Acute Toxicity of Hypofractionated and Conventionally Fractionated (Chemo)Radiotherapy Regimens for Bladder Cancer: An Exploratory Analysis from the RAIDER Trial.

AIMS: Adding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination. MATERIALS AND METHODS: Participants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests. RESULTS: Between September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20- or 32-fraction cohorts. CONCLUSION: Grade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine.

The use of treosulfan and gemcitabine in the treatment of platinum-resistant ovarian cancer.

The combination of treosulfan and gemcitabine (TG) has been shown to have activity in ovarian cancer. These two agents are thought to be synergistic, with gemcitabine causing the persistence of treosulfan-induced DNA crosslinks. This study aimed to investigate the response rates, survival and toxicity in patients with platinum-resistant ovarian cancer treated with TG. A retrospective case note review of the patients treated with TG was performed in one cancer centre between May 1st, 2000 and November 1st, 2005. Estimates of cumulative survival were obtained using the Kaplan-Meier method. Forty-nine patients were identified; median age at diagnosis was 55 years (range, 31-72) and the median follow-up was 45.1 months (range, 12.2-118.3). TG was used as second-, third-, fourth- and fifth-line chemotherapy in 15, 19, 13 and 2 patients, respectively. Fifteen patients (30.6%) had stable disease; 25 (51%), a partial response; 1 (2%), a complete response and 8 (16.3%) had progressive disease. Median survival following diagnosis was 45.1 months and the median relapse-free survival was 12 months. The median survival time from the start of TG was 13.7 months with a relapse-free survival of 6.3 months. The median number of cycles given was 7. The most common toxicity recorded was myelosuppression. There were no treatment-related deaths. TG chemotherapy produced favourable response rates in a heavily pre-treated group of patients with platinum-resistant epithelial ovarian cancer. This doublet warrants further investigation in a phase III trial setting.

Gastrointestinal stromal tumour with a KIT exon 11 mutation presenting as a paratesticular mass.

Gastrointestinal stromal tumours (GISTs) are sarcomas arising in the gastrointestinal tract. They are characterised by a gain in function mutation of the KIT oncogene and the majority express the receptor tyrosine kinase KIT, which can be detected by the immunohistochemical stain CD117. Patients with a GIST present with symptoms such as abdominal pain or gastrointestinal bleeding, or may be asymptomatic. We describe the clinical history and pathological features of a patient with a GIST who presented with a paratesticular mass which, to our knowledge, has never previously been reported. With the development of new drugs to treat GISTs, the knowledge of the type of mutations may in the future prove helpful in determining optimal treatment strategies and prognosis.