Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial.

Germline mutations in BRCA1/2 predispose individuals to breast cancer (termed germline-mutated BRCA1/2 breast cancer, gBRCA-BC) by impairing homologous recombination (HR) and causing genomic instability. HR also repairs DNA lesions caused by platinum agents and PARP inhibitors. Triple-negative breast cancers (TNBCs) harbor subpopulations with BRCA1/2 mutations, hypothesized to be especially platinum-sensitive. Cancers in putative 'BRCAness' subgroups-tumors with BRCA1 methylation; low levels of BRCA1 mRNA (BRCA1 mRNA-low); or mutational signatures for HR deficiency and those with basal phenotypes-may also be sensitive to platinum. We assessed the efficacy of carboplatin and another mechanistically distinct therapy, docetaxel, in a phase 3 trial in subjects with unselected advanced TNBC. A prespecified protocol enabled biomarker-treatment interaction analyses in gBRCA-BC and BRCAness subgroups. The primary endpoint was objective response rate (ORR). In the unselected population (376 subjects; 188 carboplatin, 188 docetaxel), carboplatin was not more active than docetaxel (ORR, 31.4% versus 34.0%, respectively; P = 0.66). In contrast, in subjects with gBRCA-BC, carboplatin had double the ORR of docetaxel (68% versus 33%, respectively; biomarker, treatment interaction P = 0.01). Such benefit was not observed for subjects with BRCA1 methylation, BRCA1 mRNA-low tumors or a high score in a Myriad HRD assay. Significant interaction between treatment and the basal-like subtype was driven by high docetaxel response in the nonbasal subgroup. We conclude that patients with advanced TNBC benefit from characterization of BRCA1/2 mutations, but not BRCA1 methylation or Myriad HRD analyses, to inform choices on platinum-based chemotherapy. Additionally, gene expression analysis of basal-like cancers may also influence treatment selection.

Changes in primary breast cancer heterogeneity may augment midtreatment MR imaging assessment of response to neoadjuvant chemotherapy.

PURPOSE: To evaluate whether changes in magnetic resonance (MR) imaging heterogeneity may aid assessment for pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in primary breast cancer and to compare pCR with standard Response Evaluation Criteria in Solid Tumors response. MATERIALS AND METHODS: Institutional review board approval, with waiver of informed consent, was obtained for this retrospective analysis of 36 consecutive female patients, with unilateral unifocal primary breast cancer larger than 2 cm in diameter who were receiving sequential anthracycline-taxane NACT between October 2008 and October 2012. T2- and T1-weighted dynamic contrast material-enhanced MR imaging was performed before, at midtreatment (after three cycles), and after NACT. Changes in tumor entropy (irregularity) and uniformity (gray-level distribution) were determined before and after MR image filtration (for different-sized features). Entropy and uniformity for pathologic complete responders and nonresponders were compared by using the Mann-Whitney U test and receiver operating characteristic analysis. RESULTS: With NACT, there was an increase in uniformity and a decrease in entropy on T2-weighted and contrast-enhanced subtracted T1-weighted MR images for all filters (uniformity: 23.45% and 22.62%; entropy: -19.15% and -19.26%, respectively). There were eight complete pathologic responders. An area under the curve of 0.84 for T2-weighted MR imaging entropy and uniformity (P = .004 and .003) and 0.66 for size (P = .183) for pCR was found, giving a sensitivity and specificity of 87.5% and 82.1% for entropy and 87.5% and 78.6% for uniformity compared with 50% and 82.1%, respectively, for tumor size change for association with pCR. CONCLUSION: Tumors become more homogeneous with treatment. An increase in T2-weighted MR imaging uniformity and a decrease in T2-weighted MR imaging entropy following NACT may provide an earlier indication of pCR than tumor size change.

Anal carcinomas: the role of endoanal ultrasound and magnetic resonance imaging in staging, response evaluation and follow-up.

Anal carcinoma is an important but rare condition, managed in specialist centres. Both endoanal ultrasound and magnetic resonance imaging (MRI) can be used in the locoregional staging and follow-up of patients with anal cancer, and both may assist in treatment planning and prognosis. Recent guidelines published by the European Society for Medical Oncology have recommended MRI as the technique of choice for assessment of locoregional disease. This paper describes the techniques for both endoanal ultrasound and MRI, and compares the relative merits and disadvantages of each in the local assessment of anal carcinoma.

MR imaging features of vaginal malignancies.

Primary vaginal malignancies are rare, accounting for only 1%-2% of all gynecologic malignancies. Squamous cell carcinoma makes up about 85% of primary vaginal malignancies. This tumor characteristically arises from the posterior wall of the upper third of the vagina. The main patterns of disease are an ulcerating or fungating mass or an annular constricting lesion. At magnetic resonance (MR) imaging, squamous cell carcinoma has intermediate signal intensity on T2-weighted images and low signal intensity on T1-weighted images. The tumors that account for the remaining 15% of primary vaginal malignancies are adenocarcinoma, melanoma, and sarcomas. The signal intensity characteristics on MR images correlate with the histologic subtypes and reflect the MR imaging appearances of these histologic subtypes elsewhere in the body. Secondary malignancy of the vagina is far more frequent than primary vaginal malignancy. Most vaginal metastases occur by means of direct local spread from the cervix, uterus, or rectum. The MR imaging appearances of these metastases reflect the MR imaging appearances of the primary tumor.

Development of a purpose built landfill system for the control of methane emissions from municipal solid waste.

In the present paper, a new system of purpose built landfill (PBLF) has been proposed for the control of methane emissions from municipal solid waste (MSW), by considering all favourable conditions for improved methane generation in tropical climates. Based on certain theoretical considerations multivariate functional models (MFMs) are developed to estimate methane mitigation and energy generating potential of the proposed system. Comparison was made between the existing waste management system and proposed PBLF system. It has been found that the proposed methodology not only controlled methane emissions to the atmosphere but also could yield considerable energy in terms of landfill gas (LFG). Economic feasibility of the proposed system has been tested by comparing unit cost of waste disposal in conventional as well as PBLF systems. In a case study of MSW management in Mumbai (INDIA), it was found that the unit cost of waste disposal with PBLF system is seven times lesser than that of the conventional waste management system. The proposed system showed promising energy generation potential with production of methane worth of Rs. 244 millions/y ($5.2 million/y). Thus, the new waste management methodology could give an adaptable solution for the conflict between development, environmental degradation and natural resources depletion.