Late Urinary Toxicity and Quality of Life With Pelvic Radiation Therapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase 3 Trial.

PURPOSE: The POP-RT phase 3 randomized trial showed improved biochemical failure-free survival and metastasis-free survival with whole pelvic radiation therapy versus prostate-only radiation therapy for high and very high-risk prostate cancer, albeit with worse RTOG late urinary toxicity. We report updated late urinary adverse effects and bladder dose-effect relations within this trial. METHODS AND MATERIALS: Late urinary toxicity and the cumulative severity of each symptom during the follow-up period were graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Bladder dosimetry in 5-Gy increments (V5, V10, V15, V65, V68Gy) in the approved radiation therapy plans was compared with urinary symptoms and overall grade 2+ toxicity. Potential factors influencing urinary toxicity were tested using multivariable logistic regression analysis. Updated urinary quality of life (QOL) scores were compared between the trial arms. RESULTS: Complete combined data for late urinary symptoms and dosimetry was available for 193 of 224 patients. At a median follow-up of 75 months, cumulative late urinary CTCAE grade 3 toxicity was low and similar for whole pelvic radiation therapy and prostate-only radiation therapy (5.2% vs 4.1%, P = .49), and grade 2 toxicity was 31.3% versus 22.7%, respectively (P = .12). Cumulative rates of each urinary symptom were similar between both arms. Multivariable analysis with age at diagnosis, known diabetes, tumor stage, trial arm, prior transurethral resection of prostate, grade 2+ acute urinary toxicity, low bladder dose (V10Gy), and moderate bladder dose (V40Gy) did not identify any significant association with late urinary toxicity. Urinary QOL scores was similar between both the arms for all the symptoms. CONCLUSIONS: During long-term follow-up, whole pelvic radiation therapy resulted in low (∼5%) and similar grade 3 cumulative urinary toxicity as prostate-only radiation therapy. The long-term patient-reported QOL scores were similar. No causative factors affecting the late urinary toxicity were identified.

Development and Validation of Single-Optimization Knowledge-Based Volumetric Modulated Arc Therapy Model Plan in Nasopharyngeal Carcinomas.

Purpose: Knowledge-based planning (KBP) has evolved to standardize and expedite the complex process of radiation therapy planning for nasopharyngeal cancer (NPC). Herein, we aim to develop and validate the suitability of a single-optimization KBP for NPC. Methods and Materials: Volumetric modulated arc therapy plans of 103 patients with NPC treated between 2016 and 2020 were reviewed and used to generate a KBP model. A validation set of 15 patients was employed to compare the quality of single optimization KBP and clinical plans using the paired t test and the Wilcoxon signed rank test. The time required for either planning was also analyzed. Results: Most patients (86.7%) were of locally advanced stage (III/IV). The median dose received by 95% of the high-risk planning target volume was significantly higher for the KBP (97.1% vs 96.4%; P = .017). The median homogeneity (0.09 vs 0.1) and conformity (0.98 vs 0.97) indices for high-risk planning target volume and sparing of the normal tissues like optic structures, spinal cord, and uninvolved dysphagia and aspiration-related structures were better with the KBP (P < .05). In the blinded evaluation, the physician preferred the KBP plan in 13 out of 15 patients. The median time required to generate the KBP and manual plans was 53 and 77 minutes, respectively. Conclusions: KBP with a single optimization is an efficient and time saving alternative for manual planning in NPC.

Triple combination of palliative oral metronomic chemotherapy in recurrent and metastatic epithelial ovarian cancer: A retrospective study.

Background: Ovarian cancer is a leading cause of death from gynecological cancer in the world and in India. This study aims to evaluate the efficacy and toxicity profile of oral metronomic chemotherapy (MCT) in the form of etoposide, cyclophosphamide, and tamoxifen in recurrent and metastatic ovarian cancer. Methods: This was a retrospective observational study that included those post-treatment patients who had the recurrent or metastatic disease after completion of treatment in 2018 at Regional Cancer Centre, Bikaner, Rajasthan. Forty patients who were unfit for further intensive intravenous chemotherapy were included. The oral MCT constituted etoposide, cyclophosphamide, and tamoxifen. Descriptive statistics and Kaplan-Meier analyses were performed. Progression-free survival (PFS) and overall survival (OS) were assessed. Results: Forty women with a median age of 62 (range: 35-80) years were enrolled in the study to receive oral MCT. The Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) was 0-1 in 28 patients and 2-3 in 12 patients. The best clinical response rate post-oral MCT was seen in the first 4 months. Objective response was observed in 24 (60%) of patients in the form of stable disease (19, 47.5%) and partial response (5, 12.5%). Disease progression was observed in 10 (25%) of patients. The median follow-up was 6.4 months (4.5-9.2 months). The median estimated OS was 6.5 months. The median estimated PFS was 3.7 months. Nineteen (47.5%) patients had grade-I/II mucositis. Grade-III/IV mucositis were observed in 9 (22.5%) patients. Thirty-seven (92.5%) patients died at the end of the study at 1 year. Dose reduction was required in 15 (37.5%) patients. Conclusion: Oral MCT was found to be an effective and well-tolerated regime with good symptomatic control and low-moderate toxicity profile in patients with relapsed and metastatic ovarian cancer. However, 22% of patients showed grade-III/IV thrombocytopenia.

Image-guidance triggered adaptive radiation therapy in head and neck squamous cell carcinoma: single-institution experience and implications for clinical practice.

PURPOSE: To report frequency and timing of adaptive radiotherapy (ART) and assess patient, disease, and treatment-related characteristics potentially triggering the need for such adaptive replanning in head and neck squamous cell carcinoma (HNSCC). METHODS: Medical records of HNSCC patients treated with definitive intensity modulated radiation therapy (IMRT) with or without concurrent systemic chemotherapy were reviewed retrospectively to identify patients undergoing image-guidance triggered adaptive replanning. Clinico-demographic characteristics of patients undergoing ART were compared with patients treated without adaptation using the chi-square test. RESULTS: Two hundred patients with squamous cell cancers of the oropharynx, larynx, or hypopharynx treated with definitive IMRT between 2014 to 2019 comprised the study cohort. Twenty-seven (13.5%) patients underwent adaptive replanning during treatment at a median of 17 fractions (inter-quartile range 14-24 fractions). There were no significant differences in the baseline patient (age, gender), disease (site of primary, staging/grouping), and treatment-related characteristics (dose-fractionation, chemotherapy usage) in patients undergoing ART compared to those treated without adaptation. Weight loss during IMRT emerged as a significant factor predicting the need for ART; patients having ≥10% weight loss from baseline were more likely to undergo treatment adaptation compared to patients with <10% weight loss (p = 0.0002). There was variable impact of ART on dose-volume statistics of organs-at-risk such parotid glands and spinal cord. CONCLUSION: Image-guidance triggered ART for HNSCC is not associated with significant improvement in OAR dosimetry. However, weight loss during definitive IMRT can be a potentially useful trigger for identifying patients who are most likely to benefit from such adaptive replanning.

Comparison of two schedules of hypo-fractionated radiotherapy in locally advanced head-and-neck cancers.

Aim: In India, more than 70% patients present as locally advanced head-and-neck cancers (LAHNC), with poor performance status and are suitable candidates for palliative radiotherapy (RT) aimed at symptom relief. This prospective study aims to compare two different short course hypo-fractionated RT regimens in patients of LAHNC at a regional cancer centre of north-west India. Materials and Methods: A total of 70 patients of LAHNC were randomized to receive palliative RT in two groups of 35 each. Group A received 30 Gy/10# over 2 weeks and Group B received 20 Gy/5# over 1 week. Baseline symptoms of pain, dysphagia, insomnia, dysphonia, bleeding, fungation, and dyspnea were assessed before the start of study. The first assessment for toxicities, subjective and objective response was done at the conclusion of RT and then after 4-6 weeks. Results: Out of total 70 patients, 71% were males and 29% were females with a median age of 54 years. The most common sites were oropharynx (39%) followed by larynx (24%), oral cavity (20%), and hypopharynx (17%). Nearly 60% of the patients in both groups presented in stage IV and 40% in stage III. At conclusion of RT and at 4-6 weeks follow-up, both groups showed similar results in terms of symptom palliation, objective response, and acute toxicities. Group B showed higher incidence of Grade III and above mucositis (P = 0.027). Median overall survival was found to be 5.9 months (range 1-15 months) in group A and 6.1 months (range 1-18 months) in Group B. Conclusion: Hypo-fractionated RT promises to effectively relieve symptoms in LAHNC and reduces the need of analgesics and hospital visits. Furthermore, a shorter overall treatment time is beneficial at high volume centers and is also welcomed by patients with shorter life expectancy.

Retinoblastoma: A review of clinical profile at a regional cancer center in Northwest India.

Background: Retinoblastoma is the most common primary intraocular malignancy of childhood. The present study was undertaken to overcome the scarcity of data regarding the epidemiology, demographic and clinical profile, and nature of the first health-care professional consulted. Materials and Methods: A retrospective analysis of medical records was performed for all cases of retinoblastoma who presented to the department of ophthalmology and oncology between 2010 and 2017. A total of 54 cases were reviewed. Results: Unilateral disease was seen in 85.2% while 14.8% presented with bilateral disease with a median age of 3 years and 2 years, respectively, at diagnosis. The male: female ratio was 2:1. The most common presenting symptom was leukocoria which was noticed in 42 patients (77.7%), followed by red eye (33.3%) and proptosis (20.3%). The most common stage of presentation was Stage I (44.4%), followed by Stage IV (20.4%), Stage III (9.3%), and Stage II (5.6%). The median time to diagnosis was 8.7 months (range, 0.5-98.7 months), and the median time to treatment was 37.4 days (range, 0-645 days). Majority of the patients were referred by local ophthalmologists (48%), followed by general practitioners (20%), nurses (19%), and quacks (13%). Enucleation was the most preferred treatment modality (48.1%), followed by chemotherapy (33.3%), radiotherapy (13%), photocoagulation (3.7%), and exenteration (1.9%). The overall remission rate was 79.6%, while 12.3% had relapse and 7.4% died. Conclusion: The study showed a dire need for timely detection and treatment of retinoblastoma which is possible with improved awareness and better accessibility to health-care facilities. It also revealed a decrease in histopathological risk factors with chemoreduction.

Systematic review and meta-analysis of randomized controlled trials comparing elective neck dissection versus sentinel lymph node biopsy in early-stage clinically node-negative oral and/or oropharyngeal squamous cell carcinoma: Evidence-base for practice and implications for research.

PURPOSE: Management of clinically node-negative (N0) neck in early-stage (T1-T2) oral and/or oropharyngeal squamous cell carcinoma (OOSCC) has been controversial. The purpose of this systematic review and meta-analysis was to compare sentinel lymph node biopsy (SLNB) with elective neck dissection (END) in early-stage OOSCC. METHODS: Studies comparing SLNB versus END in early-stage clinically node-negative OOSCC were identified using validated search strategy. To be considered eligible, trials had to include patients with early-stage, clinically node-negative OOSCC who had been randomly assigned to either SLNB or END. Primary outcome of interest was overall survival (OS), while secondary outcomes included isolated neck nodal recurrence (NNR), loco-regional recurrence (LRR), and neck-shoulder function. Outcome data was pooled using random-effects model and reported as hazard ratio (HR) or risk ratio (RR) with 95% confidence interval (CI). Any p-value < 0.05 was considered statistically significant. RESULTS: A total of 608 patients from three trials comparing SLNB versus END in early-stage clinically node-negative OOSCC were included. The pooled HR of death for SLNB versus END was 1.18 (95% CI: 0.79-1.78, p = 0.41) which was not statistically significant. The rates of isolated NNR (pooled RR = 1.11, 95% CI: 0.69-1.80, p = 0.66) and LRR (pooled RR = 1.18, 95% CI: 0.81-1.72, p = 0.39) were also similar. Pooled analysis of the neck-shoulder function significantly favoured SLNB arm (pooled RR = 1.21, 95% CI: 1.12-1.32, p < 0.00001). CONCLUSION: There is low-certainty evidence that SLNB is oncologically non-inferior to END and is associated with potentially lesser functional morbidity making it an emerging alternative standard of care in patients with early-stage clinically node-negative OOSCC.

Clinical and dosimetric impact of adaptive intensity-modulated radiotherapy in locally advanced head-and-neck cancer.

BACKGROUND: Radiotherapy in head-and-neck cancer (HNC) is a challenging task, and the anatomical alterations occurring during the course of intensity-modulated radiotherapy (IMRT) can be compensated by adaptive radiotherapy (ART) which utilizes repeat computed tomography (CT) scans during the treatment course for replanning. In this study, the clinical and dosimetric benefits of ART were compared with the conventional IMRT. MATERIALS AND METHODS: Sixty patients with locally advanced HNC were randomized into two arms to receive IMRT up to a curative dose of 70 Gy with concurrent weekly chemotherapy and were prospectively analyzed between March 2018 and March 2019. Repeat CT scan was acquired after the 3rd week of radiation. Patients in the study arm underwent replanning, whereas those in the control arm continued with the first IMRT plan. Assessment was done weekly till the end of treatment and at 1, 3, and 6 months post IMRT for disease response and toxicities. Tumor volume reduction rate (TVRR) and dose reduction to organs at risk were also recorded. RESULTS: Complete response was observed in 90% and 96.7% patients in the control and study arms, respectively, at the end of 6 months. Insignificant differences were found between the two arms in terms of toxicities. Xerostomia was statistically significantly higher in the control arm at 6 months (P = 0.01). TVRR was found to be 31.85%. Dose to spinal cord, ipsilateral, and contralateral parotid reduced by 4.3%, 6%, and 2.2%, respectively, with ART. CONCLUSION: Mid-treatment adaptive replanning can help in better target coverage and minimize toxicities in HNC patients.