Phase I/II study of stereotactic body radiotherapy boost in patients with cervical cancer ineligible for intracavitary brachytherapy.

PURPOSE: Stereotactic body radiotherapy (SBRT) boost is a promising treatment for cervical cancer patients who are ineligible for intracavitary brachytherapy (ICBT). The aim of this multicenter, single-arm, phase I/II study was to prospectively evaluate the efficacy and toxicity of SBRT boost. MATERIALS AND METHODS: ICBT-ineligible patients with untreated cervical cancer were enrolled. Patients underwent whole-pelvic radiotherapy (45 Gy in 25 fractions) with SBRT boost to the primary lesion. In the phase I dose-escalation cohort (3 + 3 design), patients were treated with SBRT boost of 21 or 22.5 Gy in three fractions. Although dose-limiting toxicity was not confirmed, a dose of 21 Gy was selected for the phase II cohort because it was difficult to reproduce the pelvic organs position in two patients during the phase I trial. The primary endpoint was 2-year progression-free survival. RESULTS: Twenty-one patients (phase I, n = 3; phase II, n = 18) were enrolled between April 2016 and October 2020; 17 (81%) had clinical stage III-IV (with para-aortic lymph node metastases) disease. The median (range) follow-up was 40 (10-84) months. The initial response was complete response in 20 patients and partial response in one patient. The 2-year locoregional control, progression-free survival, and overall survival rates were 84%, 67%, and 81%, respectively. Grade ≥ 3 toxicity was confirmed in one patient each in the acute (diarrhea) and late (urinary tract obstruction) phases. CONCLUSION: These findings suggested that a SBRT boost is more effective than the conventional EBRT boost and can be an important treatment option for ICBT-ineligible patients with cervical cancer. STUDY REGISTRATION: This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000036845).

Population-based asymmetric margins for moving targets in real-time tumor tracking.

BACKGROUND: Both geometric and dosimetric components are commonly considered when determining the margin for planning target volume (PTV). As dose distribution is shaped by controlling beam aperture in peripheral dose prescription and dose-escalated simultaneously integrated boost techniques, adjusting the margin by incorporating the variable dosimetric component into the PTV margin is inappropriate; therefore, geometric components should be accurately estimated for margin calculations. PURPOSE: We introduced an asymmetric margin-calculation theory using the guide to the expression of uncertainty in measurement (GUM) and intra-fractional motion. The margins in fiducial marker-based real-time tumor tracking (RTTT) for lung, liver, and pancreatic cancers were calculated and were then evaluated using Monte Carlo (MC) simulations. METHODS: A total of 74 705, 73 235, and 164 968 sets of intra- and inter-fractional positional data were analyzed for 48 lung, 48 liver, and 25 pancreatic cancer patients, respectively, in RTTT clinical trials. The 2.5th and 97.5th percentiles of the positional error were considered representative values of each fraction of the disease site. The population-based statistics of the probability distributions of these representative positional errors (PD-RPEs) were calculated in six directions. A margin covering 95% of the population was calculated using the proposed formula. The content rate in which the clinical target volume (CTV) was included in the PTV was calculated through MC simulations using the PD-RPEs. RESULTS: The margins required for RTTT were at most 6.2, 4.6, and 3.9 mm for lung, liver, and pancreatic cancer, respectively. MC simulations revealed that the median content rates using the proposed margins satisfied 95% for lung and liver cancers and 93% for pancreatic cancer, closer to the expected rates than the margins according to van Herk's formula. CONCLUSIONS: Our proposed formula based on the GUM and motion probability distributions (MPD) accurately calculated the practical margin size for fiducial marker-based RTTT. This was verified through MC simulations.

Dynamic tumor-tracking stereotactic body radiotherapy with real-time monitoring of liver tumors using a gimbal-mounted linac: A multi-institutional phase II study.

Background and purpose: This prospective multicenter phase II study aimed to evaluate the safety and efficacy of dynamic tumor tracking (DTT) stereotactic body radiotherapy (SBRT) with real-time monitoring of liver tumors using a gimbal-mounted system. Materials and methods: Patients with < 4 primary or metastatic liver tumors with diameters ≤ 50 mm and expected to have a respiratory motion of ≥ 10 mm were eligible. The prescribed dose was 40 Gy in five fractions. The primary endpoint was local control (LC) at 2 years. The secondary endpoints were overall survival (OS), progression-free survival (PFS), treatment-related toxicity, and tracking accuracy. Results: Between September 2015 and March 2019, 48 patients (48 lesions) with a median age of 74 years were enrolled from four institutions. Of these, 39 were diagnosed with hepatocellular carcinoma and nine with metastatic liver cancer. The median tumor diameter was 17.5 mm. DTT-SBRT was successfully performed in all patients; the median treatment time was 28 min/fraction. The median follow-up period was 36.5 months. The 2-year LC, OS, and PFS rates were 98.0 %, 88.8 %, and 55.1 %, respectively. Disease progression was observed in 33 (68.8 %) patients. One patient (0.2 %) had local recurrence, 31 (64.6 %) developed new hepatic lesions outside the irradiation field, and nine (18.8 %) had distant metastases (including overlap). Grade 3 late adverse events were observed in seven patients (14.5 %). No grade 4 or 5 treatment-related toxicity was observed. The median tracking accuracy was 2.9 mm. Conclusion: Employing DTT-SBRT to treat liver tumors results in excellent LC with acceptable adverse-event incidence.

A multicenter, randomized, placebo-controlled phase IIb trial of an autologous formalin-fixed tumor vaccine for newly diagnosed glioblastomas.

OBJECTIVE: An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV. METHODS: Eligible patients were adults with supratentorial GBMs, 16-75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration. An AFTV comprising fixed paraffin-embedded tumor tissue with immune adjuvants or an identical placebo without fixed tumor tissue was injected intradermally over three courses before and after chemoradiotherapy. The primary and secondary end points were overall survival (OS), progression-free survival (PFS), and 3-year survival rate. RESULTS: Sixty-three patients were enrolled. The average patient age was 61 years. The median KPS score was 80%, and the median resection rate was 95%. The full analysis set of 57 patients indicated no significant difference in OS (p = 0.64) for the AFTV group (median OS 25.6 months, 3-year OS rate 38%) compared with the placebo group (31.5 months and 41%, respectively) and no difference in PFS (median PFS 13.3 months in both groups, p = 0.98). For patients with imaging-based total tumor removal, the 3-year PFS rate was 81% in the AFTV group versus 46% in the placebo group (p = 0.067), whereas the 3-year OS rate was 80% versus 54% (p = 0.16), respectively. Similar results were obtained in the p53-negative subgroups. Severe adverse effects were not observed. CONCLUSIONS: The AFTV may have potential effects in certain patient subgroups. A phase III study for patients with total tumor removal remains warranted to confirm these findings. Clinical trial registration no.: UMIN000010602 (UMIN Clinical Trials Registry).

Accelerated hypofractionated radiotherapy with 3 Gy per fraction for central/ultra-central lung tumors: toxicity to mediastinal organs.

BACKGROUND: Accelerated hypofractionated radiotherapy with 3 Gy per fraction is routinely performed for central lung tumors in Japan. However, the tolerable doses to mediastinal organs at risk during this procedure are unclear. This study aimed to clarify the rate of toxicities and tolerable doses to mediastinal organs. METHODS: Patients treated with accelerated hypofractionated radiotherapy using a total dose of 60-75 Gy, with 3 Gy per fraction, for central lung tumors (July 2009-April 2021) were retrospectively reviewed. We extracted patients who received ≥30 Gy irradiation to each mediastinal organ and analyzed dosimetric factors, including doses to 0.03, 0.5, 1, 4 and 10 mL of each organ, in relation to grade 3-5 toxicities, except for radiation pneumonitis. RESULTS: In total, 251 organs in 91 (ultra-central, 24) lesions were analyzed, with a median follow-up duration of 26 months (range, 4-94). The prescribed doses were 75/72/69/66/63/60 Gy for 52/14/16/3/2/4 lesions, respectively. Grade 3 bronchopulmonary hemorrhage was confirmed in two (2.2%) patients, whose tumors were located ultra-centrally. The two patients with toxicity received up to 74.5 and 71.6 Gy to the bronchus. Among patients who received 70 Gy or more to the bronchus, the incidence rate was 7% (2/28 patients). CONCLUSION: The rate of severe toxicities was low (2.2%). Although we did not identify the dose tolerance of the organs, because of the low incidence rate, we did note that doses of >70 Gy to the bronchus were likely to cause bronchopulmonary hemorrhage.

Combination Therapy for a Severe Axillary Keloid with Abscesses: A Case Report.

Keloids are laterally growing fibroproliferative skin disorders. Severe keloids spread widely, sometimes over joints, thus significantly limiting motor function. They are associated with recurrent, very painful draining infections. Here, we report a case of a giant keloid that was successfully treated by combination therapy comprising surgery (partial resection followed by local flap transposition) and subsequent radiotherapy and steroid-plaster therapy. The keloid was first noticed when the patient was 7 years old at the site of a Bacille Calmette-Guérin vaccination she had received on her left shoulder in infancy. The keloid grew rapidly and widely after adulthood. A malignant tumor was suspected at another hospital, but a biopsy at age 45 years indicated the lesion was a keloid. Later, the keloid grew from the shoulder onto the chest and back and over the anterior axilla. At age 62 years, the patient was referred to our hospital. Under general anesthesia, the keloid was partially resected and the wound was covered with a local flap. Postoperative radiotherapy was performed 1 week later. The residual keloid was treated for 18 months with steroid tape. At 18 months after surgery, no recurrence of the keloid was observed. The patient had no pain or movement restriction. She was extremely satisfied with the results and considered the treatment to have improved her quality of life. While a standard strategy for severe keloid remains to be established, combination therapy comprising surgery, postoperative radiotherapy, and steroid-plaster therapy that aims to reduce inflammation and skin tension may be an option.

Multi-institutional phase II study on the safety and efficacy of dynamic tumor tracking-stereotactic body radiotherapy for lung tumors.

BACKGROUND AND PURPOSE: This study aimed to evaluate the safety and efficacy of dynamic tumor tracking-stereotactic body radiotherapy (DTT-SBRT) for lung tumors. MATERIALS AND METHODS: Patients with cStage I primary lung cancer or metastatic lung cancer with an expected range of respiratory motion of ≥10 mm were eligible for the study. The prescribed dose was 50 Gy in four fractions. A gimbal-mounted linac was used for DTT-SBRT delivery. The primary endpoint was local control at 2 years. RESULTS: Forty-eight patients from four institutions were enrolled in this study. Forty-two patients had primary non-small-cell lung cancer, and six had metastatic lung tumors. DTT-SBRT was delivered for 47 lesions in 47 patients with a median treatment time of 28 min per fraction. The median respiratory motion during the treatment was 13.7 mm (range: 4.5-28.1 mm). The motion-encompassing method was applied for the one remaining patient due to the poor correlation between the abdominal wall and tumor movement. The median follow-up period was 32.3 months, and the local control at 2 years was 95.2% (lower limit of the one-sided 85% confidence interval [CI]: 90.3%). The overall survival and progression-free survival at 2 years were 79.2% (95% CI: 64.7%-88.2%) and 75.0% (95% CI: 60.2%-85.0%), respectively. Grade 3 toxicity was observed in one patient (2.1%) with radiation pneumonitis. Grade 4 or 5 toxicity was not observed. CONCLUSION: DTT-SBRT achieved excellent local control with low incidences of severe toxicities in lung tumors with respiratory motion.

Clinical Outcomes and Prognostic Factors of Fractionated Stereotactic Radiosurgery for Brain Metastases ≥20 mm as a Potential Alternative to Surgery.

BACKGROUND: This study investigated the outcomes and prognostic factors of fractionated stereotactic radiosurgery (FSRS) for treatment of brain metastases (BMs) ≥20 mm and determined whether FSRS could replace surgery, the primary treatment for large BMs. METHODS: Patients with BMs ≥20 mm treated with FSRS were retrospectively examined. Patients who underwent FSRS postoperatively were excluded. Local failure, intracranial failure, and adverse events were evaluated. RESULTS: Overall, 116 lesions in 105 patients were evaluated. The performance status was 0-1, 2-4, and unknown for 86, 28, and 2 patients, respectively. The median maximum tumor diameter was 25 mm, and the median prescribed dose was 35 Gy in 3 fractions. The median follow-up period after FSRS was 8 months. The 1-year local failure, intracranial failure, and overall survival rates were 12.5%, 56.6%, and 49.0%, respectively. A maximum dose of ≥135 Gy (biological equivalent dose [α/ß = 10 Gy]) and good performance status were independent favorable prognostic factors for local control. After FSRS, 21 (20%) patients were treated with whole-brain radiotherapy because of multiple intracranial recurrences, and 4 (3.4%) patients underwent surgery because of local recurrence. CONCLUSIONS: FSRS for BMs ≥20 mm achieved good local control. Only 3.4% of patients required surgery after FSRS, suggesting that FSRS is a potential alternative to surgery. For FSRS, a higher maximum tumor dose was useful for local control.

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.

Local control of stereotactic body radiotherapy with dynamic tumor tracking for lung tumors: a propensity score-matched analysis.

BACKGROUND: Dynamic tumor tracking (DTT) is a method of respiratory motion management in radiotherapy. It reduces the radiation field but risks delivering an insufficient radiation dose to the tumor. We investigated the local control of DTT-stereotactic body radiotherapy (SBRT) for lung tumors. METHODS: Patients treated with SBRT for early-stage, non-small-cell lung cancer and lung metastases (2013-18) were retrospectively reviewed. Patients with tumor motion >1 cm were treated with DTT-SBRT (DTT group); those with tumor motion ≤1 cm were treated with static-SBRT (static group). A static planning target volume for the static-SBRT plan was also created for patients in the DTT group, and planning target volume reduction relative to the planning target volume for the DTT-SBRT plan was assessed. Patients were matched in a 1:1 ratio using a propensity score predictive of the SBRT technique. RESULTS: Of the 245 lesions in 218 patients (median follow-up, 25.4 months), 69 were treated with DTT-SBRT and 176 with static-SBRT. The median planning target volume reduction in the DTT group was 30.3%. After propensity score matching, 124 lesions were included (62 per group). Two-year local control rates for the DTT and static groups were 94.2 and 95.9%, respectively, for all lesions (P = 0.19) and 96.3 and 94.5%, respectively, for matched lesions (P = 0.79). In univariate analysis, DTT-SBRT was not associated with local control for all lesions (hazard ratio, 2.06; P = 0.20) or matched lesions (hazard ratio, 1.22; P = 0.79). No grade 4/5 toxicities were observed. CONCLUSIONS: DTT-SBRT for lung tumors reduced the planning target volume, but not local control rates. DTT was useful for respiratory motion management.

Phase 2 Clinical Trial of Separation Surgery Followed by Stereotactic Body Radiation Therapy for Metastatic Epidural Spinal Cord Compression.

PURPOSE: Stereotactic body radiation therapy (SBRT) is a postoperative treatment option for spinal metastases. Because data on surgery with SBRT are limited to retrospective studies, this single-center, single-arm, phase 2 study aimed to prospectively evaluate the outcomes of separation surgery and SBRT for metastatic epidural spinal cord compression (MESCC). METHODS AND MATERIALS: Patients with symptomatic MESCC due to a solid carcinoma were enrolled. The protocol for treatments comprised preoperative embolization, separation surgery, and spine SBRT. Surgical procedures were performed via the posterior approach, with decompression and a fixation procedure. The prescribed dose for spine SBRT was 24 Gy in 2 fractions. The primary endpoint was the 12-month local failure rate. The secondary endpoints were ambulatory functions and adverse effects. RESULTS: A total of 33 patients were registered between November 2017 and October 2019. All patients met the inclusion criteria, and all but 1 completed the protocol treatment. Of the included patients, 23 (70%) had radioresistant lesions. The Bilsky grade at registration was 1c in 3 patients, 2 in 8 patients, and 3 in 21 patients. The median follow-up duration after registration was 15 months (range, 3-35 months). Three months after the administration of treatments according to the protocol, 90% of patients (26 of 29) had disease of Bilsky grade ≤1. The 12-month local failure rate was 13%. Twenty patients could walk normally or with a cane 12 months after registration. Radiation-induced myelopathy, radiculopathy, and vertebral compression fracture were observed in 0, 1, and 6 patients, respectively. CONCLUSIONS: Separation surgery with SBRT for MESCC was effective in decompression and long-term local control. These findings suggest that larger randomized controlled trials are warranted to compare SBRT with conventional radiation therapy.

The Japan Society for Neuro-Oncology guideline on the diagnosis and treatment of central nervous system germ cell tumors.

Primary CNS germ cell tumors (GCTs) are rare neoplasms predominantly observed in the pediatric and young adult populations. In line with the hypothesis that the primordial germ cell is the cell-of-origin, histopathological examinations for this pathology involve a diverse range of components mirroring the embryogenic developmental dimensions. Chemotherapy and radiotherapy are the mainstays of treatment, with surgery having a limited role for diagnosis and debulking of residual tissue after treatment. While better management has been achieved over recent decades by modifying radiation coverage and selecting appropriate chemotherapy, standardization of treatment remains challenging, partly due to the low volume of cases encountered in each institution. As the incidence is higher in East Asia, including Japan, the Japan Society for Neuro-Oncology established a multidisciplinary task force to create an evidence-based guideline for CNS GCTs. This guideline provides recommendations for multiple dimensions of clinical management for CNS GCTs, with particular focus on diagnostic measures including serum markers, treatment algorithms including surgery, radiotherapy, and chemotherapy, and under-investigated but important areas such as treatment for recurrent cases, long-term follow-up protocols, and long-term sequelae. This guideline serves the purpose of helping healthcare professionals keep up to date with current knowledge and standards of management for patients with this rare disease in daily clinical practice, as well as driving future translational and clinical research by recognizing unmet needs concerning this tumor.

Safety of biliary stent placement followed by definitive chemoradiotherapy in patients with pancreatic cancer with bile duct obstruction.

BACKGROUND: Although patients with malignant bile duct obstruction due to pancreatic cancer are often initially treated with biliary stent placement, concurrent chemoradiotherapy with stents poses a potential risk of increased toxicity. This retrospective study aimed to evaluate the safety of biliary stent placement followed by definitive concurrent chemoradiotherapy in patients with pancreatic cancer. METHODS: Patients with pancreatic cancer who underwent either a plastic stent or a self-expanding metallic stent placement for malignant bile duct obstruction before definitive concurrent chemoradiotherapy were retrospectively reviewed. Radiotherapy was delivered in 1.8 Gy per fraction to a total dose of 50.4 Gy. Gemcitabine, TS-1 plus Gemcitabine, or TS-1 was the concurrent chemotherapy/regimen. The primary endpoint was the rate of biliary stent-related toxicities, defined as biliary bleeding, duodenal perforation, or bile duct perforation. RESULTS: Thirty patients were included. Plastic stents were placed in 23 patients and self-expanding metallic stent in seven patients at the start of irradiation. The median follow-up time was 20 (range, 2-63) months, and 27 patients (90%) completed concurrent chemoradiotherapy. Biliary stent-related toxicity (grade 3 biliary bleeding) was confirmed in one patient (3%) with a plastic stent 9 months after concurrent chemoradiotherapy. The median duration of locoregional control, progression-free survival, and overall survival were 31.1, 7.3, and 10.5 months, respectively. CONCLUSIONS: Stent placement followed by concurrent chemoradiotherapy was not associated with an apparent increase in toxicity and may be an appropriate treatment for patients with locally advanced pancreatic head cancer with bile duct obstruction.

Impact of pre-treatment C-reactive protein level and skeletal muscle mass on outcomes after stereotactic body radiotherapy for T1N0M0 non-small cell lung cancer: a supplementary analysis of the Japan Clinical Oncology Group study JCOG0403.

This study aimed to evaluate the impact of pretreatment C-reactive protein (CRP) and skeletal muscle mass (SMM) on outcomes after stereotactic body radiotherapy (SBRT) for T1N0M0 non-small cell lung cancer (NSCLC) as a supplementary analysis of JCOG0403. Patients were divided into high and low CRP groups with a threshold value of 0.3 mg/dL. The paraspinous musculature area at the level of the 12th thoracic vertebra was measured on simulation computed tomography (CT). When the area was lower than the sex-specific median, the patient was classified into the low SMM group. Toxicities, overall survival (OS) and cumulative incidence of cause-specific death were compared between the groups. Sixty operable and 92 inoperable patients were included. In the operable cohort, OS significantly differed between the CRP groups (log-rank test p = 0.009; 58.8% and 83.6% at three years for high and low CRP, respectively). This difference in OS was mainly attributed to the difference in lung cancer deaths (Gray's test p = 0.070; 29.4% and 7.1% at three years, respectively). No impact of SMM on OS was observed. The incidence of Grade 3-4 toxicities tended to be higher in the low SMM group (16.7% vs 0%, Fisher's exact test p = 0.052). In the inoperable cohort, no significant impact on OS was observed for either CRP or SMM. The toxicity incidence was also not different between the CRP and SMM groups. The present study suggests that pretreatment CRP level may provide prognostic information in operable patients receiving SBRT for early-stage NSCLC.

Risk factors for venous thromboembolism induced by prolonged bed rest during interstitial brachytherapy for gynecological cancer: a retrospective study.

BACKGROUND: Screening and management of venous thromboembolism (VTE) after surgery is important in preventing sublethal VTE. However, the risk factors for VTE during interstitial brachytherapy (ISBT) remain unknown, and appropriate screening and management strategies are yet to be established. Therefore, this study aimed to evaluate the risk factors for VTE resulting from requisite bed rest during ISBT for gynecologic cancers. METHODS: We retrospectively analyzed 47 patients. For patients without definitive preceding radiotherapy, whole pelvic irradiation (30-50 Gy) followed by ISBT of 12-30 Gy/2-5 fx/1-3 days was administered to CTV D90. For patients with preceding radiotherapy, 36-42 Gy/6-7 fx/3-4 days was delivered by ISBT alone. The supine position was required during ISBT. D-dimer (DD) was measured at initial presentation, 1 week before ISBT, pre-ISBT, on the day of, and the day following needle removal. Patients were divided into three groups according to the risk of VTE and were managed accordingly; Group 1: DD was not detected (negative) before ISBT, Group 2: VTE was not detected on venous ultrasound imaging, although DD was positive before ISBT, and Group 3: VTE was detected (positive) before ISBT. An intermittent pneumatic compression device was used during ISBT; for the patients without VTE before ISBT. Heparin or oral anticoagulants were administered to patients with VTE before ISBT. RESULTS: Overall, the median values of DD pre-ISBT, on the day of, and on the day following needle removal were 1.0 (0.4-5.8), 1.1 (0.5-88.9), and 1.5 (0.7-40.6) µg/mL, respectively. After ISBT, no patients had deep vein thrombosis (DVT) in groups 1 and 2. In group 3, 7 of 14 patients experienced worsening of VTE but remained asymptomatic. In univariate analysis, DVT diagnosed before ISBT, Caprini score ≥ 7, and difference in DD values between pre-ISBT and the day of or the day following needle removal ≥ 1 were associated with the incidence or worsening of VTE. CONCLUSION: DD should be measured before and after ISBT to detect the incidence or worsening of VTE in patients with DVT. The Caprini score may help in the prediction of VTE during or after ISBT.

Patient-reported outcomes following neoadjuvant endocrine therapy, external beam radiation, and adjuvant continuous/intermittent endocrine therapy for locally advanced prostate cancer: A randomized phase III trial.

BACKGROUND: We evaluated patient-reported outcomes (PRO) during neoadjuvant androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) followed by either adjuvant continuous ADT (CADT) or intermittent ADT (IADT) for patients with locally advanced prostate cancer (Pca). METHODS: A multicenter, randomized phase III trial enrolled 303 patients with locally advanced Pca. The patients were treated with 6 months (M) of ADT followed by 72 Gy of EBRT, and were randomly assigned to CADT or IADT after 14 M. The PROs were evaluated at sic points: baseline, 6 M, 8 M, 14 M, 20 M, and 38 M using FACT-P questionnaires and EPIC urinary, bowel, and sexual bother subscales. RESULTS: The FACT-P total scores were significantly better (p < 0.05) in IADT versus CADT at 20 M (121.6 vs.115.4) and at 38 M (119.9 vs. 115.2). The physical well-being scores (PWB) were significantly better (p < 0.05) in IADT versus CADT at 38 M (25.4 vs. 24.0). The functional scores were significantly better in IADT than those in CADT at 14 M (20.2 vs18.7, p < 0.05) and at 20 M (21.0 vs.18.9, p < 0.05). CONCLUSION: The PRO was significantly favorable in IADT on FACT-P total score at 20 M and 38 M, PWB and functional scores at 38 M.

Electron beam intraoperative radiotherapy for metastatic epidural spinal cord compression: a prospective observational study.

To assess the additional effects of intraoperative radiotherapy (IORT) with decompression surgery and adjuvant external beam radiotherapy (EBRT) for metastatic epidural spinal cord compression (MESCC). This single-arm institutional prospective observational study recruited patients between June 2017 and March 2020 and included those with symptoms of spinal cord compression owing to metastases, who were diagnosed using MRI. Patients with radiation-sensitive primary tumors and those who could not tolerate surgery were excluded. The treatment protocol comprised decompression surgery and electron beam IORT of 20 Gy in a single fraction followed by EBRT of 30 Gy in 10 fractions. The primary endpoints included the 1-year local failure rate and ambulatory functions. The study was closed in May 2019 owing to changes in treatment policies at our institution. Twenty patients were registered between June 2017 and May 2019. Although all patients completed surgery and IORT, 2 did not receive postoperative EBRT. Patients most commonly had colorectal cancer (4 patients), followed by thyroid cancer, renal cell carcinoma, lung cancer, breast cancer, sarcomas, and other cancers (3, 3, 2, 2, 2, and 4 patients, respectively). The median follow-up duration was 16 months (range 2-30 months); the 1-year local failure rate was 16%. On comparing ambulatory functions pre-treatment and at 1 year after treatment, improvement, no change, and worsening were observed in 3, 9, and 0 patients, respectively. This study's findings suggest that decompression surgery and IORT followed by EBRT are effective in achieving local control and maintaining ambulation in patients with MESCC.

Phase 2 Clinical Trial of Stereotactic Body Radiation Therapy for Painful Nonspine Bone Metastases.

PURPOSE: The present multicenter, single-arm, phase 2 study aimed to prospectively evaluate the palliative efficacy of stereotactic body radiation therapy (SBRT) in patients with painful nonspine bone metastases. METHODS AND MATERIALS: Patients with painful (≥2 points on a 0-to-10 scale) nonspine bone metastases from a solid tumor were enrolled. The prescribed dose was 35 Gy in 5 fractions. The primary endpoint was overall pain response rate (complete response [CR] and partial response [PR]) as measured per the International Consensus on Palliative Radiotherapy Endpoints guideline 6 months after SBRT. RESULTS: Forty-one osseous lesions in 38 patients were registered between June 2018 and June 2019. All lesions satisfied the inclusion criteria, and the patients completed the protocol treatment. Patients most commonly had lung cancer (22%), followed by prostate cancer, uterus cancer, and renal cell carcinoma (15%, 15%, and 12%, respectively). Bone metastases were most commonly located in coxal bones (56%). The median duration of follow-up after registration was 8 months (range, 1-19 months). Among evaluable lesions at 3 and 6 months after SBRT, the 3- and 6-month pain response rates were 78% and 75%, respectively. The local control rate at 6 months was 92%. Seven patients (17%) experienced bone fracture after irradiation, and 3 patients (7%) experienced grade 2 limb edema. One patient had regrowth of coxal bone metastases, and the tumor penetrated the sigmoid colon. Soft tissue abscess around the tumor and osteonecrosis of coxal bones were confirmed. The patient died of infection 4 months after SBRT and was determined to be a possible treatment-related death. CONCLUSIONS: This prospective clinical trial showed that SBRT for nonspine bone metastases was effective in terms of pain palliation. These findings warrant a larger randomized controlled trial to compare SBRT with conventional radiation therapy. Additionally, operation history should be considered as a risk factor for edema.

Safety of total body irradiation using intensity-modulated radiation therapy by helical tomotherapy in allogeneic hematopoietic stem cell transplantation: a prospective pilot study.

Total body irradiation using intensity-modulated radiation therapy total body irradiation (IMRT-TBI) by helical tomotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) allows for precise evaluation and adjustment of radiation dosage. We conducted a single-center pilot study to evaluate the safety of IMRT-TBI for allo-HSCT recipients. Patients with hematological malignancies in remission who were scheduled for allo-HSCT with TBI-based myeloablative conditioning were eligible. The primary endpoint was the incidence of adverse events (AEs). Secondary endpoints were engraftment rate, overall survival, relapse rate, non-relapse mortality, and the incidence of acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively). Between July 2018 and November 2018, ten patients were recruited with a median observation duration of 571 days after allo-HSCT (range, 496-614). D80% for planning target volume (PTV) in all patients was 12.01 Gy. Average D80% values for lungs, kidneys and lenses (right/left) were 7.50, 9.03 and 4.41/4.03 Gy, respectively. Any early AEs (within 100 days of allo-HSCT) were reported in all patients. Eight patients experienced oral mucositis and gastrointestinal symptoms. One patient experienced Bearman criteria grade 3 regimen-related toxicity (kidney and liver). All cases achieved neutrophil engraftment. There was no grade III-IV aGVHD or late AE. One patient died of sinusoidal obstruction syndrome 67 days after allo-HSCT. The remaining nine patients were alive and disease-free at final follow-up. Thus, IMRT-TBI was well tolerated in terms of early AEs in adult patients who underwent allo-HSCT; this warrants further study with longer observation times to monitor late AEs and efficacy.