AbstractBackgroundWe report extended follow-up of TROG99.03, a randomised phase III trial in early-stage follicular lymphoma (ESFL) including new information on the role of adjuvant rituximab and translational studies.MethodsPatients with ESFL were randomised to involved-field radiotherapy (IFRT) or IFRT plus 6-cycles cyclophosphamide/vincristine/prednisolone (IFRT+CVP). From 2006 rituximab was added to IFRT+CVP (IFRT+R-CVP). Clinical and multi-omic parameters were evaluated. Findings were validated in two independent ESFL cohorts (99 and 60 patients respectively).FindingsBetween 2000-2012, 150 (75 per arm) patients were recruited. 48% were positron emission tomography (PET)-staged. Per protocol, at median follow-up 11.3-years, progression-free survival (PFS) remained superior for IFRT+(R)CVP vs. IFRT (hazard ratio [HR]=0.60, 95%CI=0.37-0.98, p=0.043; 10-year PFS 62% vs. 43%) respectively. Although no significant difference in overall survival was observed (HR=0.44, 95%CI=0.16-1.18, p=0.11, 10-year OS 95% vs 84%), patients receiving IFRT+(R)CVP experienced fewer composite (histological transformation and death) events (p=0.045). PFS of IFRT+R-CVP-treated patients compared with all other treatments lacking rituximab (IFRT alone plus IFRT+CVP) was superior (HR=0.36, 95%CI=0.13-0.82, p=0.013). Amongst PET-staged patients, PFS differences between IFRT+R-CVP vs. IFRT were maintained (HR=0.38, 95%CI=0.16-0.89, p=0.027) indicating benefit distinct from stage migration. FL-related mutations andBCL2-translocations were not associated with PFS. However, by multivariate analysis elevated CD8A gene expression in diagnostic biopsy tissue was independently associated with improved PFS (HR=0.45, 95%CI=0.26-0.79, p=0.037), a finding confirmed in both ESFL validation cohorts. CD8A gene expression was raised (p=0.02) and CD8+ T-cell density higher within follicles in ESFL vs. advanced-stage FL (p=0.047). Human leucocyte antigen class I specific neoantigens were detected in 43% of patients, suggesting neoantigen-specific CD8+ T-cells have a role in confining the spread of the disease.InterpretationAdjuvant R-CVP and elevated intratumoural CD8 expression were independently associated with sustained disease control after radiotherapy in ESFL.FundingCancer Council Victora; National Health and Medical Research Council; Leukaemia Foundation; Mater Foundation.

BACKGROUND:We report extended follow-up of TROG99.03, a randomised phase III trial in early-stage follicular lymphoma (ESFL) including new information on the role of adjuvant rituximab and translational studies. METHODS:Patients with ESFL were randomised to involved field radiotherapy (IFRT) or IFRT plus 6-cycles cyclophosphamide/vincristine/prednisolone (IFRT + CVP). From 2006 rituximab was added to IFRT + CVP (IFRT + R-CVP). Clinical and multi-omic parameters were evaluated. Findings were validated in two independent ESFL cohorts (99 and 60 patients respectively). FINDINGS:Between 2000 and 2012, 150 (75 per arm) patients were recruited. 48% were positron emission tomography (PET)-staged. By protocol, at median follow-up 11.3-years, progression-free survival (PFS) remained superior for IFRT+(R)CVP vs. IFRT (hazard ratio [HR] = 0.60, 95% CI = 0.37-0.98, p = 0.043; 10-year PFS 62% vs. 43%) respectively. Although no significant difference in overall survival was observed (HR = 0.44, 95% CI = 0.16-1.18, p = 0.11, 10-year OS 95% vs. 84%), patients receiving IFRT+(R)CVP experienced fewer composite (histological transformation and death) events (p = 0.045). PFS of IFRT + R-CVP-treated patients compared with all other treatments lacking rituximab (IFRT alone plus IFRT + CVP) was superior (HR = 0.36, 95% CI = 0.13-0.82, p = 0.013). Amongst PET-staged patients, PFS differences between IFRT + R-CVP vs. IFRT were maintained (HR = 0.38, 95% CI = 0.16-0.89, p = 0.027) indicating benefit distinct from stage migration. FL-related mutations and BCL2-translocations were not associated with PFS. However, by multivariate analysis elevated CD8A gene expression in diagnostic biopsy tissue was independently associated with improved PFS (HR = 0.45, 95% CI = 0.26-0.79, p = 0.037), a finding confirmed in both ESFL validation cohorts. CD8A gene expression was raised (p = 0.02) and CD8+ T-cell density higher within follicles in ESFL vs. advanced-stage FL (p = 0.047). Human leucocyte antigen class I specific neoantigens were detected in 43% of patients, suggesting neoantigen-specific CD8+ T-cells have a role in confining the spread of the disease. INTERPRETATION:Adjuvant R-CVP and elevated intratumoural CD8 expression were independently associated with sustained disease control after radiotherapy in ESFL. FUNDING:Cancer Council Victora; National Health and Medical Research Council; Leukaemia Foundation; Mater Foundation.

CCR Translation for This Article from [18F]FLT–PET Imaging Does Not Always “Light Up” Proliferating Tumor Cells

9582 Background: Non-melanomatous skin cancer (NMSC) diagnoses are associated with a high risk of developing new skin cancers in adjacent areas. Patients with extensive skin field cancerization (ESFC) have large areas (generally ≥50cm2) of compromised skin characterized by pre-cancerous actinic keratoses often requiring repeated interventions. Lesion-directed therapies have excellent cure rates, but therapies targeting a wider region have limited durability, including topical agents such as 5-flurouracil. The development of volumetric modulated arc radiation therapy (VMAT) to precisely target large, curved skin surfaces has generated interest in its application to ESFC. This is a report on the efficacy, safety, and cosmetic outcomes of VMAT in the management of patients with ESFC at facilities across five Australian states. Methods: Sixty-three ESFC zones on 60 patients were prescribed widefield VMAT and prospectively enrolled in the National (Australian) Dermatology Radiation Oncology Registry (NDROR). Over 80% of patients had received up to 4 prior non-radiotherapy interventions. Fields included lower and upper limb, face, scalp, or trunk regions. Total widefield VMAT RT doses ranged from 45-50 Gy delivered in 25-30 daily fractions across 5-7 weeks. 3-, 6-, and 12-month follow-up assessments rated the percentage of disease clearance, cosmesis using the Lovett’s scale, and toxicity based on CTCAE. Results: At 12-month follow-up, 97% of treated zones had achieved and maintained clinical success, defined as > 90% field clearance. Five percent of patients exhibited recurrence of original disease, whereas 10% of patients developed a new actinic keratosis or NMSC. Cosmesis was rated as excellent or good in 98% of patients. Most patients exhibited grade 1-2 radiation-induced dermatitis during therapy, which resolved by 3-month follow-up. Grade 3 dermatitis at end of treatment was exhibited in 7% of the patients, which also resolved. Eight percent of patients discontinued treatment due to acute toxicities. The most common persistent toxicity at 12-month follow-up was localized grade 1 xerosis (dryness) at 43% and/or alopecia at 33%. Conclusions: Widefield VMAT achieved very promising clinical success in patients with ESFC for whom other therapies had failed. VMAT yielded favorable cosmetic outcomes, and treatment-related toxicity was manageable and transient in most patients. While additional follow up is necessary, these results demonstrate that widefield VMAT may be an excellent option for some patients with increasingly unmanageable presentations of ESFC.

Background Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. Methods The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42.5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236). Findings Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6.6 years. The 5-year free-from-local-recurrence rates were 92.7% (95% CI 90.6-94.4%) in the no-boost group and 97.1% (95.6-98.1%) in the boost group (hazard ratio 0.47; 0.31-0.72; p<0.001). The boost group had higher rates of grade 2 or higher breast pain (10% [8-12%] vs 14% [12-17%], p=0.003) and induration (6% [5-8%] vs 14% [11-16%], p<0.001). Interpretation In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

Purpose Evaluate the use of widefield radiation therapy (RT) in the management of extensive skin field cancerization (ESFC) with/without keratinocyte cancer (KC).Methods The National Dermatology Radiation Oncology Registry is a multidisciplinary collaboration (dermatologists and radiation oncologists). It captures disease description, prior therapies, radiation prescription, clinical effect, skin cosmesis scores, and toxicity data. This analysis included 12-month follow-up data on 89 treated fields from a subset of 83 patients.Results Clinical success (>90% field clearance) was 96% (ESFC, n = 63) and 88% (ESFC with KC, n = 26). Complete lesion response was seen in 96% of evaluable (n = 25) ESFC with KC. Recurrence (4/89 [5%]) and appearance of new lesions (10/89 [11%]) were minimal. Cosmetic outcome was excellent/good in 98% ESFC and 96% ESFC with KC. Grade 1–2 acute radiation dermatitis occurred in up to 80% of treated fields. The frequency of Grade 3 acute skin toxicities was low.Conclusions Registry data demonstrate the potential for widefield RT to treat patients with significant skin pathology who have exhausted other therapies and require durable, minimally invasive treatment options. At 12 months, observed clinical success rates were higher than those reported for topical interventions for ESFC. Ongoing follow-up is required to determine longer term outcomes.

and severity of pulmonary hypertension in asymptomatic rural residents with schistosomal infection in the Nile Delta. Trop Med Int Health 2012; 17:112–118. 7 Chen MG. Assessment of morbidity due to Schistosoma japonicum infection in China. Infect Dis Poverty 2014;3:6. 8 Li FY, Hou XY, Tan HZ, Williams GM, Gray DJ, Gordon CA, et al. Current status of schistosomiasis control and prospects for elimination in the Dongting Lake Region of the People’s Republic of China. Front Immunol 2020;11:574136. 9 LoganOT. A case of dysentery in HunanProvince caused by the trematode Schistosoma japonicum 1905. Chin Med J 1905;19:243–245. 10 ZhouXN,Guo JG,WuXH, JiangQW, Zheng J, DangH, et al.Epidemiology of schistosomiasis in the People’s Republic of China, 2004. Emerg Infect Dis 2007;13:1470–1476. 11 Raso G, Li Y, Zhao Z, Balen J, Williams GM, McManus DP. Spatial distribution of human Schistosoma japonicum infections in the Dongting Lake Region, China. PLoS One 2009;4:e6947. 12 VezozzoDC, Farias AQ, Cerri GG, DaSilva LC,Carrilho FJ. Assessment of portal hemodynamics by Doppler ultrasound and of liver morphology in the hepatosplenic and hepatointestinal forms of schistosomiasis mansoni. Dig Dis Sci 2006;51:1413–1419. 13 de Cleva R, Herman P, Pugliese V, Zilberstein B, Saad WA, Rodrigues JJ, et al. Prevalence of pulmonary hypertension in patients with hepatosplenic Mansonic schistosomiasis–prospective study. Hepatogastroenterology 2003;50:2028–2030. 14 Ferreira RC, Domingues AL, Bandeira AP, Markman Filho B, Albuqerque Filho ES, Correiade de Ara ujo AC, et al. Prevalence of pulmonary hypertension in patients with schistosomal liver fibrosis. Ann Trop Med Parasitol 2009;103:129–143. 15 Botoni FA, Marinho CC, Carvalho VT, Mickael CS, Graham BB. A retrospective study of schistosomiasis-associated pulmonary hypertension from an endemic area in Brazil. Int J Cardiol Heart Vasc 2019;24:100387. 16 Mohamed-AliQ,Elwali NE, AbdelhameedAA,Mergani A, RahoudS, Elagib KE, et al. Susceptibility to periportal (Symmers) fibrosis in human Schistosoma mansoni infections: evidence that intensity and duration of infection, gender, and inherited factors are critical in disease progression. J Infect Dis 1999;180:1298–1306. 17 SimonneauG,Gali e N,Rubin LJ, LanglebenD,SeegerW,Domenighetti G, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004;43(12, Suppl S)5S–12S. 18 Knafl D, Gerges C, King CH, Humbert M, Bustinduy AL. Schistosomiasisassociated pulmonary arterial hypertension: a systematic review. Eur Respir Rev 2020;29:190089. 19 Mauad T, Pozzan G, Lanças T, Overbeek MJ, Souza R, Jardim C, et al. Immunopathological aspects of schistosomiasis-associated pulmonary arterial hypertension. J Infect 2014;68:90–98. 20 Mickael CS, Graham BB. The role of type 2 inflammation in Schistosomainduced pulmonary hypertension. Front Immunol 2019;10:27. 21 Sibomana JP, Campeche A, Carvalho-Filho RJ, Correa RA, Duani H, Pacheco Guimaraes V, et al. Schistosomiasis pulmonary arterial hypertension. Front Immunol 2020;11:608883. 22 Knafl D, Gerges C, King CH, Humbert M, Bustinduy AL. Schistosomiasisassociated pulmonary arterial hypertension: a systematic review. Eur Respir Rev 2020;29:190089. 23 Mendes AA, Roncal CGP, Oliveira FRA, Albuquerque ES, G oes GHB, Piscoya ICV, et al. Demographic and clinical characteristics of pulmonary arterial hypertension caused by schistosomiasis are indistinguishable from other etiologies.Rev SocBrasMed Trop 2020;53: e20190418. 24 Barbosa MM, Lamounier JA, Oliveira EC, Souza MV, Marques DS, Silva AA, et al. Pulmonary hypertension in schistosomiasis mansoni. Trans R Soc Trop Med Hyg 1996;90:663–665. 25 Strange G, Stewart S, Celermajer DS, Prior D, Scalia GM, Marwick TH, et al.; NEDA Contributing Sites. Threshold of pulmonary hypertension associated with increased mortality. J Am Coll Cardiol 2019;73:2660– 2672.

Background: This Phase 2 multicentre trial in localised non-gastric marginal zone lymphoma (MZL) evaluated the effectiveness and safety of radiotherapy and documented markers of autoimmunity and Helicobacter pylori infection. Patients and methods: Eligible patients had Stages I and II or paired-organ, non-gastric MZL. Bone marrow evaluation, autoantibody panel, and H. pylori evaluation were mandatory. Involved-field or involved-site radiotherapy was delivered to 24-30.6 Gy. Detected H. pylori infections underwent eradication. Results: Between 2006 and 2014, six centres enrolled 70 patients, and 68 commenced treatment. The median age was 59 (range: 23-84) years, and 31 (46%) were male. Overall, 55 patients had Stage I disease, nine patients had Stage II disease, and four patients had paired organ-confined disease. Involved extranodal sites with three or more cases were orbital (n = 18), conjunctiva (n = 13), lacrimal (n = 8), skin (n = 8), salivary (n = 7), and muscle (n=4). Eight patients had primary nodal MZL. At the median follow-up of 5 years (range 0.7-9.4), progression-free survival and overall survival were 79% and 95%, respectively. One lymphoma-related death and two in-field failures (after 25 and 30 Gy, respectively) occurred. Distant relapse sites were skin (n = 2), lymph nodes (n = 2), duodenum, stomach, muscle, and conjunctiva (1 each). No paired-organ MZL relapsed. Apart from cataracts (n = 18), only three treatment-related late grade >= 3 adverse events occurred. Autoantibodies or autoimmune events were detected in 26 of 68 patients (38%). H. pylori infection was detected in 15 of 63 patients 24%) tested. Neither autoimmunity nor H. pylori was detected in 27 of 68 patients (40%). Conclusions: Radiotherapy was a potentially curative treatment with low toxicity in localised non-gastric MZL. Autoimmunity, H. pylori infection or both were detected in 60% of patients. (C) 2021 Published by Elsevier Ltd.

Few data measure the problems critically ill patients have with medications after hospital discharge, whichmedications are involved, and how severe the consequences are (1–3). We sought to assess the prevalence and severity of medication-related problems in intensive care unit (ICU) survivors and explore pain management strategies. We did so among patients attending a five-site post-ICU program in Scotland between September 2016 and June 2018.

INTRODUCTION:Cancer Australia guidelines recommend that hypofractionation should be considered for women over the age of 50 years with early breast cancer. GenesisCare is the largest provider of radiation therapy services in Australia. This study aimed to investigate variation in hypofractionation across 4 states encompassing the period when the most recent guidelines had been released.METHODS:Patients with T1 N0 and T2 N0 breast cancer who received radiation therapy as adjuvant therapy after breast conservation surgery between 2014 and 2016 were reviewed. Patient, treatment and disease-related variables were included in the univariate and multivariate models together with other potential explanatory variables such as the state, in which the patient was treated, radiation oncologist and distance from the treatment centre.RESULTS:Of 3374 patients included, 44% received a hypofractionated schedule. There was an increase in the use of hypofractionation from 32% in 2014 to 56% in 2016. Older patients were more likely to receive a hypofractionated treatment schedule - 75% for patients 80 years and over. Multivariate modelling revealed older age, year of treatment, higher T stage and grade, chemotherapy and the individual radiation oncologist (and state) as independent predictors of the use of hypofractionation. There was no difference in hypofractionation based on laterality.CONCLUSIONS:Guidelines from Cancer Australia may impact clinician behaviour. The influence of the individual radiation oncologist remains paramount, and their practice is affected by their immediate colleagues. Subsequent analysis of hypofractionation rates after presentation of these data has resulted in a significant increase in its use.

Fig. S1. Prevalance of acute toxicity (weeks 0–8). Fig. S2. Changes in quality of life scores with time. Fig. S3. Outcomes data (Kaplan–Meier graphs). Table S1. Patient characteristics. Table S2. Tumour control outcomes. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Background This study evaluated relapse patterns and survival in advanced Hodgkin lymphoma (HL) patients treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) with positron emission tomography (PET) used for staging and response assessment. Patients and methods Patients aged 18 years or above with newly diagnosed histologically proven Stage III or IV HL treated with ABVD at Calvary Mater Newcastle from January 2005 to December 2012 were included in this study. All patients underwent pre-chemotherapy staging with 18F-fluorodeoxyglucose PET or PET/computed tomography and post-chemotherapy PET or PET/computed tomography for the assessment of response. Results Forty-three patients were included in the study. The 5-year disease-free survival, progression-free survival and overall survival were 88%, 74% and 86%, respectively. PET complete response was seen in 35 patients (81%), and the 5-year overall survival for this group was 94%. Relapse following a PET complete response was low (three patients) and occurred predominantly at the initial sites of disease. Four of five patients with bulky disease received consolidative radiotherapy and no in-field relapses were observed. Conclusion Advanced stage HL with a PET complete response following ABVD is associated with an excellent prognosis.

Purpose: The role of involved-field radiation therapy (IFRT) with autologous stem cell transplantation (ASCT) for lymphomas remains uncertain. Methods and Materials: In this prospective, multicenter study, patients undergoing ASCT for relapsed/refractory lymphoma received peritransplant IFRT to disease sites identified at study registration (SR) (before salvage chemotherapy [SC]). Radiation dose was adapted to SC response. Survival, relapse rates/pattern, toxicity, and prognostic factors were evaluated. Results: Forty-five patients were enrolled (23 with Hodgkin lymphoma, 22 with aggressive non-Hodgkin lymphoma). Three-year overall survival and cumulative incidence of posttransplant progression rates were 72% (95% confidence interval [CI], 59%-87%) and 42% (95% CI, 27%-57%), respectively. Stage (P=.03) and elevated lactate dehydrogenase (P=.05) were significant risk factors for disease progression on multivariable analysis. Three-year actuarial in-field, marginal, and distant progression rates were 7% (95% CI, 0%-15%), 9% (95% CI, 0%-18%), and 36% (95% CI, 21%-51%), respectively. Progression occurred in 8 of 30 patients with all sites irradiated and in 13 of 15 patients without all sites irradiated. There were 117 disease sites at SR and 64 post-ASCT progression sites, of which 15 were involved at SR and 12 only at initial diagnosis. Posttransplant relapse occurred in 3 of 83 irradiated and 12 of 34 unirradiated involved sites. Of 28 sites in complete response to SC on computed tomography, there was no relapse in any of the 21 irradiated sites and in 1 of 7 unirradiated sites. Of 72 sites in complete response on positron emission tomography, relapse occurred in 1 of 50 irradiated and 10 of 22 unirradiated sites. No grade 4 nonhematologic radiation therapy toxicities were observed. Conclusions: IFRT was well tolerated and associated with a low rate of in-field progression. Progression rates were lower for patients with all disease sites irradiated. Response to SC on both computed tomography and positron emission tomography warrants further study to select sites for IFRT. (C) 2018 Elsevier Inc. All rights reserved.

PURPOSE:Follicular lymphoma (FL) is curable by involved-field radiotherapy (IFRT) in < 50% of patients with stage I to II disease. We hypothesized that adding systemic therapy to IFRT would improve long-term progression-free survival (PFS).PATIENTS AND METHODS:A multicenter randomized controlled trial enrolled patients with stage I to II low-grade FL after staging computed tomography scans and bone marrow biopsies. 18F-labeled fluorodeoxyglucose-positron emission tomography (PET) was not mandatory. Patients were randomly assigned to either arm A (30 Gy IFRT alone) or arm B (IFRT plus six cycles of cyclophosphamide, vincristine, and prednisolone [CVP]). From 2006, rituximab was added to arm B (R-CVP).RESULTS:Between 2000 and 2012, 150 patients were enrolled, 75 per arm. In arm B, 44 patients were allocated to receive CVP and 31 were allocated to receive R-CVP. At randomization, 75% had stage I, the median age was 57 years, 52% were male, and 48% were PET staged. With a median follow-up of 9.6 years (range, 3.1 to 15.8 years), PFS was superior in arm B (hazard ratio, 0.57; 95% CI, 0.34 to 0.95; P = .033). Ten-year PFS rates were 59% (95% CI, 46% to 74%) and 41% (95% CI, 30% to 57%) for arms B and A, respectively. Patients in arm B who received R-CVP had markedly superior PFS compared with contemporaneous patients in arm A (hazard ratio, 0.26; 95% CI, 0.07 to 0.97; P = .045). Fewer involved regions ( P = .047) and PET staging ( P = .056) were associated with better PFS. Histologic transformation occurred in four and 10 patients in arms B and A, respectively ( P = .1). Ten deaths occurred in arm A versus five in arm B, but overall survival was not significantly different ( P = .40; 87% and 95% at 10 years, respectively).CONCLUSION:Systemic therapy with R-CVP after IFRT reduced relapse outside radiation fields and significantly improved PFS. IFRT followed by immunochemotherapy is more effective than IFRT in early-stage FL.

Poster: 2014 CSM / R-0042 / Outcomes following CT guided multichannel cylinder brachytherapy for vaginal recurrence of endometrial cancer by: Lapuz, G. Govindarajulu, C. Dempsey, A. Capp, P. O'Brien; NEWCASTLE/AU

4543 Background: This phase III trial investigated the benefits and toxicities of a combination of weekly cisplatin and radiation therapy (Arm A) compared with radiation therapy (RT) alone (Arm B)in the definitive treatment of muscle-invasive bladder cancer (MIBC). Methods: Adult patients with localized Stage T2-T4a, bladder cancer of predominant transitional cell carcinoma histology with no contraindications to the use of pelvic radiation therapy or cisplatin chemotherapy were eligible. Othet exclusion criteria included extensive or multifocal carcinoma in situ and a contracted bladder. An initial maximal transurethral resection of the bladder tumour (TURBT) preceded randomisation. The primary outcome was local failure at 3 years. The secondary endpoints included complete response rate at3 months, overall and disease free survival, acute and late toxicity and QoL. The QoL of patients receiving organ preserving treatments for MIBC had not been previously investigated in a randomised Phase III setting. Intitial accrual target was set at 150 patients over 4 years. Slow accrual lead to early closure with Thirty eight patients were being randomised to arm A and 30 patients to arm B. Results: Compliance with RT in both arms was excellent. About 15% of patients in the chemoradiation arm required a significant reduction in cisplatin dose delivery mainly because of declining renal function. Acute and late toxicity was similar in the two arms, but in the short to medium term chemoradiation did affect QoL. Trends towards better local control, distant disease free and overall survival were noted in the chemoradiation arm. Conclusions: Overall weekly cisplatin and radiation therapy in MIBC are reasonably well tolerated. Treatment however in the short to medium term does affect Qol. Notwithstanding this negative impact, recovery does follow in the longer term. This is yet another study which suggests that chemoradiation does offer the prospect of improving local control and overall survival compared to radiation therapy alone. Clinical trial information: No NCT00330499.