Chemoradiation may increase survival for a subset of elderly head and neck cancer patients

The addition of chemotherapy (CT) to radiation therapy (RT) improves survival rates among a subset of elderly head and neck cancer patients, specifically those ages 71 to 79 with low comorbidity scores and advanced disease stage, according to University of Colorado Cancer Center research presented at the 2016 Multidisciplinary Head and Neck Cancer Symposium. While previous research has demonstrated the efficacy of combining CT with RT to improve survival for HNSCC patients, this improvement had not been shown in patients older than 70 years.

Elderly patients have been underrepresented in prospective clinical trials that have defined standards of care for head and neck cancer,” said Sana Karam, MD, PhD, CU Cancer Center investigator, assistant professor of radiation oncology at the University of Colorado School of Medicine, and senior author on the study. “Our study drew on nationwide data to assess more comprehensively how combined therapy impacts this population.”

The authors queried the National Cancer Data Base (NCDB) for records of patients older than 70 years who were treated for non-metastatic oropharyngeal, laryngeal and hypopharyngeal cancers between 1998 and 2011. The NCDB is a jointly-sponsored project of the American College of Surgeons and the American Cancer Society that aggregates data from more than 1,500 facilities accredited by the Commission on Cancer. Sixty-eight percent of the patients received RT alone, and 32 percent received CRT.

​Compared with RT alone, CRT was associated with improved survival in patients age 79 and younger with advanced disease but without comorbid conditions. Collaborators included Dr. Arya Amini, first aurthor on the study, and Drs. Bernard Jones, Antonio Jimeno, Jessica McDermott, David Raben, Debashis Ghosh and Daniel Bowles as co-authors on the study.

Patients who did not see an OS benefit from CRT tended to be age 80 or older, had a comorbidity score of two or greater, presented with less advanced disease, or were treated with three-dimensional RT. Patients age 80 or older with multiple comorbidities trended toward worse OS with CRT, though the difference was only marginally significant.

Findings may aid clinicians in discussing treatment options with their elderly HNSCC patients. Moreover, results of this study could guide future prospective trials to confirm the benefit of multimodality treatment in elderly patients, not only for head and neck cancer but for other cancer sites, as well.

Because the toxicity of concurrent chemoradiation is greater than radiation alone for definitive HNSCC treatment, many clinicians have reservations about offering CRT for elderly head and neck cancer patients,” said Karam. “However, in the era of improved radiation techniques, improved systemic therapy and better supportive care, we find that CRT does, in fact, improve survival for a large segment of this population.

The abstract, “Does Age Matter? Survival Outcomes with the Addition of Concurrent Chemotherapy for Elderly Head and Neck Cancer Patients Undergoing Definitive Radiation Using the National Cancer Data Base,” will be presented in detail as a poster presentation at the 2016 Multidisciplinary Head and Neck Cancer Symposium in Scottsdale, Arizona.

Multidisciplinary Head and Neck Cancer Symposium, 2016, Scottsdale, Arizona, USA.

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Late-stage lung cancer is often over-treated with radiation

Almost half of patients with advanced lung cancer receive more than the recommended number of radiation treatments to reduce their pain, according to a new study published in the Journal of the National Cancer Institute.

Radiation therapy that is palliative, or not intended to cure, can reduce the pain from lung tumors and improve quality of life. But unnecessary treatments add to costs and require needless trips to the hospital – and can lead to radiation toxicity and difficulty in swallowing.

Guidelines developed from clinical trials recommend no more than 15 radiation treatments be given for pain in stage 4 lung cancer. The guidelines recommend that patients not receive chemotherapy at the same time, to reduce the risk of toxicity.

The new analysis looked at 47,000 patients who received palliative radiation for stage 4 lung cancer in the U.S. between 2004 and 2012 and found that about one in five had received chemotherapy at the same time. Nearly a third of patients received more than 25 radiation treatments — 10 above the recommended maximum.

This study uncovered that there’s a lot of treatment of late-stage lung cancer with palliative radiation that goes beyond what is recommended by several national guidelines and multiple clinical trials,” said the study’s lead author, Dr. Matthew Koshy, a radiation oncologist at the University of Illinois Hospital & Health Sciences System.

More education is needed for radiation oncologists, to prevent over-treatment — which has not been proven to further improve symptoms or quality of life, and can have some significant side effects,” Koshy said.

The researchers also looked for any particular type of patient more likely to be overtreated.

Having private insurance was the number-one predictor of being overtreated,” Koshy said. Privately insured patients were 40 percent more likely than others to receive more than the recommended 15 treatments. Patients treated in community cancer centers – clinics without ties to an academic institution – were also more likely to be over-treated.

Koshy said physicians might tend to overtreat privately insured patients because services are billed per-treatment, creating a financial incentive. However, he said, “it could also be because these patients may be perceived to have better potential for a more positive outcome.”

Koshy et al. Prevalence and predictors of inappropriate delivery of palliative thoracic radiotherapy for metastatic lung cancer. J Natl Cancer Inst. 2015; 107 (12): djv278 doi: 10.1093/jnci/djv278 [Abstract]

Increased radiation offers no survival benefit for patients with low-risk prostate cancer

Increased radiation dose was only associated with higher survival rates in men with more aggressive cancers

Increased radiation dose is associated with higher survival rates in men with medium- and high-risk prostate cancer, but not men with low-risk prostate cancer, according to a new study from Penn Medicine published this week in JAMA Oncology. Already-high survival rates for men with low-risk prostate cancer were unaffected by higher radiation dosages compared to lower radiation dosages.

In 2014, low-risk prostate cancer was the most common type of prostate cancer diagnosed in the United States, affecting about 150,000 patients, many of whom undergo aggressive treatment, either complete removal of the prostate or radiation.

Our study raises the provocative question of whether radiation dose reduction for patients with low-risk prostate cancer could achieve similar cure rates while avoiding the increased risk of side effects associated with higher radiation doses,” said the study’s lead author,Anusha Kalbasi, MD, a resident in the department of Radiation Oncology at the Perelman School of Medicine at the University of Pennsylvania.

Using data from a National Cancer Database, the study employed specialized analytic methods to compare the survival rates of 42,481 men in the absence of a randomized clinical trial. Some men received standard dose of radiation while others received higher dose radiation. For men with medium- and high-risk forms of prostate cancer, the study found that for every incremental increase in radiation dose, there was a 7.8 percent and 6.3 percent reduction in the rate of death from any cause. For men with low-risk cancer, no differences in survival were found whether they received the standard dosage of radiation or a higher dosage.

The study is the first to link increased radiation dose with higher survival rates. Previous studies have linked increased radiation dose with two key measures: steady PSA scores and the absence of re-growth in tumors of the prostate following successful radiation.

The Penn-led team examined men who were diagnosed with prostate cancer between 2004 and 2006 and followed through 2012. In 2004, 56 percent of these men received higher dosages of radiation. Today, the figure is approximately 90 percent.

Kalbasi and his colleagues found that in the low-risk group of men, seven-year adjusted survival rates were 86 percent for both standard-dose and higher-dose patients. In the medium-risk group of men, seven-year adjusted survival rates were 82 percent and 78 percent for higher-dose and standard-dose patients, respectively. In the high-risk group of men, seven-year adjusted survival rates were 74 percent and 69 percent for higher-dose and standard-dose patients respectively.

Doctors divide localized prostate cancer (prostate cancer that is only in the prostate gland and which has not spread outside of the prostate) into three risk groups. Low-risk prostate cancers are unlikely to grow or spread for many years. Medium-risk cancers are unlikely to grow or spread for a few years. High-risk cancers may grow or spread within a few years. Three criteria are generally used for classifying prostate cancer risk: PSA level, Gleason score, and T stage. PSA is a protein produced by both normal and cancerous prostate cells; a high level of PSA can be a sign of cancer. The Gleason score is a qualitative assessment of any cancer cells that may be present. T stage refers to the size and extension of tumors.

Radiation therapy is associated with side effects and those side effects have been shown to increase with radiation dose, said Kalbasi. For patients undergoing prostate radiation, side effects include, fatigue, urinary frequency and urgency, changes in bowel habits, and erectile dysfunction.

Prostate cancer is the most common cancer diagnosed among American men, and causes more deaths annually among men than any other tumor except lung cancer. However, a large majority of men found to have prostate cancer ultimately die of other causes, prompting researchers to conduct studies to identify who benefits most from treatment and what those treatments should be.

Our findings show that the dose of radiation should be personalized to the specific characteristics of the prostate tumor,” said Justin Bekelman, MD, an associate professor of Radiation Oncology at Penn, and the study’s senior author. “For some patients, personalized treatment will lower the chances of toxicity while maintaining similar survival rates; for other patients, personalized treatment will mean escalating radiation dose to achieve the highest survival while protecting normal tissues, like the bladder and rectum.

Kalbasi et al. Dose-escalated irradiation and overall survival in men with nonmetastatic prostate cancer.JAMA Oncol. Published online July 16, 2015; doi:10.1001/jamaoncol.2015.2316 [Abstract]

Getting chemo first may help in rectal cancer

First things first. If cancer patients are having trouble tolerating chemotherapy after chemoradiation and surgery, then try administering it beforehand. Reordering the regimen that way enabled all but six of 39 patients to undergo a full course of standard treatment for rectal cancer, according to research to be presented at the American Society for Clinical Oncology annual meeting in Chicago.

Studies have shown that only about 60 percent of rectal cancer patients comply with postoperative chemotherapy, said lead researcher Dr. Kimberly Perez, assistant professor of medicine in the Warren Alpert Medical School of Brown University and a cancer physician at Rhode Island Hospital. In the phase II trial, “Complete Neoadjuvant Therapy in Rectal Cancer” (CONTRE), more than 90 percent of the patients were able to complete a regimen of mFOLFOX6 when it was moved to the front of the line.”The thought was, what can we do to make it more tolerable and get the benefit that we wanted,” said Perez, who will speak at 4 p.m. CDT on Saturday, May 31, 2014 at ASCO. “It’s encouraging because we were able to get the numbers up of patients who were able to get all the chemotherapy indicated.

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Only 60 percent of rectal cancer patients comply with chemotherapy after surgery. More patients complied and got the full benefit of chemotherapy when they received it first. For 13 patients in the study, the tumor (left) had disappeared when it was time for surgery. Credit: CONTRE Trial/Lifespan/Brown University

Almost all of the patients came into the study with rectal bleeding, but that symptom abated for all of them during treatment, Perez said.Regarding the cancer itself, a majority of patients, 32 of whom entered the trial at stage III and seven of whom were less advanced at stage II, responded at least to some degree to the induction chemotherapy and chemoradiation treatments. By the time they got to surgery, 13 patients had no tumor left (“pathologic complete response”), 10 got all they way back to stage I, seven were at stage II, and eight remained at stage III.

The study occurred too recently, however, to provide a measure of overall survival, Perez acknowledged. The last patient finished surgery in January 2014. The rate of side effects such as neutropenia, an adverse impact on the immune system, was not unusual.

The results of the CONTRE trial are now feeding into the development of a new national rectal cancer trial spearheaded by NRG Oncology, Perez said. That protocol will involve chemo first, then chemoradiation with biological anti-cancer agents, and finally surgery. Brown Univeristy Oncology Group and the Cancer Center of Rhode Island Hospital and associated satellites will be one of the study sites, Perez said.

 Presented at the American Society for Clinical Oncology annual meeting 2014 in Chicago.