Preventive Effect of Hippocampal Sparing on Cognitive Dysfunction of Patients Undergoing Whole-Brain Radiotherapy and Imaging Assessment of Hippocampal Volume Changes.

Objective: Preventive effect of hippocampal sparing on cognitive dysfunction of patients undergoing whole-brain radiotherapy and imaging assessment of hippocampal volume changes. Methods: Forty patients with brain metastases who attended Liaoning Cancer Hospital from January 2018 to December 2019 were identified as research subjects and were randomly divided into a control group and an experimental group, with 20 cases in each group. The control group was treated with whole-brain radiotherapy (WBRT), and the experimental group was treated with hippocampal sparing-WBRT (HS-WBRT). The Montreal Cognitive Assessment (MoCA) score, Eastern Cooperative Oncology Group (ECOG) score, cancer quality-of-life questionnaire (QLQ-C3O) score, hippocampal volume changes, and prognosis of the two groups were compared. Results: The MoCA scores decreased in both groups at 3, 6, and 12 months after radiotherapy, with significantly higher scores in the experimental group than in the control group (P < 0.05). After radiotherapy, both groups had lower ECOG scores, with those in the experimental group being significantly lower than those in the control group (P < 0.05). After radiotherapy, the QLQ-C30 score was elevated in both groups, and that of the experimental group was significantly higher than that of the control group (P < 0.05). The experimental group outperformed the control group in terms of the prognosis (P < 0.05). The hippocampal volume of the control group was significantly smaller than that of the experimental group (P < 0.05). Conclusion: The application of hippocampal sparing in patients receiving whole-brain radiotherapy is effective in preventing cognitive dysfunction, improving the quality of life and prognosis of patients, and avoiding shrinkage of hippocampal volume.

Whole-brain radiotherapy plus sequential or simultaneous integrated boost for the treatment of a limited number of brain metastases in non-small cell lung cancer: A single-institution study.

BACKGROUND: To compare the survival outcomes and neurocognitive dysfunction in non-small cell lung cancer (NSCLC) patients with brain metastases (BM ≤10) treated by whole-brain radiotherapy (WBRT) with sequential integrated boost (SEB) or simultaneous integrated boost (SIB). MATERIALS: Fifty-two NSCLC patients with a limited number of BMs were retrospectively analyzed. Twenty cases received WBRT+SEB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*3 fractions; SEB group), and 32 cases received WBRT+SIB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*10 fractions; SIB group). The survival and mini-mental state examination (MMSE) scores were compared between the groups. RESULTS: The cumulative 1-, 2-, and 3-year survival rates in the SEB vs SIB groups were 60.0% vs 47.8%, 41.1% vs 19.1%, and 27.4% vs 0%, respectively. The median survival times in the SEB and SIB groups were 15 and 10 months, respectively. The difference in survival rate was significant (P = .046). Subgroup analysis revealed that 1-, 2-, and 3-year survival rates and median survival time in the SEB group were significantly superior to those of the SIB group, especially for male patients (age <60 years) with 1-2 BMs (P < .05). The MMSE score of the SEB group at 3 months after radiation was higher than that of the SIB group (P < .05). Nevertheless, WBRT+SEB required a longer treatment time and greater cost (P < .005). CONCLUSIONS: WBRT + SEB results in better survival outcomes than WBRT+SIB, especially for male patients (age <60 years) with 1-2 BMs. WBRT+SEB also appeared to induce less neurocognitive impairment than WBRT+SIB.

Longitudinal cognitive assessment in patients with primary CNS lymphoma treated with induction chemotherapy followed by reduced-dose whole-brain radiotherapy or autologous stem cell transplantation.

INTRODUCTION: The standard treatment for primary central nervous system lymphoma (PCNSL) involves induction methotrexate-based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). As WBRT carries a substantial risk for cognitive impairment, alternative consolidation treatments have been used to reduce neurotoxicity, including reduced-dose WBRT (rdWBRT) or high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT). In this study, we characterized cognitive functions in PCNSL patients achieving long-term remission following rdWBRT or HDC-ASCT. METHODS: PCNSL patients completed cognitive evaluations at diagnosis, post-induction chemotherapy, and yearly up to 5 years following rdWBRT or HDC-ASCT. Quality of life (QoL), white matter (WM) disease, and cortical atrophy (CA) on MRI were assessed at similar intervals. RESULTS: Performance was impaired on most cognitive tests at diagnosis. Linear mixed model analyses in each group showed statistically significant improvement from baseline up to year 3 in attention/executive functions, graphomotor speed, and memory; however, there was a decline in attention/executive functions and memory after year 3 in both groups. WM abnormalities increased over time in both groups, but more patients treated with rdWBRT developed CA and WM changes. There were no significant longitudinal group differences in cognitive performance or QoL. CONCLUSIONS: Results indicated improvement in cognitive function up to 3 years post-treatment, but a decline at later time points and an increase in brain structure abnormalities in both groups. The findings suggest that rdWBRT and HDC-ASCT may be associated with delayed neurotoxicity in progression-free patients and underscore the need for long-term follow-up to characterize cognitive dysfunction in PCNSL patients.

Prospective Assessment of Patient-Reported Dry Eye Syndrome After Whole Brain Radiation.

PURPOSE: Dry eye is not typically considered a toxicity of whole brain radiation therapy (WBRT). We analyzed dry eye syndrome as part of a prospective study of patient-reported outcomes after WBRT. METHODS AND MATERIALS: Patients receiving WBRT to 25 to 40 Gy were enrolled on a study with dry mouth as the primary endpoint and dry eye syndrome as a secondary endpoint. Patients received 3-dimensional WBRT using opposed lateral fields. Per standard practice, lacrimal glands were not prospectively delineated. Patients completed the Subjective Evaluation of Symptom of Dryness (SESoD, scored 0-4, with higher scores representing worse dry eye symptoms) at baseline, immediately after WBRT (EndRT), and at 1 month (1M), 3 months, and 6 months. Patients with baseline SESoD ≥3 (moderate dry eye) were excluded. The endpoints analyzed were ≥1-point and ≥2-point increase in SESoD score at 1M. Lacrimal glands were retrospectively delineated with fused magnetic resonance imaging scans. RESULTS: One hundred patients were enrolled, 70 were eligible for analysis, and 54 were evaluable at 1M. Median bilateral lacrimal V20Gy was 79%. At 1M, 17 patients (32%) had a ≥1-point increase in SESoD score, and 13 (24%) a ≥2-point increase. Lacrimal doses appeared to be associated with an increase in SESoD score of both ≥1 point (V10Gy: P = .042, odds ratio [OR] 1.09/%; V20Gy: P = .071, OR 1.03/%) and ≥2 points (V10Gy: P = .038, OR 1.15/%; V20Gy: P = .063, OR 1.04/%). The proportion with increase in dry eye symptoms at 1M for lacrimal V20Gy ≥79% versus <79% was 46% versus 15%, respectively, for ≥1 point SESoD increase (P = .02) and 36% versus 12%, respectively, for ≥2 point SESoD increase (P = .056). CONCLUSIONS: Dry eye appears to be a relatively common, dose/volume-dependent acute toxicity of WBRT. Minimization of lacrimal gland dose may reduce this toxicity, and patients should be counseled regarding the existence of this potential side effect and treatments for dry eye.

Stereotactic radiosurgery (SRS) alone versus whole brain radiotherapy plus SRS in patients with 1 to 4 brain metastases from non-small cell lung cancer stratified by the graded prognostic assessment: A meta-analysis (PRISMA) of randomized control trials.

BACKGROUND: The present study aims to assess the therapeutic effect of whole brain radiotherapy (WBRT) for brain metastases from non-small cell lung cancer stratified by graded prognostic assessment (GPA) through meta-analysis. METHODS: The Cochrane Library, PubMed, Ovid (Elsevier) were retrieved. The included randomized controlled trials (RCT) were evaluated, and the statistical analysis was performed using RevMan 5.3 software. Cochrane handbook was applied to evaluate the methodological quality. Statistical significance was considered as P < .05. RESULTS: There were 2 randomized control trials identified eligible for the meta-analysis. Stereotactic radiosurgery (SRS)+WBRT did not significantly improved overall survival (OS) in 2 subgroups. (GPA <2: HR, 0.93; 95% confidence interval [CI], 0.61-1.40; P = .71), (GPA ≥2: HR, 1.28; 95% CI, 0.58-2.80; P = .54). The use of SRS+WBRT significantly extended brain tumor recurrence (BTR) free time in both subgroups (GPA <2: HR, 5.46; 95% CI: 2.09-14.22; P = .0005), (GPA ≥2: HR, 4.24; 95% CI: 2.24-8.04; P < .00001). The meta-analysis showed salvage therapy was more frequent among the SRS-alone in 2 subgroups (GPA <2: RR, 5.83; 95% CI: 1.47-23.06; P = .01), (GPA ≥2: RR, 2.53; 95% CI: 1.30-4.93; P = .006). The rate of grade 3 or 4 late radiation toxic effects was similar in 2 subgroups between SRS and SRS+WBRT CONCLUSIONS:: Because there are few studies to meet inclusion criteria, we cannot include more researches. The results of this analysis must be carefully interpreted in view of the unclear risk of bias in inclusion in the study. This meta-analysis of 2 randomized trails indicated that the combined treatment group did not show a survival benefit over SRS alone. However, SRS+WBRT improved BTR free time in the subgroup both GPA <2 and GPA ≥2 with the similar grade 3 or 4 late radiation toxicities.

Cost-effectiveness Analysis of Stereotactic Radiosurgery Alone Versus Stereotactic Radiosurgery with Upfront Whole Brain Radiation Therapy for Brain Metastases.

AIMS: Stereotactic radiosurgery (SRS) alone or upfront whole brain radiation therapy (WBRT) plus SRS are the most commonly used treatment options for one to three brain oligometastases. The most recent randomised clinical trial result comparing SRS alone with upfront WBRT plus SRS (NCCTG N0574) has favoured SRS alone for neurocognitive function, whereas treatment options remain controversial in terms of cognitive decline and local control. The aim of this study was to conduct a cost-effectiveness analysis of these two competing treatments. MATERIALS AND METHODS: A Markov model was constructed for patients treated with SRS alone or SRS plus upfront WBRT based on largely randomised clinical trials. Costs were based on 2016 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER) and effectiveness was measured in quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were carried out. Strategies were evaluated from the healthcare payer's perspective with a willingness-to-pay threshold of $100 000 per QALY gained. RESULTS: In the base case analysis, the median survival was 9 months for both arms. SRS alone resulted in an ICER of $9917 per QALY gained. In one-way sensitivity analyses, results were most sensitive to variation in cognitive decline rates for both groups and median survival rates, but the SRS alone remained cost-effective for most parameter ranges. CONCLUSIONS: Based on the current available evidence, SRS alone was found to be cost-effective for patients with one to three brain metastases compared with upfront WBRT plus SRS.

Cost-effectiveness of stereotactic radiosurgery versus whole-brain radiation therapy for up to 10 brain metastases.

OBJECTIVE The JLGK0901 study found that stereotactic radiosurgery (SRS) is a safe and effective treatment option for treating up to 10 brain metastases. The purpose of this study is to determine the cost-effectiveness of treating up to 10 brain metastases with SRS, whole-brain radiation therapy (WBRT), or SRS and immediate WBRT (SRS+WBRT). METHODS A Markov model was developed to evaluate the cost effectiveness of SRS, WBRT, and SRS+WBRT in patients with 1 or 2-10 brain metastases. Transition probabilities were derived from the JLGK0901 study and modified according to the recurrence rates observed in the Radiation Therapy Oncology Group (RTOG) 9508 and European Organization for Research and Treatment of Cancer (EORTC) 22952-26001 studies to simulate the outcomes for patients who receive WBRT. Costs are based on 2015 Medicare reimbursements. Health state utilities were prospectively collected using the Standard Gamble method. End points included cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The willingness-to-pay (WTP) threshold was $100,000 per QALY. One-way and probabilistic sensitivity analyses explored uncertainty with regard to the model assumptions. RESULTS In patients with 1 brain metastasis, the ICERs for SRS versus WBRT, SRS versus SRS+WBRT, and SRS+WBRT versus WBRT were $117,418, $51,348, and $746,997 per QALY gained, respectively. In patients with 2-10 brain metastases, the ICERs were $123,256, $58,903, and $821,042 per QALY gained, respectively. On the sensitivity analyses, the model was sensitive to the cost of SRS and the utilities associated with stable post-SRS and post-WBRT states. In patients with 2-10 brain metastases, SRS versus WBRT becomes cost-effective if the cost of SRS is reduced by $3512. SRS versus WBRT was also cost effective at a WTP of $200,000 per QALY on the probabilistic sensitivity analysis. CONCLUSIONS The most cost-effective strategy for patients with up to 10 brain metastases is SRS alone relative to SRS+WBRT. SRS alone may also be cost-effective relative to WBRT alone, but this depends on WTP, the cost of SRS, and patient preferences.

Impact of image guidance during whole-brain radiation therapy.

PURPOSE: Radiation oncologists are rapidly adopting image-guided radiation therapy (IGRT), warranting further evaluation of its role and value. We analyzed the impact of IGRT for one of the most common radiation treatments. METHODS AND MATERIALS: We retrospectively identified patients who received whole-brain radiation therapy (WBRT) with mask immobilization and who underwent routine IGRT with kilovoltage imaging. We calculated IGRT shifts by comparing couch positions before and after imaging. We determined the dosimetric impact of IGRT on lens maximum and dose received by 95% (D95%) of the brain and cribriform region. We calculated episode of care costs using the Medicare Physician Fee Schedule. RESULTS: A total of 206 patients received 2392 image-guided fractions. The median absolute shift was 1 mm, 1 mm, and 2 mm in the vertical, lateral, and longitudinal directions, respectively. Ninety-nine percent of shifts were ≤6 mm, 7 mm, and 9 mm in the vertical, lateral, and longitudinal directions, respectively. For the 22 patients with the largest average shift per fraction, treating without IGRT would have changed D95% brain by a median 3 cGy (interquartile range, 2-9) and D95% cribriform region by a median 39 cGy (interquartile range, 7-116). Without IGRT, lens doses would have increased for 11/22 patients and decreased for 11/22. Using a 700 cGy lens threshold, there was no net change in the proportion of patients above and below the threshold regardless of IGRT use. For a 10-fraction course, daily IGRT accounted for 10% of the total episode of care cost. CONCLUSIONS: IGRT results in small positional corrections during WBRT. Even among cases with the largest shifts, the dosimetric impact is minor for the brain and modest for the cribriform region and lenses. This study suggests mask immobilization alone is sufficient for routine cases, and it may help clinicians make evidence-based decisions about IGRT in this setting.

Photon spectrum and absorbed dose in brain tumor.

Using Monte Carlo methods a BOMAB phantom inside a treatment hall with a brain tumor nearby the pituitary gland was treated with photons produced by a Varian 6MV linac. The photon spectrum and the absorbed dose were calculated in the tumor, pituitary gland and the head. The treatment beam was collimated to illuminate only the tumor volume; however photons were noticed in the gland. Photon fluence reaching the tumor is and 15.7 times larger than the fluence in the pituitary gland, on the other hand the absorbed dose in the tumor is 37.1 times larger than the dose in the gland because photons that reach the pituitary gland are scattered, by the head and the tumor, through Compton effect.

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury.

BACKGROUND: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. METHODS AND MATERIALS: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. RESULTS: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). CONCLUSIONS: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

Play-based procedural preparation and support intervention for cranial radiation.

PURPOSE: The primary objective of this study was to examine the relationship between play-based procedural preparation and support intervention and use of sedation in children with central nervous system (CNS) tumors during radiation therapy. The secondary objective was to analyze the cost-effectiveness of the intervention compared to costs associated with daily sedation. METHODS: A retrospective chart review was conducted, and 116 children aged 5-12 years met criteria for inclusion. Outcome measures included the total number of radiation treatments received, the number of treatments received with and without sedation, and the type and duration of interventions, which consisted of developmentally appropriate play, education, preparation, and distraction provided by a certified child life specialist. RESULTS: The results of univariate analyses showed that age, tumor location, and total number and duration of interventions were significantly associated with sedation use during radiation therapy. Multivariate analyses showed that, after adjustment for age, tumor location, and craniospinal radiation, a significant relationship was found between the total number and duration of the interventions and sedation use. The implementation of a play-based procedural preparation and support intervention provided by a certified child life specialist significantly reduced health-care costs by decreasing the necessity of daily sedation. CONCLUSIONS: Support interventions provided by child life specialists significantly decreased both sedation use and the cost associated with daily sedation during cranial radiation therapy in children with CNS tumors. This study supports the value of the child life professional as a play-based developmental specialist and a crucial component of cost-effective healthcare.

Secondary analysis of RTOG 9508, a phase 3 randomized trial of whole-brain radiation therapy versus WBRT plus stereotactic radiosurgery in patients with 1-3 brain metastases; poststratified by the graded prognostic assessment (GPA).

PURPOSE: Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. METHODS AND MATERIALS: In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool (brainmetgpa.com) simplified GPA use. RESULTS: The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. CONCLUSIONS: This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted.

Decision analysis of stereotactic radiation surgery versus stereotactic radiation surgery and whole-brain radiation therapy for 1 to 3 brain metastases.

PURPOSE: Although whole-brain radiation therapy (WBRT) is effective for controlling intracranial disease, it is also associated with neurocognitive side effects. It is unclear whether a theoretically improved quality of life after stereotactic radiation surgery (SRS) alone relative to that after SRS with adjuvant WBRT would justify the omission of WBRT, given the higher risk of intracranial failure. This study compares SRS alone with SRS and WBRT, to evaluate the theoretical benefits of intracranial tumor control with adjuvant WBRT against its possible side effects, using quality-adjusted life expectancy (QALE) as a primary endpoint. METHODS AND MATERIALS: A Markov decision analysis model was used to compare QALE in a cohort of patients with 1 to 3 brain metastases and Karnofsky performance status of at least 70. Patients were treated with SRS alone or with SRS immediately followed by WBRT. Patients treated with SRS alone underwent surveillance magnetic resonance imaging and received salvage WBRT if they developed intracranial relapse. All patients whose cancer relapsed after WBRT underwent simulation as dying of intracranial progression. Model parameters were estimated from published literature. RESULTS: Treatment with SRS yielded 6.2 quality-adjusted life months (QALMs). The addition of initial WBRT reduced QALE by 1.2 QALMs. On one-way sensitivity analysis, the model was sensitive only to a single parameter, the utility associated with the state of no evidence of disease after SRS alone. At values greater than 0.51, SRS alone was preferred. CONCLUSIONS: In general, SRS alone is suggested to have improved quality of life in patients with 1 to 3 brain metastases compared to SRS and immediate WBRT. Our results suggest that immediate treatment with WBRT after SRS can be reserved for patients who would have a poor performance status regardless of treatment. These findings are stable under a wide range of assumptions.

Neurocognitive assessment following whole brain radiation therapy and radiosurgery for patients with cerebral metastases.

The treatment of metastatic brain lesions remains a central challenge in oncology. Because most chemotherapeutic agents do not effectively cross the blood-brain barrier, it is widely accepted that radiation remains the primary modality of treatment. The mode by which radiation should be delivered has, however, become a source of intense controversy in recent years. The controversy involves whether patients with a limited number of brain metastases should undergo whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) delivered only to the radiographically visible tumours. Survival is comparable for patients treated with either modality. Instead, the controversy involves the neurocognitive function (NCF) of radiating cerebrum that appeared radiographically normal relative to effects of the growth from micro-metastatic foci. A fundamental question in this debate involves quantifying the effect of WBRT in patients with cerebral metastasis. To disentangle the effects of WBRT on neurocognition from the effects inherent to the underlying disease, we analysed the results from randomised controlled studies of prophylactic cranial irradiation in oncology patients as well as studies where patients with limited cerebral metastasis were randomised to SRS versus SRS+WBRT. In aggregate, these results suggest deleterious effects of WBRT in select neurocognitive domains. However, there are insufficient data to resolve the controversy of upfront WBRT versus SRS in the management of patients with limited cerebral metastases.

Radiosurgery for brain metastases.

We discuss the current literature on the role of stereotactic radiosurgery in the multidisciplinary management of brain metastases and focus on the level of evidence that addresses key management questions. We reviewed the literature on the different roles of radiosurgery, radiotherapy, and resection, and in particular the 2009 Guidelines project of the Joint Section on Tumors of the AANS/CNS. Retrospective case series, matched cohort studies, and randomized trials show specific survival and local tumor control benefits after radiosurgery. Radiosurgery is an effective and safe minimally invasive option for patients with brain metastases. Randomized trials include tumors of different histologies which can detract from their relevance to specific tumor types.

Dose escalation beyond 30 grays in 10 fractions for patients with multiple brain metastases.

BACKGROUND: Whole-brain radiotherapy (WBRT) to 30 grays (Gy) in 10 fractions is the standard treatment in patients with multiple brain metastases in the majority of treatment centers worldwide. The current study investigated the potential benefit of dose escalation beyond 30 Gy. METHODS: Data regarding 416 patients who were treated with WBRT for multiple brain metastases were evaluated retrospectively. Survival and freedom from recurrent brain metastasis (local control) of 257 patients who were treated with 10 fractions of 3 Gy each for 2 weeks were compared with those of 159 patients treated with 45 Gy in 15 fractions for 3 weeks or 40 Gy in 20 fractions for 4 weeks. Eight additional potential prognostic factors were investigated including age, gender, Karnofsky performance score (KPS), tumor type, interval between tumor diagnosis and RT, number of metastases, extracranial metastases, and Recursive Partitioning Analysis (RPA) class. RESULTS: On multivariate analysis, improved survival was found to be associated with lower RPA class (P < .001), age <60 years (P = .026), KPS >or=70 (P < .001), and absence of extracranial metastases (P = .003). A trend was observed for number of metastases (2-3 vs >or=4; P = .07). Improved local control was associated with a KPS >or=70 (P < .001) and breast cancer (P < .001). A trend was observed for number of metastases (P = .059). The RT schedule did not appear to have any significant impact on survival (P = .86) or local control (P = .61). The subgroup analyses, performed for each of the 3 RPA classes, did not demonstrate a significantly better outcome with dose escalation. CONCLUSIONS: Dose escalation beyond 30 Gy in 10 fractions does not appear to improve survival or local control in patients with multiple brain metastases but does increase the treatment time and cost of therapy.

Improved dose targeting for a clinical epithermal neutron capture beam using optional (6)Li filtration.

PURPOSE: The aim of this study was to construct a (6)Li filter and to improve penetration of thermal neutrons produced by the fission converter-based epithermal neutron beam (FCB) for brain irradiation during boron neutron capture therapy (BNCT). METHODS AND MATERIALS: Design of the (6)Li filter was evaluated using Monte Carlo simulations of the existing beam line and radiation transport through an ellipsoidal water phantom. Changes in beam performance were determined using three figures of merit: (1) advantage depth (AD), the depth at which the total biologically weighted dose to tumor equals the maximum weighted dose to normal tissue; (2) advantage ratio (AR), the ratio of the integral tumor dose to that of normal tissue averaged from the surface to the AD; and (3) advantage depth dose rate (ADDR), the therapeutic dose rate at the AD. Dosimetry performed with the new filter installed provided calibration data for treatment planning. Past treatment plans were recalculated to illustrate the clinical potential of the filter. RESULTS: The 8-mm-thick Li filter is more effective for smaller field sizes, increasing the AD from 9.3 to 9.9 cm, leaving the AR unchanged at 5.7 but decreasing the ADDR from 114 to 55 cGy min(-1) for the 12 cm diameter aperture. Using the filter increases the minimum deliverable dose to deep seated tumors by up to 9% for the same maximum dose to normal tissue. CONCLUSIONS: Optional (6)Li filtration provides an incremental improvement in clinical beam performance of the FCB that could help to establish a therapeutic window in the future treatment of deep-seated tumors.

Radiotherapy in pediatric medulloblastoma: quality assessment of Pediatric Oncology Group Trial 9031.

PURPOSE: To evaluate the potential influence of radiotherapy quality on survival in high-risk pediatric medulloblastoma patients. METHODS AND MATERIALS: Trial 9031 of the Pediatric Oncology Group (POG) aimed to study the relative benefit of cisplatin and etoposide randomization of high-risk patients with medulloblastoma to preradiotherapy vs. postradiotherapy treatment. Two-hundred and ten patients were treated according to protocol guidelines and were eligible for the present analysis. Treatment volume (whole brain, spine, posterior fossa, and primary tumor bed) and dose prescription deviations were assessed for each patient. An analysis of first site of failure was undertaken. Event-free and overall survival rates were calculated. A log-rank test was used to determine the significance of potential survival differences between patients with and without major deviations in the radiotherapy procedure. RESULTS: Of 160 patients who were fully evaluable for all treatment quality parameters, 91 (57%) had 1 or more major deviations in their treatment schedule. Major deviations by treatment site were brain (26%), spinal (7%), posterior fossa (40%), and primary tumor bed (17%). Major treatment volume or total dose deviations did not significantly influence overall and event-free survival. CONCLUSIONS: Despite major treatment deviations in more than half of fully evaluable patients, underdosage or treatment volume misses were not associated with a worse event-free or overall survival.