Reinduction of an Anti-EGFR-based First-line Regimen in Patients with RAS Wild-type Metastatic Colorectal Cancer Enrolled in the Valentino Study.

Background: In patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC), growing evidence supports anti-epidermal growth factor receptor (EGFR) retreatment, whereas little is known on the outcomes of anti-EGFR-based reinduction therapy during the upfront strategy.

Methods: We included patients enrolled in the Valentino study who had disease progression and received at least one dose of post-progression therapy. The Kaplan-Meier method and Cox proportional hazards regression were used for the survival analysis.

Temozolomide Followed by Combination With Low-Dose Ipilimumab and Nivolumab in Patients With Microsatellite-Stable, O-Methylguanine-DNA Methyltransferase-Silenced Metastatic Colorectal Cancer: The MAYA Trial.

Purpose: This is a multicenter, single-arm phase II trial evaluating the efficacy and safety of an immune-sensitizing strategy with temozolomide priming followed by a combination of low-dose ipilimumab and nivolumab in patients with microsatellite-stable (MSS) and O-methylguanine-DNA methyltransferase (MGMT)-silenced metastatic colorectal cancer (mCRC).

Patients And Methods: Patients with pretreated mCRC were centrally prescreened for MSS status and MGMT silencing (ie, lack of MGMT expression by immunohistochemistry plus methylation by pyrosequencing). Eligible patients received two priming cycles of oral temozolomide 150 mg/sqm once daily, days 1-5, once every 4 weeks (first treatment part) followed, in absence of progression, by its combination with ipilimumab 1 mg/kg once every 8 weeks and nivolumab 480 mg once every 4 weeks (second treatment part).

Multi-institutional analysis of outcomes for thermosphere microwave ablation treatment of colorectal liver metastases: the SMAC study.

Objectives: Oligometastatic colorectal cancer benefits of locoregional treatments but data concerning microwave ablation (MWA) are limited and interactions with systemic therapy are still debated. The aim of this study is to evaluate safety and effectiveness of Thermosphere™ MWA (T-MWA) of colorectal liver metastases (CLM) and factors affecting local tumor progression-free survival (LTPFS).

Methods: In this multi-institutional retrospective study (January 2015-September 2019), patients who underwent T-MWA for CLM were enrolled.

Variant allele frequency in baseline circulating tumour DNA to measure tumour burden and to stratify outcomes in patients with RAS wild-type metastatic colorectal cancer: a translational objective of the Valentino study.

Introduction: In patients with metastatic colorectal cancer (mCRC), baseline circulating tumour DNA (ctDNA) variant allele fraction (VAF) might serve as a surrogate of disease burden and should be evaluated in comparison with CEA and RECIST-defined sum of target lesions.

Methods: In this pre-planned analysis of the VALENTINO trial, we included patients with RAS wild-type mCRC receiving upfront FOLFOX/panitumumab with available baseline liquid biopsy. CtDNA was analysed by means of a 14-gene NGS panel.

Italian results of the PRECONNECT study: safety and efficacy of trifluridine/tipiracil in metastatic colorectal cancer.

The international PRECONNECT Phase IIIb study demonstrated safety and efficacy of trifluridine/tipiracil in the management of patients with metastatic colorectal cancer. analyses in a national context are important because of the differences in disease management across countries. safety and efficacy analyses in the PRECONNECT Italian patient subset were conducted.

Prospective, randomised, multicentre, open-label trial, designed to evaluate the best timing of closure of the temporary ileostomy (early versus late) in patients who underwent rectal cancer resection and with indication for adjuvant chemotherapy: the STOMAD (STOMa closure before or after ADjuvant therapy) randomised controlled trial.

Introduction: Temporary ileostomy is a valuable aid in reducing the severity of complications related to rectal cancer surgery. However, it is still unclear what is the best timing of its closure in relation to the feasibility of an adjuvant treatment, especially considering patient-reported outcomes and health system costs. The aim of the study is to compare the results of an early versus late closure strategy in patients with indication to adjuvant chemotherapy after resection for rectal cancer.

The Added Value of Baseline Circulating Tumor DNA Profiling in Patients with Molecularly Hyperselected, Left-sided Metastatic Colorectal Cancer.

Purpose: The routine use of liquid biopsy is not recommended for the choice of initial treatment for patients with metastatic colorectal cancer (mCRC).

Experimental Design: We included patients with left-sided, wild-type, HER2-negative, and microsatellite stable mCRC, treated with upfront panitumumab/FOLFOX-4 in the Valentino study. We performed amplicon-based genomic profiling of 14 genes in baseline plasma samples and compared these data with tumor tissue ultra-deep sequencing results.

Response shift in health-related quality of life measures in the presence of formative indicators.

Background: Response shift (RS) has been defined as a change in the meaning of an individual's self-evaluation that needs to be accounted for when assessing longitudinal changes in health-related quality of life (HRQoL). RS detection through structural equation modeling is accomplished by adopting Oort's procedure based on a measurement model in which the observed variables are defined as reflective indicators of the HRQoL latent variable; that is, the latent variable causes the variation in the reflective indicators. This study aims to propose a procedure that assesses RS when formative indicators are used in measuring HRQoL; in this last case, the latent variable is considered to be a function of some formative indicators.

Systemic doxycycline for pre-emptive treatment of anti-EGFR-related skin toxicity in patients with metastatic colorectal cancer receiving first-line panitumumab-based therapy: a post hoc analysis of the Valentino study.

Introduction: The combination of anti-EGFRs and doublet chemotherapy is considered the optimal upfront option for patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer (mCRC). The prophylactic or reactive treatment with tetracyclines for EGFR inhibitor-induced skin toxicity is currently clinical practice, though non-conclusive results are available.

Methods: We performed a post hoc analysis of the Valentino study that randomized RAS wild-type mCRC patients to two panitumumab-based maintenance regimens after the first-line induction, aimed at assessing the safety and efficacy of the administration of a pre-emptive doxycycline prophylaxis for anti-EGFR-related skin toxicity.

Impact of early tumor shrinkage and depth of response on the outcomes of panitumumab-based maintenance in patients with RAS wild-type metastatic colorectal cancer.

Background: In patients with metastatic colorectal cancer (mCRC) receiving highly active first-line combination treatments, early tumor shrinkage (ETS) and depth of response (DoR) are associated with survival, but their influence on outcomes during maintenance therapy is unknown. The Valentino study showed inferior PFS in 229 RAS wild-type mCRC patients randomized to panitumumab plus FOLFOX followed by maintenance with panitumumab vs. panitumumab + 5-FU/LV.

Bone Marrow-Sparing IMRT in Anal Cancer Patients Undergoing Concurrent Chemo-Radiation: Results of the First Phase of a Prospective Phase II Trial.

Purpose: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation.

Methods: a one-armed two-stage Simon's design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0-G2 (vs. G3-G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.

Metastatic colorectal cancer prior to expanded RAS assessment: evidence from long-term outcome analysis of a real-life cohort within a dedicated colorectal cancer unit.

Background: Molecular assessment and treatment of metastatic colorectal cancer (mCRC) quickly evolved during the last decades, hampering longitudinal evaluation of prognostic markers. The aim of this study was to evaluate prognostic predictors of long-term survival in a retrospective series of mCRC, treated prior to the expanded RAS assessment era.

Methods: mCRC cases treated at the Città della Salute e della Scienza University Hospital (Turin, Italy) between January 2004 and December 2012 were evaluated, including cases with ≥ 5-year follow-up only.

Negative Hyperselection of Patients With and Wild-Type Metastatic Colorectal Cancer Who Received Panitumumab-Based Maintenance Therapy.

Purpose: We assessed the prognostic/predictive role of primary tumor sidedness and uncommon alterations of anti-epidermal growth factor receptor (EGFR) primary resistance (primary resistance in and wild-type metastatic colorectal cancer patients treated with anti-EGFR monoclonal antibodies [PRESSING] panel) in patients with / wild-type (wt) metastatic colorectal cancer (mCRC) who were randomly assigned to panitumumab plus fluorouracil, leucovorin, and oxaliplatin (FOLFOX-4) induction followed by maintenance with panitumumab with or without fluorouracil (FU) plus leucovorin (LV); Valentino trial (ClinicalTrials.gov identifier: NCT02476045).

Patients And Methods: This prespecified retrospective analysis included 199 evaluable patients with / wt.

Tailoring chemotherapy supply according to patients' preferences: a quantitative method in colorectal cancer care.

The aim of this study was to conduct a discrete choice experiment with patients affected by colorectal cancer to understand their preferences for different attributes of the chemotherapy supply. Our overall goal is to provide evidence on the relative importance of each attribute in order to tailor chemotherapy supply according to patients' priorities in the design or reorganization processes of cancer services. Focus groups were used to identify the attributes and levels for the discrete choice experiment.

Maintenance Therapy With Panitumumab Alone vs Panitumumab Plus Fluorouracil-Leucovorin in Patients With RAS Wild-Type Metastatic Colorectal Cancer: A Phase 2 Randomized Clinical Trial.

Importance: Few studies are available on the role of maintenance strategies after induction treatment regimens based on anti-epidermal growth factor receptors, and the optimal regimen for an anti-epidermal growth factor receptors-based maintenance treatment in patients with RAS wild-type metastatic colorectal cancer is still to be defined.

Objective: To determine whether maintenance therapy with single-agent panitumumab was noninferior to panitumumab plus fluorouracil and leucovorin after a 4-month induction treatment regimen.

Design, Setting, And Participants: This open-label, randomized phase 2 noninferiority trial was conducted from July 7, 2015, through October 27, 2017, at multiple Italian centers.

HER2 Positivity Predicts Unresponsiveness to EGFR-Targeted Treatment in Metastatic Colorectal Cancer.

Background: HER2 amplification is detected in 3% of patients with colorectal cancer (CRC), making tumors in the metastatic setting vulnerable to double pharmacological HER2 blockade. Preclinical findings show that it also might impair response to anti-epidermal growth factor receptor (EGFR) treatment.

Subjects And Methods: Patients with exon 2 wild-type metastatic CRC underwent molecular screening of HER2 positivity by HERACLES criteria (immunohistochemistry 3+ or 2+ in ≥50% of cells, confirmed by fluorescence in situ hybridization).

Dose to Pelvic Bone Marrow Defined with FDG-PET Predicts for Hematologic Nadirs in Anal Cancer Patients Treated with Concurrent Chemo-radiation.

Purpose: To investigate whether irradiated volume of pelvic active bone marrow (BM) may predict decreased blood cells nadirs in anal cancer patients undergoing concurrent chemo-radiation.

Methods: Forty-four patients were analyzed and pelvic active bone marrow (BM) was characterized employing FDG-PET. Dosimetric parameters on dose-volume histograms were correlated to nadirs with generalized linear modeling.

and genotyping to predict adverse events during first-line FOLFIRI or FOLFOXIRI plus bevacizumab in metastatic colorectal cancer.

Our study addresses the issue of the clinical reliability of three candidate DPYD and one UGT single nucleotide polymorphisms in predicting 5-fluorouracil- and irinotecan-related adverse events. To this purpose, we took advantage of a large cohort of metastatic colorectal cancer patients treated with first-line 5-fluorouracil- and irinotecan-based chemotherapy regimens (i.e.

Quality of life, compliance, safety and effectiveness in fit older metastatic colorectal patients with cancer treated in first-line with chemotherapy plus cetuximab: A restrospective analysis from the ObservEr study.

Objectives: The influence of age (<70 years and ≥70 years) was retrospectively studied on the quality of life (QoL), incidence of side effects (including skin reactions) and efficacy of chemotherapy plus cetuximab in patients with KRAS wild type (WT) metastatic colorectal cancer (mCRC).

Methods: 225 patients of the Observed study (PS 0-1) were retrieved based on age (< 70 and ≥70 years) and evaluated through EORTC QLQ-C30 and DLQI questionnaires.

Results: The two patient groups (141 < 70 and 84 ≥ 70 years, respectively) were balanced with no differences in any of the clinical and pathological characteristics considered.

Discovery of methylated circulating DNA biomarkers for comprehensive non-invasive monitoring of treatment response in metastatic colorectal cancer.

Objective: Mutations in cell-free circulating DNA (cfDNA) have been studied for tracking disease relapse in colorectal cancer (CRC). This approach requires personalised assay design due to the lack of universally mutated genes. In contrast, early methylation alterations are restricted to defined genomic loci allowing comprehensive assay design for population studies.

Image-guided IMRT with simultaneous integrated boost as per RTOG 0529 for the treatment of anal cancer.

Aim: To report on clinical outcomes of simultaneous integrated boost intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy as per Radiation Therapy Oncology Group (RTOG) 0529 protocol in anal cancer patients.

Methods: Clinical stage T1-T4 N0-N3 anal cancer patients were submitted to concomitant chemoradiation. Patients with cT2N0 disease were prescribed 50.

Hematologic toxicity in anal cancer patients during combined chemo-radiation: a radiation oncologist perspective.

Hematologic toxicity is an important side effect occurring in patients affected with anal cancer, undergoing combined radio-chemotherapy, with consistent clinical meaningfulness. Areas covered: Since more than a half of bone marrow is comprised within the pelvic region, the radiation dose received by this functional compartment is crucial. Modern imaging modalities may provide a useful tool to identify bone marrow and new delivery technology may enhance the radiation oncologist's possibility to selectively spare these structures, potentially decreasing acute hematologic toxicity profile in this setting.

Lumbar-sacral bone marrow dose modeling for acute hematological toxicity in anal cancer patients treated with concurrent chemo-radiation.

The aim of the study was to model acute hematologic toxicity (HT) and dose to pelvic osseous structures in anal cancer patients treated with definitive chemo-radiation (CT-RT). A total of 53 patients receiving CT-RT were analyzed. Pelvic bone marrow and corresponding subsites were contoured: ilium, lower pelvis and lumbosacral spine (LSBM).

Jaw osteonecrosis associated with aflibercept, irinotecan and fluorouracil: attention to oral district.

Introduction: The antiangiogenic monoclonal antibody aflibercept in association with fluorouracil and irinotecan improves the survival of patients with metastatic colorectal cancer (mCRC) treated previously with oxaliplatin-based therapy. Multiple reports raised the hypothesis that the concomitant use of antiresorptive drugs and antiangiogenic drugs may increase the risk of osteonecrosis of the jaw (ONJ). Some reports have been published regarding cases of ONJ during treatment with bevacizumab for mCRC.