Treatment Outcomes for Small Cell Carcinoma of the Bladder: Results From a UK Patient Retrospective Cohort Study.

PURPOSE: Small cell carcinoma of the bladder (SCCB) is rare, accounting for less than 1% of all bladder carcinomas. It is aggressive, and outcomes are poor as a result of its early metastatic spread. Owing to its rarity, there are limitations on data to propose standardized management pathways. METHODS AND MATERIALS: We conducted a retrospective analysis of patients presenting with pure or predominant-histology SCCB to 26 institutions in the United Kingdom between 2006 and 2016. The data cutoff date was February 1, 2018. We report patient characteristics, treatment received, and subsequent clinical outcomes. RESULTS: A total of 409 eligible patients were included. Among these, 306 (74.8%) were male, the median age was 71 years (range, 35-96 years), and 189 patients (46.2%) had pure-histology SCCB. At data cutoff, 301 patients (73.6%) had died. The median overall survival (OS) was 15.9 months (95% CI, 13.2-18.7 months). Two hundred patients (48.9%) were confirmed to have bladder-confined disease (N0, M0), with a median OS of 28.3 months (95% CI, 20.9-35.8 months), versus a median OS of 12.7 months (95% CI, 10.9-14.6 months) for the 172 patients (42.1%) with confirmed N1-3 and/or M1 disease (hazard ratio [HR], 2.03; 95% CI, 1.58-2.60; P < .001). A total of 247 patients (61.5%) received primary chemotherapy, with a median OS of 21.6 months (95% CI, 15.5-27.6 months), versus a median OS of 9.1 months (95% CI, 5.4-12.8 months) in patients who did not receive primary chemotherapy (HR, 0.46; 95% CI, 0.37-0.59; P < .001). Choice of chemotherapy agent did not alter outcomes. For those with bladder-confined disease, 61 (30.5%) underwent cystectomy, and 104 (52.0%) received radiation therapy. Survival outcomes were similar for both cystectomy and radiation therapy. Only 6 patients (1.5%) were identified as having brain metastases at any time point. CONCLUSIONS: To our knowledge, this is the largest retrospective study of all-stage SCCB to date. Patients have a poor prognosis overall, but survival is improved in those able to receive chemotherapy and with organ-confined disease. Brain metastases are rare.

Adaptive radiotherapy for muscle-invasive bladder cancer: optimisation of plan sizes.

INTRODUCTION: Plan-of-the-day adaptive radiotherapy (ART) that has not been optimally designed may result in inefficient plan sizes. This can lead to unused plans, which may potentially reduce overall conformality. We compared two methods of individualising ART plan sizes for muscle-invasive bladder cancer to determine which provides a more balanced distribution of plan selections. METHODS: Twenty-seven previously treated patients had small, medium and large ART plans generated from CTV contours on the simulation CT and initial cone beam CTs (CBCT). In the original clinical method, the smallest plan was based on the smallest CTV, while the experimental method used the Boolean summation of the two smallest CTVs. The large plan was identical in both methods. The medium plans were created midway between small and large CTVs. Credentialed treatment staff performed plan selection clinically for the original plans and retrospectively for the experimental plans. RESULTS: A total of 646 CBCTs from 26 patients were included. The small, medium and large adaptive CTVs, and the conventional CTV, were used 29.7%, 45.4%, 22.0% and 2.9% of the time, respectively, compared to the previous 9.8%, 49.2%, 39.5% and 1.5%. The differences were significant between previous and new CTV (small), and CTV (large). CONCLUSIONS: The new design method resulted in the three adaptive CTV choices being selected more evenly, however, a reduction in a surrogate for normal tissue irradiation was not observed.

The utility of PET/CT in staging and assessment of treatment response of nasopharyngeal cancer.

INTRODUCTION: The aim of this study was to evaluate the impact of positron emission tomography/computerised tomography (PET/CT) as an adjunct to conventional imaging (CI) in the management of nasopharyngeal cancer (NPC) both for initial staging and assessment of post-treatment response. METHODS: All NPC cases referred to the Peter MacCallum Centre for Metabolic Imaging between January 2002 and December 2007 were identified. In patients undergoing initial staging, any differences between the pre-PET/CT management plan based on CI and that following performance of the PET/CT scan were noted. Clinical impact was scored using the Centre's published criteria: 'high' if PET/CT changed the primary treatment modality or intent, 'medium' if treatment modality was unchanged but the radiotherapy technique or dose was altered, and 'low' if there was no change in treatment modality or intent. Patients undergoing PET/CT following definitive treatment were scored according to whether or not they achieved a complete metabolic response. RESULTS: Forty-eight patients underwent a staging PET/CT. The clinical impact was high in 8%, medium in 25% and low in 66% of patients. Twenty-one patients were scanned for post-treatment response. PET/CT was less frequently equivocal than MRI (3 vs 8/21). A complete metabolic response on PET/CT was associated with a 93% negative predictive value for subsequent recurrence. CONCLUSION: PET/CT is a valuable staging tool for the detection of occult metastatic disease and defining the extent of neck nodal disease. Post-treatment, a complete metabolic response on PET/CT has a very high negative predictive value with fewer equivocal results than MRI.

Possible Radiation Sensitisation by Trastuzumab Leading to Radiation-Induced Myelitis.

SUMMARY: BACKGROUND: Trastuzumab is used as adjuvant treatment in patients with HER2-positive breast cancers and has been shown to reduce the chance of recurrence by up to 50%. However, experience with it given with radiotherapy is limited and there is in vitro evidence of a radiosensiti-sation effect. We describe the first case of trastuzumab-associated radiation-induced myelitis. CASE REPORT: This patient received a calculated dose of 28 Gy to the spinal cord when receiving adjuvant radiotherapy to the chest wall and supraclavicular and axillary lymph nodes. This is well below the accepted radiation tolerance of the spinal cord (50-60 Gy) but she developed radiation-induced myelitis of her spinal cord with characteristic magnetic resonance imaging changes. We postulate that trastuzu-mab given concurrently with radiation may have acted as a radiosensitiser and that normal repair mechanisms in the acute stage were affected by trastuzumab blockage of epidermal growth factor receptors, resulting in demy-elination at a lower dose of radiation than normally seen. CONCLUSIONS: Concomitant radiotherapy and adjuvant trastuzumab treatment should be given with caution and consideration made of delaying trastuzumab until after radiotherapy has been completed. As longer-term data become available for patients who received trastuzumab and radiation, it will become clearer whether there is a significant interaction on organs such as the heart and spinal cord in the radiation field.