A.A. Solanki

Concurrent chemotherapy is associated with improved survival in elderly patients with bladder cancer undergoing radiotherapy

The current study was conducted to compare the overall survival (OS) of concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in elderly patients (those aged ≥80 years) with muscle‐invasive bladder cancer (MIBC).

Future directions in combined modality therapy for rectal cancer: reevaluating the role of total mesorectal excision after chemoradiotherapy.

Most patients who develop rectal cancer present with locoregionally advanced (T3 or node-positive) disease. The standard management of locoregionally advanced rectal cancer is neoadjuvant concurrent chemoradiotherapy (nCRT), followed by radical resection (low-anterior resection or abdominoperineal resection with total mesorectal excision). Approximately 15% of patients can have a pathologic complete response (pCR) at the time of surgery, indicating that some patients can have no detectable residual disease after nCRT. The actual benefit of surgery in this group of patients is unclear. It is possible that omission of surgery in these patients, termed selective nonoperative management, can limit the toxicities associated with standard, multimodal combined modality therapy without compromising disease control. In this review, we discuss the clinical experiences to date using selective nonoperative management and various attempts at escalation of nCRT to improve the number of patients who have a pCR. We also explore several clinical, laboratory, imaging, histopathologic, and genetic biomarkers that have been tested as tools to predict which patients are most likely to have a pCR after nCRT.

Adjuvant Radiotherapy Use by US Radiation Oncologists After Radical Cystectomy for Muscle-invasive Bladder Cancer

AIMS Historic trials suggested significant toxicity with adjuvant radiotherapy (ART) after radical cystectomy for muscle-invasive bladder cancer (MIBC). However, recent trials have found improved locoregional control and the 2016 National Comprehensive Cancer Network (NCCN) guidelines recommend ART consideration for select patients at high risk of local recurrence. ART practice patterns among US radiation oncologists are unknown and we carried out a survey to explore current trends. MATERIALS AND METHODS We conducted a survey of US radiation oncologists regarding the management of patients with cT2-3N0M0 transitional cell MIBC. Responses were reported using descriptive statistics. Chi-square and univariate logistic regression of clinical and demographic covariates were conducted, followed by multivariable logistic regression analysis to identify factors predicting for ART use. RESULTS In total, 277 radiation oncologists completed our survey. Nearly half (46%) have used ART for MIBC at least once in the past. In ART users, indications for ART include gross residual disease (93%), positive margins (92%), pathological nodal involvement (64%), pT3 or T4 disease (46%), lymphovascular invasion (16%) and high-grade disease (13%). On univariate logistic regression, ART use was associated with the number of years in practice (P=0.04), pre-cystectomy radiation oncology consultation (P=0.004), primarily treating MIBC patients fit for cystectomy (P=0.01) and intensity-modulated radiotherapy use (P=0.01). On multivariable logistic regression analysis, routine pre-cystectomy radiation oncology consultation (odds ratio 1.91, 95% confidence interval 1.04-3.51; P=0.04) and intensity-modulated radiotherapy use (odds ratio 2.77, 95% confidence interval 1.48-5.22; P=0.002) remained associated with ART use. CONCLUSIONS ART use is controversial in bladder cancer, yet unexpectedly has commonly been used among US radiation oncologists treating patients with MIBC after radical cystectomy. NRG-GU001 was a randomised trial in the US randomizing patients with high-risk pathological findings for observation or ART after cystectomy. However, due to poor accrual it recently closed and thus it will be up to other international trials to clarify the role of ART and identify patients benefiting form this adjuvant therapy.

Adjuvant Radiotherapy Versus Wait-and-see Strategy for Pathologic T3 or Margin-positive Prostate Cancer: A Meta-analysis

Objective: To conduct a meta-analysis of the randomized controlled trials (RCTs) comparing adjuvant radiotherapy (ART) to wait-and-see (WS) strategy in pathologic T3 or margin-positive prostate cancer. Methods: A comprehensive EMBASE, MEDLINE, http://www.clinicaltrails.gov, and Cochrane Library search for RCTs of ART versus WS was done. Results were synthesized for metastasis-free, biochemical progression-free, clinical progression-free, hormone-free, and overall survival as well as gastrointestinal (GI) and genitourinary (GU) toxicities. Either random-effects model or fixed-effects model were used based on the test of heterogeneity. Results: Three RCTs (EORTC22911, SWOG8794, ARO96-02/AUO-AP09/95) were identified with 1737 patients. ART resulted in greater biochemical progression-free survival (hazard ratio [HR]=0.48, P<0.00001) including benefit in all subsets, greater clinical progression-free survival (HR=0.73, P=0.0003) including benefit in subsets with margin-positive or seminal vesicle invasion and, greater hormone-free survival (HR=0.64, 95% confidence interval, 0.51-0.80, P=0.0001). Ten-year metastasis-free survival was significantly improved with ART (odds ratio=0.77, P=0.02). There was no survival benefit (HR=0.97; P=0.89). With ART compared with WS, there was significantly increased toxicity of any grade (50% vs. 38.6%), grade 2 or greater GU toxicity (17.1% vs. 10.3%), grade 2 or greater GI toxicity (2.5% vs. 1.1%), urinary stricture rates (11.1% vs. 5.7%) and, urinary incontinence (6.9% vs. 2.7%). Conclusions: Ten-year metastasis-free survival is significantly improved with ART compared with WS. Biochemical progression-free, clinical progression-free, and hormone-free survival were also improved with ART. Grade 2 or higher GI and GU toxicities were greater in ART. Therefore, ART should be offered to patients with these high-risk features.

Optimizing the Role of Surgery and Radiation Therapy in Urethral Cancer Based on Histology and Disease Extent

PURPOSE Urethral cancer is rare, with limited data guiding treatment. A national hospital-based registry was used to evaluate the role of local therapy in these patients. METHODS AND MATERIALS We performed a retrospective cohort study of patients who, between 2004 and 20013, received a diagnosis of T0-4N0-2 M0 urethral cancer. Local therapy was radiation therapy (RT), surgery (S), or S and RT (S+RT). The Cox proportional hazards model was used to assess the impact of therapy type on overall survival (primary endpoint). Subgroup analysis by extent of disease (early stage [T0-2 N0] vs locally advanced [T3+ or N+]) and histology was performed. RESULTS In our study, 2614 patients had a median follow-up of 28 months. Three-year overall survival was 54%. In 501 patients with locally advanced disease, S+RT was associated with improved survival versus S alone (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.42-0.80). There was no difference for patients with squamous cell carcinoma by treatment type, but patients with adenocarcinoma (RT vs S: HR 0.20; 95% CI, 0.07-0.60) or transitional cell carcinoma (S+RT vs S: HR 0.45, 95% CI, 0.26-0.77) had improved OS with RT as part of treatment. In 1705 early-stage patients, there was no association with survival when comparing S+RT versus S. CONCLUSIONS For patients with locally advanced disease and transitional cell carcinoma undergoing S, the addition of RT is associated with improved overall survival and should be considered. An RT-based approach may be preferred for adenocarcinoma, but there was no clear association with survival by therapy type for squamous cell carcinoma. This study is hypothesis generating; prospective trials are necessary.

Report from the SWOG Radiation Oncology Committee: Research Objectives Workshop 2017

The Radiation Therapy Committee of SWOG periodically evaluates its strategic plan in an effort to maintain a current and relevant scientific focus, and to provide a standard platform for future development of protocol concepts. Participants in the 2017 Strategic Planning Workshop included leaders in cancer basic sciences, molecular theragnostics, pharmaceutical and technology industries, clinical trial design, oncology practice, and statistical analysis. The committee discussed high-priority research areas, such as optimization of combined modality therapy, radiation oncology–specific drug design, identification of molecular profiles predictive of radiation-induced local or distant tumor responses, and methods for normal tissue-specific mitigation of radiation toxicity. The following concepts emerged as dominant questions ready for national testing: (i) what is the role of radiotherapy in the treatment of oligometastatic, oligorecurrent, and oligoprogressive disease? (ii) How can combined modality therapy be used to enhance systemic and local response? (iii) Can we validate and optimize liquid biopsy and other biomarkers (such as novel imaging) to supplement current response criteria to guide therapy and clinical trial design endpoints? (iv) How can we overcome deficiencies of randomized survival endpoint trials in an era of increasing molecular stratification factors? And (v) how can we mitigate treatment-related side effects and maximize quality of life in cancer survivors? The committee concluded that many aspects of these questions are ready for clinical evaluation and example protocol concepts are provided that could improve rates of cancer cure and quality of survival. Clin Cancer Res; 24(15); 3500–9. ©2018 AACR.

Transitioning from a Low Dose Rate to a High Dose Rate Prostate Brachytherapy Program: Comparing Initial Dosimetry and Improving Workflow Efficiency through Targeted Interventions

Purpose We transitioned from a low-dose-rate (LDR) to a high-dose-rate (HDR) prostate brachytherapy program. The objective of this study was to describe our experience developing a prostate HDR program, compare the LDR and HDR dosimetry, and identify the impact of several targeted interventions in the HDR workflow to improve efficiency. Methods and Materials We performed a retrospective cohort study of patients treated with LDR or HDR prostate brachytherapy. We used iodine-125 seeds (145 Gy as monotherapy, and 110 Gy as a boost) and preoperative planning for LDR. For HDR, we used iridium-192 (13.5 Gy × 2 as monotherapy and 15 Gy × 1 as a boost) and computed tomography–based planning. Over the first 18 months, we implemented several targeted interventions into our HDR workflow to improve efficiency. To evaluate the progress of the HDR program, we used linear mixed-effects models to compare LDR and HDR dosimetry and identify changes in the implant procedure and treatment planning durations over time. Results The study cohort consisted of 122 patients (51 who received LDR and 71 HDR). The mean D90 was similar between patients who received LDR and HDR (P = .28). HDR mean V100 and V95 were higher (P < .0001), but mean V200 and V150 were lower (P < .0001). HDR rectum V100 and D1cc were lower (P < .0001). The HDR mean for the implant procedure duration was shorter (54 vs 60 minutes; P = .02). The HDR mean for the treatment planning duration dramatically improved with the implementation of targeted workflow interventions (3.7 hours for the first quartile to 2.0 hours for the final quartile; P < .0001). Conclusions We successfully developed a prostate HDR brachytherapy program at our institution with comparable dosimetry to our historic LDR patients. We identified several targeted interventions that improved the efficiency of treatment planning. Our experience and workflow interventions may help other institutions develop similar HDR programs.

Improving the Accessibility of Patient Care Through Integration of the Hospital and Radiation Oncology Electronic Health Records

PURPOSE Radiation therapy (RT)-specific aspects of a patients cancer care commonly are documented and scheduled through a radiation oncology electronic health record (rEHR). However, patients who receive RT also receive multidisciplinary care from providers who use the hospital EHR (hEHR). We created an electronic interface to integrate our hEHR and rEHR to improve communication of the RT aspects of care between our department and the rest of the hospital. The objective of this study was to assess the impact of rEHR and hEHR integration on the accessibility of the RT-specific aspects of patient care to providers. METHODS AND MATERIALS We performed a preintegration and postintegration survey of 175 staff members at our academic cancer center. Respondents rated the importance and accessibility of several RT encounters and documents on a Likert scale. The Wilcoxon-Mann-Whitney, χ2, and Fishers exact tests were used to compare preintegration and postintegration responses. RESULTS There were 32 and 19 responses to the pre- and postintegration surveys, respectively. rEHR items most commonly reported to be at least moderately important were the dates of first treatment (n = 29 [91%]), last treatment (n = 29 [91%]), brachytherapy (n = 22 [69%]), radiosurgery (n = 22 [69%]), and computed tomography simulation (n = 21 [66%]). A drastic improvement was found in most items made visible in the hEHR through the interface. CONCLUSION By integrating our hEHR and rEHR, we improved the communication of patient care between the RT department and the multidisciplinary team. Institutions should pursue and support integration of the EHRs to improve the quality of care provided to patients with cancer.