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.

Simultaneous boost radiotherapy versus conventional dose radiotherapy for patients with newly diagnosed glioblastoma: a multi-institutional analysis.

We compared survival outcomes of high-dose concomitant boost radiotherapy (HDCBRT) and conventional dose radiotherapy (CRT) for newly diagnosed glioblastoma (GB). Patients treated with intensity-modulated radiation therapy for newly diagnosed GB were included. In HDCBRT, specific targets received 69, 60, and 51 Gy in 30 fractions, while 60 Gy in 30 fractions was administered with a standard radiotherapy method in CRT. Overall survival (OS) and progression-free survival (PFS) were compared using the Log-rank test, followed by multivariate Cox analysis. The inverse probability of treatment weighting (IPTW) method was also applied to each analysis. Among 102 eligible patients, 45 received HDCBRT and 57 received CRT. With a median follow-up of 16 months, the median survival times of OS and PFS were 21 and 9 months, respectively. No significant differences were observed in OS or PFS in the Kaplan-Meier analyses. In the multivariate analysis, HDCBRT correlated with improved OS (hazard ratio, 0.49; 95% confidence interval, 0.27-0.90; P = 0.021), and this result remained consistent after IPTW adjustments (P = 0.028). Conversely, dose suppression due to the proximity of normal tissues and IMRT field correlated with worse OS and PFS (P = 0.008 and 0.049, respectively). A prospective study with a stricter protocol is warranted to validate the efficacy of HDCBRT for GB.

Late genitourinary toxicity in salvage radiotherapy for prostate cancer after radical prostatectomy: impact of daily fraction doses.

OBJECTIVE: To evaluate the impact of daily fraction doses on late genitourinary (GU) toxicity after salvage radiotherapy (SRT) for prostate cancer. METHODS: This multi-institutional retrospective study included 212 patients who underwent SRT between 2008 and 2018. All patients received image-guided intensity-modulated SRT at a median dose of 67.2 Gy in 1.8-2.3 Gy/fraction. The cumulative rates of late grade ≥2 GU and gastrointestinal (GI) toxicities were compared using Gray test, stratified by the ≤2.0 Gy/fraction (n = 137) and ≥2.1 Gy/fraction groups (n = 75), followed by multivariate analyses. The total dose was represented as an equivalent dose in 2-Gy fractions (EQD2) with α/ß = 3 Gy. RESULTS: After a median follow-up of 63 months, the cumulative rates of 5-year late grade ≥2 GU and GI toxicities were 14% and 2.5%, respectively. The cumulative rates of 5-year late grade ≥2 GU toxicity in the ≥2.1 Gy/fraction and ≤2.0 Gy/fraction groups were 22% and 10%, respectively (P = .020). In the multivariate analysis, ≥2.1 Gy/fraction was still associated with an increased risk of late grade ≥2 GU toxicity (hazard ratio, 2.37; 95% confidence interval, 1.12-4.99; P = .023), while the total dose was not significant. CONCLUSION: The present results showed that ≥2.1 Gy/fraction resulted in a higher incidence of late grade ≥2 GU toxicity in SRT. ADVANCES IN KNOWLEDGE: The impact of fraction doses on late GU toxicity after SRT remains unknown. The results suggest that higher fraction doses may increase the risk of late GU toxicity in SRT.

Impact of radiation doses on clinical relapse of biochemically recurrent prostate cancer after prostatectomy.

The relationship between radiation doses and clinical relapse in patients receiving salvage radiotherapy (SRT) for biochemical recurrence (BCR) after radical prostatectomy (RP) remains unclear. We identified 292 eligible patients treated with SRT between 2005 and 2018 at 15 institutions. Clinical relapse-free survival (cRFS) between the ≥ 66 Gy (n = 226) and < 66 Gy groups (n = 66) were compared using the Log-rank test, followed by univariate and multivariate analyses and a subgroup analysis. After a median follow-up of 73 months, 6-year biochemical relapse-free survival, cRFS, cancer-specific survival, and overall survival rates were 58, 92, 98, and 94%, respectively. Six-year cRFS rates in the ≥ 66 Gy and < 66 Gy groups were 94 and 87%, respectively (p = 0.022). The multivariate analysis revealed that Gleason score ≥ 8, seminal vesicle involvement, PSA at BCR after RP ≥ 0.5 ng/ml, and a dose < 66 Gy correlated with clinical relapse (p = 0.015, 0.012, 0.024, and 0.0018, respectively). The subgroup analysis showed the consistent benefit of a dose ≥ 66 Gy in patients across most subgroups. Doses ≥ 66 Gy were found to significantly, albeit borderline, increase the risk of late grade ≥ 2 GU toxicity compared to doses < 66 Gy (14% vs. 3.2%, p = 0.055). This large multi-institutional retrospective study demonstrated that a higher SRT dose (≥ 66 Gy) resulted in superior cRFS.

[Case of Long-Term Response to Radiotherapy for Intramedullary Spinal Cord Metastasis from Ovarian Cancer after Surgery].

Intramedullary spinal cord metastasis(ISCM)often causes spinal cord neuropathy and should be treated as an oncologic emergency. However, it recurs in most cases after treatment, ISCM is a disease with a very unfavorable prognosis. Herein, we report a successfully treated case of ISCM with emergent and high-dose radiotherapy. A 53-year-old woman had difficulty walking without assistance 2 years after surgery for ovarian cancer. She received emergent radiotherapy at a total dose of 50 Gy in 25 fractions. Her neurological symptoms dramatically improved over 3 weeks after radiotherapy. ISCM has been controlled using the imaging tests at 5 years after radiotherapy. We believe that both emergent and high-dose radiotherapy were effective for ISCM.

Symptomatic radiation-induced rib fractures after stereotactic body radiotherapy for early-stage non-small cell lung cancer.

Background and purpose: The present study investigated the relationships between the risk of radiation-induced rib fractures (RIRF) and clinical and dosimetric factors in stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). We also examined dosimetric parameters associated with symptomatic or asymptomatic RIRF and the dosimetric threshold for symptomatic RIRF. Materials and methods: We reviewed 244 cases of early-stage NSCLC treated with SBRT. Gray's test and the Fine-Gray model were performed to examine the relationships between clinical and dosimetric factors and grade ≥ 2 (i.e., symptomatic) RIRF. The effects of each dose parameter on grade ≥ 1 and ≥ 2 RIRF were assessed with the Fine-Gray model. The t-test was used to compare each dose parameter between the grade 1 and grade ≥ 2 groups. Optimal thresholds were tested using receiver operating characteristic (ROC) curves. Results: With a median follow-up period of 48 months, the 4-year cumulative incidence of grade ≥ 1 and grade ≥ 2 RIRF were 26.4 % and 8.0 %, respectively. Regarding clinical factors, only age was associated with the development of grade ≥ 2 RIRF (p = 0.024). Among dosimetric parameters, only V40Gy significantly differed between the grade 1 and grade ≥ 2 groups (p = 0.015). The ROC curve analysis of grade ≥ 2 RIRF showed that the optimal diagnostic thresholds for D3cc, D4cc, D5cc, and V40Gy were 45.86 Gy (area under the curve [AUC], 0.706), 39.02 Gy (AUC, 0.705), 41.62 Gy (AUC, 0.702), and 3.83 cc (AUC, 0.730), respectively. These results showed that V40Gy ≤ 3.83 cc was the best indicator of grade ≥ 2 RIRF. The 4-year incidence of grade ≥ 2 RIRF in the V40Gy ≤ 3.83 cc vs. > 3.83 cc groups was 1.8 % vs. 14.2 % (p = 0.001). Conclusion: The present results recommend V40Gy ≤ 3.83 cc as the threshold for grade ≥ 2 RIRF in SBRT.

Dosimetric and radiobiological analyses of a de-escalation strategy for elective nodal regions in human papillomavirus-associated oropharyngeal cancer.

Introduction: In this simulation study, we examined the effects of a de-escalation strategy with a reduced dose to subclinical nodal regions in patients with human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC). Methods: We created two patterns of intensity-modulated radiotherapy for 16 patients with HPV-associated OPC. In the standard and de-escalation plans, the initial field including elective nodal regions received 46 and 30 Gy, followed by 20 and 36 Gy to the cutdown field, respectively. Comparison metrics were set for each organ at risk (OAR). We compared these metric values and the probability of adverse effects based on the normal tissue complication probability (NTCP) model between the two plans. Results: Both plans generally met the dose constraints for the targets and all OAR. Among the comparison metrics, the mean doses to the brain, pharyngeal constrictor muscle, thyroid, and skin and the dose to a 1 % volume of the skin were higher in the standard plan than in the de-escalation plan (P = 0.031, 0.007, < 0.001, < 0.001, and 0.006, respectively). NTCP analyses revealed that the probability of adverse effects in the ipsilateral parotid gland and thyroid was higher in the standard plan than in the de-escalation plan (standard vs. de-escalation plans: ipsilateral parotid gland, 6.4 % vs. 5.0 %, P = 0.016; thyroid, 3.3 % vs. 0.5 %, P < 0.001). Conclusions: A de-escalation strategy with elective nodal regions is a promising treatment to prevent a decline in the quality of life in patients with HPV-associated OPC, particularly xerostomia, dysphagia, and hypothyroidism.

Clinical Outcomes of Radiation Therapy for Angiosarcoma of the Scalp and Face: A Multi-Institutional Observational Study.

Angiosarcoma of the scalp and face (ASF) is a rare, aggressive tumor often treated with multimodal therapy, including radiation therapy (RT). This study assessed RT outcomes for ASF and identified prognostic factors. Data from 68 non-metastatic ASF patients undergoing RT with or without other therapies were analyzed. Median radiation dose was 66 Gy in 33 fractions (interquartile range (IQR) 60-70 Gy in 28-35 fractions). Local control (LC), progression-free survival (PFS), and overall survival (OS) rates were calculated using Kaplan-Meier analysis. Multivariate analyses and adverse event evaluation were conducted. Median patient age was 75 years (IQR 71-80 years), with a median follow-up of 17 months (IQR 11-42 months). One-/three-year LC rates were 57/37%, PFS rates were 44/22%, and OS rates were 81/44%. Multivariate analyses showed that an equivalent dose in a 2 Gy fraction (EQD2) >66 Gy correlated with improved LC (HR 2.35, 95% CI 1.03-5.32, p = 0.041). Combining chemotherapy (HR 2.43, 95% CI 1.08-5.46, p = 0.032) or surgery (HR 2.41, 95% CI 1.03-5.59, p = 0.041) improved PFS. No factors influenced OS. Late grade 3+ toxicities occurred in 1%, with one patient developing a grade 4 skin ulcer. These findings suggest that EQD2 > 66 Gy and combining chemotherapy or surgery can enhance LC or PFS in ASF. Further prospective studies are needed to determine the optimal treatment strategy for this rare malignancy, particularly in elderly patients.

Intensity-modulated radiation therapy with the central shielding technique for patients with uterine cervical cancer†.

We aimed to examine outcomes and toxicities of intensity-modulated radiation therapy (IMRT) with the central shielding (CS) technique for patients with uterine cervical cancer. This retrospective study included 54 patients with International Federation of Gynecology and Obstetrics IB-IVA cancer. Whole pelvic radiotherapy or extended-field radiotherapy were performed at the dose of 50.4 Gy in 28 fractions with helical tomotherapy (HT). Six patients had para-aortic lymph node metastases. The CS technique with HT was utilized after a total dose of 28.8-41.4 Gy to reduce doses to the rectum and bladder. The prescribed dose of intracavitary brachytherapy was mainly 18-24 Gy in three or four fractions at point A. Concurrent chemotherapy was used for 47 patients (87%). Median follow-up time was 56 months. Seventeen patients (31%) developed recurrence. The recurrence of the cervix was observed in two patients (4%). The 5-year rates of the locoregional control, progression-free survival (PFS) and overall survival were 79, 66 and 82%, respectively. Among several factors evaluated, histological type of adenocarcinoma was only a significantly worse prognostic factor for PFS by multivariate analysis (hazard ratio, 4.9 [95% confidence interval, 1.3-18], P = 0.018). Grade 2 or higher late toxicities were observed in nine patients (17%). Two patients (4%) each had grade 3 proctitis and grade 3 ileus, respectively. No grade 4 toxicity or treatment-related death was observed. The results suggest that IMRT with the CS technique allows a high local control without increasing the risk of complications for cervical cancer patients.

Clinical and dosimetric factors for symptomatic radiation pneumonitis after stereotactic body radiotherapy for early-stage non-small cell lung cancer.

Background and purpose: The present study attempted to identify risk factors for symptomatic radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) in patients with early-stage non-small cell lung cancer (NSCLC). Materials and methods: We reviewed 244 patients with early-stage NSCLC treated with SBRT. The primary endpoint was the incidence of grade ≥2 RP. Gray's test was performed to examine the relationship between clinical risk factors and grade ≥2 RP, and the Fine-Gray model was used for a multivariate analysis. The effects of each dose parameter on grade ≥2 RP were evaluated with the Fine-Gray model and optimal thresholds were tested using receiver operating characteristic (ROC) curves. Results: With a median follow-up period of 48 months, the 4-year cumulative incidence of grade ≥2 RP was 15.3%. Gray's test revealed that tumor size, a central tumor, interstitial pneumonia, and the biologically effective dose correlated with RP. In the multivariate analysis, a central tumor and interstitial pneumonia remained significant factors (p < 0.001, p = 0.002). Among dose parameters, the total lung volume (%) receiving at least 8 Gy (V8), V10, V20, and the mean lung dose correlated with RP (p = 0.012, 0.011, 0.022, and 0.014, respectively). The results of the Fine-Gray model and ROC curve analyses showed that V10 >16.7% was the best indicator of symptomatic RP among dose parameters. Conclusion: The present results suggest that a central tumor and interstitial pneumonia are independent risk factors for symptomatic RP and lung V10 ≤16.7% is recommended as the threshold in SBRT.

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.

Comparison of Recurrence Patterns between Adenocarcinoma and Squamous Cell Carcinoma after Stereotactic Body Radiotherapy for Early-Stage Lung Cancer.

We compared recurrence patterns between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) after stereotactic body radiotherapy (SBRT) for early-stage lung cancer. Patients with ADC and SCC histology, who were treated with SBRT for clinical stage IA1-IIA lung cancer at our institution, were included in the analysis. The rates of disease-free survival (DFS), overall survival (OS), local recurrence (LR), lymph node metastasis (LNM), and distant metastasis (DM) were calculated using the Kaplan-Meier method or the cumulative incidence function. Among the 204 patients analyzed, 138 and 66 were in the ADC and SCC groups, respectively. The median follow-up period was 60 months. The five-year DFS and OS rates were 57% vs. 41% and 69% vs. 48% in the ADC and SCC groups, respectively (p = 0.015 and 0.019, respectively). In the multivariate analysis, the histological type was not associated with DFS or OS. Five-year LR, LNM, and DM rates were 10% vs. 24%, 12% vs. 20%, and 25% vs. 27% in the ADC and SCC groups, respectively (p = 0.0067, 0.074, and 0.67, respectively). The multivariate analysis identified the histological type of SCC as an independent factor for LR (hazard ratio, 2.41; 95% confidence interval, 1.21-4.77; p = 0.012). The present results suggest that the risk of LR after SBRT is higher for SCC than for ADC.

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.

Daily irradiation versus irradiation at two- to three-day intervals in stereotactic radiotherapy for patients with 1-5 brain metastases: study protocol for a multicenter open-label randomized phase II trial.

BACKGROUND: Radiobiological daily changes within tumors are considered to be quite different between stereotactic radiotherapy (SRT) (e.g., 50 Gy in 4 fractions) and conventional radiotherapy (e.g., 60 Gy in 30 fractions). We aim to assess the optimal interval of irradiation in SRT and compare outcomes of daily irradiation with irradiation at two- to three-day intervals in SRT for patients with one to five brain metastases (BM). METHODS: This study is conducted as a multicenter open-label randomized phase II trial. Patients aged 20 or older with one to five BM, less than 3.0 cm diameter, and Karnofsky Performance Status ≥70 are eligible. A total of 70 eligible patients will be enrolled. After stratifying by the number of BMs (1, 2 vs. 3-5) and diameter of the largest tumor (< 2 cm vs. ≥ 2 cm), we randomly assigned patients (1:1) to receive daily irradiation (Arm 1), or irradiation at two- to three-day intervals (Arm 2). Both arms are performed with total dose of 27-30 Gy in 3 fractions. The primary endpoint is an intracranial local control rate, defined as intracranial local control at initially treated sites. We use a randomized phase II screening design with a two-sided α of 0∙20. The phase II trial is positive with p < 0.20. All analyses are intention to treat. This study is registered with the UMIN-clinical trials registry, number UMIN000048728. DISCUSSION: This study will provide an assessment of the impact of SRT interval on local control, survival, and toxicity for patients with 1-5 BM. The trial is ongoing and is recruiting now. TRIAL REGISTRATION: UMIN000048728. Date of registration: August 23, 2022. https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000055515 .

Dosimetric Comparison of Helical Tomotherapy and Intensity-Modulated Proton Therapy in Hippocampus- and Scalp-Sparing Whole Brain Radiotherapy.

Objective: Cognitive decline and alopecia after radiotherapy are challenging problems. We aimed to compare whole brain radiotherapy (WBRT) plans reducing radiation dose to the hippocampus and scalp between helical tomotherapy (HT) and intensity-modulated proton therapy (IMPT). Methods: We conducted a planning study of WBRT for 10 patients. The clinical target volume was defined as the whole brain excluding the hippocampus avoidance (HA) region. The prescribed dose was 30 Gy in 10 fractions to cover 95% of the target. Constraint goals were defined for the target and organs at risk (OAR). Results: Both techniques met the dose constraints for the target and OAR. However, the coverage of the target (dose covering 95% [D95%] and 98% [D98%] of the volume) were better in IMPT than HT (HT vs IMPT: D95%, 29.9 Gy vs 30.0 Gy, P < .001; D98%, 26.7 Gy vs 28.1 Gy, P = .002). The homogeneity and conformity of the target were also better in IMPT than HT (HT vs IMPT: homogeneity index, 1.50 vs 1.28, P < .001; conformity index, 1.30 vs 1.14, P < .001). IMPT reduced the D100% of the hippocampus by 59% (HT vs IMPT: 9.3 Gy vs 3.8 Gy, P < .001) and reduced the Dmean of the hippocampus by 37% (HT vs IMPT: 11.1 Gy vs 7.0 Gy, P < .001) compared with HT. The scalp IMPT reduced the percentage of the volume receiving at least 20 Gy (V20Gy) and V10Gy compared with HT (HT vs IMPT: V20Gy, 56.7% vs 6.6%, P < .001; V10Gy, 90.5% vs 37.1%, P < .001). Conclusion: Both techniques provided acceptable target dose coverage. Especially, IMPT achieved excellent hippocampus- and scalp-sparing. HA-WBRT using IMPT is a promising treatment to prevent cognitive decline and alopecia.

Radiotherapy for a rare phosphaturic mesenchymal tumor in the middle ear presenting with oncogenic osteomalacia: A case report.

RATIONALE: Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm causing oncogenic osteomalacia. Surgery remains the definitive treatment for PMT, and radiotherapy is seldom employed. However, surgery for PMT involving the head and neck is often difficult due to the local invasion and complicated anatomy. We report the first case of PMT, which was successfully treated with the combination of radiotherapy and supplementation of activated vitamin D. PATIENT CONCERNS: A 55-year-old woman suffered from pain in the hip and bilateral femur. Serum phosphate and calcium decreased to abnormal levels. Serum alkaline phosphatase and fibroblast growth factor 23 increased to abnormal levels. The hearing loss of the right ear had continued and a middle ear tumor was revealed. DIAGNOSES: Subsequent biopsy provided the diagnosis of PMT that caused oncogenic osteomalacia. These clinical and pathological characteristics were consistent with and provided the final diagnosis of benign PMT. INTERVENTIONS: Surgery of the PMT was difficult and the patient underwent radiotherapy. The prescribed dose was 36 Gy in 10 fractions. Simultaneously, the patient started supplementation of 1,25-dihydroxyvitamin D3 (1-2 µg/day) and continued for 2 years. OUTCOMES: Near-complete resolution of the symptoms was achieved and abnormal laboratory values recovered. At 5 years of follow-up, the irradiated tumor showed no regrowth. Severe hearing loss of the right ear was not observed. LESSONS: Radiotherapy was effective for the PMT and could be an important treatment option for inoperable cases.

Dosimetric Comparison of Helical Tomotherapy, Volumetric-Modulated Arc Therapy, and Intensity-Modulated Proton Therapy for Angiosarcoma of the Scalp.

OBJECTIVE: We compared radiotherapy plans among helical tomotherapy (HT), volumetric-modulated arc therapy (VMAT), and intensity-modulated proton therapy (IMPT) for angiosarcoma of the scalp (AS). METHODS: We conducted a planning study for 19 patients with AS. The clinical target volume (CTV) 1 and CTV2 were defined as the gross tumor volume with a specific margin and total scalp, respectively. For HT and VMAT, the planning target volume (PTV) 1 and PTV2 were defined as CTV1 and CTV2 with 0.5-cm margins, respectively. For IMPT, robust optimization was used instead of a CTV-PTV margin (i.e. CTV robust). The targets of the HT and VMAT plans were the PTV, whereas the IMPT plans targeted the CTV robust. In total, 70 Gy and 56 Gy were prescribed as the D95% (i.e. dose to 95% volume) of PTV1 (or CTV1 robust) and PTV2 (or CTV2 robust), respectively, using the simultaneous integrated boost (SIB) technique. Other constraint goals were also defined for the target and organs at risk (OAR). RESULTS: All dose constraint parameters for the target and OAR met the goals within the acceptable ranges for the 3 techniques. The coverage of the targets replaced by D95% and D98% were almost equivalent among the 3 techniques. The homogeneity index of PTV1 or CTV1 robust was equivalent among the 3 techniques, whereas that of PTV2 or CTV2 robust was significantly higher in the IMPT plans than in the other plans. IMPT reduced the Dmean of the brain and hippocampus by 49% to 95%, and the Dmax of the spinal cord, brainstem, and optic pathway by 70% to 92% compared with the other techniques. CONCLUSION: The 3 techniques with SIB methods provided sufficient coverage and satisfactory homogeneity for the targets, but IMPT achieved the best OAR sparing.

Relationship between radiation doses to heart substructures and radiation pneumonitis in patients with thymic epithelial tumors.

Radiation doses to the heart are potentially high in patients undergoing radiotherapy for thymoma or thymic carcinoma because of their origin site and propensity for pericardial invasion. We investigated potential relationships between radiation pneumonitis (RP) and the dosimetric parameters of lung and heart substructures in patients with thymic epithelial tumors. This retrospective study included 70 consecutive patients who received definitive or postoperative radiotherapy at a median dose of 58.3 Gy. Heart substructures were delineated according to a published atlas. The primary end point of ≥ grade 2 RP was observed in 13 patients (19%) despite a low lung dose; median lung V20 (i.e. percentage of the volume receiving at least 20 Gy) was only 16.6%. In a univariate analysis, four lung parameters, heart V35, three pulmonary artery (PA) parameters, two left ventricle parameters, and left atrium V35 were associated with the development of RP. In a multivariate analysis, only PA V35 remained significant (hazard ratio 1.04; 95% CI 1.01-1.07, p = 0.007). PA V35 of the RP versus non-RP groups were 84.2% versus 60.0% (p = 0.003). The moderate dose sparing of PA could be a candidate as a planning constraint for reducing the risk of RP in thoracic radiotherapy.

Efficacy of herbal medicine TJ-14 for acute radiation-induced enteritis: a multi-institutional prospective Phase II trial.

The purpose of this multi-institutional Phase II trial study was to prospectively investigate the efficacy of the herbal medicine TJ-14 for acute radiation-induced enteritis (ARE). TJ-14 was administered orally as a first-line treatment for ARE. The primary end point was efficacy at 1 week. The secondary end points were: (i) the efficacy of TJ-14 at 2 and 3 weeks after its administration, (ii) the quality of life score (FACT-G) at 1, 2 and 3 weeks after its administration, and (iii) adverse events. If the efficacy of TJ-14 was observed in eight patients or fewer, its efficacy was rejected. Results: Forty patients receiving pelvic radiotherapy were enrolled. Of these, 22 developed ARE and received TJ-14. Among these, 19 had cervical cancer and 9 received chemoradiotherapy. TJ-14 efficacy was shown in 19 out of the 22 patients (86%). Stool frequency per day at 1 week significantly decreased (mean ± SD: 4.9 ± 2.1 vs 3.7 ± 1.9, P = 0.02). This effect continued at 2 (2.2 ± 1.4, P = 0.004) and 3 weeks (2.1 ± 0.9, P = 0.05). Thirteen out of the 22 patients (59%) continued TJ-14 until the end of radiotherapy. FACT-G score deterioration was not observed after the administration of TJ-14. Grade 1 hypokalemia was observed in 4 patients, and Grade 1 constipation in 3. We concluded that TJ-14 is sufficiently promising to be examined in a Phase III trial. A randomized controlled trial is currently being planned.

Helical tomotherapy for chemo-refractory multiple liver metastases.

BACKGROUND: Despite advances in chemotherapy, curing multiple liver metastases is quite rare. Even when response is obtained, regrowth of the tumors is almost inevitable. We aimed to evaluate the efficacy and adverse events of helical tomotherapy for chemo-refractory multiple liver metastases. METHODS: Forty-five patients with chemo-refractory multiple (3-10) liver metastases after standard systemic chemotherapy entered the single-institutional prospective study. Liver metastases were the major disease; however, 31 also had uncontrolled primary lesions and/or other metastases. The prescribed dose was 55 Gy in 25 fractions. The median planning target volume (PTV) and normal liver volume (NLV) of first treatment were 128 cm3 and 1175 cm3 , respectively. The median of V15Gy , V30Gy , and mean dose to NLV were 45%, 23%, and 19.4 Gy, respectively. RESULTS: Forty-two patients (93%) completed the planned treatment. Median survival time (MST) for all patients was 8 months, and the 1-year survival rate was 29%. The median local control (LC) period was 5 months and the 6-month control rate of irradiated tumors was 33%. A ≥30% decrease in tumor markers was observed in 31%. The most common grade 3 toxicity was lymphocytopenia (40%), followed by fatigue (6%). Radiation-induced liver disease (RILD) was not observed. Pancreatic cancer as the primary tumor, distant metastases outside the liver, low pretreatment neutrophil-to-lymphocyte ratio (NLR), and low pretreatment monocyte-to-lymphocyte ratio (MLR) were associated with poorer prognoses. CONCLUSIONS: Helical tomotherapy for chemo-refractory multiple liver metastases is a feasible and potentially effective treatment. Incorporating tomotherapy into the first-line treatment in combination with systemic chemotherapy should be considered. TRIAL REGISTRATION NUMBER: CROG 12005.