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.

Final results of the randomized intergroup EORTC, LYSA (Lymphoma Study Association), FIL (Fondazione Italiana Linfomi) H10 trial presented at the 13th International Conference on Malignant Lymphoma in Lugano, Switzerland, show that early FDG-PET ( 2-deoxy-2[F-18]fluoro-D-glucose positron emission tomography) adapted treatment improves the outcome of early FDG-PET-positive patients with stages I/II Hodgkin lymphoma.

Dr. John Raemaekers of the Radboud University Medical Center Nijmegen and the Rijnstate Hospital Arnhem, The Netherlands, and EORTC principal study coordinator on behalf of the EORTC/LYSA/FIL Intergroup H10 team says, "Even though the prognosis for patients with stage I/II HL is excellent if they are treated with the standard regimen of chemotherapy combined with radiotherapy, tumor control could still be improved for specific subgroups of patients, and late toxicity could be reduced for others. This trial, therefore, addressed two questions. First, can the outcome for early FDG-PET-positive patients with stages I/II Hodgkin lymphoma be improved by administering early intensification of chemotherapy? Second, can involved-node radiotherapy be omitted from the standard combined modality treatment in early PET-negative patients?"

This intergroup trial demonstrated that patients with stage I/II Hodgkin Lymphoma, who are still FDG-PET positive after two cycles of ABVD chemotherapy, significantly benefit in terms of progression free survival from intensification to BEACOPPesc chemotherapy followed by involved-node radiotherapy compared to patients who continue standard ABVD chemotherapy followed by involved-node radiotherapy (5yr progression-free survival rates 91% versus 77%, HR=0.42, 95%CI:0.23 to 0.74, p=0.002, with a difference of 13%, 95%CI:5% to 21%). The analysis of the early PET negative group confirmed the conclusions of the previously published interim analysis. We could not demonstrate that treatment with chemotherapy only is non-inferior to the standard combined modality treatment in terms of progression free survival.

Breast cancer survivors with a family history of the disease, including those who carry BRCA1 and BRCA2 gene mutations, gained more weight over the course of four years than cancer-free women - especially if they were treated with chemotherapy, according to a prospective study by Johns Hopkins Kimmel Cancer Center researchers.

Data from earlier studies suggest that breast cancer survivors who gain weight may have a higher risk of having their cancer return, the researchers say, noting that gains of 11 pounds or more are also associated with a higher risk of developing cardiovascular disease.

For the study, the researchers reviewed a baseline questionnaire and a follow-up one completed four years later by 303 breast cancer survivors and 307 cancer-free women enrolled in an ongoing and long-term study at the Kimmel Cancer Center of women with a family history of breast or ovarian cancer. Study participants completed a baseline and at least one follow-up questionnaire between 2005 and 2013, and one-quarter of the subjects were premenopausal.

In the four-year span, survivors gained significantly more weight - 3.6 pounds on average - than cancer-free women. Among 180 survivors diagnosed with cancer during the last five years of the study period, 37 (21 percent) gained at least 11 pounds over a four-year period compared with 35 of 307 (11 percent) of their cancer-free peers. The weight change findings remained the same after accounting for other factors associated with weight gain, such as increasing age, transition to menopause and level of physical activity, the researchers say.

"Our study suggests that chemotherapy may be one of the factors contributing to weight gain among survivors," says Kala Visvanathan, M.B.B.S., M.H.S., an associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health and director of the Clinical Cancer Genetics and Prevention Service at the Kimmel Cancer Center. Women who completed chemotherapy within five years of the study were 2.1 times as likely as cancer-free women to have gained at least 11 pounds during the study.

"There is limited data on weight change in breast cancer survivors, including those at higher risk for the disease compared to the general population," Visvanathan says. "A lot of studies have focused on breast cancer survivors alone, so we don't get a sense of whether women without cancer gain more or less weight, or whether the gain is due to the cancer or the treatment."

In patients with soft tissue sarcoma, whose disease had progressed during or after prior chemotherapy, pazopanib improved progression-free survival but did not change health-related quality of life. This observed improvement in progression-free survival without impairment of health-related quality of life was considered a meaningful result.

There has not been a lot of research that has looked into the quality of life of patients with advanced soft tissue sarcoma. The results of this European Organisation for Research and Treatment of Cancer (EORTC) health related quality of life study show that the application of pazopanib for soft tissue sarcoma is quite complicated. This study included an array of outcome assessments including not only efficacy and toxicity but also cost effectiveness and patient-reported outcomes, and it has provided much needed data.

Dr. Andrew Bottomley, Head of the EORTC Quality of Life Department and co-author of this study says "This is one of the few randomized clinical trials with quality of life studies undertaken in metastatic soft-tissue sarcoma in such a robust manner. It's so important to better understand what treatment options we can offer to these patients, and we hope our results shed more light onto a field that in the past had remained much in the dark."

Prof. Winette van der Graaf of Radboud University Medical Center Nijmegen, The Netherlands and coordinator of EORTC trial 62072 points out, "The EORTC health related quality of life study was comprehensive, and although multiple indicators might complicate interpretation of the results, they also provide a more thorough assessment of the impact of pazopanib therapy on the patients and on the impact on the health care system. In the end, this is what is needed to translate clinical trial results to the bedside."

Corneel Coens, EORTC Biostatistician and lead author of this study explains, "One of the intentions of this study was to investigate if, by delaying tumor progression, pazopanib would improve the quality of life of these sarcoma patients. An ambitious project as this is a relative rare and mixed patient population with little prior data about quality of life. This study informs us about the treatment balance between improving outcome at the cost of side effects."

This study was conducted by the EORTC Soft-Tissue Sarcoma Group and the EORTC Quality of Life Department and supported by a grant from GlaxoSmithKline. Health-related quality of life was assessed using the 30-item core EORTC Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline and at weeks 4, 8, and 12 in patients who received treatment on protocol.

Coens et al. Health-related quality-of-life results from PALETTE: A randomized, double-blind, phase 3 trial of pazopanib versus placebo in patients with soft tissue sarcoma whose disease has progressed during or after prior chemotherapy—a European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Global Network Study (EORTC 62072). Cancer. 2015; doi: 10.1002/cncr.29426 [Abstract]

Results show significantly worse survival rates with chemoradiation compared to total laryngectomy.

Despite findings of previous studies and published guidelines, nearly two-thirds of patients with T4a larynx ("voice box") cancer are not receiving a total laryngectomy (surgical removal of the larynx), the recommended form of treatment, and as a result, have significantly worse survival rates versus those treated with a total laryngectomy, a new study published in the International Journal of Radiation Oncology, Biology and Physics by experts at Penn Medicine found. Patients who underwent a laryngectomy, on average, lived nearly two years longer than those on chemotherapy and radiation therapy.

"Larynx preservation via chemoradiation is an excellent, organ-preserving option to total laryngectomy for many patients with less advanced larynx cancers," said Alexander Lin, MD, an assistant professor and chief of Head and Neck Service in the department of Radiation Oncology at the Perelman School of Medicine at the University of Pennsylvania, the study's senior author. "But it's inferior for patients with the most locally-advanced larynx caners. These patients should be treated with a total laryngectomy--and our are study shows that most of them are not."

In stage T4a larynx cancer the tumor grows through the thyroid cartilage and/or into tissues beyond the larynx, such as the thyroid gland, trachea, esophagus, tongue muscles, or neck muscles.

The all-Penn study identified 969 patients from 2003 to 2006 who received curative-intent treatment for T4a larynx cancer from the National Cancer Database. A total of 616 patients (64 percent) received larynx preservation chemoradiation, and 353 (36 percent) received total laryngectomy. Median overall survival for total laryngectomy patients was 61 months versus 39 months for patients receiving chemoradiation.

The survival of patients with stage T4a larynx cancer who are untreated is typically less than one year. The symptoms associated with untreated disease include severe pain and inability to eat, drink, and swallow. Death can frequently occur due to asphyxiation of the airway from the untreated tumor.

Patients with the lowest body mass index (BMI) had the shortest overall survival in an analysis of bevacizumab studies in metastatic colorectal cancer (mCRC) presented for the first time at the ESMO 17th World Congress on Gastrointestinal Cancer 2015 in Barcelona.

"There is good evidence that obesity increases the risk of getting colorectal cancer and that it increases the risk of colorectal cancer recurrence after curative therapy," said lead study author Dr Yousuf Zafar, associate professor of medicine at Duke Cancer Institute in Durham, North Carolina. "What we did not know prior to these results is whether there is a relationship between obesity and survival in patients with metastatic colorectal cancer."

He continued: "There is evidence that, at least in the US, obese patients may be at risk to receive lower doses of chemotherapy, so we hypothesised that obesity would be associated with worse survival in patients with colorectal cancer."

The current study analysed overall survival and progression-free survival according to four categories of BMI (<25, 25-<30, 30-35, >35 kg/m2) in patients treated with bevacizumab in the first line for mCRC. The researchers used a pooled dataset of patients with previously untreated mCRC who received bevacizumab with chemotherapy in four large prospective US and European registry studies, namely BEAT, BRiTE, AWB and CONCERT.