Recent advances in gynecologic radiation oncology.

PURPOSE OF REVIEW: Radiation has long been a primary treatment modality in locally advanced gynecologic carcinomas and a tool for palliation of metastatic disease. Here we review advances in imaging and radiation technologies and the corresponding clinical evolution of the role for radiation oncology in the treatment of gynecologic malignancies. RECENT FINDINGS: Advances in MRI are impacting diagnosis, radiation target delineation, planning, treatment delivery, and response assessment. The combination of MRI and PET-computed tomography (PET-CT) has the potential to significantly change treatment recommendations as compared with a single imaging modality. Advances in radiation delivery including intensity modulated radiation therapy (IMRT) and stereotactic ablative radiotherapy (SABR) have expanded the role for radiation in the definitive treatment of high risk and oligometastatic ovarian cancer. Finally, global disparities in oncology resources has led to the development of resource stratified treatment guidelines for gynecologic malignancies. The use of ultrasound for brachytherapy planning may help improve access to this critical treatment modality. SUMMARY: As imaging and radiation technologies advance, the indications for radiation in the treatment of gynecologic malignancies continues to evolve. Here we review the changing landscape of radiation oncology in the multidisciplinary management of gynecologic cancers.

Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study.

BACKGROUND: Head and neck cancers positive for human papillomavirus (HPV) are exquisitely radiosensitive. We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma. METHODS: We did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod performance status scores of 0 or 1. Patients received two cycles of induction chemotherapy with 175 mg/m2 paclitaxel and carboplatin (target area under the curve of 6) given 21 days apart, followed by intensity-modulated radiotherapy with daily image guidance plus 30 mg/m2 paclitaxel per week concomitantly. Complete or partial responders to induction chemotherapy received 54 Gy in 27 fractions, and those with less than partial or no responses received 60 Gy in 30 fractions. The primary endpoint was progression-free survival at 2 years, assessed in all eligible patients who completed protocol treatment. This study is registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195. FINDINGS: Between Oct 4, 2012, and March 3, 2015, 45 patients were enrolled with a median age of 60 years (IQR 54-67). One patient did not receive treatment and 44 were included in the analysis. 24 (55%) patients with complete or partial responses to induction chemotherapy received 54 Gy radiation, and 20 (45%) with less than partial responses received 60 Gy. Median follow-up was 30 months (IQR 26-37). Three (7%) patients had locoregional recurrence and one (2%) had distant metastasis; 2-year progression-free survival was 92% (95% CI 77-97). 26 (39%) of 44 patients had grade 3 adverse events, but no grade 4 events were reported. The most common grade 3 events during induction chemotherapy were leucopenia (17 [39%]) and neutropenia (five [11%]), and during chemoradiotherapy were dysphagia (four [9%]) and mucositis (four [9%]). One (2%) of 44 patients was dependent on a gastrostomy tube at 3 months and none was dependent 6 months after treatment. INTERPRETATION: Chemoradiotherapy with radiation doses reduced by 15-20% was associated with high progression-free survival and an improved toxicity profile compared with historical regimens using standard doses. Radiotherapy de-escalation has the potential to improve the therapeutic ratio and long-term function for these patients. FUNDING: University of California.

The patient's perspective on radiation for rectal cancer: Initial expectations versus actual experience.

BACKGROUND: The aim of this study was to compare patient perceptions of radiotherapy (RT) before and after treatment to better inform future patients and providers. METHODS: Seventy-eight consecutive patients with rectal adenocarcinoma treated with neo- or adjuvant chemoradiation, surgical resection, and adjuvant chemotherapy from 2009 to 2018 and who were without recurrence were included. Patients were surveyed ≥6 months after ileostomy reversal or ≥3 months after adjuvant chemotherapy. The survey assessed patients' baseline knowledge and fears of RT, how their short- and long-term side effects compared with initial expectations, and how their experiences compared for each modality (RT, surgery, and chemotherapy). RESULTS: Forty patient-responses were received. Before treatment, 70% of patients indicated little to no knowledge of RT, though 43% reported hearing frightening stories about RT. The most commonly top-ranked fears included organ damage (26%), skin burns (14%), and inability to carry out normal daily activities (10%). Eighty percent reported short-term effects of RT to be less than or as expected, with urinary changes (93%), abdominal discomfort (90%), and anxiety (88%) most commonly rated as less than or as expected. 85% reported long-term effects to be less than or as expected, with pain (95%), changes to the appearance of the treated area (85%), and dissatisfaction with body image (80%) most commonly rated as less than or as expected. Surgery was most commonly rated as the most difficult treatment (50%) and most responsible for long-term effects (55%). RT was least commonly rated as the most difficult treatment (13%), and chemotherapy was least commonly rated as most responsible for long-term effects (13%). CONCLUSIONS: The majority of patients indicated short- and long-term side effects of RT for rectal cancer to be better than initial expectations. In the context of trimodality therapy, patients reported RT to be the least difficult of the treatments.

The Patient's perspective on radiation therapy for anal cancer: Evaluation of expectations and stigma.

BACKGROUND: Little is known regarding anal cancer patients' perspectives on undergoing radiation therapy. Additionally, the stigma surrounding anal cancer diagnosis warrants a better understanding of the barriers to complete disclosure in patient-healthcare team interactions. METHODS: Included patients had squamous cell carcinoma of the anus treated with definitive chemoradiation (CRT) from 2009 to 2018. Survey questions were adapted from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and Discrimination and Stigma Scale. RESULTS: A total of 46 anal cancer patients who underwent CRT were surveyed, of which 72% responded. 73% of respondents indicated little to no pre-treatment knowledge of CRT. 70% reported overall short-term effects as worse than expected, most commonly with bowel habits (82%), energy (73%), and interest in sexual activity (64%). 39% reported overall long-term effects to be worse than expected, most commonly with changes to bowel habits (73%), sexual function (67%), and interest in sexual activity (58%). However, 94% agreed they were better off after treatment. Regarding stigma, a subset reported hiding their diagnosis (12%, 24%) and side effects (24%, 30%) from friends/family or work colleagues, respectively, and 15% indicating they stopped having close relationships due to concerns over stigma. CONCLUSIONS: Although patients' perceptions of the severity of short-term CRT side effects were worse than expectations, the vast majority agreed they were better off after treatment. Targeted counseling on common concerns may improve the anal cancer treatment experience. A notable subset reported stigma associated with treatment, warranting further evaluation to understand the impact on the patient experience.

The Timeliness Initiative: Continuous Process Improvement for Prompt Initiation of Radiation Therapy Treatment.

PURPOSE: The ambulatory patient experience is heavily influenced by wait times for provider care. Delayed patient visit start times may negatively affect overall satisfaction, and increased wait times affect the perception of the information, instructions, and treatment given by health care providers. Improving institutional practices overall requires the determination of the essential quality metrics that will make such an achievement possible. A protracted time leading up to the initiation of radiation therapy may promote poor satisfaction and perceived quality of care for both patients and referring providers alike, which may then create a barrier to patients being treated with radiation therapy. This institution piloted and sucessfully completed a study into improving the timeliness of initiation of patient radiation therapy for our patients. METHODS AND MATERIALS: This work sought to identify inefficiencies in radiation therapy treatment planning to shorten the time each patient waited for treatment. We examined the time between simulation to the start of the first fraction of treatment. This period includes simulation, contouring, treatment planning, and quality assurance of the plan. RESULTS: Before the study, the planning process would typically take 2 weeks. Target and organs-at-risk contouring were found to be the main inefficiency delaying treatment start dates. This delineating process includes drawing contours on radiologic images, typically computed tomography and magnetic resonance imaging. We focused on the time needed for the contouring process to be completed and took steps to increase efficiency. The length of time from simulation to contour approval was decreased by more than 60%, a reduction from an average of more than 4 days to less than 1.5 days. Overall planning time dropped from 2 weeks to less than 5 days. CONCLUSIONS: Process improvements and implementation of task-specific tools improved the timeliness of patient treatments, reducing the overall planning time from simulation to treatments to less than 5 days. Continuous monitoring and modification of these processes revealed that the successes achieved toward better quality of care have been sustained.

Hazards of sparing the ipsilateral parotid gland in the node-positive neck with intensity modulated radiation therapy: Spatial analysis of regional recurrence risk.

PURPOSE: The practice of deliberately sparing the ipsilateral parotid gland with intensity modulated radiation therapy (IMRT) in patients with node-positive head and neck cancer is controversial. We sought to compare the clinical outcomes among consecutive cohorts of patients with head and neck cancer who were treated with differing strategies to spare the parotid gland that is ipsilateral to the involved neck using IMRT. METHODS AND MATERIALS: A total of 305 patients were treated with IMRT for node-positive squamous cell carcinoma of the head and neck. The first 139 patients were treated with IMRT whereby the ipsilateral parotid gland was delineated and intentionally designated as an avoidance structure during planning. The subsequent 166 patients were treated by IMRT without the deliberate sparing of the ipsilateral parotid gland. RESULTS: The 2-year estimates of overall survival, local-regional control, and distant metastasis-free survival were 84%, 73%, and 87%, respectively. The 2-year estimates of overall survival were 77% and 86% among patients who were treated by IMRT with and without the sparing of the ipsilateral parotid gland, respectively (P = .01). The respective rates of 2-year regional control were 76% and 90% (P < .001). A trend was observed between increased nodal burden in the ipsilateral cervical neck and the likelihood of regional failure for both groups. A spatial evaluation revealed a significantly higher incidence of marginal failures and true misses in the cohort of patients who underwent IMRT with the sparing of the ipsilateral parotid gland. CONCLUSION: Caution is urged when using IMRT to spare patients' parotid gland on the involved side of neck disease. Our study showed a significantly higher preponderance of regional failure, which highlights the need for careful patient selection and consideration of clinical and pathological factors that influence the likelihood of disease recurrence in the ipsilateral neck.

Precision Medicine: Genomic Profiles to Individualize Therapy.

Precision medicine is the application of genotypic and Omics biomarkers to determine the most appropriate, outcome-driven therapy for individual patients. To determine the best choice of therapy, institutions use significant information technology-enabled data from imaging, electronic medical records, sensors in the clinic/hospitals, and wearable sensors to determine treatment response. With genomic profiling, targets to affect a disease course are continuing to be developed. As clonal mutational prevalence continues to be understood, information can be communicated to patients to inform them that resistance is common, requiring collection of more genetic mutations from patients with further biopsies or blood collection.

Considerations for Quality Improvement in Radiation Oncology Therapy for Patients with Uncomplicated Painful Bone Metastases.

Background: There is an increasing need for evidence-based efficiency in providing a growing amount of cancer care. One example of a quality gap is the use of multiple-fraction palliative radiation for patients with advanced cancer who have uncomplicated bone metastases; evidence suggests similar pain outcomes for treatment regimens with a lower burden of treatments. Methods: During the first phase of quality improvement work, we used RAND/UCLA appropriateness methodology to understand how radiation oncologists at one academic medical center rate the appropriateness of different treatment regimens for painful uncomplicated bone metastases. We compared radiation oncologist appropriateness ratings for radiation treatments with radiation therapy provided by these oncologists to patients with painful bone metastases between July 2012 and June 2013. Results: Appropriateness ratings showed that single-fraction (8 Gy) treatment (a low burden treatment) was consistently considered an appropriate option to treat a variety of uncomplicated bone metastases. The use of >10 fractions was consistently rated as inappropriate regardless of other factors. Eighty-one patients receiving radiation therapy for painful bone metastases during the study period had an available medical record for chart abstraction. Almost one-third of metastases were considered complicated because of a concern of spinal cord compression, a history of prior irradiation, or an associated pathological fracture. Among uncomplicated bone metastases, 25% were treated with stereotactic body radiation treatment (SBRT). Among the 54 uncomplicated bone metastases treated with conformal radiation, only one was treated with single-fraction treatment and 32% were treated with greater than 10 fractions. Conclusions: Treatment at the study site demonstrates room for improvement in providing low-burden radiation oncology treatments for patients with painful bone metastases. Choosing a radiation treatment schedule for patients with advanced cancer and painful bone metastases requires consideration of many medical and patient-centered factors. Our experience suggests that it will take more than the existence of guidelines to change practice in this area.

Skin surface brachytherapy: A survey of contemporary practice patterns.

PURPOSE: The aim of this study was to define current patterns of care among radiation oncologists who use skin surface brachytherapy for the treatment of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) in academic and community settings. METHODS AND MATERIALS: A 30-question electronic survey was administered to clinician members of the American Brachytherapy Society. The respondents were asked to provide details regarding their clinical practice and their approach to skin surface brachytherapy. RESULTS: A total of 16 surveys were returned. Among the respondents, aggregate experience varied from 8 to 1800 cases. Most preferred brachytherapy over external beam radiation because of shorter treatment course, conformality of treatment for irregular or curved targets, and shallow dose deposition. Of the total, 60% of respondents routinely estimated lesion depth via ultrasound before initiating treatment. Treatment margin on gross disease varied widely (range, 3-15 mm; median, 5 mm). Hypofractionation was the preferred dose schedule. Prescribed doses ranged from 30 Gy in five fractions to 64 Gy in 32 fractions (EQD2, 40 Gy-65 Gy). There was a tendency to increase the number of fractions for larger targets, although some used the same fractionation regardless of anatomic location or lesion size. There was no consensus on dosimetric constraints, and some respondents reported cases of severe toxicity, particularly when treating the pretibial skin. CONCLUSIONS: This pattern of care study suggests that skin brachytherapy can be a convenient and safe tool for treatment of BCC and cSCC. Prospective trials and the development of expert consensus guidelines would be beneficial for optimizing skin surface brachytherapy and reducing practice variation.