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Squamous cell subgroups respond differently to treatment

Sat, Jan 28, 2012

Oral Cancer News

Source: www.medscape.com
Author: Nancy A. Melville

A long-term follow-up of patients with head and neck squamous cell carcinoma suggests that only certain high-risk subgroups benefit from radiation plus chemotherapy. This information will spare patients who will not benefit from undergoing the additional treatment.

According to the study, presented here at the 2012 Multidisciplinary Head and Neck Cancer Symposium, patients with microscopically involved resection margins and/or extracapsular spread of disease had a lower risk for cancer recurrence with radiation plus chemotherapy 10 years later, whereas those with tumors in multiple lymph nodes did not benefit from combination treatment; they fared better with radiation alone.

“The clinical implication of these findings is that the high-risk group of patients is not as homogenous a group as we believed it was before the study started,” lead author Jay S. Cooper, MD, director of the Maimonides Cancer Center, in Brooklyn, New York, told Medscape Medical News.

Dr. Cooper and his colleagues analyzed 10 years of follow-up data from the Radiation Therapy Oncology Group (RTOG) 9501/Intergroup phase 3 trial, which examined 410 patients with high-risk resected head and neck cancers.

The patients were considered high risk for cancer recurrence because they had microscopically involved resection margins, extracapsular spread of disease, or multiple lymph node involvement.

“The allocation was equally divided [according to treatment regimen] at the beginning of the study; the groups were not intended to be balanced for the different [risk] factors,” Dr. Cooper said. “We thought they were all equally important.”

The treatment regimen was either postoperative radiation therapy (60 Gy in 6 weeks) or identical radiation therapy plus intravenous cisplatin 100 mg/m² on days 1, 22, and 43.

Whereas an earlier follow-up of surviving patients at 45.9 months showed improvements in local-regional control and disease-free survival in the radiation plus chemotherapy group in general, the different responses in risk-factor subgroups was not observed, Dr. Cooper said.

In the 10-year follow-up, however, the analysis showed trends in the subgroups.

The local-regional failure rate with radiation alone was 28.8% and with radiation plus chemotherapy was 22.3% (P = .10). Disease-free survival was 19.1% and 20.1% (P = .25) and overall survival was 27.0% and 29.1% (P = .31), respectively.

In the unplanned subgroups of patients with microscopically involved resection margins and/or extracapsular spread of disease, local-regional failure occurred in 33.1% of the group treated with radiation alone and in 21.0% of the group treated with radiation plus chemotherapy (P = .02).

Disease-free survival in the high-risk subgroups was 12.3% with radiation alone and 18.4% with radiation plus chemotherapy group (P = .05); overall survival was 19.6% and 27.1%, respectively (P = .07).

Patients with tumors in multiple lymph nodes received no benefit from postoperative radiation plus chemotherapy in the longer-term follow-up, compared with radiation alone.

Cause-specific survival rates showed a trend toward improved outcome in patients receiving radiation plus chemotherapy whose death was due to the study cancer, compared with those receiving radiation alone. However, an increased number of deaths related to causes other than the study cancer was observed in patients treated with radiation plus chemotherapy, the authors noted.

“These findings tell us that these subgroups of high-risk patients — who had either a tumor at the margin or extracapsular spread of the disease — do benefit from the addition of chemotherapy in terms of better local control, even at 10-year follow-up. Simultaneously, patients who have multiple node involvement but who don’t have a tumor at the margin or extracapsular spread of the disease do not benefit from chemotherapy,” Dr. Cooper said.

“In a crazy way, it’s a win–win situation, in that we now know how to spare some of the patients we thought were high risk from the toxicity of chemotherapy,” he said.

“For patients we identified as truly high risk, at least in terms of their response to chemotherapy, we now have a better therapy.”

Although similar findings have been observed before, this analysis sheds light on the longer-term response of high-risk patients, said Stuart J. Wong, MD, associate professor of medicine and otolaryngology at the Medical College of Wisconsin in Milwaukee, who moderated the session.

“There was a combined analysis of RTOG 9501 and the EORTC postop study, which had an identical study design,” said Dr. Wong.

“This was a landmark analysis that defines how we currently treat high-risk patients in the postoperative setting.”

“The long-term analysis of RTOG 9501 by Dr. Cooper and colleagues reiterates these findings,” he added. “These key study results are being used in the design of ongoing and future Radiation Therapy Oncology Group (RTOG) studies.”

The study authors and Dr. Wong have disclosed no relevant financial relationships.

Source: 2012 Multidisciplinary Head and Neck Cancer Symposium (MHNCS): Abstract 1. Presented January 26, 2012.

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