Dosimetric Comparison of 3D Conformal Radiotherapy (3D-CRT), Intensity-Modulated Radiotherapy (IMRT), and Volumetric-Modulated Arc Therapy (VMAT) in Cardiac-Sparing Whole Lung Irradiation.

Introduction Whole lung irradiation (WLI) is used for the treatment of lung metastasis in Wilms tumor and Ewing sarcoma; however, cardiac complications are one of the concerns. We report the dosimetric advantages of WLI using volumetric-modulated arc therapy (VMAT) and present a dosimetric comparison of VMAT with anteroposterior-posteroanterior (AP-PA) and static-field intensity-modulated radiation therapy (IMRT). Additionally, we evaluated the dosimetric impact of respiratory motion and intra-fractional motion during VMAT treatment. Methods Seven patients were recruited in this study. AP-PA, IMRT, one-isocenter (1-IC) VMAT, and 2-IC VMAT were planned on the maximum inspiration and expiration CT, respectively. The prescribed dose was 15 Gy in 10 fractions. To determine the effects of respiratory motion, the CT series was replaced and the dose was evaluated while maintaining the beam information. To determine the effect of patient motion, perturbed dose calculations were performed using a two-IC VMAT. The perturbation doses were calculated by shifting only the IC of the one side beam by 3 mm or 5 mm in the right-to-left (RL) direction. Results The mean heart dose was 1467.0 cGy, 790.0 cGy, 764.2 cGy, and 738.4 cGy for AP-PA, IMRT, 1-IC VMAT, and 2-IC VMAT, respectively. When the expiration CT plan was recalculated with inspiration CT, Dmax increased approximately by 8%. In the 2-IC VMAT plan, the D50%, D98%, and D2% dose differences were within ±2%, even with a 5 mm IC shift. Conclusion We confirmed a significant dosimetric advantage of VMAT over other techniques. 2-IC VMAT should be considered an effective treatment option during irradiation for large target volumes.

Whole lung irradiation as a novel treatment for COVID-19: Final results of the prospective randomized trial (WINCOVID trial).

BACKGROUND AND PURPOSE: The ability of low dose radiotherapy (LDRT) to control the unprecedented cytokine release associated with COVID-19 pathogenesis has been an area of widespread research since the COVID pandemic. It has not been studied adequately whether the anti-inflammatory effect of LDRT provides additional benefit when used concurrently with steroids amongst other standard pharmacologic therapy. MATERIAL AND METHODS: 51 RT-PCR positive COVID-19 patients were recruited between November 2020 and July 2021. 34 patients were allotted to receive 0.5 Gy single session LDRT along with standard pharmacologic therapy while 17 patients received standard pharmacologic therapy alone. All had SpO2 <94% on room air, respiratory frequency >24/min and SpO2/FiO2 (SF) ratio between >89 but <357. All patients underwent a baseline CT scan. They were followed up for 28 days during when serial SF ratio, blood biomarkers (CRP, Serum ferritin, IL-6), Absolute lymphocyte count (ALC), repeat CT scan were performed at pre-defined time points. RESULTS: LDRT showed a statistically significant early improvement in oxygenation, an early time to clinical recovery, early hospital discharge and better radiological resolution compared to control group. There was no statistically significant difference between the two groups with respect to ALC or blood biomarkers at any of the measured time points. The 28-day mortality rate did not show statistically significant difference between the two groups. CONCLUSION: LDRT can be considered for selected oxygen-dependent moderate to severe COVID-19 patients for rapid relief of respiratory distress. It can be safely combined with standard pharmacologic treatment in such patients for added clinical benefit.

Low-dose whole-lung irradiation in severe COVID-19 pneumonia: a controlled clinical trial.

INTRODUCTION: The COVID-19 pandemic has caused significant morbidity and mortality thus far. Considering the historical uses of high-voltage X-ray beams for unresolvable pneumonia, we aimed to assess whether low-dose whole-lung irradiation (WLI) could provide any benefits for patients with refractory COVID-19 pneumonia. METHODS: Eleven patients with refractory COVID-19 pneumonia were treated with WLI to a total dose of 1 Gy and compared to 11 patients in a matched control group from June to November 2020. The study's primary endpoint was improvement of chest X-ray severity score (CXRS), followed by changes in mean oxygen (O2) saturation and 28-day mortality as secondary endpoints. RESULTS: The final CXRS was significantly lower in the WLI group (8.7 ± 2.5) compared to the control group (12.3 ± 3.3) (P: 0.016). Change of CXRS from the first to the last chest X-ray was -2.2 ± 3.1 for the WLI group and 0.7 ± 3.9 for the control group, which showed a trend for lower CXRS in the WLI group (U = 30, p: 0.085). Mean O2 saturation showed insignificant improvement in the first 24 hours after radiotherapy (mean difference: 2.5 ± 4.1, Z=-1.6, P value: 0.11). Overall survival after 28 days was 32% in the WLI group and 11% in the control group (P: 0.48). The reason for death in many patients was not merely respiratory failure, but also other adverse situations like pneumothorax, cardiogenic shock and pulmonary thromboembolism. CONCLUSIONS: Low-dose WLI could improve the CXR severity score and O2 saturation in severely ill COVID-19 patients, but larger studies are required to determine its impact on mortality.

Cardiac-Sparing and Breast-Sparing Whole Lung Irradiation Using Intensity-Modulated Proton Therapy.

PURPOSE: Whole lung irradiation (WLI) is indicated for certain pediatric patients with lung metastases. This study investigated whether WLI delivered as intensity-modulated proton therapy (IMPT) could significantly spare the heart and breasts when compared with conventional WLI delivered with anteroposterior/posteroanterior photon fields and with intensity-modulated photon therapy (IMRT) WLI. MATERIALS AND METHODS: Conventional, IMRT, and IMPT plans were generated for 5 patients (aged 5-22 years). The prescription dose was 16.5 GyRBE in 1.5-GyRBE fractions. Conventional plans used 6-MV photons prescribed to the midline and a field-in-field technique to cover the planning target volume (the internal target volume [ITV] + 1 cm). IMRT plans used 6-MV photons with a 7-beam arrangement with dose prescribed to the planning target volume. IMPT plans used scenario-based optimization with 5% range uncertainty and 5-mm positional uncertainty to cover the ITV robustly. Monte Carlo dose calculation was used for all IMPT plans. Doses were compared with paired Student t test. RESULTS: The ITV Dmean was similar for the IMPT, conventional, and IMRT plans, but the IMPT plans had a lower Dmin and a higher Dmax at tissue interfaces than conventional plans (Dmean ratio: 0.96, P > .05; Dmin ratio: 0.9, P < .001; Dmax ratio: 1.1, P = .014). Dmeans for breast and heart substructures were lower with IMPT plans than with conventional/IMRT plans (heart ratios, 0.63:0.73; left ventricle ratios, 0.61:0.72; right ventricle ratios, 0.45:0.57; left atrium ratios, 0.79:0.85; right atrium ratios, 0.81:0.86; left breast ratios, 0.40:0.51; right breast ratio, 0.46:0.52; all P < .05). CONCLUSIONS: IMPT resulted in comparable ITV coverage and lower mean doses to the heart and breasts when compared with other techniques. Whole lung irradiation delivered as IMPT warrants prospective evaluation in pediatric patients.

The risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19: estimation based on a virtual case.

BACKGROUND: Recently, low dose radiotherapy delivered to the whole lung has been proposed as treatment for the pneumonia due to COVID-19. Although there is biological plausibility for its use, the evidence supporting its effectiveness is scarce, and the risks associated with it may be significant. Thus, based on a virtual case simulation, we estimated the risks of radiation-induced cancer (RIC) and cardiac disease. METHODS: Lifetime attributable risks (LAR) of RIC were calculated for the lung, liver, esophagus, and breast of female patients. The cardiovascular risk of exposure-induced death (REID) due to ischemic heart disease was also calculated. The doses received by the organs involved in the treatment were obtained from a simulation of conformal radiotherapy (RT) treatment, delivering a dose of 0.5 Gy-1.5 Gy to the lungs. We considered a LAR and REID <1% as acceptable, 1-2% cautionary, and >2% unacceptable. RESULTS: The lung was at the highest risk for RIC (absolute LAR below 5200 cases/100,000 and 2250 cases/100,000 for women and men, respectively). For women, the breast had the second-highest LAR, especially for young women. The liver and esophagus had LARs below 700/100,000 for both sexes, with a higher incidence of esophageal cancer in women and liver cancer in men. Regarding the LAR cutoff, we observed an unacceptable or cautionary LAR for lung cancer in all women and men <60 years with an RT dose >1 Gy. LAR for lung cancer with an RT dose of 1 Gy was cautionary for women >60 years of age and men <40 years of age. No LAR estimation was unacceptable for the RT dose ≤0.7 Gy in all groups irrespective of sex or age at exposure. Only 0.5 Gy had an acceptable REID. CONCLUSIONS: A RT dose ≤0.5 Gy provides an acceptable LAR estimate (≤1%) for RIC and REID, irrespective of sex and age. The current ongoing trials should initially use doses ≤0.5 Gy to maintain the risks at an acceptable level and include only patients who fail or do not have any other treatment option.

A New Proton Therapy Solution Provides Superior Cardiac Sparing Compared With Photon Therapy in Whole Lung Irradiation for Pediatric Tumor Patients.

OBJECTIVE: Whole lung irradiation (WLI) plays a crucial role in local control in pediatric patients with lung metastases and improves patient survival. The intention of this research was to explore the advantage of cardiac sparing between photons and protons during WLI. We also propose a new solution for cardiac sparing with proton techniques. METHODS: Eleven patients with pediatric tumors and pulmonary metastasis treated with 12 Gy WLI (all received volumetric-modulated arc therapy (VMAT)) in our institute between 2010 and 2019 were retrospectively selected. Each patient was replanned with intensity-modulated radiation therapy (IMRT), helical tomotherapy (HT), and two intensity-modulated proton radiotherapy (IMPT) plans (IMPT-1 and IMPT-2). IMPT-1 considered the whole lung as the planning target volume (PTV), utilizing the anteroposterior technique (0/180°). IMPT-2 was a new proton solution that we proposed in this research. This approach considered the unilateral lung as the PTV, and 3 ipsilateral fields were designed for each lung. Then, IMPT-2 was generated by summing two unilateral lung plans. The primary objective was to obtain adequate coverage (95% of the prescription dose to the PTV) while maximally sparing the dose to the heart. The PTV coverage, conformity index (CI), homogeneity index (HI), and dose-volume statistics of the heart and substructures were assessed by means of the averages of each comparison parameter. RESULTS: All treatment techniques achieved the target volume coverage required by clinical practice. HT yielded the best coverage and homogeneity for the target structure compared with other techniques. The CI from IMRT was excellent. For photon radiation therapy, the HT plan afforded superior dose sparing for the V5, V6, V7, V8, and Dmean of the heart and Dmean of the right ventricle (RV). IMRT displayed the most notable dose reductions in the V9, V10, V11, and V12 of the heart and Dmean of the right atrium (RA). The VMAT plan was the least effective on the heart and substructures. However, compared with photon radiation therapy, IMPT-1 did not show an advantage for heart protection. Interestingly, IMPT-2 provided significant superiority in cardiac sparing, including maximum dose sparing for the V5, V6, V7, V8, V9 and Dmean of the heart and Dmean of the RA, RV, left atrium (LA) and left ventricle (LV) compared to all other techniques. CONCLUSIONS: Considering the complex anatomical relation between target volumes and organs at risk (OARs), IMPT can provide a dose advantage for organs located outside of the target area rather than within or surrounding the area. It is hoped that advances in proton therapy (PT) plan design will lead to further improvements in radiotherapy approaches and provide the best treatment choice for individual patients.

Effective heart-sparing whole lung irradiation using volumetric modulated arc therapy: a case report.

BACKGROUND: Late cardiovascular disease-related adverse events are one of the most common causes of premature mortality among long-term survivors of childhood cancer. As it is difficult to reduce the heart dose with traditional anteroposterior-posteroanterior field whole lung irradiation for pulmonary metastasis, improved radiation techniques are highly desirable. We report a case treated with whole lung irradiation using volumetric modulated arc therapy. CASE PRESENTATION: A 3-year-old Japanese girl with pulmonary metastases of Wilms' tumor received 12 Gy in 8 fractions of whole lung irradiation using volumetric modulated arc therapy. The treatment was well tolerated, and the course was completed as planned without any toxicity. We found statistically significant reduced volumetric modulated arc therapy irradiation doses to organs at risk relative to those of the standard anteroposterior-posteroanterior field technique. The mean heart dose was 8.5 Gy for volumetric modulated arc therapy and 12.3 Gy for the anteroposterior-posteroanterior field. The doses to liver and thyroid were also more favorable with volumetric modulated arc therapy than with the anteroposterior-posteroanterior field technique. We confirmed the dosimetric advantages of volumetric modulated arc therapy over anteroposterior-posteroanterior field in whole lung irradiation in terms of superior normal organ protection. CONCLUSIONS: Effective heart sparing is possible for whole lung irradiation using volumetric modulated arc therapy. Large-scale studies using standardized procedures should be conducted to validate our results.

Local therapy to distant metastatic sites in stage IV rhabdomyosarcoma.

PURPOSE: To determine the impact of surgery and/or radiation therapy on distant metastatic sites (DMS) in children with stage IV rhabdomyosarcoma (RMS). METHODS: A retrospective chart review was conducted on all patients with stage IV RMS at Texas Children's Hospital from 1992 to 2012. Data analyzed included age, gender, primary site, histologic subtype, number and sites of metastases, treatment including local therapy to DMS, and Oberlin score. RESULTS: The 5-year progression-free survival (PFS) and overall survival (OS) rates were 20% and 25%. The 5-year PFS in patients receiving local therapy to all DMS (n = 16) and to less than all DMS (n = 19) was 31.3% versus 0% (P = 0.002), whereas the 5-year OS was 37.3% versus 0% (P < 0.001), respectively. The 5-year PFS in patients with isolated lung metastasis versus other types of metastasis was 29% versus 7% (P = n.s.), whereas the 5-year OS was 43% versus 10% (P = 0.01). The 5-year pulmonary local control was improved by the use of whole lung irradiation (WLI; 56% vs. 10%, P = 0.03). CONCLUSIONS: Local treatment to all metastatic sites was associated with improved PFS and OS at 5 years. The use of WLI improved pulmonary control in patients with lung metastasis. We recommend an aggressive approach including local therapy to DMS in children with stage IV RMS.

A dosimetric comparison of whole-lung treatment techniques in the pediatric population.

To demonstrate the dosimetric advantages and disadvantages of standard anteroposterior-posteroanterior (S-AP/PAAAA), inverse-planned AP/PA (IP-AP/PA) and volumetry-modulated arc (VMAT) radiotherapies in the treatment of children undergoing whole-lung irradiation. Each technique was evaluated by means of target coverage and normal tissue sparing, including data regarding low doses. A historical approach with and without tissue heterogeneity corrections is also demonstrated. Computed tomography (CT) scans of 10 children scanned from the neck to the reproductive organs were used. For each scan, 6 plans were created: (1) S-AP/PAAAA using the anisotropic analytical algorithm (AAA), (2) IP-AP/PA, (3) VMAT, (4) S-AP/PANONE without heterogeneity corrections, (5) S-AP/PAPB using the Pencil-Beam algorithm and enforcing monitor units from technique 4, and (6) S-AP/PAAAA[FM] using AAA and forcing fixed monitor units. The first 3 plans compare modern methods and were evaluated based on target coverage and normal tissue sparing. Body maximum and lower body doses (50% and 30%) were also analyzed. Plans 4 to 6 provide a historic view on the progression of heterogeneity algorithms and elucidate what was actually delivered in the past. Averages of each comparison parameter were calculated for all techniques. The S-AP/PAAAA technique resulted in superior target coverage but had the highest maximum dose to every normal tissue structure. The IP-AP/PA technique provided the lowest dose to the esophagus, stomach, and lower body doses. VMAT excelled at body maximum dose and maximum doses to the heart, spine, and spleen, but resulted in the highest dose in the 30% body range. It was, however, superior to the S-AP/PAAAA approach in the 50% range. Each approach has strengths and weaknesses thus associated. Techniques may be selected on a case-by-case basis and by physician preference of target coverage vs normal tissue sparing.

Whole-lung irradiation in the treatment of metastatic synovial sarcoma.

Whole-lung irradiation (WLI) is standard of care in the treatment of patients with rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor and pulmonary metastases. However, it is not routinely utilized in the treatment of pulmonary metastases arising from other soft tissue sarcoma histologies. A patient presented with synovial sarcoma of his groin and punctate pulmonary metastases. After completion of multimodality treatment to his primary lesion, he received WLI. The patient is without evidence of disease at 3.8 years. This case demonstrates the need for further study of WLI in synovial sarcoma as it may improve outcomes in patients with this disease.