Jani, Ashesh B.

428 Background: Trimodality therapy (TMT) with maximal TURBT followed by chemoradiation(CRT) is a standard of care for select patients with muscle invasive bladder cancer (MIBC). This trial evaluates the activity of atezolizumab (atezo) in MIBC in combination with TMT. This trial was designed with pre-specified safety analyses of the first 80 patients (40 in each arm). At the time of SWOG fall 2020 DSMC report deadline we had enrolled 84 patients but data on only 73 patients were available. The same data are being submitted to ASCO GU meeting. Methods: This trial is testing atezo every 3 weeks for 6 months given concurrently and adjuvantly with CRT vs. CRT alone in 475 patients with MIBC T2-T4aN0M0 disease. Patients are stratified based on PS; T2 vs T3 or T4; choice of chemotherapy; and radiation field (bladder only vs small pelvis). Patients undergo biopsy 3 months after finishing CRT to assess treatment response. Patients are followed for 5 years for recurrence or survival. This trial was not preceded by a phase I study but was designed with a safety run in of 80 patients. Study team agreed on the study design based on available data from other tumor types and initial experience from investigators running smaller similar trials. It was pre-specified that if we observe more than 25% patients having grade 3-5 colitis or cystitis in the atezo arm or any other toxicity which is deemed clinically significant and related to atezo, the trial investigators and DSMC would consider stopping further enrollment. Results: 36 patients were enrolled on the TMT alone arm and 37 patients on the TMT + atezo arm. No grade 3 or higher colitis was reported in the atezo arm. Only one patient had treatment related grade 3 radiation cystitis which was diagnosed after finishing atezo treatment. No steroids were given. Overall 23 grade 3 or higher toxicity events were reported in the atezo arm vs 11 in non- atezo arm. Most common toxicity was hematological which was considered non-immune related. None of the grade 3 or higher toxicities were considered to be immune related by the treating investigator. Conclusions: There is no evidence of increased immune related grade 3-5 AEs.DSMC has recommended to continue enrollment. Adverse Events with No Entries for Grades 3 to 5 Have Been Suppressed Clinical trial information: NCT03775265 . [Table: see text]

Abstract Background The ability to accurately monitor response to treatment in patients with metastatic castration resistant prostate cancer (mCRPC) on chemotherapy has been a challenge. Conventional methods of therapy response assessment have limitations and molecular imaging has been explored as an important alternative. We set out t o determine if anti-1-amino-3-anti-1-amino-3-[18F]-fluorocyclobutane-1-carboxylic acid ([18F]fluciclovine) positron emission tomography/computed tomography (PET/CT) changes reflect response to docetaxel chemotherapy in mCRPC. Results Seven patients with mCRPC were enrolled. Each patient was scheduled to have [18F]fluciclovine PET/CT at baseline, and after 1 and 6 cycles of chemotherapy. Uptake parameters were recorded in the prostate/bed and up to 10 metastatic lesions. Decrease in uptake of ≥30% was considered response (R); appearance of new lesions or >30% increase in uptake was progressive disease (PD); and change of < 30% uptake was stable disease (SD). Prostate specific antigen (PSA) was obtained at baseline and before each cycle. Bone scintigraphy and CT were acquired at baseline and after the 6th cycle. Assessment of response was based on Prostate Cancer Clinical Trial Working Group 3 recommendations. Correlation between [18F]fluciclovine uptake and time to PSA progression was also determined. All patients completed the 1 st and 2 nd [18F]fluciclovine PET/CT, while 4/7 patients completed all 3 scans. PET response correlated with PSA response in 3/7 (42.9%) patients and 3/4 (75%) patients after 1 and 6 cycles of docetaxel, respectively. Bone scan and CT correlated with PSA response in 1/4 (25%) patients. Mean SUVmax and SUVmean were significantly higher in patients with progressive disease versus non-progressive disease after 6 cycles of docetaxel (p<0.05), but not at baseline or after 1 cycle of docetaxel. There was non-significant correlation of changes in [18F]fluciclovine uptake with changes in PSA after 1 and 6 cycles of docetaxel. There was no significant correlation between PET parameters and time to PSA progression. Conclusion [18F]fluciclovine PET/CT has better correlation than CT or bone scan with PSA response for patients with mCRPC treated with docetaxel. [18F]fluciclovine PET/CT did not predict time to PSA progression. Larger studies exploring the utility of [18F]fluciclovine PET for response assessment are recommended.

PURPOSE Provide evidence- and expert-based recommendations for optimal use of imaging in advanced prostate cancer. Due to increases in research and utilization of novel imaging for advanced prostate cancer, this guideline is intended to outline techniques available and provide recommendations on appropriate use of imaging for specified patient subgroups. METHODS An Expert Panel was convened with members from ASCO and the Society of Abdominal Radiology, American College of Radiology, Society of Nuclear Medicine and Molecular Imaging, American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology to conduct a systematic review of the literature and develop an evidence-based guideline on the optimal use of imaging for advanced prostate cancer. Representative index cases of various prostate cancer disease states are presented, including suspected high-risk disease, newly diagnosed treatment-naïve metastatic disease, suspected recurrent disease after local treatment, and progressive disease while undergoing systemic treatment. A systematic review of the literature from 2013 to August 2018 identified fully published English-language systematic reviews with or without meta-analyses, reports of rigorously conducted phase III randomized controlled trials that compared ≥ 2 imaging modalities, and noncomparative studies that reported on the efficacy of a single imaging modality. RESULTS A total of 35 studies met inclusion criteria and form the evidence base, including 17 systematic reviews with or without meta-analysis and 18 primary research articles. RECOMMENDATIONS One or more of these imaging modalities should be used for patients with advanced prostate cancer: conventional imaging (defined as computed tomography [CT], bone scan, and/or prostate magnetic resonance imaging [MRI]) and/or next-generation imaging (NGI), positron emission tomography [PET], PET/CT, PET/MRI, or whole-body MRI) according to the clinical scenario.

Purpose To report a multicenter experience treating anal canal cancer patients with concurrent chemotherapy and intensity-modulated radiation therapy (IMRT). Patients and Methods From October 2000 to June 2006, 53 patients were treated with concurrent chemotherapy and IMRT for anal squamous cell carcinoma at three tertiary-care academic medical centers. Sixty-two percent were T1-2, and 67% were N0; eight patients were HIV positive. Forty-eight patients received fluorouracil (FU)/mitomycin, one received FU/cisplatin, and four received FU alone. All patients underwent computed tomography–based treatment planning with pelvic regions and inguinal nodes receiving a median of 45 Gy. Primary sites and involved nodes were boosted to a median dose of 51.5 Gy. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 3.0. All late toxicity was scored using Radiation Therapy Oncology Group criteria. Results Median follow-up was 14.5 months (range, 5.2 to 102.8 months). Acute grade 3+ toxicity included 15.1% GI and 37.7% dermatologic toxicity; all acute grade 4 toxicities were hematologic; and acute grade 4 leukopenia and neutropenia occurred in 30.2% and 34.0% of patients, respectively. Treatment breaks occurred in 41.5% of patients, lasting a median of 4 days. Forty-nine patients (92.5%) had a complete response, one patient had a partial response, and three had stable disease. All HIV-positive patients achieved a complete response. Eighteen-month colostomy-free survival, overall survival, freedom from local failure, and freedom from distant failure were 83.7%, 93.4%, 83.9%, and 92.9%, respectively. Conclusion Preliminary outcomes suggest that concurrent chemotherapy and IMRT for anal canal cancers is effective and tolerated favorably compared with historical standards.