Sarcopenia in gastric cancer: when the loss costs too much

Sarcopenia is a complex syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength. Malignancy is a major determinant of sarcopenia, and gastric cancer (GC) is among the most common causes of this phenomenon. As sarcopenia is a well-recognized poor prognostic feature in GC and has been associated with worse tolerance of surgical and medical treatments, members of the multidisciplinary team should be aware of the clinical relevance, pathogenic mechanisms, and potential treatments for this syndrome. The importance of sarcopenia is often underestimated in everyday practice and clinical trials, particularly among elderly or fragile patients. As treatment options are improving in all disease stages, deeper knowledge and greater attention to the metabolic balance in GC patients could further increase the benefit of novel therapeutic strategies and dramatically impact on quality of life. In this review, we describe the role of sarcopenia in different phases of GC progression. Our aim is to provide oncologists and surgeons dealing with GC patients with a useful tool for comprehensive assessment and timely management of this potentially life-threatening condition

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

Monocyte-to-lymphocye ratio (MLR) and LDH level in metastatic colorectal cancer (mCRC) patients (pts)

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The IMPACT study: early loss of skeletal muscle mass in advanced pancreatic cancer patients

Abstract Background Pancreatic cancer (PC) patients have multiple risk factors for sarcopenia and loss of skeletal muscle mass (LSMM), which may cause greater treatment toxicities, reduced response to cancer therapy, prolonged hospitalization, impaired quality of life, and worse prognosis. Methods This is a retrospective study on advanced PC patients treated at the Department of Oncology of Udine, Italy, from January 2012 to November 2017. Among 162 patients who received chemotherapy, 94 consecutive patients with an available computed tomography (CT) scan were retrospectively analyzed. The primary objective of our study was to explore if an early LSMM ≥ 10% (measured at first radiological evaluation and compared with baseline) and/or baseline sarcopenia may impact prognosis. Baseline sarcopenia was defined according to Prado's criteria. Skeletal muscle area was measured as cross‐sectional areas (cm2) using CT scan data through the Picture archiving and communication system (PACS) image system. Results In the whole cohort, 48% of patients were ≤70 years old, and 50% had metastatic disease. At baseline, 73% of patients had sarcopenia, and 16% presented a visceral fat area ≥ 44 cm2/m2. Overall, 21% experienced an early LSMM ≥ 10%. Approximately 33% of sarcopenic patients at baseline and ~35% of patients with early LSMM ≥ 10% had a body mass index > 25 kg/m2. Of note, 71% of patients were evaluated by a nutritionist, and 56% received a dietary supplementation (oral and/or parenteral). After a median follow‐up of 30.44 months, median overall survival (OS) was 11.28 months, whereas median progression‐free survival (PFS) was 5.72 months. By multivariate analysis, early LSMM ≥ 10% was significantly associated with worse OS [hazard ratio (HR): 2.16; 95% confidence interval (CI) 1.23–3.78; P = 0.007] and PFS (HR: 2.31; 95% CI 1.30–4.09; P = 0.004). Moreover, an exploratory analysis showed that inflammatory indexes, such as neutrophil–lymphocyte ratio variation, impact early LSMM ≥ 10% (odds ratio 1.31, 95% CI 1.06–1.61, P = 0.010). Conclusions Early LSMM ≥ 10% has a negative prognostic role in advanced PC patients. Further prospective investigations are needed to confirm these preliminary data

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

Biologically driven cut-off definition of lymphocyte ratios in metastatic breast cancer and association with exosomal subpopulations and prognosis

High neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) are respectively associated with systemic inflammation and immune suppression and have been associated with a poor outcome. Plasmatic exosomes are extracellular vesicles involved in the intercellular communication system that can exert an immunosuppressive function. Aim of this study was to investigate the interplay between the immune system and circulating exosomes in metastatic breast cancer (MBC). A threshold capable to classify patients according to MLR, NLR and PLR, was computed through a receiving operator curve analysis after propensity score matching with a series of female blood donors. Exosomes were isolated from plasma by ExoQuick solution and characterized by flow-cytometry. NLR, MLR, PLR and exosomal subpopulations potentially involved in the pre-metastatic niche were significantly different in MBC patients with respect to controls. MLR was significantly associated with number of sites at the onset of metastatic disease, while high levels of MLR and NLR were found to be associated with poor prognosis. Furthermore, exosomal subpopulations varied according to NLR, MLR, PLR and both were associated with different breast cancer subtypes and sites of distant involvement. This study highlights the nuanced role of immunity in MBC spread, progression and outcome. Moreover, they suggest potential interaction mechanisms between immunity, MBC and the metastatic niche

Skeletal metastases from breast cancer: pathogenesis of bone tropism and treatment strategy

Breast cancer (BC) is the most common female cancer worldwide with approximately 10 % of new cases metastatic at diagnosis and 20-50 % of patients with early BC who will eventually develop metastatic disease. Bone is the most frequent site of colonisation and the development of skeletal metastases depends on a complex multistep process, from dissemination and survival of malignant cells into circulation to the actual homing and metastases formation inside bone. Disseminated tumor cells (DTCs) can be detected in bone marrow in approximately 30 % of BC patients, likely reflecting the presence of minimal residual disease that would eventually account for subsequent metastatic disease. Patients with bone marrow DTCs have poorer overall survival compared with patients without them. Although bone-only metastatic disease seems to have a rather indolent behavior compared to visceral disease, bone metastases can cause severe and debilitating effects, including pain, spinal cord compression, hypercalcemia and pathologic fractures. Delivering an appropriate treatment is therefore paramount and ideally it should require interdisciplinary care. Multiple options are currently available, from bisphosphonates to new drugs targeting RANK ligand and radiotherapy. In this review we describe the mechanisms underlying bone colonization and provide an update on existing systemic and locoregional treatments for bone metastases