Effectiveness of intraoral stents in reducing oral adverse events during radiotherapy for maxillary or nasal cavity malignant tumors.

PURPOSE: Many patients experience oral adverse events during head and neck cancer radiotherapy (RT). The methods of management of such events are under debate. One such technique is the intraoral stent (IOS) technique, which removes normal tissue from the irradiation field. This retrospective study examined the factors associated with the occurrence of oral mucositis (OM) and dysgeusia and the efficacy of IOSs in preventing them. METHODS: Twenty-nine patients who underwent RT in the maxilla or nasal cavity between 2016 and 2022 were included. They were investigated for background characteristics, treatment factors (IOS and dose-volume histogram), and oral adverse events (OM and dysgeusia). RESULTS: Significant risk factors for the incidence of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) OM were the non-use of IOSs (p = 0.004) and diabetes (p = 0.025). A significant risk factor for the incidence of grade ≥ 1 dysgeusia was concomitant chemotherapy (p = 0.019). The radiation dose to the tongue was significantly lower in the IOS group than in the non-IOS group. CONCLUSION: Our findings suggest that the use of an IOS during RT reduces the severity of OM by reducing irradiation to the tongue. Therefore, the use of an IOS is recommended during RT performed in the maxilla or nasal cavity.

Clinical Results and Hematologic Predictors of Linear Accelerator-Based Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy for Brain Metastasis in Patients Aged 75 Years or Older: A Retrospective Study.

OBJECTIVE: This study aimed to evaluate prognostic factors including pre-radiosurgical blood count in elderly patients (EPs) with brain metastasis (BM) who were treated using linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. METHODS: Between January 2011 and November 2021, 101 consecutive EPs with BM were treated by LINAC-based SRS or fSRT using LINAC with a micro-multileaf collimator. EPs were defined as patients aged ≥75 years. RESULTS: The tumors originated from the lungs (n = 90; 89.1%), colon (n = 2; 2.0%), and others (n = 9; 8.8%) in these EPs. The median pretreatment Karnofsky Performance Status was 80 (range, 40-100). The median follow-up time was 10 months (range, 0-76), as was the median survival. The 6-month, 1-year, and 2-year survival in the EP group was 58.3%, 43.2%, and 28.5%, respectively. Freedom from local failure at 6 months and 1 and 2 years was 97%, 95%, and 91.5%, respectively. Freedom from distant failure at 6 months and 1 and 2 years in EPs was 70.6%, 59.4%, and 54.2%, respectively. A high neutrophil/lymphocyte ratio >5.33 was an unfavorable predictor of prognosis for EPs with BMs treated with SRS and fSRT (P < 0.001). In the EPs, the prognostic factors associated with prolonged survival in the Cox proportional hazards model were being female and a good pretreatment Karnofsky Performance Status. CONCLUSIONS: The findings of our study highlight the efficacy of LINAC-based SRS and fSRT with a micro-multileaf collimator in the treatment of EPs with BMs. Neutrophil/lymphocyte ratio can be an important factor in treatment decisions for EPs with BMs.

Quality of life in patients who underwent robot-assisted radical prostatectomy compared with those who underwent low-dose-rate brachytherapy.

BACKGROUND: To compare the quality of life (QOL) in patients who underwent robot-assisted radical prostatectomy (RARP) or low-dose-rate brachytherapy (LDR-BT) for prostate cancer. METHODS: We enrolled patients who underwent LDR-BT (LDR-BT alone [n = 540] or LDR-BT plus external beam radiation therapy [n = 428]) and RARP (n = 142). QOL was evaluated using the International Prostate Symptom Score, Expanded Prostate Cancer Index Composite (EPIC), Sexual Health Inventory for Men (SHIM), and 8-item Short Form (SF-8) health survey. The two groups were compared using propensity score matching analysis. RESULTS: At 24 months after treatment, the number of patients with worsened urinary QOL in the urinary domain of EPIC compared with baseline was 78/111 (70%) and 63/137 (46%) in the RARP and LDR-BT groups, respectively (p < 0.001). In the urinary incontinence and function domain, this number was higher in the RARP group versus the LDR-BT group. However, in the urinary irritative/obstructive domain, the number of patients with improved urinary QOL at 24 months compared with baseline was 18/111 (16%) and 9/137 (7%), respectively (p = 0.01). Regarding the SHIM score, sexual domain of EPIC, and mental component summary of SF-8, there were more number of patients with worsened QOL in the RARP group than in the LDR-BT group. In the EPIC bowel domain, the number of patients with worsened QOL was lower in the RARP group versus the LDR-BT group. CONCLUSION: The differences in QOL observed between patients treated with RARP and LDR-BT could assist in treatment selection for prostate cancer.

Local dose (biologically effective dose ≥180 Gy2) is an important predictor of biochemical recurrence in patients undergoing low-dose-rate brachytherapy.

OBJECTIVES: To evaluate prognostic factors of biochemical recurrence (BCR) in each risk group of prostate cancer patients who underwent low-dose-rate brachytherapy (LDR-BT). METHODS: A total of 944 patients with clinically confirmed prostate cancer (cT1c-3aN0M0) who had underwent LDR-BT were enrolled. The low-, intermediate-, and high-risk groups included 278, 498, and 168 patients, respectively. The median age, PSA value at diagnosis, and the follow-up period were 70 years (range: 48-84), 7.2 ng/ml (range: 1.2-113), and 91 months (range: 2-192), respectively. We evaluated the BCR-free rate, BCR-free survival, clinical recurrence-free rate, overall survival (OS), and cancer-specific survival (CSS). We conducted multivariate analysis to elucidate prognostic factors of BCR for all patients and for each risk group. RESULTS: The 5- and 10-year OS rates were 96.0% and 89.5% and the 5- and 10-year CSS rates were 99.8% and 99.1%, respectively, while the 5- and 10-year BCR-free rates were 96.6% and 92.5% in low-risk patients, 95.7% and 90.7% in intermediate-risk patients and 93.8% and 89.0% in high-risk patients, respectively. There were no significant differences between the risk groups. Age-adjusted multivariate analysis indicated biologically effective dose (BED) <180 Gy2 as an independent prognostic factor of BCR in all patients (p = 0.005). There were no independent factors in the low- and high-risk groups, but neoadjuvant androgen deprivation therapy (ADT) (p = 0.022) and BED <180Gy2 (p = 0.042) were independent prognostic factors in the intermediate-risk group. CONCLUSIONS: LDR-BT can achieve a higher recurrence-free survival with an adequate local radiation dose (BED ≥ 180 Gy2).

Long-Term Survival after Linac-Based Stereotactic Radiosurgery and Radiotherapy with a Micro-Multileaf Collimator for Brain Metastasis.

BACKGROUND: this study aimed to evaluate the prognostic factors associated with long-term survival after linear accelerator (linac)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for brain metastasis (BM). METHODS: This single-center retrospective study included 226 consecutive patients with BM who were treated with linac-based SRS or fSRT with a micro-multileaf collimator between January 2011 and December 2018. Long-term survival (LTS) was defined as survival for more than 2 years after SRS/fSRT. RESULTS: The tumors originated from the lung (n = 189, 83.6%), breast (n = 11, 4.9%), colon (n = 9, 4.0%), stomach (n = 4, 1.8%), kidney (n = 3, 1.3%), esophagus (n = 3, 1.3%), and other regions (n = 7, 3.1%). The median pretreatment Karnofsky performance scale (KPS) score was 90 (range: 40-100). The median follow-up time was 13 (range: 0-120) months. Out of the 226 patients, 72 (31.8%) were categorized in the LTS group. The median survival time was 43 months and 13 months in the LTS group and in the entire cohort, respectively. The 3-year, 4-year, and 5-year survival rate in the LTS group was 59.1%, 49.6%, and 40.7%, respectively. Multivariate regression logistic analysis showed that female sex, a pre-treatment KPS score ≥ 80, and the absence of extracranial metastasis were associated with long-term survival. CONCLUSIONS: female sex, a favorable pre-treatment KPS score, and the absence of extracranial metastasis were associated with long-term survival in the current cohort of patients with BM.

Late genitourinary and gastrointestinal toxicity and radiation-induced second primary cancers in patients treated with low-dose-rate brachytherapy.

OBJECTIVES: To evaluate late genitourinary (GU) and gastrointestinal (GI) toxicities and radiation-induced second primary cancers (RISPCs) in patients who received low-dose-rate brachytherapy (LDR-BT) with or without external beam radiotherapy for prostate cancer. METHODS: This retrospective study included 897 consecutive patients who received LDR-BT between July 2004 and July 2015 in our institution. Adverse events and the incidence of second primary cancers were evaluated at 1, 3, 6, 12, 18, 24, 30, 36, 48, 54, and 60 mo after LDR-BT and then once a year. Related factors to ≥grade 2 (G2) toxicity were evaluated using the Cox proportional-hazards model. RESULTS: The median follow-up time was 85.2 (interquartile range: 66.8-111.3) mo. The cumulative incidence rates of ≥G2 GU toxicity at 5 and 10 yrs after LDR-BT were 11.2% and 14.7%, respectively. The International Prostate Symptom Score before LDR-BT (continuous) (hazard ratio [HR]: 1.03), no neoadjuvant androgen deprivation therapy (HR: 1.69), and combination external beam radiotherapy (HR: 3.30) were risk factors related to the incidence of ≥G2 GU toxicity. The cumulative incidence rates of ≥G2 GI toxicity at 5 and 10 yrs after LDR-BT were 3.3% and 3.3%, respectively. Age (continuous) (HR: 1.09), body mass index (continuous) (HR: 0.87), and rectum V100 (continuous) (HR: 1.64) were risk factors related to ≥G2 GI toxicity. A total of 12 (1.3%) patients developed metachronous RISPCs (bladder cancer: 9; rectal cancer: 3). CONCLUSION: The incidence rates of late GU and GI toxicities and RISPCs after LDR-BT were low.

Mirabegron Reduces Urinary Frequency and Improves Overactive Bladder Symptoms at 3 Months After 125I-brachytherapy for Prostate Cancer: An Open-Labeled, Randomized, Non-Placebo-Controlled Study.

OBJECTIVE: To evaluate the additional effects of mirabegron to alpha-1 adrenergic antagonist on lower urinary tract symptoms of patients who underwent 125I-brachytherapy for prostate cancer. PATIENTS AND METHODS: Patients who underwent 125I-brachytherapy for prostate cancer (cT1-cT3aN0M0) in a single institute between September 2016 and October 2018 were enrolled in the randomized, non-placebo, open-labeled, paralleled study. Patients were randomly distributed (1:1) to combination group (tamsulosin (0.2 mg/day) plus mirabegron (50 mg/day)) or tamsulosin-alone group after 125I -brachytherapy by envelope method. The primary endpoint was the change from baseline in mean voided volume per micturition 3 months after 125I brachytherapy. The secondary endpoints included the changes from baseline of International Prostate Symptom Score, Overactive Bladder Symptom Score, and Expanded Prostate Cancer Index Composite scores and 24 hours urinary frequency after 3 months after 125I brachytherapy. RESULTS: The mean changes in volume voided per micturition in the combination (n = 108) and tamsulosin-alone (n = 110) groups were -62.5 (standard deviation, ±53.8) and -68.0 (standard deviation, ±52.7), respectively (P = .17). The change in Overactive Bladder Symptom Score in combination group (P = .02) was more moderate than in tamsulosin-alone group; and 24 hour urinary frequency in combination group was lower (P = .03) than in tamsulosin-alone group. Retention rates within 3 months after 125I-brachytherapy in the mirabegron and tamsulosin-alone groups were 7.3% (9/122) and 6.0% (7/118), respectively (P = .80). CONCLUSION: Tamsulosin and mirabegron combination therapy after 125I-brachytherapy did not improve voided volume per micturition compared to tamsulosin-only treatment. However, it could improve frequent urination and overactive bladder symptoms.

Impact of neoadjuvant androgen deprivation therapy on postimplant prostate D90 and prostate volume after low-dose-rate brachytherapy for localized prostate cancer.

OBJECTIVE: Higher quality of postimplant dosimetric evaluation is associated with higher biochemical recurrence-free survival rates after low-dose-rate brachytherapy for localized prostate cancer. Postimplant prostate D90 is a key dosimetric parameter showing the quality of low-dose-rate brachytherapy. In this study, to improve the quality of low-dose-rate brachytherapy for localized prostate cancer, we investigated pre-implant factors affecting the reduction of postimplant prostate D90. METHODS: A total of 441 patients underwent low-dose-rate brachytherapy monotherapy and 474 patients underwent low-dose-rate brachytherapy with external beam radiation therapy. Logistic regression analysis was carried out to identify predictive factors for postimplant D90 decline. The cut-off value of the D90 decline was set at 170 Gy and 130 Gy in the low-dose-rate brachytherapy monotherapy group and low-dose-rate brachytherapy with external beam radiation therapy group, respectively. RESULTS: On multivariate analysis, neoadjuvant androgen deprivation therapy was identified as an independent predictive factor for the decline of postimplant D90 in both the low-dose-rate brachytherapy monotherapy group (P < 0.001) and low-dose-rate brachytherapy with external beam radiation therapy group (P = 0.003). Prostate volume changes and computed tomography/transrectal ultrasound prostate volume ratio were significantly and negatively correlated with the postimplant D90. The prostate volume changes and computed tomography/transrectal ultrasound prostate volume ratio were significantly higher in patients with neoadjuvant androgen deprivation therapy than those without neoadjuvant androgen deprivation therapy (P < 0.001). CONCLUSIONS: Neoadjuvant androgen deprivation therapy decreased postimplant D90 with substantial prostate gland swelling after low-dose-rate brachytherapy. When neoadjuvant androgen deprivation therapy is required to reduce prostate volume for patients with large prostate glands and offer adequate local control for patients with high-risk prostate cancer before low-dose-rate brachytherapy, intraoperative D90 adjustment might be necessary.

Erectile dysfunction and sexual quality of life in patients who underwent low-dose-rate brachytherapy alone for prostate cancer.

This study evaluated erectile function and sexual quality of life (QoL), and predictive factors for erectile dysfunction (ED) and the deterioration of sexual QoL in 70 patients who underwent low-dose-rate brachytherapy (LDR-BT) alone for prostate cancer without androgen deprivation therapy. Erectile function and sexual QoL were evaluated before and 1, 3, 6, 12, 24, 36, 48 and 60 months after LDR-BT. Binary logistic regression analysis was used to determine whether age, prostate volume, hypertension, diabetes, Brinkman's index, testosterone, baseline Sexual Health Inventory for Men (SHIM) score and post-implant dosimetry parameters could predict ED and deterioration of sexual QoL at 24 and 60 months after LDR-BT. After 24 and 60 months, ED was noted in 39 of 70 patients and 42 of 64 patients respectively. Furthermore, sexual QoL worsened in 42 of 70 and 43 of 64 patients respectively. Baseline SHIM score was identified as a significant predictor of ED (24 months: odds ratio [OR]: 0.83, p = 0.02; 60 months: OR: 0.83, p = 0.03) and the deterioration of sexual QoL (24 months: OR: 0.84, p = 0.03). LDR-BT for prostate cancer promoted decreased erectile function and sexual QoL, with high preimplant potency being a significant predictor of ED and the deterioration of sexual QoL.

Factors affecting urinary frequency after low-dose-rate brachytherapy for prostate cancer.

OBJECTIVES: Lower urinary tract symptoms are transiently exacerbated by low-dose-rate brachytherapy (LDR-BT) for prostate cancer and recover to pretreatment levels 1 year thereafter. Generally, these symptoms are influenced by temperature. We aimed to search for factors affecting the lower urinary tract symptoms after seed implant including seasons. METHODS: We retrospectively enrolled 812 patients who underwent LDR-BT at Nara Medical University Hospital from January 2010 to December 2018 and for whom the International Prostate Symptom Score, Overactive Bladder Symptom Score, and frequency volume charts were available. We investigated the relationships between lower urinary tract symptoms, 24-hours urinary frequency, 24-hours urinary volume before and after seed implant, radiation dose, and season of seed implant. RESULTS: The mean age was 69.5 years. The mean prostate volume was 24.2 mL. The International Prostate Symptom Score, Overactive Bladder Symptom Score, and 24-hours urinary frequency increased until 3 months and gradually decreased over 6 months after seed implant. Multiple linear regression analysis revealed that 24-hours urinary frequency at 3 months after seed implant was significantly influenced by external beam radiotherapy, larger prostate volume before implant, higher 24-hours urinary frequency at baseline, larger 24-hours urinary volume at 3 months after implant, and performance of implant in summer. CONCLUSIONS: Lower urinary tract symptoms worsened 3 months after seed implant of LDR-BT regardless of the season of implant. The urinary frequency 3 months after seed implant was slightly lower when seed implant was performed in the summer.

Salvage Surgical Resection after Linac-Based Stereotactic Radiosurgery for Newly Diagnosed Brain Metastasis.

BACKGROUND: This study aimed to assess the clinical outcomes of salvage surgical resection (SSR) after stereotactic radiosurgery and fractionated stereotactic radiotherapy (SRS/fSRT) for newly diagnosed brain metastasis. METHODS: Between November 2009 and May 2020, 318 consecutive patients with 1114 brain metastases were treated with SRS/fSRT for newly diagnosed brain metastasis at our hospital. During this study period, 21 of 318 patients (6.6%) and 21 of 1114 brain metastases (1.9%) went on to receive SSR after SRS/fSRT. Three patients underwent multiple surgical resections. Twenty-one consecutive patients underwent twenty-four SSRs. RESULTS: The median time from initial SRS/fSRT to SSR was 14 months (range: 2-96 months). The median follow-up after SSR was 17 months (range: 2-78 months). The range of tumor volume at initial SRS/fSRT was 0.12-21.46 cm3 (median: 1.02 cm3). Histopathological diagnosis after SSR was recurrence in 15 cases, and radiation necrosis (RN) or cyst formation in 6 cases. The time from SRS/fSRT to SSR was shorter in the recurrence than in the RNs and cyst formation, but these differences did not reach statistical significance (p = 0.067). The median survival time from SSR and from initial SRS/fSRT was 17 and 74 months, respectively. The cases with recurrence had a shorter survival time from initial SRS/fSRT than those without recurrence (p = 0.061). CONCLUSIONS: The patients treated with SRS/fSRT for brain metastasis need long-term follow-up. SSR is a safe and effective treatment for the recurrence, RN, and cyst formation after SRS/fSRT for brain metastasis.

Comparison of disease-specific quality of life in prostate cancer patients treated with low-dose-rate brachytherapy: A randomized controlled trial of silodosin versus naftopidil.

OBJECTIVES: To compare the effects of naftopidil and silodosin administration on the quality of life of patients with prostate cancer who underwent low-dose-rate brachytherapy. METHODS: In total, 141 men diagnosed with localized prostate cancer who were treated with low-dose-rate brachytherapy were enrolled. Patients were randomized (1:1) to the naftopidil (75 mg/day, n = 63) or silodosin group (8 mg/day, n = 64). Naftopidil and silodosin were administered 1 day after low-dose-rate brachytherapy, and were continued for at least 3 months. Using the University of California at Los Angeles Prostate Cancer Index and Sexual Health Inventory for Men scores, the mean changes and rates of deterioration from baseline were compared. The deterioration rates in the quality of life of patients at 1 and 3 months after low-dose-rate brachytherapy were evaluated based on the minimal important difference. RESULTS: The rates of deterioration from baseline to 1 and 3 months after low-dose-rate brachytherapy were not significantly different between the two groups in terms of urinary function, urinary bother, bowel bother, sexual function or Sexual Health Inventory for Men scores. In contrast, there were significant differences in bowel function (naftopidil 1 month, 52%; 3 months, 52%; silodosin 1 month, 28%; 3 months, 34%; 1 month, P < 0.01; 3 months, P = 0.048) and sexual bother (naftopidil 3 months, 11%; silodosin 3 months, 29%; P = 0.01). CONCLUSIONS: Naftopidil and silodosin provide different disease-specific quality of life outcomes in patients undergoing, especially in terms of bowel function and sexual bother. These findings can help in the selection of α-1 adrenoceptor antagonists after low-dose-rate brachytherapy.

Coverage of the external prostatic region by the hybrid method compared with the conventional method of prostate low-dose-rate brachytherapy: A randomized controlled study.

OBJECTIVES: To compare the dose evaluation parameters between conventional (using loose seed alone) and hybrid (using loose seeds in combination with stranded seeds) low-dose rate brachytherapy for prostate cancer. METHODS: Between 2014 and July 2016, a total of 219 patients who underwent low-dose rate brachytherapy were enrolled in a randomized controlled trial (trial number: UMIN 000012780). Patients were randomized and allocated to two groups (conventional method vs hybrid method). Post-dosimetric parameters (%D90, minimal percentage of the dose received by 90% of the prostate gland; V100, percentage of the prostate volume receiving 100% of the prescribed minimal peripheral dose; V150, percentage of the prostate volume receiving 150% of the prescribed minimal peripheral dose; %UD30, minimal percentage of the dose received by 30% of the urethra; R100, rectal volume [mL] receiving 100% of the prescribed dose) calculated at 1 month after seed implantation by computed tomography scan were compared between the two groups, as well as the post-dosimetric parameters using the planning target volume of the prostate + 5-mm margin. RESULTS: Regarding dose evaluation parameters, the prostate dose (%D90, V100, V150) and the urethral dose (%UD30) were not significantly different between the two groups, whereas V100 (+5-mm margin) and %D90 (+5-mm margin) were significantly higher in the hybrid method group compared with the conventional method group (P < 0.001). CONCLUSION: The present randomized study shows that the hybrid method of low-dose rate brachytherapy can achieve a higher coverage of the periprostatic region compared with the conventional method while maintaining an acceptable level of urethral and rectal doses.

A prospective study of oral 5-aminolevulinic acid to prevent adverse events in patients with localized prostate cancer undergoing low-dose-rate brachytherapy: Protocol of the AMBER study.

BACKGROUND: Radiotherapy is one of the most frequently selected treatment options for patients with prostate cancer. However, adverse effects related to the irradiated surrounding normal organs are significant clinical concerns. Specifically, genitourinary and gastrointestinal toxicities can lead to a dramatically reduced quality of life. The aim of this clinical trial is to determine the efficacy of oral 5-aminolevulinic acid (ALA) phosphate with sodium ferrous citrate (SFC) in patients treated with low-dose-rate brachytherapy (LDR-BT) using an iodine-125 seed source. METHODS: The AMBER study is a prospective, single-center trial in patients with localized prostate cancer undergoing LDR-BT. Patients who undergo supplementary extra-beam radiotherapy are excluded, whereas those who undergo pre-implantation short-term (4-6 months) androgen deprivation therapy to decrease the prostate volume and/or improve oncological outcomes are included. After the screening and registration, the patients will be instructed to take capsules of ALA-SFC twice a day (200 mg and 229.42 mg per day) for 6 months from the day of seed implantation (prescribed radiation dose of 160 Gy). Patient data will be collected before the implantation; during oral ALA-SFC treatment; and 1, 3, 6, 9, and 12 month(s) after seed implantation. The primary endpoint of this trial is the urinary frequency 3 months after seed implantation. At each visit, the 24-h urinary frequency, total voided volume, and mean voided volume on a frequency volume chart and other patient-reported outcomes are recorded. The data of the trial cases will be compared with those of historical controls, who are consecutive patients undergoing LDR-BT without supplementary extra-beam radiotherapy between January 2016 and January 2019. The number of subjects has been set to be 50 for trial cases and 150 for the historical control cases. Pre- and post-treatment clinicopathologic factors are compared between two groups. DISCUSSION: The goal of this trial is to determine the potential benefit of ALA-SFC in patients who undergo LDR-BT. To the best of our knowledge, this is the first study investigating the potential clinical benefit of oral ALA-SFC after radiotherapy. More evidence from a further randomized controlled trial is needed to change the standard of care and lead to better post-radiotherapy management. TRIAL REGISTRATION: This clinical trial was prospectively registered with the Japan Registry of Clinical Trials on 5 December 2019. The reference number is jRCTs051190077, nara0013 (Certified Review Board of Nara Medical University).

Biochemical control of the combination of cyclooxygenase-2 inhibitor and 125 I-brachytherapy for prostate cancer: Post hoc analysis of an open-label controlled randomized trial.

OBJECTIVES: To evaluate the use of cyclooxygenase-2 inhibitors in patients receiving low-dose-rate brachytherapy for prostate cancer. METHODS: A total of 310 patients with prostate cancer (cT1c-3aN0M0) who received low-dose-rate brachytherapy between May 2010 and July 2013 were enrolled and allocated to one of the two treatment groups (tamsulosin alone 0.2 mg/day for 6 months vs tamsulosin 0.2 mg/day for 6 months plus celecoxib 200 mg/day for 3 months). The primary end-point was the chronological change in international prostate symptom score, and the number of patients was assessed for the primary end-point. Biochemical recurrence-free, cancer-specific survival and overall survival rates 5 years after the last patient received low-dose-rate brachytherapy were retrospectively examined. RESULTS: The median follow-up period after low-dose-rate brachytherapy was 72.0 months (range 3-99 months). A total of 12 (3.9%) patients experienced biochemical recurrence. The biochemical recurrence-free rate in the celecoxib group (5-year biochemical recurrence-free rate 98.5%) was significantly better (log-rank test P = 0.023, 95% confidence interval 0.07-0.63, hazard ratio 0.20) than that in the tamsulosin group (5-year biochemical recurrence-free rate 93.4%). None of the patients died from prostate cancer. However, 14 (4.5%) patients died of other causes. No significant difference was observed in terms of overall survival between the celecoxib and tamsulosin groups. CONCLUSIONS: The combination of cyclooxygenase-2 inhibitor and low-dose-rate brachytherapy can contribute to a better biochemical control of prostate cancer.

Linac-based fractionated stereotactic radiotherapy with a micro-multileaf collimator for large brain metastasis unsuitable for surgical resection.

The aim of this study was to assess clinical outcomes using linac-based, fractionated, stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for large brain metastasis (LBM) unsuitable for surgical resection. Between January 2009 and October 2018 we treated 21 patients with LBM using linac-based fSRT. LBM was defined as a tumor with ≥30 mm maximal diameter in gadolinium-enhanced magnetic resonance images. LBMs originated from the lung (n = 17, 81%), ovary (n = 2, 9.5%), rectum (n = 1, 4.8%) and esophagus (n = 1, 4.8%). The median pretreatment Karnofsky performance status was 50 (range: 50-80). Recursive partition analysis (RPA) was as follows: Classes 2 and 3 were 7 and 14 patients, respectively. The median follow-up was 5 months (range: 1-86 months). The range of tumor volume was 8.7-26.5 cm3 (median: 17.1 cm3). All patients were basically treated with 35Gy in 5 fractions, except in three cases. The progression-free survival was 3.0 months. The median survival time was 7.0 months. There was no permanent radiation injury in any of the patients. Radiation-caused central nervous system necrosis, according to the Common Terminology Criteria for Adverse Events version 4.0, occurred in one patient (grade 3). One patients received bevacizumab for radiation necrosis. Two patients underwent additional surgical resection due to local progression and cyst formation. For patients with LBM unsuitable for surgical resection, linac-based fSRT is a promising therapeutic alternative.

Prostate-specific antigen bounce after 125I-brachytherapy for prostate cancer is a favorable prognosticator in patients who are biochemical recurrence-free at 4 years and correlates with testosterone.

BACKGROUND: Because patients with prostate-specific antigen (PSA) bounce do not experience biochemical recurrence (BCR) until PSA bounce occurs, the period until PSA bounce ends can be considered the so-called lead-time bias. Therefore, we evaluated differences in BCR-free rate in prostate cancer patients who were BCR-free 4 years after 125I-brachytherapy alone. Furthermore, we evaluated predictors for PSA bounce and the correlation between testosterone and PSA bounce. METHODS: From 2004 to 2012, 256 patients with prostate adenocarcinoma underwent 125I-brachytherapy alone. PSA and testosterone levels were monitored prior to 125I-brachytherapy, at 1, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months after 125I-brachytherapy and yearly after 5-year follow-up. PSA bounce was defined as ≥0.2 ng/ml increase above the interval PSA nadir, followed by a decrease to nadir or below. RESULTS: BCR-free rate in patients with PSA bounce (100% 7-year BCR-free rate) was significantly better (P < 0.044) than that in patients without PSA bounce (95.7% 7-year BCR-free rate) in patients who were BCR-free 4 years after 125I-brachytherapy alone (n = 223). Age was the only predictor (odds ratio: 0.93, 95% confidence interval: 0.88-0.98, P = 0.004) for PSA bounce (n = 177). The testosterone level at PSA bounce was significantly higher (P = 0.036) than that at nadir before PSA bounce (87 cases). CONCLUSIONS: Patients with PSA bounce had good BCR-free rate even in patients who were BCR-free 4 years after 125I-brachytherapy alone. Testosterone levels were higher at PSA bounce; increased testosterone levels may be a cause of PSA bounce.

Linac-Based Fractionated Stereotactic Radiotherapy with a Micro-Multileaf Collimator for Brainstem Metastasis.

BACKGROUND: To assess the neuroimaging and clinical outcomes in patients with brainstem metastasis (BSM) treated with linac-based fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. METHODS: Between May 2007 and January 2017, 24 patients (15 male and 9 female) with BSM (25 lesions: midbrain, 10; pons, 13; and medulla oblongata, 2) were consecutively treated with linac-based fSRT. BSM originated from the lung (n = 18, 75.0%), colon (n = 3, 12.5%), and breast (n = 3, 12.5%). The median patient age was 67.0 (range: 42-80) years. Recursive partition analysis classified 2 patients as class I, 17 as class II, and 5 as class III. Overall survival was calculated using the Kaplan-Meier method. RESULTS: Tumor volume ranged from 0.01 to 7.49 cm3 (median: 0.233 cm3), and patients were treated with a dose of 24-40 Gy in 7-13 fractions. The median OS was 9 months after fSRT (95% confidence interval 4.104-13.896). Large tumor volume, presence of brainstem-related symptoms, poor pretreatment Karnofsky performance status, and recursive partition analysis class III were significantly associated with low overall survival. Tumor volume decreased in 18 metastatic lesions, remained stable in 6, and increased in 1. No patient exhibited permanent radiation injury. Grade 2 nausea and vomiting according to the Common Terminology Criteria for Adverse Events 4.0 occurred in 1 patient who received corticosteroids. CONCLUSIONS: Linac-based fSRT with a micro-multileaf collimator delivered in the doses of 24-40 Gy in 7-13 fractions is a safe and effective local therapy for patients with BSM.

Changes in lower urinary tract symptoms after iodine-125 brachytherapy for prostate cancer.

PURPOSE: To investigate chronological changes in lower urinary tract symptoms (LUTS) in patients who received iodine-125 brachytherapy (BT) for prostate cancer. METHODS: We enrolled 706 patients who received BT. Of these, 265 (38%) received BT combined with external beam radiation therapy (EBRT). An International Prostate Symptom Score (IPSS), IPSS quality of life (IPSS-QOL) score, and overactive bladder symptom score (OABSS) were recorded before BT (baseline, BL), and 1, 3, 6, 12, 24, 36, 48, and 60 months after BT. The sum of frequency (2), urgency (4) and nocturia (7) of the IPSS questionnaire was defined as the storage symptoms score, whereas the sum of emptying (1), intermittency (3), weak stream (5), and hesitancy (6) was defined as the voiding symptom score. RESULTS: Total IPSS significantly increased at 3 months following BT compared with BL (mean score: 17.1 vs. 7.99, P < 0.001) and returned to BL by 36 months. The storage symptom score did not return to BL 36 months after BT. Total OABSS significantly increased 3 months after BT compared with BL (mean score: 6.52 vs. 3.45, P < 0.001), and returned to BL 48 months after BT. The IPSS-QOL score was the highest score (mean score: 2.46 vs. 3.9, P < 0.001) 3 months after BT and returned to BL 48 months after BT, however the IPSS-QOL score was lower than BL (mean score: 2.01 vs 2.46, P < 0.001) at 60 months. The risk factors for LUTS within 1 year after BT were BL IPSS (P < 0.001) and PV (P < 0.001). Patients who received combined EBRT experienced transient storage symptoms 24 and 36 months after BT, whereas those who received BT alone did not. However, the storage symptom score of the patients who received combined EBRT was improving 48 months after BT and eventually showed no significant difference compared with those treated with BT alone. CONCLUSION: Three months after BT, LUTS, including storage symptoms, deteriorated the most but improved with time. The urinary symptom in patients who received combined EBRT can potentially flare again in 24 and 36 months after BT. Knowledge of changes in LUTS associated with BT may influence treatment recommendations and enable patients to make better-informed decisions.