Development of a technique to detect the activated form of the progesterone receptor and correlation with clinical and histopathological characteristics of endometrioid adenocarcinoma of the uterine corpus.

OBJECTIVE: Hormonal therapy is generally reserved for patients with endometrial cancers that fail cytotoxic chemotherapy, but there is a lack of sufficiently sensitive diagnostics to identify potential responders. We sought to develop a diagnostic technique to detect activated progesterone receptors (APR) in endometrial cancers using routine immunohistochemistry (IHC) and to correlate the presence of APR with other histopathological features and clinical disease stage. METHODS: Seventy-two tumor block specimens from patients with endometrial cancer were processed with conventional IHC methods for estrogen receptor-α (ERα), progesterone receptor (PR) and Ki67, a marker of proliferation. Tumor specimens were analyzed for the PR nuclear distribution patterns in individual tumor cells: APR positive (APR(pos)) tumors were prospectively defined as any tumor with >5% countable malignant cells with an aggregated nuclear pattern. Tumor APR status was analyzed against other biomarkers including ERα expression, Ki67 and tumor grade. RESULTS: Fifty-six of 72 samples were endometrioid. Twenty-six of 49 PR-positive endometrioid tumors (53%; 95% CI 39-67%) were APR(pos). Percent of ER(pos) cells correlated with % PR(pos) malignant cells (p=0.001, rho=0.44). APR positivity did not correlate with % PR(pos) cells in a given tumor, nor did it correlate with % Ki67 positivity; APR positivity was independent of disease stage and tumor grade (p=NS). CONCLUSIONS: In this study, approximately half of endometrioid tumors were APR(pos). APR is independent of histopathological and other known risk factors. Refining conventional PR detection has the potential to prospectively identify patients with endometrial cancer who may benefit from anti-progestin therapy.

A Hangover Under 177 Lu-PSMA-617 Therapy : A Red Flag for Brain 68 Ga-PSMA-11 PET/MRI?

ABSTRACT: Leptomeningeal carcinomatosis in prostate cancer is extremely rare. Because of the low overall penetration of drugs into the brain and the prolonged survival of castration-resistant prostate cancer (CRPC) patients, a special attention should be paid to the appearance of neurological symptoms in long-term CRPC survivors. A patient suffering from a CRPC with bone metastases underwent 4 cycles of 177 Lu-PSMA (prostate-specific membrane antigen)-617. Starting from the third cycle, he reported an increasing feeling of a permanent hangover. A 68 Ga-PSMA-11 brain PET/MRI was carried out after the fourth cycle. It revealed intraparenchymatous brain metastases with intense uptake and evidences of leptomeningeal carcinomatosis.

[MiT family translocation renal cell carcinomas: Natural history, molecular features and multidisciplinary management]. / Les carcinomes du rein à translocation de la famille MiT : histoire naturelle, caractéristiques moléculaire et prise en charge multidisciplinaire.

MiT family translocation renal cell carcinomas (tRCC) represent a rare subtype of renal cell carcinomas. These tumors have been introduced for the first time in the World Health Classification (WHO) classification of kidney cancers in 2004. tRCC are characterized by reccurent translocations involving members of the MiT family transcription factors, mainly TFE3 and TFEB. The estimated incidence of these tumors is ∼1-5 % among all renal cell carcinomas, with female prodominance. tRCC were initially described in children, and the spectrum has been expanded over time to encompass adolescents and adults. TFE3- and TFEB-rearranged RCC harbor characteristic clinicopathological and immunohistochemical features and fluorescent hybridization in situ is considered the gold standard for their diagnosis, although it has some limitations especially when the partners are located in the vicinity of TFE3. Nephron-sparing surgery is an efficient treatment of localized cases when achievable. In metastatic setting, targeted agents and immunotherapy showed modest efficacy, with response rates and median overall survival inferior to those observed in clear-cell renal cell carcinomas. Management of tRCC necessite a multidisciplinary team and accrual in clinical trials have to be encouraged when possible. Novel biological insights are urgently awaited to better understand the mechanisms associated with kidney oncogenesis in this setting, and ultimately help to identify therapeutic targets.

Impact of early palliative care on overall survival of patients with metastatic upper gastrointestinal cancers treated with first-line chemotherapy: a randomised phase III trial.

INTRODUCTION: Palliative care (PC) has usually been offered at the end-of-life stage, although the WHO recommends providing PC as early as possible in the course of the disease. A recent study has shown that early PC (EPC) provides a more meaningful effect on quality of life and, surprisingly, on overall survival (OS) than standard treatment for patients with metastatic lung cancer. Whether EPC benefits also apply to patients with metastatic upper gastrointestinal (GI) cancers is unknown. METHODS AND ANALYSIS: EPIC is a randomised phase III trial comparing EPC plus standard oncologic care versus standard oncologic care in patients with metastatic upper GI cancers. Its primary objective is to evaluate the efficacy of EPC in terms of OS. Its secondary objectives are to assess the effects of EPC on patient-reported outcomes (quality of life, depression and anxiety) and the effect of EPC on the number of patients receiving chemotherapy in their last 30 days of life. Assuming an exponential distribution of survival time, 381 deaths are required to ensure an 80% power for an absolute difference of 10% in 1 year OS rates (40% vs 50.3%, HR=0.75; log rank test two-sided alpha=5%), leading to a planned sample size of 480 patients enrolled over 3 years and a final analysis at 4 years. The main analysis will be performed on the intent-to-treat dataset. ETHICS AND DISSEMINATION: This study was approved by the 'Comité de Protection des Personnes Nord-Ouest I' (4 April 2016), complies with the Helsinki declaration and French laws and regulations and follows the International Conference on Harmonisation E6 (R1) Guideline for Good Clinical Practice. The trial results, even if they are inconclusive, will be presented at international oncology congresses and published in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: EudraCT: 2015-A01943-46; Pre-results. NCT02853474.