Comment on Ivanov et al. Ultra-Hypofractionated vs. Moderate Fractionated Whole Breast Three Dimensional Conformal Radiotherapy during the COVID-19 Pandemic. Medicina 2022, 58, 745.

I read the paper by Ivanov et al. [...].

Ultra-Hypofractionated vs. Moderate Fractionated Whole Breast Three Dimensional Conformal Radiotherapy during the COVID-19 Pandemic.

Background and Objectives: Reducing time of treatment during COVID-19 outbreaks has been recommended by the leading Radiation Oncology societies. Still minimizing radiation induced tissue toxicity is one of the most important issues in breast cancer patients. The study aimed to investigate compliance, clinical and dosimetry normal tissue toxicity, and cosmetic results between moderated and ultra-fractionated regimes for breast cancer patients during COVID-19 pandemic. Materials and Methods: This pilot prospective randomized study included 60 patients with early breast cancer after preserving surgery, 27 patients advocated to ultra-hypofractionated whole-breast three dimensional (3D) conformal radiotherapy of 26 Gy in 5 fractions over 1 week and 33 patients with moderate fractionated breast 3D conformal radiotherapy patients between March 2020 and July 2020, during the COVID pandemic outbreak. The compliance to treatment, dosimetric parameters, acute and late skin toxicity, subcutaneous tissue toxicity, cosmetic results and clinical follow up for 18 months for the two regimes were analyzed and compared. Results: When two regimes were compared 5 fraction group had significantly lower prevalence of newly infected cases of SARS-CoV-2 and thus delayed/interrupted treatment (p = 0.05), comparable grade 1 CTCAE v5, acute skin toxicity (p = 0.18), Grade 1 Radiation Morbidity Scoring Scheme (RESS) subcutaneous tissue toxicity (p = 0.18), Grade 1 RESS late skin toxicity (p = 0.88) and cosmetic results (p = 0.46). Dosimetric results reveled that patients in 5 fraction group received significantly lower median ipsilateral lung doses (p < 0.01) in addition to left breast cancer patients that received significantly lower median heart dose (p < 0.01) and median left anterior descending artery (LAD) dose (p < 0.01). Conclusion: Ultra-hypofractionated radiotherapy for breast cancer is comparable to moderate hypofractionation regimen regarding grade 1 acute skin toxicity, grade 1 subcutaneous tissue toxicity, late skin toxicity and cosmetic results. Application of ultra-hypofractionated radiotherapy with significantly lower radiation doses for lung and heart could be crucial in reducing the risk of acute/late pulmonary and heart radiation-induced toxicity.

Estimating cancer risks due to whole lungs low dose radiotherapy with different techniques for treating COVID-19 pneumonia.

BACKGROUND: Low dose radiotherapy (LDRT) of whole lungs with photon beams is a novel method for treating COVID-19 pneumonia. This study aimed to estimate cancer risks induced by lung LDRT for different radiotherapy delivery techniques. METHOD: Four different radiotherapy techniques, including 3D-conformal with anterior and posterior fields (3D-CRT AP-PA), 3D-conformal with 8 coplanar fields (3D-CRT 8 fields), eight fields intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy using 2 full arcs (VMAT) were planned on the CT images of 32 COVID-19 patients with the prescribed dose of 1 Gy to the lungs. Organ average and maximum doses, and PTV dose distribution indexes were compared between different techniques. The radiation-induced cancer incidence and cancer-specific mortality, and cardiac heart disease risks were estimated for the assessed techniques. RESULTS: In IMRT and VMAT techniques, heart (mean and max), breast (mean, and max), and stomach (mean) doses and also maximum dose in the body were significantly lower than the 3D-CRT techniques. The calculated conformity indexes were similar in all the techniques. However, the homogeneity indexes were lower (i.e., better) in intensity-modulated techniques (P < 0.03) with no significant differences between IMRT and VMAT plans. Lung cancer incident risks for all the delivery techniques were similar (P > 0.4). Cancer incidence and mortality risks for organs located closer to lungs like breast and stomach were higher in 3D-CRT techniques than IMRT or VMAT techniques (excess solid tumor cancer incidence risks for a 30 years man: 1.94 ± 0.22% Vs. 1.68 ± 0.17%; and women: 6.66 ± 0.81% Vs. 4.60 ± 0.43%: cancer mortality risks for 30 years men: 1.63 ± 0.19% Vs. 1.45 ± 0.15%; and women: 3.63 ± 0.44% Vs. 2.94 ± 0.23%). CONCLUSION: All the radiotherapy techniques had low cancer risks. However, the overall estimated risks induced by IMRT and VMAT radiotherapy techniques were lower than the 3D-CRT techniques and can be used clinically in younger patients or patients having greater concerns about radiation induced cancers.

Postoperative Radiotherapy for Locally Advanced NSCLC: Implications for Shifting to Conformal, High-Risk Fields.

BACKGROUND: To examine the effect of radiotherapy field size on survival outcomes and patterns of recurrence in patients treated with postoperative radiotherapy (PORT) for non-small-cell lung cancer (NSCLC). METHODS: We retrospectively reviewed the records of 216 patients with T1-4 N1-2 NSCLC following surgery and PORT using whole mediastinum (WM) or high-risk (HR) nodal fields from 1998 to 2015. Survival rates were calculated using the Kaplan-Meier method. Univariate and multivariable analyses were conducted using Cox proportional hazards modeling for outcomes and logistic regression analysis for treatment toxicities. RESULTS: Median follow-up was 28 months (interquartile range [IQR] 13-75 months) and 38 months (IQR 19-73 months) for WM (n = 131) and HR (n = 84) groups, respectively. Overall survival (OS) was not significantly different between groups (median OS: HR 49 vs. WM 32 months; P = .08). There was no difference in progression-free survival (PFS), freedom from locoregional recurrence (LRR), or freedom from distant metastasis (P > .2 for all). Field size was not associated with OS, PFS, or LRR (P > .40 for all). LRR rates were 20% for HR and 26% for WM groups (P = .30). There was no significant difference in patterns of initial site of LRR between groups (P > .1). WM fields (OR 3.73, P = .001) and concurrent chemotherapy (odds ratio 3.62, P = .001) were associated with grade ≥2 toxicity. CONCLUSIONS: Locoregional control and survival rates were similar between PORT groups; an improved toxicity profile was observed in the HR group. Results from an ongoing prospective randomized clinical trial will provide further insight into the consequences of HR PORT fields.

Could pulmonary low-dose radiation therapy be an alternative treatment for patients with COVID-19 pneumonia? Preliminary results of a multicenter SEOR-GICOR nonrandomized prospective trial (IPACOVID trial).

PURPOSE: To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Inclusion criteria comprised patients with COVID-19-related moderate-severe pneumonia warranting hospitalization with supplemental O2 and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO2) or the pulse oximetry saturation (SpO2) to fractional inspired oxygen (FiO2) ratio of at least 20% at 24 h with respect to the preirradiation value. RESULTS: Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X­ray. All patients received dexamethasone treatment. Mean SpO2 pretreatment value was 94.28% and the SpO2/FiO2 ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported. CONCLUSIONS: LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.

Acute and sub-acute toxicity profile of ultra-hypofractionated low-dose total skin electron beam with two 4 Gy fractions for cutaneous T cell lymphoma.

PURPOSE: Low-dose total skin electron beam therapy (TSEBT) over 3 weeks has proved to be a safe and effective treatment for cutaneous T cell lymphomas (CTCL). In this prospective trial, we examined the feasibility of ultra-hypofractionated low-dose TSEBT regimen in two fractions with 4 Gy combined with systemic therapy to minimize the number of visits to radiation centers. PATIENTS AND METHODS: Six patients with mycosis fungoides (MF) or Sézary syndrome (SS) received TSEBT with a total radiation dose of 8 Gy in two fractions between April 2020 and June 2020. Patient and treatment characteristics, tumor burden, the impact on the quality of life using Skindex-29 questionnaires, and acute toxicities were analyzed. RESULTS: During TSEBT, all patients developed grade 1 toxicities while two patients developed grade 2 toxicities. One patient experienced sepsis. The most common adverse effects were erythema and edema. All grade 2 toxicities regressed after 4 weeks following TSEBT. Based on the reported symptoms measured by Skindex-29, we detected a significant reduction in total Skindex-29 score after 8 weeks of radiation (P = 0.03), particularly in the symptoms (P = 0.01) and emotional domains (P = 0.04). CONCLUSION: Ultra-hypofractionated low-dose TSEBT followed by systemic therapy seems to be a safe and feasible alternative to conventional fractionated TSEBT for patients with MF/SS. The skin tumor burden and the health-related quality of life have been significantly improved within 8 weeks following radiotherapy.

COVID-19 and radiotherapy: potential new strategies for patients management with hypofractionation and telemedicine.

COVID-19 disease is one of the biggest public health challenges in Italy and global healthcare facilities, including radiotherapy departments, faced an unprecedented emergency. Cancer patients are at higher risk of COVID-19 infection because of their immunosuppressive state caused by both tumor itself and anticancer therapy adopted. In this setting, the radiation therapy clinical decision-making process has been partly reconsidered; thus, to reduce treatment duration and minimize infection risk during a pandemic, hypofractionated regimens have been revised. Moreover, telemedicine shows its helpfulness in the radiotherapy field, and patients get the supportive care they need minimizing their access to hospitals. This review aims to point out the importance of hypofractionated RT and telemedicine in cancer patient management in the COVID-19 era.