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.

Radiotherapy for ductal carcinoma of the prostate: an analysis based on the Japanese radiation oncology study group survey.

BACKGROUND: The clinical characteristics of prostate ductal carcinoma is still unclear, and treatment strategy has not yet been established due to its rarity. Therefore, we conducted a multicenter survey of radiation therapy for prostate ductal carcinoma in Japan. METHOD: Data of patients with ductal carcinoma of the prostate treated with radiation therapy between 1996 and 2018 were extracted from the database of each facility. RESULTS: Fifty-two treatment records of 41 patients were collected from nine institutions. The treatment purpose and situations were varied curative intent to palliation. Twenty-eight patients received curative treatments. The median follow-up period of these patients was 68 months. Androgen deprivation therapy was combined with radiation therapy in 26 cases (93%). X-ray and particle irradiation was used. Radiation dose range was 63-78 Gy; 5-year overall survival, progression-free survival and biochemical relapse-free survival were 87.0, 79.3 and 79.3%, respectively. One patient experienced Grade 3 radiation proctitis and one experienced Grade 3 radiation cystitis. There were no Grade 4 or worse adverse events. CONCLUSION: Most patient received similar treatment with adenocarcinoma of prostate, and the clinical results were compatible. For more reliable evidence, further studies are required.

[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.

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 .

Impact of treatment planning using a structure block function on the target and organ doses related to patient movement in cervical esophageal cancer: A phantom study.

Helical tomotherapy (HT) can restrict beamlets passing through the virtual contour on computed tomography (CT) image in dose optimization, reducing the dose to organs at risk (OARs). Beamlet restriction limits the incident beamlet angles; thus, the proper planning target volume (PTV) margin may differ from that of the standard treatment plan without beamlet restriction, depending on the patient's movement during dose delivery. Dose distribution changes resulting from patient movement have not been described for treatment plans with beamlet restriction. This study quantified changes in dose distribution to the target and OARs when beamlet restriction is applied to cervical esophageal cancer treatment plan using HT by systematically shifting a phantom. Treatment plans for cervical esophageal cancers with and without beamlet restriction modes [directional block (DB) and nonblock (NB), respectively] were designed for CT images of the RANDO phantom. The PTV margin for the DB mode was set to be the same as that for the NB mode (5 mm). The CT image was intentionally shifted by ±1, ±2, and ±3 voxels in the left-right, anterior-posterior, and superior-inferior directions, and the dose distribution was recalculated for each position using the fluence for the NB or DB mode. When the phantom shift was within the same PTV margin as the NB mode, changes in doses to the targets, lungs, heart, and spinal cord in the DB mode were small as those in the NB mode. In conclusion, the virtual contour shape used in this study would provide safe delivery even with patient movement within the same PTV margin as for the NB mode.

Gross tumor volume in sinonasal tract cancer as a predictor of local recurrence after chemoradiotherapy.

OBJECTIVE: This study investigated whether gross tumor volume of the primary tumor before treatment was a predictor for local recurrence in patients with resectable sinonasal tract squamous cell carcinoma who were treated by chemoradiotherapy. METHODS: A total of 24 patients were enrolled. Pretreatment gross tumor volume of primary tumor was assessed by palpitation, perception and imaging. The cut-off value of the gross tumor volume for local recurrence was determined by receiver-operating curve analysis. A log-rank test and Cox's proportional hazards model were used for univariate and multivariate analyses with adjustment for the clinical T category (cT1-T4a/cT4b), respectively. RESULTS: In the univariate analysis, patients with the gross tumor volume ≥83.7 ml were significantly associated with shorter local recurrence-free rate (P = 0.0023) and disease-free survival (P = 0.0064) than those with gross tumor volume <83.7 ml. In the multivariate analysis, gross tumor volume ≥83.7 ml were significantly associated with shorter local recurrence-free rate (P = 0.041). CONCLUSIONS: Pretreatment gross tumor volume of primary tumor ≥83.7 ml was significantly associated with local recurrence-free rate in resectable sinonasal tract squamous cell carcinoma.

Propensity Score Analysis of Radical Hysterectomy Versus Definitive Chemoradiation for FIGO Stage IIB Cervical Cancer.

OBJECTIVE: The aim of this study was to compare the outcomes and toxicities of radical hysterectomy (RH) and definitive chemoradiation (CRT) for International Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer. MATERIALS AND METHODS: A retrospective analysis was performed on FIGO stage IIB patients who underwent RH with adjuvant radiotherapy (surgery group) or intended to receive CRT (CRT group). The distributions of disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Propensity score matching (PSM) was performed for the 2 groups based on age, tumor diameter, histological type, and pelvic node metastasis in pretreatment imaging tests. RESULTS: Median follow-up times were 58 months in the surgery group (n = 75) and 55 months in the CRT group (n = 65). Propensity score matching identified 37 patients with similar characteristics from each group. Significant differences were observed in the ratio of the chemotherapy combination between the surgery and CRT groups before (47% vs 98%) and after PSM (51% vs 100%). Five-year DFS rates were slightly higher in the surgery group than in the CRT group before PSM (69% vs 58%, P = 0.30) but were similar after PSM (76% vs 82%, P = 0.36). Five-year OS rates were similar between the surgery and CRT groups before (70% vs 75%, P = 0.59) and after PSM (78% vs 77%, P = 0.97). The results of multivariate analyses also showed that neither DFS nor OS was associated with the treatment modalities regardless of PSM. The incidence of late toxicities grade 2 or greater was similar between the surgery and CRT groups before (17% vs 23%, P = 0.31) and after PSM (19% vs 24%, P = 0.78). CONCLUSIONS: The results of this study suggest that RH with adjuvant radiotherapy and definitive CRT are equivalent treatment options for patients with FIGO stage IIB cancer. However, prospective larger studies are needed to confirm this.

Role of Extensive Lymphadenectomy in Early-Stage Cervical Cancer Patients With Radical Hysterectomy Followed by Adjuvant Radiotherapy.

OBJECTIVES: The objective of this study was to assess the effect of extensive lymphadenectomy on survival of early-stage cervical cancer patients with radical hysterectomy followed by adjuvant radiotherapy (RT). MATERIALS AND METHODS: A retrospective analysis was performed on early-stage patients with high-risk factors who received radical hysterectomy with lymphadenectomy followed by adjuvant RT. All patients were divided into the less than or equal to 40 dissected pelvic lymph nodes (DPLN ≤40) and greater than 40 dissected pelvic lymph nodes (DPLN >40) groups to assess the effect of extensive lymphadenectomy. Distributions of disease-free survival (DFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Significance of survival was assessed by the log-rank test. Cox proportional hazards models were applied to assess the effects of the factors on survival by univariate and multivariate analyses. RESULTS: After a median follow-up of 76 months for a total of 178 patients, 5-year DFS of the DPLN >40 group was significantly higher than that of the DPLN ≤40 group (86% vs 74%, P = 0.045). Five-year OS was comparable between the 2 groups (85% vs 78%, P = 0.49). The multivariate analysis showed that the DPLN ≤40 group was at a significantly higher risk of recurrence (hazard ratio, 2.3; 95% confidence interval (CI), 1.1-4.8; P = 0.020), whereas OS was not affected by the DPLN group (P = 0.26). Positive pelvic lymph node, parametrial invasion, histological type, and the absence of RT-combined chemotherapy remained significant prognostic factors for lower DFS and OS by the multivariate analysis. Adjusted hazard ratio of DPLN ≤40 for DFS was 1.2 (95% CI, 0.11-12; P = 0.91) in patients with negative pelvic lymph node (PLN) whereas it was 2.6 (95% CI, 1.1-5.8; P = 0.024) in patients with positive PLN. CONCLUSIONS: These results suggest that more extensive lymphadenectomy significantly improve the outcomes of patients with positive PLN even followed by adjuvant RT.

Comparisons of the clinical outcomes of different postoperative radiation strategies for treatment of head and neck squamous cell carcinoma.

PURPOSE: We previously reported unfavorable locoregional control with limited field postoperative radiotherapy for head and neck squamous cell carcinoma patients and thus revised the strategy to cover the whole neck. Head and neck squamous cell carcinoma Patients' outcomes were retrospectively analyzed to compare the efficacy of two treatments. MATERIAL AND METHODS: Before 2010, the clinical target volume covered the tumor bed and/or involved the neck region. Since 2011, whole-neck irradiation was planned. Univariate analysis, multivariate analysis, and propensity score matching were performed. The study included 275 patients: 186 received limited field postoperative radiotherapy and 89 received whole-neck postoperative radiotherapy. The median follow-up time for the entire cohort was 40.8 months. RESULTS: In univariate analysis, the radiation strategy had no significant effect on overall survival and progression-free survival. In multivariate analysis, whole-neck postoperative radiotherapy was a favorable factor for overall survival, progression-free survival, and locoregional control. Propensity score matching resulted in a cohort comprising 118 well-matched patients evenly divided between the limited field postoperative radiotherapy and whole-neck postoperative radiotherapy groups. Whole-neck postoperative radiotherapy group achieved a significantly better 2-year overall survival (56.4% vs. 78.1%; P = 0.003), 2-year progression-free survival (34.7% vs. 59.8%; P = 0.009), and 2-year locoregional control (54.4% vs. 83.2%; P < 0.001). The limited field postoperative radiotherapy group developed significantly more locoregional recurrences both in-field (35.2% vs. 15.1%, P = 0.003) and out-of-field (25.0% vs. 0%, P < 0.001) in the matched-pair cohort. CONCLUSION: Whole-neck postoperative radiotherapy is a more appropriate choice than limited field postoperative radiotherapy to improve overall survival, progression-free survival and locoregional control.

Clinical outcome of definitive radiation therapy for superficial esophageal cancer.

OBJECTIVE: To analyze the clinical outcome of concurrent chemoradiotherapy in superficial esophageal cancer patients. METHODS: We retrospectively analyzed data for 123 patients with superficial esophageal cancer who received external beam radiotherapy without intracavitary brachytherapy plus systemic chemotherapy during 1998-2015. Elective nodal irradiation was not performed. The dosage to planning treatment volume was 60 Gy in 30 fractions. The main outcome measure was overall survival. RESULTS: Patient characteristics were as follows: median age, 66 (41-83) years; male/female ratio, 106/17; squamous cell carcinoma/other, 122/1; cT1a/cT1b, 27/96; cervical esophagus/upper thoracic esophagus/middle thoracic esophagus/lower thoracic esophagus, 7/9/66/41 and concurrent chemoradiotherapy/radiotherapy alone, 100/23. Cisplatin and 5-fluorouracil were the most commonly used agents (85%). At the last follow-up (median 60.5 months), 91 (74%) patients were alive. Complete response was achieved in 116 (94.4%) patients. The 5-year overall survival, progression-free survival and local control rates were 77.0, 46.9 and 62.7%, respectively, similar to that in the elderly patients (P = 0.878, 0.754 and 0.648, respectively). There were 55 failures: 42 local, 10 regional and 3 distant failures. Nine local and seven regional failures developed out-of-field. Thirty-eight local failures (90%) were successfully salvaged, of which 30 (71%) were salvaged via endoscopic removal; only 2 regional failures (20%) were salvaged. Fifteen G3 acute toxicities occurred. One pneumonitis (G3), one pneumothorax (G3) and two pericardial effusion (G2) were the late toxicities observed. There were no G4 toxicities or treatment-related deaths. CONCLUSIONS: Concurrent chemoradiotherapy without intracavitary brachytherapy was effective and safe for superficial esophageal cancer, even in elderly patients.

Analysis of modulation factor to shorten the delivery time in helical tomotherapy.

A low modulation factor (MF) maintaining a good dose distribution contributes to the shortening of the delivery time and efficiency of the treatment plan in helical tomotherapy. The purpose of this study was to reduce the delivery time using initial values and the upper limit values of MF. First, patients with head and neck cancer (293 cases) or prostate cancer (181 cases) treated between June 2011 and July 2015 were included in the analysis of MF values. The initial MF value (MFinitial ) was defined as the average MFactual value, and the upper limit of the MF value (MFUL ) was defined according the following equation: MFUL = 2 × standard deviation of MFactual value + the average MFactual Next, a treatment plan was designed for patients with head and neck cancer (62 cases) and prostate cancer (13 cases) treated between December 2015 and June 2016. The average MFactual value for the nasopharynx, oropharynx, hypopharynx, and prostate cases decreased from 2.1 to 1.9 (p = 0.0006), 1.9 to 1.6 (p < 0.0001), 2.0 to 1.7 (p < 0.0001), and 1.8 to 1.6 (p = 0.0004) by adapting the MFinitial and the MFUL values, respectively. The average delivery time for the nasopharynx, oropharynx, hypopharynx, and prostate cases also decreased from 19.9 s cm-1 to 16.7 s cm-1 (p < 0.0001), 15.0 s cm-1 to 13.9 s cm-1 (p = 0.025), 15.1 s cm-1 to 13.8 s cm-1 (p = 0.015), and 23.6 s cm-1 to 16.9 s cm-1 (p = 0.008) respectively. The delivery time was shortened by the adaptation of MFinitial and MFUL values with a reduction in the average MFactual for head and neck cancer and prostate cancer cases.

Clinical results of definitive intensity-modulated radiation therapy for oropharyngeal cancer: retrospective analysis of treatment efficacy and safety.

OBJECTIVE: To evaluate the clinical outcomes of intensity-modulated radiotherapy for patients with oropharyngeal carcinoma. METHODS: Ninety-three oropharyngeal carcinoma patients histopathologically diagnosed with squamous cell carcinoma and treated with definitive intensity-modulated radiotherapy using helical tomotherapy between January 2006 and December 2013 were analyzed. Planning target volume primary and involved nodes was delivered 66-70 Gy at 2 Gy per fraction, while planning target volume prophylactic was delivered 54 Gy using the simultaneous integrated boost technique. RESULTS: The median follow-up period among the surviving patients was 40 months (range, 13-96). There were 76 males and 17 females with a median age of 60 years (range, 34-80). The disease was Stage II in 13%, Stage III in 10% and Stage IV in 77% of patients. Ninety-two patients received chemotherapy (99%); 68 patients received induction chemotherapy (73%), while 21 received concurrent chemotherapy (23%). The 3-year overall survival, progression-free survival and locoregional control rates were 80, 68 and 79%, respectively. Multivariate analysis identified an advanced T-category (T3-4), having double cancer, and smoking habit as significantly unfavorable factors for overall survival, progression-free survival and both progression-free survival and locoregional control, respectively. Only two patients who achieved disease control required percutaneous endoscopic gastrostomy tubes in the last follow-up. The rate of Grade 2 xerostomia at 2 years was 23%. CONCLUSIONS: Intensity-modulated radiotherapy using helical tomotherapy for patients with oropharyngeal carcinoma provided not only sufficient efficacy, but also preserved parotid function.

Retrospective analysis of the clinical efficacy of definitive chemoradiotherapy for patients with hypopharyngeal cancer.

OBJECTIVE: A retrospective analysis was performed to evaluate the clinical efficacy of definitive chemoradiotherapy including intensity-modulated radiotherapy for patients with hypopharyngeal cancer. METHODS: Previously untreated 204 patients with hypopharyngeal cancer were treated with definitive chemoradiotherapy. Of note, 66-70 Gy was delivered to the primary and involved nodes and 36-54 Gy was delivered to the prophylactic lymph node using standard fractionated radiotherapy. One hundred and forty-six patients received induction chemotherapy as a larynx preservation strategy, followed by definitive radiotherapy with or without concurrent chemotherapy. Intensity-modulated radiotherapy was also performed after 2006. RESULTS: The median follow-up time of this cohort was 43.4 months (range; 6.9-151.0). The 3-year overall survival, progression-free survival and larynx preservation survival rates were 78.8% (95% confidence interval; 73.0-85.0), 58.4% (95% confidence interval; 51.8-65.9) and 67.5% (95% confidence interval; 61.0-74.7), respectively. Multivariate analyses identified the following significant prognostic factors: an advanced age, the T category and N category for overall survival, the T category and N category for progression-free survival and the T category for larynx preservation survival. Acute toxicities of Grade 3 or higher were observed in 47 patients (23.0%). Two patients (1.0%) had Grade 4 pharyngeal edema. Suspicious treatment-related death due to lethal pharyngeal hemorrhage occurred in 1 (0.4%) patient. The rates of Grade 2 xerostomia in patients treated with intensity-modulated radiotherapy were 28.1, 17.4 and 9.5% at 6 months, 1 and 2 years after the completion of radiotherapy, respectively. CONCLUSIONS: The efficacy and safety of definitive chemoradiotherapy are considered feasible with sufficient laryngeal preservation.

The Charlson comorbidity index is a prognostic factor in sinonasal tract squamous cell carcinoma.

OBJECTIVE: High Charlson comorbidity index values have been reported to be associated with shorter overall survival in various types of cancer. We investigated whether Charlson comorbidity index values were correlated with overall survival in patients with resectable sinonasal tract squamous cell carcinoma. METHODS: Seventy-nine patients with resectable sinonasal tract squamous cell carcinoma were treated with curative intent. The Charlson comorbidity index values were calculated by the summation of the weight scores of 19 medical conditions (other than sinonasal tract squamous cell carcinoma) before treatment. The survival rate was analyzed according to the Kaplan-Meier method. Univariate and multivariate survival analyses were performed using the Wilcoxon test and the Cox proportional hazards model, respectively. RESULTS: According to a univariate analysis, a Charlson comorbidity index value ≥6 was found to be significantly correlated with shorter overall survival (P < 0.02). In the multivariate survival analysis with adjustment for the clinical T and N classification, age, sex, anatomical location, treatment group (radiotherapy/surgery) and chemotherapy (presence/absence), a Charlson comorbidity index value ≥6 was found to be associated with the significantly shorter overall survival. CONCLUSIONS: These results suggest that the Charlson comorbidity index functions as a prognostic factor in cases of resectable sinonasal tract squamous cell carcinoma.

Efficacy of palliative radiotherapy for gastric bleeding in patients with unresectable advanced gastric cancer: a retrospective cohort study.

BACKGROUND: Bleeding negatively impacts quality of life in patients with unresectable advanced gastric cancer and has the potential to be lethal. When blood transfusion and endoscopic hemostasis are unsuccessful to stop bleeding, radiation to stomach is selected in patients with unsuitable condition for surgery. We performed a retrospective cohort study to clarify the utility of radiotherapy in treating gastric bleeding, particularly for patients with limited life expectancy. METHODS: We evaluated the efficacy and safety of palliative radiotherapy in patients with advanced gastric cancer between January 2007 and December 2012 in Aichi Cancer Center Hospital. All patients had gastric bleeding requiring blood transfusion. We defined hemostasis as an increase in hemoglobin level to more than 7.0 g/dL together with the cessation of melena or hematemesis for at least 1 week. RESULTS: During the study period, 313 advanced gastric cancer patients treated in our institution. Of these 17 patients received gastric radiotherapy to stop bleeding. Two patients were excluded from analysis due to combined treatment of intravascular embolization. Eleven out of 15 patients (73 %) had undergone two or more previous chemotherapy regimens. Ten patients (67 %) had an Eastern Cooperative Oncology Group performance status of 3 and 14 patients (93 %) were in palliative prognostic index group B or C. The median total planned radiation dose was 30 Gy in 10 fractions. At a median interval of 2 days after initiation of radiotherapy, 11 patients (73 %) achieved hemostasis; rebleeding was observed in four patients (36 %). The median hemoglobin level before radiotherapy was significantly increased from 6.0 to 9.0 g/dL (p < 0.0001). The median volume of red blood cell transfusion was significantly decreased from 1120 to 280 mL (p = 0.007). The median rebleeding-free survival interval was 27 days, with a median overall survival of 63 days. The cause of death was bleeding in 1 patient (7 %) and cancer progression without bleeding in 12 patients (80 %). There were no severe adverse events attributable to radiotherapy. CONCLUSIONS: Palliative radiotherapy for gastric bleeding achieves hemostasis within a short time frame. This appears to be a useful treatment option, especially for patients with end-stage, unresectable advanced gastric cancer.

International prostate symptom score (IPSS) change and changing factor in intensity-modulated radiotherapy combined with androgen deprivation therapy for prostate cancer.

The purposes of this study on prostate cancer are to demonstrate the time course of International Prostate Symptom Score (IPSS) after intensity-modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) and to examine the factor associated with the IPSS change. This study included 216 patients treated with IMRT between 2006 and 2010. Patients were evaluated in three groups according to baseline IPSS as defined by the American Urological Association classification, where IPSSs of 0 to 7, 8 to 19, and 20 to 35 represent mild (n = 124), moderate (n = 70), and severe (n = 22) symptom groups, respectively. The average IPSSs ± standard deviation at baseline vs. those at 24 months after IMRT were 3.5 ± 2.1 vs. 5.1 ± 3.6 in the mild group (P < 0.001), 12.6 ± 3.4 vs. 10.0 ± 6.0 in the moderate group (P = 0.0015), and 23.8 ± 2.9 vs. 14.4 ± 9.1 in the severe group (P < 0.001). Among factors of patient and treatment characteristics, age, IPSS classification, pretreatment GU medications, and positive biopsy rates were associated with the IPSS difference between baseline and 24 months (P = 0.023, < 0.001, 0.044, and 0.028, respectively). In conclusion, patients with moderate to severe urinary symptoms can exhibit improvement in urinary function after IMRT, whereas patients with mild symptoms may have slightly worsened functions. Age, baseline IPSS, GU medications, and tumor burden in the prostate can have an effect on the IPSS changes.

Clinical efficacy of alternating chemoradiotherapy by conformal radiotherapy combined with intracavitary brachytherapy for high-risk cervical cancer.

OBJECTIVE: The purpose of this study was to assess the outcome of alternating chemoradiotherapy in patients with high-risk cervical cancer. METHODS: We performed definitive alternating chemoradiotherapy in cervical cancer patients with at least one high-risk factor such as International Federation of Gynecology and Obstetrics III or IVA disease, primary tumor diameter ≥50 mm, positive pelvic node, and positive para-aortic node. Our chemoradiotherapy protocol was as follows: (i) alternating chemoradiotherapy with 5-fluorouracil and nedaplatin; (ii) whole pelvic radiotherapy with the dynamic conformal technique combined with intracavitary brachytherapy; (iii) prophylactic irradiation to the para-aortic region for International Federation of Gynecology and Obstetrics III/IVA or positive pelvic node and full-dose radiotherapy for positive para-aortic node. Between 1998 and 2010, 121 patients were treated with this protocol. RESULTS: The median follow-up period was 53.7 months (7.6-162.2). International Federation of Gynecology and Obstetrics stages were IB; (9.1%), IIA; 6 (5.0%), IIB; 53 (43.8%), IIIA; 7 (5.8%), IIIB; 37 (30.6%) and IVA; 7 (5.8%), respectively. Nodal involvement was reported in 77 patients (63.6%) at the pelvis and 25 (20.7%) at the para-aortic region. The 5-year overall survival and progression-free survival rates were 80.0 and 63.4%, respectively. Regarding Grade ≥3 late toxicities, three patients developed urinary and three developed intestinal toxicities. We encountered no treatment-related death. CONCLUSIONS: The clinical results of our alternating chemoradiotherapy protocol for high-risk cervical cancer are promising.

Japanese structure survey of high-precision radiotherapy in 2012 based on institutional questionnaire about the patterns of care.

OBJECTIVE: The purpose of this study was to clarify operational situations, treatment planning and processes, quality assurance and quality control with relevance to stereotactic radiotherapy, intensity-modulated radiotherapy and image-guided radiotherapy in Japan. METHODS: We adopted 109 items as the quality indicators of high-precision radiotherapy to prepare a questionnaire. In April 2012, we started to publicly open the questionnaire on the website, requesting every institution with radiotherapy machines for response. The response ratio was 62.1% (490 out of 789 institutions responded). RESULTS: Two or more radiotherapy technologists per linear accelerator managed linear accelerator operation in ∼90% of the responded institutions while medical physicists/radiotherapy quality managers were engaged in the operation in only 64.9% of the institutions. Radiotherapy certified nurses also worked in only 18.4% of the institutions. The ratios of the institutions equipped for stereotactic radiotherapy of lung tumor, intensity-modulated radiotherapy and image-guided radiotherapy were 43.3, 32.6 and 46.8%, respectively. In intensity-modulated radiotherapy planning, radiation oncologists were usually responsible for delineation while medical physicists/radiotherapy quality managers or radiotherapy technologists set up beam in 33.3% of the institutions. The median time required for quality assurance of intensity-modulated radiotherapy at any site of brain, head and neck and prostate was 4 h. Intensity-modulated radiotherapy quality assurance activity had to be started after clinical hours in >60% of the institutions. CONCLUSIONS: This study clarified one major issue in the current high-precision radiotherapy in Japan. A manpower shortage should be corrected for high-precision radiotherapy, especially in the area relevant to quality assurance/quality control.

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.

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.