Challenging Endocrine Sensitivity of Hormone Receptor-Positive/HER2-Negative Advanced Breast Cancer with the Combination of Eribulin and Endocrine Therapy: The REVERT Study.

BACKGROUND: Luminal advanced breast cancer (ABC) patients eventually progress on endocrine therapy. REVERT aimed to explore whether eribulin could restore endocrine sensitivity in a randomized, non-comparative phase II trial. METHODS: Aromatase inhibitor (AI)-resistant patients with luminal ABC were randomized 1:1 to receive eribulin +/- AI. Patients were stratified by prior cyclin-dependent kinases 4/6 inhibitor (CDK4/6i) treatment. The primary endpoint was an investigator-assessed overall response rate (ORR) according to RECIST version 1.1 in the eribulin + AI arm. An interim analysis was planned with 11 evaluable patients according to a two-stage Simon design. RESULTS: Twenty-two patients were enrolled (15 eribulin + AI arm; 7 eribulin arm). The trial was terminated early in March 2021, with eight (36.4%) patients still on treatment. ORR was 26.7% in the eribulin + AI arm (95% CI, 7.8-55.1%; p = 0.0541). In the eribulin arm, two (28.6%) patients had an objective response (95% CI, 3.7-71.0%). The difference between the study arms was not significant (p = 0.918). The addition of AI to eribulin also failed to show improvement in other efficacy endpoints. A significant interaction between the treatment arm and previous CDK4/6i treatment was observed for ORR (p = 0.018) and progression-free survival (p = 0.084). Overall, the toxicity profile was consistent with the known safety profile of eribulin. No treatment-related deaths were reported. CONCLUSION: Eribulin + AI does not seem to improve outcomes compared with eribulin monotherapy in patients with AI-resistant luminal ABC. This chemo-endocrine approach deserves further investigation after progression to CDK4/6i-based therapy.

SEOM-TTCC clinical guideline in nasopharynx cancer (2021).

Nasopharyngeal carcinoma (NPC) is distinct from other cancers of the head and neck in biology, epidemiology, histology, natural history, and response to treatment. Radiotherapy (RT) is the cornerstone of locoregional treatment of non-disseminated disease and the association of chemotherapy improves the rates of survival. In the case of metastatic disease stages, treatment requires platinum/gemcitabine-based chemotherapy and patients may achieve a long survival time.

Prognosis Value of Immunoregulatory Molecules in Oral Cancer Microenvironment: An Immunohistochemical Study.

OBJECTIVES: To evaluate the relationship of the immune-checkpoint PD-1/PD-L1 with the clinical evolution of OSCC; to assess survival in OSCC based on the characteristics of TME and histologic risk score; to evaluate the clinical and histopathological relationship of OSCC with immunological TME. MATERIAL AND METHODS: A retrospective study was carried out on 65 samples from patients with OSCC on the floor of the mouth or tongue. Clinicopathological variables and the expression of the biomarkers PD-1, PD-L1, FoxP3, CD4, CD8, CSF1R, and p16 were recorded. The relationship of the clinical and histological variables with the expression of the biomarkers and survival was studied. RESULTS: The univariate and multivariate analysis indicated that positive PD-1 expression was an independent protective factor for survival (overall, disease-free, disease-specific survival) and that high PD-L1 also improved survival. Poorly differentiated histological grades and metastasis were associated with a worse prognosis. CONCLUSIONS: PD-1 is a protective survival factor that is maintained independently of PD-L1 expression. High values of PD-L1 expression also improve survival. Higher expression of PD-1 is observed in smaller tumors, and higher expression of PD-L1 is more likely in women. No relationship between the tumor microenvironment and histologic risk score was found to influence the survival patterns studied in the OSCC. There is no evidence of a relationship between the histopathological features and the studied markers, although the positive PD-1 and PD-L1 cases have a lower risk of a high WPOI score, and positive PD-1 expression was associated with a lower DOI.

An Unusual Case of Hypopituitarism as an Adverse Effect of Vandetanib and Remission of Breast Metastases in a Patient with Medullary Thyroid Cancer.

INTRODUCTION: Tyrosine kinase inhibitors have been a breakthrough in the treatment of advanced medullary thyroid cancer (MTC), and they can prolong progression-free survival (PFS). CASE PRESENTATION: A patient with MTC and metastatic spread to the lymph nodes, lungs, bones, breast, and cerebellum started treatment with vandetanib. During treatment, she developed secondary adrenal insufficiency and hypogonadotropic hypogonadism. After 9 years of vandetanib therapy, the disease has not progressed and the patient maintains a complete response of the breast metastases and a partial response of the other metastatic lesions. CONCLUSION: To our knowledge, this is the first reported case of secondary adrenal insufficiency and hypogonadotropic hypogonadism related to therapy with vandetanib. Moreover, the prolonged PFS and the complete disappearance of some of the metastatic lesions in this patient are truly unusual.

mTOR pathway inhibition in renal cell carcinoma.

Renal cell carcinoma therapy has changed in a very significant way in the last few years. Up to 5 new agents have been developed, improving the results previously achieved with cytokine therapy. Bevacizumab, sorafenib, sunitinib, temsirolimus, and everolimus are now part of the therapeutic arsenal for this illness. Particularly, this has been the first tumoral type in which inhibition of mammalian target of rapamycin (mTOR) has proved its efficacy in phase III trials, either as first-line therapy for poor prognosis patients (temsirolimus, CCI-779) or as second-line therapy after failure of tyrosine-kinase inhibitors (everolimus, RAD001). In this paper, we review the basis for mTOR inhibition in RCC, and discuss the results of the trials involving temsirolimus and everolimus for the treatment of this disease.

Cirrhosis-like radiological pattern in patients with breast cancer.

INTRODUCTION: Hepatic toxicity of breast cancer therapy is well known, usually consisting of elevation in the serum levels of hepatic enzymes or fatty infiltration of the liver. The chemotherapeutic agents most commonly linked to hepatotoxic effects are methotrexate, anthracyclines, taxanes and cyclophosphamide. There are few reports of patients with liver metastasis having radiological findings mimicking cirrhosis, both in the presence or the absence of prior systemic chemotherapy. Hepatotoxicity of antineoplastic drugs and cellular necrosis induced by response of liver metastases to chemotherapy may play a critical role in its physiopathology. MATERIALS AND METHODS: This article reports a series of ten women with breast cancer (nine with liver metastasis) treated with chemotherapy or hormonotherapy. RESULTS: They had low risk factors for hepatic disease, but developed a cirrhosis-like appearance in the computed tomography scan. The patient without liver metastasis is the second of this kind described in the literature. Relatively few reports have documented clinical sequelae of portal hypertension. In our series, three patients had oesophageal bleeding varices needing be hospitalised. To our knowledge, these are the first cases reported in the literature. CONCLUSIONS: This suggests that some manifestations of portal hypertension may develop in association with the cirrhosis- like pattern induced by breast cancer therapy.