Comparing different boost concepts and beam configurations for proton therapy of pancreatic cancer.

Background and Purpose: Interfractional geometrical and anatomical variations impact the accuracy of proton therapy for pancreatic cancer. This study investigated field-in-field (FIF) and simultaneous integrated boost (SIB) concepts for scanned proton therapy treatment with different beam configurations. Materials and Methods: Robustly optimized treatment plans for fifteen patients were generated using FIF and SIB techniques with two, three, and four beams. The prescribed dose in 20 fractions was 60 Gy(RBE) for the internal gross tumor volume (IGTV) and 46 Gy(RBE) for the internal clinical target volume. Verification computed tomography (vCT) scans was performed on treatment days 1, 7, and 16. Initial treatment plans were recalculated on the rigidly registered vCTs. V100% and D95% for targets and D2cm3 for the stomach and duodenum were evaluated. Robustness evaluations (range uncertainty of 3.5 %) were performed to evaluate the stomach and duodenum dose-volume parameters. Results: For all techniques, IGTV V100% and D95% decreased significantly when recalculating the dose on vCTs (p < 0.001). The median IGTV V100% and D95% over all vCTs ranged from 74.2 % to 90.2 % and 58.8 Gy(RBE) to 59.4 Gy(RBE), respectively. The FIF with two and three beams, and SIB with two beams maintained the highest IGTV V100% and D95%. In robustness evaluations, the ΔD2cm3 of stomach was highest in two beams plans, while the ΔD2cm3 of duodenum was highest in four beams plans, for both concepts. Conclusion: Target coverage decreased when recalculating on CTs at different time for both concepts. The FIF with three beams maintained the highest IGTV coverage while sparing normal organs the most.

Dose Prescription to Isodose Lines in Static Multi-Beam Stereotactic Body Radiotherapy for Lung Tumors: Which Line Is Optimal?

This study investigated the appropriate dose prescription method in static multi-beam stereotactic body radiotherapy for lung tumors. Static multi-beam stereotactic body radiotherapy is a mainstream treatment in Japan. Based on the hypothesis that dose prescription to lower isodose lines may improve planning target volume dose coverage and decrease doses to organs at risk, we investigated changes in dose-volume histograms with prescription to various isodose lines for planning target volume in static multi-beam stereotactic body radiotherapy. In all treatment plans, 45 Gy in 4 fractions were prescribed to 95% of the planning target volume. By adjusting the leaf margins of each beam, various prescription isodose lines encompassing 95% volume of the planning target volume were generated. The prescription isodose lines investigated were 40, 50, 60, 70, 80 and 90% lines relative to the maximum dose of each planning target volume. The conformity index, homogeneity index, mean lung dose, and V5-V40 of the lung were evaluated. The dose was calculated by the adaptive convolve algorithm. The conformity index was lowest in the 70% or 80% isodose plan. The mean lung doses and V10-V40 of the lung decreased steeply from the 90% to the 70% isodose plan, and was lowest in the 60% and 70% isodose plans. These indices increased in the 40% and 50% isodose plans. The optimal stereotactic body radiotherapy plans appeared to be dose prescription to the 60% or 70% isodose line. Further investigation is warranted to clarify the advantage of using this method clinically.

Clinical Outcomes of Radiation Therapy for Choroidal Metastases and A Literature Review.

INTRODUCTION: Radiation therapy (RT) for choroidal metastasis (CM) aims to preserve vision and achieve local control (LC), thereby maintaining quality of life. The present study reports the clinical outcomes of RT for CM and reviews the literature. METHODS: We retrospectively collected data on 11 patients with CM; their primary tumors were breast cancer (n=3), lung cancer (n=3), leukemia (n=2), lymphoma (n=2), and gastric cancer (n=1). Four patients had bilateral CM. The median radiation dose was 39 Gy in 13 fractions (range, 20-50 Gy in 10-25 fractions). We investigated changes in visual acuity, tumor responses, morbidities, LC, and overall survival (OS). A systematic review of literature published between 1990 and 2020 was performed using the PubMed database. RESULTS: One, 1, and 6 patients had improved, stabilized, and worse visual acuity, respectively (data missing for 3 patients). Nevertheless, eight patients considered their visual acuity to have improved or remained the same after RT. Among 15 lesions in 11 patients, complete and partial responses were observed in 2 and 6, respectively (data missing for 7 lesions in 4 patients). Three-year LC and OS rates were 100 and 32%, respectively. Grade ≥ 3 morbidities were not observed. In the literature review, the most common primary cancer was breast cancer followed by lung cancer. Improvements in or the stabilization of visual acuity was observed in 80% of patients (range, 47-100), and the median survival time was 11 months (range, 4.9-23). CONCLUSION: RT is an efficient and safe palliative treatment for CM without severe toxicity.

Importance of the Number and Location of Lymph Node Metastasis in Oropharyngeal Cancer.

BACKGROUND/AIM: The 8th edition of the American Joint Committee on Cancer staging system classifies oropharyngeal cancer (OPC) by the expression of p16. The discrepancy observed in this system between pathological and clinical N-stages in p16-positive OPC has provoked controversy. Therefore, this study investigated prognostic factors not included in the new staging system for p16-positive OPC patients. PATIENTS AND METHODS: Patients with non-metastatic OPC receiving radiotherapy were reviewed. Clinical lymph node statuses were reassessed based on contrast-enhanced computed tomography and fluorodeoxyglucose positron emission tomography. Overall survival (OS) and cause-specific survival (CSS) were analyzed using multivariate analyses to adjust baseline imbalances. RESULTS: In total, 166 OPC patients were reviewed. Among them, 81 patients with p16-positive were analyzed. Three or more lymph node metastases (LNM) were observed in 21 p16-positive OPCs. Retropharyngeal lymph node metastasis (Rp) was found in 12. Three-year OS, CSS, and progression-free survival rates in p16-positive patients were 76, 88, and 81%, respectively. In multivariate analyses of p16-positive OPC, LNM ≥3 was a prognostic factor of OS (hazard ratio=9.30, p<0.001) and CSS (hazard ratio=17.80, p=0.005). Rp was associated with poor CSS (hazard ratio=8.73, p=0.03). In N0-1 p16-positive patients, LNM ≥3 trended to be associated with poor OS (hazard ratio=3.93, p=0.06). CSS in patients with Rp was unfavorable (hazard ratio=70.16, p=0.05). CONCLUSION: LNM ≥3 and Rp may be predictive of OS and CCS in p16-positive OPC. These are also possibly used to subcategorize p16-positive cN0-1 OPC. Further validation of lymph node staging is needed to refine the clinical staging system.

Non-Surgical Definitive Treatment for Operable Breast Cancer: Current Status and Future Prospects.

This article reviews the results of various non-surgical curative treatments for operable breast cancer. Radiotherapy is considered the most important among such treatments, but conventional radiotherapy alone and concurrent chemoradiotherapy do not achieve high cure rates. As a radiosensitization strategy, intratumoral injection of hydrogen peroxide before radiation has been investigated, and high local control rates (75-97%) were reported. The authors treated 45 patients with whole-breast radiotherapy, followed by stereotactic or intensity-modulated radiotherapy boost, with or without a radiosensitization strategy employing either hydrogen peroxide injection or hyperthermia plus oral tegafur-gimeracil-oteracil potassium. Stages were 0-I in 23 patients, II in 19, and III in 3. Clinical and cosmetic outcomes were good, with 5-year overall, progression-free, and local recurrence-free survival rates of 97, 86, and 88%, respectively. Trials of carbon ion radiotherapy are ongoing, with promising interim results. Radiofrequency ablation, focused ultrasound, and other image-guided ablation treatments yielded complete ablation rates of 20-100% (mostly ≥70%), but long-term cure rates remain unclear. In these treatments, combination with radiotherapy seems necessary to treat the extensive intraductal components. Non-surgical treatment of breast cancer is evolving steadily, with radiotherapy playing a major role. In the future, proton therapy with the ultra-high-dose-rate FLASH mode is expected to further improve outcomes.

Biological effects of prostaglandin E2-EP4 antagonist (AAT-008) in murine colon cancer in vivo: enhancement of immune response to radiotherapy and potential as a radiosensitizer.

Background: Prostaglandin E2 (PGE2) promotes tumor growth and metastasis by acting on a family of four receptors (EP1-4). We investigated the radiosensitizing effects of a newly developed antagonist of PGE2-EP4 (AAT-008) in mouse colon cancer cells in vivo and explored the mechanism using flow cytometry (FCM). Methods: CT26WT cells grown in Balb/c mice were used. AAT-008 at doses of 0, 3, 10, and 30 mg/kg/day was orally administered once or twice daily for up to 19 days. On day 3, the tumors were irradiated at 9 Gy in the radiotherapy (RT) group. Tumor sizes were measured every other day. For the first FCM series, AAT-008 (10 mg/kg/day) was administered from day 0 to 18 and RT (9 Gy) was given on day 3. The population of effector T cells (Teff), defined as CD45+CD8+CD69+, in the tumors was investigated on day 19. For the second FCM series, AAT-008 (30 mg/kg/day) was administered from day 0 to 12. The populations of Teff and regulatory T cells (Treg), and the ratio of Teff/Treg were investigated on day 13. Results: The growth delay effect of AAT-008 administered alone (3-30 mg/kg/day) appeared minimal. In the first growth delay experiment where AAT-008 was administered once daily, the combined effect of AAT-008 (30 mg/kg/day) and RT appeared additive. In the second growth delay experiment where AAT-008 was administered twice daily, the combined effect appeared additive at 3 and 10 mg/kg/day and supra-additive at 30 mg/kg/day. In the first FCM series, the mean Teff proportions in the tumors were 43% and 31% in the 10 mg + RT and 0 mg + RT groups, respectively. Notably, 67% Teff was observed in responsive mice in the 10 mg + RT group. In the second FCM series, the mean Treg proportion and Teff/Treg ratio in the 0 mg + RT and 30 mg + RT groups were 4.0% and 1.5%, respectively (P=0.04) and 10 and 22, respectively (P=0.04). Conclusions: AAT-008 potentially enhances the radiosensitivity of colon cancer cells, apparently by stimulating the immune system against the cancer cells.

Acute genitourinary toxicity of pencil beam scanning proton therapy for localized prostate cancer: utility of the transition zone index and average urinary flow rate in predicting acute urinary retention.

BACKGROUND: The purpose of this study was to evaluate the incidence of acute genitourinary toxicities in patients undergoing pencil beam scanning proton therapy for prostate cancer and investigate predictive factors associated with acute urinary retention. METHODS: A total of 227 patients treated between 2018 and 2021 were divided into the normo-fractionated proton therapy group (n = 107) and the moderately hypo-fractionated proton therapy group (n = 120), with prescribed doses of 76-78 Gy relative biological effectiveness in 38-39 fractions and 60-63 Gy relative biological effectiveness in 20-21 fractions, respectively. Uroflowmetry parameters and the transition zone index were prospectively evaluated. RESULTS: Forty-five patients (42%) in the normo-fractionated proton therapy and 33 (28%) in the moderately hypo-fractionated proton therapy developed acute grade 2 genitourinary toxicities (P = 0.02). The most common acute genitourinary toxicity was acute urinary retention. Thirty-nine patients (36%) treated with normo-fractionated proton therapy and 27 (23%) treated with moderately hypo-fractionated proton therapy developed grade 2 acute urinary retention (P = 0.02). No patients developed grade ≥ 3 toxicity. Univariate analysis showed the transition zone index, prostate volume, international prostate symptom score, voided volume, maximum flow rate and average flow rate were associated with grade 2 acute urinary retention. Multivariate analysis in both groups revealed the transition zone index (P = 0.025 and 0.029) and average flow rate (P = 0.039 and 0.044) were predictors of grade 2 acute urinary retention. CONCLUSIONS: The incidence of acute genitourinary toxicities was lower in the moderately hypo-fractionated proton therapy compared with the normo-fractionated proton therapy. Lower pretreatment average flow rate and a higher transition zone index were useful predictors of grade 2 acute urinary retention.

Optimal timing of a γH2AX analysis to predict cellular lethal damage in cultured tumor cell lines after exposure to diagnostic and therapeutic radiation doses.

Phosphorylated H2AX (γH2AX) is a sensitive biomarker of DNA double-strand breaks (DSBs). To assess the adverse effects of low-dose radiation (<50 mGy), γH2AX levels have typically been measured in human lymphocytes within 30 min of computed tomography (CT) examinations. However, in the presence of DSB repair, it remains unclear whether γH2AX levels within 30 min of irradiation completely reflect biological effects. Therefore, we investigated the optimal timing of a γH2AX analysis to predict the cell-surviving fraction (SF). Three tumor cell lines were irradiated at different X-ray doses (10-4000 mGy), and the relationships between SF and relative γH2AX levels were investigated 15 min and 2, 6, 12 and 24 h after irradiation. Data were analyzed for high-dose (0-4000 mGy) and low-dose (0-500 mGy) ranges. Correlations were observed between SF and the relative number of γH2AX foci/nucleus at 12 h only (R2 = 0.68, P = 0.001 after high doses; R2 = 0.37, P = 0.016 after low doses). The relative intensity of γH2AX correlated with SF 15 min to 12 h after high doses and 2 to 12 h after low doses, with the maximum R2 values being observed 2 h after high doses (R2 = 0.89, P < 0.001) and 12 h after low doses (R2 = 0.65, P < 0.001). Collectively, cellular lethal damage in tumor cells was more accurately estimated with residual DSBs 12 h after low-dose (10-500 mGy) irradiation. These results may contribute to determination of the optimal timing of biodosimetric analyses using γH2AX in future studies.

Clinical Outcomes of Intraoperative Radiotherapy, Postoperative Radiotherapy, and Definitive Radiotherapy for Non-metastatic Pancreatic Cancer.

OBJECTIVE: The aim of this study is to evaluate the utility of adjuvant radiotherapy (intraoperative radiotherapy, IORT; postoperative radiotherapy, PORT), and definitive radiotherapy for non-metastatic pancreatic cancer. METHODS: Ninety-nine patients were analyzed. Thirty patients underwent IORT with surgery, 31 underwent PORT after surgery, and 38 underwent definitive radiotherapy. Tumor stage [Union for International Cancer Control (UICC) 2009] was as follows: Stage I, 7; IIA, 16; IIB, 31; III, 45. The doses for IORT, PORT, and definitive radio therapy were 20 to 30, 40 to 64.6, and 50.4 to 61.2 Gy, respectively. Associations between clinical parameters including age, gender, tumor site, stage, performance status, surgical margin, and use of chemotherapy and local control (LC) or overall survival (OS) were analyzed. RESULTS: Follow-up periods for all patients were 1.1-145 months (median, 11). OS rate in the IORT, PORT, and definitive radiotherapy groups was 22%, 16%, and 6%, respectively, at 2 years. The 5-year OS rate was 13%, 3.2%, and 0%, respectively. Local control rate at 2 years was 33%, 35%, and 0%, respectively. No Grade ≥ 3 tox icities were observed. Distant metastasis was less common in the IORT group. Stage and surgical margin were sig nificant factors for OS after IORT. Performance status and chemotherapy were significant factors for OS after PORT and definitive radiotherapy. CONCLUSIONS: The present study showed the safety of the three treatment modalities, but the outcomes were not satisfactory. More intensive strategies including radiotherapy should be investigated.

Carbon Dioxide Angiography for the Detection of Lower Gastrointestinal Arterial Bleeding Initially Occult to Angiography with Iodinated Contrast Media.

This study evaluated the utility of carbon dioxide (CO2) in angiography for the detection of lower gastrointestinal arterial bleeding initially occult to angiography with iodinated contrast media. Fourteen patients underwent CO2-enhanced angiography. In all patients, extravasation was identified by contrast-enhanced computed tomography but not by initial iodinated contrast-enhanced angiography. After iodinated contrast-enhanced angiography, CO2-enhanced angiography was performed from the same catheter position. The detection capability for extravasation on CO2-enhanced angiography was evaluated. CO2-enhanced angiography allowed for the visualization of extravasation and subsequent transcatheter arterial embolization in 11 of 14 (79%) cases, with extravasation seen during either CO2-enhanced angiography (n = 8) or subsequent repeat iodinated contrast-enhanced angiography immediately after negative CO2-enhanced angiography (n = 3). Conservative treatment was performed in the remaining 3 cases. In conclusion, CO2-enhanced angiography appears useful for identifying occult lower gastrointestinal bleeding.

Erratum to "Ependymoma of the broad ligament mimicking an ovarian surface epithelial tumor" [Radiology Case Reports 16 (2021) 210-214].

[This corrects the article DOI: 10.1016/j.radcr.2020.10.046.].

Definitive radiotherapy with stereotactic or IMRT boost with or without radiosensitization strategy for operable breast cancer patients who refuse surgery.

For breast cancer (BC) patients who refused surgery, we developed a definitive treatment employing modern sophisticated radiation techniques. Thirty-eight operable BC patients were treated by conventionally fractionated whole-breast (WB) radiotherapy in combination with stereotactic (for primary tumor) or intensity-modulated (for primary tumor with/without regional lymph nodes [LN]) radiotherapy (IMRT) boost. Standard doses were 50 Gy/25 fractions, 21 Gy/3 fractions and 20 Gy/8 fractions, respectively, for the three radiation modalities. Disease stages were 0 (ductal carcinoma in situ [DCIS]) in seven patients, I in 12, II in 16 and III in three. In 26 patients, intratumoral hydrogen peroxide injection or hyperthermia with oral tegafur-gimeracil-oteracil potassium (S-1) was also used to sensitize the tumors to radiation. Hormonal and standard systemic therapy were administered in 25 and 13 patients, respectively. Complete and partial responses were obtained in 19 patients each; in patients with partial response, no further regrowth of the residual mass was observed, except for two patients who developed local recurrence. During a follow-up of 8-160 months (median, 50 months for living patients), two, one and two patients developed local relapse, sub-clavicular node metastasis and distant metastasis, respectively. The 5-year rates for overall, progression-free and local relapse-free survival were 97.2, 90.9 and 93.4%, respectively. Fourteen patients developed Grade 3 radiation dermatitis but all recovered after treatment. In 47%, the affected breast became better-rounded, and the nipple of the irradiated breast became higher by ≥1 cm than the contralateral nipple. Our method might be a treatment option for operable BC patients.

Utility of unsupervised deep learning using a 3D variational autoencoder in detecting inner ear abnormalities on CT images.

BACKGROUND AND PURPOSE: To examine the diagnostic performance of unsupervised deep learning using a 3D variational autoencoder (VAE) for detecting and localizing inner ear abnormalities on CT images. METHOD: Temporal bone CT images of 6663 normal inner ears and 113 malformations were analyzed. For unsupervised learning, 113 images from both the malformation and normal cases were used as test data. Other normal images were used for training. A colored difference map representing differences between input and output images of 3D-VAE and the ratio of colored to total pixel numbers were calculated. Supervised learning was also investigated using a 3D deep residual network and all data were classified as normal or malformation using 10-fold cross-validation. RESULTS: For unsupervised learning, a significant difference in the colored pixel ratio was seen between normal (0.00021 ± 0.00022) and malformation (0.00148 ± 0.00087) cases with an area under the curve of 0.99 (specificity = 92.0%, sensitivity = 99.1%). Upon evaluation of the difference map, abnormal regions were partially and not highlighted in 7% and 0% of the malformations, respectively. For supervised learning, which achieved 99.8% specificity and 90.3% sensitivity, a part of and no abnormal regions were highlighted on interpretation maps in 34% and 8% of the malformations, respectively. Abnormal regions were not highlighted in 4 malformation cases diagnosed as malformations and were highlighted in 6 cases misdiagnosed as normal. CONCLUSIONS: Unsupervised deep learning of 3D-VAE precisely detected inner ear malformations and localized abnormal regions. Supervised learning did not identify whole abnormal regions frequently and basis for diagnosis was sometimes unclear.

Comparison of intensity-modulated radiotherapy with the 5-field technique, helical tomotherapy and volumetric modulated arc therapy for localized prostate cancer.

The outcomes of three methods of intensity-modulated radiation therapy (IMRT) for localized prostate cancer were evaluated. Between 2010 and 2018, 308 D'Amico intermediate- or high-risk patients were treated with 2.2 Gy daily fractions to a total dose of 74.8 Gy in combination with hormonal therapy. Overall, 165 patients were treated with 5-field IMRT using a sliding window technique, 66 were then treated with helical tomotherapy and 77 were treated with volumetric modulated arc therapy (VMAT). The median age of patients was 71 years. The median follow-up period was 75 months. Five-year overall survival (OS) and biochemical or clinical failure-free survival (FFS) rates were 95.5 and 91.6% in the 5-field IMRT group, 95.1 and 90.3% in the tomotherapy group and 93.0 and 88.6% in the VMAT group, respectively, with no significant differences among the three groups. The 5-year cumulative incidence of late grade ≥2 genitourinary and gastrointestinal toxicities were 7.3 and 6.2%, respectively, for all patients. Late grade ≥2 gastrointestinal toxicities were less frequent in patients undergoing VMAT (0%) than in patients undergoing 5-field IMRT (7.3%) and those undergoing tomotherapy (11%) (P = 0.025), and this finding appeared to be correlated with the better rectal DVH parameters in patients undergoing VMAT. Other toxicities did not differ significantly among the three groups, although bladder dose-volume parameters were slightly worse in the tomotherapy group than in the other groups. Despite differences in the IMRT delivery methods, X-ray energies and daily registration methods, all modalities may be used as IMRT for localized prostate cancer.

Helical tomotherapy for asymptomatic chemotherapy-refractory or -unfit multiple (3 or more) metastases.

Background: Despite chemotherapy innovations, prognosis of patients with chemotherapy-refractory or -unfit multiple metastases (CRMM/CUMM) remains poor. In this prospective study, the efficacy and toxicity of helical tomotherapy for CRMM/CUMM were evaluated. Materials and methods: Between 2014 and 2020, asymptomatic patients with CRMM/CUMM with ≥ 3 lesions and no prior radiotherapy of the targets were enrolled. Patients who had intolerable toxicities to chemotherapy and those who refused chemotherapy were included in the CRMM and CUMM groups, respectively. Prostate cancer patients and patients with metastases mainly localized in the liver, lung, or brain were excluded. By helical tomotherapy, up to 10 lesions per patient were irradiated in order of volume. The standard dose was 50-60 Gy in 25-30 fractions. Results: Forty-five patients (median age, 63 years; 35 CRMM/10 CUMM) were enrolled. Primary tumors included lung, gynecological, and gastrointestinal cancers. The most frequently treated targets were lymph node metastases, followed by peritoneal/pleural disseminations and bone tumors. The 1-year survival rate was 51% (median, 12.5 months). In the 35 patients with CRMM, the median survival time was 12.5 months, and the median pre-radiation chemotherapy period was 8.8 months (p > 0.05). The 6-month target control rate was 78%. Acute adverse events (grade ≥ 2) occurred in 33 patients: hematologic toxicities in 23, dermatitis in 6, and others in 8. Late grade ≥ 2 toxicities occurred in 6 patients: pneumonitis in 4 and gastric hemorrhage in 2. Conclusion: Tomotherapy for CRMM/CUMM resulted in median survival times > 1 year. This treatment should be investigated further in larger prospective studies.

Outcomes of proton therapy for non-small cell lung cancer in patients with interstitial pneumonia.

BACKGROUND: Interstitial pneumonia (IP) is a disease with a poor prognosis. In addition, IP patients are more likely to develop lung cancer. Since IP patients frequently develop toxicities during cancer treatment, minimally invasive cancer treatment is warranted for such patients to maintain their quality of life. This study retrospectively investigated the efficacy and safety of proton therapy (PT) for non-small cell lung cancer (NSCLC) in patients with IP. METHODS: Twenty-nine NSCLC patients with IP were treated with PT between September 2013 and December 2019. The patients had stage IA to IIIB primary NSCLC. Ten of the 29 patients exhibited the usual interstitial pneumonia pattern. The prescribed dose was 66-74 Grays (relative biological effectiveness) in 10-37 fractions. RESULTS: The median follow-up period was 21.1 months [interquartile range (IQR), 15.6-37.3] for all patients and 37.2 months (IQR, 24.0-49.9) for living patients. The median patient age was 77 years (IQR, 71-81). The median planning target volume was 112.0 ml (IQR, 56.1-246.3). The 2-year local control, progression-free survival, and overall survival rates were 85% (95% confidence interval: 57-95), 30% (15-47), and 45% (26-62), respectively. According to the Common Terminology Criteria for Adverse Events (version 4.0), grade 3 acute radiation pneumonitis (RP) was observed in 1 patient. Two patients developed grade 3 late RP, but no other patients experienced serious toxicities. The patients' quality of life (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-LC13 and SF-36) scores had not changed after 3 months. CONCLUSIONS: PT may be a relatively safe treatment for NSCLC patients with IP, without deteriorating quality of life scores within 3 months.

Variability of α/ß ratios for prostate cancer with the fractionation schedule: caution against using the linear-quadratic model for hypofractionated radiotherapy.

BACKGROUND: Prostate cancer (PCa) is known to be suitable for hypofractionated radiotherapy due to the very low α/ß ratio (about 1.5-3 Gy). However, several randomized controlled trials have not shown the superiority of hypofractionated radiotherapy over conventionally fractionated radiotherapy. Besides, in vivo and in vitro experimental results show that the linear-quadratic (LQ) model may not be appropriate for hypofractionated radiotherapy, and we guess it may be due to the influence of fractionation schedules on the α/ß ratio. Therefore, this study attempted to estimate the α/ß ratio in different fractionation schedules and evaluate the applicability of the LQ model in hypofractionated radiotherapy. METHODS: The maximum likelihood principle in mathematical statistics was used to fit the parameters: α and ß values in the tumor control probability (TCP) formula derived from the LQ model. In addition, the fitting results were substituted into the original TCP formula to calculate 5-year biochemical relapse-free survival for further verification. RESULTS: Information necessary for fitting could be extracted from a total of 23,281 PCa patients. A total of 16,442 PCa patients were grouped according to fractionation schedules. We found that, for patients who received conventionally fractionated radiotherapy, moderately hypofractionated radiotherapy, and stereotactic body radiotherapy, the average α/ß ratios were 1.78 Gy (95% CI 1.59-1.98), 3.46 Gy (95% CI 3.27-3.65), and 4.24 Gy (95% CI 4.10-4.39), respectively. Hence, the calculated α/ß ratios for PCa tended to become higher when the dose per fraction increased. Among all PCa patients, 14,641 could be grouped according to the risks of PCa in patients receiving radiotherapy with different fractionation schedules. The results showed that as the risk increased, the k (natural logarithm of an effective target cell number) and α values decreased, indicating that the number of effective target cells decreased and the radioresistance increased. CONCLUSIONS: The LQ model appeared to be inappropriate for high doses per fraction owing to α/ß ratios tending to become higher when the dose per fraction increased. Therefore, to convert the conventionally fractionated radiation doses to equivalent high doses per fraction using the standard LQ model, a higher α/ß ratio should be used for calculation.

Utilization of an Occlusion Balloon Catheter during Stent-Graft Placement to Treat Postsurgical Visceral Arterial Hemorrhage.

The utility of occluding the bleeding artery using an occlusion balloon catheter during stent-graft placement for visceral artery bleeding was evaluated. Stent-graft placement for visceral artery bleeding was performed using a balloon catheter in 6 patients. All bleeding occurred after biliary or pancreatic surgery. Since 1 patient underwent the procedure twice, 7 procedures were assessed in total. Technical success, procedure-related adverse events, and 30-day mortality rates were evaluated. Technical success was defined as the placement of the stent-graft at the target site and the resolution of extravasation or pseudoaneurysm. In all procedures, stent-graft placement was successfully performed (technical success rate, 100%). Focal liver infarction occurred in 2 of 7 patients (29%), but did not require further treatment and was considered a minor adverse event. The 30-day mortality rate was 0%. In conclusion, the use of an occlusion balloon in the feeding artery facilitated successful stent-graft repair of hemorrhage from visceral arteries.

Survey of malignant pleural mesothelioma treatment in Japan: Patterns of practice and clinical outcomes in tomotherapy facilities.

We conducted a nationwide survey of tomotherapy for malignant pleural mesothelioma (MPM) in Japan. Fifty-six facilities were surveyed and data on 31 patients treated curatively between 2008 and 2017 were collected from 14 facilities. Twenty patients received hemithorax irradiation after extrapleural pneumonectomy (EPP) (first group). Five patients received irradiation without EPP (second group), while six received salvage radiotherapy for local recurrence (salvage group). Among the seven patients not undergoing EPP, five (four in the second group and one in the salvage group) were treated with lung sparing pleural irradiation (LSPI) and two with irradiation to visible tumors. Two-year overall survival (OS) rates in the first and second groups were 33% and 60%, respectively (median, 13 vs 30 months, P = 0.82). In the first and second groups, 2-year local control (LC) rates were 53 and 67%, respectively (P = 0.54) and 2-year progression-free survival (PFS) rates were 16% and 60%, respectively (P = 0.07). Distant metastases occurred in 15 patients in the first group and three in the second group. In the salvage group, the median OS was 18 months. Recurrence was observed in the irradiated volume in four patients. The contralateral lung dose was higher in LSPI than in hemithorax irradiation plans (mean, 11.0 ± 2.2 vs 6.1 ± 3.1 Gy, P = 0.002). Grade 3 or 5 lung toxicity was observed in two patients receiving EPP and hemithorax irradiation, but not in those undergoing LSPI. In conclusion, outcomes of EPP and hemithorax irradiation were not satisfactory, whereas LSPI appeared promising and encouraging.

Patient-Reported Quality of Life Outcomes after Moderately Hypofractionated and Normofractionated Proton Therapy for Localized Prostate Cancer.

We retrospectively evaluated the three-year patient-reported quality of life (QOL) after moderately hypofractionated proton therapy (MHPT) for localized prostate cancer in comparison with that after normofractionated PT (NFPT) using the Expanded Prostate Cancer Index Composite-50. Patients who received MHPT (60-63 Gy (relative biological effectiveness equivalents; RBE)/20-21 fractions) (n = 343) or NFPT (74-78 Gy (RBE)/37-39 fractions) (n = 296) between 2013 and 2016 were analyzed. The minimum clinically important difference (MCID) threshold was defined as one-half of a standard deviation of the baseline value. The median follow-up was 56 months and 83% completed questionnaires at 36 months. Clinically meaningful score deterioration was observed in the urinary domain at 1 month in both groups and in the sexual domain at 6-36 months in the NFPT group, but not observed in the bowel domain. At 36 months, the mean score change for urinary summary was -0.3 (MHPT) and -1.6 points (NFPT), and that for bowel summary was +0.1 and -2.0 points; the proportion of patients with MCID was 21% and 24% for urinary summary and 18% and 29% for bowel summary. Overall, MHPT had small negative impacts on QOL over three years, and the QOL after MHPT and NFPT was similar.