Kabir Mohammed

Medium-term Outcomes of Active Surveillance for Localised Prostate Cancer

BACKGROUND Active surveillance (AS) aims to allow men with favourable-risk, localised prostate cancer to avoid unnecessary treatment. OBJECTIVE To describe the clinical outcomes of a prospective study of AS. DESIGN, SETTING, AND PARTICIPANTS A single-centre, prospective cohort study. Eligibility criteria included histologically proven prostate adenocarcinoma, age 50-80 yr, stage T1/T2, prostate-specific antigen level (PSA) <15 ng/ml, Gleason score (GS) ≤ 3+3 (GS ≤ 3+4 if aged >65 yr), and percent positive biopsy cores (PPC) ≤ 50%. INTERVENTION Patients were assessed by serum PSA level, and digital rectal examination at 3-mo intervals in year 1, 4-mo intervals in year 2, and at 6-mo intervals thereafter. Transrectal ultrasound-guided prostate biopsy was performed after 18-24 mo and every 2 yr thereafter. Treatment was recommended for PSA velocity (PSAV) >1 ng/ml per year or adverse histology, defined as GS ≥ 4+3 or PPC >50%. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Outcomes described, using Kaplan-Meier methods, were rate of adverse histology on repeat biopsy, freedom from treatment, biochemical control after deferred treatment, and overall survival. Analyses using Cox regression were performed to determine predictors of deferred treatment and adverse histology. RESULTS AND LIMITATIONS The study enrolled 471 eligible patients from 2002 to 2011. Median age was 66 yr and median initial PSA value was 6.4 ng/ml. Eighty-eight percent of patients had T1 disease and 93% had GS ≤ 3+3. At median follow-up of 5.7 yr, the 5-yr rate of adverse histology and treatment-free probability was 22% (95% confidence interval [CI], 16-29%) and 70% (95% CI, 65-75%), respectively. There were two deaths from prostate cancer. Predictors of time to adverse histology were GS 7, PSAV >1 ng/ml per year, low ratio of free PSA to total PSA, and PPC >25%. Longer follow-up is needed to confirm the safety of this strategy. CONCLUSIONS This study demonstrates satisfactory medium-term outcomes for AS in selected men with localised prostate cancer.

Long-term outcome of HER2 positive metastatic breast cancer patients treated with first-line trastuzumab

BACKGROUND Trastuzumab has changed the natural history of metastatic HER2 positive breast cancer. Some patients remain well and in remission for many years. There is currently no established duration after which trastuzumab in the advanced setting can be safely discontinued. This study aims to evaluate long-term efficacy and cardiac safety of trastuzumab when used as first-line treatment for patients with metastatic HER2 positive breast cancer. PATIENT AND METHODS We retrospectively identified 215 patients with HER2 positive, locally advanced or metastatic breast cancer who commenced first line trastuzumab-containing therapy for metastatic disease between 2001 and 2010 at The Royal Marsden Hospital. RESULTS The median progression free survival for all patients was 12 months (95%CI: 10.3-14.6 months); 103 (48%) patients remained in remission beyond one year, 59 (27%) beyond two years and 25 (12%) beyond five years. The median overall survival was 2.6 years (95% confidence interval (CI): 2.2-3.3). The objective response rate (ORR) was 65% with 17 (8%) complete responses and 120 (57%) partial responses. Trastuzumab was well tolerated. Twenty eight (13%) patients recorded any grade of left ventricular dysfunction. There was no significant difference in cardiac toxicity between those patients on less than or more than one year of trastuzumab. CONCLUSION Trastuzumab is associated with long-term remissions in a significant proportion of patients with metastatic HER2 positive disease when used in the first-line advanced setting.

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.

The efficacy and tolerability of pomalidomide in relapsed/refractory myeloma patients in a “real-world” study: the Royal Marsden Hospital experience

Multiple myeloma (MM) is a molecularly and clinically heterogeneous disease, making it challenging to control. Despite the impact of novel agents, including the immunomodulatory drugs (IMiDs) thali...

Problem-focussed interactive telephone therapy for cancer patients: a phase II feasibility trial

The study aimed to evaluate Problem‐Focussed Interactive Telephone Therapy, an individual psychological therapy based on cognitive‐behavioural therapy adapted for telephone delivery to cancer patients with high psychological needs.

Immunohistochemical Phenotype of Breast Cancer during 25-Year Follow-up of the Royal Marsden Tamoxifen Prevention Trial

The randomized, double-blinded Royal Marsden Tamoxifen Breast Cancer Prevention Trial in healthy high-risk women started in 1986 and is still blinded. Eligible participants (n = 2,471) were randomly assigned to tamoxifen (20 mg/d) or placebo for 8 years. Analysis in 2006 showed a 30% risk reduction of estrogen receptor (ER)-positive invasive breast cancer mostly in the posttreatment period. Biomarker analysis in this population may identify any subgroup-specific preventive effects tamoxifen. After a median follow-up of 18.4 years, 242 patients had developed invasive cancer, 134 on placebo and 108 on tamoxifen. From these, 180 tissue blocks were available and ER, progesterone receptor (PgR), Ki67, HER2, and EGFR were immunohistochemically analyzed. A 32% reduction in ER+ and PgR+ invasive cancers resulted after 8 years of treatment. Quantitative levels of ER and PgR were lower in the tamoxifen-treated group, significantly so for ER (P = 0.001). These lower ER levels were restricted to the posttreatment period (P = 0.018). Among the ER+ group, there was a similar proportional decrease in PgR+ and PgR− tumors by tamoxifen. The median levels of Ki67 were similar in both arms. The numbers of HER2-positive and EGFR-positive cancers were higher in the tamoxifen arm but not significantly so. In conclusion, the preventive effects of tamoxifen result in reduced ER-positive but not ER-negative tumors and reduced ER expression in the ER-positive cases largely confined to the posttreatment period. Overall reductions in PgR expression are explained by lower frequency of ER-positive cases. Impact on Ki67, HER2, and EGFR was modest. Cancer Prev Res; 10(3); 171–6. ©2017 AACR.

Clinical profile and outcome of urotheliotropic viral haemorrhagic cystitis following haematopoietic stem cell transplantation: a 7-year tertiary centre analysis

Abstract Viral haemorrhagic cystitis (HC) is a significant complication after haematopoietic stem cell transplantation (HSCT), with a potential for major morbidity. The aim of this 7-year analysis of 1160 HSCT patients was to evaluate risk factors for the incidence, severity, toxicity of therapy, clinical course, and outcome of this condition. The overall incidence of HC was 5·8%, with most cases occurring after allogeneic HSCT. Unrelated donors (P = 0·001), non-peripheral blood stem cell source (P = 0·005), myeloablative conditioning (P<0·001), use of alemtuzumab in conditioning (P = 0·001), and severe acute graft versus host disease (P<0·001) were independent risk factors for an increased incidence of HC post-allogeneic transplant on multivariate analysis. Severe forms of HC were associated with grades II–IV acute graft versus host disease and a longer duration of haematuria. Contrary to previous studies which were carried out on smaller patient populations, busulphan, cyclophosphamide, anti-thymocyte globulin, and total body irradiation were not found to independently increase the risk of viral HC, unless used in a myeloablative combination. Neither duration of viriuria nor peak viral load in urine influenced the severity of HC on multivariate analysis. Severe HC contributed to the deaths of two patients. Overall survival was not statistically different between patient subgroups with non-severe and severe HC.

Randomized controlled trial of dietary fiber for the prevention of radiation-induced gastrointestinal toxicity during pelvic radiotherapy

Background: Therapeutic radiotherapy is an important treatment of pelvic cancers. Historically, low-fiber diets have been recommended despite a lack of evidence and potentially beneficial mechanisms of fiber.Objective: This randomized controlled trial compared low-, habitual-, and high-fiber diets for the prevention of gastrointestinal toxicity in patients undergoing pelvic radiotherapy.Design: Patients were randomly assigned to low-fiber [≤10 g nonstarch polysaccharide (NSP)/d], habitual-fiber (control), or high-fiber (≥18 g NSP/d) diets and received individualized counseling at the start of radiotherapy to achieve these targets. The primary endpoint was the difference between groups in the change in the Inflammatory Bowel Disease Questionnaire-Bowel Subset (IBDQ-B) score between the starting and nadir (worst) score during treatment. Other measures included macronutrient intake, stool diaries, and fecal short-chain fatty acid concentrations.Results: Patients were randomly assigned to low-fiber (n = 55), habitual-fiber (n = 55), or high-fiber (n = 56) dietary advice. Fiber intakes were significantly different between groups (P < 0.001). The difference between groups in the change in IBDQ-B scores between the start and nadir was not significant (P = 0.093). However, the change in score between the start and end of radiotherapy was smaller in the high-fiber group (mean ± SD: -3.7 ± 12.8) than in the habitual-fiber group (-10.8 ± 13.5; P = 0.011). At 1-y postradiotherapy (n = 126) the difference in IBDQ-B scores between the high-fiber (+0.1 ± 14.5) and the habitual-fiber (-8.4 ± 13.3) groups was significant (P = 0.004). No significant differences were observed in stool frequency or form or in short-chain fatty acid concentrations. Significant reductions in energy, protein, and fat intake occurred in the low- and habitual-fiber groups only.Conclusions: Dietary advice to follow a high-fiber diet during pelvic radiotherapy resulted in reduced gastrointestinal toxicity both acutely and at 1 y compared with habitual-fiber intake. Restrictive, non-evidence-based advice to reduce fiber intake in this setting should be abandoned. This trial was registered at clinicaltrials.gov as NCT 01170299.

Telephone-delivered individual cognitive behavioural therapy for cancer patients: An equivalence randomised trial

To evaluate Telephone‐Delivered Cognitive Behavioural Therapy (T‐CBT) compared to CBT face to face treatment as usual (TAU‐CBT), in cancer patients with high psychological needs, in terms of mental health and coping.

Cisplatin Substitution with Carboplatin During Radical Chemoradiotherapy for Oesophagogastric Carcinoma: Outcomes from a Tertiary Centre

Background/Aim: Cisplatin-based radical chemoradiotherapy (CRT) is utilised in oesophagogastric (OG) cancer but the toxicity profile of cisplatin limits its use. This study aimed to evaluate the clinical characteristics and outcomes of patients treated with either cisplatin or carboplatin based CRT at our institution. Materials and Methods: This is a retrospective analysis of patients with localised OG cancer undergoing CRT with cisplatin/fluoropyrimidine (CX/F) or carboplatin/fluoropyrimidine (CarboX/F) between January 2001 and December 2014. Results: A total of 91 eligible patients were included. Median age was 65 years (IQR=57-75) for CX/F and 77 years (IQR=69-80) for CarboX/F. Adenocarcinoma histology and Charlson comorbidity index were higher in the CarboX/F group. Endoscopic complete response (CR) was achieved in 64% of CX/F group and 48% of CarboX/F group (p=0.19). The median PFS for CX/F was 31.0 months (95%CI=18.2-NE) vs. 18.7 months for CarboX/F (95%CI=13.5-30.4; HR=1.49, p=0.21). Conclusion: Despite significant differences in baseline clinical characteristics, patients treated with carboplatin CRT demonstrated no significant difference in PFS or endoscopic CR rate, compared to those treated with cisplatin.