Difference in SARS-CoV-2 Antibody Status Between Patients With Cancer and Health Care Workers During the COVID-19 Pandemic in Japan.

Importance: Patients with cancer and health care workers (HCWs) are at high risk of SARS-CoV-2 infection. Assessing the antibody status of patients with cancer and HCWs can help understand the spread of COVID-19 in cancer care. Objective: To evaluate serum SARS-CoV-2 antibody status in patients with cancer and HCWs during the COVID-19 pandemic in Japan. Design, Setting, and Participants: Participants were enrolled for this prospective cross-sectional study between August 3 and October 30, 2020, from 2 comprehensive cancer centers in the epidemic area around Tokyo, Japan. Patients with cancer aged 16 years or older and employees were enrolled. Participants with suspected COVID-19 infection at the time of enrollment were excluded. Exposures: Cancer of any type and cancer treatment, including chemotherapy, surgery, immune checkpoint inhibitors, radiotherapy, and targeted molecular therapy. Main Outcomes and Measures: Seroprevalence and antibody levels in patients with cancer and HCWs. Seropositivity was defined as positivity to nucleocapsid IgG (N-IgG) and/or spike IgG (S-IgG). Serum levels of SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins were measured by chemiluminescent enzyme immunoassay. Results: A total of 500 patients with cancer (median age, 62.5 years [range, 21-88 years]; 265 men [55.4%]) and 1190 HCWs (median age, 40 years [range, 20-70 years]; 382 men [25.4%]) were enrolled. In patients with cancer, 489 (97.8%) had solid tumors, and 355 (71.0%) had received anticancer treatment within 1 month. Among HCWs, 385 (32.3%) were nurses or assistant nurses, 266 (22.4%) were administrative officers, 197 (16.6%) were researchers, 179 (15.0%) were physicians, 113 (9.5%) were technicians, and 50 (4.2%) were pharmacists. The seroprevalence was 1.0% (95% CI, 0.33%-2.32%) in patients and 0.67% (95% CI, 0.29%-1.32%) in HCWs (P = .48). However, the N-IgG and S-IgG antibody levels were significantly lower in patients than in HCWs (N-IgG: ß, -0.38; 95% CI, -0.55 to -0.21; P < .001; and S-IgG: ß, -0.39; 95% CI, -0.54 to -0.23; P < .001). Additionally, among patients, N-IgG levels were significantly lower in those who received chemotherapy than in those who did not (median N-IgG levels, 0.1 [interquartile range (IQR), 0-0.3] vs 0.1 [IQR, 0-0.4], P = .04). In contrast, N-IgG and S-IgG levels were significantly higher in patients who received immune checkpoint inhibitors than in those who did not (median N-IgG levels: 0.2 [IQR, 0.1-0.5] vs 0.1 [IQR, 0-0.3], P = .02; S-IgG levels: 0.15 [IQR, 0-0.3] vs 0.1[IQR, 0-0.2], P = .02). Conclusions and Relevance: In this cross-sectional study of Japanese patients with cancer and HCWs, the seroprevalence of SARS-CoV-2 antibodies did not differ between the 2 groups; however, findings suggest that comorbid cancer and treatment with systemic therapy, including chemotherapy and immune checkpoint inhibitors, may influence the immune response to SARS-CoV-2.

Prognostic significance of tumor regression grade for patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy followed by surgery.

BACKGROUND AND OBJECTIVES: To clarify prognostic factors for the patients with esophageal squamous cell carcinoma (ESCC) through an assessment of surgically resected specimens modified by neoadjuvant chemotherapy (nCT). METHODS: We retrospectively reviewed the clinicopathological data of 143 consecutive patients with ESCC who underwent nCT followed by surgery between 2008 and 2012 at our institution and conducted survival analysis. The tumor regression grade (TRG) was classified based on the proportion of residual tumor cells in the area where the tumor was thought to have existed before nCT as follows: Grade 0 (no therapeutic effect), Grade 1a (residual tumor cells ≥2/3), Grade 1b (1/3≤ residual tumor cells <2/3), Grade 2 (residual tumor cells <1/3), and Grade 3 (no residual tumor). RESULTS: The 3-year OS and RFS of patients with tumor regression grade 0/1a/1b-3 were 53.6%/73.3%/88.6% and 37.7%/60.5%/83.8%, respectively. A multivariate analysis demonstrated that TRG was an independent predictor of OS (TRG 1a-3: HR, 0.46; 95%CI, 0.23-0.89), in addition to venous invasion, and of RFS (TRG 1a-3: HR, 0.49; 95%CI, 0.28-0.84), in addition to ypT factor, and venous invasion. CONCLUSIONS: TRG is a critical prognostic factor in patients with ESCC who had undergone nCT followed by surgery. J. Surg. Oncol. 2016;113:390-396. © 2016 Wiley Periodicals, Inc.

Feasibility of oxaliplatin and infusional fluorouracil/leucovorin (FOLFOX4) for Japanese patients with unresectable metastatic colorectal cancer.

BACKGROUND: A combination of oxaliplatin and infusional fluorouracil/leucovorin (FOLFOX4) is one of the standard regimens for palliative and adjuvant chemotherapy for colorectal cancer. However, the feasibility of FOLFOX4 for Japanese patients has not been determined. We conducted this prospective study to evaluate the feasibility of FOLFOX4. METHODS: Previously treated or untreated patients with unresectable metastatic colorectal cancer were enrolled. The primary endpoint was the rate of completion which was defined as completion of the first 4 cycles with relative dose-intensity of oxaliplatin of 80% or higher. RESULTS: Of the 32 enrolled patients, 31 received FOLFOX4. Twenty-four patients (75%) had received prior chemotherapy. The rate of completion of the first four cycles was 87% (27/31; 95% CI, 70.2-96.4%). With the median number of cycles of nine (range, 1-26), grade 3 or 4 hematological toxicity and non-hematological toxicity were seen in 12 (39%) and 5 (16%) patients, respectively. Grade 1 or 2 sensory neuropathy was seen in 28 patients (90%), but no grade 3 or 4 neuropathy was seen. Grade 1 or 2 allergic reaction was seen in five patients (16%). One patient developed fatal interstitial pneumonitis and died of respiratory failure. Objective response rate was 28.6% (6/21; 95% CI, 11.3-52.2%) in the patients with measurable lesions. Median progression-free survival was 6.5 months (95% CI, 4.6-8.5 months) in all patients. CONCLUSIONS: The completion rate of the first four cycles was as high as expected with manageable toxicity, although fatal pneumonitis developed in one case. FOLFOX4 is feasible for Japanese patients.

Phase I/II study of oxaliplatin with weekly bolus fluorouracil and high-dose leucovorin (ROX) as first-line therapy for patients with colorectal cancer.

BACKGROUND: Infusional fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin is one of the current standard regimens for the treatment of patients with metastatic colorectal cancer. Weekly bolus 5-FU with high-dose LV (Roswell Park Memorial Institute Regimen: RPMI) is the most commonly used regimen in Japan. The objectives of this study were to determine the recommended dose (RD) of RPMI combined with oxaliplatin and to evaluate the toxicity and efficacy at the RD. METHODS: The subjects were 18 patients with metastatic colorectal cancer. Oxaliplatin (85 mg/m2) was given intravenously over 2 h on days 1 and 15 with l-LV (250 mg/m2) given intravenously over 2 h and 5-FU as an intravenous bolus on days 1, 8, and 15. This treatment was repeated every 4 weeks. The dose of 5-FU was escalated from 400 mg/m2 (level 1) to 500 mg/m2 (level 2). RESULTS: A total of 14 patients received level 1, and 4 received level 2. Three of the patients had dose-limiting toxicity (DLT) in cycle 1 of level 2 (grade 3 thrombocytopenia, grade 4 neutropenia and grade 2 neutropenia in one patient each), requiring that treatment was delayed for longer than 7 days. None of the 14 patients given level 1 had DLT or grade 3 or 4 gastrointestinal toxicity. Sensory neuropathy occurred in all patients. Objective response rates were 61% in the 18 patients studied and 64% at level 1. The median time to progression was 171 days, and the median overall survival time was 603 days in the 18 patients studied. CONCLUSIONS: Oxaliplatin (85 mg/m2) with weekly bolus 5-FU (400 mg/m2) and high-dose l-LV (250 mg/m2) is recommended for further phase III studies in patients with metastatic colorectal cancer.