Dynamic Monitoring of Circulating Tumor DNA in Patients With Metastatic Colorectal Cancer.

PURPOSE: Plasma circulating tumor DNA (ctDNA) is a valuable resource for tumor characterization and for monitoring of residual disease during treatment; however, it is not yet introduced in metastatic colorectal cancer (mCRC) routine clinical practice. In this retrospective exploratory study, we evaluated the role of ctDNA in patients with mCRC treated with chemotherapy plus bevacizumab. MATERIALS AND METHODS: Fifty-three patients were characterized for RAS and BRAF status on tumor tissue before the start of treatment. Plasma was collected at baseline, at first clinical evaluation, and at disease progression. ctDNA analysis was performed using Oncomine Colon cfDNA Assay on the Ion S5 XL instrument. RESULTS: At baseline, from a plasma sample, RAS, BRAF, or PIK3CA mutations were detected in 44 patients. A high correspondence was observed between ctDNA and tumor tissue mutations (KRAS 100%, NRAS 97.9%, BRAF 97.9%, PIK3CA 90%). Low baseline variant allele frequency (VAF) was found to be associated with longer median progression-free survival (PFS) compared with those with high VAF (15.9 v 12.2 months, P = .02). A higher PFS {12.29 months (95% CI, 9.03 to 17.9) v 8.15 months (95% CI, 2.76 to not available [NA]), P = .04} and overall survival (34.1 months [95% CI, 21.68 to NA] v 11.1 months [95% CI, 3.71 to NA], P = .003) were observed in patients with large decline in VAF at first evaluation. CONCLUSION: ctDNA analysis is useful for molecular characterization and tumor response monitoring in patients with mCRC. Quantitative variations of released ctDNA are associated with clinical outcomes.

Association between Pre-Treatment Biological Indicators and Compliance to Neoadjuvant/Perioperative Chemotherapy in Operable Gastric Cancer.

BACKGROUND AND AIMS: Perioperative treatment is currently the gold standard approach in Europe for locally advanced gastric cancer (GC). Unfortunately, the phenomenon of patients dropping out of treatment has been frequently observed. The primary aims of this study were to verify if routine blood parameters, inflammatory response markers, sarcopenia, and the depletion of adipose tissues were associated with compliance to neoadjuvant/perioperative chemotherapy. METHODS AND STUDY DESIGN: Blood samples were considered before the first and second cycles of chemotherapy. Sarcopenia and adipose indices were calculated with a CT scan before starting chemotherapy and before surgery. Odds ratios (OR) from univariable and multivariable models were calculated with a 95% confidence interval (95% CI). RESULTS: A total of 84 patients with locally advanced GC were identified between September 2010 and January 2021. Forty-four patients (52.4%) did not complete the treatment according to the number of cycles planned/performed. Eight patients (9.5%) decided to suspend chemotherapy, seven patients (8.3%) discontinued because of clinical decisions, fourteen patients (16.7%) discontinued because of toxicity and fifteen patients (17.9%) discontinued for miscellaneous causes. Seventy-nine (94%) out of eighty-four patients underwent gastrectomy, with four patients having surgical complications, which led to a suspension of treatment. Sarcopenia was present in 38 patients (50.7%) before chemotherapy began, while it was present in 47 patients (60%) at the CT scan before the gastrectomy. At the univariable analysis, patients with basal platelet to lymphocyte ratio (PLR) ≥ 152 (p = 0.017) and a second value of PLR ≥ 131 (p = 0.007) were more frequently associated with an interruption of chemotherapy. Patients with increased PLR (p = 0.034) compared to the cut-off were associated with an interruption of chemotherapy, while patients with increased monocytes between the first and second cycles were associated with a lower risk of treatment interruption (p = 0.006); patients who underwent 5-fluorouracil plus cisplatin or oxaliplatin had a higher risk of interruption (p = 0.016) compared to patients who underwent a 5-fluorouracil plus leucovorin, oxaliplatin and docetaxel (FLOT) regimen. The multivariable analysis showed a higher risk of interruption for patients who had higher values of PLR compared to the identified cut-off both at pretreatment and second-cycle evaluation (OR: 5.03; 95% CI: 1.34-18.89; p = 0.017) as well as for patients who had a lower PLR than the identified cut-off at pretreatment evaluation and had a higher PLR value than the cut-off at the second cycle (OR: 4.64; 95% CI: 1.02-21.02; p = 0.047). Becker regression was neither affected by a decrease of sarcopenia ≥ 5% (p = 0.867) nor by incomplete compliance with chemotherapy (p = 0.281). CONCLUSIONS: Changes in PLR values which tend to increase more than the cut-off seem to be an immediate indicator of incomplete compliance with neoadjuvant/perioperative treatment. Fat loss and sarcopenia do not appear to be related to compliance. More information is needed to reduce the causes of interruption.

Patient centered radiology: investigating 3 Tesla whole body MRI acceptance in cancer patients.

INTRODUCTION: Whole body magnetic resonance imaging (WB-MRI) is a promising emerging imaging technology for detecting bone and soft tissue pathology, especially in the onco-hematological field. This study aims to evaluate cancer patients' experience of WB-MRI performed on a 3T scanner compared to other diagnostic total body examinations. MATERIAL AND METHOD: In this prospective committee-approved study, patients completed a questionnaire in person (n = 134) after undergoing a WB-MRI scan to collect data on their physical and psychological reactions during the scan, the global satisfaction level, and preference for other types of MRI or computed tomography (CT), or positron emission tomography (PET/CT). Of all patients who had performed a CT or PET/CT the previous year, 61.9% had already undergone an MRI. The most common symptoms reported were: 38.1% perceived a localized increase in temperature and 34.4% numbness and tingling of the limbs. The scan time averaged 45 min and was well tolerated by most patients (112, 85.5%). Overall, WB-MRI was appreciated by the majority (121/134-90.3%) of patients who said they would probably undergo the procedure again. Patients preferred the WB-MRI in 68.7% of cases (92/134), followed by CT in 15.7% of cases (21/134) and by PET/CT in 7.4% (10/134), with 8.4% (11/134) of patients without any preference. The preference for imaging modalities was age-dependent (p = 0.011), while (p > 0.05) was independent of sex and a primary cancer site. CONCLUSION: These results demonstrate a high degree of WB-MRI acceptance from a patient's point of view.

Computed tomography based analyses of body mass composition in HER2 positive metastatic breast cancer patients undergoing first line treatment with pertuzumab and trastuzumab.

Body composition parameters (BCp) have been associated with outcome in different tumor types. However, their prognostic value in patients with HER2-positive metastatic breast cancer (BC) receiving first line treatment with dual anti-HER2 antibody blockade is unknown. Preclinical evidences suggest that adipocytes adjacent to BC cells can influence response to anti-HER2 treatments. We retrospectively analyzed Computed Tomography (CT)-based BCp from 43 patients with HER2-positive metastatic BC who received first line pertuzumab/trastuzumab-based treatment between May 2009 and March 2020. The impact of baseline CT-based BCp on progression-free survival (PFS) was tested using Kaplan-Meier estimates and univariate and multivariate Cox regression models. We found a significantly worse PFS for patients with high baseline subcutaneous fat index (median 7.9 vs 16.1 months, p = 0.047, HR = 2.04, 95%CI 1-4.17) and for those with high total abdominal fat index (8.1 vs 18.8 months, p = 0.030, HR = 2.17, 95%CI 1.06-4.46). Patients with baseline sarcopenia did not show shorter PFS compared to those without sarcopenia (10.4 vs 9.2 months, p = 0.960, HR = 0.98, 95%CI 0.47-2.03). Total abdominal fat index remained a significant predictor of PFS at multivariate analysis. Our findings suggest that a high quantity of total abdominal fat tissue is a poor prognostic factor in patients receiving trastuzumab/pertuzumab-based first-line treatment for HER2-positive metastatic BC.

Radiology imaging management in an Italian cancer center (IRST IRCCS) during the COVID-19 pandemic.

In Italy, the first case of the coronavirus disease 2019 (COVID-19) was officially reported on 20.02.2020. The disease has since rapidly evolved, causing a public health emergency throughout the country but especially in our region, one of the most widely affected areas. We reorganized the daily routine of our cancer center to reduce the risk of contagion. A temporary tensile structure was set up as an entry-point triage, and a COVID-19 route was created with a dedicated CT scanner. A pre-access telephonic triage was performed the day before a patient was scheduled to come in for an examination. At the time of writing (May 4), 4053 patients had been to our center since the emergency officially began (9.03.2020) and the COVID-19 route had been activated for only 9 paucisymptomatic outpatients and 7 symptomatic inpatients. We also re-evaluated patient radiology examination lists and rescheduled non-urgent tests in consensus with the referring oncologist. Out of a total of 1438 patients scheduled for radiological examinations, 456 were postponed for a total volume reduction of 29.1%. Nine asymptomatic patients with typical CT findings of COVID-19 were identified during routine CTs, but none were RT-PCR-positive for SARS-CoV-2. We guaranteed all urgent and semi-urgent examinations, including those to stage newly diagnosed cancers and to evaluate response to treatment, ensuring the continuation of the diagnostic and therapeutic pathway of our patients. The measures we took were instrumental in keeping the institute COVID-19-free. We also describe the planned measures to resume normal clinical practice at the center.

Evaluation of Multifocality and Multicentricity With Breast Magnetic Resonance Imaging in Each Breast Cancer Subtype.

INTRODUCTION: The purpose of this study was to evaluate whether diagnostic performance of breast magnetic resonance imaging (MRI) for detection of multifocality and multicentricity (MFMC) of breast cancer (BC) can be influenced by different histotypes or immunophenotypes in newly diagnosed patients with breast cancer. MATERIALS AND METHODS: In this institutional review board-approved retrospective study, 289 patients who underwent both preoperative breast MRI and radical or modified mastectomy in our institution because of primary BCs were selected. Patients were stratified based on the pathologic report in 2 main histotypes and 5 immunophenotypes. By matching the radiologic report with the corresponding pathologic report for each patient, breast MRI performance for detection of MFMC were obtained in each histotype and immunophenotype and subsequently compared. RESULTS: Overall breast MRI sensitivity for MFMC detection was 88.1%, specificity was 80.0%, positive predictive value 82.1%, negative predictive value 85.8%, diagnostic accuracy 83.7%, and area under the curve 0.835. Breast MRI sensitivity for MFMC detection in triple-negative BC was 84.6% (P = .88), specificity 70.8% (P = .63), positive predictive value 61.1% (P = .02), negative predictive value 89.5% (P = .20), diagnostic accuracy 75.7% (P = .65), and area under the curve 0.777 (P = .87). CONCLUSION: Performance of breast MRI for the detection of MFMC are not influenced by the BC histotypes, in accordance with published literature. Conversely, the triple-negative immunophenotypes demonstrated lower performance, statistically significant only for positive predictive value (P = .02), for the detection of MFMC.