Prospective Randomized Phase 2 Trial of Hypofractionated Stereotactic Radiation Therapy of 25 Gy in 5 Fractions Compared With 35 Gy in 5 Fractions in the Reirradiation of Recurrent Glioblastoma.

PURPOSE: The aim of this work was to investigate whether reirradiation of recurrent glioblastoma with hypofractionated stereotactic radiation therapy (HSRT) consisting of 35 Gy in 5 fractions (35 Gy/5 fx) compared with 25 Gy in 5 fractions (25 Gy/5 fx) improves outcomes while maintaining acceptable toxicity. METHODS AND MATERIALS: We conducted a prospective randomized phase 2 trial involving patients with recurrent glioblastoma (per the 2007 and 2016 World Health Organization classification). A minimum interval from first radiation therapy of 5 months and gross tumor volume of 150 cc were required. Patients were randomized 1:1 to receive HSRT alone in 25 Gy/5 fx or 35 Gy/5 fx. The primary endpoint was progression-free survival (PFS). We used a randomized phase 2 screening design with a 2-sided α of 0.15 for the primary endpoint. RESULTS: From 2011 to 2019, 40 patients were randomized and received HSRT, with 20 patients in each group. The median age was 50 years (range, 27-71); a new resection before HSRT was performed in 75% of patients. The median PFS was 4.9 months in the 25 Gy/5 fx group and 5.2 months in the 35 Gy/5 fx group (P = .23). Six-month PFS was similar at 40% (85% CI, 24%-55%) for both groups. The median overall survival (OS) was 9.2 months in the 25 Gy/5 fx group and 10 months in the 35 Gy/5 fx group (P = .201). Grade ≥3 necrosis was numerically higher in the 35 Gy/5 fx group (3 [16%] vs 1 [5%]), but the difference was not statistically significant (P = .267). In an exploratory analysis, median OS of patients who developed treatment-related necrosis was 14.1 months, and that of patients who did not was 8.7 months (P = .003). CONCLUSIONS: HSRT alone with 35 Gy/5 fx was not superior to 25 Gy/5 fx in terms of PFS or OS. Due to a potential increase in the rate of clinically meaningful treatment-related necrosis, we suggest 25 Gy/5 fx as the standard dose in HSRT alone. During follow-up, attention should be given to differentiating tumor progression from potentially manageable complications.

Fractionated Stereotactic Radiotherapy Compared to Stereotactic Radiosurgery for Vestibular Schwannoma in Patients with Type 2 Neurofibromatosis.

BACKGROUND: The use of radiotherapy (RT) for the treatment of vestibulocochlear schwannomas is standard in patients with type 2 neurofibromatosis (NF2). In the general population, fractionated RT (FRT) can achieve good results compared to single-dose radiosurgery (SRS). We aimed to assess whether this is true for NF2 patients as well. METHODS: This retrospective cohort study included 34 patients and 54 lesions treated between 2010 and 2023 in a single university hospital. RESULTS: Thirty-four patient charts were assessed. The median follow-up was 62.6 months (range, 7.1-135.8 months). Lesion size (median larger diameter, 2.5 cm) was correlated with the use of FRT (P > 0.001). Younger age also was correlated with FRT (P = 0.006). Median overall survival and progression-free survival (PFS) were not reached. The overall control rate was 76.5%, and the mean PFS was 49.8 months, compared with . 90.5% and 57.2 months, respectively, for SRS and 66.7% and 44.9 months, respectively, for FRT. There were no differences between the 2 groups in hearing loss, tinnitus, and facial palsy. CONCLUSIONS: In the NF2 population, FRT may yield worse control rates than SRS. Whenever possible, it is preferable to not fractionate treatment for these patients. Nevertheless, the FRT results were still good. More and larger prospective trials are warranted.

Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy for Arteriovenous Malformation.

BACKGROUND: The best management for AVM, particularly high-grade ones and those that have been ruptured before, is still unknown. Data from prospective data lacks support for the best approach. METHODS: We retrospectively review patients with AVM at a single institution that were treated with radiation or a combination of radiation and embolization. These patients were divided into two groups based on radiation fractionation: SRS and fSRS. RESULTS: One-hundred and thirty-five (135) patients were first assessed and 121 met study criteria. Mean age at treatment was 30.5 years, and most patients were male. The groups were otherwise balanced, except for nidus size. SRS group had smaller lesions (P > 0.005). SRS correlates to better chance of nidus occlusion and lesser chance of retreatment. Complications such as radionecrosis (5%) and bleeding after nidus occlusion (1 patient) were rare. CONCLUSIONS: Stereotactic radiosurgery plays an important role on the treatment of AVM. Whenever possible, SRS should be preferred. Data from prospective trials about larger and previously ruptured lesions are needed.

Comparative analysis of somatostatin analog uptake between successfully irradiated and non-irradiated meningiomas.

OBJECTIVE: To evaluate whether there is a significant difference in somatostatin analog uptake in meningiomas treated or not with radiation therapy. METHODS: A cross-sectional study was performed comparing measurements of somatostatin analog (68Ga-DOTATATE) uptake in two independent groups of ten patients each - one consisting of patients with meningiomas previously treated with radiation therapy and another comprising patients who had never been submitted to radiation therapy. All patients underwent PET/CT and MRI scans in an interval shorter than 24 hours between exams. RESULTS: A total of 32 meningiomas from 20 patients were analyzed, all presenting significant somatostatin analog uptake in different degrees. The uptake levels of somatostatin analog were similar between the lesions treated or not with radiation therapy, and the mean values of SUVmax were 27.62 and 24.82, respectively (p=0.722). For SUVmean, the values were 16.20 and 14.82, respectively (p=0.822). CONCLUSION: Comparative analysis between the groups showed no significant differences in degree of somatostatin analog uptake in successfully irradiated and non-irradiated meningiomas.

Radiotherapy in Adult Burkitt Lymphoma: A Retrospective Analysis in a Large University Center.

Radiotherapy is not usually a part of standard Burkitt lymphoma treatment. We aim to assess patient and treatment characteristics of Burkitt lymphoma, particularly RT use, and how they relate to survival. Retrospective cohort of adult patients treated from 2008 to 2019 in an academic hospital. All patients had biopsy-proven Burkitt's lymphoma staged I to IV according to St. Jude's/Murphy staging system. Patients were followed for at least six-months or until death. Forty-eight consecutive patients were selected. Median age at diagnosis was 36.9 years (18-62). Median follow-up was 7.78 months (0.5-187.5). Most were male (81.3%) and had good performance by ECOG scale on their first hematologist appointment (56.2% were ECOG 0). Median OS and PFS were 8.4 months (interquartile range Q1-Q3: 3.96-152.2) and 8.3 months (interquartile range Q1-Q3: 6.7-not reached), respectively, with 32 deaths. A total of 43 patients (89.6%) were HIV-positive and had a median CD4 + level of 193.5 cells/mm3 at diagnosis. Patients that did not present a drop in CD4 + levels after treatment had better OS than those that did (p = 0.020). 11 patients underwent radiotherapy (22.9%) who had better OS than those who did not (p = 0.015). Our findings show that adult patients living with HIV presenting Burkitt lymphoma who maintained their immune status throughout treatment had better prognosis than those who presented CD4 + cells drops. Also, patients treated with radiotherapy-either with palliative intent or as consolidation after chemotherapy-had statistically significant better OS than those not irradiated. Prospective data is warranted for radiotherapy as a consolidative and as a palliative treatment.

Targeted Marrow Irradiation Intensification of Reduced-Intensity Fludarabine/Busulfan Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation.

Reduced-intensity conditioning (RIC) regimens frequently provide insufficient disease control in patients with high-risk hematologic malignancies undergoing allogeneic hematopoietic stem cell transplantation (HSCT). We evaluated intensification of fludarabine/busulfan (Flu/Bu) RIC with targeted marrow irradiation (TMI) in a dose escalation with expansion phase I clinical trial. TMI doses were delivered at 1.5 Gy in twice daily fractions on days -10 through -7 (dose levels: 3 Gy, 4.5 Gy, and 6 Gy), Flu (30 mg/m2 for 5 days) and Bu (area under the curve, 4800 µM*minute for 2 days). Eligible patients were age ≥18 years with high-risk hematologic malignancy and compromised organ function ineligible for myeloablative transplantation (n = 26). The median patient age was 64 years (range, 25 to 76 years). Nineteen patients (73%) had active or measurable residual disease at transplantation. One-year disease-free survival and overall survival were 55% (95% confidence interval [CI], 34% to 76%) and 65% (95% CI, 46% to 85%), respectively. Day +100 and 1 year transplantation-related mortality were 4% (95% CI, 0.6% to 27%) and 8.5% (95% CI, 2% to 32%), respectively. The 1-year cumulative incidence of relapse was 43% (95% CI, 27% to 69%). Rates of grade II-IV and III-IV acute GVHD rates were 57% (95% CI, 39% to 84%) and 22% (95% CI, 9% to 53%), respectively. Whole blood immune profiling demonstrated enrichment of central/transitional memory-like T cells with higher TMI doses, which correlated with improved survival compared with control samples from patients undergoing allogeneic HSCT. Intensification of a Flu/Bu RIC regimen with TMI is feasible with a low incidence of transplantation-related mortality in medically frail patients with advanced malignancies. The recommended phase 2 TMI dose is 6 Gy.

Comparative analysis of somatostatin analog uptake between successfully irradiated and non-irradiated meningiomas

Abstract Objective To evaluate whether there is a significant difference in somatostatin analog uptake in meningiomas treated or not with radiation therapy. Methods A cross-sectional study was performed comparing measurements of somatostatin analog (68Ga-DOTATATE) uptake in two independent groups of ten patients each - one consisting of patients with meningiomas previously treated with radiation therapy and another comprising patients who had never been submitted to radiation therapy. All patients underwent PET/CT and MRI scans in an interval shorter than 24 hours between exams. Results A total of 32 meningiomas from 20 patients were analyzed, all presenting significant somatostatin analog uptake in different degrees. The uptake levels of somatostatin analog were similar between the lesions treated or not with radiation therapy, and the mean values of SUVmax were 27.62 and 24.82, respectively (p=0.722). For SUVmean, the values were 16.20 and 14.82, respectively (p=0.822). Conclusion Comparative analysis between the groups showed no significant differences in degree of somatostatin analog uptake in successfully irradiated and non-irradiated meningiomas.

Early-onset symptomatic radiation necrosis after stereotactic radiosurgery in the setting of COVID-19 infection.

In this brief report, we describe the case of a previously healthy 51-year gentleman who was treated with stereotactic radiosurgery to a dose of 12 Gy to a small right-sided vestibular schwannoma. MRI of the brain performed after treatment revealed stable treated disease but subsequently, the patient developed symptomatic COVID-19 based on PCR along with multiple cranial neurologic deficits, including right facial paralysis, hemifacial anesthesia, and anesthesia of the ipsilateral hard palate and tongue. MRI of the brain was repeated and demonstrated radiation necrosis in the adjacent brainstem for which he was treated with Pentoxifylline and Vitamin E, dexamethasone, and Bevacizumab with only partial improvement. The dose-volume metrics of the brainstem from his radiotherapy plan as well as the trajectory of his imaging findings do not match this clinical picture from radiotherapy alone. We review the basic pathogenesis of the inflammatory response to infection from the SARS-CoV-2 virus as well as the pathogenesis of radiation necrosis. Heightened awareness about potential risks with high-dose radiotherapy in patients with symptomatic COVID-19 should be considered.

Radiotherapy for early and advanced stages Follicular Lymphoma.

OBJECTIVES: To evaluate the results of radiotherapy (RT) for follicular lymphoma (FL) under different management scenarios. METHODS: We retrospectively assessed consecutive patients with FL who had undergone irradiation between 2010 and 2018. All patients had biopsy-proven FL and were positron emission tomography-staged, although some (35.3%) were reassessed with computed tomography after treatment alone. Rituximab was only available to FL patients after 2016. RESULTS: Thirty-four patients were selected, with a mean age at diagnosis of 61.6 years (34-89 years). The median follow-up duration was 49.4 months. Most patients were female (58.8%) and showed good performance on the Eastern Cooperative Oncology Group (ECOG) scale (ECOG 0-55.9%). The mean overall survival (OS) and progression-free survival were 48.7 and 33.6 months, respectively, with four deaths reported. OS rates at 2 and 3 years were 94.1% and 91.2%, respectively. Four patients showed transformation into aggressive lymphomas and underwent rituximab-based systemic treatment. Transformation-free survival was 47.8 months, and all patients with transformed disease were alive at assessment. Five patients had in-field relapse, all of them also relapsed elsewhere, and the mean relapse-free survival time was 40.3 months. No median end points were reached on assessment. CONCLUSION: FL is an indolent disease. Our findings show good outcomes for patients treated with radiation, with a low transformation rate and excellent management of relapsed disease. RT is an important part of these results.

Radiotherapy for early and advanced stages Follicular Lymphoma

OBJECTIVES To evaluate the results of radiotherapy (RT) for follicular lymphoma (FL) under different management scenarios. METHODS We retrospectively assessed consecutive patients with FL who had undergone irradiation between 2010 and 2018. All patients had biopsy-proven FL and were positron emission tomography-staged, although some (35.3%) were reassessed with computed tomography after treatment alone. Rituximab was only available to FL patients after 2016. RESULTS Thirty-four patients were selected, with a mean age at diagnosis of 61.6 years (34-89 years). The median follow-up duration was 49.4 months. Most patients were female (58.8%) and showed good performance on the Eastern Cooperative Oncology Group (ECOG) scale (ECOG 0-55.9%). The mean overall survival (OS) and progression-free survival were 48.7 and 33.6 months, respectively, with four deaths reported. OS rates at 2 and 3 years were 94.1% and 91.2%, respectively. Four patients showed transformation into aggressive lymphomas and underwent rituximab-based systemic treatment. Transformation-free survival was 47.8 months, and all patients with transformed disease were alive at assessment. Five patients had in-field relapse, all of them also relapsed elsewhere, and the mean relapse-free survival time was 40.3 months. No median end points were reached on assessment. CONCLUSION FL is an indolent disease. Our findings show good outcomes for patients treated with radiation, with a low transformation rate and excellent management of relapsed disease. RT is an important part of these results.

Survival and consolidative radiotherapy in patients living with HIV and treated for diffuse large B-cell lymphoma.

OBJECTIVES: Current guidelines tend to treat HIV positive (HIV+) patients as their seronegative counterparts with diffuse large B-cell lymphoma (DLBCL) but little is known about their radiotherapy responses differences. PATIENTS AND METHODS: A retrospective cohort of all consecutive HIV+ DBCL patients treated with chemotherapy between 2004 and 2018 was assessed. All patients had biopsy-proven lymphomas. They were included if the proposed radical treatment was done without progression or death during chemotherapy and had at least 6 months of follow-up or were followed until death. RESULTS: Fifty-three (53) patients were selected, with a median age at diagnosis of 41.39 years (20-65 years). Median follow-up of 35.16 months (1.4-178.7 months). Male patients accounted for 54.7% and most had a good performance in the ECOG scale at diagnoses (81.1% are ECOG 0-1). Median overall survival was not reached. Mean OS was 41.5 months with 16 deaths. Age had an impact on OS, with patients older than 60 years at more risk (p = 0.044), as did longtime use of HAART, with those that started antiretroviral therapy within the diagnose of the lymphoma at greatest risk (p = 0.044). RT did not have an impact on OS (p = 0.384) or PFS (p = 0.420), although survival curves show better OS in the radiotherapy group. Toxicities were rare, since none of the patients had grade 3 or superior toxicity. CONCLUSION: RT did not impact survival or progression in our limited sample, but a longer OS may occur after the first-year post RT. RT should be tested in prospective data in the HIV+ population with DLBCL.

Impact of HIV infection on consolidative radiotherapy for non-Hodgkin diffuse large B-cell lymphoma.

OBJECTIVES: Even though frequent, it is not known how HIV infection and treatment impact in the consolidation by radiotherapy of non-Hodgkin diffuse large B-cell lymphomas (DBCL). This article aim to assess that difference that HIV makes on radiation treatment. PATIENTS AND METHODS: A retrospective cohort of all DBCL patients treated with chemotherapy and consolidative radiotherapy at a single institution between 2010 and 2018 was assessed. All patients had biopsy-proven lymphoma and were included if radiation was part of the treatment and had at least 6 months of follow-up or were followed until death. RESULTS: Three-hundred fifty-nine (359) patients were selected, with a median age at diagnosis of 57.7 years (13-90 years). Twenty-eight patients (7.8%) were HIV positive. Median follow-up was 48.0 months. Female patients were 51.3% and most had a good performance in the ECOG scale (78.8% are ECOG 0-1). Median overall survival was not reached, but mean OS was 50.1 months with 86 deaths. Median progression-free survival was 48.7 months. HIV infection had no impact on OS (p = 0.580) or PFS (p = 0.347) among patients treated with RT. HIV positive patients were more frequently staged only with CT (p > 0.05) with no impact on PFS (p = 0.191). No HIV positive patient received rituximab due to local policy restrictions and HIV positive patients were more prone to receive CHOP-like chemotherapy (p < 0.05), specially ones with etoposide (CHOEP). CHOP was associated with better survival (p = 0.015) in the overall population and in the HIV negative population (p = 0.002), but not in the HIV positive population (p = 0.982). RT toxicities were not overall more frequent in the HIV positive population (p = 0.567), except for fatigue (p < 0.05) and hematological toxicities (p = 0.022). CONCLUSION: HIV status did not influence on survival when patients were treated with consolidative radiotherapy. HIV infection was a bias on our sample for staging methods and chemotherapy regimens choices. For HIV positive patients there was an increase in fatigue and hematological toxicities of any grade with radiation.

Involvement of the central nervous system in neuroblastomas: A potential direct pathway.

Although frequently disseminated to other anatomical sites, neuroblastoma (NB) is rarely reported as involving the central nervous system (CNS), which may reflect insufficient research in poorly controlled systemic disease. Here we demonstrate the involvement of the CNS in patients with NB over 18 months of age at diagnosis of extensive systemic disease. Meningeal metastases were observed even in the presence of complete systemic control. Although no improvement in patient's survival was observed, radiotherapy was effective in preventing CNS recurrence after observation of actual or previous dural disease. In conclusion, this study uncovered the uncommon pathologic involvement of the CNS in children with advanced NB and underscores the meningeal surface as a potential pathway for this to occur.

Intensity-modulated ventricular irradiation for intracranial germ-cell tumors: Survival analysis and impact of salvage re-irradiation.

BACKGROUND AND PURPOSE: The roles of surgery, chemotherapy, and parameters of radiation therapy for treating very rare central nervous system germ cell tumors (CNS-GCT) are still under discussion. We aimed to evaluate the survival and recurrence patterns of patients with CNS-GCT treated with chemotherapy followed by whole ventricle irradiation with intensity-modulated radiation therapy. MATERIALS AND METHODS: We reviewed the clinical outcomes of 20 consecutive patients with CNS-GCT treated with chemotherapy and intensity-modulated radiation therapy from 2004 to 2014 in two partner institutions. RESULTS: Twenty children with a median age of 12 years were included (16 males). Sixteen tumors were pure germinomas, and 4 were non-germinomatous germ cell tumors (NGGCT). All patients were treated with intensity-modulated radiation therapy guided by daily images, and 70% with volumetric intensity-modulated arc radiotherapy additionally. The median dose for the whole-ventricle was 25.2 Gy (range: 18-30.6 Gy) and 36 Gy (range: 30-54 Gy) for the tumor bed boost. The median post-radiation therapy follow-up was 57.5 months. There were 3 recurrences (2 NGGCT and 1 germinoma that recurred as a NGGCT), with 1 death from the disease and the other 2 cases each successfully rescued with chemotherapy and craniospinal irradiation. The overall survival at 5 years was 95% and disease-free survival was 85%. CONCLUSIONS: The results of this study suggest that the combined use of chemotherapy followed by whole ventricle irradiation with intensity-modulated radiation therapy is effective for CNS-GCTs, especially pure germinomas. Even being rescued with craniospinal irradiation, the NGGCT cases have markedly worse prognoses and should be more rigorously selected for localized treatment.

Consensus for vaginal stenosis prevention in patients submitted to pelvic radiotherapy.

OBJECTIVE: To propose a consensus for prevention of vaginal stenosis in patients submitted to pelvic radiotherapy. METHOD: In this methodological study, Delphi technique was applied for content validation on vaginal stenosis prevention. Data regarding content validation were collected from 32 specialists practicing in the oncology profession. The content validity index of items in the consensus was calculated based on the evaluations by the specialists. RESULTS: In the first round, of the 38 items evaluated, 29 items reached a Content Validity Index (CVI-I) greater than 80%, and 9 items had a CVI lower than 80%. Of the items that did not obtain agreement, 2 items were excluded, and 7 were reformulated and included in the second round. In the second round, all 7 items obtained a CVI-I greater than 80%. The final instrument consisted of 29 items validated in the first round, plus 7 items reformulated and consolidated in the second round. The judges agreed that it is the responsibility of the health professionals to consult the patients undergoing radiation therapy in the area of sexuality to patients. The radiation oncologist should be the first professional to address this issue and the nurse oncologist in the follow-up consultation should pass the guidelines to the patients as comprehensively as possible. Patients should be informed about vaginal dilation, regardless of whether they are sexually active or have a partner. They should also be informed of when they can resume sexual activity. The procedure of vaginal dilation should be individualized. The prescribed vaginal dilators should be used with a lubricant for a duration of at least 5-10 minutes, 2-3 times a week, as per the need of each patient (sexual activity and/or clinical follow-up) for an indefinite time. Patients should seek medical help in case they experience pain, discomfort, or bleeding during dilation. CONCLUSION: The Brazilian version of the consensus for vaginal stenosis prevention in patients submitted to pelvic radiotherapy was validated with 36 items in 7 categories related to Responsibility; Target population; Rationale; Vaginal dilator; Content instructions; Information provision; and Patient support. In Brazil, the educational practices on vaginal dilation for patients submitted to radiotherapy partly revealed similar difficulties as identified in other studies as well as countries with reference to specific guidelines for the start and duration of vaginal dilation. The final consensus developed in this study could strengthen the guidelines for education of patients in Brazil and provide a future scope to establish a single and safe guideline.

Adjuvant Radiotherapy Did Not Reduce Recurrence of World Health Organization Grade I Meningiomas with Venous Sinus Involvement: A Propensity Score Adjusted Analysis and Literature Review.

BACKGROUND: Most meningiomas are classified as World Health Organization (WHO) grade I. Adjuvant radiation therapy (RT) is commonly recommended for subtotal resections with documented progressive regrowth of lesions with venous sinus involvement. We investigated if recurrence of WHO grade I meningiomas was influenced by adjuvant RT. METHODS: From 2000 to 2014, patients with grade I meningiomas with at least one venous sinus involvement and at least 4 years of follow-up were included. Demographics, venous sinus involvement, histology, and extent of resection (EOR) were characterized. Because patients undergoing RT tend to differ from those for whom adjuvant therapy was not prescribed, we used propensity scores to adjust for confounding variables. RESULTS: Sixty-two patients were included; of these, 18 (29.0%) had recurrences. The mean age was 52.8 ± 12.3 years, and 79.0% were women. A total of 34 cases (54.8%) were submitted to adjuvant RT. Adjuvant RT was more frequent in those who had tumor recurrence (77.8% vs. 45.5%, P = 0.020). RT was more frequent in superior sagittal sinus (SSS) invasion (76.5% vs. 50.0%, P = 0.030) and less prevalent after gross total resection (GTR) (32.4% vs. 67.9%, P = 0.005). Propensity score adjusted analysis suggested no adjuvant RT benefit (odds ratio [OR], 2.51; 95% confidence interval [CI], 0.68-9.28; P = 0.167), independent of the EOR. SSS involvement increased recurrence risk (OR, 12.69; 95% CI, 1.46-110.27; P = 0.021), whereas GTR tended to decrease it (OR, 0.26; 95% CI, 0.06-1.09; P = 0.065). CONCLUSIONS: Adjuvant RT does not seem to be a pivotal criterion to reduce the recurrence rate in patients with grade I meningioma, even when venous sinuses are involved.

Intensity-modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) for head and neck cancer: cost-effectiveness analysis.

BACKGROUND: A cost-effectiveness analysis of IMRT compared to 3D-CRT for head and neck cancer patients (HNCPs) was conducted in the Brazilian Public Health System. METHODS: A Markov model was used to simulate radiation therapy-induced dysphagia and xerostomia in HNCPs. Data from the PARSPORT trial and the quality-of-life study were used as parameters. The incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained were calculated. RESULTS: At 2 years, IMRT was associated with an incremental benefit of 0.16 QALYs gained per person, resulting in an ICER of BRL 31,579 per QALY gained. IMRT was considered cost-effective when using the guideline proposed by the World Health Organization (WHO) of three times the national gross domestic product (GDP) per capita (BRL 72,195). Regarding life expectancy (15 years), the incremental benefit of IMRT was 1.16 QALYs gained per person, with an ICER of BRL 4,341. IMRT was also cost-effective using the WHO definition, which states that the maximum cost is equal to the GDP per capita (BRL 24,065). CONCLUSIONS: IMRT was considered cost-effective from the perspective of the Brazilian public health system.

Prognostic models for patients with brain metastases after stereotactic radiosurgery with or without whole brain radiotherapy: a validation study.

PURPOSE/OBJECTIVE(S): To compare the performance of five prognostic models [RTOG recursive partitioning analysis (RPA), Score Index for Radiosurgery in Brain Metastases (SIR), Barnholtz-Sloan-Kattan nomogram (BSKN), diagnosis-specific Graded Prognostic Assessment (dsGPA), and Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA)] against actual survival in patients with brain metastases treated with SRS +/- WBRT. MATERIALS/METHODS: 100 consecutive patients treated with SRS +/- WBRT between January 2006 and July 2012 were retrospectively analyzed. Patients were binned according to 33 percentiles of the predicted survival distribution for the BSKN and dsGPA models to compare with LungmolGPA, RPA and SIR. Pearson's correlation coefficients between predicted and observed survival were estimated to quantify the proportion of variance in observed survival. RESULTS: Median survival for the entire cohort was 13.5 months, with predicted vs actual MS by BSKN, SIR, dsGPA, RPA, adenocarcinoma Lung-molGPA, and nonadenocarcinoma Lung-molGPA was 3.8 vs 15.6 months, 7 vs 13.5 months, 9.4 vs 13.5 months, 10.3 vs 13.5 months, 13.7 vs 13.7 months, and 9.8 vs 9.7 months, respectively. The BSKN model and adenocarcinoma LungmolGPA created three groups with a statistically significantly different MS (p = 0.002 and p = 0.01, respectively). CONCLUSION: All models under-predicted MS and only the BSKN and Lung-molGPA model stratified patients into three risk groups with statistically significant actual MS. The prognostic groupings of the adenocarcinoma Lung-molGPA group was the best predictor of MS, and showed that we are making improvements in our prognostic ability by utilizing molecular information that is much more widely available in the current treatment era.

Evaluation of a new predictor of heart and left anterior descending artery dose in patients treated with adjuvant radiotherapy to the left breast.

BACKGROUND: Heart-sparing techniques are time and resource intensive, although not all patients require the use of these strategies. This study evaluates the performance of different distance metrics in predicting the need for breath-hold radiotherapy in left-sided breast cancer patients receiving adjuvant radiotherapy. METHODS: Fifty left-sided breast cancer patients treated with breast conserving surgery and adjuvant radiotherapy to the breast from a single institution were retrospectively studied. The left breast and organs at risk were contoured in accordance to guidelines and a plan with tangents was obtained using the free-breathing CT in supine position. Heart (mean heart dose (MHD), heart V25 Gy) and left anterior descending artery dosimetry were computed and compared against distance metrics under investigation (Contact Heart, 4th Arch and 5th Arch). Recursive partitioning analysis (RPA) was used to determine optimal cut-points for distance metrics for dosimetric end points. Receiver operating characteristic curves and Pearson correlation coefficients were used to evaluate the association between distance metrics and dosimetric endpoints. Univariable and multivariable logistic regression analysis was performed to identify significant predictors of dosimetric end points. RESULTS: The mean MHD and heart V25 Gy were 2.3 Gy and 10.4 cm3, respectively. With tangents, constraints for MHD (< 1.7 Gy and V25 Gy < 10 cm3) were unattainable in 80% and 46% of patients, respectively. Optimal RPA thresholds included: Contact Heart (73 mm), 4th Arch (7 mm) and 5th Arch (41 mm). Of these, the 4th Arch had the highest overall accuracy, sensitivity, concordance index and correlation coefficient. All metrics were statistically significant predictors for MHD ≥ 1.7 Gy based on univariable logistic regression. Fifth Arch did not reach significance for heart V25 Gy ≥ 10 cm3. Fourth Arch was the only predictor to remain statistically significant after multivariable analysis. CONCLUSIONS: We propose a novel "4th Arch" metric as an accurate and practical tool to determine the need for breath-hold radiotherapy for left-sided breast cancer patients undergoing adjuvant radiotherapy with standard tangents. Further validation in an external cohort is necessary.

Genitourinary and gastrointestinal toxicity among patients with localized prostate cancer treated with conventional versus moderately hypofractionated radiation therapy: systematic review and meta-analysis.

BACKGROUND: Hypofractionated (HRT) prostate radiation therapy has the potential to deliver a higher biologically effective dose over a shorter time compared with conventional fractionation (CRT). HRT, giving fewer fractions each with higher dose, might improve the therapeutic ratio, resource use and patient convenience but the toxicity is still controversial. Our objective was to compare the gastroinstestinal (GI) and genitourinary (GU) toxicity of HRT versus CRT. METHODS: Systematic review and meta-analysis of randomized clinical trials studies in PubMed, Cochrane and EMBASE databases published through December 2016 was done. Only randomized trials that evaluated patients with localized prostate cancer (PCa) undergoing CRT or HRT were included. In these studies, the daily dose was 1.8 Gy or 2 Gy per day for CRT and 2.4 to 3.4 Gy for HRT. RESULTS: 7317 patients in nine studies were analyzed. Six studies included acute GU toxicity data which showed similar rates for both HRT and CRT (32.6vs. 31.9%; RD 0.00; 95% CI; -0.03,0.03; p = .81; I2 = 0%). Similarly, seven studies showed no difference in late GU toxicity based on treatment schedule (28.7 vs. 28.0%; RD -0.01; 95% CI; -0.04,0.03; p = .67; I2 = 52%). GI toxicity at three months after radiotherapy was higher in patients treated with HRT in six studies (27.5 vs. 21.9%; RD 0.06; 95% CI; 0.02,0.10; p = .004; I2 = 39%); however, eight studies showed GI toxicity 12 months or more after radiotherapy that was statistically the same (12.9 HRT vs. 16.2% CRT; RD -0.01; 95% CI; -0.04,0.02; p = .41; I2 = 58%). CONCLUSION: In meta-analysis of the available randomized trials on moderate HRT versus CRT for prostate cancer, acute and late GU toxicity were similar for both treatment schemes. While HRT was associated with higher acute GI toxicity, late toxicity was similar.