Photon Versus Proton Beam Therapy for T1–3 Squamous Cell Carcinoma of the Thoracic Esophagus Without Lymph Node Metastasis

Background and PurposeWe compared treatment outcomes and toxicities of photon radiotherapy versus proton beam therapy (PBT) and evaluated radiation field effects for T1–3 squamous cell carcinoma of the thoracic esophagus (EC) without lymph node metastasis.MethodsMedical records of 77 patients with T1–3N0M0 thoracic EC treated with radiotherapy between 2011 and 2019 were retrospectively analyzed. Among these patients, 61 (79.2%) individuals had T1 EC. The initial clinical target volume encompassed the whole esophagus with or without supraclavicular and/or abdominal lymph nodes (extended-field radiotherapy; 67 patients, 87.0%) or the area 3–5 cm craniocaudally and 1–2 cm radially from the gross tumor volume (involved-field radiotherapy; 10 patients, 13.0%). The final clinical target volume included margins of at least 1 cm from the gross tumor volume, with total radiation doses of 50–66 (median, 66) cobalt gray equivalent. Three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and PBT were used in twenty-four, five, and forty-eight patients, respectively. Concurrent chemotherapy was administered to 17 (22.0%) patients overall and only five (8.0%) T1 patients.ResultsPBT showed significantly lower lung and heart radiation exposure in mean dose, V5, V10, V20, and V30 than photon radiotherapy. The median follow-up for all patients was 46 (interquartile range, 22–72) months. The 5-year progression-free survival and overall survival rates were 56.5 and 64.9%, respectively, with no significant survival difference between photon radiotherapy and PBT. In patients with T1 EC, 5-year progression-free survival and overall survival rates were 62.6 and 73.5%, respectively.ConclusionsExtended-field radiotherapy using modern radiotherapy techniques without chemotherapy showed satisfactory clinical outcomes for lymph node-negative T1 EC

Positional Reproducibility and Effects of a Rectal Balloon in Prostate Cancer Radiotherapy

Despite the increasing use of the rectal balloon in prostate cancer radiotherapy, many issues still remain to be verified objectively including its positional reproducibility and relevance to treatment morbidity. We have developed a custom rectal balloon that has a scale indicating the depth of insertion and dilates symmetrically ensuring positional reproducibility. Fifty patients with prostate cancer treated by definitive 3D-conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) with rectal balloon were analyzed. Each of first five patients undergone computed tomography (CT) three times with a rectal balloon. The positional reproducibility was tested by Intraclass Correlation Coefficient (ICC) from the CT-to-CT fusion images. Planning variables and clinical acute toxicities were compared between when or not applying balloon. An ICC of greater than 0.9 in all directions revealed an excellent reproducibility of the balloon. Rectal balloon improved considerably the mean dose and V45Gy-V65Gy in plan comparison, and especially in 3D-CRT the rectal volume exposed to more than 60 Gy dropped from 41.3% to 19.5%. Clinically, the balloon lowered acute toxicity, which was lowest when both the balloon and IMRT were applied simultaneously. The rectal balloon carries excellent reproducibility and reduces acute toxicity in 3D-CRT and IMRT for prostate cancer

Hepatic stellate cells and innate immunity in alcoholic liver disease

Constant alcohol consumption is a major cause of chronic liver disease, and there has been a growing concern regarding the increased mortality rates worldwide. Alcoholic liver diseases (ALDs) range from mild to more severe conditions, such as steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The liver is enriched with innate immune cells (e.g. natural killer cells and Kupffer cells) and hepatic stellate cells (HSCs), and interestingly, emerging evidence suggests that innate immunity contributes to the development of ALDs (e.g. steatohepatitis and liver fibrosis). Indeed, HSCs play a crucial role in alcoholic steatosis via production of endocannabinoid and retinol metabolites. This review describes the roles of the innate immunity and HSCs in the pathogenesis of ALDs, and suggests therapeutic targets and strategies to assist in the reduction of ALD

Dosimetric Comparisons between Proton Beam Therapy and Modern Photon Radiation Techniques for Stage I Non-Small Cell Lung Cancer According to Tumor Location

Herein, we investigated the dosimetric benefits for proton beam therapy (PBT) over modern photon radiation techniques according to tumor location (central, peripheral, and close to the chest wall) for stage I non-small cell lung cancer (NSCLC) patients. A total of 42 patients with stage I NSCLC were treated with PBT with a total dose of 50–70 Gy in four or 10 fractions considering the risk of treatment-related toxicities. Simulation plans for three-dimensional conformal radiation therapy (3D-CRT), static-field intensity-modulated radiotherapy (IMRT), and volumetric-modulated arc therapy (VMAT) were retrospectively generated using the same treatment volumes as implemented in the PBT plans for these patients. Dosimetric improvements were observed with PBT as compared with all the photon-based radiation techniques with regards to the mean lung dose, lung V5 and V10, mean heart dose, and heart V5 and V10 in all locations. Moreover, lower radiation exposure to the chest wall was observed within PBT for peripherally located and close to the chest wall tumors. All radiotherapy modalities achieved clinically satisfactory treatment plans in the current study. Notably, the usage of PBT resulted in significant dosimetric improvements in the lung and heart over photon-based techniques at all tumor locations, including the periphery, for stage I NSCLC

Proton Beam Therapy versus Photon Radiotherapy for Stage I Non-Small Cell Lung Cancer

Proton beam therapy (PBT) and photon radiotherapy for stage I non-small cell lung cancer (NSCLC) were compared in terms of clinical outcomes and dosimetry. Data were obtained from patients who underwent PBT or photon radiotherapy at two institutions—the only two facilities where PBT is available in the Republic of Korea. Multivariate Cox proportional hazards models and propensity score-matched analyses were used to compare local progression-free survival (PFS) and overall survival (OS). Survival and radiation exposure to the lungs were compared in the matched population. Of 289 patients included in the analyses, 112 and 177 underwent PBT and photon radiotherapy, respectively. With a median follow-up duration of 27 months, the 2-year local PFS and OS rates were 94.0% and 83.0%, respectively. In the multivariate analysis, a biologically effective dose (BED10, using α/β = 10 Gy) of ≥125 cobalt gray equivalents was significantly associated with improved local PFS and OS. In the matched analyses, the local PFS and OS did not differ between groups. However, PBT showed significantly lower lung and heart radiation exposure in the mean dose, V5, and V10 than photon radiotherapy. PBT significantly reduced radiation exposure to the heart and lungs without worsening disease control in stage I NSCLC patients

Toxicity of Proton Therapy versus Photon Therapy on Salvage Re-Irradiation for Non-Small Cell Lung Cancer

This study evaluated the toxicity associated with radiation techniques on curative re-irradiation (re-RT) in patients with thoracic recurrence of non-small cell lung cancer (NSCLC). From 2011 to 2019, we retrospectively reviewed the data of 63 patients with salvage re-RT for in-field or marginal recurrence of NSCLC at two independent institutions. Re-RT techniques using X-ray beams and proton beam therapy (PBT) were also included. Re-RT had a 2-year overall survival (OS) and local progression-free survival of 48.0% and 52.0%, respectively. Fifteen patients experienced grade 3 or higher toxicity after re-RT. The complication rates were 18.2% (4/22) and 26.8% (11/41) in PBT patients and X-ray patients, respectively. Airway or esophageal fistulas occurred in seven patients (11.1%). Fistulas or severe airway obstruction occurred in patients with tumors adjacent to the proximal bronchial tree and esophagus, who underwent hypofractionated radiotherapy (RT) or concurrent chemotherapy, and with a higher dose exposure to the esophagus. In conclusion, salvage re-RT was feasible even in patients with local recurrence within the previous RT field. PBT showed similar survival outcomes and toxicity to those of other techniques. However, thoracic re-RT should be performed carefully considering tumor location and RT regimens such as the fraction size and concurrent chemotherapy

Inhibition of IL-17A Suppresses Enhanced-Tumor Growth in Low Dose Pre-Irradiated Tumor Beds

<div><p>Ionizing radiation induces modification of the tumor microenvironment such as tumor surrounding region, which is relevant to treatment outcome after radiotherapy. In this study, the effects of pre-irradiated tumor beds on the growth of subsequently implanted tumors were investigated as well as underlying mechanism. The experimental model was set up by irradiating the right thighs of C3H/HeN mice with 5 Gy, followed by the implantation of HCa-I and MIH-2. Both implanted tumors in the pre-irradiated bed showed accelerated-growth compared to the control. Tumor-infiltrated lymphocyte (TIL) levels were increased, as well as pro-tumor factors such as IL-6 and transforming growth factor-beta1 (TGF-β1) in the pre-irradiated group. In particular, the role of pro-tumor cytokine interleukin-17A (IL-17A) was investigated as a possible target mechanism because IL-6 and TGF-β are key factors in Th17 cells differentiation from naïve T cells. IL-17A expression was increased not only in tumors, but also in CD4+ T cells isolated from the tumor draining lymph nodes. The effect of IL-17A on tumor growth was confirmed by treating tumors with IL-17A antibody, which abolished the acceleration of tumor growth. These results indicate that the upregulation of IL-17A seems to be a key factor for enhancing tumor growth in pre-irradiated tumor beds.</p></div

A Comparative Analysis of Photon versus Proton Beam Therapy in Neoadjuvant Concurrent Chemoradiotherapy for Intrathoracic Squamous Cell Carcinoma of the Esophagus at a Single Institute

Background: Proton beam therapy (PBT), as a neoadjuvant chemoradiotherapy (nCRT) modality, is expected to result in better outcomes than photon-based radiotherapy (RT) for esophageal cancer, particularly adenocarcinoma. This study reports the results of nCRT for locally advanced esophageal squamous cell carcinoma (ESCC) using both modalities. Methods: We retrospectively reviewed the records of patients who underwent nCRT for ESCC between 2001 and 2020. A median of 41.4 Gy or cobalt gray equivalents of radiation was delivered using either photons or protons, with concurrent chemotherapy. Dosimetric and clinical parameters were compared between the two groups. Results: Of the 31 patients, the lungs and heart of the proton group (n = 15) were exposed to significantly less radiation compared to the photon group (n = 16). No significant differences in short-term postoperative outcomes or lymphocyte count were observed between the groups, and there were no significant differences between the photon and proton groups in 2-year overall survival (67.8% vs. 68.6%, p = 0.867) or 2-year disease-free survival (33.3% vs. 34.5%, p = 0.749), with a median follow-up of 17 months. Conclusions: PBT provided a significant dosimetric benefit over photon-based RT during nCRT for ESCC; however, it did not improve clinical outcomes

The effect of treatment with α-IL-17A neutralizing antibody on tumor growth.

<p>(A and C) Growth delay and (B and D) IL-17A expression of HCa-I and MIH-2 tumors implanted in 5 Gy irradiated beds or non-irradiated beds by α-IL-17A treatment, respectively (n = 5 mice per group). Error bars denote ± SEM. *p<0.05, pre 5 Gy/D3/α-IL-17 <i>vs</i> pre 5 Gy/D3/IgG2a (ANOVA).</p