Short-course Palliative Hypofractionated Radiotherapy in Patients with Poor-prognosis High-grade Glioma: Survival and Quality of Life Outcomes from a Prospective Phase II Study.

AIMS: To report longitudinal quality of life (QoL) outcomes and survival in patients with poor-prognosis high-grade glioma (HGG) treated with palliative hypofractionated radiotherapy. MATERIALS AND METHODS: Patients with poor-prognosis HGG were accrued on a prospective study of short-course palliative hypofractionated radiotherapy (35 Gy/10 fractions/2 weeks). The European Organization for Research and Treatment of Cancer QoL core questionnaire (QLQ-C30) and brain cancer module (BN20) were used in English or validated Indian vernacular languages (Hindi and Marathi) for QoL assessment at baseline (before radiotherapy), the conclusion of radiotherapy, 1 month post-radiotherapy and subsequently at 3-monthly intervals until disease progression/death. Baseline QoL scores were compared with corresponding scores from a historical HGG cohort. Summary QoL scores were compared longitudinally over time by related samples Friedman's two-way test. Progression-free survival and overall survival were calculated using the Kaplan-Meier method and reported as 1-year estimates with 95% confidence intervals. RESULTS: Forty-nine (89%) of 55 patients completed the planned course of hypofractionated radiotherapy. Longitudinal QoL data were available in 42 (86%) of 49 patients completing radiotherapy, comprising the present cohort. The median age of included patients, comprised mainly of glioblastoma patients (81%), was 57 years, with an interquartile range (IQR) of 50-66 years and a median baseline Karnofsky score of 60 (IQR = 50-60). Baseline QoL scores were significantly worse for several domains compared with a historical institutional cohort of HGG patients treated previously with conventionally fractionated radiotherapy, indicating negative selection bias. QoL scores remained stable for most domains after palliative hypofractionated radiotherapy, with statistically significant improvements in fatigue (P = 0.032), dyspnoea (P = 0.042) and motor dysfunction (P = 0.036) over time. At a median follow-up of 8 months, Kaplan-Meier estimates of 1-year progression-free survival and overall survival were 33.3% (95% confidence interval 21.7-51.1%) and 38.1% (95% confidence interval 25.9-56%), respectively. CONCLUSION: Short-course palliative hypofractionated radiotherapy in patients with poor-prognosis HGG is associated with stable and/or improved QoL scores in several domains, making it a viable resource-sparing regimen.

Post-cricoid and Upper Oesophagus Cancers Treated with Organ Preservation Using Intensity-modulated Image-guided Radiotherapy: a Phase II Prospective Study of Outcomes, Toxicity and Quality of Life.

AIMS: To prospectively examine the outcomes, toxicity and quality of life (QoL) of patients with post-cricoid and upper oesophagus (PCUE) cancers treated with an organ-preservation approach of (chemo)-radiotherapy using intensity-modulated image-guided radiotherapy (IM-IGRT). MATERIALS AND METHODS: This phase II prospective study was conducted at a tertiary cancer centre from February 2017 to January 2020. Forty patients with squamous cell carcinoma of PCUE of stage T1-3, N0-2, M0 were accrued. Gross exolaryngeal extension/dysfunctional larynx were major exclusion criteria. Patients received 63-66 Gy in once-daily fractions using volumetric modulated arc therapy with daily IGRT. Outcome measures included disease-related outcomes, patterns of failure, Radiation Therapy Oncology Group toxicities, feeding tube dependency and QoL. RESULTS: The median follow-up was 22 months. Twenty-six (87.5%) patients had locoregionally advanced disease and 34 (85%) patients received (chemo)-radiotherapy. A complete response was observed in 26 (65%) patients. The 2-year locoregional control, event-free survival and cause-specific survival were 59.6%, 40.2% and 44.8%, respectively. The volume of primary tumour (GTVPvol) exceeding 28 cm3 had inferior overall survival (P = 0.005) on univariate analysis. Multivariable analysis showed GTVPvol and positron emission tomography-computed tomography maximum standardised uptake value to be independently predictive for event-free and overall survival. A feeding tube requirement at presentation was seen in 11 (27.5%) patients, whereas long-term feeding tube dependency at 6 months was seen in 10 (37%) patients. For QoL, a statistical improvement in pain, appetite loss and swallowing was observed over time. CONCLUSION: Although the outcomes of PCUE cancers remain dismal, the use of state of the art diagnostic modalities, careful case selection and modern radiotherapy techniques improved outcomes as compared with before in this exclusive analysis of PCUE cancers.

Prospective Longitudinal Assessment of Quality of Life and Activities of Daily Living as Patient-Reported Outcome Measures in Recurrent/Progressive Glioma Treated with High-dose Salvage Re-irradiation.

AIMS: To evaluate quality of life (QOL) and activities of daily living (ADL) longitudinally in patients treated with salvage re-irradiation for recurrent/progressive glioma. Secondary end points included post-re-irradiation survival. MATERIALS AND METHODS: Patients with diffuse glioma, aged 18-70 years with preserved performance status and unequivocal evidence of recurrence/progression with a minimum 2-year time interval from index radiation therapy were eligible. QOL was assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) and brain cancer module (BN20). ADL was assessed using a modified Barthel's index. Assessments were carried out longitudinally, first before re-irradiation, at completion of re-irradiation and subsequently periodically on follow-up. Summary scores were calculated from raw scores as per the EORTC scoring manual; higher functional scores and lower symptom scores indicating better QOL. Summary mean scores for the modified Barthel's index were also calculated, with lower scores indicating higher disability. Differences between the summary scores at different time points were tested using the Friedman test. RESULTS: In total, 225 assessments were carried out in 60 patients accrued on the study. A significant improvement in scores was noted for physical function (P < 0.001), emotional function (P = 0.002), cognitive function (P = 0.009) and social functioning (P = 0.047) over time. Role function scores (P = 0.182) and global health status scores (P = 0.074) remained stable. Among symptom scores, fatigue showed a statistically significant improvement over time (P = 0.01), whereas other symptom scores remained largely stable. There was a significant increase in the modified Barthel's index score over time (P = 0.001), suggesting greater functional independence. At a median follow-up of 12.9 months, the 1-year Kaplan-Meier estimates with 95% confidence intervals of post-re-irradiation progression-free survival and overall survival were 45.1% (31.5-58.7%) and 62.2% (49.2-75.2%), respectively. CONCLUSIONS: High-dose salvage re-irradiation in carefully selected patients with recurrent/progressive glioma is associated with stable QOL (preserved functional domains and reduced symptom burden) and improvement in ADL (greater functional independence) over time with encouraging survival outcomes.

Safety and Efficacy of Ultra-hypofractionation in Node-positive Prostate Cancer.

AIMS: The safety and efficacy of stereotactic body radiotherapy (SBRT) in localised prostate cancer are now established through phase III randomised trials. Its utility in node-positive prostate cancer is restricted due to a lack of controlled studies specifically addressing this subgroup. Herein we report the safety and efficacy of SBRT in this subgroup. MATERIALS AND METHODS: In total, 60 patients treated with SBRT to prostate and pelvis were analysed. All patients received neoadjuvant androgen deprivation therapy for at least 6 months and long-term adjuvant hormonal therapy (70% medical and 30% surgical). All patients were treated with daily image-guided rotational intensity-modulated radiotherapy. The dose delivered to the prostate and gross node was 35-37.5 Gy and 25 Gy in five fractions to the elective pelvic nodal region on alternate days. Acute and late toxicities were graded as per Radiation Therapy Oncology Group common toxicity criteria. RESULTS: Forty-one (68%) patients had a Gleason score ≥8. The median prostate-specific antigen level at diagnosis was 39 ng/ml. Twenty (33%) patients had common iliac nodal uptake on initial prostate-specific membrane antigen positron emission tomography-computed tomography. After the median follow-up of 30 months, no acute or late Radiation Therapy Oncology Group grade ≥3 gastrointestinal toxicity was noted. Acute grade 2 genitourinary and gastrointestinal toxicities were 8.3% and 11.7%, respectively. Late grade 2 genitourinary and gastrointestinal toxicities were 3.3% and 8.3%, respectively. Late grade 3 genitourinary toxicity was seen in two (3.3%) patients. Three-year overall survival and biochemical failure-free survival was 89% and 77%, respectively. CONCLUSION: SBRT to the prostate and pelvis is safe and efficacious in node-positive prostate cancer even with common iliac nodal involvement (stage M1a).