Efficacy of surgery combined with postoperative 125 I interstitial brachytherapy for treatment of acinic cell carcinoma of the parotid gland in children and adolescents.

BACKGROUND: Acinic cell carcinoma (AciCC) is rare in children; therefore, reaching a consensus on its management is challenging and radiotherapy is limited by concerns about long-term toxicity. The purpose of this study is to analyze the effectiveness and safety of surgery plus postoperative 125 I interstitial brachytherapy (IBT) for children and adolescents with AciCC of the parotid gland (PG) treated at a single institution. PROCEDURE: Sixteen patients ≤ 18 years old with AciCC of the PG treated with surgery plus 125 I IBT from 2007 to 2018 were included. Surgery was the primary treatment; ten patients underwent total gross excision and six subtotal gross excision. The matched peripheral dose was 60-120 Gy. Overall survival, disease-free survival (DFS), local control rate, distant metastasis, and radiation-associated toxicities were analyzed, and factors influencing outcomes were evaluated. RESULTS: During follow-up (1.8-12.6 years; mean, 6.3 years), lymph node metastasis was observed in one case, 2.6 years after 125 I IBT treatment. The five-year overall and DFS rates were 100% and 91.7%, respectively. On univariate analysis, tumor size ≥ 3 cm (100% vs 50%; P = 0.025) and extraglandular extension (100% vs 50%; P = 0.025) were significant prognostic indicators for DFS. No severe radiation-associated complications occurred. CONCLUSIONS: Children and adolescents with AciCC of the PG with high-risk features can be managed using surgery plus postoperative 125 I IBT with excellent local control. Radiation-related complications were minor. Patients with facial nerve involvement can have their facial nerves preserved. Residual tumors can be safely managed using adjuvant 125 I IBT.

Metastasis, Mortality, and Quality of Life for Men With NCCN High and Very High Risk Localized Prostate Cancer After Surgical and/or Combined Modality Radiotherapy.

PURPOSE: To compare metastasis-free survival, overall survival, and patient-reported quality of life (QOL) of men with National Comprehensive Cancer Network high or very high risk prostate cancer after definitive surgery and/or multimodal radiotherapy (RT). PATIENTS AND METHODS: We studied a retrospective cohort study of 586 patients treated between the years 2000 and 2017 receiving radical prostatectomy with or without postoperative RT, external-beam RT (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy (Brachy) boost + ADT. Patient-reported QOL for urinary, bowel, sexual, and overall physical and mental functioning was assessed using the American Urological Association symptom scale, the Sexual Health Inventory in Men, the Rectal-Function Assessment Scale, the Expanded Prostate Cancer Index Composite, and the Veterans RAND 12-Item Health Survey. RESULTS: Median follow-up for survival was 5 years. No significant differences between the treatments were observed for overall survival or metastasis-free survival at the P < .05 threshold. The propensity-adjusted 5-year metastasis-free survival estimates for EBRT + ADT, EBRT + Brachy + ADT, and surgery were 74.6%, 94.8%, and 83.1%, respectively. The EBRT + Brachy + ADT and surgery cohorts had significantly worse mean American Urological Association symptom scores at 6 months than the EBRT + ADT cohort, which resolved by 1 year. Surgical patients had better rectal function scores than EBRT + ADT patients at years 1 to 3, but similar function thereafter. Adjuvant or salvage RT resulted in significant declines in various Expanded Prostate Cancer Index Composite urinary, sexual, and bowel domains, and Veterans RAND 12-Item Health Survey physical but not mental domains. CONCLUSION: Men with very and/or high-risk localized prostate cancer are likely to require multimodal therapy. The overall differences in survival and long-term QOL are similar for men choosing surgical versus RT pathways.

Tumor burden and liver function in HCC patient selection for selective internal radiation therapy: SARAH post-hoc study.

Aim: To determine whether a liver tumor burden ≤25% and well-preserved liver function (albumin-bilirubin grade 1) are appropriate criteria for identifying patients with unresectable hepatocellular carcinoma who may benefit from selective internal radiation therapy (SIRT) using 90yttrium resin microspheres versus sorafenib. Patients & methods: Post-hoc analysis of patients in the intention-to-treat population of the SARAH trial (SIRT vs sorafenib) with ≤25% tumor burden and albumin-bilirubin grade 1. Primary end point: overall survival. Results: Median overall survival was 21.9 months (95% CI: 15.2-32.5, n = 37) with SIRT and 17.0 months (11.6-20.8, n = 48) with sorafenib (hazard ratios: 0.73; 95% CI: 0.44-1.21; p = 0.22). Conclusion: A combination of good liver function and low tumor burden may be relevant for selection of hepatocellular carcinoma patients for SIRT.

Definitive Radiation Treatment Patterns and Outcomes for Low and Intermediate Risk Prostate Cancer Patients: A Cross-Continental Comparative Study.

PURPOSE: To evaluate early-stage prostate cancer (PCa) radiotherapy treatment patterns and outcomes among Ghanaian men (GM) compared with US men (USM). MATERIALS AND METHODS: This retrospective study consists of 987 National Comprehensive Cancer Network low risk, favorable intermediate risk, and unfavorable intermediate risk PCa patient subgroups; GM (173) and USM (814). Differences in baseline covariates and clinical characteristics between GM and USM were analyzed using χ and Mann-Whitney test while Cox Proportional Hazards model was used to assess freedom from biochemical failure differences between the study groups. RESULTS: Median follow-up for this study was 40 months. GM were diagnosed at a younger median age (64 vs. 68 y, P<0.001) with heavier unfavorable intermediate risk disease burden (32.4% vs. 19.2%) compared with USM. Significant differences were identified in median external beam radiotherapy dose (72.4 vs. 78 Gy, P<0.001); brachytherapy utilization (49.7% vs. 80.6%, P<0.001) and androgen deprivation therapy for intermediate risk disease (48.4% vs. 21.0%, P<0.001) between GM and USM, respectively. GM with low risk and favorable intermediate risk PCa were at increased risk of biochemical recurrence compared with USM with adjusted hazard ratio: 5.15 (1.27 to 20.7), P=0.02 and 4.64 (1.20 to 17.92), P=0.02, respectively. CONCLUSIONS: Compared with USM, GM with low and favorable intermediate risk PCa may experience less durable disease control following standard treatment recommendations. Results suggest differences in radiation treatment and possible inherent differences between the 2 populations. This data will aid in developing research strategies to improve treatment outcomes in GM.

Prostate brachytherapy with iodine-125 seeds: analysis of a single institutional cohort

ABSTRACT Objectives: Brachytherapy (BT) with iodine-125 seeds placement is a consolidated treatment for prostate cancer. The objective of this study was to assess the clinical outcomes in patients with prostate cancer who underwent low-dose-rate (LDR) -BT alone in a single Brazilian institution. Materials and Methods: Patients treated with iodine-125 BT were retrospectively assessed after at least 5 years of follow-up. Patients who received combination therapy (External beam radiation therapy-EBRT and BT) and salvage BT were not included. Results: 406 men were included in the study (65.5% low-risk, 30% intermediate-risk, and 4.5% high-risk patients). After a median follow-up of 87.5 months, 61 (15.0%) patients developed biochemical recurrence. The actuarial biochemical failure-free survival (BFFS) at 5 and 10 years were 90.6% and 82.2%, respectively. A PSA nadir ≥ 1 ng / mL was associated with a higher risk of biochemical failure (HR = 5.81; 95% CI: 3.39 to 9.94; p ≤ 0.001). The actuarial metastasis-free survival (MFS) at 5 and 10 years were 98.3% and 94%, respectively. The actuarial overall survival (OS) at 5 and 10 years were 96.2% and 85.1%, respectively. Acute and late grade 2 and 3 gastrointestinal toxicities were observed in 5.6%, 0.5%, 4.6% and 0.5% of cases, respectively. For genitourinary the observed acute and late grade 2 and 3 toxicities rates were 57.3%, 3.6%, 28% and 3.1%, respectively. No grade 4 and 5 were observed. Conclusions: BT was effective as a definitive treatment modality for prostate cancer, and its endpoints and toxicities were comparable to those of the main series in the literature.

Prostate brachytherapy with iodine-125 seeds: analysis of a single institutional cohort.

OBJECTIVES: Brachytherapy (BT) with iodine-125 seeds placement is a consolidated treatment for prostate cancer. The objective of this study was to assess the clinical outcomes in patients with prostate cancer who underwent low-dose-rate (LDR) -BT alone in a single Brazilian institution. MATERIALS AND METHODS: Patients treated with iodine-125 BT were retrospectively assessed after at least 5 years of follow-up. Patients who received combination therapy (External beam radiation therapy-EBRT and BT) and salvage BT were not included. RESULTS: 406 men were included in the study (65.5% low-risk, 30% intermediate-risk, and 4.5% high-risk patients). After a median follow-up of 87.5 months, 61 (15.0%) patients developed biochemical recurrence. The actuarial biochemical failure-free survival (BFFS) at 5 and 10 years were 90.6% and 82.2%, respectively. A PSA nadir ≥ 1 ng / mL was associated with a higher risk of biochemical failure (HR = 5.81; 95% CI: 3.39 to 9.94; p ≤ 0.001). The actuarial metastasis-free survival (MFS) at 5 and 10 years were 98.3% and 94%, respectively. The actuarial overall survival (OS) at 5 and 10 years were 96.2% and 85.1%, respectively. Acute and late grade 2 and 3 gastrointestinal toxicities were observed in 5.6%, 0.5%, 4.6% and 0.5% of cases, respectively. For genitourinary the observed acute and late grade 2 and 3 toxicities rates were 57.3%, 3.6%, 28% and 3.1%, respectively. No grade 4 and 5 were observed. CONCLUSIONS: BT was effective as a definitive treatment modality for prostate cancer, and its endpoints and toxicities were comparable to those of the main series in the literature.

Low dose rate brachytherapy (LDR-BT) as monotherapy for early stage prostate cancer in Italy: practice and outcome analysis in a series of 2237 patients from 11 institutions.

OBJECTIVE: Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure. METHODS: Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes. RESULTS: Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p < 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT. CONCLUSION: This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer. ADVANCES IN KNOWLEDGE: Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome.

Safety and efficacy of intraoperative iodine-125 seed implantation brachytherapy for rectal cancer patients: A retrospective clinical research.

BACKGROUND: This pilot study was performed to evaluate the risk of anastomotic leakage (AL) and pelvic autonomic nerve dysfunction, and the effects of (125) I brachytherapy after intraoperative permanent implantation of iodine-125 seeds within the patients with rectal carcinoma. METHODS: In a cohort consisting of 80 rectal cancer patients who received potentially curative resection of rectal carcinoma with implantation of (125) I brachytherapy or radical resection of rectal carcinoma underwent total mesorectal excision. The incidences of AL, fecal incontinence, urinary dysfunction, and sexual dysfunction were calculated for comparison, and risk factors for these complications were analyzed by logistic regression. Rates of tumor recurrence and overall survival were evaluated. RESULTS: Six out of 17 (35.29%) patients in the (125) I implant group and 1 out of 34 (2.94%) patients in the non-implant group were complicated with AL (P = 0.006). The incidences of urinary dysfunction (P = 0.005) and fecal incontinence (P = 0.023) were significantly different between the two groups. Multivariate analyses revealed that (125) I brachytherapy was an independent risk factor for AL (odds ratio, 18.702; 95%CI, 1.802-194.062; P = 0.014) and urinary dysfunction (odds ratio, 4.340; 95%CI, 1.158-16.264; P = 0.029), respectively. At postoperative 2-year, the recurrence rates were 5.56% in the (125) I implant group and 9.09% in the non-implant group (P = 0.029). CONCLUSIONS: Intraoperative implantation of (125) I brachytherapy significantly increases the risk of AL, fecal incontinence, urinary dysfunction, and improves local control and do not improve overall survival after total mesorectal excision.

Risk Group and Death From Prostate Cancer: Implications for Active Surveillance in Men With Favorable Intermediate-Risk Prostate Cancer.

IMPORTANCE: Active surveillance (AS), per the National Comprehensive Cancer Network (NCCN) guidelines, is considered for patients with low-risk prostate cancer (PC) and a life expectancy of at least 10 years. However, given the grade migration following the 2005 International Society of Urologic Pathology consensus conference, AS may be appropriate for men presenting with favorable intermediate-risk PC. OBJECTIVE: To estimate and compare the risk of PC-specific mortality (PCSM) and all-cause mortality (ACM) following brachytherapy among men with low and favorable intermediate-risk PC. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 5580 consecutively treated men (median age, 68 years) with localized adenocarcinoma of the prostate treated with brachytherapy at the Prostate Cancer Foundation of Chicago between October 16, 1997, and May 28, 2013. INTERVENTION: Standard of practice per the NCCN guidelines. MAIN OUTCOMES AND MEASURES: Fine and Gray competing risks regression and Cox regression analyses were used to assess whether the risks of PCSM and ACM, respectively, were increased in men with favorable intermediate-risk vs low-risk PC. Analyses were adjusted for age at brachytherapy, year of treatment, and known PC prognostic factors. RESULTS: After median follow-up of 7.69 years, 605 men had died (10.84% of total cohort), 34 of PC (5.62% of total deaths). Men with favorable intermediate-risk PC did not have significantly increased risk of PCSM and ACM compared with men with low-risk PC (adjusted hazard ratio [HR], 1.64; 95% CI, 0.76-3.53; P = .21 for PCSM; adjusted HR, 1.11; 95% CI, 0.88-1.39; P = .38 for ACM). Eight-year adjusted point estimates for PCSM were low: 0.48% (95% CI, 0.23%-0.93%) and 0.33% (95% CI, 0.19%-0.56%) for men with favorable intermediate-risk PC and low-risk PC, respectively. The respective estimates for ACM were 10.45% (95% CI, 8.91%-12.12%) and 8.68% (95% CI, 7.80%-9.61%). CONCLUSIONS AND RELEVANCE: Men with low-risk PC and favorable intermediate-risk PC have similarly low estimates of PCSM and ACM during the first decade following brachytherapy. While awaiting the results of ProtecT, the randomized trial of AS vs treatment, our results provide evidence to support AS as an initial approach for men with favorable intermediate-risk PC.

Is modern external beam radiotherapy with androgen deprivation therapy still a viable alternative for prostate cancer in an era of robotic surgery and brachytherapy: a comparison of Australian series.

INTRODUCTION: We compare the results of modern external-beam radiotherapy (EBRT), using combined androgen deprivation and dose-escalated intensity-modulated radiotherapy with MRI-CT fusion and daily image guidance with fiducial markers (DE-IG-IMRT), with recently published Australian series of brachytherapy and surgery. METHODS: Five-year actuarial biochemical disease-free survival (bDFS), metastasis-free survival (MFS) and prostate cancer-specific survival (PCaSS) were calculated for 675 patients treated with DE-IG-IMRT and androgen deprivation therapy (ADT). Patients had intermediate-risk (IR) and high-risk (HR) disease. A search was conducted identifying Australian reports from 2005 onwards of IR and HR patients treated with surgery or brachytherapy, reporting actuarial outcomes at 3 years or later. RESULTS: With a median follow-up of 59 months, our 5-year bDFS was 93.3% overall: 95.5% for IR and 91.3% for HR disease. MFS was 96.9% overall (99.0% IR, 94.9% HR), and PCaSS was 98.8% overall (100% IR, 97.7% HR). Prevalence of Grade 2 genitourinary and gastrointestinal toxicity at 5 years was 1.3% and 1.6%, with 0.3% Grade 3 genitourinary toxicity and no Grade 3 gastrointestinal toxicity. Eight reports of brachytherapy and surgery were identified. The HDR brachytherapy series' median 5-year bDFS was 82.5%, MFS 90.0% and PCaSS 97.9%. One surgical series reported 5-year bDFS of 65.5% for HR patients. One LDR series reported 5-year bDFS of 85% for IR patients. CONCLUSIONS: Modern EBRT is at least as effective as modern Australian surgical and brachytherapy techniques. All patients considering treatment for localised prostate cancer should be referred to a radiation oncologist to discuss EBRT as an equivalent option.

High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term hormonal therapy for high-risk and very high-risk prostate cancer: outcomes after 5-year follow-up.

The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent (192)Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent ≥ 6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow-up was 61 months (range, 25-94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach.

Laparoscopic radical hysterectomy after preoperative brachytherapy for stage IB1 cervical cancer: feasibility, results, and surgical implications in a large bicentric study of 162 consecutive cases.

PURPOSE: To examine the feasibility and to report the results of laparoscopic radical hysterectomy (LRH) after initial uterovaginal brachytherapy (BT) for stage IB1 cervical cancer. METHODS: We retrospectively reviewed patients at 2 comprehensive cancer centers who underwent initial BT followed 6-8 weeks later by LRH and lymph node dissection. RESULTS: Between 2003 and 2010, a total of 162 patients underwent LRH. The procedure was feasible via this approach in 160 cases (98.8%) (2 conversions to laparotomy). Eight perioperative complications occurred. Nineteen patients had nodal involvement. Peri- or postoperative ureteral morbidity occurred in 10 patients (6%). Twenty-four patients (15%) experienced postoperative dysuria. Histologically, only 9 patients had residual cervical disease ≥5 mm, and only 1 patient had parametrial lymphovascular space involvement (associated with nodal spread). No patient had vaginal disease or involved surgical margins. After a median follow-up of 39 (range 3-118) months, 9 patients experienced relapse. Five-year overall survival was 95% (range 88.2-97.9%). CONCLUSIONS: Radical hysterectomy using a laparoscopic approach is feasible and reproducible after initial BT for stage IB1 cervical cancer and is associated with excellent survival. Morbidity is close to that reported in patients treated with up-front surgery. In this large series, the morbidity associated with parametrial dissection and the fact that parametrial spread was observed in only 0.6% of the patients suggest that a simple extrafascial hysterectomy is perhaps sufficient in this context; the rate of urinary tract morbidity would then be reduced.

Can high-dose-rate brachytherapy prevent the major genitourinary complication better than external beam radiation alone for patients with previous transurethral resection of prostate?

PURPOSE: To compare the grade 3 genitourinary toxicity and oncological outcome for localized prostate cancer between high-dose-rate (HDR) brachytherapy and external beam radiation therapy (EBRT) alone in patients with previously undergone Transurethral resection of the prostate (TURP). MATERIALS AND METHODS: From November 1998 to November 2008, 78 patients with a history of TURP underwent radiation therapy for localized prostate cancer. Of these, 59 were enrolled in this study. In this study, 34 patients underwent HDR brachytherapy and 25 patients underwent EBRT alone. RESULTS: Grade 3 genitourinary complication was observed in 8.8 % of HDR brachytherapy group and 44 % in EBRT alone group. Five-year urinary incontinence rate was 2.9 % in HDR brachytherapy and 24 % in EBRT alone group. The results showed that significant higher incidence of grade 3 genitourinary complication (p = 0.003) and urinary incontinence was the most significant (p = 0.023) in the EBRT alone group. Five-year biochemical survival rate was 82.4 % in HDR brachytherapy group and 72.0 % in EBRT alone group (p = 0.396). CONCLUSIONS: In patients with prostate cancer who have previously undergone TURP, we observed that HDR brachytherapy was able to control prostate cancer with fewer GU morbidities and oncological outcomes that were similar to those associated with traditional EBRT alone. Moreover, HDR brachytherapy led to a decrease in major GU toxicity and also preserved the sphincter function more than that in TURP patients who underwent EBRT alone.

Radioembolization in combination with systemic chemotherapy as first-line therapy for liver metastases from colorectal cancer.

PURPOSE: To report clinical experience with radioembolization (RE) plus systemic chemotherapy as a first-line treatment for liver metastases from colorectal cancer (CRC). MATERIALS AND METHODS: Clinical outcomes were evaluated retrospectively among 19 patients with unresectable liver metastases from CRC who had a good performance status and a low burden of extrahepatic disease (EHD) and were eligible for RE. Most (74%) had disease confined to the liver. Concurrent treatment with 5-fluorourail/leucovorin (n = 7) or 5-fluorourail/leucovorin/oxaliplatin (FOLFOX; n = 12) was started 3-4 days before single treatment with RE. RESULTS: Overall response rate according to the Response Evaluation Criteria in Solid Tumors was 84% (two complete responses and 14 partial responses). Median progression-free survival (PFS) time was 10.4 months and median overall survival (OS) time was 29.4 months. For patients with disease confined to the liver, PFS improved (10.7 mo vs 3.6 mo; P = .09), with significant prolongation of OS (median, 37.8 mo vs 13.4 mo; P = .03) compared with those who had EHD. Nine patients, including three long-term (> 3 y) survivors, remained alive after a median follow-up of 18.6 months. Serious treatment-related toxicities included febrile neutropenia with concurrent FOLFOX treatment, a perforated duodenal ulcer, and one death from hepatic toxicity. CONCLUSIONS: The present findings confirm the effectiveness of RE plus systemic chemotherapy for metastatic CRC. Patients with liver-confined disease derived the greatest benefit, with median survival times beyond 36 months. Larger datasets from ongoing phase III trials are needed to further define the safety and efficacy of RE in the first-line setting.

Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost +/- hyperthermia for glioblastoma multiforme.

PURPOSE: To determine if adjuvant interstitial hyperthermia (HT) significantly improves survival of patients with glioblastoma undergoing brachytherapy boost after conventional radiotherapy. METHODS AND MATERIALS: Adults with newly-diagnosed, focal, supratentorial glioblastoma < or = 5 cm in diameter were registered postoperatively on a Phase II/III randomized trial and treated with partial brain radiotherapy to 59.4 Gy with oral hydroxyurea. Those patients whose tumor was still implantable after teletherapy were randomized to brachytherapy boost (60 Gy at 0.40-0.60 Gy/h) +/- HT for 30 min immediately before and after brachytherapy. Time to progression (TTP) and survival from date of diagnosis were estimated using the Kaplan-Meier method. RESULTS: From 1990 to 1995, 112 eligible patients were entered in the trial. Patient ages ranged from 21-78 years (median, 54 years) and KPS ranged from 70-100 (median, 90). Most commonly due to tumor progression or patient refusal, 33 patients were never randomized. Of the patients, 39 were randomized to brachytherapy ("no heat") and 40 to brachytherapy + HT ("heat"). By intent to treat, TTP and survival were significantly longer for "heat" than "no heat" (p = 0.04 and p = 0.04). For the 33 "no heat" patients and 35 "heat" patients who underwent brachytherapy boost, TTP and survival were significantly longer for "heat" than "no heat" (p = 0.045 and p = 0.02, respectively; median survival 85 weeks vs. 76 weeks; 2-year survival 31% vs. 15%). A multivariate analysis for these 68 patients adjusting for age and KPS showed that improved survival was significantly associated with randomization to "heat" (p = 0.008; hazard ratio 0.51). There were no Grade 5 toxicities, 2 Grade 4 toxicities (1 on each arm), and 7 Grade 3 toxicities (1 on "no heat" and 6 on the "heat" arm). CONCLUSION: Adjuvant interstitial brain HT, given before and after brachytherapy boost, after conventional radiotherapy significantly improves survival of patients with focal glioblastoma, with acceptable toxicity.