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.

Plasma-induced signatures reveal an extracellular milieu possessing an immunoregulatory bias in treatment-naive paediatric inflammatory bowel disease.

The inflammatory state associated with Crohn's disease (CD) and ulcerative colitis (UC) remains incompletely defined. To understand more clearly the extracellular milieu associated with inflammatory bowel disease (IBD), we employed a bioassay whereby plasma of treatment naive paediatric IBD patients (n = 22 CD, n = 15 UC) and unrelated healthy controls (uHC, n = 10) were used to induce transcriptional responses in a healthy leucocyte population. After culture, gene expression was measured comprehensively with microarrays and analysed. Relative to uHC, plasma of CD and UC patients induced distinct responses consisting, respectively, of 985 and 895 regulated transcripts [|log2 ratio| ≥ 0·5 (1·4-fold); false discovery rates (FDR) ≤ 0·01]. The CD:uHC and UC:uHC signatures shared a non-random, commonly regulated, intersection of 656 transcripts (χ(2)  = P < 0·001) and were highly correlative [Pearson's correlation coefficient = 0·96, 95% confidence interval (CI) = 0.96, 0.97]. Despite sharing common genetic susceptibility loci, the IBD signature correlated negatively with that driven by plasma of type 1 diabetes (T1D) patients (Pearson's correlation coefficient = -0·51). Ontological analyses revealed the presence of an immunoregulatory plasma milieu in IBD, as transcripts for cytokines/chemokines, receptors and signalling molecules consistent with immune activation were under-expressed relative to uHC and T1D plasma. Multiplex enzyme-linked immunosorbent assay (ELISA) and receptor blockade studies confirmed transforming growth factor (TGF)-ß and interleukin (IL)-10 as contributors to the IBD signature. Analysis of CD patient signatures detected a subset of transcripts associated with responsiveness to 6-mercaptopurine treatment. Through plasma-induced signature analysis, we have defined a unique, partially TGF-ß/IL-10-dependent immunoregulatory signature associated with IBD that may prove useful in predicting therapeutic responsiveness.

Preoperative long-course chemoradiation for localized rectal cancer: A retrospective comparison of response and outcome between 5-fluorouracil/leucovorin versus capecitabine.

BACKGROUND: Preoperative concurrent chemoradiation therapy (CRT) with either capecitabine or 5-florouracil/leucovorin (5 FU/LV) is the standard of care in locally advanced rectal cancer (LARC). Literature comparing the toxicity and response of these two regimens in Indian patients is sparse. Our objective was to compare the pathological response (PR) and clinical outcome of capecitabine versus 5 FU/LV in CRT for LARC. MATERIALS AND METHODS: Sixty patients with LARC treated with preoperative CRT with capecitabine or 5FU/LV from January 2009 to May 2014 were analyzed. Ryan's tumor regression grading was used for PR assessment and tumor downstaging was defined as a reduction in the T and N stages by at least one level. Toxicity was assessed with RTOG acute toxicity assessment criteria and CTCAE 4.0 version. Statistical analysis was done using IBM SPSS 20 software. Percentage of patients with respect to response rates and toxicities was computed in each of the treatment groups. To test the statistical significance of the difference in PR rates and toxicities between the two groups, Chi-square test was used. Kaplan-Meier estimate of survival rate was computed for each group. To test the statistical significance of the difference in survival rate, the log-rank test was applied. RESULTS AND CONCLUSION: The two groups (5 FU/LV vs. capecitabine) were comparable with respect to pathological complete response (20% vs. 24%), pathological downstaging (76% vs. 69%), sphincter preservation rates, and acute complication rates. Both regimens were well tolerated. Overall survival and disease-free survival also did not show a statistically significant difference between the two groups (P values 0.720 and 0.255, respectively). In summary, our analysis showed the equivalence of both regimens in the preoperative CRT setting.