Shaista Hafeez

Advances in bladder cancer imaging

The purpose of this article is to review the imaging techniques that have changed and are anticipated to change bladder cancer evaluation. The use of multidetector 64-slice computed tomography (CT) and magnetic resonance imaging (MRI) remain standard staging modalities. The development of functional imaging such as dynamic contrast-enhanced MRI, diffusion-weighted MRI and positron emission tomography (PET)-CT allows characterization of tumor physiology and potential genotypic activity, to help stratify and inform future patient management. They open up the possibility of tumor mapping and individualized treatment solutions, permitting early identification of response and allowing timely change in treatment. Further validation of these methods is required however, and at present they are used in conjunction with, rather than as an alternative to, conventional imaging techniques.

The potential of MRI-guided online adaptive re-optimisation in radiotherapy of urinary bladder cancer

BACKGROUND AND PURPOSE Adaptive radiotherapy (ART) using plan selection is being introduced clinically for bladder cancer, but the challenge of how to compensate for intra-fractional motion remains. The purpose of this study was to assess target coverage with respect to intra-fractional motion and the potential for normal tissue sparing in MRI-guided ART (MRIGART) using isotropic (MRIGARTiso), an-isotropic (MRIGARTanIso) and population-based margins (MRIGARTpop). MATERIALS AND METHODS Nine bladder cancer patients treated in a phase II trial of plan selection underwent 6-7 weekly repeat MRI series, each with volumetric scans acquired over a 10 min period. Adaptive re-planning on the 0 min MRI scans was performed using density override, simulating a hypo-fractionated schedule. Target coverage was evaluated on the 10 min scan to quantify the impact of intra-fractional motion. RESULTS MRIGARTanIso reduced the course-averaged PTV by median 304 cc compared to plan selection. Bladder shifts affected target coverage in individual fractions for all strategies. Two patients had a v95% of the bladder below 98% for MRIGARTiso. MRIGARTiso decreased the bowel V25 with 15-46 cc compared to MRIGARTpop. CONCLUSION Online re-optimised ART has a considerable normal tissue sparing potential. MRIGART with online corrections for target shift during a treatment fraction should be considered in ART for bladder cancer.

Radium-223 for the treatment of prostate cancer

Introduction: Bone metastases cause significant morbidity and mortality in castration-resistant prostate cancer (CRPC). Until recently, treatment options have been limited, but now six drugs are known to extend life expectancy, with docetaxel the current standard first-line cytotoxic therapy. Phase III studies have also shown a survival advantage for sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and radium-223. Radium-223 is unique among these agents, as the only bone-directed therapy shown to prolong survival in CRPC. Areas covered: This review covers the current standard of care for CRPC and recent drug developments that have demonstrated a survival benefit. It focuses on bone-directed therapies, in particular radium-223, the first-in-class alpha-emitting radionuclide and discusses the pivotal studies to date. A PubMed search using the keywords below was performed. Expert opinion: Radium-223 is set to become a new standard of care for the treatment of bony metastatic CRPC. It improves both survival and quality of life, delays skeletal events and is well tolerated. Its optimal use in the evolving treatment strategies for men with CRPC and bone metastases is yet to be determined.

Selective organ preservation with neo-adjuvant chemotherapy for the treatment of muscle invasive transitional cell carcinoma of the bladder

Background:Radiotherapy for muscle invasive bladder cancer (MIBC) aims to offer organ preservation without oncological compromise. Neo-adjuvant chemotherapy provides survival advantage; response may guide patient selection for bladder preservation and identify those most likely to have favourable result with radiotherapy.Methods:Ninety-four successive patients with T2-T4aN0M0 bladder cancer treated between January 2000 and June 2011 were analysed at the Royal Marsden Hospital. Patients received platinum-based chemotherapy following transurethral resection of bladder tumour; repeat cystoscopy (±biopsy) was performed to guide subsequent management. Responders were treated with radiotherapy. Poor responders were recommended radical cystectomy. Progression-free survival (PFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan–Meier method; univariate and multivariate analyses were performed using the Cox proportional hazard regression model.Results:Response assessment was performed in 89 patients. Seventy-eight (88%) demonstrated response; 53 (60%) achieved complete response (CR); 74 responders had radiotherapy; 4 opted for cystectomy. Eleven (12%) demonstrated poor response, 10 received cystectomy. Median survival for CR was 90 months (95% CI 64.7, 115.9) compared with 16 months (95% CI 5.4, 27.4; P<0.001) poor responders. On multivariate analysis, only response was associated with significantly improved PFS, OS and DSS. After a median follow-up of 39 months (range 4–127 months), 14 patients (16%) required salvage cystectomy (8 for non-muscle invasive disease, 5 for invasive recurrence, 1 for radiotherapy related toxicity). In all, 82% had an intact bladder at last follow-up after radiotherapy; 67% had an intact bladder at last follow-up or death. Our study is limited by its retrospective nature.Conclusions:Response to neo-adjuvant chemotherapy is a favourable prognostic indicator and can be used to select patients for radiotherapy allowing bladder preservation in >80% of the selected patients.

Multiparametric Magnetic Resonance Imaging for Bladder Cancer: Development of VI-RADS (Vesical Imaging-Reporting And Data System)

CONTEXT Management of bladder cancer (BC) is primarily driven by stage, grade, and biological potential. Knowledge of each is derived using clinical, histopathological, and radiological investigations. This multimodal approach reduces the risk of error from one particular test, but may present a staging dilemma when results conflict. Multiparametric magnetic resonance imaging (mpMRI) may improve patient care through imaging of the bladder with better resolution of the tissue planes than computed tomography and without radiation exposure. OBJECTIVE To define a standardized approach to imaging and reporting mpMRI for BC, by developing a VI-RADS score. EVIDENCE ACQUISITION We created VI-RADS (Vesical Imaging-Reporting And Data System) through consensus using existing literature. EVIDENCE SYNTHESIS We describe standard imaging protocols and reporting criteria (including size, location, multiplicity, and morphology) for bladder mpMRI. We propose a five-point VI-RADS score, derived using T2-weighted MRI, diffusion-weighted imaging, and dynamic contrast enhancement, which suggests the risks of muscle invasion. We include sample images used to understand VI-RADS. CONCLUSIONS We hope that VI-RADS will standardize reporting, facilitate comparisons between patients, and in future years, will be tested and refined if necessary. While we do not advocate mpMRI for all patients with BC, this imaging may compliment pathology or reduce radiation-based imaging. Bladder mpMRI may be most useful in patients with non-muscle-invasive cancers, in expediting radical treatment or for determining response to bladder-sparing approaches. PATIENT SUMMARY Magnetic resonance imaging (MRI) scans for bladder cancer are becoming more common and may provide accurate information that helps improve patient care. Here, we describe a standardized reporting criterion for bladder MRI. This should improve communication between doctors and allow better comparisons between patients.

Advantages and Limitations

CT alone has conventionally informed radiotherapy planning. It provides anatomical information for delineation and electron density for dose calculation. Integrating PET-CT for radiotherapy planning offers the opportunity to individualize treatment and improve patient outcome. PET-CT’s molecular insight of tumour biology could facilitate a move away from ‘one-size-fits-all’ prescription to more accurate personalized radiotherapy [1].

Clinical Outcomes of Image Guided Adaptive Hypofractionated Weekly Radiation Therapy for Bladder Cancer in Patients Unsuitable for Radical Treatment

Purpose and Objectives We report on the clinical outcomes of a phase 2 study assessing image guided hypofractionated weekly radiation therapy in bladder cancer patients unsuitable for radical treatment. Methods and Materials Fifty-five patients with T2-T4aNx-2M0-1 bladder cancer not suitable for cystectomy or daily radiation therapy treatment were recruited. A “plan of the day” radiation therapy approach was used, treating the whole (empty) bladder to 36 Gy in 6 weekly fractions. Acute toxicity was assessed weekly during radiation therapy, at 6 and 12 weeks using the Common Terminology Criteria for Adverse Events version 3.0. Late toxicity was assessed at 6 months and 12 months using Radiation Therapy Oncology Group grading. Cystoscopy was used to assess local control at 3 months. Cumulative incidence function was used to determine local progression at 1 at 2 years. Death without local progression was treated as a competing risk. Overall survival was estimated using the Kaplan-Meier method. Results Median age was 86 years (range, 68-97 years). Eighty-seven percent of patients completed their prescribed course of radiation therapy. Genitourinary and gastrointestinal grade 3 acute toxicity was seen in 18% (10/55) and 4% (2/55) of patients, respectively. No grade 4 genitourinary or gastrointestinal toxicity was seen. Grade ≥3 late toxicity (any) at 6 and 12 months was seen in 6.5% (2/31) and 4.3% (1/23) of patients, respectively. Local control after radiation therapy was 92% of assessed patients (60% total population). Cumulative incidence of local progression at 1 year and 2 years for all patients was 7% (95% confidence interval [CI] 2%-17%) and 17% (95% CI 8%-29%), respectively. Overall survival at 1 year was 63% (95% CI 48%-74%). Conclusion Hypofractionated radiation therapy delivered weekly with a plan of the day approach offers good local control with acceptable toxicity in a patient population not suitable for radical bladder treatment.

Magnitude of observer error using cone beam CT for prostate interfraction motion estimation: effect of reducing scan length or increasing exposure.

Objective: Cone beam CT (CBCT) enables soft-tissue registration to planning CT for position verification in radiotherapy. The aim of this study was to determine the interobserver error (IOE) in prostate position verification using a standard CBCT protocol, and the effect of reducing CBCT scan length or increasing exposure, compared with standard imaging protocol. Methods: CBCT images were acquired using a novel 7 cm length image with standard exposure (1644 mAs) at Fraction 1 (7), standard 12 cm length image (1644 mAs) at Fraction 2 (12) and a 7 cm length image with higher exposure (2632 mAs) at Fraction 3 (7H) on 31 patients receiving radiotherapy for prostate cancer. Eight observers (two clinicians and six radiographers) registered the images. Guidelines and training were provided. The means of the IOEs were compared using a Kruzkal–Wallis test. Levenes test was used to test for differences in the variances of the IOEs and the independent prostate position. Results: No significant difference was found between the IOEs of each image protocol in any direction. Mean absolute IOE was the greatest in the anteroposterior direction. Standard deviation (SD) of the IOE was the least in the left–right direction for each of the three image protocols. The SD of the IOE was significantly less than the independent prostate motion in the anterior–posterior (AP) direction only (1.8 and 3.0 mm, respectively: p = 0.017). IOEs were within 1 SD of the independent prostate motion in 95%, 77% and 96% of the images in the RL, SI and AP direction. Conclusion: Reducing CBCT scan length and increasing exposure did not have a significant effect on IOEs. To reduce imaging dose, a reduction in CBCT scan length could be considered without increasing the uncertainty in prostate registration. Precision of CBCT verification of prostate radiotherapy is affected by IOE and should be quantified prior to implementation. Advances in knowledge: This study shows the importance of quantifying the magnitude of IOEs prior to CBCT implementation.

Exploration of the treatment challenges in men with intellectual difficulties and testicular cancer as seen in Down syndrome: single centre experience

Down syndrome is the most common chromosomal disorder in humans as well as the most common cause of inherited intellectual disability. A spectrum of physical and functional disability is associated with the syndrome as well as a predisposition to developing particular malignancies, including testicular cancers. These tumours ordinarily have a high cure rate even in widely disseminated disease. However, individuals with Down syndrome may have learning difficulties, behavioural problems, and multiple systemic complications that have the potential to make standard treatment more risky and necessitates individualized approach in order to avoid unacceptable harm. There is also suggestion that tumours may have a different natural history. Further, people with learning disabilities have often experienced poorer healthcare than the general population. In order to address these inequalities, legislation, professional bodies, and charities provide guidance; however, ultimately, consideration of the person in the context of their own psychosocial issues, comorbidities, and possible treatment strategies is vital in delivering optimal care. We aim to present a review of our own experience of delivering individualized care to this group of patients in order to close the existing health inequality gap.

Selective organ preservation for the treatment of muscle-invasive transitional cell carcinoma of the bladder: a review of current and future perspectives

Radical treatment remains underutilized for those with muscle-invasive bladder cancer. Radical radiotherapy, in particular, continues to be perceived by many as reserved only for patients unfit for cystectomy. However, with concurrent use of radiosensitizers, radiotherapy can achieve excellent local control and survival comparable to modern surgical series, thus presenting a real alternative to surgery. The possibility of further enhancing patient outcome is likely to come from both advances in radiotherapy treatment delivery and appropriate candidate selection. Growing evidence from selective bladder preservation trials demonstrate long term survival with functional organ preservation. In the era of personalized medicine, we review the evidence supporting an individualized treatment approach, in particular case selection for radical radiotherapy.