Long term outcomes of nonmyeloablative allogeneic stem cell transplantation with TSEB TLI and ATG for Mycosis Fungoides and Sezary Syndrome.

Advanced stage (IIB-IVB) Mycosis Fungoides (MF) and Sezary Syndrome (SS) have a poor prognosis with median survival <5 years. We report long-term outcomes of a non-myeloablative allogeneic stem cell transplantation regimen consisting of total skin electron beam therapy, total lymphoid irradiation and antithymocyte globulin. Our prospective cohort consisted of 41 patients with a higher proportion of MF (34MF, 7SS). Acute GVHD Grade 2 to 4 was seen in 31.7% and chronic GVHD Grade 2 to 4 in 24%. The cumulative incidence of non-relapse mortality was 9.8% at 1 year and 12.6% at 2 years. At Day +90 post-transplant 66% of patients had a complete response (CR). With a median post-transplant follow up of 5.27 years, the 5-year overall survival rate was 37.7% (MF 36.7%, SS 57.1%). The 5-year cumulative incidence of progressive disease or relapse was 52.7% in all patients but only 20.8% in those with CR at transplant compared to 70.6% in those not in CR at transplant (p = 0.006). Long term survival is possible in advanced MF and SS with non-myeloablative transplantation and outcomes are improved in patients with CR at transplant.

A Repurposing Programme Evaluating Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design.

AIMS: Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. MATERIALS AND METHODS: The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. RESULTS: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited. FUTURE: Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway.

Evaluating inter-fractional changes in volume and position during bladder radiotherapy and the effect of volume limitation as a method of reducing the internal margin of the planning target volume.

AIMS: To quantify the inter-fractional variation in bladder volume and position during a course of bladder radiotherapy, and to assess the feasibility of reducing the planning target volume (PTV) internal margin using an empty bladder protocol. MATERIALS AND METHODS: Weekly computed tomography scans were taken immediately after micturition on 15 patients undergoing radical radiotherapy for bladder cancer. Bladder volume and positional variation were compared by co-registration of the serial computed tomography scans with the initial planning scan and a single 'full' scan at the onset of treatment for each patient. A PTV was generated on the initial planning scan using both our departmental standard of 1.5cm and a reduced 1cm isotropic internal margin around the target (whole bladder) and the relative proportion of the bladder breaching the PTV using both margins compared. RESULTS: The mean post void residual volume from the planning scan was 112cm(3) (standard deviation 42cm(3)). The mean weekly variation in bladder volume relative to the planning volume was 0-12% (standard deviation 20-34%) with no observable trends over time. No statistically significant differences were seen in the proportion of bladder breaching the 1.5 and 1cm internal margin (P=0.18). Regression analysis showed that it is possible to ensure complete coverage of the bladder with a 1cm margin, providing the volume did not exceed over 50% of the initial planning scan volume. CONCLUSION: Using an empty bladder protocol and where on-line imaging is available it is feasible to reduce the internal margin of the PTV from 1.5 to 1cm, providing the volumes do not exceed >50% of the planning scan volume.

Evaluating the effect of reducing the high-dose volume on the toxicity of radiotherapy in the treatment of bladder cancer.

AIMS: The radiation dose used to treat bladder cancer is limited by the risk of inducing severe late bladder toxicity. Retrospective data suggest that radiation tolerance is greater for partial rather than whole bladder irradiation. Limiting the high-dose region to a section of the bladder may reduce toxicity, opening the way for dose escalation. The aims of this study were to establish the efficacy and compare the late toxicity between (1) a two-phase technique limiting the high-dose area and (2) a conventional single-phase radiotherapy to the whole bladder. MATERIALS AND METHODS: A cohort study was undertaken of 229 patients with invasive bladder cancer treated with computed tomography-planned radical radiotherapy at the Royal Marsden Hospital from 1984 to 1998. In total, 154 patients received a single-phase treatment to the whole bladder with a 2 cm margin. Seventy-five patients with solitary, well-localised tumours were selected for treatment using a two-phase technique. The first phase (12 Gy) aimed to treat the tumour with a 2 cm margin. A second phase treated the whole bladder with 52 Gy. One hundred and forty-one patients were planned to receive a dose of 60-64 Gy/30-32 fractions over 6-6.5 weeks, whereas 88 patients received an accelerated regime. Data on late bladder and bowel toxicity (using Radiation Therapy Oncology Group criteria) were collected prospectively at the annual review. RESULTS: At the 5-year follow-up there was no difference in overall survival (hazard ratio = 0.91, 95% confidence interval 0.64-1.3) or failure-free survival (hazard ratio = 1.02, 95% confidence interval 0.73-1.43) between the two techniques. The two-phase reduced volume treatment was less toxic, with a 19% absolute reduction in overall grade 3-4 late toxicity (P = 0.02). These differences were more marked for bladder toxicity compared with bowel toxicity. CONCLUSIONS: The two-phase reduced volume technique was associated with less bladder and bowel toxicity than conventional whole bladder radiotherapy without evidence of impaired survival.

Small-cell carcinoma of the urinary bladder: 10-year experience.

AIMS: Small-cell carcinoma of the urinary bladder is rarely encountered in clinical practice. We report on our clinical experience with affected patients presenting to our institution from 1986 to 1996. MATERIALS AND METHODS: We retrospectively analysed 14 pathologically confirmed cases, specifically looking at stage, presenting features, treatment and overall survival. The median age at presentation was 74 years (range 54-91 years). RESULTS: Ten patients presented with stage III disease, and four patients with stage IV disease (1 = nodal, 3 = distant metastases). Four patients were treated with radical radiotherapy (one patient receiving neoadjuvant chemotherapy) and two underwent a radical cystoprostatectomy. Five patients received palliative bladder radiotherapy and three were too frail for treatment at presentation. The overall median survival was 5 months. Patients receiving radical treatment had a median overall survival of 21 months, with only one long-term survivor. CONCLUSION: This highly aggressive tumour tends to affect an elderly population who are generally frail and have significant comorbidity. Many are unfit for radical treatment. In patients with disease confined to the pelvis who are able to tolerate radical intervention, the results of local therapy alone are poor. It therefore remains incumbent on treating clinicians to explore means of improving these results. Initial chemotherapy analogous to small-cell lung cancer may offer a durable response with a better chance for long-term survival.

High dose rate prostate brachytherapy: an overview of the rationale, experience and emerging applications in the treatment of prostate cancer.

The technological advances in real-time ultrasound image guidance for high dose rate (HDR) prostate brachytherapy places this treatment modality at the forefront of innovation in radiotherapy. This review article will explore the rationale for HDR brachytherapy as a highly conformal method of dose delivery and safe dose escalation to the prostate, in addition to the particular radiobiological advantages it has over low dose rate and external beam radiotherapy. The encouraging outcome data and favourable toxicity profile will be discussed before looking at emerging applications for the future and how this procedure will feature alongside stereotactic radiosurgery.

A feasibility study of using gold seeds as fiducial markers for bladder localization during radical radiotherapy.

Target localization and verification of the treatment position is important for the accurate delivery of conformal radiotherapy. The bladder in particular is a deformable structure whose shape and position continually varies throughout a course of radiation treatment as a result of bladder filling. We report a novel technique of organ localization using gold seeds as fiducial markers that are implanted into the bladder using a specially adapted applicator that is passed through a rigid cystoscope. The seeds are readily apparent on electronic portal imaging taken at the time of radiotherapy and can thus act as a surrogate for bladder position. The feasibility and technical aspects of performing such a procedure on eight patients were assessed. In all of the patients, some of the seeds were visible on the planning CT scan and remained within the bladder wall throughout the course of radiotherapy treatment. The drop-out rate was minimized by the use of cystodiathermy at the site of seed insertion. It was possible to place the seeds in both areas of normal and diseased bladder tissue. The procedure was associated with minimal toxicity. This technique will form the basis for planning further studies on bladder localization.

Distortion-corrected T2 weighted MRI: a novel approach to prostate radiotherapy planning.

The purpose of this study was to evaluate distortion-corrected MRI as a radiotherapy planning tool for prostate cancer and the resultant implications for dose sparing of organs at risk. 11 men who were to be treated with radical conformal radiotherapy for localized prostate cancer had an MRI scan under radiotherapy planning conditions, which was corrected for geometric distortion. Radiotherapy plans were created for planning target volumes derived from the MRI- and CT-defined prostate. Dose volume histograms were produced for the rectum, bladder and penile bulb. The mean volume of the prostate as defined on CT and MRI was 41 cm3 and 36 cm3, respectively (p = 0.009). The predicted percentage of the rectum treated to dose levels of 45-65 Gy was significantly lower for plans delineating the prostate with MRI than for those with CT. The rectal-sparing effect was confined to the lowermost 4 cm of the rectum (anal canal). There were no differences between the predicted doses to bladder or penile bulb (as defined using MRI) between plans. In conclusion, prostate radiotherapy planning based on distortion-corrected MRI is feasible and results in a smaller target volume than does CT. This leads to a lower predicted proportion of the rectum, in particular the lower rectum (anal canal), treated to a given dose than with CT.