Management and Outcomes of Older Patients (Age ≥ 70 Years) with Advanced Soft Tissue Sarcoma and Role of Geriatric Assessment and Oncological Multidimensional Prognostic Index (Onco-MPI) in a Real-World Setting.

Background: Incidences of soft tissue sarcomas (STS) steadily increase with age. Yet, despite the high prevalence in advanced age, older patients (pts) are underrepresented in sarcoma clinical trials and evidence-based guidelines for chemotherapy are lacking. International oncological societies suggest using geriatric tools to evaluate older patients with cancer to optimise treatment indication. Comprehensive geriatric assessment (CGA) is a multidimensional assessment of older subjects, based on which pts can be classified as fit, vulnerable or frail. Onco-MPI (multidimensional prognostic index) is a CGA-based score which also considers tumour characteristics, classifying pts into three risk groups of death at one year: high-risk, intermediate-risk and low-risk. Methods: This is a single-centre retrospective study which aims at describing real-word management and outcomes of older pts with advanced stage STS and at assessing the ability of CGA and onco-MPI to predict survival in these pts. Consecutive pts with advanced stage STS aged 70 years or older and treated at the Istituto Oncologico Veneto from January 2009 to June 2020 were retrieved from a prospectively maintained database. Pts' demographics, CGA assessments and tumour characteristics were analysed. Statistical analysis was performed with R version 3.4.3 Results: Out of 101 pts, with a median age of 77 years, 76 received chemotherapy (75.3%), which was anthracycline-based for 46 pts (60.5%). Anthracyclines were used in a higher proportion in fit pts (58.9% fit vs. 45.1% vulnerable vs. 12.5% frail pts). Frail pts and pts in the onco-MPI high-risk group experienced a higher rate of chemotherapy-related toxicities. Median OS was 13.8 months (95% CI 11.3-17.7 months). According to CGA, the median OS was 19.53 months (95% CI 15.23-36.8) for fit pts, 12.83 months (95% CI 9.7-17.5) for vulnerable and 7.75 months (95% CI 2.73-30) for frail pts (p = 0.005). Onco-MPI confirmed a predictive value for 1-year survival with intermediate risk pts not reaching a median OS at 1 year, and high-risk pts having a median one-year OS of 11.5 months (95%CI 9.7-NA), p = 0.02. In multivariate analysis, onco-MPI and CGA were associated with survival (high risk onco-MPI: HR 5.5, 95%CI 1.25-24.7 p = 0.02; fitness at CGA HR 0.552 95% 0.314-0.973; p = 0.040) as well as chemotherapy use (HR 0.24, 95% CI 0.11-0.51, p < 0.005). Conclusions: Both CGA and onco-MPI retain prognostic value for survival in pts with metastatic STS. Pts frail/vulnerable at CGA and pts within the onco-MPI high risk category should be offered an oncogeriatric management approach in order to optimise treatment-related survival and reduce toxicity.

Hypertransaminasemia in metastatic renal cell carcinoma patients receiving immune-based combinations: a meta-analysis.

Aims: We performed a meta-analysis to assess the relative risk (RR) of all-grade and grade 3-4 hypertransaminasemia in studies comparing immune-based combinations with sunitinib in treatment-naive patients with advanced renal cell carcinoma. Materials & methods: Outcomes of interest included all-grade and grade 3-4 hypertransaminasemia measured as RRs and 95% confidence intervals (CIs). Results: RRs for all-grade hypertransaminasemia were 1.73 (95% CI: 1.25-2.4) and 1.63 (95% CI: 1.25-2.12) in patients receiving immunocombinations and sunitinib, respectively. The pooled RRs for grade 3-4 hypertransaminasemia were 3.24 and 3.04 in patients treated with immunocombinations or sunitinib. Conclusion: Immune-based combinations were associated with higher hypertransaminasemia risk. Physicians should pay attention to these common but overlooked events. Careful monitoring of tolerability remains a crucial need.

In our study, we aimed to determine the risk for developing alterations in liver function in treatment-naive patients with metastatic renal cell carcinoma, receiving an immunotherapic compound plus a tyrosine-kinase inhibitor or sunitinib alone. We found that combination treatment, compared with sunitinib, is associated with an increased risk to present this type of liver's toxicity, even a high-grade one.

ctDNA as promising tool for the assessment of minimal residual disease (MRD) and the need of an adjuvant treatment in gastroesophageal adenocarcinoma.

Gastroesophageal adenocarcinoma is a challenging disease due to its poor prognosis and the presence of few therapeutic options. For these reasons, it is mandatory to identify the subgroup of patients who are at high risk for relapse after curative-intention surgery. In the last years, liquid biopsy has aroused great interest in cancer treatment for its feasibility and the possibility to capture tumor heterogeneity in a real-time way. In postoperative setting, the interest is directed to the identification of Minimal Residual Disease (MRD), defined as isolated or small cluster of cancer cells that residues after curative-intention surgery, and are undetectable by conventional radiological and clinical exams. This review wants to summarize current evidence on the use of liquid biopsy in gastroesophageal cancer, focusing on the detection of ctDNA in the postoperative setting and its potential role as a guide for treatment decision.

HER2 in Colorectal Cancer: The Long and Winding Road From Negative Predictive Factor to Positive Actionable Target.

Human epidermal growth factor receptor 2 (HER2) is a well-known oncogenic driver in different tumors and an approved therapeutic target in breast and gastroesophageal cancer. In metastatic colorectal cancer, only 3% to 5% of patients present with HER2 alterations: somatic mutations and amplifications. HER2 was first assessed as a biomarker of resistance to anti-EGFR therapy; however, in more recent years, its role as a potential actionable target has emerged. In this article, we discuss the predictive and prognostic value of HER2 in metastatic colorectal cancer, its emerging role as an actionable therapeutic target, and its possible future developments.

The impact of panitumumab treatment on survival and quality of life in patients with RAS wild-type metastatic colorectal cancer.

Panitumumab is a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR). It is currently approved for the treatment of RAS wild-type (WT) metastatic colorectal cancer (mCRC) in combination with chemotherapy in first- and second-line and as monotherapy in chemorefractory patients. This review will provide an overview of main efficacy data on panitumumab from its early development up to latest evidences, including novel perspectives on predictive biomarkers of anti-EGFRs efficacy and mechanisms of secondary resistance. Quality of life (QoL) related issues and panitumumab safety profile will be addressed as well.

Ramucirumab: the long and winding road toward being an option for mCRC treatment.

INTRODUCTION: Colorectal cancer (CRC) is one of the main causes of cancer-related morbidity and mortality worldwide. Mortality is most often attributable to metastatic disease. Despite the progress achieved so far, life expectancy continues to be limited in most patients. Ramucirumab, a most recent antiangiogenic drug, is vying in the race to metastatic CRC (mCRC) treatment since its approval by the Food and Drug Administration (FDA), based on the results of the RAISE study. AREAS COVERED: This article reviews the role of ramucirumab in mCRC, including clinical indication, safety issues, and future perspectives. EXPERT OPINION: The use of Ramucirumab in clinical practice is still limited, probably due to economic burden and the lack of specific biomarkers. Future efforts will be addressed to improve our knowledge in the use of this drug and better guide us in patients' care.

Prevalence of pain in patients with cancer aged 70 years or older: A prospective observational study.

BACKGROUND: Pain is a common symptom among patients with cancer, yet pain prevalence and management in older cancer pts. are poorly known. METHODS: Patients aged ≥70 years referred to Istituto Oncologico Veneto IRCCS from January 2011 to December 2013 were evaluated with Comprehensive Geriatric Assessment (CGA). Pain was assessed by means of short form of McGill Pain Questionnaire (MPQ-sf), Brief Pain Inventory (BPI-sf), and numerical rating scale (NRS). Pts with completed CGA, no severe cognitive impairment and completed pain assessment were enrolled. RESULTS: Enrolled patients were 745; 51% male, median age 76 years, median ECOG Performance Status (PS) 1. Frail patients at CGA were 45.2%. Patients with pain were 266 (35.7%). Mean Average Pain Intensity (API) was significantly higher among females, patients fit at CGA, with advanced disease, poorer PS and more comorbidity. Pain was detected by the oncologist in 20.4% of cases and deemed cancer-related in 54.8%. Gender, PS, status of disease, stage, function disability, mood, cognitive functioning and frailty were significantly associated with reporting of pain. At BPI, moderate-severe pain was found in 81 patients. The degree of agreement between API and pain intensity evaluated by physician was minimal. Patients on pain medications were 184, with 113 patients reporting rates of pain relief ≥50%. CONCLUSION: About one third of older patients with cancer report pain, which is not cancer-related in about half of cases. Female gender, fitness at CGA, advanced stage, poorer PS, higher number of comorbidities and primary site were associated with significant differences in pain reporting.