Search

The primary aim of this trial was to compare the incidence of grade 2 or above acute gastrointestinal (GI) toxicity for patients undergoing 3DCRT versus IMRT in the preoperative setting for locally-advanced rectal cancer. Secondary objectives included quality of life and other acute and late toxicity. The trial was designed to have 80% power to detect a difference between a hypothesized 37% acute toxicity rate in the 3DCRT arm (Bosset et al, 2006) and 20% in the IMRT arm, with a sample size of 120 per arm, and a 0.05 two-sided level of significance. Eligible participants were adults aged 18 or over scheduled to receive pre-operative pelvic chemo-radiotherapy for histologically-confirmed rectal adenocarcinoma. Exclusion criteria included prior pelvic radiotherapy, inflammatory bowel disease, hip replacements, and previous bowel surgery. Prescription dose was 50.4 Gray in 28 fractions over 5.5 weeks with concurrent 5-fluorouracil or capecitabine chemotherapy. Participants were centrally randomized 1:1 to receive 3DCRT or IMRT. Each individual radiotherapy volume and plan was reviewed centrally to ensure compliance with the trial's RTQA specifications. Toxicity was graded and reported according to CTCAE version 4.0 (National Institutes of Health National Cancer Institute). Acute toxicity was assessed weekly during radiotherapy, and at 2- and 4-weeks post-treatment. 94 patients were enrolled. 77% were male and median age was 59.4. Two participants from the 3DCRT arm did not complete radiotherapy as planned and were excluded from analysis. 25 (56%) of participants from the 3dCRT arm and 23 (49%) from the IMRT arm experienced acute grade 2 or above GI toxicity (p=.670). Rates for grade 3 GI toxicity were 8 (18%) and 5 (11%) for 3dCRT and IMRT, respectively (p=.494). Grade 3 GI events included diarrhea (n=11), nausea (n=2), intestinal obstruction (n=1), oral mucositis (n=1), and rectal pain (n=1). The study closed early due to absence of evidence of a difference between arms at the interim analysis. No significant difference in rates of acute GI toxicity with IMRT versus 3DCRT for locally advanced rectal cancer was seen. Although IMRT can reduce dose to organs at risk, it appears to be similarly safe in terms of acute GI toxicity to deliver this treatment with 3DCRT. [ABSTRACT FROM AUTHOR]

Published data supports the use of very high dose intensity modulated radiotherapy (IMRT) in achieving high efficacy and low toxicity for high-risk prostate cancer (HRPCa). This phase II multi-institutional non-randomized prospective dose escalation study using intensity modulated radiotherapy (IMRT) for high risk N0M0 prostate cancer was designed to investigate dose escalation using 1.8 Gy increments from baseline 75.6 Gy up to maximum 81 Gy, once dose volume constraints were adhered to. Inclusion criteria were patients undergoing a radical course of RT for high and very high-risk disease, defined as one or more of the criteria ≥ T3*, ≥ Gleason 8, Prostate specific antigen (PSA) > 20ng/ml. All patients received Androgen Deprivation Therapy (ADT) and none had radiological evidence of distant metastatic disease. The primary objective was to determine if dose escalated IMRT for high risk localized prostate cancer could provide freedom from biochemical relapse (BR; PSA rising > nadir +2ng/mL or initiation of salvage hormone therapy) similar to that reported in the literature. The Kaplan-Meier method was used to estimate survival times. Secondary objectives included OS, Disease Free Survival (DFS), and the incidence and severity of Genito-urinary (GU), Gastro-intestinal (GI) and erectile dysfunction (ED) toxicities (CTCAE v.3). Toxicities and performance status were collected and graded weekly during RT, 2 months after completing RT, 8 months' post RT, and 6 monthly thereafter to year five and annually thereafter to year nine. A total of 230 evaluable patients were enrolled between April 2009 and June 2016. The median follow-up was 7.3 years. The cumulative proportion of patients surviving without BR at 5 years was 91% (95% Confidence Interval (CI): 86% to 94%). Overall survival at 5 and 7 years was 92% (88% to 95%) and 89% (83% to 92%) respectively, while the cumulative proportion of patients free from disease was 89% (84% to 93%) at 5 years and 81% (75% to 86%) at 7 years. The incidence of acute G2 and G3 toxicities were; GU; 57.8% G2, 12.6% G3, GI; 15.2% G2, 0.4% G3, ED; 30.0% G2 and 61.7% G3. The incidence of late G2, G3 and G4 toxicities were; GU; 40.9% G2, 8.7% G3, GI; 36.5% G2, 2.2% G3, 0.4% G4, ED; 11.7% G2 and 86.1% G3. The percentage of patients receiving each dose level was; 3.5% received 75.6Gy in 42 fractions, 2.2% received 77.4Gy in 43 fractions, 93% received 81Gy in 45 fractions. The findings indicate that high-dose IMRT is well tolerated and is associated with excellent long-term tumor-control outcomes in patients with localized high and very high-risk prostate cancer, with 91% of patients surviving at 5 years without biochemical relapse. The rates of long term G3 GU and GI toxicity were low at 8.7% and 0.4% respectively. [ABSTRACT FROM AUTHOR]

The ability to deliver radical thoracic re-irradiation is limited by the balance between efficacy and potential toxicity. The aim of our study was to evaluate the safety and efficacy of radical thoracic re-irradiation. A single institution retrospective analysis was performed on all patients who received two or more courses of radical thoracic radiotherapy, for sequential malignancies, between January 2011 and October 2019. All radical dose-fractionation schemes were included. The dose was converted to a Biologically Equivalent Dose, to ensure the cumulative dose delivered to the organs at risk (OAR) with re-irradiation did not exceed standard limits. The primary endpoint was the rate of acute (within 6 weeks) and late (within 1 year) toxicity as assessed by CTCAE V4.0. Secondary endpoints included progression free survival and overall survival which were calculated from the date of last radiotherapy using the Kaplan-Meier method. The study was approved by the institutional ethics board and patients provided informed consent. 43 patients had received at least one prior course of radical thoracic radiotherapy. 7/43(16%) and 2/43(5%) had received two and three prior courses respectively. The median follow-up from last completed radiotherapy was 19.8 months (0 - 64 months). The median age was 73 and 23/43(53%) of the cohort were female. Stereotactic Ablative Body Radiotherapy and External Beam Radiotherapy techniques were used in 48/97(49%) and 49/97(51%) of the treatment courses respectively. The primary tumor was non-small cell lung cancer in 78/97(80%), small cell lung cancer in 8/97(8%), head and neck cancer in 6/97(6%) and breast cancer in 5/97(5%). The median time from 1st to 2nd radiotherapy was 19 months. Following last re-irradiation, acute grade 1 and 2 toxicities were observed in 30/43(70%). The acute toxicities were cough 14/43(33%), dyspnea 9/43(21%), esophagitis 11/43(26%), fatigue 24/43(56%), erythema 6/43 (14%) and chest wall pain 2/43(5%). One patient had a fatal event during re-irradiation after an acute upper gastrointestinal hemorrhage but causality could not be established. Another patient had a grade 3 respiratory infection. Cumulative late grade 1 and 2 toxicities were observed in 7/31(23%) of the evaluable cohort including hemoptysis 1/31 (3%), cough 2/31(6%), dyspnea 3/31(10%), chest wall pain 3/31(10%) and fatigue 3/31(10%). There was no other grade 3 or higher acute or late toxicities. At time of analysis 33/43(77%) of patients had died. One-year overall survival and progression free survival were 64% (95%CI: 50-79%) and 49% (95%CI: 33-64%) respectively. Limitations of the study include its retrospective nature and patient heterogeneity. Radical thoracic re-irradiation was generally well tolerated in a typical clinical setting when the cumulative dose delivered to OAR did not exceed standard constraints. [ABSTRACT FROM AUTHOR]

Radiotherapy plays a key role in the of the management of head and neck cancer patients with approximately 80% of patients receiving RT at least once during their cancer journey. Immobilization of patients during radiotherapy treatment, is essential to ensure treatment accuracy, and requires the use of a facemask. However, masks are associated with significant treatment related distress and a phenomenon called "mask anxiety". Many patients have difficulty swallowing and breathing which makes a closed facemask even less tolerable. In order to improve patients' radiotherapy treatment experience, we piloted a "faceless" open mask in our department to investigate whether such masks could be used, to reduce patients' distress without impacting on treatment accuracy, by comparing set up data for full versus open masks. Over an 18-month period, all head and neck cancer patients undergoing radical radiotherapy, with a history of anxiety or claustrophobia, were offered open masks. Once 30 patients had completed radiotherapy treatment with the open mask, we analyzed the set-up data by comparing this consecutive cohort of patients, to patients in standard closed masks treated during the same time period. Our standard institutional IGRT protocol includes daily CBCT for first 3 fractions, followed by weekly CBCT. The one-dimensional standard deviations (SD) of the systematic and random set-up errors were calculated for all three orthogonal directions (x, y, z). Mann-Whitney U and independent t-test were used to determine any significant differences between rotational set up data for open and closed masks. Sixty patients were included. Thirty patients had closed masks and thirty had open masks. The SD of the systematic error (reproducibility of treatment position) in mm was slightly less for closed mask than for the open mask in all directions (vertical 0.079 vs 0.106, lateral 0.068 vs 0.101, longitudinal 0.054 vs 0.080). The SD of the random error was less for closed than for open mask in vertical, 0.219 vs 0.225, and lateral,0.144 vs 0.174, directions. It was slightly more in the longitudinal direction (0.176 compared to 0.171). The margin requirements for the faceless mask were greater than the full mask. Margins for set-up uncertainty were 3.5, 3, and 3mm (Ant Post, Sup Inf and Right Left, respectively) for closed mask, and 4, 3, and 4mm respectively for open mask. There was no significant difference in pitch, roll and yaw between open and closed masks. In this study, we have shown that open masks are able to maintain accuracy at levels comparable to closed masks and may be offered to patients suffering mask anxiety. However, a slightly larger PTV margin may be required. For open masks to become the standard of care for all head and neck patients, a larger randomized study should be performed. Customized head rests and real time intrafraction monitoring using 3-dimensional surface imaging could also be an advantage for this cohort of patients. [ABSTRACT FROM AUTHOR]

The aim of the study was to compare the use of 3D-CRT and IMRT in pre-operative long course chemo-radiotherapy for locally advanced rectal cancer. We herein evaluate the impact of the two treatment modalities on quality of life (QOL), a secondary objective of the study. 94 patients with rectal adenocarcinoma were enrolled in a prospective randomized phase II trial across three institutions between 2014 and 2020. Eligible patients had stage T3-4, N(any) or circumferential resection margin at risk with no evidence of metastatic disease. All patients were prescribed 50.4Gy in 28 fractions with concomitant 5-fluorouracil or capecitabine. Patients were randomly assigned (1:1) to 3D-CRT and IMRT planning techniques. QOL was assessed using the EORTC QLQ C30 and QLQ CR29 questionnaires at baseline, during the final week of radiotherapy and at six and twelve months after radiotherapy. A paired sample t test was used to compare differences in QOL from baseline to each follow-up. One-way between-group analyses of covariance (ANCOVA) were conducted to compare the effect of the trial arms on each QOL score. At a median follow-up of 14 months, the trial was terminated early due to failure to establish efficacy in the primary outcome, acute gastrointestinal toxicity. The median age was 59 years and 72/94 (77%) were male. 86/94 (91%) patients completed the baseline and at least one other QOL assessments. QOL data at one year was available in 55/94(58%). At baseline, there was no difference in QOL scores between trial arms. Overall, emotional functioning had improved at six months but physical, cognitive, role and social functioning had declined. At six months, there was a significant improvement in constipation, blood and mucous in stool, bloating, urinary frequency, buttock pain and anxiety scores compared to baseline. There was a significant deterioration in dyspnea, fatigue, nausea/vomiting, taste, hair loss, erectile dysfunction, body image and global health scores from baseline to 6-month follow-up. After adjusting for pre-intervention score, the IMRT arm had better physical functioning (p=0.038) and role functioning (p=0.014) during the final week of radiotherapy compared to the 3DCRT arm. The end of radiotherapy embarrassment score, for those without a stoma, was significantly worse in the IMRT arm (p=0.032). There was no other significant difference in QOL scores between the two arms, at either the final week of radiotherapy or at 6 months, after adjustment for pre-intervention scores. The limitations of the study include its early termination, the potential for type 1 error and the possible influence of other factors on QOL data such as chemotherapy and postoperative complications. There are limited QOL benefits of IMRT compared to 3D-CRT in the neoadjuvant setting for rectal cancer. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Radiotherapy (RT) dose escalation for localized prostate cancer has not demonstrated improvement in overall survival (OS) from individual trials. It is unclear if the use of androgen deprivation therapy (ADT) effects the potential benefit of dose escalation. Therefore, to achieve sufficient power to answer this question, we performed a meta-analysis of randomized trials evaluating the benefit of RT dose escalation in localized prostate cancer.Materials/methods: The Meta-Analysis of Randomized clinical trials in Cancer of the Prostate (MARCAP) Consortium was formed to obtain IPD from multiple randomized controlled trials. Patients were categorized based on RT dose and use and duration of ADT. Short-term ADT (STADT) was defined as ≤6 months, long-term ADT (LTADT) as 18-36 months, and low and high dose RT as < or ≥74 Gy EQD2. IPD from 15 trials (n = 13,864 patients) were used. The primary endpoint of all analyses was OS, with metastasis-free survival (MFS) and the incidence of biochemical recurrence (BCR) as secondary endpoints. Sensitivity analyses using only trials with direct and relevant randomization (10 trials; n = 9,775 patients) were used to perform a network meta-analysis (NMA).Results: The median follow-up was 8.5 years (IQR 5.6-11.2). Escalating dose in the absence of ADT did not improve OS (HR 0.92, 95% CI 0.79-1.08) or MFS (HR 0.91, 95% CI 0.78-1.07). In the presence of STADT, high dose RT significantly improved OS (HR 0.79, 95% CI 0.67-0.94) and MFS (HR 0.80, 95% CI 0.68-0.94), as well as in the presence of LTADT for OS (HR 0.64, 95% CI 0.50-0.82) and MFS (HR 0.71, 95% CI 0.57-0.89). On sensitivity analysis using the NMA, dose escalation did not significantly improve outcomes in the absence of ADT (OS: HR 1.00, 95% CI 0.75-1.34; MFS: HR 0.97, 95% CI 0.67-1.41) or in the presence of STADT (OS: HR 0.95, 95% CI 0.54-1.67; MFS: HR 0.89, 95% CI 0.46-1.70) or LTADT (OS: HR 0.75, 95% CI 0.38-1.47; MFS: HR 0.78, 95% CI 0.36-1.67). In both the pooled comparison and the NMA, dose escalation improved BCR without ADT (NMA HR 0.53, 95% CI 0.32-0.88) in the presence of STADT (NMA HR 0.37, 95% CI 0.16-0.84), but not in the presence of LTADT (NMA HR 0.46, 95% CI 0.18-1.21).Conclusion: Dose-escalation alone does not improve MFS or OS. In the presence of STADT or LTADT, the impact of dose-escalation differed when pooling non-randomized comparisons (which is prone to selection bias) versus performing an NMA restricted to only direct randomized comparisons (which is affected by limited network connectivity). BCR was more consistently improved. Given the uncertain impact on survival and the potential for increased toxicity, future studies using biomarker selection are needed to better personalize which patients benefit most from dose escalation. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): To conduct the first global individual patient data (IPD) meta-analysis of randomized trials to assess the impact of androgen deprivation therapy (ADT) use and duration with definitive radiotherapy (RT) in localized prostate cancer.Materials/methods: The MARCAP Consortium was formed from international trial groups (NRG/RTOG, EORTC, TROG, DART/GICOR, and ICORG). IPD for 10,131 patients enrolled across 11 RT trials were available for three pre-specified meta-analyses: addition of ADT to RT (5 trials; n = 4736), addition of long-term adjuvant ADT (12-30 months) to short-term ADT (4 trials; n = 3674), and addition of longer neoadjuvant ADT (3-7 months) to short-term ADT (3 trials; n = 2213). The primary endpoint of all meta-analyses was overall survival (OS), with metastasis-free survival (MFS) as a secondary endpoint. Interaction tests between treatment and receipt of dose-escalated RT (≥74 Gy in 2 Gy fractions) were performed.Results: After a median follow-up of 12.0 years, the addition of ADT to RT improved 12-year OS (absolute 7.2%, HR 0.87, 95% CI 0.8-0.95) and 12-year MFS (absolute 8.3%, HR 0.85, 95% CI 0.79-0.92). After a median follow-up of 10.9 years, prolongation of adjuvant ADT improved 12-year OS (absolute 6.3%, HR 0.86, 95% CI 0.78-0.94) and 12-year MFS (absolute 6.3%, HR 0.83, 95% CI 0.77-0.90). After a median follow-up of 10.3 years, prolongation of neoadjuvant ADT was not associated with a significant benefit in any endpoint (MFS HR 0.95, 95% CI 0.83-1.09; OS HR 0.94, 95% CI 0.82-1.09). On subgroup analysis, there was no evidence of a treatment effect interaction between RT dose and ADT use (OS P-interaction 0.59) or adjuvant ADT prolongation (OS P-interaction 0.13). In the setting of dose-escalated RT, adjuvant ADT prolongation significantly improved OS (HR 0.70, 95% CI 0.53-0.92).Conclusion: This study represents the strongest evidence to support ADT use and prolongation of adjuvant ADT to at least 18 months in localized prostate cancer in conjunction with definitive RT. The relative benefit of ADT use and adjuvant ADT prolongation was consistent irrespective of RT dose-escalation. In contrast, prolongation of neoadjuvant ADT beyond 2 months did not improve survival outcomes and should not routinely be employed. [ABSTRACT FROM AUTHOR]