Interinstitutional patient transfers between rapid chemotherapy cycles were feasible to utilize proton beam therapy for pediatric Ewing sarcoma family of tumors.

AIM: To assess the feasibility of transferring to the University of Tsukuba Hospital for proton beam therapy (PBT) during intensive chemotherapy in children with Ewing sarcoma family of tumors (ESFT) who had been diagnosed and started their first-line treatment at prefectural or regional centers for pediatric oncology. BACKGROUND: The treatment of ESFT relies on a multidisciplinary approach using intensive neoadjuvant and adjuvant chemotherapies with surgery and radiotherapy. Multi-agent chemotherapy comprising vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide (VDC-IE) is widely used for ESFT, and the interval between each course is very important for maintaining the intensity and effect of chemotherapy. MATERIALS AND METHODS: Clinical information of patients who received PBT and VDC-IE between April 2009 and May 2016 was collected retrospectively. The intervals between each course of VDC-IE and adverse events were assessed. RESULTS: Fifteen patients were evaluated. No delays in the intervals of chemotherapy due to transfer were observed. There were no adverse events caused during/just after transfer and no increases in adverse events. The estimated 4-year overall and event-free survival rates were 94.6% and 84.8%, respectively. DISCUSSION: Although the results of efficacy are preliminary, survival rates were comparable with past studies. More experience and follow-up are required to further assess the efficacy of PBT for patients with ESFT. CONCLUSION: Multidisciplinary therapy for children with ESFT involving transfer to our hospital for PBT during VDC-IE was feasible without treatment delay or an increase in adverse events.

Comparison of radiofrequency ablation and ablative external radiotherapy for the treatment of intrahepatic malignancies: A hybrid meta-analysis.

Background & Aims: Radiofrequency ablation (RFA) and ablative external beam radiotherapy (ablative RT) are commonly used to treat small intrahepatic malignancies. We meta-analysed oncologic outcomes and systematically reviewed the clinical consideration of tumour location and size. Methods: PubMed, Medline, Embase, and Cochrane Library databases were searched on February 24, 2022. Studies comparing RFA and ablative RT, providing one of the endpoints (local control or survival), and encompassing ≥5 patients in each arm were included. Results: Twenty-one studies involving 4,638 patients were included. Regarding survival, the odds ratio (OR) was 1.204 (p = 0.194, favouring RFA, not statistically significant) among all studies, 1.253 (p = 0.153) among hepatocellular carcinoma (HCC) studies, and 1.002 (p = 0.996) among colorectal cancer metastasis studies. Regarding local control, the OR was 0.458 (p <0.001, favouring ablative RT) among all studies, 0.452 (p <0.001) among HCC studies, favouring the ablative RT arm, and 0.649 (p = 0.484) among colorectal cancer metastasis studies. Pooled 1- and 2-year survival rates for HCC studies were 91.8% and 77.7% after RFA, and 89.0% and 76.0% after ablative RT, respectively; and for metastasis studies were 88.2% and 66.4% after RFA and 82.7% and 60.6% after RT, respectively. Literature analysis suggests that ablative RT can be more effective than RFA for tumours larger than 2-3 cm or for specific sublocations in the liver (e.g. subphrenic or perivascular sites), with moderate quality of evidence (reference to the grading system of the American Society for Radiation Oncology Primary Liver Cancer Clinical Guidelines). The pooled grade ≥3 complication rates were 2.9% and 2.8% in the RFA and ablative RT arms, respectively (p = 0.952). Conclusions: Our study shows that ablative RT can yield oncologic outcomes similar to RFA, and suggests that it can be more effective for the treatment of tumours in locations where RFA is difficult to perform or for large-sized tumours. Systematic Review Registration: This study was registered with PROSPERO (Protocol No: CRD42022332997). Impact and implications: Radiofrequency ablation (RFA) and ablative radiotherapy (RT) are non-surgical modalities for the treatment of small intrahepatic malignancies. Ablative RT showed oncologic outcomes at least similar to those of RFA, and was more effective at specific locations (e.g. perivascular or subphrenic locations).

Treatment of Uveal Melanoma With Radioactive Iodine 125 Implant Compared With Proton Beam Radiotherapy.

OBJECTIVE: To review the current state of radiation therapy for uveal melanoma and compare particle radiation and brachytherapy. PATIENTS AND METHODS: The medical records of 156 patients treated for uveal melanoma between May 30, 2012, and March 16, 2020, were retrospectively reviewed. Treatments consisted of either radioactive iodine 125 implant (RAI) or fractionated proton radiation (proton beam therapy [PBT]). Baseline characteristics were compared using a Wilcoxon rank sum test or χ2 test. Outcomes were compared using Cox proportional hazards regression models or logistic regression models. RESULTS: The median length of follow-up after treatment was 2.7 years (range, 0.5 to 9.0 years). Patients who underwent treatment with RAI were older (median age, 67 vs 59 years; P<.001) and had a lower tumor classification (American Joint Commission on Cancer; P=.001) compared with those who underwent PBT. There was no significant difference between RAI and PBT in the outcomes of liver metastases, death, enucleation, tearing, vision loss, retinal detachment, tumor thickness, conjunctivitis, optic neuropathy, iris neovascularization, or neovascular glaucoma (all P>.05). Patients who underwent RAI treatment had significantly higher risk of diplopia (P<.001), cataract progression (P<.001), and maculopathy (P=.03) compared with those who received PBT. Patients who underwent RAI were at higher risk of eyelash loss (P=.006) compared with the PBT group. CONCLUSION: Treatment with PBT and RAI has similar efficacy; however, there are differences in the adverse outcomes associated with these 2 modalities.

Stereotactic body radiation therapy for hepatocellular carcinoma: From infancy to ongoing maturity.

Hepatocellular carcinoma (HCC) accounts for 90% of liver tumours and is one of the leading causes of mortality. Cirrhosis due to viral hepatitis, alcohol or steatohepatitis is the major risk factor, while liver dysfunction due to cirrhosis is a deciding factor in its treatment. The treatment modalities for HCC include liver transplant, hepatectomy, radiofrequency ablation, transarterial chemoembolisation, transarterial radioembolisation, targeted therapy, immunotherapy, and radiation therapy. The role of radiation therapy has been refined with the increasing use of stereotactic body radiation therapy (SBRT). Trials over the past two decades have shown the efficacy and safety of SBRT in recurrent and definitive HCC, leading to its acceptance and adoption in some more recent guidelines. However, high quality level I evidence supporting its use is currently lacking. Smaller randomised trials of external beam radiation therapy suggest high efficacy of radiation therapy compared to other treatments for patients with unresectable HCC, and phase III trials comparing SBRT with other modalities are ongoing. In this review, we discuss the rationale for SBRT in HCC and present evidence on its efficacy, associated toxicity, and technological advances.

A study on predicting cases that would benefit from proton beam therapy in primary liver tumors of less than or equal to 5 cm based on the estimated incidence of hepatic toxicity.

Background: For small primary liver tumors, favorable outcomes have been reported with both of proton beam therapy (PBT) and X-ray therapy (XRT). However, no clear criteria have been proposed in the cases for which and when of PBT or XRT has to be used. The aim of this study is to investigate cases that would benefit from PBT based on the predicted rate of hepatic toxicity. Materials and methods: Eligible patients were those who underwent PBT for primary liver tumors with a maximum diameter of ≤ 5 cm and Child-Pugh grade A (n = 40). To compare the PBT-plan, the treatment plan using volumetric modulated arc therapy was generated as the XRT-plan. The rate of predicted hepatic toxicity was estimated using five normal tissue complication probability (NTCP) models with three different endpoints. The differences in NTCP values (ΔNTCP) were calculated to determine the relative advantage of PBT. Factors predicting benefits of PBT were analyzed by logistic regression analysis. Results: From the dose-volume histogram comparisons, an advantage of PBT was found in sparing of the normal liver receiving low doses. The factors predicting the benefit of PBT differed depending on the selected NTCP model. From the five models, the total tumor diameter (sum of the target tumors), location (hepatic hilum vs other), and number of tumors (1 vs 2) were significant factors. Conclusions: From the radiation-related hepatic toxicity, factors were identified to predict benefits of PBT in primary liver tumors with Child-Pugh grade A, with the maximum tumor diameter of ≤ 5 cm.

Comparison of intensity modulated proton therapy beam configurations for treating thoracic esophageal cancer.

Background and purpose: Specific proton-beam configurations are needed to spare organs at risk (OARs), including lungs, heart, and spinal cord, when treating esophageal squamous cell carcinoma (ESCC) in the thoracic region. This study aimed to propose new intensity-modulated proton therapy (IMPT) beam configurations and to demonstrate the benefit of IMPT compared with intensity-modulated x-ray therapy (IMXT) for treating ESCC. Material and methods: IMPT plans with three different beam angle configurations were generated on CT datasets of 25 ESCC patients that were treated with IMXT. The IMPT beam designs were two commonly-used beam configurations (anteroposterior and posterior oblique) and a recently proposed beam configuration (anterosuperior with posteroinferior). The target doses were 50-54 Gy(RBE) and 60-64 Gy(RBE) to the low-risk and high-risk target volumes, respectively. Robust optimization was applied for the IMPT plans. The differences in the dose-volume parameters between the IMXT and IMPT plans were compared. Results: With target coverage comparable to standard IMXT, IMPT had significantly lower mean doses to the OARs. IMPT with an anteroposterior opposing beam generated the lowest lung dose (mean = 7.1 Gy(RBE), V20 = 14.1%) and the anterosuperior with posteroinferior beam resulted in the lowest heart dose (mean = 12.8 Gy(RBE), V30 = 15.7%) and liver dose (mean = 3.9 Gy(RBE), V30 = 5.9%). For the subgroup of patients with an inferior tumor location (PTVs overlapping a part of the contoured heart), the novel beam demonstrated the optimal OARs sparing. Conclusion: Compared with IMXT, the IMPT plans significantly reduced the radiation dose to the surrounding organs when treating ESCC. IMPT beam configuration selection depends on the tumor location relative to the heart.

Proton beam therapy delivered using pencil beam scanning vs. passive scattering/uniform scanning for localized prostate cancer: Comparative toxicity analysis of PCG 001-09.

BACKGROUND AND PURPOSE: Patient-level benefits of proton beam therapy (PBT) relative to photon therapy for prostate cancer (PC) continue to be the focus of debate. Although trials comparing the two modalities are underway, most are being conducted using "conventional" PBT (passive scattering/uniform scanning [PS/US]) rather than pencil beam scanning (PBS). The dosimetric benefits of PBS are well-known, but comparative data are limited. This analysis compares PBS toxicity rates with those of PS/US in a prospective multicenter registry. METHODS: We evaluated acute/late gastrointestinal (GI) and genitourinary (GU) toxicity rates for men with low-to-intermediate risk PC enrolled in PCG 001-09. Acute toxicities with the two techniques were compared using χ2 tests, and the cumulative incidence methods for late toxicity. Multivariable analyses (MVAs) for acute toxicity were performed using logistic regression, and cox proportional hazards models for late toxicity. RESULTS: Patients were treated using PS/US (n = 1105) or PBS (n = 238). Acute grade ≥2 GI toxicity in PBS did not significantly differ from that with PS/US (2.9% and 2.1%, respectively; P = 0.47). Acute grade ≥2 GU toxicity was significantly higher with PBS (21.9% and 15.1%; P < 0.01). In MVA, PBS was significantly associated with increased acute grade ≥2 GU toxicity (RR = 1.57, p < 0.001). Late grade ≥2 GI and GU toxicities did not differ significantly between groups. CONCLUSIONS: This is the first multi-institutional comparative effectiveness evaluation of PBT techniques in PC. Differences in acute GU toxicity warrant further evaluation, and highlight the urgent need for prospective data using PBT.