Effect of 5-Fluorouracil on cellular response to proton beam in esophageal cancer cell lines according to the position of Spread-Out Bragg Peak

Introduction: To investigate enhancement by 5-fluorouracil (5-FU) of the sensitivity of cancer cells to proton beam irradiation and clarify the differences in the responses of the 5-FU-treated cells to proton beam irradiation according to the position of the cells on the spread-out Bragg peak (SOBP). Methods: OE21 human esophageal squamous cells were irradiated with a 235-MeV proton beam at four different positions on the SOBP. The effects of the irradiation plus 5-FU treatment on the cell sur- vival were assessed by clonogenic assays and determination of the sensitizer enhancement ratio (SER). In addition, DNA double-strand breaks were estimated by measuring phospho-histone H2AX (cH2AX) foci formation in the cells at 0.5 and 24 h after irradiation.Results: The relative biological effectiveness (RBE) of proton beam irradiation against vehicle-control cells tended to increase with an increase in the depth of the cells on the SOBP. On the other hand, the degree of enhancement of the cellular sensitivity to proton beam irradiation by 5-FU was similar across all the positions on the SOBP. Furthermore, a marked increase in the number of residual cH2AX foci at 24 h post-irradiation was observed in the cells at the distal end of the SOBP.Conclusions: Our data indicated that the degree of enhancement by 5-FU of the sensitivity of OE21 cells to 235-MeV proton beam irradiation did not differ significantly depending on the position of the cells on the SOBP. Furthermore, the degree of increase in the number of cH2AX foci at 24 h after pro- ton beam irradiation with or without 5-FU exposure did not differ significantly according to the pos- ition on the SOBP. The effect of 5-FU in enhancing the effect of proton beam irradiation on cancer cells may be constant for all positions on the SOBP

Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced esophageal squamous cell carcinoma

Abstract Background The purpose of this study was to perform a dosimetric comparison between proton beam therapy (PBT) and photon radiation therapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were treated with PBT in our institution. In addition, we evaluated the correlation between toxicities and dosimetric parameters, especially the doses to normal lung or heart tissue, to clarify the clinical advantage of PBT over photon radiation therapy. Methods A total of 37 consecutive patients with Stage III thoracic ESCC who had received PBT with or without concurrent chemotherapy between October 2012 and December 2015 were evaluated in this study. The dose distributions of PBT were compared with those of dummy 3-dimensional conformal radiation therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT), focusing especially on the doses to organs at risk, such as normal lung and heart tissue. Results Of the 37 patients, the data from 27 patients were analyzed. Among these 27 patients, four patients (15%) developed grade 2 pericardial effusion as a late toxicity. None of the patients developed grade 3 or worse acute or late pulmonary and cardiac toxicities. When the dosimetric parameters between PBT and planned 3DCRT were compared, all the PBT domestic variables for the lung dose except for lung V10 GyE and V15 GyE were significantly lower than those for the dummy 3DCRT plans, and the PBT domestic variables for the heart dose were also significantly lower than those for the dummy 3DCRT plans. When the PBT and IMRT plans were compared, all the PBT domestic variables for the doses to the lung and heart were significantly lower than those for the dummy IMRT plans. Regarding the correlation between the grades of toxicities and the dosimetric parameters, no significant correlation was seen between the occurrence of grade 2 pericardial effusion and the dose to the heart. Conclusions When the dosimetric parameters of the dose distributions for the treatment of patients with locally advanced stage III ESCC were compared between PBT and 3DCRT or IMRT, PBT enabled a significant reduction in the dose to the lung and heart, compared with 3DCRT or IMRT

Comparative analysis of the immune responses in cancer cells irradiated with X-ray, proton and carbon-ion beams.

Radiotherapy (RT) is an effective treatment option for cancer; however, its efficacy remains less than optimal in locally advanced cancer. Immune checkpoint inhibitor-based therapy, including the administration of anti-PD-L1 antibodies, is a promising approach that works synergistically with RT. Proton beam therapy and carbon-ion therapy are common options for patients with cancer. Proton and carbon ions are reported to induce an immune reaction in cancer cells; however, the underlying mechanisms remain unclear. Here, we aimed to compare the immune responses after irradiation (IR) with X-ray, protons, and carbon ions in an oesophageal cancer cell line and the underlying mechanisms. An oesophageal cancer cell line, KYSE450, was irradiated with 1 fraction/15 GyE (Gy equivalent) of X-ray, proton, or carbon-ion beams, and then, the cells were harvested for RNA sequencing and gene enrichment analysis. We also knocked out STING and STAT1 in the quest for mechanistic insights. RNA sequencing data revealed that gene expression signatures and biological processes were different in KYSE450 irradiated with X-ray, proton, and carbon-ion beams 6-24 h after IR. However, after 3 days, a common gene expression signature was detected, associated with biological pathways involved in innate immune responses. Gene knock-out experiments revealed that the STING-STAT1 axis underlies the immune reactions after IR. X-Ray, proton, and carbon-ion IRs induced similar immune responses, regulated by the STING-STAT1 axis

Comparison of hypofractionated and conventionally fractionated whole-breast irradiation for early breast cancer patients: a single-institute study of 1,098 patients.

PURPOSE: To evaluate the efficacy and safety of hypofractionated whole-breast irradiation (HF-WBI) compared with conventionally fractionated (CF) WBI. MATERIALS AND METHODS: Patients with early breast cancer (stages 0-II and <3 positive lymph nodes) who had undergone breast-conserving surgery were eligible for the HF-WBI study. HF-WBI was administered at 43.2 Gy in 16 fractions over 3.2 weeks to the whole breast with an additional tumor-bed boost of 8.1 Gy in 3 fractions over 3 days for positive surgical margins or those <5 mm. CF-WBI was administered at 50 Gy in 25 fractions over 5 weeks to the whole breast with an additional tumor-bed boost of 16 Gy in 8 fractions over 1.4 weeks to 6 Gy in 3 fractions over 3 days, depending on margin status. RESULTS: From April 1, 2006, to December 31, 2010, 717 patients were registered and 734 breasts were treated by HF-WBI. In the same period, 381 patients and 393 breasts who matched the study criteria chose CF-WBI, so the total number of patients in this comparison was 1,098. Grade 2 acute skin reactions were observed for 24 patients (3 %) in the HF-WBI group and 53 patients (14 %) in the CF-WBI (p < 0.001) group. The median follow-up period was 27 months. Two cases of intrabreast tumor recurrence were observed in each treatment group. Regional lymph node recurrence was observed in 1 HF-WBI patient and 2 CF-WBI patients. CONCLUSION: HF-WBI is superior to CF-WBI in terms of acute skin reaction and has the same short-term efficacy

Additional file 2: Figure S2. of Difference in the relative biological effectiveness and DNA damage repair processes in response to proton beam therapy according to the positions of the spread out Bragg peak

Surviving fraction following irradiation at 6 Gy and 8 Gy in the OE21 and KYSE450 cells. Error bars indicate the standard error of the mean. (*p < 0.05, **p < 0.01, ***p < 0.001) (TIFF 337 kb

Palliative radiotherapy for tumor bleeding in patients with unresectable pancreatic cancer: a single-center retrospective study

Abstract Background Patients with unresectable pancreatic cancer (PC) sometimes experience gastrointestinal bleeding (GIB) due to tumor invasion of the gastrointestinal tract (tumor bleeding); no standard treatment has been established yet for this complication. Palliative radiotherapy (PRT) could be promising, however, there are few reports of PRT for tumor bleeding in patients with unresectable PC. Therefore, we evaluated the outcomes of PRT for tumor bleeding in patients with unresectable PC. Methods We reviewed the medical records of patients with unresectable PC diagnosed at our institution between May 2013 and January 2022, and identified patients with endoscopically confirmed tumor bleeding who had received PRT. PRT was administered at a total dose of 30 Grays (Gy) in 10 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction, and the dose selection was left to the discretion of the attending radiation oncologists. Results During the study period, 2562 patients were diagnosed as having unresectable PC at our hospital, of which 225 (8.8%) developed GIB. Among the 225 patients, 63 (2.5%) were diagnosed as having tumor bleeding and 20 (0.8%) received PRT. Hemostasis was achieved in 14 of the 20 patients (70%) who received PRT, and none of these patients developed grade 3 or more adverse events related to the PRT. The median time to hemostasis was 8.5 days (range 7–14 days). The rebleeding rate was 21.4% (3/14). The median hemoglobin level increased significantly (p < 0.001) from 5.9 to 9.1 g/dL, and the median volume of red blood cell transfusion tended (p = 0.052) to decrease, from 1120 mL (range 280–3360 mL) to 280 mL (range 0–5560 mL) following the PRT. The median overall survival (OS) was 52 days (95% confidence interval [CI] 39–317). Of the 14 patients in whom hemostasis was achieved following PRT, chemotherapy could be started/resumed in seven patients (50%), and the median OS in these patients was 260 days (95% CI 76–not evaluable [NE]). Three patients experienced rebleeding (21.4%), on days 16, 22, and 25, after the start of PRT. Conclusion This study showed that PRT is an effective and safe treatment modality for tumor bleeding in patients with unresectable PC

Additional file 1: Figure S1. of Difference in the relative biological effectiveness and DNA damage repair processes in response to proton beam therapy according to the positions of the spread out Bragg peak

Survival curves of 6 different esophageal squamous cell carcinoma cell lines irradiated with a 150-kV photon beam in preliminary experiments. Each experiment was conducted in triplicate. Error bars indicate the standard error of the mean. (TIFF 343 kb

Prospective evaluation of the setup errors and its impact on safety margin for cervical cancer pelvic conformal radiotherapy

AimThe primary objective was to assess set-up errors (SE) and secondary objective was to determine optimal safety margin (SM)BackgroundTo evaluate the SE and its impact on the SM utilizing electronic portal imaging (EPI) for pelvic conformal radiotherapy.Material and methods20 cervical cancer patients were enrolled in this prospective study. Supine position with ankle and knee rest was used during CT simulation. The contouring was done using consensus guideline for intact uterus. 50 Gy in 25 fractions were delivered at the isocenter with ≥95% PTV coverage. Two orthogonal (Anterior and Lateral) digitally reconstructed radiograph (DRR) was constructed as a reference image. The pair of orthogonal [Anterior-Posterior and Right Lateral] single exposure EPIs during radiation was taken. The reference DRR and EPIs were compared for shifts, and SE was calculated in the X-axis, Y-axis, and Z-axis directions.Results320 images (40 DRRs and 280 EPIs) were assessed. The systematic error in the Z-axis (AP EPI), X-axis (AP EPI), and Y-axis (Lat EPI) ranged from -12.0 to 11.8 mm, -10.3 to 7.5 mm, and -8.50 to 9.70 mm, while the random error ranged from 1.60 to 6.15 mm, 0.59 to 4.93 mm, and 1.02 to –4.35 mm. The SM computed were 7.07, 6.36, and 7.79 mm in the Y-axis, X-axis, and Z-axis by Van Herk’s equation, and 6.0, 5.51, and 6.74 mm by Stroom’s equation.ConclusionThe computed SE helps defining SM, and it may differ between institutions. In our study, the calculated SM was approximately 8 mm in the Z-axis, 7 mm in X and Y axis for pelvic conformal radiotherapy