Eduardo Weltman

A multi-institutional review of radiosurgery alone vs. radiosurgery with whole brain radiotherapy as the initial management of brain metastases

PURPOSE Data collected from 10 institutions were reviewed to compare survival probabilities of patients with newly diagnosed brain metastases managed initially with radiosurgery (RS) alone vs. RS + whole brain radiotherapy (WBRT). METHODS AND MATERIALS A database was created from raw data submitted from 10 institutions on patients treated with RS for brain metastases. The major exclusion criteria were resection of a brain metastasis and interval from the end of WBRT until RS >1 month (to try to ensure that the up-front intent was to combine RS + WBRT and that RS was not given for recurrent brain metastases). Survival was estimated using the Kaplan-Meier method from the date of first treatment for brain metastases until death or last follow-up. Survival times were compared for patients managed initially with RS alone vs. RS + WBRT using the Cox proportional hazards model to adjust for known prognostic factors or Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class. RESULTS Out of 983 patients, 31 were excluded because treatment began after 6/1/98; 159 were excluded because brain metastases were resected; 179 were excluded because there was an interval >1 month from WBRT until RS; and 45 were excluded for other reasons. Of the 569 evaluable patients, 268 had RS alone initially (24% of whom ultimately had salvage WBRT), and 301 had RS + up-front WBRT. The median survival times for patients treated with RS alone initially vs. RS + WBRT were 14.0 vs. 15.2 months for RPA Class 1 patients, 8.2 vs. 7.0 months for Class 2, and 5.3 vs. 5.5 months for Class 3, respectively. With adjustment by RPA class, there was no survival difference comparing RS alone initially to RS + up-front WBRT (p = 0.33, hazard ratio = 1.09). CONCLUSIONS Omission of up-front WBRT does not seem to compromise length of survival in patients treated with RS for newly diagnosed brain metastases.

RADIOSURGERY FOR PATIENTS WITH BRAIN METASTASES: A MULTI-INSTITUTIONAL ANALYSIS, STRATIFIED BY THE RTOG RECURSIVE PARTITIONING ANALYSIS METHOD

PURPOSE To estimate the potential improvement in survival for patients with brain metastases, stratified by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class and treated with radiosurgery (RS) plus whole brain radiotherapy (WBRT). METHODS AND MATERIALS An analysis of the RS databases of 10 institutions identified patients with brain metastates treated with RS and WBRT. Patients were stratified into 1 of 3 RPA classes. Survival was evaluated using Kaplan-Meier estimates and proportional hazard regression analysis. A comparison of survival by class was carried out with the RTOG results in similar patients receiving WBRT alone. RESULTS Five hundred two patients were eligible (261 men and 241 women, median age 59 years, range 26-83). The overall median survival was 10.7 months. A higher Karnofsky performance status (p = 0.0001), a controlled primary (median survival = 11.6 vs. 8.8 months, p = 0.0023), absence of extracranial metastases (median survival 13.4 vs. 9.1 months, p = 0.0001), and lower RPA class (median survival 16.1 months for class I vs. 10.3 months for class II vs. 8.7 months for class III, p = 0.000007) predicted for improved survival. Gender, age, primary site, radiosurgery technique, and institution were not prognostic. The addition of RS boosted results in median survival (16.1, 10.3, and 8.7 months for classes I, II, and III, respectively) compared with the median survival (7.1, 4.2, and 2.3 months, p <0.05) observed in the RTOG RPA analysis for patients treated with WBRT alone. CONCLUSION In the absence of randomized data, these results suggest that RS may improve survival in patients with BM. The improvement in survival does not appear to be restricted by class for well-selected patients.

RADIOSURGERY FOR BRAIN METASTASES: WHO MAY NOT BENEFIT?

PURPOSE To select a group of patients with brain metastases for whom stereotactic radiosurgery (SRS) may not be beneficial. PATIENTS, MATERIALS, AND METHODS Actuarial survival of 87 patients with brain metastases treated with SRS between July 1993 and May 1999 was retrospectively analyzed under stratification by the Score Index for Stereotactic Radiosurgery for Brain Metastases (SIR). To identify the group of patients most likely to survive less than 6 months after SRS, Cox model survival curves were calculated for all SIR values, and Kaplan-Meier survival curves were calculated for two SIR subsets (0-5 and 6-10) and were compared by log-rank test. RESULTS Overall median survival after SRS was 6.88 months. The stratification of patients into two SIR subsets (0-5 and 6-10) sustained statistical significance regarding survival with p = 0.0001. The median survival time for the group of patients with SIR between 0 and 5 was 4.52 months (95% confidence interval of 2.82 to 5.84 months). Survival probability at 6 months for this group of patients with poor prognosis was 35.6%. CONCLUSION Patients with brain metastases and SIR of 5 or lower have an expected median survival of less than 6 months after treatment with radiosurgery. Thus, radiosurgery may not be beneficial for this group of patients.

Radiosurgical boost for primary high-grade gliomas.

The purpose of this study was to retrospectively evaluate the survival of patients with high-grade gliomas treated with external beam radiotherapy with or without radiosurgical boost. From July 1993 to April 1998, 32 patients were selected, 15 of which received radiosurgery. Inclusion criteria were age >18 years, histological confirmation of high-grade glioma, primary tumor treatment with curative intent, unifocal tumor and supratentorial location. All patients were found to be in classes III–VI, according to the recursive partitioning analysis proposed by the Radiation Therapy Oncology Group. The median interval between radiotherapy and radiosurgery was 5 weeks (range 1–13). Treatment volumes ranged from 2.9 to 70.3 cc (median 15.0 cc). Prescribed radiosurgery doses varied from 8.0 to 12.5 Gy (median 10.0 Gy). Radiosurgery and control groups were well balanced with respect to prognostic factor distributions. Median actuarial survival time in radiosurgery and control groups was 21.4 months and 11.6 months, respectively (p=0.0254). Among patients with KPS≥80, median survival time was 11.0 months and 53.9 months in the control and radiosurgery groups, respectively (p=0.0103). Radiosurgery was the single factor correlated with survival on Cox model analysis (p=0.0362) and was associated with a 2.76 relative reduction in the risk of cancer death (95% confidence interval (CI) 1.07–7.13). Our results suggest that radiosurgery may confer a survival advantage for patients in RPA classes III–VI, especially for those with Karnofsky performance status ≥80. The definitive role of radiosurgical boost for patients with high-grade gliomas awaits the results of randomized trials.

Radiotherapy alone in the treatment of uterine cervix cancer with telecobalt and low-dose-rate brachytherapy: retrospective analysis of results and variables

PURPOSE This retrospective analysis aims to report results and variables from patients with cervix cancer treated by radiation therapy alone with telecobalt and low-dose-rate brachytherapy (LDRB). METHODS AND MATERIALS Between September 1989 and September 1995, 190 patients with histologic diagnosis of cervix carcinoma were treated with telecobalt for external beam radiotherapy (EBR), followed by one or two insertions of LDRB. Stage distribution according to patients was the following: IB, 12; IIA, 4; IIB, 105; and IIIB, 69. Median dose of EBR at whole pelvis was 40 Gy, and median parametrial doses for Stages II and III patients were 50 Gy and 60 Gy, respectively. Median doses of LDRB at point A for patients treated with one and two insertions were 38 Gy and 50 Gy, respectively. RESULTS Median follow-up time was 70 months (range: 8-127 months). Overall survival, disease-free survival, and 5-year local control of patients at Stages I, II, and III were 83%, 78%, and 46%; 83%, 82%, and 49%; and 92%, 87%, and 58%, respectively. Overall incidence of late complications in the rectum, small bowel, and urinary tract was 15.3% (19/190), 4.2% (8/190), and 6.8% (13/190), respectively. The actuarial 5-year rectal, small bowel, and urinary incidence of late complications was 16.1%, 4.6%, and 7.6%, respectively. Clinical stage was the only significant variable for overall 5-year survival (p = 0.001), for disease-free survival (p = 0.001), and for local control (p = 0.001). Stage II patients more than 50 years old had better disease-free survival and local control at 5 years (p = 0.004). None of the analyzed variables influenced the actuarial 5-year incidence of late complications. CONCLUSIONS Results of this series suggest that the use of telecobalt equipment for EBR with doses up to 50 Gy at whole pelvis, prior to brachytherapy, is an acceptable technique for radiation therapy alone in the treatment of cervix cancer, especially in developing countries, including Brazil, where telecobalt machines still prevail.

Minimizing the uncertainties regarding the effects of delaying radiotherapy for Glioblastoma: A systematic review and meta-analysis

BACKGROUND AND PURPOSE Previous studies have provided no clear conclusions regarding the effects of delaying radiotherapy (RT) in GBM patients. We present a systematic review and meta-analysis to address the effect of delayed RT on the overall survival (OS) of GBM patients. METHODS A systematic search retrieved 19 retrospective studies published between 1975 and 2014 reporting on the waiting time (WT) to RT for GBM patients. The meta-analysis was performed by converting WT to RT studies intervals into a regression coefficient (β) and standard error expressing the effect size on OS per week of delay. RESULTS Data required to calculate the effect size on OS per week of delay were available for 12 studies (5212 patients). A non-adjusted model and a meta-regression model based on well-recognized prognostic factors were performed. No association between WT to RT, per week of delay, and OS was found (HR=0.98; 95% CI 0.90-1.08; p=0.70). The meta-regression adjusted for prognostic factors weighted by the inverse-variance (1/SE(2)) showed no clear evidence of the effect of WT to RT, per week of delay, on OS. CONCLUSIONS This meta-analysis, despite limitations, provided no evidence of a true effect on OS by delaying RT in GBM patients.

Intensity modulated radiotherapy for localized prostate cancer: rigid compliance to dose-volume constraints as a warranty of acceptable toxicity?

BackgroundTo report the toxicity after intensity modulated radiotherapy (IMRT) for patients with localized prostate cancer, as a sole treatment or after radical prostatectomy.MethodsBetween August 2001 and December 2003, 132 patients with prostate cancer were treated with IMRT and 125 were evaluable to acute and late toxicity analysis, after a minimum follow-up time of one year. Clinical and treatment data, including normal tissue dose-volume histogram (DVH) constraints, were reviewed. Gastro-intestinal (GI) and genito-urinary (GU) signs and symptoms were evaluated according to the Radiation Therapy Oncology Group (RTOG) toxicity scales. Median prescribed dose was 76 Gy. Median follow-up time was of 26.1 months.ResultsFrom the 125 patients, 73 (58.4%) presented acute Grade 1 or Grade 2 GI and 97 (77.2%) presented acute Grade 1 or Grade 2 GU toxicity. Grade 3 GI acute toxicity occurred in only 2 patients (1.6%) and Grade 3 GU acute toxicity in only 3 patients (2.4%). Regarding Grade 1 and 2 late toxicity, 26 patients (20.8%) and 21 patients (16.8%) presented GI and GU toxicity, respectively. Grade 2 GI late toxicity occurred in 6 patients (4.8%) and Grade 2 GU late toxicity in 4 patients (3.2%). None patient presented any Grade 3 or higher late toxicity. Non-conformity to DVH constraints occurred in only 11.2% of treatment plans. On univariate analysis, no significant risk factor was identified for Grade 2 GI late toxicity, but mean dose delivered to the PTV was associated to higher Grade 2 GU late toxicity (p = 0.042).ConclusionIMRT is a well tolerable technique for routine treatment of localized prostate cancer, with short and medium-term acceptable toxicity profiles. According to the data presented here, rigid compliance to DHV constraints might prevent higher incidences of normal tissue complication.

Comparison of conformal and intensity modulated radiation therapy techniques for treatment of pelvic tumors. Analysis of acute toxicity

BackgroundThis retrospective analysis reports on the comparative outcome of acute gastrointestinal (GI) and genitourinary (GU) toxicities between conformal radiation therapy (CRT) and intensity modulated radiation therapy (IMRT) techniques in the treatment of patients with pelvic tumors.MethodsFrom January 2002 to December 2008, 69 patients with pelvic tumors underwent whole pelvic CRT and 65 underwent whole pelvic IMRT to treat pelvic lymph nodes and primary tumor regions. Total dose to the whole pelvis ranged from 50 to 50.4 Gy in 25 to 28 daily fractions. Chemotherapy (CT) regimen, when employed, was based upon primary tumor. Acute GI and GU toxicities were graded by RTOG/EORTC acute radiation morbidity criteria.ResultsAbsence of GI symptoms during radiotherapy (grade 0) was more frequently observed in the IMRT group (43.1% versus 8.7; p < 0.001) and medication for diarrhea (Grade 2) was more frequently used in the CRT group (65.2% versus 38.5%; p = 0.002). Acute GI grade 1 and 3 side effects incidence was similar in both groups (18.5% versus 18.8%; p = 0.95 and 0% versus 7.2%; p = 0.058, respectively). Incidence of GU toxicity was similar in both groups (grade 0: 61.5% versus 66.6%, p = 0.54; grade 1: 20% versus 8.7%, p = 0.06; grade 2: 18.5% versus 23.5%, p = 0.50 and grade 3: 0% versus 1.5%, p > 0.99).ConclusionsThis comparative case series shows less grade 2 acute GI toxicity in patients treated with whole pelvic IMRT in comparison with those treated with CRT. Incidence of acute GU toxicity was similar in both groups.

Glioblastoma: approach to treat elderly patients

Treating elderly cancer patients is a challenge for oncologists, especially considering the several therapeutic modalities in glioblastoma. Extensive tumor resection offers the best chance of local control. Adequate radiotherapy should always be given to elderly patients if they have undergone gross total resection and have maintained a good performance status. Rather than being ruled out, chemotherapy should be considered, and temozolomide is the chosen drug. A comprehensive geriatric assessment is a valuable tool to help guiding treatment decisions in elderly patients with glioblastoma.

Waiting time to radiotherapy as a prognostic factor for glioblastoma patients in a scenario of medical disparities

OBJECTIVE To evaluate the effect of waiting time (WT) to radiotherapy (RT) on overall survival (OS) of glioblastoma (GBM) patients as a reliable prognostic variable in Brazil, a scenario of medical disparities. METHOD Retrospective study of 115 GBM patients from two different health-care institutions (one public and one private) in Brazil who underwent post-operative RT. RESULTS Median WT to RT was 6 weeks (range, 1.3-17.6). The median OS for WT ≤ 6 weeks was 13.5 months (95%CI , 9.1-17.9) and for WT > 6 weeks was 14.2 months (95%CI, 11.2-17.2) (HR 1.165, 95%CI 0.770-1.762; p = 0.470). In the multivariate analysis, the variables associated with survival were KPS (p < 0.001), extent of resection (p = 0.009) and the adjuvant treatment (p = 0.001). The KPS interacted with WT to RT (HR 0.128, 95%CI 0.034-0.476; p = 0.002), showing that the benefit of KPS on OS depends on the WT to RT. CONCLUSION No prognostic impact of WT to RT could be detected on the OS. Although there are no data to ensure that delays to RT are tolerable, we may reassure patients that the time-length to initiate treatment does not seem to influence the control of the disease, particularly in face of other prognostic factors.