Multi-Institutional Clinical Outcomes of Biopsy Gleason Grade Group 5 Prostate Cancers Treated With Contemporary High-Dose Radiation and Long-Term Androgen Deprivation Therapy.

AIMS: This multicentric retrospective study reports long-term clinical outcomes of non-metastatic grade group 5 prostate cancers treated with external beam radiotherapy (EBRT) alone with long-term androgen deprivation therapy (ADT). MATERIALS AND METHODS: Patients treated across 19 institutions were studied. The key endpoints that were evaluated were 5-year biochemical recurrence-free survival (bRFS), metastases-free survival (MFS), overall survival, together with EBRT-related acute and late toxicities. The impact of various prognostic factors on the studied endpoints was analysed using univariate and multivariate analyses. RESULTS: Among the 462 patients, 88% (405) had Gleason 9 disease and 31% (142) had primary Gleason pattern 5. A prostate-specific membrane antigen positron emission tomography-computed tomography scan was used for staging in 33% (153), 80% (371) were staged as T3/T4 and 30% (142) with pelvic nodal disease. The median ADT duration was 24 months; 66% received hypofractionated EBRT and 71.4% (330) received pelvic nodal irradiation. With a median follow-up of 56 months, the 5-year bRFS, MFS and overall survival were 73.1%, 77.4% and 90.5%, respectively. Primary Gleason pattern 5 was associated with worse bRFS, MFS and overall survival with hazard ratios of 0.51 (95% confidence interval 0.35 to 0.73, P < 0.001), 0.64 (95% confidence interval 0.43 to 0.96, P = 0.031) and 0.52 (95% confidence interval 0.28 to 0.97, P = 0.040), respectively, whereas pelvic nodal disease was associated with worse bRFS (hazard ratio 0.67, 95% confidence interval 0.46 to 0.98, P = 0.039) and MFS (hazard ratio 0.56, 95% confidence interval 0.37 to 0.85, P = 0.006). The acute and late radiation-related toxicities were low overall and pelvic nodal irradiation was associated with higher toxicities. CONCLUSION: Contemporary EBRT and long-term ADT led to excellent 5-year clinical outcomes and low rates of toxicity in this cohort of non-metastatic grade group 5 prostate cancers. Primary Gleason pattern 5 and pelvic node disease portends inferior clinical outcomes.

Testicular seminoma: Are clinical features and treatment outcomes any different in India?

AIM: This study aims to identify clinical features, treatment outcomes, and prognostic factors for relapse and survival in patients with testicular seminoma. MATERIALS AND METHODS: Retrospective analysis of all patients with pure seminoma treated at our center during over a decade (January 2005-December 2014) was carried out. Patient demographics, tumor characteristics, and treatment details and pattern of recurrence were recorded in a structured format, and disease-free survival and overall survival were calculated. RESULTS: Sixty-three patients' case records were included in the analysis. Ten patients developed disease in the undescended testis. All patients underwent orchiectomy as the initial treatment procedure. Majority of the patients were Stage I (57.14%) followed by Stage II (39.6%). Among the patients with Stage I, 55.5% received adjuvant chemotherapy while 22.2% received adjuvant radiation and the rest opted for surveillance. The compliance for active surveillance was very poor. Among patients with Stage II disease, majority (80%) were treated with adjuvant chemotherapy and the rest with radiation. At a median follow-up of 49 months, there were four recurrences of which three were salvaged successfully, and one patient remained alive with disease. There were no disease-related deaths. CONCLUSIONS: Testicular seminoma remains to be relatively low and majority of them presented with Stage I disease and single agent carboplatin appeared to be the preferred adjuvant treatment. Advanced disease patients were treated with etoposide and cisplatin/bleomycin, etoposide and cisplatin chemotherapy and the clinical outcome is comparable with the Western literature.

Do Contemporary Randomized Controlled Trials Meet ESMO Thresholds for Meaningful Clinical Benefit?

Background: The European Society for Medical Oncology (ESMO) recently released a magnitude of clinical benefit scale (ESMO-MCBS) for systemic therapies for solid cancers. Here, we evaluate contemporary randomized controlled trials (RCTs) against the proposed ESMO thresholds for meaningful clinical benefit. Methods: RCTs evaluating systemic therapy for breast cancer, nonsmall cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic cancer published 2011-2015 were reviewed. Data were abstracted regarding trial characteristics and outcomes, and these were applied to the ESMO-MCBS. We also determined whether RCTs were designed to detect an effect that would meet clinical benefit as defined by the ESMO-MCBS. Results: About 277 eligible RCTs were included (40% breast, 31% NSCLC, 22% CRC, 6% pancreas). Median sample size was 532 and 83% were funded by industry. Among all 277 RCTs, the experimental therapy was statistically superior to the control arm in 138 (50%) trials: results of only 31% (43/138) of these trials met the ESMO-MCBS clinical benefit threshold. RCTs with curative intent were more likely to meet clinically meaningful thresholds than those with palliative intent [61% (19/31) versus 22% (24/107), P < 0.001]. Among the 226 RCTs for which the ESMO-MCBS could be applied, 31% (70/226) were designed to detect an effect size that could meet ESMO-MCBS thresholds. Conclusion: Less than one-third of contemporary RCTs with statistically significant results meet ESMO thresholds for meaningful clinical benefit, and this represents only 15% of all published trials. Investigators, funding agencies, regulatory agencies, and industry should adopt more stringent thresholds for meaningful benefit in the design of future RCTs.

Pentoxifylline to treat radiation proctitis: a small and inconclusive randomised trial.

This prospective randomised controlled study of 40 patients could not show a statistically significant advantage with 6 months of pentoxifylline compared with standard measures for late radiation-induced rectal bleeding. However, a modest benefit cannot be excluded and larger randomised placebo-controlled trials with longer durations of pentoxifylline treatment may be justified.

Permanent disabilities in childhood survivors of Langerhans cell histiocytosis.

This study evaluates the permanent disabilities in children treated for Langerhans cell histiocytosis (LCH). From January 1983 to December 1993, 50 patients with newly diagnosed biopsy proven LCH were seen at the Regional Cancer Centre, Trivandrum, India. Disease pattern, treatment, survival, and disabilities of the patients were studied. Patients with localized disease had surgery, irradiation, or steroids. Patients with disseminated disease had combination chemotherapy. Follow-up ranged from 36 to 156 months (median follow-up 85 months). Twelve of the 41 surviving patients (29.2%) had one or more disabilities. Growth retardation was seen in 8 patients, diabetes insipidus in 7, loss of teeth in 6, and mandibular defect, chronic aural discharge, partial hearing loss, facial palsy, and proptosis in 2 each. In short, a significant proportion of survivors of LCH had sequelae, which affected their quality of life. More intensive chemotherapy at the beginning might be helpful in reducing the disabilities.

Bone marrow relapse in primary mucinous carcinoma of skin.

Primary mucinous carcinoma of skin is a rare adnexal tumor arising from the eccrine sweat gland. The tumors grow slowly and have low rates of local recurrence and rare chances of distant metastasis. The authors report a 70-year-old man with primary mucinous skin carcinoma who had a relapse in bone marrow 19 months after initial treatment.

Disseminated Langerhans cell histocytosis in children: treatment outcome.

Langerhans cell histiocytosis is an interesting disorder with a variety of presentations and variable outcomes. This study evaluates response to treatment, recurrence, and survival in disseminated Langerhans cell histiocytosis treated at Regional Cancer Centre, Trivandrum, India from 1983 through 1994. Thirty-five patients with disseminated Langerhans cell histiocytosis were seen. Six had group A disease, 21 had group B disease, and eight had group C disease. In group A, five of six patients are disease free at a median follow-up of 48 months. Two had recurrence after initial treatment, which was salvaged. In group B, 13 of 15 patients had complete response after chemotherapy, nine of whom experienced recurrence later. Three of five patients who received irradiation alone experienced recurrence. One died of progressive disease. Two patients were lost to follow-up. Seventeen of 20 are alive with median follow-up of 67 months. In group C, one of eight patients are alive after multiple recurrences. Of the surviving patients, 29% had significant sequelae. In summary, group A and B patients do well with treatment, and most of the recurrences can be salvaged. A significant proportion of patients have sequelae. Newer aggressive protocols must be developed for treating group C patients. Measures to prevent sequelae must also be developed.

Clear cell sarcoma kidney: clinical features and outcome.

Clear cell sarcoma of kidney (CCSK) is a rare, highly malignant tumor. The clinical features and treatment outcome of 12 patients with CCSK are reported. From 1982 through December 1996, 12 cases of CCSK were seen at the Regional Cancer Centre, Trivandrum, India. Patients were staged according to NWTS III recommendation. They were treated with chemotherapy containing vincristine, actinomycin, and Adriamycin and radiotherapy. The survival curve was calculated by the Kaplan-Meier method. Mass and pain in the abdomen were the presenting symptoms. Male/female ratio was 3:1. Six had stage I, 4 had stage II, and 2 had stage III disease. Of the 12, 10 were evaluable, 6 are alive, and 3 recurred in 9 evaluable. Six patients are alive free of disease 10 to 108 months after diagnosis. The overall survival and disease-free survival of the 10 patients are 64 and 56%. It would appear that combined modality treatment can cure two thirds of children with CCSK. Effective treatment needs to be developed for children who fail after first line treatment.

Langerhans cell histiocytosis in children less than 2 years of age.

OBJECTIVE: To study the clinical profile and outcome of langerhans cell histiocytosis in children upto 2 years of life. DESIGN: Retrospective analysis. METHODS: Medical records of Children upto 2 years of age with a diagnosis of langerhans cell histiocytosis (LCH) were analyzed. Their clinical pattern, treatment modalities and outcome were studied. The patients Were categorized into 2 groups according to their clinical presentation: (i) Subject without organ dysfunction; and (ii) cases with organ dysfunction. Treatment considered of surgical intervention, radiotherapy, chemotherapy or combination of all these modalities depending upto the extent of disease. RESULTS: There were 20 children upto 2 years of age with histiocytosis during the 12 year period (January 1983 - December 1994). The median age at diagnosis was 18 months (range 52 days - 24 months). Of the twenty patients,13 patients didn't have organ dysfunction and 7 had organ dysfunction. Out of the 13 children without organ dysfunction eleven patients received treatment and all of them are alive free of disease with a median follow up of 62 months. But all children with organ dysfunction succumbed to disease within a few weeks. CONCLUSION: Children under 2 years of age with localised and or multifocal LCH without organ dysfunction have a good prognosis and they should not be exposed to aggressive form of treatment. All children with organ dysfunction require multi-agent chemotherapy.

Ovarian carcinoma relapsing as a cerebellopontine angle tumour.

Involvement of the central nervous system in epithelial ovarian carcinoma is rare. A 46-year-old woman with ovarian carcinoma relapsing with brain metastasis is described. She received radiotherapy for the metastasis and survived for 18 months.