Adjuvant Endocrine Therapy in Premenopausal Women With Hormone Receptor-Positive Early-Stage Breast Cancer: Risk Stratification in a Real-World Setting.

BACKGROUND: Ovarian function suppression (OFS) and hormone therapy (HT) represent an adjuvant option in premenopausal hormone receptor-positive early breast cancer (HR+EBC). The SOFT-TEXT trials showed improved outcomes upon receiving aromatase inhibitors (AIs)/OFS. METHODS: In order to estimate the magnitude of absolute improvements, we conducted a retrospective study applying composite risk (CR) to 237 premenopausal HR+EBC patients. RESULTS: Overall, 119 of these received tamoxifen (T)/OFS and 118 received AIs/OFS. The median age was 45 years (ys). After a median follow up of 65 months, recurrence was 6.7% in T patients and 10.2% in AI ones. CR (cutoff: 2.67) and ET duration (five-year cutoff) was found to have a significant impact on DFS. Invasive disease-free survival (IDFS) at 5 ys amounted to 82.9% for a CR>2.67 and 95% with CR

Multicentre match-paired analysis of advanced biliary cancer long-term survivors: The BILONG study.

BACKGROUND: Advanced biliary cancers (ABC) are aggressive malignancies with a median overall survival (mOS) <12 months when treated with first-line chemotherapy. Nevertheless, a subset of patients experiencing longer survival has been described in the updated analysis of ABC-02 trial. We aimed to provide a real-world description of ABC long-term survivors (LS), identifying which factors impact on survival. METHODS: Patients diagnosed with ABC at three Institutions between 2002 and 2019, and who survived ≥18 months, were retrospectively identified. We compared them with a control cohort (C) with a mOS <18 months, matched on age, gender, ECOG PS, disease status, primary tumor site, prior surgery, and treatment modality. Their clinical features, treatments, and outcome were analyzed. RESULTS: A total of 78 patients was included, 39 in each group. Both LS and C cohorts had superimposable baseline characteristics, without significant differences. mOS was 29 (95%CI 24.6-33.5) and 9 months (95%CI 6.6-12.9) in the two groups, respectively. After performing a logistic regression analysis, three factors were significantly associated with long-term outcome: low neutrophil-to-lymphocyte ratio (NLR < 3) (Odds Ratio [OR] 0.38), achievement of objective response to treatment (OR 0.16), and the number of lines received (OR 0.29). CONCLUSIONS: We described a considerable subset of ABC experiencing long-term survival with conventional chemotherapy in a real-world scenario. Beyond clinical factors, we identified low NLR as a prognostic determinant that may allow for a more accurate selection of long survivors. While waiting for a deeper molecular characterization of this subgroup, we propose NLR as a stratification factor for daily practice and clinical trials.

Third-line chemotherapy in advanced biliary cancers (ABC): pattern of care, treatment outcome and prognostic factors from a multicenter study.

OBJECTIVES: Here, we aim at describing the pattern of care, survival outcome and prognostic factors of ABC patients (pts) receiving third-line chemotherapy. METHODS: Institutional registries across three academic medical centers were retrospectively reviewed. Kaplan-Meier estimators were used to calculate survival, the log-rank test to make comparisons, and the Cox proportional hazard models to assess the progostic impact of variables. RESULTS: Among 101 pts included in the analysis. 68 (67.3%), 19 (18.8%) and 14 (13.8%) had intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer, respectively. Atotal of 63 (62.3%) pts received monochemotherapy, while 38 (37.6%) were treated with adoublet. The median OS and PFS were 5 and 3 months, respectively. Disease control rate was achieved in 23 (22.7%) pts, with 2 (2%) partial responses. Grade 3-4 treatment-related adverse events were reported in 22 (21.7%) pts. At multivariate analysis, ECOG PS (p < 0.001), tumor burden (p = 0.01) and lymphocyte-to-monocyte ratio (p =0.02) were independent predictors of survival. CONCLUSIONS: Third-line chemotherapy displayed limited activity in this real-world cohort, although prognostic factors have been identified that may assist in treatment decision. The results of this multicenter experience, highlight the need for more effective therapies and provide a benchmark for future trials in this setting.

mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus.

BACKGROUND: Everolimus (Eve), which is a mammalian target of Rapamicin (mTOR) inhibitor, is part of the therapeutic armamentarium of neuroendocrine tumors (NETs). Currently, there are no validated biomarkers predicting Eve efficacy in NETs. In this study, we explore whether the expression of phosphorilated (p)-mTOR and p70S6-kinase (S6K), a downstream effector of mTOR, correlates with the outcome of patients with NET that were treated with Eve. METHODS: Tissue specimens that were derived from NETs treated with Eve at our Institution were examined for the expression levels of p-mTOR and p-S6K by immunohistochemistry. Response rate (RR), progression-free survival (PFS), and overall survival (OS) were analyzed in two groups: p-mTOR/p-S6K positive (group 1) and p-mTOR/p-S6K negative (group 2). Univariate and multivariate Cox regression analysis were performed. RESULTS: Twenty-four patients with advanced NETs that were treated with Eve were included in the analysis. Eight out 24 (33.3%) patients were both p-mTOR and p-S6K positive. A better median PFS and OS in group 1 (18.2 and 39.9 months) as compared to group 2 (13 and 32.4 months) was depicted, with a toxicity profile that was comparable with data literature. CONCLUSIONS: Our study suggests that the activation of mTOR pathway can predict better outcomes in patients with NET treated with Eve. However, these results warrant further confirmation in a prospective setting.

Nivolumab-Induced Impressive Response of Refractory Pulmonary Sarcomatoid Carcinoma with Brain Metastasis.

BACKGROUND: Pulmonary sarcomatoid carcinoma is a rare, poorly differentiated, and highly aggressive type of non-small cell lung cancer. High tumor mutational burden and PD-L1 overexpression make it an excellent candidate for immunotherapy. OBJECTIVES AND METHOD: We presented the case of a patient who underwent left inferior lobectomy with concurrent right paravertebral muscular metastasectomy for an infiltrative neoplastic mass, whose final diagnosis was consistent with stage IV pulmonary sarcomatoid carcinoma. He received first- and second-line chemotherapy without any benefit. Since March 2016, he has been treated with the anti-PD1 agent nivolumab with a dramatic improvement of symptoms, disappearance of a brain lesion, and partial response on other metastatic sites. He tolerated the treatment well and is still responding after 22 months from the beginning. RESULTS AND CONCLUSIONS: In very lethal non-small cell lung cancer subtypes such as the sarcomatoid variants, high tumor burden and deteriorated general conditions should not preclude, at least in some cases, the use of immunotherapy. Anti-PD1 may also have a reliable role in disease control in the brain. Lastly, the strong rationale behind sarcomatoid histology should further prompt trials exploring immunotherapeutic approaches in this subset of non-small cell lung cancer.

Metronomic Capecitabine Effectively Blocks Leptomeningeal Carcinomatosis From Breast Cancer: A Case Report and Literature Review.

BACKGROUND Meningeal carcinomatosis is a rare complication in breast cancer patients. At present, there are no defined guidelines for its management. The efficacy of systemic treatment seems to depend on its ability to cross the blood-brain-barrier and its interaction with tumor vasculature. Metronomic chemotherapy is a known modality of drug administration able to inhibit tumor angiogenesis. CASE REPORT We present a case of symptomatic leptomeningeal carcinomatosis from breast cancer successfully treated with capecitabine. Based on the hypothesis that angiogenesis contributes to neoplastic meningitis, the patient was treated with a metronomic schedule that provided long-term clinical benefit with a very low toxicity profile. CONCLUSIONS To assess the real impact of metronomic chemotherapy in patients with meninges involvement, a phase II study will be starting soon in our institution. A review of the literature concerning the management of meningeal carcinomatosis is also presented.

A Dose-finding and Biomarker Evaluation Phase Ib Study of Everolimus in Association With 5-Fluorouracil and Pelvic Radiotherapy as Neoadjuvant Treatment of Locally Advanced Rectal Cancer (E-LARC Study).

BACKGROUND: During the past 20 years, considerable improvement has occurred in the treatment of patients with locally advanced rectal cancer (LARC). With the introduction of multimodal treatment, refinements in preclinical staging and improvements in surgical skills, local relapse is no longer the major problem for patients with LARC. However, many patients die of metastatic disease. The present phase Ib study aimed to establish the maximum tolerated dose of everolimus combined with 5-fluorouracil and radiotherapy in patients with LARC. PATIENTS AND METHODS: Patients were sequentially assigned to 4 cohorts with an increasing dose of everolimus, starting from 14 days before 5-fluorouracil and radiotherapy and continuing throughout concomitant treatment. The secondary endpoints were the Dworak tumor regression grade, pathologic complete response rate, neoadjuvant rectal score, biomarker assessment (phosphorylated mTOR [mammalian target of rapamycin] protein and phosphorylated-p70S6K protein). RESULTS: At the time of this report, 12 patients had been treated, and no dose-limiting toxicity was recorded. The most frequently reported acute toxicities were rectal tenesmus, skin rash, diarrhea, and dysuria. All 12 patients underwent curative R0 resection. Two patients had Dworak tumor regression grade 4 (pathologic complete response). No everolimus-related postoperative complications were observed. No relationship was found between biomarker expression and the clinicopathologic outcomes. CONCLUSION: Although the addition of everolimus did not appear to worsen the toxicity of chemoradiation in patients with LARC, evaluation of its activity deserves further investigation in larger clinical trials.