Association of COVID-19 Lockdown With the Tumor Burden in Patients With Newly Diagnosed Metastatic Colorectal Cancer.

Importance: The COVID-19 pandemic has been associated with substantial reduction in screening, case identification, and hospital referrals among patients with cancer. However, no study has quantitatively examined the implications of this correlation for cancer patient management. Objective: To evaluate the association of the COVID-19 pandemic lockdown with the tumor burden of patients who were diagnosed with metastatic colorectal cancer (mCRC) before vs after lockdown. Design, Setting, and Participants: This cohort study analyzed participants in the screening procedure of the PANIRINOX (Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab vs FOLFOX + Panitumumab in Metastatic Colorectal Cancer Patients Stratified by RAS Status from Circulating DNA Analysis) phase 2 randomized clinical trial. These newly diagnosed patients received care at 1 of 18 different clinical centers in France and were recruited before or after the lockdown was enacted in France in the spring of 2020. Patients underwent a blood-sampling screening procedure to identify their RAS and BRAF tumor status. Exposures: mCRC. Main Outcomes and Measures: Circulating tumor DNA (ctDNA) analysis was used to identify RAS and BRAF status. Tumor burden was evaluated by the total plasma ctDNA concentration. The median ctDNA concentration was compared in patients who underwent screening before (November 11, 2019, to March 9, 2020) vs after (May 14 to September 3, 2020) lockdown and in patients who were included from the start of the PANIRINOX study. Results: A total of 80 patients were included, of whom 40 underwent screening before and 40 others underwent screening after the first COVID-19 lockdown in France. These patients included 48 men (60.0%) and 32 women (40.0%) and had a median (range) age of 62 (37-77) years. The median ctDNA concentration was statistically higher in patients who were newly diagnosed after lockdown compared with those who were diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL; P < .001). Patients with mCRC and high ctDNA concentration had lower median survival compared with those with lower concentration (14.7 [95% CI, 8.8-18.0] months vs 20.0 [95% CI, 14.1-32.0] months). This finding points to the potential adverse consequences of the COVID-19 pandemic and related lockdown. Conclusions and Relevance: This cohort study found that tumor burden differed between patients who received an mCRC diagnosis before vs after the first COVID-19 lockdown in France. The findings of this study suggest that CRC is a major area for intervention to minimize pandemic-associated delays in screening, diagnosis, and treatment.

Clinical Relevance of Viable Circulating Tumor Cells in Patients with Metastatic Colorectal Cancer: The COLOSPOT Prospective Study.

BACKGROUND: Circulating tumor cells (CTCs) allow the real-time monitoring of tumor course and treatment response. This prospective multicenter study evaluates and compares the early predictive value of CTC enumeration with EPISPOT, a functional assay that detects only viable CTCs, and with the CellSearch® system in patients with metastatic colorectal cancer (mCRC). METHODS: Treatment-naive patients with mCRC and measurable disease (RECIST criteria 1.1) received FOLFIRI-bevacizumab until progression or unacceptable toxicity. CTCs in peripheral blood were enumerated at D0, D14, D28, D42, and D56 (EPISPOT assay) and at D0 and D28 (CellSearch® system). Progression-free survival (PFS) and overall survival (OS) were assessed with the Kaplan-Meier method and log-rank test. RESULTS: With the EPISPOT assay, at least 1 viable CTC was detected in 21% (D0), 15% (D14), 12% (D28), 10% (D42), and 12% (D56) of 155 patients. PFS and OS were shorter in patients who remained positive, with viable CTCs between D0 and D28 compared with the other patients (PFS = 7.36 vs. 9.43 months, p = 0.0161 and OS = 25.99 vs. 13.83 months, p = 0.0178). The prognostic and predictive values of ≥3 CTCs (CellSearch® system) were confirmed. CONCLUSIONS: CTC detection at D28 and the D0-D28 CTC dynamics evaluated with the EPISPOT assay were associated with outcomes and may predict response to treatment.

Exclusive concurrent radiochemotherapy for advanced head and neck cancers with 'fractionated' 5-fluorouracil and cisplatin.

Concurrent radiochemotherapy (CRC) is a standard treatment in patients with inoperable locoregionally advanced ear-nose-throat (ENT) cancer. We report the safety and efficacy of CRC with daily fractionated 5-fluorouracil and cisplatin ('F' 5FU-CDDP) in a monocentric retrospective cohort. From January 2006 to August 2012, all patients with unresectable (or inoperable) nonmetastatic locoregionally advanced ENT cancer treated curatively by means of radiotherapy (normal fractionated 70 Gy to the macroscopic tumor and prophylactic 50 Gy) with three courses (week 1-week 4-week 7) of 'F' 5FU-CDDP regimen (800 mg/m/day of 5-fluorouracil and 20 mg/m/day of CDDP from day 1 to day 4) were included. Seventy patients underwent CRC (86% men, median age 58 years old, 100% squamous cell carcinoma, 97% stage III/IV). Fifty-six patients received the three complete courses of chemotherapy with cumulative doses of CDDP of 217 mg/m/patient (dose intensity ratio of 90.5%). After a median follow-up period of 30.7 months, median overall and disease-free survivals were 34.1 [95% confidence interval (CI) (21.6-56.8)] and 50.2 months [95% CI (17.4-NA)] with 71% [95% CI (57.5-81)] and 67% [95% CI (51.8-78.5)] for locoregional control at 2 and 5 years, respectively. In all, 58.5% of grade 3 or higher mucositis and 24% of radioepithelitis were observed, but only 11.5, 3, and 1.5% of grade 3 or higher neutropenia, nephrotoxicity, and neurotoxicity were observed, respectively. No deaths from toxicity occurred. CRC with three courses of 'F' 5FU-CDDP appears effective and could be an alternative to standard CRC treatment. Randomized studies are required to be able to use this treatment regimen routinely.

Feasibility and safety of dose-dense modified docetaxel-cisplatin or carboplatin and 5-fluorouracil regimen (mTPF) in locally advanced or metastatic head and neck cancers: a retrospective monocentric study.

BACKGROUND: Docetaxel-cisplatin and 5-fluorouracil (TPF) chemotherapy (days 1-21) represents a standard but toxic regimen for advanced head and neck cancer (HNC). We report a retrospective monocentric study evaluating the safety and the efficacy of a dose-dense modified TPF (mTPF) regimen (days 1-14) in patients with stage III-IV HNC. METHODS: Thirty-seven patients retrospectively included from May 2011 to May 2014 were treated with a bimonthly dose-dense mTPF regimen (40 mg/m(2) docetaxel, 40 mg/m(2) cisplatin or AUC2 carboplatin, folinic acid 400 mg/m(2) for 2 h, bolus 5-FU 400 mg/m(2) for 10 min and 5-FU 1,000 mg/m(2)/day) by continuous infusion over 46 h). RESULTS: Chemotherapy was used as induction or palliative treatment in 12 and 25 patients, respectively, with a median age of 60 years (range 46-83). Median follow-up time was 7.4 months (2.53-16.7 months). There was no intestinal toxicity in 25 patients (68 %). Grade 3-4 hematological toxicity was noticed for 5 (13.5 %) patients. Granulocyte-colony stimulating factor was used as primary prophylaxis in 30 patients (81 %). After at least 4 delivered cycles, complete responses, partial responses and stable diseases were reported in 5 (15 %), 13 (39 %) and 5 (15 %) of the 33 evaluable patients, respectively, yielding an objective response rate of 54.5 % (39 % for palliative chemotherapy and 90 % for induction chemotherapy). CONCLUSION: Dose-dense mTPF (days 1-14) is safe and seems to be as effective as TPF (days 1-21). Future prospective trials are required to confirm our results.