Abstract Purpose/Objective Definitive radiotherapy (RT) is an alternative to radical cystectomy for select patients with muscle invasive bladder cancer (MIBC); however, there is limited data on dose-painted RT approaches. We report the clinical and dosimetric outcomes of a cohort of MIBC patients treated with dose-painted RT. Material/Methods This was a single institution retrospective study of cT2-4N0M0 MIBC patients treated with external beam radiotherapy (EBRT) to the bladder, and sequential or concomitant boost to the tumor bed. The target delineation was guided by either intravesical injection of Lipiodol or through fusion of the pre-treatment imaging. The majority were treated with daily image-guidance. Kaplan-Meier was used to characterize overall survival (OS) and progression-free survival (PFS). Cumulative incidence function (CIF) was used to estimate local (intravesical) recurrence (LR), regional recurrence (RR) and distant metastasis (DM). Univariable and multivariable cause-specific hazard model was used to assess factors associated with LR and OS. Results 117 patients were analyzed. The median age was 73 years (range 43, 95). The median EQD2 to the boost volume was 66 Gy (range 52.1, 70). Lipiodol injection was used in 64 patients (55%), all treated with IMRT/VMAT. 95 (81%) received concurrent chemotherapy, of whom, 44 (38%) received neoadjuvant chemotherapy. The median follow-up was 37 months (IQR 16.2, 83.3). At 5-year, OS and PFS were 79% (95% CI 70.5–89.2) and 46% (95% CI 36.5–57.5). Forty-five patients had bladder relapse, of which 30 patients (67%) were at site of the tumor bed. Nine patients underwent salvage-cystectomy. Late high-grade (G3-G4) genitourinary and gastrointestinal toxicity were 3% and 1%. Conclusion Partial boost RT in MIBC is associated with good local disease control and high rates of cystectomy free survival. We observed a pattern of predominantly LR in the tumor bed, supporting the use of a dose-painted approach/de-escalation strategy to the uninvolved bladder. Prospective trials are required to compare oncological and toxicity outcomes between dose-painted and homogeneous bladder RT techniques.

Background: Urine cytology and cystoscopy are routinely employed during follow-up of patients after trimodal therapy (TMT) for muscle-invasive bladder cancer (MIBC). The significance of positive or equivocal cytology without visible disease recurrence on cystoscopy during follow-up is unknown, and studies informing outcomes in this scenario are lacking. This study aims to investigate the temporal trends of positive/equivocal cytology in the absence of visible disease recurrence and the association with bladder cancer recurrence and survival outcomes. Methods: One hundred and twenty-nine patients with available post-TMT cytology data and negative cystoscopy from a single academic institution between 2002 and 2017 with a median follow-up of 3.4 (range 0.1-14.2) years were analyzed. Cytology results, first post-TMT cytology positive/equivocal (CP) and negative (CN), were evaluated for association with disease recurrence and survival. Kaplan. Meier and competing risks methods were used to assess time-to-negative cytology in CP patients with >= 2 interval post-TMT cytology results (n = 33), time-to-recurrence, and disease-specific mortality (DSM) stratified by first post-TMT cytology result. Results: At first follow-up (6-8 weeks post-TMT completion), CP was observed in 41 (32%) and CN in 88 (68%) of patients. With further follow-up of CP patients with >= 2 interval post-TMT cytology results, the probability of developing negative cytology was 57% (95% CI 42, 77) at 6 months post-TMT, and the median time-to-negative cytology was 3.2 months (95% CI 2.99, 5.80). The median time-to-recurrence was reduced in CP patients compared to CN (24.3 vs. 78.1 months, p = 0.1), corresponding with an apparent increase in the cumulative incidence of recurrence rate at 3 years in the CP vs. CN group (62% vs. 42%, p = 0.1). No significant difference was observed in the 3-year DSM rates. On univariable analysis, the hazards of recurrence and DSM for patients with CP were 1.5 (95% CI 0.9, 2.5, p = 0.1) and 2.1 (95% CI 0.9, 4.7, p = 0.07) respectively. Conclusion: This is the first study to investigate the significance of a positive/equivocal cytology without visible disease following TMT for MIBC. Positive cytology is common and does not preclude subsequent negative cytology supporting a watchful waiting approach rather than proceeding immediately to biopsy. However, cytology that remains positive at subsequent follow-up may be associated with adverse recurrence and survival outcomes. (C) 2022 Elsevier Inc. All rights reserved.

Patients with metastatic NSCLC have significant disease and treatment-related morbidity. In Ontario, Canada, cancer patients complete Edmonton Symptom Assessment System (ESAS) questionnaires, a tool that elicits patients' self-reported severity of common cancer-associated symptoms at clinical encounters. ESAS domains are: anxiety, depression, drowsiness, appetite, nausea, pain, shortness of breath, tiredness and well-being. The purpose of this study is to examine moderate-to-severe symptom burden in the 12 months following a diagnosis of stage IV NSCLC.

Immune checkpoint inhibitors (ICIs) are now widely used as standard of care treatments for metastatic non-small cell lung cancer (m-NSCLC) alongside palliative radiotherapy (RT). Commonly used ICIs have long half-lives, typically between 3-4 weeks, and with reported effect even months after discontinuation. The safety of RT based on timing and biologically effective dose (BED) with respect to ICIs is not yet elucidated. This study hypothesized that RT use within 3 months interval prior and after ICI does not increase grade ≥2 toxicities from either ICIs or RT. This retrospective analysis includes m-NSCLC patients treated with both RT and ICIs at the Sunnybrook Odette Cancer Centre, Toronto from June 2014 to January 2019. Patients were identified by both our chemotherapy computerized physician order entry system, OPIS and radiation database. ICIs and RT-related toxicities after first ICIs dose were graded as per CTCAE v4.0. Based on timing and location, toxicities attributed to either ICIs or RT by clinicians. Forty-four m-NSCLC patients treated with ICIs (nivolumab, pembrolizumab, or atezolizumab) and RT were identified. Twenty one (47.7%) were females, median age 67.5 (33.4- 83.2) years, 36 (81.8%) Caucasian, 42 (95.5%) non-squamous histology, 34 (77.3%) previous or current smokers, PD-L1 1-49% in 7 (15.9%) patients and ≥50% in 15 (34.1%), 9 (20.5%) EGFR/ALK positive, 40 (90.9%) ECOG 0-1. Median follow-up was 10.6 (0.7- 54.6) months. Twenty-five patients (group 1) received RT within 3 months prior and after ICIs (60 courses total, 32 (53.3%) extracranial), with median biologically effective dose with α/β= 10 (BED10) 59.5 (14.4-72.0) Gy10, while 19 had no RT in that interval (group 2). Overall, group 1 had 142 RTs (82 outside interval), with median BED10 52.7 (14.4-120) Gy10, while group 2 had 51 RTs, with median BED10 52.8 (10.1-105.6) Gy10. Grade ≥2 toxicities (8 total, 7 ICIs-related, 1 RT-related) occurred in 7 (28.0%) patients from group 1, and in 4 patients (26.3%) in group 2 (6 total all ICIs-related); this was not statistically significant (χ2 p= 0.60). Five grade 3 toxicities were: pneumonitis (2), hepatitis (1), colitis (1), and nausea (1). No grade 4 or 5 toxicity was reported. Palliative RT within 3 months of ICIs did not increase ICIs and RT-induced grade ≥2 toxicities. Proceeding with ICIs while receiving palliative RT for m-NSCLC is likely safe. Further research incorporating larger cohort is planned to verify these safety results.

Use of SABR to treat pulmonary oligometastases, and more recently, oligoprogression to delay the need to change systemic therapy, is increasing despite no randomized evidence. This project reviewed the outcomes of treating pulmonary metastases from a large single-institution. From a prospective stereotactic ablative radiation therapy (SABR) database, 180 pulmonary metastases in 120 patients were treated from November 2008 and December 2013. Indications for SABR were: 1) oligometastases, where the goal was to irradiate all sites of disease; 2) oligoprogression, where the goal was to irradiate only those tumors which were progressing while a systemic therapy strategy was controlling all other tumors; and 3) dominant areas of progression, where the goal was to irradiate dominant tumors, even if other tumors were progressing, usually in patients with indolent disease not on systemic therapy. Doses of 48–52 Gy in 4–5 fractions were delivered as per institutional policy depending on tumor location and histology. Since 2010, the dose for peripheral colorectal cancer (CRC) metastases was increased to 60 Gy in 4 fractions after a preliminary analysis revealed a higher local failure rate in those tumors. Median age of patients was 66.5 years. Median duration of follow-up was 21.1 months. Median biological effective dose (BED) was 120 Gy10. We observed 1 (<1%) grade 5, 1 (<1%) grade 3, and 8 (7%) grade 2 radiation pneumonitis. Two-year local control (LC) of irradiated tumors was 81%. Non-CRC metastases had higher 2-year LC compared to CRC tumors (94% vs 70%, P = .002). In the subgroup of patients with CRC metastases, delivering 60 Gy was associated with significantly higher 2-year LC compared to lower doses (88% vs 61%, P = .011). In 79 patients with oligometastases treated with SABR, the 2-year progression-free probability (PFP), progression-free survival (PFS) and overall survival (OS) were 63%, 42%, and 73%, respectively. In 27 patients with oligoprogression treated with SABR, the 2-year PFP, PFS, and OS were 42%, 24%, and 70%, respectively. At 2 years, no change in systemic therapy was seen in 56% of the patients irradiated for oligoprogression, with a median time to changing systemic therapy of 30.8 months. In the 12 oligoprogression patients, where a change of systemic therapy strategy occurred after SABR, the median time to systemic therapy change was 8.3 months. Colorectal cancer metastases require higher SABR doses to optimize their LC. Outcomes for patients with oligometastases and oligoprogression treated with SABR seem favorable, but prospective clinical trials are needed to confirm these benefits.

Modern radiation therapy (RT) of head and neck cancer (HNC) offers precise delivery to the defined targets while maintaining low doses to surrounding critical organs - in part due to the enhanced ability to define the gross tumor volume (GTV) with the additional use of MRI and PET scans. Traditionally, a high dose clinical target volume (CTV) of 5 mm is routinely added to the GTV to ensure proper coverage of microscopic disease. However, HN tumors often respond during RT, which suggests that the microscopic CTV through a significant portion of the treatment is shrinking to < 5 mm and could be reduced. This study intends to quantify the decrease in CTV margin in a series of HNC patients through the course of the treatment. A prospective study in 2009 enrolled advanced HNC patients undergoing curative IMRT (70 Gy in 33 fractions, with or without chemotherapy) to receive a dynamic pre-treatment fluorodeoxyglucose (FDG) PET-CT simulator scan (with mask), which was also repeated during the 2nd-3rd week. Sixty patients with different HNC were evaluated. Two radiation oncologists separately contoured GTVs in the pre- and intra-treatment scans to account for inter-observer variability. Rigid fusion of the planning CT to pre- and intra- treatment PET-CT scans was performed using the image fusion module. Margin expansions ranging from 1-25 mm were performed on the pre-treatment GTV to volumetrically match the original clinical target volume (CTV) (as defined by the treating radiation oncologist), based on optimal Dice Similarity Indices (DSI). A similar process took place with the intra-treatment scan, where the intra-treatment GTV was expanded to the original treatment CTV. Results from 16 patients are reported with the full patient cohort to follow. Volume matching given by DSI showed that the pre-treatment GTV needed an average 3.12 ± 1.36 mm expansion to optimally match the clinical CTV (DSI = 0.78 ± 0.04) while the 2nd-3rd week GTV required a margin of 5.65 ± 2.03 mm (DSI = 0.70 ± 0.06). On average, the radial size of the primary CTV decreased by 2.53 ± 2.44 mm between pre- and 2nd-3rd week scans. Our results indicate that HNC tumor shrinkage during RT provides an inherent margin that may allow for an overall smaller GTV to CTV expansion. The determination of an optimized CTV margin could permit dose escalation in HNC patients while minimizing normal tissue toxicities.

patients either would have disease-free bladder intact survival or transition to locoregional failure, metastatic recurrence, or death. Patients with locoregional failure from TMT transition into nonsalvageable disease or salvageable disease. Patients with salvageable disease prompted a salvage cystectomy. Model probabilities and utilities were extracted from the literature. Costs were derived from 2019 National Medicare Fee Schedule. RESULTS: RC and TMT were associated with quality adjusted life years (QALY) of 2.88 and 3.38 respectively (incremental QALYs of 0.5 favoring TMT). The mean costs of RC and TMT were $37,107 and $23,916 respectively. TMT was less expensive with an incremental cost of $13,191. CONCLUSIONS: In patients aged 65 and older with MIBC, TMT was the dominant strategy as compared to RC, as it was both cheaper and associated with increased QALYs based upon model assumptions. The results of this study are the first to evaluate the cost effectiveness of RC and TMT and can inform the ongoing discussion regarding the use of TMT and RC in MIBC.