Malnutrition and muscle wasting are frequently reported in cancer patients, either linked to the tumor itself or caused by oncologic therapies. Understanding the value of nutritional care during cancer treatment remains crucial. In fact, cancer-associated sarcopenia plays a key role in determining higher rates of morbidity, mortality, treatment-induced toxicities, prolonged hospitalizations and reduced adherence to anticancer treatment, worsening quality of life and survival. Planning baseline screening to intercept nutritional troubles earlier, organizing timely reassessments, and providing adequate counselling and dietary support, healthcare professional may positively interfere with this process and improve patients’ overall outcomes during the whole disease course. Several screening tools have been proposed for this purpose. Nutritional Risk Screening (NRS), Mini Nutritional Assessment (MNA), Patient Generated Subjective Global Assessment (PG-SGA) are the most common studied. Interestingly, second-level tools including skeletal muscle index (SMI) and bioelectric impedance analysis (BIA) provide a more precise assessment of body composition, even if they are more complex. However, nutritional assessment is not currently used in clinical practice and procedures must be standardized in order to improve the efficacy of standard chemotherapy, targeted agents or even checkpoint inhibitors that is potentially linked with the patients’ nutritional status. In the present review, we will discuss about malnutrition and the importance of an early nutritional assessment during chemotherapy and treatment with novel checkpoint inhibitors, in order to prevent treatment-induced toxicities and to improve survival outcomes.

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.

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.

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.

In resectable gastric or gastroesophageal junction cancer (GC/GEJC), the powerful positive prognostic effect and the potential predictive value for a lack of benefit from the combination of adjuvant/peri-operative chemotherapy for the MSI-high status was demonstrated. Given the high sensitivity of MSI-high tumors for immunotherapy, exploratory trials showed that combination immunotherapy induces a high rate of complete pathological response (pCR), potentially achieving cancer cure without surgery. INFINITY is an ongoing phase II, multicentre, single-arm, multi-cohort trial investigating the activity and safety of tremelimumab and durvalumab as neoadjuvant (Cohort 1) or potentially definitive (Cohort 2) treatment for MSI-high/dMMR/EBV-negative, resectable GC/GEJC. About 310 patients will be pre-screened, to enroll a total of 31 patients, 18 and 13 in Cohort 1 and 2, at 25 Italian Centres. The primary endpoint of Cohort 1 is rate of pCR (ypT0N0) and negative ctDNA after neoadjuvant immunotherapy, of Cohort 2 is 2-year complete response rate, defined as absence of macroscopic or microscopic residual disease (locally/regionally/distantly) at radiological examinations, tissue and liquid biopsy, during non-operative management without salvage gastrectomy. The ongoing INFINITY proof-of-concept study may provide evidence on immunotherapy and the potential omission of surgery in localized/locally advanced GC/GEJC patients selected for dMMR/MSI-high status eligible for radical resection.

Introduction: The broad use of immunotherapy is revolutionizing the treatment paradigms of many solid tumors. Although chemotherapy remains the treatment backbone for advanced gastric cancer, improvements in its molecular characterization and progresses in understanding its underpinning biology have supported clinical development of novel immunotherapies. However, the results of recent trials testing these new agents raise the question on how to identify the patients that could greatly benefit. Areas covered: This article summarizes the current understanding on the biology and the mechanisms underlying different clinical features of gastric cancers. Particularly, after a comprehensive literature search, we speculate whether specific molecular subsets of patients could derive more benefit from immunotherapy. Expert commentary: Most cancers may evade the immune response, which is normally regulated by a delicate balance between activating and inhibitory signals. For example, both CTLA-4 and PD-1, once linked to PD-L1/2, may inhibit T-cell signaling. The use of agent to harness the power of the immune system appears to be the ultimate frontier in gastric cancer treatment. While anti-CTLA-4 antibodies are minimally active, there is growing evidence for the efficacy of PD1/-L1 inhibitors. The search of predictive factors for immunotherapy will provide key hints towards the optimal use of these agents.