Heterogeneous immunogenicity of SARS-CoV-2 vaccines in cancer patients receiving radiotherapy.

The immunogenicity of SARS-CoV-2 vaccines in cancer patients receiving radiotherapy is unknown. This prospective cohort study demonstrates that anti-SARS-CoV-2 spike antibody and neutralization titers are reduced in a subset of thoracic radiotherapy patients, possibly due to immunosuppressive conditions. Antibody testing may be useful to identify candidates for additional vaccine doses.

Immunogenicity and Reactogenicity of SARS-CoV-2 Vaccines in Patients With Cancer: The CANVAX Cohort Study.

PURPOSE: The immunogenicity and reactogenicity of SARS-CoV-2 vaccines in patients with cancer are poorly understood. METHODS: We performed a prospective cohort study of adults with solid-organ or hematologic cancers to evaluate anti-SARS-CoV-2 immunoglobulin A/M/G spike antibodies, neutralization, and reactogenicity ≥ 7 days following two doses of mRNA-1273, BNT162b2, or one dose of Ad26.COV2.S. We analyzed responses by multivariate regression and included data from 1,638 healthy controls, previously reported, for comparison. RESULTS: Between April and July 2021, we enrolled 1,001 patients; 762 were eligible for analysis (656 had neutralization measured). mRNA-1273 was the most immunogenic (log10 geometric mean concentration [GMC] 2.9, log10 geometric mean neutralization titer [GMT] 2.3), followed by BNT162b2 (GMC 2.4; GMT 1.9) and Ad26.COV2.S (GMC 1.5; GMT 1.4; P < .001). The proportion of low neutralization (< 20% of convalescent titers) among Ad26.COV2.S recipients was 69.9%. Prior COVID-19 infection (in 7.1% of the cohort) was associated with higher responses (P < .001). Antibody titers and neutralization were quantitatively lower in patients with cancer than in comparable healthy controls, regardless of vaccine type (P < .001). Receipt of chemotherapy in the prior year or current steroids were associated with lower antibody levels and immune checkpoint blockade with higher neutralization. Systemic reactogenicity varied by vaccine and correlated with immune responses (P = .002 for concentration, P = .016 for neutralization). In 32 patients who received an additional vaccine dose, side effects were similar to prior doses, and 30 of 32 demonstrated increased antibody titers (GMC 1.05 before additional dose, 3.17 after dose). CONCLUSION: Immune responses to SARS-CoV-2 vaccines are modestly impaired in patients with cancer. These data suggest utility of antibody testing to identify patients for whom additional vaccine doses may be effective and appropriate, although larger prospective studies are needed.

Low Rates of Chest Wall Toxicity When Individualizing the Planning Target Volume Margin in Patients With Early Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy.

PURPOSE: Chest wall (CW) toxicity is a potentially debilitating complication of stereotactic body radiation therapy for non-small cell lung cancer, occurring in 10% to 40% of patients. Smaller tumor-to-CW distance has been identified as a risk factor for CW toxicity. We report our experience with individualizing the planning target volume (PTV) along the CW in an effort to reduce the volume of this organ at risk receiving 30 Gy to 50 Gy. METHODS AND MATERIALS: We performed an institutional review board-approved retrospective analysis of patients with stage I (T1-2aN0M0) non-small cell lung cancer who received stereotactic body radiation therapy between June 2009 and July 2016. Four-dimensional computed tomography was used for treatment planning. A uniform 5-mm expansion of the internal target volume was generated for the PTV. Areas of overlap with the CW were removed from the PTV. Treatment was delivered with cone beam computed tomography guidance. CW toxicity was assessed per the Common Terminology Criteria for Adverse Events, version 5. Descriptive statistics were used to analyze outcomes. RESULTS: The median follow-up time was 36.8 months. A total of 260 tumors were treated in 225 patients. 225 tumors in 203 patients were peripheral. The internal target volumes for 143 tumors (63.6%) were located within 5 mm of the CW. The median total dose was 48 Gy (range, 42-60 Gy) in 4 fractions (range, 3-5 fractions). The overall rate of grade 1 to 2 CW toxicity was 2.2%, and 2.8% for tumors located within 5 mm of the CW. There were no grade 3/4 cases and no increase in local recurrences with the use of a truncated PTV with a 3-year local control of 92.1% (95% confidence interval, 87.4%-96.8%). CONCLUSIONS: Truncation of the PTV margin along the CW resulted in a marked reduction of CW toxicity for tumors in close proximity to the CW, with only a 2.8% rate of grade 1 to 2 CW toxicity. Despite PTV reduction, there was no appreciable increase in local failures. A multi-institutional validation of this technique is needed before general incorporation into clinical practice.

Assessment of a Contralateral Esophagus-Sparing Technique in Locally Advanced Lung Cancer Treated With High-Dose Chemoradiation: A Phase 1 Nonrandomized Clinical Trial.

IMPORTANCE: Severe acute esophagitis occurs in up to 20% of patients with locally advanced lung cancer treated with chemoradiation therapy to at least 60 Gy once daily and represents a dose-limiting toxic event associated with poor outcomes. OBJECTIVE: To assess whether formalized sparing of the contralateral esophagus (CE) is associated with reduced risk of severe acute esophagitis. DESIGN, SETTING, AND PARTICIPANTS: This single-center phase 1 nonrandomized clinical trial assessing an empirical CE-sparing technique enrolled patients from July 2015 to January 2019. In total, 27 patients with locally advanced non-small cell lung carcinoma (with or without solitary brain metastasis) or limited-stage small cell lung carcinoma with gross tumor within 1 cm of the esophagus were eligible. INTERVENTIONS: Intensity-modulated radiation therapy to 70 Gy at 2 Gy/fraction concurrent with standard chemotherapy with or without adjuvant durvalumab. The esophageal wall contralateral to gross tumor was contoured as an avoidance structure to guide a steep dose falloff gradient. Target coverage was prioritized over CE sparing, and 99% of internal and planning target volumes had to be covered by 70 Gy and at least 63 Gy, respectively. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of at least grade 3 acute esophagitis as assessed by Common Terminology Criteria for Adverse Events, version 4. RESULTS: Of 27 patients enrolled, 25 completed chemoradiation therapy. Nineteen patients had non-small cell lung carcinoma, and 6 had small cell lung carcinoma. The median age at diagnosis was 67 years (range, 51-81 years), and 15 patients (60%) were men. Thirteen patients (52%) had stage IIIA cancer, 10 (40%) had stage IIIB cancer, and 2 (8%) had stage IV cancer. The median CE maximum dose was 66 Gy (range, 44-71 Gy); the median volume of CE receiving at least 55 Gy was 1.4 cm3 (range, 0-5.3 cm3), and the median volume of CE receiving at least 45 Gy was 2.7 cm3 (range, 0-9.2 cm3). The median combined percentage of lung receiving at least 20 Gy was 25% (range, 11%-37%). The median follow-up was 33.3 months (range, 11.1-52.2 months). Among the 20 patients who had treatment breaks of 0 to 3 days and were thus evaluable for the primary end point, the rate of at least grade 3 esophagitis was 0%. Other toxic events observed among all 25 patients included 7 (28%) with grade 2 esophagitis, 3 (12%) with at least grade 2 pneumonitis (including 1 with grade 5), and 2 (8%) with at least grade 3 cardiac toxic event (including 1 with grade 5). There was no isolated local tumor failure. The 2-year progression-free survival rate was 57% (95% CI, 33%-75%), and the 2-year overall survival rate was 67% (95% CI, 45%-82%). CONCLUSIONS AND RELEVANCE: This phase 1 nonrandomized clinical trial found that the CE-sparing technique was associated with reduced risk of esophagitis among patients treated uniformly with chemoradiation therapy (to 70 Gy), with no grade 3 or higher esophagitis despite tumor within 1 cm of the esophagus. This technique may be translated into clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02394548.