Liquid biopsy in colorectal cancer: Onward and upward.

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide. In recent years, liquid biopsy has emerged as one of the most interesting areas of research in oncology, leading to innovative trials and practical changes in all aspects of CRC management. RNAs and cell free DNA (cfDNA) methylation are emerging as promising biomarkers for early diagnosis. Post-surgical circulating tumour DNA (ctDNA) can aid in evaluating minimal residual disease and personalising adjuvant treatment. In rectal cancer, ctDNA could improve response assessment to neoadjuvant therapy and risk stratification, especially in the era of organ-preservation trials. In the advanced setting, ctDNA analysis offers the opportunity to monitor treatment response and identify driver and resistance mutations more comprehensively than traditional tissue analysis, providing prognostic and predictive information. The aim of this review is to provide a detailed overview of the clinical applications and future perspectives of liquid biopsy in CRC.

Chemotherapy in patients with early breast cancer: clinical overview and management of long-term side effects.

INTRODUCTION: Neo/adjuvant therapy for early-stage breast cancer has become increasingly common in the last few decades; as a consequence, the number of breast cancer survivors experiencing often debilitating long-term side effects has increased, and thus the need for a comprehensive approach to the variety of symptoms involved. AREAS COVERED AND METHODS: We performed a literature search on the main public scientific databases (PubMed, Embase, Cochrane, and CrossRef) from 2000 to April 2022 to identify prevention and management strategies for the most common long-term side effects, including fatigue, insomnia, peripheral neuropathy, cognitive impairment, estrogen deprivation, cardiotoxicity, and second cancers. EXPERT OPINION: Long-term toxicities may affect a majority of breast cancer survivors, significantly interfering with their quality of life. Although there are guidelines for the management of isolated side effects, such as peripheral neuropathy, we aim to provide a more inclusive clinical-oriented approach, focusing on both prevention and therapeutic strategies.

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.

The SAFFO Study: Sex-Related Prognostic Role and Cut-Off Definition of Monocyte-to-Lymphocyte Ratio (MLR) in Metastatic Colorectal Cancer.

Background: Emerging data suggest that gender-related immune system composition affects both immune response and efficacy of immunotherapy in cancer patients (pts). This study aimed to investigate the sex-related prognostic role of MLR in metastatic colorectal cancer (mCRC) pts. Methods: We analyzed a retrospective consecutive cohort of 490 mCRC patients treated from 2009 to 2018 at the Oncology Departments of Aviano and Pordenone (training set) and Udine (validation set), Italy. The prognostic impact of MLR on overall survival (OS) was evaluated with uni- and multivariable Cox regression models. The best cut-off value to predict survival was defined through ROC analyses. Results: Overall, we identified 288 males (59%) and 202 females (41%); 161 patients (33%) had a right-sided, 202 (42%) a left-sided primary, and 122 (25%) a rectal tumor. Interestingly, gender was associated with MLR (p = 0.004) and sidedness (p = 0.006). The obtained cut-off value for MLR in females and males was 0.27 and 0.49, respectively. According to univariate analysis of the training set, MLR (HR 9.07, p ≤ 0.001), MLR > 0.27 in females (HR 1.95, p = 0.003), and MLR > 0.49 in males (HR 2.65, p = 0.010) were associated with poorer OS, which was also confirmed in the validation set. In multivariate analysis, MLR > 0.27 in females (HR 2.77, p = 0.002), MLR > 0.49 in males (HR 5.39, p ≤ 0.001), BRAF mutation (HR 3.38, p ≤ 0.001), and peritoneal metastases (HR 2.50, p = 0.003) were still independently associated with worse OS. Conclusions: Males and females have a different immune response. Our study showed that high MLR, both in males and females, is an unfavorable Independent prognostic factor. Further prospective studies are needed to confirm these data.

Prognostic role of visceral fat for overall survival in metastatic colorectal cancer: A pilot study.

BACKGROUND: Body composition, has been established as a risk factor for colorectal cancer diagnosis and disease progression. Aim of this study was to investigate the prognostic role of adiposity, especially visceral fat (VAT), in patients (pts) with metastatic colorectal cancer (MCRC). MATERIAL AND METHODS: A retrospective cohort of 71 MCRC pts treated between 2013 and 2017 was evaluated. VAT was measured as cross-sectional (cm2) area at the L3 level divided by the square of the height (m2). A ROC analysis was performed to define a prognostic threshold according to VAT. RESULTS: Before first-line therapy start, 40 pts (56%) had a body mass index (BMI) > 25 kg/m2. The obtained cut-off value for VAT was 44. Median OS was 30.97 months. At univariate analysis, primary tumor resection (HR 0.40, p = 0.029), VAT>44 (HR 2.85, p = 0.011) and metastasectomy (HR 0.22, p = 0.005) were significantly associated with OS. By multivariate analysis, VAT>44 (HR 2.6; p = 0.020) and metastasectomy were still significantly associated with OS. CONCLUSION: This exploratory study suggests a prognostic role for VAT in MCRC pts, with higher VAT values predicting worse outcome.

The SENECA study: Prognostic role of serum biomarkers in older patients with metastatic colorectal cancer.

BACKGROUND: Aging induces meaningful changes in the immune system and inflammation response with increase in monocyte-lymphocyte ratio (MLR) and serum lactate dehydrogenase (LDH) levels. Aim of this study was to explore the prognostic role of MLR and LDH levels in older patients (pts) with metastatic colorectal cancer (mCRC). METHODS: We conducted a retrospective analysis of a consecutive cohort of 168 older (>70 years) patients with mCRC. The prognostic impact of MLR and LDH levels on overall survival (OS) was investigated through uni-and multivariate Cox regression analyses. Moreover, we categorized patients into three groups according to MLR and LDH levels (group 1: MLR-low and LDH-low; group 2: MLR-high or LDH-high; group 3: MLR-high and LDH-high). RESULTS: By univariate analysis, high LDH level (HR 1.74, 95% CI 1.05-2.90) and high MLR level (HR 2.19, 95% CI 1.48-3.44) were significantly associated with a worse OS. Conversely, primary tumor resection and left-sidedness were significantly associated with a longer OS. By multivariate analysis, high LDH level (HR 2.00, 95% CI 1.13-3.55) and high MLR level (HR 2.99, 95% CI 1.68-5.33) were independent prognostic factors of worse prognosis. Compared to group 1, a shorter survival was reported for patients included in group 2 (HR 1.97, 95% CI 1.21-3.23 in univariate; HR 2.54, 95% CI 1.43-4.51 in multivariate) or in group 3 (HR 2.42, 95% CI 24-4.74, p = .010 in univariate; HR 5.59, 95% CI 2.15-14.54 in multivariate) CONCLUSIONS: High baseline levels of LDH, MLR or both are independent unfavorable prognostic factors in older patients treated with first-line chemotherapy for mCRC.

Assessing the tolerability and efficacy of first-line chemotherapy in elderly patients with metastatic HER2-ve breast cancer.

BACKGROUND: In metastatic breast cancer (MBC), there is no consensus regarding the optimal regimen sequence and whether adults >65 years old (OA) are at increased risk from chemotherapy toxicity. Treatment decisions are often driven by the ability to tolerate treatment and maintain the quality of life. This study was designed to assess current practice in an oncology hospital in the UK. METHODS: Retrospective data were collected about treatments used for 87 OA with MBC in a single centre between 2009 and 2016 to assess the tolerability and efficacy of first-line chemotherapy. Student's T-tests and Kaplan-Meier statistical methods were applied. RESULTS: 70% of patients were commenced on standard dose (SD) of chemotherapy; 84% (21/25) of the anthracycline group (AG), 65% (20/31) of the capecitabine group (CG), 48% (10/21) of the taxane group (TG) and 100% (10/10) of other agents. 32% of patients had dose reductions; 16% in AG, 19% in TG and 58% in CG. Overall 30% of patients received six cycles of SD of chemotherapy; 36% in AG, 29% in CG and 14% in TG. 23% of patients suffered ≥grade 3 toxicity; 28% in AG, 29% in CG and 10% in TG. There were four treatment-related deaths; two in AG and one in both CG and TG. 61% of the CG received 6+ cycles with a mean on treatment time of 445 days (1-2,150). There was no statistical significance in progression- free survival (PFS) between groups. The median PFS for all patients was 244 days (87-381). Performance status, haemoglobin and estimated glomerular filtration rates prior to starting chemotherapy were all useful in predicting PFS. CONCLUSIONS: A relevant number of patients required dose reduction but dose-reduced chemotherapy was tolerated well. Anthracycline-based regimens were used in patients who had not received adjuvant chemotherapy. Capecitabine required the most dose reductions. Taxanes were generally started at reduced doses, resulting in fewer grade 3+ toxicities. As well as age, underlying physiological reserve, current performance status and co-morbidities should guide physicians who should consider lower starting doses in OA and recognise that dose reductions may be required to improve tolerability. The PFS of all regimens were similar in this study. This study highlights the need for further research to define the optimal first-line chemotherapy and starting dose in OA with MBC.

Mucosal Injury during Anti-Cancer Treatment: From Pathobiology to Bedside.

Mucositis is one of the most common debilitating side effects related to chemotherapy (CT), radiation therapy (RT), targeted agents and immunotherapy. It is a complex process potentially involving any portion of the gastrointestinal tract and injuring the mucosa, leading to inflammatory or ulcerative lesions. Mechanisms and clinical presentation can differ according both to the anatomic site involved (oral or gastrointestinal) and the treatment received. Understanding the pathophysiology and management of mucosal injury as a secondary effect of anti-cancer treatment is an important area of clinical research. Prophylaxis, early diagnosis, and adequate management of complications are essential to increase therapeutic success and, thus, improve the survival outcomes of cancer patients. This review focuses on the pathobiology and management guidelines for mucositis, a secondary effect of old and new anti-cancer treatments, highlighting recent advances in prevention and discussing future research options.