Chemotherapy Duration for Various Indications in Colorectal Cancer: a Review.

PURPOSE OF REVIEW: The treatment of colorectal cancer (CRC) has evolved and become more personalized during the past several years. For example, depotentiation/reduced duration of systemic therapies has proven to be beneficial in both advanced and early stages of the disease. RECENT FINDINGS: In particular, recent randomized studies of stage III and high-risk stage II CRC showed that a shorter duration (3 months), when compared to the historical 6-month comparator, provides nearly similar overall survival (OS) and disease-free survival (DFS). In the setting of advanced, inoperable CRC, a relatively short induction phase (six to eight cycles) followed by biological agents is the current standard of care in RAS wild-type (wt). versus RAS mutated cases. With regard to potentially operable stage IV disease (with the aim of converting liver metastases to operability), a relatively short number of cycles (four to six cycles) should be offered with re-staging and re-evaluation for surgery as soon as possible in most cases. For inoperable liver metastases, a relatively intensive triplet or doublet plus targeted therapy may attain conversion in some cases and may even result in cure. Rectal cancer treatment continues to be a complex disease in terms of treatment and oncological results. Recent data seem to showcase the benefits of more prolonged sequential strategies (total neoadjuvant therapy, all treatment delivered before surgery, to reduce the risk of distant metastases and local control). In recent years, different strategies regarding treatment intensity have been employed in CRC in adjuvant and metastatic setting. Introduction of triplets as first-line therapy for colon cancer and as induction phase for rectal cancer are now therapeutic options. Conversely in stage II disease or low-risk stage III resected CRC, a reduced chemotherapy length is a new standard of care.

Multidisciplinary management of immunotherapy-related adverse events in solid tumors: An inter-institutional and telemedicine-based working team.

BACKGROUND: Although immune checkpoint inhibitors (ICIs) show a more favorable toxicity profile than classical cytotoxic drugs, their mechanism of action is responsible for peculiar new toxicities. There is an urgent need for a multidisciplinary approach to advice on how to manage organ-specific toxicities. METHODS: Our project aims to integrate the practices of two different hospitals into a single Italian regional collaborative model to treat immune-related adverse events (irAEs). The team structure is a multi-professional and multidisciplinary cooperative network that consists of different medical specialists. The team referrer is the medical oncologist and an existing telematic platform is used for specialists' cooperation. The leading oncologist first evaluates patients' clinical condition, therefore team intervention and teleconsultation are planned to activate proper management. After a first phase structured for general setting, outcomes analysis, data collection, and identification of critical issues, it is planned to define appropriate key performance indicators (KPIs) in quality, structure, process, and outcome settings. Therefore, a second phase would serve to implement KPIs. In the third phase, the proposal for the enlargement of the network with the extension to more centers in the context of the Regional Health Service will be performed. DISCUSSION: The multidisciplinary management of irAEs based on telemedicine fits into the debate on the renewal of healthcare systems and the push for change toward multidisciplinary with the rising use of telemedicine. To our knowledge, this is the first project reporting a multi-institutional experience for change of service in irAEs management.

Hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis: HCC and Steatosis or Steatohepatitis.

BACKGROUND AND AIMS: Hepatic steatosis of nonalcoholic etiology (nonalcoholic fatty liver disease; NAFLD) is an emergent condition that may lead to hepatic cirrhosis and finally to liver cancer. We evaluate the risk of developing hepatocellular carcinoma (HCC) and quantify the prognosis in terms of recurrence (DFS) as well as HCC-specific and overall survival (CSS and OS) of patients with and without NAFLD. METHODS: We searched published articles that evaluated the risk and outcomes of HCC in patients with steatosis/steatohepatitis from inception to July 2021 were identified by searching the PubMed, EMBASE, and Cochrane Library databases. Prospective cohort, case-control, or retrospective studies were selected that were published in English and provided incidence and survival rates of HCC patients with NAFLD. A random-effects model was created to estimate the pooled effect size. The primary outcome of interest was HCC incidence. The secondary endpoints were DFS, CSS, and OS. RESULTS: In total, 948 217 patients with NAFLD were analyzed, from n = 103 observational studies. NAFLD significantly increased the risk of HCC (HR = 1.88 [95% CI, 1.46-2.42]; P < .01] but not risk of recurrence (HR = 0.99 [95% CI, 0.85-1.15]; P = .9) or overall mortality (HR = 1.04 [95% CI, 0.88-1.24]; P = 0.64). Conversely, NAFLD increased HCC-related mortality risk (HR = 2.16 [95% CI, 0.85-5.5]; P = .1). Risk of HCC was increased in Western countries but not in Asian countries. CONCLUSIONS: Patients with NAFLD have an increased risk of HCC as compared to patients without NAFLD. NAFLD also increases liver cancer (HCC) mortality. These results justify applying general measures to patients with proven NAFLD and monitoring patients with NASH and fibrosis.

Steroids use and survival in patients with glioblastoma multiforme: a pooled analysis.

INTRODUCTION: Steroids are commonly used for managing brain edema in patients with glioblastoma multiforme (GBM), treated with surgery and concomitant temozolomide-based chemoradiotherapy (CTRT). The adverse effects of glucocorticoids include lymphopenia, hyperglycemia, and risk of infection. We report the results of a meta-analysis evaluating the effects of steroids on outcome when associated with the treatment of GBM. METHODS: PubMed, the Cochrane Library, and Embase were searched from inception until September 2019 for observational or prospective studies reporting prognosis of adult patients with GBM and treated or not treated with steroids. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The effect size was reported as hazard ratios (HRs) with a 95% confidence interval (CI), and an HR > 1 associated with the worst outcome in steroid users compared to non-users. RESULTS: Twenty-two publications were retrieved from studies selected for a total of 8,752 patients. In the primary analysis (n = 22 studies reporting data), OS was reduced in GBM patients taking steroids during treatment (HR = 1.54, 95% CI 1.37-1.75; p < 0.01). Similarly, PFS was inferior in steroid users in n = 9 studies with data available (HR = 1.28, 95% CI 1.1-1.49; p < 0.01). CONCLUSIONS: In patients with GBM and treated with RT and/or CT, association with steroids significantly reduces survival and PFS. Use of the lowest dose of glucocorticoids for the shortest period needed to achieve the treatment goals and prevention of steroid-associated complications are essential aims of treatment of this disease.

Association of Obesity With Survival Outcomes in Patients With Cancer: A Systematic Review and Meta-analysis.

Importance: Obesity, defined as a body mass index (BMI) greater than 30, is associated with a significant increase in the risk of many cancers and in overall mortality. However, various studies have suggested that patients with cancer and no obesity (ie, BMI 20-25) have worse outcomes than patients with obesity. Objective: To assess the association between obesity and outcomes after a diagnosis of cancer. Data Sources: PubMed, the Cochrane Library, and EMBASE were searched from inception to January 2020. Study Selection: Studies reporting prognosis of patients with obesity using standard BMI categories and cancer were included. Studies that used nonstandard BMI categories, that were limited to children, or that were limited to patients with hematological malignant neoplasms were excluded. Screening was performed independently by multiple reviewers. Among 1892 retrieved studies, 203 (17%) met inclusion criteria for initial evaluation. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were reporting guideline was followed. Data were extracted by multiple independent reviewers. Risk of death, cancer-specific mortality, and recurrence were pooled to provide an adjusted hazard ratio (HR) with a 95% CI . A random-effects model was used for the retrospective nature of studies. Main Outcomes and Measures: The primary outcome of the study was overall survival (OS) in patients with cancer, with and without obesity. Secondary end points were cancer-specific survival (CSS) and progression-free survival (PFS) or disease-free survival (DFS). The risk of events was reported as HRs with 95% CIs, with an HR greater than 1 associated with a worse outcome among patients with obesity vs those without. Results: A total of 203 studies with 6 320 365 participants evaluated the association of OS, CSS, and/or PFS or DFS with obesity in patients with cancer. Overall, obesity was associated with a reduced OS (HR, 1.14; 95% CI, 1.09-1.19; P < .001) and CSS (HR, 1.17; 95% CI, 1.12-1.23; P < .001). Patients were also at increased risk of recurrence (HR, 1.13; 95% CI, 1.07-1.19; P < .001). Conversely, patients with obesity and lung cancer, renal cell carcinoma, or melanoma had better survival outcomes compared with patients without obesity and the same cancer (lung: HR, 0.86; 95% CI, 0.76-0.98; P = .02; renal cell: HR, 0.74; 95% CI, 0.53-0.89; P = .02; melanoma: HR, 0.74; 95% CI, 0.57-0.96; P < .001). Conclusions and Relevance: In this study, obesity was associated with greater mortality overall in patients with cancer. However, patients with obesity and lung cancer, renal cell carcinoma, and melanoma had a lower risk of death than patients with the same cancers without obesity. Weight-reducing strategies may represent effective measures for reducing mortality in these patients.

Aortic dissection after ramucirumab infusion.

A female patient in her seventies affected by a signet-ring cell carcinoma G3pT4N3 (24/29), with lymphovascular invasion, HER2-negative. After completing three cycles of first-line systemic treatment in combination with cisplatin (CDDP) + 5-fluorouracil (5FU), a new systemic therapy line with paclitaxel + Cyramza (ramucirumab) was planned. On the day after the first administration the patient manifested a Standford type A aortic dissection (AD), with a diameter of around 6.5 cm and dissection flap originating in the ascending aorta below the brachiocephalic trunk, extended to the whole descending aorta until the carrefour. The causal relationship between adverse drug reactions and Cyramza, calculated using the Naranjo algorithm, led to a result of 'probable' correlation between ramucirumab and AD. The endothelial dysfunction associated with vascular endothelial growth factor pathway inhibitors (VPIs) would seem to be the most plausible explanation for such events: it causes thromboembolic events and cardiovascular complications.

Survival of Patients Treated with Antibiotics and Immunotherapy for Cancer: A Systematic Review and Meta-Analysis.

Antibiotics (ABs) are common medications used for treating infections. In cancer patients treated with immune checkpoint inhibitors (ICIs), concomitant exposure to ABs may impair the efficacy of ICIs and lead to a poorer outcome compared to AB non-users. We report here the results of a meta-analysis evaluating the effects of ABs on the outcome of patients with solid tumours treated with ICIs. PubMed, the Cochrane Library and Embase were searched from inception until September 2019 for observational or prospective studies reporting the prognoses of adult patients with cancer treated with ICIs and with or without ABs. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The effect size was reported as hazard ratios (HRs) with a 95% confidence interval (CI) and an HR > 1 associated with a worse outcome in ABs users compared to AB non-users. Fifteen publications were retrieved for a total of 2363 patients. In the main analysis (n = 15 studies reporting data), OS was reduced in patients exposed to ABs before or during treatment with ICIs (HR = 2.07, 95%CI 1.51-2.84; p < 0.01). Similarly, PFS was inferior in AB users in n = 13 studies with data available (HR = 1.53, 95%CI 1.22-1.93; p < 0.01). In cancer patients treated with ICIs, AB use significantly reduced OS and PFS. Short duration/course of ABs may be considered in clinical situations in which they are strictly needed.

A Review of Clinical Practice Guidelines and Treatment Recommendations for Cancer Care in the COVID-19 Pandemic.

The COVID-19 pandemic has inevitably caused those involved in cancer care to change clinical practice in order to minimize the risk of infection while maintaining cancer treatment as a priority. General advice during the pandemic suggests that most patients continue with ongoing therapies or planned surgeries, while follow-up visits may instead be delayed until the resolution of the outbreak. We conducted a literature search using PubMed to identify articles published in English language that reported on care recommendations for cancer patients during the COVID-19 pandemic from its inception up to 1st June 2020, using the terms "(cancer or tumor) AND (COVID 19)". Articles were selected for relevance and split into five categories: (1) personal recommendations of single or multiple authors, (2) recommendations of single authoritative centers, (3) recommendations of panels of experts or of multiple regional comprehensive centers, (4) recommendations of multicenter cooperative groups, (5) official guidelines or recommendations of health authorities. Of the 97 included studies, 10 were personal recommendations of single or multiple independent authors, 16 were practice recommendations of single authoritative cancer centers, 35 were recommendations provided by panel of experts or of multiple regional comprehensive centers, 19 were cooperative group position papers, and finally, 17 were official guidelines statements. The COVID-19 pandemic is a global emergency, and has rapidly modified our clinical practice. Delaying unnecessary treatment, minimizing toxicity, and identifying care priorities for surgery, radiotherapy, and systemic therapies must be viewed as basic priorities in the COVID-19 era.

Incidence and outcomes of severe acute respiratory syndrome coronavirus 2 infection in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Patients with cancer are at increased risk of complicated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but it is still unclear if the risk of mortality is influenced by cancer type or ongoing anti-cancer treatments. An interesting debate concerning the potential relationship between androgen deprivation therapy (ADT) and SARS-CoV-2 infection has recently been opened in the case of prostate cancer (PC), and the aim of this multi-centre cohort study was to investigate the incidence and outcomes of SARS-CoV-2 infection in patients with metastatic castration-resistant prostrate cancer (mCRPC). PATIENTS AND METHODS: We retrospectively reviewed the clinical records of patients with mCRPC who developed SARS-CoV-2 infection, and recorded their baseline clinical characteristics, their history of PC and SARS-CoV-2 infection, and their oncological status and treatment at the time of infection. The primary study end point was the death rate and the possible impact of the patients' PC-related history and treatments on mortality. RESULTS: Thirty-four of the 1433 patients with mCRPC attending the participating centres (2.3%) developed SARS-CoV-2 infection, 22 (64.7%) of whom were hospitalised. Most of the patients were symptomatic, the most frequent symptoms being fever (70.6%), dyspnoea (61.8%), cough (52.9%) and fatigue (38.2%). After a median follow-up of 21 days (interquartile range: 13-41), 13 patients had died (38.2%), 17 recovered (50.0%) and four (11.7%) were still infected. The number of treatments previously administered for mCRPC had a significant impact on mortality (p = 0.004). CONCLUSIONS: Our findings contribute additional data to the current debate concerning the postulated protective role of ADT, which seems to be less in patients with metastatic PC.

Case report of a 65-year-old man with biatrial metastatic localisation from poorly differentiated cutaneous squamous cell carcinoma.

We report the case of an immunocompetent 65-year-old man affected by cutaneous squamous cell carcinoma (cSCC) with lung and biatrial metastatic localisation. In May 2018, the patient underwent lower limb amputation due to the finding of a large ulceration which upon biopsy was found to be a poorly differentiated squamous cell carcinoma (SCC), ulcerated, full-thickness infiltrating from the skin to the underlying bone tissue. After 1 month, a radiological restaging found multiple pulmonary localisations and a right-atrial metastatic localisation. The patient was then studied in-depth and a transesophageal echocardiogram found that the patient had two 2 and 5 cm metastatic localisations in the left atrium and a 3-cm metastatic localisation in the right atrium. Informed about the clinical situation and about the risks of a chemotherapeutic treatment, the patient decided not to start any treatment. This case represents, to our knowledge, the only case of a biatrial metastatic localisation from cSCC and is representative of how cardiac symptoms and signs in patients affected by this disease must be evaluated.

Bevacizumab-based neoadjuvant chemotherapy for colorectal cancer liver metastases: Pitfalls and helpful tricks in a review for clinicians.

Bevacizumab added to chemotherapy has shown encouraging efficacy in the neoadjuvant therapy of colorectal cancer liver metastases. In absence of biological predictor factors of efficacy to bevacizumab-based treatment, the assessment of response may be a crucial point to select patients who may benefit the most from surgery. At the same time the pathological response after liver resection could represent a guide for the next therapeutic plan. In the pre-surgical phase, conventional computed tomography and response evaluation with RECIST criteria may underestimate the response to anti-angiogenic drugs. Modified computed tomography criteria of response, morphologic changes as well as novel imaging techniques and metabolic assessment by fluorodeoxyglucose positron emission tomography seem to be promising methods for the assessment of response and for leading the clinical choices. Pathological response at the time of surgery is an important prognostic factor and a surrogate of survival for resected patients. Different classification criteria to assess pathological response have been developed, residual viable tumor, tumor regression grade (TRG), modified TRG and tumor thickness at the tumor-normal interface, but to date a superiority of one approach over the others has not been clearly established. In this review, we evaluate the available data with the aim to help the clinicians in the pre- and post-surgical care of patient with colorectal cancer liver metastases treated with bevacizumab-based neoadjuvant strategy.

A phase II study of sunitinib in advanced hepatocellular carcinoma.

BACKGROUND: In 2007, sorafenib was the first drug able to improve overall survival in patients with advanced hepatocellular carcinoma. AIM: In 2005 we designed a phase II study to assess safety and efficacy of sunitinib. METHODS: This is a single arm, open-label, single-centre phase II trial. Eligibility criteria were advanced hepatocellular carcinoma; no prior chemotherapy, performance status 0-1; and Child≤B8. The treatment schedule was 50mg each day orally, 4 weeks on, 2 weeks off. RESULTS: Between 10/2007 and 10/2010, 34 patients were enrolled. A significant worsening of liver functional reserve after sunitinib was observed. Grade 3/4 adverse effects occurred in 80% of patients and included fatigue (47%), nausea (15%), liver failure (15%), encephalopathy (12%) and upper gastrointestinal bleeding (12%). Six patients (18%) died within 60 days of enrolment. A partial response was observed in 4 patients (12%). Median time to tumour progression was 2.8 months and median overall survival was 5.8 months. CONCLUSION: A dose of 50mg/d induces a high rate of severe adverse events. Toxicity remains a key concern also at the dose of 37.5mg/d. However, sunitinib is able to induce a prolonged response in some patients. Positron Emission Tomography/Computed Tomography scans may select good responders.

Complete Metabolic Response with Recanalization of Portal Vein Tumor Thrombosis after Sunitinib in a Patient with Advanced Hepatocellular Carcinoma.

The prognosis of patients with advanced hepatocellular carcinoma (HCC) is very poor. The outcome of these patients is particularly bleak when the disease is complicated by portal vein tumor thrombosis (PVTT), since the increased portal pressure often causes serious gastrointestinal bleedings. Before the introduction of sorafenib (SOR), a tyrosine kinase inhibitor, no effective treatment was available for patients with advanced disease. SOR is now considered the standard treatment even for patients with tumor thrombosis, although the well-known interference between tyrosine kinase inhibitors and the coagulation pathway calls for caution against their use in this setting. Here, we report the case of a 74-year-old male patient with advanced HCC and PVTT treated with sunitinib (SUN), another multikinase inhibitor. During the third cycle, our patient experienced a life-threatening hematemesis with hemorrhagic shock that required intensive care treatment and SUN discontinuation. However, he completely recovered, and the PET/CT scan performed 1 year after the adverse effect demonstrated no evidence of the tumor together with portal vein recanalization. The short course of SUN causing both tumor response and gastrointestinal bleeding warrants further studies on the effectiveness of SUN in this setting as well as on the duration of treatment with multikinase inhibitors in patients with tumor thrombosis.