Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Oral cancer among patients under the age of 35 years

BACKGROUND: Cancer of the oral cavity is one of the commonest cancers among males. AIMS: To assess the aetiological factors, patient characteristics, treatment and the outcome in young patients with oral cancer. SETTINGS AND DESIGN: A retrospective descriptive study of patients under the age of 35 years with cancer of the oral cavity treated between 1982-1996, with the last follow-up till 2001, using the tumour registry data of Regional Cancer Centre (RCC), Trivandrum, Kerala, India. SUBJECT AND METHOD: The detailed clinical, treatment and follow-up data were obtained from the computerised records of RCC and recorded on a preset proforma. This was analysed with emphasis on age, sex, risk factors, site, histology, clinical extent and treatment methods and survival in the study group. STATISTICAL ANALYSIS: The survival analysis was carried by Kaplan-Meier method and the difference in survival was analysed using log-rank test. RESULTS: Out of 264 patients analysed, tongue was the commonest site identified in 136 (52%) patients followed by buccal mucosa in 69 (26%) patients. A male female ratio of 2.3:1 was observed with a significantly higher male preponderance in buccal mucosa (4.3:1). Prior exposure to tobacco or alcohol was noted in 59.4% patients, with more habitués in buccal mucosa cancer. Histological confirmation was present only in 83.7% patients and among them most were squamous cell carcinoma (85.9%). Radiotherapy, surgery or combined modalities of treatment were employed for majority of patients. The 5-year survival was 57.3%. T stage of the tumour was found to be significant in predicting disease free survival (P=0.03). CONCLUSIONS: The importance of early detection for clinical down staging is stressed. There is a need to investigate the aetiology of intra oral cancers in younger patients since a significant proportion (almost 40%) of these patients do not have associated risk factors for cancer

Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

© 2014 Elsevier Inc. Recent genomic analyses of pathologically defined tumor types identify 'within-a-tissue' disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-oforigin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pancancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)