This study confirmed the prognostic role of NLR in mCRC pts treated with bevacizumab plus chemotherapy in the first line, showing the worse prognosis of pts with high NLR. The advantage of the triplet is independent of NLR at baseline.

Pancreatic cancer is one of the leading causes of cancer death worldwide. Its high mortality rate has remained unchanged for years. Radiotherapy and surgery are considered standard treatments in early and locally advanced stages. Chemotherapy is the only option for metastatic patients. Two treatment regimens, i. e. the association of 5-fluorouracil-irinotecan-oxaliplatin (FOLFIRINOX) and the association of nabpaclitaxel with gemcitabine, have been shown to improve outcomes for metastatic pancreatic adenocarcinoma patients. However, there are not standardized predictive biomarkers able to identify patients who benefit most from treatments. CA19-9 is the most studied prognostic biomarker, its predictive role remains unclear. Other clinical, histological and molecular biomarkers are emerging in prognostic and predictive settings. The aim of this review is to provide an overview of prognostic and predictive markers used in clinical practice and to explore the most promising fields of research in terms of treatment selection and tailored therapy in pancreatic cancer.

Background: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need. Methods: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. The complete blood count before the first cycle of therapy was assessed by calculating neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI). Clinical factors included pre-treatment International Metastatic RCC Database Consortium (IMDC) score, line of therapy, and metastatic sites. Results: From October 2015 to November 2019, 571 mRCC patients received nivolumab as second- and further-line treatment in 69% and 31% of cases. In univariable and multivariable analyses all inflammatory indices, IMDC score, and bone metastases significantly correlated with overall survival (OS). The multivariable model with NLR, IMDC score, and bone metastases had the highest c-index (0.697) and was chosen for the developing of the score (Schneeweiss scoring system). After internal validation (bootstrap re-sampling), the final index (Meet-URO score) composed by NLR, IMDC score, and bone metastases had a c-index of 0.691. It identified five categories with distinctive OSs: group 1 (median OS – mOS = not reached), group 2 (mOS = 43.9 months), group 3 (mOS = 22.4 months), group 4 (mOS = 10.3 months), and group 5 (mOS = 3.2 months). Moreover, the Meet-URO score allowed for a fine risk-stratification across all three IMDC groups. Conclusion: The Meet-URO score allowed for the accurate stratification of pretreated mRCC patients receiving nivolumab and is easily applicable for clinical practice at no additional cost. Future steps include its external validation, the assessment of its predictivity, and its application to first-line combinations.

Introduction In the last decades, the therapeutic decision-making approach to metastatic renal cell cancer (mRCC) has dramatically changed thanks to the introduction in the treatment scenario of, first, anti-angiogenic agents and, afterward, immune-checkpoint inhibitors (ICIs). Immunotherapy is now the standard of care in pretreated mRCC patients and has recently entered even the first line setting. Nevertheless, in mRCC as well as in other tumor settings, a durable and clinically meaningful benefit from treatment with ICIs is not obtained for all patients treated. Therefore, the necessity to identify and validate predictive biomarkers of response to immunotherapy has emerged, in order to design the optimal treatment strategy for mRCC patients. Discussion In this review, we present and discuss the most promising predictive biomarkers of response to ICIs in mRCC with the recent data available. In details, the first marker that was investigated is the immunohistochemical expression of programmed death receptor ligand 1 (PD-L1), showing a negative prognostic role in mRCC, but the debate about its potential predictive value is still open. Additionally, the high heterogeneity in PD-L1 determination methods adds complexity to this issue. Second, the tumor mutational or neoantigen burden is an emerging biomarker of increased response to immunotherapy, hypothesizing that the higher the TMB, the higher is the production of neoantigens, and thus the stimulation of anti-tumor immune response, even though controversial results have been obtained. Third, the tumor microenvironment, namely the different populations of the immune infiltrate, plays a key role in tumor progression and in the response to immunotherapy. Finally, several studies have collected evidence on the potential association of the occurrence of immune-related adverse events (irAEs) with the benefit from ICIs, first in non-small cell lung cancer (NSCLC) and melanoma, and recently even in mRCC. Conclusion Several promising biomarkers of response to immunotherapy with ICIs have been identified, though without conclusive results upon their potential predictive value in mRCC. Therefore, the results of the exploratory analyses of the recently presented first-line trials and hopefully of future prospective, biomarker-driven studies could provide useful tools to be applied in the everyday clinical practice.

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