were among those in the normal-weight and overweight categories, the investigators said (Arch. Surg. 2012 [doi:10.1001/archsurg.2012.713]).

It was noteworthy that patients with higher BMI did not have higher complication rates than did thinner patients. Rates of wound infection, excessive bleeding, hypocalcemia, respiratory problems, and reintubations were similar across all BMI categories. "However, the number of patients was underpowered to detect a less than 3% complication rate," Dr. Harari and her associates noted.

Obese and morbidly obese patients were significantly more likely to have laryngeal nerve dysfunction after thyroidectomy – a rate of 12%, compared with a 2.6% rate in overweight patients and a 2.0% rate in normal-weight patients. But that was because the obese and morbidly obese patients already had vocal cord dysfunction at presentation, concordant with their more advanced local disease.

"We believe that the cause of [the] increase in aggressive papillary thyroid cancer in the overweight and obese population could be multifactorial," the researchers said.

One such factor may be that diagnosis is delayed in patients with higher BMI because it is more difficult to palpate thyroid nodules in the obese neck, so tumors are more advanced when they are finally detected. Another possibility is that certain biomarkers common in obesity, such as high leptin levels, are associated with cancer development and progression.

It is also likely that obesity and thyroid cancer are both linked to third biological factor, such as diabetes. A recent study of diet and health in older Americans found an increased risk of papillary thyroid cancer among women with diabetes, Dr. Harari and her colleagues said.

"Given our findings, we believe that obese patients are at a higher risk of developing aggressive thyroid cancers and thus should be screened ... by sonography, which has been shown to be more sensitive in detecting thyroid cancer than physical examination alone," they said.

No potential financial conflicts of interest were reported.

PHOENIX – Late oral effects of head and neck cancer therapy are "multiple, underreported, and underappreciated."

That is the perspective of Joel Epstein, D.M.D., who has worked extensively with head and neck cancer patients experiencing severe dental and other oral problems following radiation therapy.

"The acute complications of head and neck cancer therapy are pretty well known, but the late complications are underappreciated," Dr. Epstein, director of oral medicine at City of Hope National Medical Center, Duarte, Calif., told attendees at the symposium.

As head and neck cancer treatments have advanced and patients are living longer, the spectrum of treatment complications has shifted, he explained. In a 5-year, prospective longitudinal study of 122 patients with oral carcinoma, dry mouth, sticky saliva, speech changes, dental problems, and sleep disturbance were reported by all patients except those treated only with surgery. These complications persisted at 1 and 5 years and affected quality of life (Head Neck 2008;30:461-70).

According to Dr. Epstein, the data illustrate the need for better collaboration between oncologists and dentists. "While people discuss the concept of multidisciplinary [and] interdisciplinary teams for the benefit of our patients, it is unfortunate that dentistry developed separately from physicians and surgeons. So while we need to interact, we’re not really well prepared to do so, particularly in the community," he said.

Photos courtesy Dr. Joel Epstein

Clinically, it’s important to evaluate oral care, including brushing, flossing, fluoride, and tobacco abstinence, at all head and neck cancer treatment follow-up visits. Patients should be assessed for xerostomia, speech, swallowing, mucosal sensitivity, and taste. Head and neck and oral exams should include assessments for saliva (wet mucosa), exposed bone, infection, and new lesions or recurrent cancer, and a dental exam (for plaque, caries, and periodontal health), Dr. Epstein recommended.

Dry mouth, in particular, can lead to a host of other chronic problems related to swallowing, eating, sleeping, and dental health. When the 50-item Vanderbilt Head and Neck Symptom Survey was administered to a total of 70 patients, 67 reported having dry mouth at more than 6 months’ follow up (Head Neck 2011 Aug. 24 [doi:10.1002/hed.21816]).

The majority reported that dry mouth makes chewing/swallowing difficult (65) and that it affects their ability to sleep (67) and talk (64). With regard to eating and swallowing, similar majorities reported trouble eating solids (67) and drinking liquids (68), with food getting stuck in their mouth (66) and throat (67).

And, of concern, the same numbers of patients reported the sensation of choking or strangling on solids (66) and liquids (68). "The impact on function from the lack of saliva and the change in quality of saliva are issues we need to be more ready and willing to address," Dr. Epstein commented.

Taste and smell may also be profoundly altered. In the Vanderbilt survey, most patients reported altered taste (68), a decreased desire to eat (68), altered food choices (66), and a decrease in food eaten (66). A change in sense of smell was reported by 69 patients.

Such alterations often result in changes in diet, including decreased consumption of high-fiber food and of vitamins and other nutrients, along with increased consumption of fats, caffeine, and sugar. All of these factors increase the risk for dietary deficiencies, as well as dental caries.

Yet, altered taste sensation is not something patients might think to mention. "Half of patients experience altered taste sensation. But if they think you’re not interested or you don’t ask, you may not know," Dr. Epstein commented.

Periodontal health is often compromised by hyposalivation, which can lead to inflammation, bone/attachment loss, oral infection, and necrosis. Dental demineralization and cavitation may develop as early as 2-3 months after cancer treatment and progress rapidly, leading to fractures of the gum line, tooth loss, and necrosis.

Demineralization appears as a change to white, which may not be recognized as a problem because of the belief that white teeth are healthy. However, recognition at this stage is critical in order to prevent further dental damage, he said.

"The white change near the gum line and the tips of the teeth represent demineralization, and [in] time reversal can be accomplished prior to structural breakdown. Once cavitation has occurred, fillings are needed and prevention must be instituted or the cavities will recur and progress," Dr. Epstein said in an interview.

In the Vanderbilt survey, reported dental problems included difficulty chewing because of teeth/dentures (54 of the 70 patients); tooth sensitivity to hot, cold, or sweet foods (52); teeth feeling looser (51); teeth cracking/chipping (50); and trouble with dentures (24).

Oral candidiasis is another common problem, affecting approximately 39% of head and neck cancer patients during treatment and 33% afterward. One common clinical mistake is prescribing these patients antifungals that contain sugar, such as nystatin. "Nystatin is very high in sugar, and one of the [most commonly] used antifungals. The message is to avoid sugar-sweetened products in dry mouth patients and utilize alternatives," Dr. Epstein said in the interview.

Mucosal sensitivity and pain is also frequent. In a meta-analysis of 22 studies published between 1990 and 2008, the prevalence of trismus was 25.4% in patients who received conventional radiotherapy and 5% for the few intensity-modulated radiation therapy studies that were included, suggesting that the newer radiation modality might diminish the problem (Support. Care Cancer 2010;18:1033-8).

Data suggest that the radiation effect on mandibular movement correlates with the radiation dose to the mastication muscles, with a steep dose-response curve. Onset is typically 2-6 months post treatment and is ongoing. Concurrent chemotherapy may increase the incidence and/or severity of mandibular immobility (Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 1999;88:365-73).

In the Vanderbilt survey, most patients reported burning in the throat or mouth (69); sensitivity to hot, spicy, or acid food (67); sensitivity to dryness (69); and changes in food intake because of mucosal sensitivity (67); most patients also reported that mucosal sensitivity prevents tooth brushing (63). "Mucosal sensitivity is a quality of life issue," Dr. Epstein said.

The Vanderbilt survey was particularly illuminating, Dr. Epstein commented. Studies that utilize claims data probably underrepresent the problem of long-term oral complications because dental and medical insurance are separate and the data are not easily combined, he added.

"Late oral effects are best diagnosed [and] managed in a multidisciplinary team with close communication between medical and dental providers. ... We really need to come together."

The Multinational Association of Supportive Care in Cancer is developing tools to improve communication between dentistry and medicine. These could be available for beta testing as early as this fall.

Dr. Epstein said he had no relevant financial disclosures.

PHOENIX – Late oral effects of head and neck cancer therapy are "multiple, underreported, and underappreciated."

That is the perspective of Joel Epstein, D.M.D., who has worked extensively with head and neck cancer patients experiencing severe dental and other oral problems following radiation therapy.

"The acute complications of head and neck cancer therapy are pretty well known, but the late complications are underappreciated," Dr. Epstein, director of oral medicine at City of Hope National Medical Center, Duarte, Calif., told attendees at the symposium.

As head and neck cancer treatments have advanced and patients are living longer, the spectrum of treatment complications has shifted, he explained. In a 5-year, prospective longitudinal study of 122 patients with oral carcinoma, dry mouth, sticky saliva, speech changes, dental problems, and sleep disturbance were reported by all patients except those treated only with surgery. These complications persisted at 1 and 5 years and affected quality of life (Head Neck 2008;30:461-70).

According to Dr. Epstein, the data illustrate the need for better collaboration between oncologists and dentists. "While people discuss the concept of multidisciplinary [and] interdisciplinary teams for the benefit of our patients, it is unfortunate that dentistry developed separately from physicians and surgeons. So while we need to interact, we’re not really well prepared to do so, particularly in the community," he said.

Photos courtesy Dr. Joel Epstein

Clinically, it’s important to evaluate oral care, including brushing, flossing, fluoride, and tobacco abstinence, at all head and neck cancer treatment follow-up visits. Patients should be assessed for xerostomia, speech, swallowing, mucosal sensitivity, and taste. Head and neck and oral exams should include assessments for saliva (wet mucosa), exposed bone, infection, and new lesions or recurrent cancer, and a dental exam (for plaque, caries, and periodontal health), Dr. Epstein recommended.

Dry mouth, in particular, can lead to a host of other chronic problems related to swallowing, eating, sleeping, and dental health. When the 50-item Vanderbilt Head and Neck Symptom Survey was administered to a total of 70 patients, 67 reported having dry mouth at more than 6 months’ follow up (Head Neck 2011 Aug. 24 [doi:10.1002/hed.21816]).

The majority reported that dry mouth makes chewing/swallowing difficult (65) and that it affects their ability to sleep (67) and talk (64). With regard to eating and swallowing, similar majorities reported trouble eating solids (67) and drinking liquids (68), with food getting stuck in their mouth (66) and throat (67).

And, of concern, the same numbers of patients reported the sensation of choking or strangling on solids (66) and liquids (68). "The impact on function from the lack of saliva and the change in quality of saliva are issues we need to be more ready and willing to address," Dr. Epstein commented.

Taste and smell may also be profoundly altered. In the Vanderbilt survey, most patients reported altered taste (68), a decreased desire to eat (68), altered food choices (66), and a decrease in food eaten (66). A change in sense of smell was reported by 69 patients.

Such alterations often result in changes in diet, including decreased consumption of high-fiber food and of vitamins and other nutrients, along with increased consumption of fats, caffeine, and sugar. All of these factors increase the risk for dietary deficiencies, as well as dental caries.

Yet, altered taste sensation is not something patients might think to mention. "Half of patients experience altered taste sensation. But if they think you’re not interested or you don’t ask, you may not know," Dr. Epstein commented.

Periodontal health is often compromised by hyposalivation, which can lead to inflammation, bone/attachment loss, oral infection, and necrosis. Dental demineralization and cavitation may develop as early as 2-3 months after cancer treatment and progress rapidly, leading to fractures of the gum line, tooth loss, and necrosis.

Demineralization appears as a change to white, which may not be recognized as a problem because of the belief that white teeth are healthy. However, recognition at this stage is critical in order to prevent further dental damage, he said.

"The white change near the gum line and the tips of the teeth represent demineralization, and [in] time reversal can be accomplished prior to structural breakdown. Once cavitation has occurred, fillings are needed and prevention must be instituted or the cavities will recur and progress," Dr. Epstein said in an interview.

In the Vanderbilt survey, reported dental problems included difficulty chewing because of teeth/dentures (54 of the 70 patients); tooth sensitivity to hot, cold, or sweet foods (52); teeth feeling looser (51); teeth cracking/chipping (50); and trouble with dentures (24).

Oral candidiasis is another common problem, affecting approximately 39% of head and neck cancer patients during treatment and 33% afterward. One common clinical mistake is prescribing these patients antifungals that contain sugar, such as nystatin. "Nystatin is very high in sugar, and one of the [most commonly] used antifungals. The message is to avoid sugar-sweetened products in dry mouth patients and utilize alternatives," Dr. Epstein said in the interview.

Mucosal sensitivity and pain is also frequent. In a meta-analysis of 22 studies published between 1990 and 2008, the prevalence of trismus was 25.4% in patients who received conventional radiotherapy and 5% for the few intensity-modulated radiation therapy studies that were included, suggesting that the newer radiation modality might diminish the problem (Support. Care Cancer 2010;18:1033-8).

Data suggest that the radiation effect on mandibular movement correlates with the radiation dose to the mastication muscles, with a steep dose-response curve. Onset is typically 2-6 months post treatment and is ongoing. Concurrent chemotherapy may increase the incidence and/or severity of mandibular immobility (Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 1999;88:365-73).

In the Vanderbilt survey, most patients reported burning in the throat or mouth (69); sensitivity to hot, spicy, or acid food (67); sensitivity to dryness (69); and changes in food intake because of mucosal sensitivity (67); most patients also reported that mucosal sensitivity prevents tooth brushing (63). "Mucosal sensitivity is a quality of life issue," Dr. Epstein said.

The Vanderbilt survey was particularly illuminating, Dr. Epstein commented. Studies that utilize claims data probably underrepresent the problem of long-term oral complications because dental and medical insurance are separate and the data are not easily combined, he added.

"Late oral effects are best diagnosed [and] managed in a multidisciplinary team with close communication between medical and dental providers. ... We really need to come together."

The Multinational Association of Supportive Care in Cancer is developing tools to improve communication between dentistry and medicine. These could be available for beta testing as early as this fall.

Dr. Epstein said he had no relevant financial disclosures.

PHOENIX – Late oral effects of head and neck cancer therapy are "multiple, underreported, and underappreciated."

That is the perspective of Joel Epstein, D.M.D., who has worked extensively with head and neck cancer patients experiencing severe dental and other oral problems following radiation therapy.

"The acute complications of head and neck cancer therapy are pretty well known, but the late complications are underappreciated," Dr. Epstein, director of oral medicine at City of Hope National Medical Center, Duarte, Calif., told attendees at the symposium.

As head and neck cancer treatments have advanced and patients are living longer, the spectrum of treatment complications has shifted, he explained. In a 5-year, prospective longitudinal study of 122 patients with oral carcinoma, dry mouth, sticky saliva, speech changes, dental problems, and sleep disturbance were reported by all patients except those treated only with surgery. These complications persisted at 1 and 5 years and affected quality of life (Head Neck 2008;30:461-70).

According to Dr. Epstein, the data illustrate the need for better collaboration between oncologists and dentists. "While people discuss the concept of multidisciplinary [and] interdisciplinary teams for the benefit of our patients, it is unfortunate that dentistry developed separately from physicians and surgeons. So while we need to interact, we’re not really well prepared to do so, particularly in the community," he said.

Photos courtesy Dr. Joel Epstein

Clinically, it’s important to evaluate oral care, including brushing, flossing, fluoride, and tobacco abstinence, at all head and neck cancer treatment follow-up visits. Patients should be assessed for xerostomia, speech, swallowing, mucosal sensitivity, and taste. Head and neck and oral exams should include assessments for saliva (wet mucosa), exposed bone, infection, and new lesions or recurrent cancer, and a dental exam (for plaque, caries, and periodontal health), Dr. Epstein recommended.

Dry mouth, in particular, can lead to a host of other chronic problems related to swallowing, eating, sleeping, and dental health. When the 50-item Vanderbilt Head and Neck Symptom Survey was administered to a total of 70 patients, 67 reported having dry mouth at more than 6 months’ follow up (Head Neck 2011 Aug. 24 [doi:10.1002/hed.21816]).

The majority reported that dry mouth makes chewing/swallowing difficult (65) and that it affects their ability to sleep (67) and talk (64). With regard to eating and swallowing, similar majorities reported trouble eating solids (67) and drinking liquids (68), with food getting stuck in their mouth (66) and throat (67).

And, of concern, the same numbers of patients reported the sensation of choking or strangling on solids (66) and liquids (68). "The impact on function from the lack of saliva and the change in quality of saliva are issues we need to be more ready and willing to address," Dr. Epstein commented.

Taste and smell may also be profoundly altered. In the Vanderbilt survey, most patients reported altered taste (68), a decreased desire to eat (68), altered food choices (66), and a decrease in food eaten (66). A change in sense of smell was reported by 69 patients.

Such alterations often result in changes in diet, including decreased consumption of high-fiber food and of vitamins and other nutrients, along with increased consumption of fats, caffeine, and sugar. All of these factors increase the risk for dietary deficiencies, as well as dental caries.

Yet, altered taste sensation is not something patients might think to mention. "Half of patients experience altered taste sensation. But if they think you’re not interested or you don’t ask, you may not know," Dr. Epstein commented.

Periodontal health is often compromised by hyposalivation, which can lead to inflammation, bone/attachment loss, oral infection, and necrosis. Dental demineralization and cavitation may develop as early as 2-3 months after cancer treatment and progress rapidly, leading to fractures of the gum line, tooth loss, and necrosis.

Demineralization appears as a change to white, which may not be recognized as a problem because of the belief that white teeth are healthy. However, recognition at this stage is critical in order to prevent further dental damage, he said.

"The white change near the gum line and the tips of the teeth represent demineralization, and [in] time reversal can be accomplished prior to structural breakdown. Once cavitation has occurred, fillings are needed and prevention must be instituted or the cavities will recur and progress," Dr. Epstein said in an interview.

In the Vanderbilt survey, reported dental problems included difficulty chewing because of teeth/dentures (54 of the 70 patients); tooth sensitivity to hot, cold, or sweet foods (52); teeth feeling looser (51); teeth cracking/chipping (50); and trouble with dentures (24).

Oral candidiasis is another common problem, affecting approximately 39% of head and neck cancer patients during treatment and 33% afterward. One common clinical mistake is prescribing these patients antifungals that contain sugar, such as nystatin. "Nystatin is very high in sugar, and one of the [most commonly] used antifungals. The message is to avoid sugar-sweetened products in dry mouth patients and utilize alternatives," Dr. Epstein said in the interview.

Mucosal sensitivity and pain is also frequent. In a meta-analysis of 22 studies published between 1990 and 2008, the prevalence of trismus was 25.4% in patients who received conventional radiotherapy and 5% for the few intensity-modulated radiation therapy studies that were included, suggesting that the newer radiation modality might diminish the problem (Support. Care Cancer 2010;18:1033-8).

Data suggest that the radiation effect on mandibular movement correlates with the radiation dose to the mastication muscles, with a steep dose-response curve. Onset is typically 2-6 months post treatment and is ongoing. Concurrent chemotherapy may increase the incidence and/or severity of mandibular immobility (Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 1999;88:365-73).

In the Vanderbilt survey, most patients reported burning in the throat or mouth (69); sensitivity to hot, spicy, or acid food (67); sensitivity to dryness (69); and changes in food intake because of mucosal sensitivity (67); most patients also reported that mucosal sensitivity prevents tooth brushing (63). "Mucosal sensitivity is a quality of life issue," Dr. Epstein said.

The Vanderbilt survey was particularly illuminating, Dr. Epstein commented. Studies that utilize claims data probably underrepresent the problem of long-term oral complications because dental and medical insurance are separate and the data are not easily combined, he added.

"Late oral effects are best diagnosed [and] managed in a multidisciplinary team with close communication between medical and dental providers. ... We really need to come together."

The Multinational Association of Supportive Care in Cancer is developing tools to improve communication between dentistry and medicine. These could be available for beta testing as early as this fall.

Dr. Epstein said he had no relevant financial disclosures.

PHOENIX – Pretreatment CD4 levels predicted response to induction chemotherapy among 97 patients with advanced laryngeal cancer, but not for 66 patients with advanced oropharyngeal cancer, according to a retrospective analysis of data from two clinical trials.

The two groups of head and neck cancer patients were enrolled in two identical prospective, phase II trials of induction chemotherapy and organ preservation, in which tumor response after one cycle of cisplatin and 5-fluorouracil was used to select those who would undergo surgery or definitive chemoradiation (J. Clin. Oncol. 2006;24:593-8 in laryngeal cancer; J. Clin. Oncol. 2008;26:3138-46 in oropharyngeal cancer).

Several lymphocyte subsets were measured before treatment via routine flow cytometry in peripheral blood in the laryngeal cancer patients, but only CD4 (helper cell) levels were significantly associated with chemotherapy response. Both absolute CD4 counts and CD4 percentages were higher among induction chemotherapy responders than nonresponders (P = .006 and P = .04, respectively).

Investigators also saw a trend for responders to have an increased percentage of CD3 cells (P = .13), decreased percentage of CD8 cells (P = .11), and higher CD4/CD8 ratios.

"Host immune parameters are important factors in treatment outcome, and may be useful in identifying subsets of patients with cancers that are responsive to organ-preserving therapy," said Dr. Gregory T. Wolf, who presented the data at a head and neck cancer symposium sponsored by the American Society for Radiation Oncology.

"It is likely that immunobiology of head and neck cancers differ significantly by tumor site and predisposing factors," added Dr. Wolf, a professor in the department of otolaryngology at the University of Michigan, Ann Arbor.

The median length of follow-up in the two studies was 7.9 years for the patients with laryngeal cancer and 6.6 years for those with cancer of the oropharynx. Disease-free survival was 86% at 3 years and 82% at 5 years for laryngeal cancer, and 78% at 3 years and 76% at 4 years for oropharyngeal cancer. The proportions responding to induction chemotherapy were 75% in the laryngeal cancer trial and 82% in the oropharyngeal cancer study.

In an interview, Dr. Wolf said that having two identical treatment trials provided an opportunity to determine whether correlations of pretreatment CD4 levels with chemoresponse differed by tumor site. When the laryngeal and oropharyngeal cancer patient groups were combined, higher CD4 levels were still associated with response, but this was primarily because of the strong correlation among the larynx cancer patients.

Statistical regression testing determined that for patients with oropharyngeal cancer, CD8 cells were more closely associated with chemotherapy response, but the relationship was not as strong as the strong correlation of CD4 levels among laryngeal cancer patients.

There was a trend toward improved survival by both CD4 percentage (P = .36) and absolute CD4 count (P = .15) in the laryngeal cohort, but not in the oropharyngeal cohort. None of the other lymphocyte subsets predicted survival in either group, Dr. Wolf said.

Results for the oropharyngeal cancer patients were further stratified by human papillomavirus status, and were combined with the laryngeal cancer group. Both lower CD4/CD8 ratio and higher CD8 levels were consistent with better prognosis among patients who were HPV positive (P = .02 and P = .06, respectively).

"We combined the results to get the largest sample size and [to see] if the relationship was independent of tumor site, since the biology of these cancers is so different. It was remarkable that the prediction differed by tumor site, with CD4 cells being predictive for larynx and CD8 cells predictive for oropharynx," Dr. Wolf explained in an interview. This finding likely reflects the major biological differences between these cancers, and is why it was important to also include HPV status, he added.

Dr. Wolf is a consultant for IRX Therapeutics, Inc.

PHOENIX – Pretreatment CD4 levels predicted response to induction chemotherapy among 97 patients with advanced laryngeal cancer, but not for 66 patients with advanced oropharyngeal cancer, according to a retrospective analysis of data from two clinical trials.

The two groups of head and neck cancer patients were enrolled in two identical prospective, phase II trials of induction chemotherapy and organ preservation, in which tumor response after one cycle of cisplatin and 5-fluorouracil was used to select those who would undergo surgery or definitive chemoradiation (J. Clin. Oncol. 2006;24:593-8 in laryngeal cancer; J. Clin. Oncol. 2008;26:3138-46 in oropharyngeal cancer).

Several lymphocyte subsets were measured before treatment via routine flow cytometry in peripheral blood in the laryngeal cancer patients, but only CD4 (helper cell) levels were significantly associated with chemotherapy response. Both absolute CD4 counts and CD4 percentages were higher among induction chemotherapy responders than nonresponders (P = .006 and P = .04, respectively).

Investigators also saw a trend for responders to have an increased percentage of CD3 cells (P = .13), decreased percentage of CD8 cells (P = .11), and higher CD4/CD8 ratios.

"Host immune parameters are important factors in treatment outcome, and may be useful in identifying subsets of patients with cancers that are responsive to organ-preserving therapy," said Dr. Gregory T. Wolf, who presented the data at a head and neck cancer symposium sponsored by the American Society for Radiation Oncology.

"It is likely that immunobiology of head and neck cancers differ significantly by tumor site and predisposing factors," added Dr. Wolf, a professor in the department of otolaryngology at the University of Michigan, Ann Arbor.

The median length of follow-up in the two studies was 7.9 years for the patients with laryngeal cancer and 6.6 years for those with cancer of the oropharynx. Disease-free survival was 86% at 3 years and 82% at 5 years for laryngeal cancer, and 78% at 3 years and 76% at 4 years for oropharyngeal cancer. The proportions responding to induction chemotherapy were 75% in the laryngeal cancer trial and 82% in the oropharyngeal cancer study.

In an interview, Dr. Wolf said that having two identical treatment trials provided an opportunity to determine whether correlations of pretreatment CD4 levels with chemoresponse differed by tumor site. When the laryngeal and oropharyngeal cancer patient groups were combined, higher CD4 levels were still associated with response, but this was primarily because of the strong correlation among the larynx cancer patients.

Statistical regression testing determined that for patients with oropharyngeal cancer, CD8 cells were more closely associated with chemotherapy response, but the relationship was not as strong as the strong correlation of CD4 levels among laryngeal cancer patients.

There was a trend toward improved survival by both CD4 percentage (P = .36) and absolute CD4 count (P = .15) in the laryngeal cohort, but not in the oropharyngeal cohort. None of the other lymphocyte subsets predicted survival in either group, Dr. Wolf said.

Results for the oropharyngeal cancer patients were further stratified by human papillomavirus status, and were combined with the laryngeal cancer group. Both lower CD4/CD8 ratio and higher CD8 levels were consistent with better prognosis among patients who were HPV positive (P = .02 and P = .06, respectively).

"We combined the results to get the largest sample size and [to see] if the relationship was independent of tumor site, since the biology of these cancers is so different. It was remarkable that the prediction differed by tumor site, with CD4 cells being predictive for larynx and CD8 cells predictive for oropharynx," Dr. Wolf explained in an interview. This finding likely reflects the major biological differences between these cancers, and is why it was important to also include HPV status, he added.

Dr. Wolf is a consultant for IRX Therapeutics, Inc.

PHOENIX – Pretreatment CD4 levels predicted response to induction chemotherapy among 97 patients with advanced laryngeal cancer, but not for 66 patients with advanced oropharyngeal cancer, according to a retrospective analysis of data from two clinical trials.

The two groups of head and neck cancer patients were enrolled in two identical prospective, phase II trials of induction chemotherapy and organ preservation, in which tumor response after one cycle of cisplatin and 5-fluorouracil was used to select those who would undergo surgery or definitive chemoradiation (J. Clin. Oncol. 2006;24:593-8 in laryngeal cancer; J. Clin. Oncol. 2008;26:3138-46 in oropharyngeal cancer).

Several lymphocyte subsets were measured before treatment via routine flow cytometry in peripheral blood in the laryngeal cancer patients, but only CD4 (helper cell) levels were significantly associated with chemotherapy response. Both absolute CD4 counts and CD4 percentages were higher among induction chemotherapy responders than nonresponders (P = .006 and P = .04, respectively).

Investigators also saw a trend for responders to have an increased percentage of CD3 cells (P = .13), decreased percentage of CD8 cells (P = .11), and higher CD4/CD8 ratios.

"Host immune parameters are important factors in treatment outcome, and may be useful in identifying subsets of patients with cancers that are responsive to organ-preserving therapy," said Dr. Gregory T. Wolf, who presented the data at a head and neck cancer symposium sponsored by the American Society for Radiation Oncology.

"It is likely that immunobiology of head and neck cancers differ significantly by tumor site and predisposing factors," added Dr. Wolf, a professor in the department of otolaryngology at the University of Michigan, Ann Arbor.

The median length of follow-up in the two studies was 7.9 years for the patients with laryngeal cancer and 6.6 years for those with cancer of the oropharynx. Disease-free survival was 86% at 3 years and 82% at 5 years for laryngeal cancer, and 78% at 3 years and 76% at 4 years for oropharyngeal cancer. The proportions responding to induction chemotherapy were 75% in the laryngeal cancer trial and 82% in the oropharyngeal cancer study.

In an interview, Dr. Wolf said that having two identical treatment trials provided an opportunity to determine whether correlations of pretreatment CD4 levels with chemoresponse differed by tumor site. When the laryngeal and oropharyngeal cancer patient groups were combined, higher CD4 levels were still associated with response, but this was primarily because of the strong correlation among the larynx cancer patients.

Statistical regression testing determined that for patients with oropharyngeal cancer, CD8 cells were more closely associated with chemotherapy response, but the relationship was not as strong as the strong correlation of CD4 levels among laryngeal cancer patients.

There was a trend toward improved survival by both CD4 percentage (P = .36) and absolute CD4 count (P = .15) in the laryngeal cohort, but not in the oropharyngeal cohort. None of the other lymphocyte subsets predicted survival in either group, Dr. Wolf said.

Results for the oropharyngeal cancer patients were further stratified by human papillomavirus status, and were combined with the laryngeal cancer group. Both lower CD4/CD8 ratio and higher CD8 levels were consistent with better prognosis among patients who were HPV positive (P = .02 and P = .06, respectively).

"We combined the results to get the largest sample size and [to see] if the relationship was independent of tumor site, since the biology of these cancers is so different. It was remarkable that the prediction differed by tumor site, with CD4 cells being predictive for larynx and CD8 cells predictive for oropharynx," Dr. Wolf explained in an interview. This finding likely reflects the major biological differences between these cancers, and is why it was important to also include HPV status, he added.

Dr. Wolf is a consultant for IRX Therapeutics, Inc.

PHOENIX – Thermal imaging was able to detect small and early changes in the temperature of mucosal surfaces – a possible predictor of the development of mucositis – among 34 patients who were treated with chemoradiotherapy for locally advanced squamous cell carcinoma of the head and neck.

"Detection of these early changes using sensitive thermal imaging technology would allow identification of patients who will require more intensive supportive care," said Dr. Ezra Cohen, who presented the pilot study at the head and neck cancer symposium sponsored by the American Society for Radiation Oncology.

Images courtesy Dr. Ezra Cohen

Radiotherapy-associated mucositis manifests initially as erythematous areas in the treatment field, which are accompanied by an intense inflammatory response histologically. Thus, Dr. Cohen and his associates had hypothesized that patients destined to display severe mucocutaneous toxicity would demonstrate greater alterations in thermal intensity early in therapy, compared with identically treated counterparts who do not subsequently develop the toxicity.

The researchers further hypothesized that they could measure those changes with infrared thermal imaging, a noninvasive technique that allows visualization and quantification of changes in skin or mucosal surface temperature.

The 34 patients (28 male, mean age 58 years) in the pilot study were treated with identical chemoradiotherapy regimens of 5-fluorouracil and hydroxyurea with a median radiation dose of 74 Gy for cancers of the oral cavity or oropharynx.

Using a portable device developed at Argonne National Laboratory in Illinois, the investigators conducted noninvasive baseline and weekly thermal imaging. The device detects infrared light naturally emitted from the skin or mucosal surface and generates an electrical signal, which is amplified and converted into digital data flow that is visualized in color on a monitor.

Grade 3 mucositis based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events v3.0 was observed in 53% of the patients, and dermatitis in 21%. All patients displayed an increase in temperature within the radiation field.

Investigators charted a statistically significant positive association between an early rise in temperature in oral mucous membranes when compared with a reference area and mucositis grade (P = .03). For every 1  C increase in temperature, compared with the reference (temperature near the medial angle of one eye), there was a 0.157 increase in average subsequent mucositis grade, reported Dr. Cohen, codirector of the head and neck cancer program at the University of Chicago.

Mucositis and its clinical sequelae are consistently reported as the most clinically significant acute toxicity in the treatment of locally advanced squamous cell carcinoma of the head and neck with chemoradiotherapy, according to Dr. Cohen, who also chaired the meeting. Patient to patient variability in mucositis is related to radiotherapy dosing, fractionation, and volumes, but there also appear to be individual differences in "normal tissue tolerance," even among patients on the same treatment regimen, he said.

"Larger studies with greater dynamic ranges in mucositis scoring are warranted to evaluate whether this tool can help predict which patients would be in need of early intervention to prevent acute complications," he said.

The study was funded by the National Institutes of Health and the University of Chicago Comprehensive Cancer Center. Dr. Cohen and his associates said they had no relevant financial disclosures.

PHOENIX – Thermal imaging was able to detect small and early changes in the temperature of mucosal surfaces – a possible predictor of the development of mucositis – among 34 patients who were treated with chemoradiotherapy for locally advanced squamous cell carcinoma of the head and neck.

"Detection of these early changes using sensitive thermal imaging technology would allow identification of patients who will require more intensive supportive care," said Dr. Ezra Cohen, who presented the pilot study at the head and neck cancer symposium sponsored by the American Society for Radiation Oncology.

Images courtesy Dr. Ezra Cohen

Radiotherapy-associated mucositis manifests initially as erythematous areas in the treatment field, which are accompanied by an intense inflammatory response histologically. Thus, Dr. Cohen and his associates had hypothesized that patients destined to display severe mucocutaneous toxicity would demonstrate greater alterations in thermal intensity early in therapy, compared with identically treated counterparts who do not subsequently develop the toxicity.

The researchers further hypothesized that they could measure those changes with infrared thermal imaging, a noninvasive technique that allows visualization and quantification of changes in skin or mucosal surface temperature.

The 34 patients (28 male, mean age 58 years) in the pilot study were treated with identical chemoradiotherapy regimens of 5-fluorouracil and hydroxyurea with a median radiation dose of 74 Gy for cancers of the oral cavity or oropharynx.

Using a portable device developed at Argonne National Laboratory in Illinois, the investigators conducted noninvasive baseline and weekly thermal imaging. The device detects infrared light naturally emitted from the skin or mucosal surface and generates an electrical signal, which is amplified and converted into digital data flow that is visualized in color on a monitor.

Grade 3 mucositis based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events v3.0 was observed in 53% of the patients, and dermatitis in 21%. All patients displayed an increase in temperature within the radiation field.

Investigators charted a statistically significant positive association between an early rise in temperature in oral mucous membranes when compared with a reference area and mucositis grade (P = .03). For every 1  C increase in temperature, compared with the reference (temperature near the medial angle of one eye), there was a 0.157 increase in average subsequent mucositis grade, reported Dr. Cohen, codirector of the head and neck cancer program at the University of Chicago.

Mucositis and its clinical sequelae are consistently reported as the most clinically significant acute toxicity in the treatment of locally advanced squamous cell carcinoma of the head and neck with chemoradiotherapy, according to Dr. Cohen, who also chaired the meeting. Patient to patient variability in mucositis is related to radiotherapy dosing, fractionation, and volumes, but there also appear to be individual differences in "normal tissue tolerance," even among patients on the same treatment regimen, he said.

"Larger studies with greater dynamic ranges in mucositis scoring are warranted to evaluate whether this tool can help predict which patients would be in need of early intervention to prevent acute complications," he said.

The study was funded by the National Institutes of Health and the University of Chicago Comprehensive Cancer Center. Dr. Cohen and his associates said they had no relevant financial disclosures.

PHOENIX – Thermal imaging was able to detect small and early changes in the temperature of mucosal surfaces – a possible predictor of the development of mucositis – among 34 patients who were treated with chemoradiotherapy for locally advanced squamous cell carcinoma of the head and neck.

"Detection of these early changes using sensitive thermal imaging technology would allow identification of patients who will require more intensive supportive care," said Dr. Ezra Cohen, who presented the pilot study at the head and neck cancer symposium sponsored by the American Society for Radiation Oncology.

Images courtesy Dr. Ezra Cohen

Radiotherapy-associated mucositis manifests initially as erythematous areas in the treatment field, which are accompanied by an intense inflammatory response histologically. Thus, Dr. Cohen and his associates had hypothesized that patients destined to display severe mucocutaneous toxicity would demonstrate greater alterations in thermal intensity early in therapy, compared with identically treated counterparts who do not subsequently develop the toxicity.

The researchers further hypothesized that they could measure those changes with infrared thermal imaging, a noninvasive technique that allows visualization and quantification of changes in skin or mucosal surface temperature.

The 34 patients (28 male, mean age 58 years) in the pilot study were treated with identical chemoradiotherapy regimens of 5-fluorouracil and hydroxyurea with a median radiation dose of 74 Gy for cancers of the oral cavity or oropharynx.

Using a portable device developed at Argonne National Laboratory in Illinois, the investigators conducted noninvasive baseline and weekly thermal imaging. The device detects infrared light naturally emitted from the skin or mucosal surface and generates an electrical signal, which is amplified and converted into digital data flow that is visualized in color on a monitor.

Grade 3 mucositis based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events v3.0 was observed in 53% of the patients, and dermatitis in 21%. All patients displayed an increase in temperature within the radiation field.

Investigators charted a statistically significant positive association between an early rise in temperature in oral mucous membranes when compared with a reference area and mucositis grade (P = .03). For every 1  C increase in temperature, compared with the reference (temperature near the medial angle of one eye), there was a 0.157 increase in average subsequent mucositis grade, reported Dr. Cohen, codirector of the head and neck cancer program at the University of Chicago.

Mucositis and its clinical sequelae are consistently reported as the most clinically significant acute toxicity in the treatment of locally advanced squamous cell carcinoma of the head and neck with chemoradiotherapy, according to Dr. Cohen, who also chaired the meeting. Patient to patient variability in mucositis is related to radiotherapy dosing, fractionation, and volumes, but there also appear to be individual differences in "normal tissue tolerance," even among patients on the same treatment regimen, he said.

"Larger studies with greater dynamic ranges in mucositis scoring are warranted to evaluate whether this tool can help predict which patients would be in need of early intervention to prevent acute complications," he said.

The study was funded by the National Institutes of Health and the University of Chicago Comprehensive Cancer Center. Dr. Cohen and his associates said they had no relevant financial disclosures.