Primary Tumor Resection for Metastatic Colorectal, Gastric and Pancreatic Cancer Patients: In Search of Scientific Evidence to Inform Clinical Practice

The management of the primary tumor in metastatic colorectal, gastric and pancreatic cancer patients may be challenging. Indeed, primary tumor progression could be associated with severe symptoms, compromising the quality of life and the feasibility of effective systemic therapy, and might result in life-threatening complications. While retrospective series have suggested that surgery on the primary tumor may confer a survival advantage even in asymptomatic patients, randomized trials seem not to definitively support this hypothesis. We discuss the evidence for and against primary tumor resection for patients with metastatic gastrointestinal (colorectal, gastric and pancreatic) cancers treated with systemic therapies and put in context the pros and cons of the onco-surgical approach in the time of precision oncology. We also evaluate current ongoing trials on this topic, anticipating how these will influence both research and everyday practice

Neutrophil-to-lymphocyte and lymphocyte-to-monocyte ratios in breast cancer

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Immunotherapy for colorectal cancer: where are we heading?

Introduction: In the last few years, significant advances in molecular biology have provided new therapeutic options for colorectal cancer (CRC). The development of new drugs that target the immune response to cancer cells seems very promising and has already been established for other tumor types. In particular, the use of immune checkpoint inhibitors seems to be an encouraging immunotherapeutic strategy. Areas covered: In this review, the authors provide an update of the current evidence related to this topic, though most immunotherapies are still in early-phase clinical trials for CRC. To understand the key role of immunotherapy in CRC, the authors discuss the delicate balance between immune-stimulating and immune-suppressive networks that occur in the tumor microenvironment. Expert opinion: Modulation of the immune system through checkpoint inhibition is an emerging approach in CRC therapy. Nevertheless, selection criteria that could enable the identification of patients who may benefit from these agents are necessary. Furthermore, potential prognostic and predictive immune biomarkers based on immune and molecular classifications have been proposed. As expected, additional studies are required to develop biomarkers, effective therapeutic strategies and novel combinations to overcome immune escape resistance and enhance effector response

Do platinum salts fit all triple negative breast cancers?

Triple-negative breast cancer (TNBC) is an aggressive disease with limited treatment options and poor prognosis once metastatic. Pre-clinical and clinical data suggest that TNBC could be more sensitive to platinum-based chemotherapy, especially among BRCA1/2-mutated patients. In recent years, several randomised trials have been conducted to evaluate platinum efficacy in both early-stage and advanced TNBC, with conflicting results especially for long-term outcomes. Experimental studies are now focusing on identifying biomarkers of response to help selecting patients who may benefit most from platinum-based therapies, including BRCA1/2 mutational status and genomic instability signatures (such as HRD-LOH or HRD-LST scores). A standard therapy for TNBC is still missing and platinum-based regimens represent an emerging therapeutic option for selected patients with a defect in the homologous recombination repair system. The identification of these patients through validated biomarker assays will be crucial to optimize the use of currently approved agents in TNBC

A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring

Lenvatinib (LENVA) is an oral antineoplastic drug used for the treatment of hepatocellular carcinoma and thyroid carcinoma. LENVA therapeutic drug monitoring (TDM) should be mandatory for a precision medicine to optimize the drug dosage. To this end, the development of a sensitive and robust quantification method to be applied in the clinical setting is essential. The aim of this work was to develop and validate a sensitive, rapid, and cost-effective LC-MS/MS method for the quantification of LENVA in human plasma. On this premise, sample preparation was based on a protein precipitation and the chromatographic separation was achieved on a Synergi Fusion RP C18 column in 4 min. The method was completely and successfully validated according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines, with good linearity in the range of 0.50–2000 ng/mL (R≥0.9968). Coefficient of variation (CV) for intra- and inter-day precision was ≤11.3% and accuracy ranged from 96.3 to 109.0%, internal standard normalized matrix effect CV% was ≤2.8% and recovery was ≥95.6%. Successful results were obtained for sensitivity (signal to noise (S/N) ratio >21) and selectivity, dilution integrity (CV% ≤ 4.0% and accuracy 99.9–102%), and analyte stability under various handling and storage conditions both in matrix and solvents. This method was applied to quantify LENVA in patient’s plasma samples and covered the concentration range achievable in patients. In conclusion, a sensitive and robust quantification method was developed and validated to be applied in the clinical setting

Pattern of metastasis and outcome in patients with breast cancer

There is growing evidence about differences in metastatic spread among breast cancer (BC) biologic subtypes (BS). Aim of this study was to analyze the pattern of metastasization according to BS and to explore the corresponding prognosis. A series of 544 consecutive patients receiving anticancer therapy for metastatic BC from 2004 to 2013, was analyzed. BS were defined by immunohistochemistry according to St Gallen 2013 criteria. Association between BS and the different distant localizations was analyzed. Prognosis was described in terms of overall survival (OS), progression free survival (PFS) and post progression survival (PPS). Results were reported taking luminal A BC as reference. Triple negative BC showed a higher tropism for lung (OR 4.30 95% CI 1.41-13.1), while non luminal HER2 subtype was associated with a higher rate of liver metastases (OR 3.61 95% CI 1.36-9.58). All subtypes were associated with a lower risk of bone-only localization. Central nervous system (CNS) involvement was more common in HER2 positive BC (OR 6.3, 95% CI 1.08-36.66). Liver, lung and CNS involvement influenced negatively OS (HR 1.64, 95% CI 1.29-2.07; HR 1.49, 95% CI 1.18-1.90; HR 2.891, 95% CI 1.85-4.51, respectively) and PFS (HR 1.39, 95% CI 1.13-1.71; HR 1.26, 95% CI 1.02-1.55; HR 1.75, 95% CI 1.12-2.71, respectively). Multivariate analysis confirmed liver involvement as independent predictor of worse OS (HR 1.64, 95% CI 1.15-2.34). Stratification by metastatic pattern showed significant differences in terms of PPS but not in terms of PFS. The study suggests that BS may be characterized by typical patterns of metastatic spread and have different impact on clinical outcome

Systemic Treatments for Advanced Small Bowel Adenocarcinoma: A Systematic Review

Small bowel adenocarcinoma (SBA) is a rare disease for which scarce evidence is available. We summarized data available on systemic treatment of advanced SBA. Methods: Scientific literature was evaluated to find phase II or phase III clinical trials on systemic treatment for advanced SBA. MeSH terms were selected and combined for the initial search, then inclusion and exclusion criteria were set in a search protocol. Four medical oncologists looked for evidence on Medline, EMBASE and Cochrane databases. Moreover, abstracts from 2016 to June 2021 from the American Society for Clinical Oncology, European Society for Medical Oncology, Gastrointestinal Cancer Symposium and World Congress on Gastrointestinal Cancer were browsed. The selected studies, matching the inclusion and exclusion criteria, were finally tabulated and analyzed. Results: The trials finally selected were 18 phase II/III clinical trials. Four small phase II trials support the activity of oxaliplatin-based doublets in first-line treatment (CAPOX and mFOLFOX). Conclusion: No good level evidence is available on the use of bevacizumab, anti-epidermal growth factor receptor, targeted agents or immunotherapy. First-line treatments are largely derived from colorectal cancer protocols, mainly oxaliplatin-based doublets

Epstein-Barr virus BART microRNAs in EBV- associated Hodgkin lymphoma and gastric cancer

Background: EBV produces miRNAs with important functions in cancer growth, tumor invasion and host immune surveillance. The discovery of EBV miR-BARTs is recent, and most of their functions are still unknown. Nonetheless, some new studies underline their key roles in EBV-associated malignancies. Main body: In EBV-associated tumors, the expression profile of miR-BARTs varies according to the cell type, autophagic process and signals received from the tumor microenvironment. By the same way of interest is the interaction between tumor cells and the tumor environment by the release of selected EBV miR-BARTs in addition to the tumor proteins trough tumor exosomes. Conclusion: In this review, we discuss new findings regarding EBV miR-BARTs in Hodgkin lymphoma and gastric cancer. The recent discovery that miRNAs are released by exosomes, including miR-BARTs, highlights the importance of tumor and microenvironment interplay with more specific effects on the host immune response