The overall goal is to update the healthcare professional’s knowledge of cancer detection and prevention and to understand current and new research regarding state-of-the-art care for those with or at risk for cancer.
Intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.
Upon completion, participants should be able to:
Dannemiller is approved by the California Board of Registered Nursing, Provider Number 4229, for 1.0 contact hour. CBRN credit is not accepted by the Michigan and Utah State licensing boards.
The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial companies pertaining to this activity.
This activity is provided free of charge to participants.
The poly (ADP-ribose) polymerase (PARP) inhibitor veliparib exhibits antitumor activity and is safe and tolerable on a continuous dosing schedule when used for the treatment of patients with BRCA-positive and BRCA–wild type tumors. Data from a phase I trial indicate better clinical activity in patients with BRCA-positive tumors and a recommended phase II dose of 400 mg twice daily, said Shalu Pahuja, MD, at the 2014 ASCO Breast Cancer Symposium. Abstract 135
Veliparib is an oral small-molecule inhibitor of PARP 1 and PARP 2. “BRCA1 and BRCA2 defective tumors are intrinsically sensitive to PARP inhibitors,” said Pahuja, an oncology fellow at the University of Pittsburgh Cancer Institute. PARP inhibitors exploit these alterations in DNA repair, as outlined by the concept of “synthetic lethality.”
This phase I study was conducted in two cohorts of patients: a cohort with a documented BRCA 1/2 mutation (BRCA-positive cohort) and a BRCA–wild type cohort consisting of patients with triple-negative breast cancer or platinum-refractory ovarian, fallopian tube, or primary peritoneal cancer.
At final enrollment, there were 70 BRCA-positive patients and 28 BRCA-wild type patients. In the wild type group, 86% of patients had triple-negative breast cancer, and 14% had ovarian cancer. In the BRCA-positive group, 23% had breast tumors, and 54% had ovarian tumors. Patients in the BRCApositive group had a median of six prior treatments before enrollment, and those in the wild type group had a median of four.
There was no difference in the dose-limiting toxicities between the two groups. Dose-limiting toxicities included seizure at 400 mg twice daily in the wild type group and at 500 mg twice daily in the BRCA-positive group. There was one grade 3 incidence of nausea/vomiting at 400 mg twice daily in the BRCA-positive patients. Based on toxicities, 400 mg twice daily was recommended as the phase II dose.
No difference in the toxicity profiles was observed between the BRCA-positive versus BRCA–wild type patients. The most common all-grade toxicities were nausea, experienced by 37% of patients, lymphopenia (35%), fatigue (19%), and vomiting (9%). These were largely grade 1 or 2 toxicities. Forty percent of patients at the recommended phase II dose required dose reduction for low-grade nausea or flu-like symptoms.
Among the 24 BRCA-wild type patients (21 with breast tumors), “the triple-negative breast cancer patients received modest clinical benefit, including one patient with partial response and an additional eight patients with stable disease,” said Pahuja. There were too few patients with ovarian cancer in this cohort (n = 3) to draw conclusions. “In contrast, clinical activity was greater in the BRCA-mutation cohort,” she said. “At all dose levels combined, the objective response rate [ORR] was 23% with a clinical benefit rate of 37% for all tumor types.”
Among patients with breast cancer in this cohort, the ORR was 29% with a 36% clinical benefit rate. In the patients with ovarian cancer, the ORR was 20% and the clinical benefit rate was 33%.
PARP inhibitors have demonstrated promising results in patients with BRCA mutation–related breast and ovarian cancers. The study performed by Pahuja et al, however, revealed the effectiveness of this type of medication in both BRCA-positive and BRCA-wild type patients. The study revealed that the PARP inhibitor veliparib, when used as single agent, was responsive in both BRCA-positive and BRCA-wild type tumors compared with other single-agent PARP inhibitors.
Normal cells use PARP to repair themselves; however, cancer cells may use PARP to repair DNA damage, therefore prolonging their uncontrolled growth. This abnormality can subsequently cause resistance to treatment. PARP inhibitors work to prevent repair of damaged DNA of cancer cells.
Veliparib is another addition to the growing understanding of the science of breast and ovarian cancer, and knowing upfront which patients would benefit from these drugs is another positive step towards personalized medicine.
A new analysis of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial presented at the ASTRO 56th Annual Meeting offers substantial evidence that treatment with radiation therapy does not increase the incidence of lymphedema in patients with node-negative breast cancer. Abstract 1463
“These results provide much-needed reassurance to breast cancer patients regarding the impact of radiation therapy on lymphedema risk,” said lead study author Susan McCloskey, MD, MSHS, assistant professor of radiation oncology at the UCLA David Geffen School of Medicine. “The study findings argue convincingly that radiation therapy to the level 1 axilla, considered unavoidable ‘collateral damage’ when radiating the whole breast, does not contribute to lymphedema risk beyond surgery.”
In the original NSABP B-32 study, 5611 women with clinically node-negative breast cancer were randomized to sentinel node biopsy (SNB) or SNB + axillary lymph node dissection (ALND). The goal of the study was to determine if SNB was as effective as ALND with fewer side effects. The results showed that the SNB+ALND combination was associated with a significantly greater risk of lymphedema versus SNB alone.
Importantly, for the secondary analysis presented at ASTRO, the trial also provided the opportunity to evaluate the impact of radiation therapy (RT) on lymphedema risk, a significant concern for women undergoing breast cancer treatment.
Among the 3916 women in the trial with lymphedema assessments, including 1936 randomly assigned to SNB+ALND and 1980 randomly assigned to SNB, 82.2% (n = 3220) received RT and 17.2% (n = 674) did not.
Measures of lymphedema were collected at baseline prior to RT and every 6 months during the 3-year follow-up period. Lymphedema was assessed both by standardized arm measurements by clinicians (objective lymphedema) and via questionnaires completed by patients (subjective lymphedema).
Objective lymphedema (clinician measured) was defined as relative arm volume difference (RAVD) >10%, and was determined by a water displacement method. Subjective lymphedema was defined as patient-reported ipsilateral swelling that was “somewhat,” “quite” or “very” bothersome.
Overall, researchers found no greater risk of lymphedema among women receiving RT versus those who did not receive RT. There was no significant difference in standardized arm measurements and no significant difference in patient reports of bothersome arm swelling during 3 years of follow up, suggesting that radiation does not contribute to lymphedema risk beyond surgery over time.
A subgroup analysis at 36 months of follow-up found that among patients in the SNB+ALND group who also received RT, RAVD >10% was detected in 12.4% of women, and 7.4% reported bothersome swelling. In patients who did not receive RT, 16.7% of patients who underwent SNB+ALND had a RAVD >10%, and 8.8% were bothered by swelling.
In the SNB-only group, 7.4% of patients who received RT had RAVD >10%, and 3.2% reported bothersome swelling, versus 4.5% and 4.8%, respectively, among those in this cohort who did not have RT.
OWith the use of MRI imaging to restrict doses to erectile tissues, nearly half of men treated with external beam radiation therapy (EBRT) for prostate cancer were able to be sexually active without aids or medications 5 years later, and nearly 80% could be sexually active if such support was an option, according to the results of a study presented at the 2014 ASTRO Annual Meeting. Abstract 111
For the study, the researchers evaluated 91 men treated with EBRT at the University of Michigan Providence Cancer Institute whose treatment was guided by MRI-based planning for the restriction of doses to the sub-apex region and specific erectile tissues. About half of the participants were treated simultaneously with brachytherapy, but none received androgen-deprivation therapy. The authors prospectively gathered information on their sexual function and compared results from the EBRT-alone group (n = 42) with those in the combination group (n = 49). The patients reported their level of sexual function at baseline, 2 years after treatment, and 5 years after treatment using two scales: the International Index of Erectile Function (IIEF), which emphasizes sexual function adequate for intercourse, and a three-question scale (Q3) that asked men if they were able to be sexually active without aids or medication; with aid; or not at all. Scores from the Q3 showed that 2 years after treatment, 59.2% of men taking the therapy combination and 64.3% of those receiving EBRT alone were able to be sexually active without aid, while all of the combination patients and 76.1% of the EBRT-alone cohort could be sexually active if aid was an option.
The percentages of men with preserved sexual function were lower according the IIEF scale. At baseline, 36 men in the combination arm and 22 in the EBRT-only arm reported having normal sexual function. At 2 years, 69.4% and 63.6% of those men, respectively, reported that they could be sexually active without aid; with aid as an option, those percentages rose to 75% with the combination and 72.7% with EBRT alone. At 5 years, 55.6% and 59.1% of patients in the combination and EBRT groups, respectively, reported that they could function sexually without aid, versus 66.7% and 63.6% if aid was an option.
Those results were still “spectacular,” since the men on both arms were given very high-dose treatments, said the presenter of the data, lead study author Patrick W. McLaughlin, MD, medical director of Radiation Oncology at the University of Michigan Providence Cancer Institute. “In the past, men with prostate cancer expected to pay a high toll in loss of quality of life to achieve cure and were willing to accept that as necessary,” said McLaughlin."
This study makes it clear that even with combination radiation protocols . . . avoidance of critical adjacent tissues, such as vessel-sparing, makes cure and quality of life an achievable goal for many men.”
Timing of metastatic development, lymph node involvement, and type of disease all factor into the overall survival (OS) rate of patients with stage IV non–small cell lung cancer (NSCLC) and could offer a potential risk stratification scheme for ablative therapy, according to a meta-analysis presented at the ASTRO 56th Annual Meeting. Abstract 168
The analysis looked at data from 757 patients from 20 hospitals worldwide and found that aggressively treating “low-risk” patients with NSCLC, those with metachronous metastases, with surgery or stereotactic ablative radiotherapy (SABR) elicited a 5-year OS rate of 47.8%. The OS rate was 36.2% for intermediate-risk patients and 13.8% for high-risk. Among all patients, median OS was 26 months, median progressionfree survival was 11 months, and 5-year OS was 29.4%.
“We hope our study’s results will help determine which stage IV NSCLC patients are most likely to benefit from aggressive treatments, and equally as important, help identify those patients most likely to fail, thus sparing them from futile and potentially harmful treatments,” explained lead study author Allison Ashworth, MD, a radiation oncologist who completed the study as part of her training at Western University in London, Ontario.
In the trial, patients were stratified based on timing of metastatic development (synchronous versus metachronous, P <.001), lymph node involvement (P = .002), and adenocarcinoma histology (P = .036). Low-risk patients (n = 146) were defined as those with metachronous metastases while intermediaterisk patients (n = 201) had synchronous metastases and no evidence of involved lymph nodes in the chest. High-risk (n = 184) patients were defined as those with synchronous metastases and evidence of lymph node involvement in the chest.
Patients were treated with surgical metastectomy, SABR, stereotactic radiosurgery or radical external-beam radiotherapy, and curative-intent treatment of the primary lung cancer. Surgery was the most commonly used treatment for both the primary tumor and metastases (83.9%). Despite aggressive treatment, more than half of all patients in the analysis progressed in previously treated areas or developed new disease sites within 1 year.
Ashworth noted that patients in this analysis were “a very select minority of stage IV patients who are younger, more physically fit, with a lower burden and slower pace of disease than the average stage IV patient.”
As a retrospective analysis, the true impact of aggressive treatment still needs to be determined in a randomized trial. However, this risk classification scheme could be utilized in guiding the selection of patients for future studies of ablative treatment, the authors of the study noted.
“We must await the results of randomized clinical trials to answer this question,” Ashworth said. “In the meantime, it is our hope that our study will help cancer specialists in making treatment decisions and in the development of clinical trials.”
It is always good to see efforts and progress being made in terms of outcomes for Stage IV NSCLC, even when it is a retrospective analysis as opposed to a randomized clinical trial. This meta-analysis provides much-needed insight as to treatment approaches and the associated outcomes for this population, but in particular, for those with low-risk disease. Here, it was not much of a surprise to read that those with high risk–factor disease had poorer outcomes. On the other hand, it seems somewhat intuitive that the low-risk population would have the most to gain from aggressive treatment and these results point in that direction.
That being said, a shortcoming of this analysis is the admitted favorable performance status (PS) throughout the population studied. Arguably, this puts the applicability of these results in a “best-case” patient population context that is too infrequently found. In that surgery and radiation therapy were the only treatment modalities mentioned, it would be interesting to know what role chemotherapy played, if any, in the outcomes, given that the PS of these patients would seem to have allowed for at least single-agent chemotherapy assuming that they had evaluable disease. Furthermore, did any of these patients have targetable disease profiles and how would that have affected the outcomes?
If these results are tested in randomized trials and hold true, it would be imperative to disseminate this information to those affected. Patients with this stage of disease, whose treatment options beyond ablative therapy may be few, can be appropriately counseled by their treatment team. This counseling should allow them to realize when, given their risk factors, aggressive treatment may lead to a more favorable outcome and when their risk factors may lead to doing more harm than good.
Radiotherapy is equally as effective in the palliation of dysphagia (difficulty swallowing) as chemoradiotherapy for patients with advanced esophageal cancer, according to a phase III study presented at the 56th American Society for Radiation Oncology (ASTRO) Annual Meeting—offering clinicians an option to relieve this common complication without the added toxicity of chemotherapy. Abstract CT-03
Patients who received radiotherapy alone reported a dysphagia response of 67.89% at any point compared with a 73.87% response with chemoradiotherapy (P = .343).
Lead author Michael Penniment, MBBS, MBA, FRANZCR, noted that chemotherapy is commonly administered to patients with advanced esophageal cancer based on standard practice for less advanced disease. There is some disagreement on this approach, however, because some clinicians “believe no treatment should be offered” as it may be “futile and potentially toxic.”
“These results will allow us to simplify the treatment for patients who cannot be cured but who can expect an improvement in swallowing and quality of life as a result of radiotherapy alone; these patients can be spared the extra toxicity and cost of chemotherapy,” said Penniment, who is director of radiation oncology at the Royal Adelaide Hospital and the Alan Walker Cancer Care Centre in Australia.
In this international multicenter trial, 220 patients were randomized to palliative radiotherapy (n = 109) or concomitant chemoradiotherapy with cisplatin and 5-FU (n = 111). Baseline parameters were well matched at randomization, the authors noted. Radiotherapy was administered at 35 Gy in 15 fractions to 115 patients in Australia and New Zealand and 30 Gy in 10 fractions to 105 patients in Canada and the United Kingdom. The primary endpoint of this trial was focused on the proportion of patients with improved dysphagia at week 9 and maintained until week 13.
Dysphagia was determined using the Mellow system, which measures the patient’s ability to swallow liquids or solids on a scale of 0 to 5. Toxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE) v2, whereas quality of life was evaluated with two patient questionnaires: EORTC QLQ30 and oesophagus module (OES-18).
Though dysphagia responses were equal, there were toxicity differences reported between the two arms. The chemoradiotherapy arm experienced higher rates of nausea (P = .0019) and vomiting (P = .0072) compared with the radiotherapy-alone arm, and median survival was about the same between the two arms: 210 days versus 203 days, respectfully. The authors on the study noted that though patients in both arms showed equally poor survival, 21 patients were still alive 2 years after treatment.
“This study was the largest, randomized, phase III trial of advanced esophageal cancer and was a significant undertaking for a ‘palliative care’ trial, namely where the emphasis was on the best, yet simplest and least toxic, treatment to alleviate pain,” Penniment said.
Authors on the study wrote that this is the first randomized phase III trial examining the response, toxicity, or role of palliative chemoradiotherapy in advanced esophageal cancer. Quality of life, toxicity, and durable palliative responses will continue to be analyzed and will be published.
There are several different types of cancer clinical trials, with each type of trial designed to answer different research questions. Quality of life trials explore ways to assist patients who are experiencing side effects from cancer or its treatments. Phase III trials focus on how a new treatment compares with standard treatment. Comparing treatments with each other often shows which one is more effective or has fewer side effects.
Dysphagia is more prevalent in head and neck cancers, and can be a problem even before treatment begins. This phase III trial of advanced esophageal cancer reveals that radiation therapy is equally as effective as chemoradiotherapy in providing relief from swallowing difficulties that often come with latestage esophageal cancer. Patients can be spared from the reported nausea and vomiting that comes with chemoradiotherapy along with the expense and additional time that chemotherapy adds to treatment.
There were two areas measured in this study of 220 patients: improved swallowing ability at different segments and quality of life. Dysphagia can include difficulties with speaking, drooling, aspiration, pain, and loneliness. It’s not surprising then that quality of life improves when an individual’s swallowing ability improves.
The individual with oral and head and neck cancer requires more rehabilitation, additional emotional support, and struggles with several quality of life issues. In recent years progress has been made in prevention awareness, early detection and improved surgical reconstructions. Because of these efforts, head and neck cancers have improved survival rates and improved quality of life at every stage.
Despite a recent decline in utilization, consolidated radiation therapy (RT) has been shown to improve 10-year survival rates for patients with stage I/II Hodgkin’s lymphoma following treatment with chemotherapy, according to data from a large analysis presented at the 2014 ASTRO Meeting. Abstract CT-08
The use of RT for patients with early-stage Hodgkin’s lymphoma has decreased from 56% to 41% between 1998 and 2011. In 88.4% of the patients, the physician-reported reason for not administering RT was that it was not part of the planned initial treatment strategy. Based on the results of the analysis, the authors of the study suggested that since combined modality therapy contributed significantly to the cure rate for patients with early stage Hodgkin’s lymphoma, RT should remain standard practice.
“Multiple prospective, randomized trials have shown a significant improvement in disease control with the addition of RT, however previous trials were limited by low patient numbers and limited follow-up and thus, were unable to demonstrate an overall survival benefit,” lead study author Rahul R. Parikh, MD, a radiation oncologist at Mount Sinai Beth Israel and an Assistant Professor of Radiation Oncology at Icahn School of Medicine at Mount Sinai, said in a statement. “This is the largest dataset in this patient population to demonstrate a survival benefit with the addition of RT.”
For the study, 41,502 patients with an average age of 37 who had been diagnosed with stage I and II Hodgkin’s lymphoma between 1998 and 2011 were selected from National Cancer Data Base. The median follow-up for patients in the database was 7.5 years. Of the patients selected, 96% (n= 39,842) had received multiagent chemotherapy and 49% (n = 20,441) had received RT at a median dose of 30.6 Gy.
The 10-year overall survival (OS) rate for the entire group of patients was 80.8%. After a median of 10 years, the OS rate for patients who received RT was 84.4% compared with 76.4% for those who did not (HR = 0.51; 95% CI, 0.46-0.56, P <.00001). The omission of RT was associated with higher rates of transplant procedures performed, a surrogate for persistent/relapsed disease (P =.04). Additionally, initiating chemotherapy within 30 days after diagnosis was associated with improved OS at 10 years (84.5% vs 78.3%, P <.00001), even when adjusting for all covariables (HR = 0.86; 95% CI 0.77-0.95, P = .005).
The research also indicated that RT use was associated with younger patients (≤40 years), who had a higher socioeconomic status, who had access to health insurance, and who received treatment at comprehensive cancer centers (P <.0001).
“Given that the utilization of RT was associated with younger age, insurance status, higher socioeconomic status, and treatment at comprehensive cancer centers, we have highlighted ongoing disparities in Hodgkin’s Disease treatment and it is important that we recognize these findings as potential barriers to care,” Parikh said.
“Given the survival benefit demon-strated in this study, radiotherapy should be included in the combined modality approach of multiagent chemotherapy followed by consolidation RT in order to maintain high overall survival rates for this curable disease.”
The adverse events associated with the addition of radiation therapy were not noted in the analysis. Short-term side effects of RT generally include skin reaction, fatigue, nausea, and diarrhea. In general, long-term adverse events represent a leading concern facing the administration of RT for patients with early-stage Hodgkin’s lymphoma. These side effects usually do not manifest for 10 to 20 years following treatment. While newer approaches for administering RT hope to ameliorate these concerns, further data are still required to analyze this risk.
Radiation therapy (RT) in combination with chemotherapy has been a common treatment for early stage Hodgkin’s lymphoma. Previous studies have shown using RT results in an improvement in controlling the disease; however, due to low enrollment and lack of long-term follow up, improved overall survival has not been clearly identified. This large analysis of more than 41,000 patients with Hodgkin’s lymphoma diagnosed and treated during a 13-year period, shows that patients who received multi-agent chemotherapy with consolidative radiotherapy have significantly improved survival over patients who did not receive radiation.
Physicians report a recent decline in the use of RT for early stage Hodgkin’s. Reasons for not including RT in the treatment plan include lack of data regarding long-term overall survival and side effects. Short-term side effects of radiation are generally well-tolerated and controlled with supportive care, such as antiemetics, antidiarrheals, and good skin care. However, the long-term effects can include secondary malignancies, and this could impact on treatment decisions, especially when long-term benefit versus risk has not been clear. Newer techniques for administering radiation that limit the field and exposure to uninvolved tissue may mitigate this risk, but more research and long-term follow-up is needed. This latest research, with demonstrated improvement in outcomes, supports the use of RT for this patient population and should be considered as part of the initial treatment plan.
The interesting finding that younger patients from a higher socioeconomic group with access to comprehensive cancer centers are more likely to receive RT highlights the disparity that exists in healthcare today. In a perfect world, all patients should have access to the same information and state-of-the art care, but in the real world, this remains a challenge. Patients across all socioeconomic groups need to be educated by healthcare professionals about the most current information pertaining to their disease with risks versus benefits and take part in the treatment planning process.