The Journal of Community and Supportive Oncology

Radiotherapy after mastectomy for women with one to three positive nodes significantly reduces the risk of recurrence and breast cancer mortality, researchers found in a meta-analysis.

With follow-up of 20 years for breast cancer mortality, a review of 22 randomized trials found that among women with one to three positive nodes after mastectomy and axillary dissection, radiotherapy reduced the rates of overall recurrence by almost a third (relative risk, 0.68; 95% confidence interval, 0.57-0.82; P = .00006) and breast cancer mortality by a fifth (RR, 0.80; 95% CI, 0.67-0.95; P = .01), investigators reported online March 19 in the Lancet.

This benefit from radiotherapy in women with one to three positive nodes held up when women also received chemotherapy and/or hormone treatment. The proportional reductions in the rates of any first recurrence and breast cancer mortality did not differ significantly according to whether or not systemic therapy was given, the investigators said.

The group analyzed outcomes for 8,135 women enrolled in 22 studies, randomized to receive radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery, or to receive the same surgery with no radiotherapy. The median length of follow-up per woman was about 9 years, although many in the studies have now been followed for up to 20 years. Most had positive nodes at dissection (72%); 20% had node-negative disease, and nodal status was unknown for the remainder.

For women with no positive nodes, radiotherapy had no significant effect on locoregional recurrence, overall recurrence, or breast cancer morality, but did however increase overall mortality (RR, 1.23; 95% CI, 1.02-1.49; P = .03). For women with axillary dissection and four or more positive nodes, radiotherapy reduced overall recurrence (RR, 0.79; 95% CI, 0.69-0.90; P = .0003) and breast cancer mortality (RR, 0.87; 95% CI, 0.77-0.99; P = .04).

All of the studies were conducted between 1964 and 1986. Benefits could be even greater today, "... because radiotherapy planning has changed substantially and women today receive better coverage of target areas. Furthermore, doses to normal tissues are lower today, so the risks of radiotherapy are also likely to be lower," wrote the investigators with the Early Breast Cancer Trialists’ Collaborative Group, which conducted the analysis (Lancet 2014 March 19 [doi: 10.1016/S0140-6736(14)60488-8]).

"Breast cancer is a disease with a long natural history," the researchers wrote. "Many of the women in these trials have now been followed up for 20 years and therefore they provide information about the long-term benefits of radiotherapy. Radiotherapy techniques have improved in the past few decades, and so the proportional benefits of radiotherapy are likely to be larger than in these trials."

However, they added, "the absolute risks of breast cancer recurrence and mortality have [been] reduced in many countries because of advances in detection and treatment of breast cancer, so the absolute benefits from postmastectomy radiotherapy today are likely to be smaller than those reported here."

The study group is funded by Cancer Research UK, the British Heart Foundation, and the UK Medical Research Council. None of the members reported any financial disclosures.

Radiotherapy after mastectomy for women with one to three positive nodes significantly reduces the risk of recurrence and breast cancer mortality, researchers found in a meta-analysis.

With follow-up of 20 years for breast cancer mortality, a review of 22 randomized trials found that among women with one to three positive nodes after mastectomy and axillary dissection, radiotherapy reduced the rates of overall recurrence by almost a third (relative risk, 0.68; 95% confidence interval, 0.57-0.82; P = .00006) and breast cancer mortality by a fifth (RR, 0.80; 95% CI, 0.67-0.95; P = .01), investigators reported online March 19 in the Lancet.

This benefit from radiotherapy in women with one to three positive nodes held up when women also received chemotherapy and/or hormone treatment. The proportional reductions in the rates of any first recurrence and breast cancer mortality did not differ significantly according to whether or not systemic therapy was given, the investigators said.

The group analyzed outcomes for 8,135 women enrolled in 22 studies, randomized to receive radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery, or to receive the same surgery with no radiotherapy. The median length of follow-up per woman was about 9 years, although many in the studies have now been followed for up to 20 years. Most had positive nodes at dissection (72%); 20% had node-negative disease, and nodal status was unknown for the remainder.

For women with no positive nodes, radiotherapy had no significant effect on locoregional recurrence, overall recurrence, or breast cancer morality, but did however increase overall mortality (RR, 1.23; 95% CI, 1.02-1.49; P = .03). For women with axillary dissection and four or more positive nodes, radiotherapy reduced overall recurrence (RR, 0.79; 95% CI, 0.69-0.90; P = .0003) and breast cancer mortality (RR, 0.87; 95% CI, 0.77-0.99; P = .04).

All of the studies were conducted between 1964 and 1986. Benefits could be even greater today, "... because radiotherapy planning has changed substantially and women today receive better coverage of target areas. Furthermore, doses to normal tissues are lower today, so the risks of radiotherapy are also likely to be lower," wrote the investigators with the Early Breast Cancer Trialists’ Collaborative Group, which conducted the analysis (Lancet 2014 March 19 [doi: 10.1016/S0140-6736(14)60488-8]).

"Breast cancer is a disease with a long natural history," the researchers wrote. "Many of the women in these trials have now been followed up for 20 years and therefore they provide information about the long-term benefits of radiotherapy. Radiotherapy techniques have improved in the past few decades, and so the proportional benefits of radiotherapy are likely to be larger than in these trials."

However, they added, "the absolute risks of breast cancer recurrence and mortality have [been] reduced in many countries because of advances in detection and treatment of breast cancer, so the absolute benefits from postmastectomy radiotherapy today are likely to be smaller than those reported here."

The study group is funded by Cancer Research UK, the British Heart Foundation, and the UK Medical Research Council. None of the members reported any financial disclosures.

Radiotherapy after mastectomy for women with one to three positive nodes significantly reduces the risk of recurrence and breast cancer mortality, researchers found in a meta-analysis.

With follow-up of 20 years for breast cancer mortality, a review of 22 randomized trials found that among women with one to three positive nodes after mastectomy and axillary dissection, radiotherapy reduced the rates of overall recurrence by almost a third (relative risk, 0.68; 95% confidence interval, 0.57-0.82; P = .00006) and breast cancer mortality by a fifth (RR, 0.80; 95% CI, 0.67-0.95; P = .01), investigators reported online March 19 in the Lancet.

This benefit from radiotherapy in women with one to three positive nodes held up when women also received chemotherapy and/or hormone treatment. The proportional reductions in the rates of any first recurrence and breast cancer mortality did not differ significantly according to whether or not systemic therapy was given, the investigators said.

The group analyzed outcomes for 8,135 women enrolled in 22 studies, randomized to receive radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery, or to receive the same surgery with no radiotherapy. The median length of follow-up per woman was about 9 years, although many in the studies have now been followed for up to 20 years. Most had positive nodes at dissection (72%); 20% had node-negative disease, and nodal status was unknown for the remainder.

For women with no positive nodes, radiotherapy had no significant effect on locoregional recurrence, overall recurrence, or breast cancer morality, but did however increase overall mortality (RR, 1.23; 95% CI, 1.02-1.49; P = .03). For women with axillary dissection and four or more positive nodes, radiotherapy reduced overall recurrence (RR, 0.79; 95% CI, 0.69-0.90; P = .0003) and breast cancer mortality (RR, 0.87; 95% CI, 0.77-0.99; P = .04).

All of the studies were conducted between 1964 and 1986. Benefits could be even greater today, "... because radiotherapy planning has changed substantially and women today receive better coverage of target areas. Furthermore, doses to normal tissues are lower today, so the risks of radiotherapy are also likely to be lower," wrote the investigators with the Early Breast Cancer Trialists’ Collaborative Group, which conducted the analysis (Lancet 2014 March 19 [doi: 10.1016/S0140-6736(14)60488-8]).

"Breast cancer is a disease with a long natural history," the researchers wrote. "Many of the women in these trials have now been followed up for 20 years and therefore they provide information about the long-term benefits of radiotherapy. Radiotherapy techniques have improved in the past few decades, and so the proportional benefits of radiotherapy are likely to be larger than in these trials."

However, they added, "the absolute risks of breast cancer recurrence and mortality have [been] reduced in many countries because of advances in detection and treatment of breast cancer, so the absolute benefits from postmastectomy radiotherapy today are likely to be smaller than those reported here."

The study group is funded by Cancer Research UK, the British Heart Foundation, and the UK Medical Research Council. None of the members reported any financial disclosures.

Customized adjuvant chemotherapy for non–small-cell lung cancer proved feasible in a phase II trial in 150 patients, but the unreliability of some biomarker tests led to cancellation of a planned phase III study of the efficacy of individualizing treatment based on biomarker status.

The prospective phase II trial at 29 French centers enrolled patients who had completely resected nonsquamous cell, stage II or IIIA (non-N2) tumors and had no prior chemotherapy. Within 2 months of surgery, 80% of all patients had complete biomarker status results and were able to start adjuvant treatment, showing that timely customized adjuvant therapy is feasible, Dr. Marie Wislez and her associates reported in the Journal of Clinical Oncology.

The study randomized 74 patients to a control group receiving conventional treatment with four courses of cisplatin (75 mg/m²) plus pemetrexed (500 mg/m²) every 21 days plus vitamin B₁₂ supplements and corticosteroids. Among 76 patients randomized to the customized treatment group, 7 patients with activated epidermal growth factor receptor (mutations were treated with oral erlotinib 150 mg/day for 1 year. In the customized group, 53 patients who were negative for excision repair cross-complementation group 1 (ERCC1) were to receive the same cisplatin/pemetrexed regimen as the control group, and 16 ERCC1-positive patients were simply followed, the investigators reported (J. Clin. Oncol. 2014 March 17 [doi:10.1200/JCO.2013.53.1525]).

Patients were to be followed every 6 months for the first 5 years after surgery. The adjuvant therapies generally were well tolerated.

The investigators discovered unexpectedly, however, that assays for ERCC1 expression were unreliable, reported Dr. Wislez of Tenon Hospital, Paris, and her associates. ERCC1-positive patients made up 25% of patients in the study, compared with 44% of patients with non–small-cell lung cancer in the previous IALT (International Adjuvant Lung Cancer) trial (N. Engl. J. Med. 2006;355:983-91).

When Dr. Wislez and her associates restained biosamples from the IALT trial using the 8F1 antibody test commercially available in 2011, they found important discrepancies between the IALT’s results from 2006 and those obtained in 2001.The unreliability of the ERCC1 immunohistochemical readouts led them to cancel the planned phase III TASTE (Tailored Postsurgical Therapy in Early-Stage NSCLC) trial until ERCC1 testing methodology can be improved.

The current phase II trial also found that the epidermal growth factor receptor mutation rate (6.7%) was lower than expected based on previously published data, whether analyzed using probe-specific polymerase chain reaction or by direct sequencing methodology.

Some of Dr. Wislez’s associates in the study reported financial associations with Roche, Eli Lilly, Pfizer, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb, Pfizer, and/or Amgen.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Customized adjuvant chemotherapy for non–small-cell lung cancer proved feasible in a phase II trial in 150 patients, but the unreliability of some biomarker tests led to cancellation of a planned phase III study of the efficacy of individualizing treatment based on biomarker status.

The prospective phase II trial at 29 French centers enrolled patients who had completely resected nonsquamous cell, stage II or IIIA (non-N2) tumors and had no prior chemotherapy. Within 2 months of surgery, 80% of all patients had complete biomarker status results and were able to start adjuvant treatment, showing that timely customized adjuvant therapy is feasible, Dr. Marie Wislez and her associates reported in the Journal of Clinical Oncology.

The study randomized 74 patients to a control group receiving conventional treatment with four courses of cisplatin (75 mg/m²) plus pemetrexed (500 mg/m²) every 21 days plus vitamin B₁₂ supplements and corticosteroids. Among 76 patients randomized to the customized treatment group, 7 patients with activated epidermal growth factor receptor (mutations were treated with oral erlotinib 150 mg/day for 1 year. In the customized group, 53 patients who were negative for excision repair cross-complementation group 1 (ERCC1) were to receive the same cisplatin/pemetrexed regimen as the control group, and 16 ERCC1-positive patients were simply followed, the investigators reported (J. Clin. Oncol. 2014 March 17 [doi:10.1200/JCO.2013.53.1525]).

Patients were to be followed every 6 months for the first 5 years after surgery. The adjuvant therapies generally were well tolerated.

The investigators discovered unexpectedly, however, that assays for ERCC1 expression were unreliable, reported Dr. Wislez of Tenon Hospital, Paris, and her associates. ERCC1-positive patients made up 25% of patients in the study, compared with 44% of patients with non–small-cell lung cancer in the previous IALT (International Adjuvant Lung Cancer) trial (N. Engl. J. Med. 2006;355:983-91).

When Dr. Wislez and her associates restained biosamples from the IALT trial using the 8F1 antibody test commercially available in 2011, they found important discrepancies between the IALT’s results from 2006 and those obtained in 2001.The unreliability of the ERCC1 immunohistochemical readouts led them to cancel the planned phase III TASTE (Tailored Postsurgical Therapy in Early-Stage NSCLC) trial until ERCC1 testing methodology can be improved.

The current phase II trial also found that the epidermal growth factor receptor mutation rate (6.7%) was lower than expected based on previously published data, whether analyzed using probe-specific polymerase chain reaction or by direct sequencing methodology.

Some of Dr. Wislez’s associates in the study reported financial associations with Roche, Eli Lilly, Pfizer, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb, Pfizer, and/or Amgen.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Customized adjuvant chemotherapy for non–small-cell lung cancer proved feasible in a phase II trial in 150 patients, but the unreliability of some biomarker tests led to cancellation of a planned phase III study of the efficacy of individualizing treatment based on biomarker status.

The prospective phase II trial at 29 French centers enrolled patients who had completely resected nonsquamous cell, stage II or IIIA (non-N2) tumors and had no prior chemotherapy. Within 2 months of surgery, 80% of all patients had complete biomarker status results and were able to start adjuvant treatment, showing that timely customized adjuvant therapy is feasible, Dr. Marie Wislez and her associates reported in the Journal of Clinical Oncology.

The study randomized 74 patients to a control group receiving conventional treatment with four courses of cisplatin (75 mg/m²) plus pemetrexed (500 mg/m²) every 21 days plus vitamin B₁₂ supplements and corticosteroids. Among 76 patients randomized to the customized treatment group, 7 patients with activated epidermal growth factor receptor (mutations were treated with oral erlotinib 150 mg/day for 1 year. In the customized group, 53 patients who were negative for excision repair cross-complementation group 1 (ERCC1) were to receive the same cisplatin/pemetrexed regimen as the control group, and 16 ERCC1-positive patients were simply followed, the investigators reported (J. Clin. Oncol. 2014 March 17 [doi:10.1200/JCO.2013.53.1525]).

Patients were to be followed every 6 months for the first 5 years after surgery. The adjuvant therapies generally were well tolerated.

The investigators discovered unexpectedly, however, that assays for ERCC1 expression were unreliable, reported Dr. Wislez of Tenon Hospital, Paris, and her associates. ERCC1-positive patients made up 25% of patients in the study, compared with 44% of patients with non–small-cell lung cancer in the previous IALT (International Adjuvant Lung Cancer) trial (N. Engl. J. Med. 2006;355:983-91).

When Dr. Wislez and her associates restained biosamples from the IALT trial using the 8F1 antibody test commercially available in 2011, they found important discrepancies between the IALT’s results from 2006 and those obtained in 2001.The unreliability of the ERCC1 immunohistochemical readouts led them to cancel the planned phase III TASTE (Tailored Postsurgical Therapy in Early-Stage NSCLC) trial until ERCC1 testing methodology can be improved.

The current phase II trial also found that the epidermal growth factor receptor mutation rate (6.7%) was lower than expected based on previously published data, whether analyzed using probe-specific polymerase chain reaction or by direct sequencing methodology.

Some of Dr. Wislez’s associates in the study reported financial associations with Roche, Eli Lilly, Pfizer, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb, Pfizer, and/or Amgen.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

A 60-year-old woman presented with worsening right lower extremity swelling for 2 days. The patient had no history of trauma or prolonged immobilization and denied further symptoms, including lower extremity pain, fever, dyspnea, chest pain, and abdominal pain. The patient’s medical history included chronic hepatitis C secondary to intravenous drug use, a history of deep venous thrombosis 25 years prior to her presentation, and a history of right-sided breast cancer 20 years prior to that was treated with lumpectomy, radiation therapy, chemotherapy, and tamoxifen (discontinued by the patient after 3 years). The family history was unknown as the patient was adopted.

Click on the PDF icon at the top of this introduction to read the full article.

A 60-year-old woman presented with worsening right lower extremity swelling for 2 days. The patient had no history of trauma or prolonged immobilization and denied further symptoms, including lower extremity pain, fever, dyspnea, chest pain, and abdominal pain. The patient’s medical history included chronic hepatitis C secondary to intravenous drug use, a history of deep venous thrombosis 25 years prior to her presentation, and a history of right-sided breast cancer 20 years prior to that was treated with lumpectomy, radiation therapy, chemotherapy, and tamoxifen (discontinued by the patient after 3 years). The family history was unknown as the patient was adopted.

Click on the PDF icon at the top of this introduction to read the full article.

A 60-year-old woman presented with worsening right lower extremity swelling for 2 days. The patient had no history of trauma or prolonged immobilization and denied further symptoms, including lower extremity pain, fever, dyspnea, chest pain, and abdominal pain. The patient’s medical history included chronic hepatitis C secondary to intravenous drug use, a history of deep venous thrombosis 25 years prior to her presentation, and a history of right-sided breast cancer 20 years prior to that was treated with lumpectomy, radiation therapy, chemotherapy, and tamoxifen (discontinued by the patient after 3 years). The family history was unknown as the patient was adopted.

Click on the PDF icon at the top of this introduction to read the full article.

An elderly woman with a family history of cholangiocarcinoma is diagnosed with primary squamous cell carcinoma of the liver after clinical evaluation, imaging, and tumor markers suggest that metastatic SCC to the liver was not likely.

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An elderly woman with a family history of cholangiocarcinoma is diagnosed with primary squamous cell carcinoma of the liver after clinical evaluation, imaging, and tumor markers suggest that metastatic SCC to the liver was not likely.

Click on the PDF icon at the top of this introduction to read the full article.

An elderly woman with a family history of cholangiocarcinoma is diagnosed with primary squamous cell carcinoma of the liver after clinical evaluation, imaging, and tumor markers suggest that metastatic SCC to the liver was not likely.

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Dabrafenib was recently approved by the US Food and Drug Administration for treatment of unresectable or metastatic melanoma with BRAF V600E mutations as detected by an FDA-approved test. The THxID BRAF assay, for detection of BRAF V600E mutations was concurrently approved. Dabrafenib is not indicated for the treatment of patients with wild-type BRAF melanoma, because of the potential risk of tumor promotion. About 50% of melanomas have an activating mutation in the BRAF gene, with about 80%-90% of those having a V600E mutation, and 10%-20% having a V600K mutation.

Click on the PDF icon at the top of this introduction to read the full article.

Dabrafenib was recently approved by the US Food and Drug Administration for treatment of unresectable or metastatic melanoma with BRAF V600E mutations as detected by an FDA-approved test. The THxID BRAF assay, for detection of BRAF V600E mutations was concurrently approved. Dabrafenib is not indicated for the treatment of patients with wild-type BRAF melanoma, because of the potential risk of tumor promotion. About 50% of melanomas have an activating mutation in the BRAF gene, with about 80%-90% of those having a V600E mutation, and 10%-20% having a V600K mutation.

Click on the PDF icon at the top of this introduction to read the full article.

Dabrafenib was recently approved by the US Food and Drug Administration for treatment of unresectable or metastatic melanoma with BRAF V600E mutations as detected by an FDA-approved test. The THxID BRAF assay, for detection of BRAF V600E mutations was concurrently approved. Dabrafenib is not indicated for the treatment of patients with wild-type BRAF melanoma, because of the potential risk of tumor promotion. About 50% of melanomas have an activating mutation in the BRAF gene, with about 80%-90% of those having a V600E mutation, and 10%-20% having a V600K mutation.

Click on the PDF icon at the top of this introduction to read the full article.

Background Capecitabine is an oral fluoropyrimidine that is used to treat various malignancies. Hand-foot syndrome (HFS) is a dose-limiting toxicity of capecitabine that can limit the use of this agent in some patients. Some investigators have observed that pyridoxine (vitamin B6) can ameliorate HFS that is caused by capecitabine. We designed a prospective trial to determine if pyridoxine can prevent HFS in patients who receive capecitabine.

Methods In our double-blind, placebo-controlled trial, we randomly assigned eligible patients who were treated with capecitabine to receive either daily pyridoxine 100 mg or placebo along with their capecitabine-containing chemotherapy regimen. Patients were observed during the first 4 cycles of capecitabine treatment. The primary endpoint was the incidence and grade of HFS that occurred in both study arms.

Results Between 2008 and 2011, 77 patients were randomly assigned to receive either pyridoxine (n = 38) or placebo (n = 39). Dosages of capecitabine were equally matched between both arms of the study. HFS occurred after a median of 2 chemotherapy cycles in both groups. HFS developed in 10 of 38 (26%) patients in the pyridoxine group and in 8 of 39 (21%) patients in the placebo group (P = .547). Therefore, the risk of HFS was 5 percentage points higher in pyridoxine group (95% confdence interval [CI] for difference, –13 percentage points to +25 percentage points). Given our study results, a true beneft from pyridoxine can be excluded. No difference in HFS grades was observed.

Limitations Single-institution study.

Conclusion Prophylactic pyridoxine (vitamin B6), given concomitantly with capecitabine-containing chemotherapy, was not effective for the prevention of HFS.

*To read the full article, click on the PDF icon at the top of this introduction.

Background Capecitabine is an oral fluoropyrimidine that is used to treat various malignancies. Hand-foot syndrome (HFS) is a dose-limiting toxicity of capecitabine that can limit the use of this agent in some patients. Some investigators have observed that pyridoxine (vitamin B6) can ameliorate HFS that is caused by capecitabine. We designed a prospective trial to determine if pyridoxine can prevent HFS in patients who receive capecitabine.

Methods In our double-blind, placebo-controlled trial, we randomly assigned eligible patients who were treated with capecitabine to receive either daily pyridoxine 100 mg or placebo along with their capecitabine-containing chemotherapy regimen. Patients were observed during the first 4 cycles of capecitabine treatment. The primary endpoint was the incidence and grade of HFS that occurred in both study arms.

Results Between 2008 and 2011, 77 patients were randomly assigned to receive either pyridoxine (n = 38) or placebo (n = 39). Dosages of capecitabine were equally matched between both arms of the study. HFS occurred after a median of 2 chemotherapy cycles in both groups. HFS developed in 10 of 38 (26%) patients in the pyridoxine group and in 8 of 39 (21%) patients in the placebo group (P = .547). Therefore, the risk of HFS was 5 percentage points higher in pyridoxine group (95% confdence interval [CI] for difference, –13 percentage points to +25 percentage points). Given our study results, a true beneft from pyridoxine can be excluded. No difference in HFS grades was observed.

Limitations Single-institution study.

Conclusion Prophylactic pyridoxine (vitamin B6), given concomitantly with capecitabine-containing chemotherapy, was not effective for the prevention of HFS.

*To read the full article, click on the PDF icon at the top of this introduction.

Background Capecitabine is an oral fluoropyrimidine that is used to treat various malignancies. Hand-foot syndrome (HFS) is a dose-limiting toxicity of capecitabine that can limit the use of this agent in some patients. Some investigators have observed that pyridoxine (vitamin B6) can ameliorate HFS that is caused by capecitabine. We designed a prospective trial to determine if pyridoxine can prevent HFS in patients who receive capecitabine.

Methods In our double-blind, placebo-controlled trial, we randomly assigned eligible patients who were treated with capecitabine to receive either daily pyridoxine 100 mg or placebo along with their capecitabine-containing chemotherapy regimen. Patients were observed during the first 4 cycles of capecitabine treatment. The primary endpoint was the incidence and grade of HFS that occurred in both study arms.

Results Between 2008 and 2011, 77 patients were randomly assigned to receive either pyridoxine (n = 38) or placebo (n = 39). Dosages of capecitabine were equally matched between both arms of the study. HFS occurred after a median of 2 chemotherapy cycles in both groups. HFS developed in 10 of 38 (26%) patients in the pyridoxine group and in 8 of 39 (21%) patients in the placebo group (P = .547). Therefore, the risk of HFS was 5 percentage points higher in pyridoxine group (95% confdence interval [CI] for difference, –13 percentage points to +25 percentage points). Given our study results, a true beneft from pyridoxine can be excluded. No difference in HFS grades was observed.

Limitations Single-institution study.

Conclusion Prophylactic pyridoxine (vitamin B6), given concomitantly with capecitabine-containing chemotherapy, was not effective for the prevention of HFS.

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As practicing oncologists, we know the importance of having a professional support system in place, platforms that allow us to dissect and discuss all aspects of our work, from diagnosis to therapy decisions, that rare case presentation, supportive and palliative care, maintenance therapy, and yes, practice management, the impact of health reform, the dreaded EMRs, and much more. Such exchanges, whether they take the form of routine roundtable meetings, conference calls, or tumor boards and whether they are in-person or online, are crucial in shaping how we practice our specialty at both the individual and collective levels.

As practicing oncologists, we know the importance of having a professional support system in place, platforms that allow us to dissect and discuss all aspects of our work, from diagnosis to therapy decisions, that rare case presentation, supportive and palliative care, maintenance therapy, and yes, practice management, the impact of health reform, the dreaded EMRs, and much more. Such exchanges, whether they take the form of routine roundtable meetings, conference calls, or tumor boards and whether they are in-person or online, are crucial in shaping how we practice our specialty at both the individual and collective levels.

As practicing oncologists, we know the importance of having a professional support system in place, platforms that allow us to dissect and discuss all aspects of our work, from diagnosis to therapy decisions, that rare case presentation, supportive and palliative care, maintenance therapy, and yes, practice management, the impact of health reform, the dreaded EMRs, and much more. Such exchanges, whether they take the form of routine roundtable meetings, conference calls, or tumor boards and whether they are in-person or online, are crucial in shaping how we practice our specialty at both the individual and collective levels.