Receipt of brachytherapy is an independent predictor of survival in glioblastoma in the Surveillance, Epidemiology, and End Results database.

INTRODUCTION: There has been a resurgence of interest in brachytherapy as a treatment for glioblastoma, with several currently ongoing clinical trials. To provide a foundation for the analysis of these trials, we analyze the Surveillance, Epidemiology, and End Results (SEER) database to determine whether receipt of brachytherapy conveys a survival benefit independent of traditional prognostic factors. MATERIALS AND METHODS: We identified 60,456 glioblastoma patients, of whom 362 underwent brachytherapy. We grouped patients based on receipt of brachytherapy and compared clinical and demographic variables between groups using Student's t-test and Pearson's chi-squared test. We assessed survival using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Median overall survival was 16 months in patients who received brachytherapy compared to 9 months in those who did not (log-rank p < 0.001). Patients who underwent brachytherapy tended to be younger (p < 0.001), suffered from smaller tumors (< 4 cm, p < 0.001), and were more likely to have undergone gross total resection (GTR, p < 0.001). In univariable Cox models, these variables were independently associated with improved overall survival. Additionally, improved survival was associated with known receipt of chemotherapy (HR 0.459, p < 0.001), external beam radiation (HR 0.447, p < 0.001), and brachytherapy (HR 0.637, p < 0.001). The association between brachytherapy and improved survival remained robust (HR 0.859, p = 0.031) in a multivariable model that adjusted for patient age, tumor size, tumor location, GTR, receipt of chemotherapy, and receipt of external beam radiation. CONCLUSION: Our SEER analysis indicates that brachytherapy is associated with improved survival in glioblastoma after controlling for age, tumor size/location, extent of resection, chemotherapy, and external beam radiation.

Augmenting Total Body Irradiation with a Cranial Boost before Stem Cell Transplantation Protects Against Post-Transplant Central Nervous System Relapse in Acute Lymphoblastic Leukemia.

The purpose of this study was to determine the effect of a pretransplant cranial boost (CB) on post-transplant central nervous system (CNS) relapse and survival in acute lymphoblastic leukemia (ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) using a total body irradiation (TBI)-containing preparation regimen. Two hundred thirteen ALL patients were treated consecutively at our institution with allogeneic HSCT. Conditioning included TBI (1320 cGy in 8 fractions given twice daily) and cyclophosphamide (120 mg/kg) with or without fludarabine (75 mg/m2). Patients were divided into 4 groups based on history of CNS disease and whether a CB was given. Of the 160 patients with no history of CNS disease, none received a CB (CNS-/CB-). Of the 53 patients with prior CNS disease, 41 had not received prior cranial irradiation. Thirty of these 41 received a CB of 900 to 1000 cGy in 5 daily fractions (CNS+/CB+), whereas the other 11 did not receive a CB because of physician preference (CNS+/CB-). The remaining 12 patients with prior CNS involvement had previously received cranial irradiation and thus were not candidates for a CB (CNS + PriorRT). Two-year CNS relapse risk, overall survival (OS), and disease-free survival (DFS) were calculated using Kaplan-Meier analysis. Seven patients experienced post-transplant CNS relapse: 4 in the CNS-/CB- group, 2 in the CNS+/CB- group, and 1 in the CNS + PriorRT group. None of the 30 patients who received a CB relapsed in the CNS. Two-year CNS relapse risk was 0% in the CNS+/CB+ group compared with 21% (95% CI, 0% to 45%) in the CNS+/CB- group (P = .03). Two-year OS and DFS did not differ between the groups. In conclusion, among ALL patients with prior CNS leukemia, there was a trend toward a reduced risk of post-transplant CNS relapse in patients who received a CB. However, the addition of a CB did not appear to have an impact on OS or DFS.

Alternative donor hematopoietic cell transplantation for Fanconi anemia.

Historically, alternative donor hematopoietic cell transplantation (HCT) for Fanconi anemia (FA) patients resulted in excessive morbidity and mortality. To improve outcomes, we made sequential changes to the HCT conditioning regimen. A total of 130 FA patients (median age, 9.0 years; range, 1-48) underwent alternative donor HCT at the University of Minnesota between 1995 and 2012. All patients received cyclophosphamide (CY), single fraction total body irradiation (TBI), and antithymocyte globulin (ATG) with or without fludarabine (FLU), followed by T-cell-depleted bone marrow or unmanipulated umbilical cord blood transplantation. The addition of FLU enhanced engraftment 3-fold. The incidence of grades 2-4 acute and chronic graft-versus-host disease was 20% and 10%, respectively. Severe toxicity was highest in patients >10 years of age or those with a history of opportunistic infections or transfusions before HCT. Mortality was lowest in patients without a history of opportunistic infection or transfusions and who received conditioning with TBI 300 cGy, CY, FLU, and ATG. These patients had a probability of survival of 94% at 5 years. Alternative donor HCT is now associated with excellent survival for patients without prior opportunistic infections or transfusions and should be considered for all FA patients after the onset of marrow failure. These studies were registered at http://www.clinicaltrials.gov as NCT00005898, NCT00167206, and NCT00352976.

Patterns of recurrence after radiotherapy for high-risk neuroblastoma: Implications for radiation dose and field.

BACKGROUND: Prognosis for patients with high-risk neuroblastoma (HR-NBL) is guarded despite aggressive therapy, and few studies have characterized outcomes after radiotherapy in relation to radiation treatment fields. METHODS: Multi-institutional retrospective cohort of 293 patients with HR-NBL who received autologous stem cell transplant (ASCT) and EBRT between 1997-2021. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis. Follow-up was defined from the end of EBRT. Event-free survival (EFS) and OS were analyzed by Kaplan-Meier method. Cumulative incidence of locoregional progression (CILP) was analyzed using competing risks of distant-only relapse and death with Gray's test. RESULTS: Median follow-up was 7.0 years (range: 0.01-22.4). Five-year CILP, EFS, and OS were 11.9 %, 65.2 %, and 77.5 %, respectively. Of the 31 patients with LRR and imaging review, 15 (48.4 %) had in-field recurrences (>12 Gy), 6 (19.4 %) had marginal failures (≤12 Gy), and 10 (32.3 %) had both in-field and marginal recurrences. No patients receiving total body irradiation (12 Gy) experienced marginal-only failures (p = 0.069). On multivariable analyses, MYCN amplification had higher risk of LRR (HR: 2.42, 95 % CI: 1.06-5.50, p = 0.035) and post-consolidation isotretinoin and anti-GD2 antibody therapy (HR: 0.42, 95 % CI: 0.19-0.94, p = 0.035) had lower risk of LRR. CONCLUSIONS: Despite EBRT, LRR remains a contributor to treatment failure in HR-NBL with approximately half of LRRs including a component of marginal failure. Future prospective studies are needed to explore whether radiation fields and doses should be defined based on molecular features such as MYCN amplification, and/or response to chemotherapy.

Idiopathic Pneumonitis Syndrome After Total Body Irradiation in Pediatric Patients Undergoing Myeloablative Hematopoietic Stem Cell Transplantation: A PENTEC Comprehensive Review.

PURPOSE: Pulmonary complications, especially idiopathic pneumonitis syndrome (IPS), are potentially life altering or fatal sequelae of hematopoietic cell transplantation (HCT). Total body irradiation (TBI) as part of the conditioning regimen has been implicated in IPS. A comprehensive PENTEC (Pediatric Normal Tissues in the Clinic) review was performed to increase our understanding of the role of TBI in the development of acute, noninfectious IPS. METHODS AND MATERIALS: A systematic literature search was conducted using the MEDLINE, PubMed, and Cochrane library databases for articles describing pulmonary toxicity in children treated with HCT. Data pertaining to TBI and pulmonary endpoints were extracted. Risk of IPS was analyzed in relation to patient age, TBI dose, fractionation, dose rate, lung shielding, timing, and type of transplant, with the goal to better understand factors associated with this complication in children undergoing HCT. A logistic regression model was developed using a subset of studies with comparable transplant regimens and sufficient TBI data. RESULTS: Six studies met criteria for modeling of the correlation of TBI parameters with IPS; all consisted of pediatric patients undergoing allogeneic HCT with a cyclophosphamide-based chemotherapy regimen. IPS was variably defined, but all studies that reported IPS were included in this analysis. The mean incidence of post-HCT IPS was 16% (range, 4%-41%). Mortality from IPS, when it occurred, was high (median, 50%; range, 45%-100%). Fractionated TBI prescription doses encompassed a narrow range of 9 to 14 Gy. Many differing TBI methods were reported, and there was an absence of 3-dimensional dose analysis of lung blocking techniques. Thus, a univariate correlation between IPS and total TBI dose, dose fractionation, dose rate, or TBI technique could not be made. However, a model, built from these studies based on prescribed dose using a normalized dose parameter of equivalent dose in 2-Gy fractions (EQD2), adjusted for dose rate, suggested correlation with the development of IPS (P = .0004). The model-predicted odds ratio for IPS was 24.3 Gy-1 (95% confidence interval, 7.0-84.3). Use of TBI lung dose metrics (eg, midlung point dose) could not be successfully modeled, potentially because of dosimetric uncertainties in the actual delivered volumetric lung dose and imperfections in our modeling process. CONCLUSIONS: This PENTEC report is a comprehensive review of IPS in pediatric patients receiving fractionated TBI regimens for allogenic HCT. IPS was not clearly associated with 1 single TBI factor. Modeling using dose-rate adjusted EQD2 showed a response with IPS for allogeneic HCT using a cyclophosphamide-based chemotherapy regimen. Therefore, this model suggests IPS mitigation strategies can focus on not just the dose and dose per fraction but also the dose rate used in TBI. More data are needed to confirm this model and to determine the influence of chemotherapy regimens and contribution from graft-versus-host disease. The presence of confounding variables (eg, systemic chemotherapies) that affect risk, the narrow range of fractionated TBI doses found in the literature, and limitations of other reported data (eg, lung point dose) may have prevented a more straightforward link between IPS and total dose from being observed.

Intensity modulated radiation therapy replaces 3-dimensional conformal radiotherapy as prostate cancer treatment.

PURPOSE: We describe trends in the use of intensity modulated radiotherapy vs 3-dimensional conformal radiotherapy for prostate cancer and identified predictors of intensity modulated radiotherapy use. MATERIALS AND METHODS: From the SEER (Surveillance, Epidemiology and End Results)-Medicare database we identified 52,290 men with incident nonmetastatic prostate cancer from 2000 to 2007 who were treated with radiotherapy. We tracked trends in the use of intensity modulated radiotherapy, 3-dimensional conformal radiotherapy, brachytherapy and combinations. Patient demographic and clinical characteristics were described and compared using chi-square and multivariate logistic regression. Trends at the place of service were also examined. RESULTS: Intensity modulated radiotherapy use increased from 1% of all radiotherapy in 2000 to 70% in 2007. Three-dimensional conformal radiotherapy use decreased from 75% to 12%. Most cases were treated with intensity modulated radiotherapy monotherapy. In 2007, 12% of the cohort received intensity modulated radiotherapy plus brachytherapy. In 2005, 81% of all external radiation was given as intensity modulated radiotherapy. Except for geography there were minimal differences in patient demographic and clinical characteristics between those treated with 3-dimensional conformal radiotherapy vs intensity modulated radiotherapy. On multivariate analysis significant predictors of the odds of receiving intensity modulated radiotherapy vs 3-dimensional conformal radiotherapy were low Gleason score, high education, white or Asian race and urban place of residence. The odds of receiving intensity modulated radiotherapy varied greatly by registry. A lesser part of the growth in intensity modulated radiotherapy use occurred at freestanding facilities. CONCLUSIONS: Intensity modulated radiotherapy has replaced 3-dimensional conformal radiotherapy as the primary form of external radiation for prostate cancer. The choice of intensity modulated radiotherapy over 3-dimensional conformal radiotherapy is not related to common clinical factors such as age, comorbidities or tumor aggressiveness. Although geographic variations exist, by 2007 intensity modulated radiotherapy dominated in all regions studied.

Three-dimensional external beam radiotherapy for prostate cancer increases the risk of hip fracture.

BACKGROUND: Hip fracture is associated with high morbidity and mortality. Pelvic external beam radiotherapy (EBRT) is known to increase the risk of hip fractures in women, but the effect in men is unknown. METHODS: From the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, 45,662 men who were aged ≥66 years and diagnosed with prostate cancer in 1992-2004 were identified. By using Kaplan-Meier methods and Cox proportional hazards models, the primary outcome of hip fracture risk was compared among men who received radical prostatectomy (RP), EBRT, EBRT plus androgen suppression therapy (AST), or AST alone. Age, osteoporosis, race, and other comorbidities were statistically controlled. A secondary outcome was distal forearm fracture as an indicator of the risk of fall-related fracture outside the radiation field. RESULTS: After covariates were statistically controlled, the findings showed that EBRT increased the risk of hip fractures by 76% (hazards ratio [HR], 1.76; 95% confidence interval [CI], 1.38-2.40) without increasing the risk of distal forearm fractures (HR, 0.80; 95% CI, 0.56-1.14). Combination therapy with EBRT plus AST increased the risk of hip fracture 145% relative to RP alone (HR, 2.45; 95% CI, 1.88-3.19) and by 40% relative to EBRT alone (HR, 1.40; 95% CI, 1.17-1.68). EBRT plus AST increased the risk of distal forearm fracture by 43% relative to RP alone (HR, 1.43; 95% CI, 0.97-2.10). The number needed to treat to result in 1 hip fracture during a 10-year period was 51 patients (95% CI, 31-103). CONCLUSIONS: In men with prostate cancer, pelvic 3-D conformal EBRT was associated with a 76% increased risk of hip fracture. This risk was slightly increased further by the addition of short-course AST to EBRT. This risk associated with EBRT must be site-specific as there was no increase in the risk of fall-related fractures in bones that were outside the radiation field.

Rapid Interval Recurrence of Glioblastoma Following Gross Total Resection: A Possible Indication for GammaTileⓇ Brachytherapy.

Glioblastoma recurrence between initial resection and standard-of-care adjuvant chemoradiotherapy (CRT) is a negative prognostic factor in an already highly aggressive disease. Re-resection with GammaTileⓇ(GT Medical Technologies Inc., Tempe, AZ) placement affords expedited adjuvant radiation to mitigate the likelihood of such growth. Here, we report a glioblastoma patient who underwent re-resection and GammaTileⓇ (GT) placement within two months of the initial gross total resection due to regrowth that reached the size of the original presenting tumor. The patient subsequently received concurrent temozolomide and 60 Gy external beam to regions outside of the brachytherapy range, fulfilling the generally accepted Stupp regimen. The patient tolerated the treatment without complication. The dosimetrics and implications of the case presentation are reviewed.

Biological Principles of Stereotactic Body Radiation Therapy (SBRT) and Stereotactic Radiation Surgery (SRS): Indirect Cell Death.

PURPOSE: To review the radiobiological mechanisms of stereotactic body radiation therapy stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). METHODS AND MATERIALS: We reviewed previous reports and recent observations on the effects of high-dose irradiation on tumor cell survival, tumor vasculature, and antitumor immunity. We then assessed the potential implications of these biological changes associated with SBRT and SRS. RESULTS: Irradiation with doses higher than approximately 10 Gy/fraction causes significant vascular injury in tumors, leading to secondary tumor cell death. Irradiation of tumors with high doses has also been reported to increase the antitumor immunity, and various approaches are being investigated to further elevate antitumor immunity. The mechanism of normal tissue damage by high-dose irradiation needs to be further investigated. CONCLUSIONS: In addition to directly killing tumor cells, high-dose irradiation used in SBRT and SRS induces indirect tumor cell death via vascular damage and antitumor immunity. Further studies are warranted to better understand the biological mechanisms underlying the high efficacy of clinical SBRT and SRS and to further improve the efficacy of SBRT and SRS.

A single institution experience using sequential multi-modality adjuvant chemotherapy and radiation in the "sandwich" method for high risk endometrial carcinoma.

OBJECTIVE: We sought to evaluate the outcomes and feasibility associated with delivering sequential chemotherapy and radiation in advanced stage endometrial cancer. METHODS: We conducted a retrospective analysis of patients treated at the University of Minnesota with sequential chemotherapy and radiation for advanced stage endometrial cancer from 1999 to 2007. Inclusion criteria were endometrial cancer patients treated with comprehensive surgical staging followed by adjuvant therapy consisting of sequential chemotherapy, radiation, and consolidation chemotherapy in a "sandwich" fashion. Progression free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier (KM) method. RESULTS: Twenty-three patients met entry criteria and were included in the analysis. The median age was 57 years (range 28-78). The majority of patients were stage III (78%) and the most common histologic type was serous (52%). The combination of a taxane and carboplatin was administered in 100% of cases. All planned cycles of chemotherapy were completed (100%) with the majority being prescribed six cycles (82%). Of the 23 patients, 5 progressed of which 3 died during the follow up period. The KM estimate of 1, 3, and 5 year PFS is 100%, 80%, and 74%, respectively. The KM estimate for 1, 3, and 5 year OS is 100%, 88% and 79%, respectively. CONCLUSION: Adjuvant therapy delivered in a "sandwich" fashion was feasible, well-tolerated and resulted in excellent long-term progression free and overall survival. A prospective study is currently ongoing at our institution.

Influence of Total Body Irradiation Dose Rate on Idiopathic Pneumonia Syndrome in Acute Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation.

PURPOSE: To determine the relationship between dose rate and other factors in the development of idiopathic pneumonia syndrome (IPS) in patients with acute lymphoblastic leukemia or acute myeloid leukemia who are undergoing total body irradiation (TBI)-based myeloablative conditioning for allogeneic hematopoietic cell transplantation (HCT). METHODS AND MATERIALS: From 2006 to 2016, 202 patients with acute leukemia (111 acute lymphoblastic leukemia, 91 acute myeloid leukemia) ranging in age from 1 to 57 years (median, 25 years) underwent allogeneic HCT at University of Minnesota. Pretransplantation conditioning included cyclophosphamide (120 mg/kg) with (68%) or without fludarabine (75 mg/m2) followed by 13.2 Gy TBI given in 8 twice-daily fractions of 1.65 Gy over 4 days. Dose rate varied based on linear accelerator availability and ranged from 8.7 to 19.2 cGy/min. Patients were stratified by receipt of high-dose-rate (HDR; >15 cGy/min; 56%) or low-dose-rate (LDR; ≤15 cGy/min; 44%) TBI for all 8 fractions. IPS was defined as pulmonary injury based on clinical symptoms, radiographic evidence, or pulmonary function testing within 100 days of HCT in the absence of concurrent infection. RESULTS: IPS developed in 42 patients (21%) between 4 and 73 days (median, 16 days) after transplantation. HDR TBI was associated with a higher rate of IPS compared with LDR TBI (29% vs 10%; P < .01). On multiple regression analysis, HDR remained a significant predictor of IPS (hazard ratio, 2.6; 95% confidence interval, 1.2-5.3; P = .01), and this led to inferior 1-year overall survival (60% vs 76%; P = .01) and increased 1-year nonrelapse mortality (28% vs 15%; P = .02). CONCLUSIONS: TBI dose rates ≤15 cGy/min reduce the risk of posttransplantation IPS and improve overall survival. LDR TBI should be strongly considered as an easily implemented parameter to improve the safety of pretransplantation TBI-based conditioning.

Reoxygenation and Repopulation of Tumor Cells after Ablative Hypofractionated Radiotherapy (SBRT and SRS) in Murine Tumors.

In this work, we investigated the change in tumor microenvironment caused by semi-ablative high-dose irradiation and its implication on tumor cell survival, reoxygenation of hypoxic cells and repopulation in FSaII tumors grown subcutaneously in the hind legs of C3H mice. Tumors were exposed to 10-30 Gy of X-ray radiation in a single exposure, and the vascularity and blood perfusion were assessed based on the levels of CD31 expression and Hoechst 33342 perfusion, respectively. The tumor hypoxia was assessed by staining for pimonidazole adduct formation and the expression of hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase 9 (CA9). Tumor cell survival was determined using in vivo-in vitro excision assay method. The proportion of hypoxic cells in the tumor was determined from the surviving cell fraction in tumors exposed to a test dose under aerobic and hypoxic conditions. Radiation expsoure markedly reduced the functional vascularity and blood perfusion, and profoundly increased the expression of HIF-1α and CA9 pointing to an increase in tumor hypoxia. The overall clonogenic cell survival progressively decreased during 2-5 days postirradiation, most likely due to the radiation-induced vascular dysfunction. In turn, the proportion of surviving hypoxic cells decreased over several days postirradiation, presumably due to reoxygenation of hypoxic cells. The oxygen supplied through small fractions of blood vessels that survived the high-dose exposure, together with a reduction of oxygen consumption due to massive cell death, appeared to be the cause of the reoxygenation of hypoxic cells. The surviving tumor cells then subsequently repopulated. The findings from this study using a murine tumor model suggest that the efficacy of stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) may be significantly improved by allowing an inter-fraction time for reoxygenation while avoiding repopulation.

Allogeneic hematopoietic cell transplantation in children with relapsed acute lymphoblastic leukemia isolated to the central nervous system.

Allogeneic hematopoietic cell transplantation (HCT) is the standard of care for pediatric patients with early medullary relapse of acute lymphoblastic leukemia (ALL). Most patients with isolated central nervous system (CNS) relapse have good outcomes when treated with intrathecal and systemic chemotherapy followed by irradiation to the neuroaxis. However, the role of HCT remains unclear for those patients with early isolated CNS relapse (<18 months) or who had high risk disease at diagnosis. We therefore compared the HCT outcomes of 116 children treated at the University of Minnesota from 1991 to 2006 with relapsed ALL involving the CNS alone (CNS, n = 14), the bone marrow alone (BM, n = 85), or both bone marrow and CNS (BM + CNS, n = 17). There were no significant differences among groups in age at diagnosis or transplant, length of first complete remission (CR1), remission status (CR2 versus >or=CR3), graft source, or preparative regimen. The incidence of acute GVHD was similar between groups. Patients with isolated CNS relapse had the lowest cumulative incidence of mortality following transplant (CNS: 0%, BM: 19%, BM + CNS: 29%, P = .03) and relapse (CNS: 0% BM: 30%, BM + CNS: 12%, at 2 years, P = .01) and highest leukemia-free survival (CNS: 91%, BM: 35%, BM + CNS: 46%, P < .01) at 5 years. Risk factors for poor survival were: T cell leukemia or BCR-ABL gene rearrangement, history of marrow relapse, and receipt of HLA-mismatched marrow. These data support the use of allogeneic HCT in the treatment of children with poor prognosis isolated CNS relapse.

Consolidative Radiotherapy After Autologous Stem Cell Transplantation for Relapsed or Refractory Diffuse Large B-cell Lymphoma.

INTRODUCTION: We evaluated the role of consolidative radiotherapy (RT) for patients undergoing high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: We reviewed the medical records of 72 consecutive patients who had undergone ASCT for relapsed or refractory DLBCL at our institution from 2006 to 2014. Pretransplant conditioning consisted of HDC and total body irradiation. Of the 72 patients, 13 received post-transplant consolidative RT at the discretion of the consulted radiation oncologist. RESULTS: Consolidative RT was associated with significantly improved 2-year locoregional control (LRC) (92% vs. 68%; P = .04). However, no difference was seen in either the 2-year progression-free survival (PFS) (69% vs. 54%; P = .25) or overall survival (OS) (85% vs. 59%; P = .44). Analysis of the subgroup of 19 patients with persistent residual masses ≥ 2 cm on post-transplant imaging demonstrated a significant improvement in LRC (100% vs. 36%; P < .01), PFS (88% vs. 27%; P = .01), and OS (100% vs. 45%; P = .02) with consolidative RT. CONCLUSION: The use of consolidative RT after HDC and ASCT for relapsed or refractory DLBCL appears to significantly improve LRC. For patients with masses ≥ 2 cm after ASCT, improved 2-year PFS and OS were seen. Prospective trials are needed to further identify the patients who would derive the most benefit from consolidative RT in the ASCT setting.

Treatment of a facial nerve neuroma with fractionated stereotactic radiotherapy.

BACKGROUND: Facial nerve neuromas are extremely rare and are often mistaken for acoustic neuromas when located near the vestibular nerve. Usually presenting with facial weakness and hearing loss, facial nerve neuromas of the cerebellopontine angle have commonly been managed by surgery. We present the first reported case of a facial nerve neuroma treated with fractionated stereotactic radiotherapy (FSRT). METHODS: The patient was a 40-year-old woman who presented with tinnitus, dizziness and decreased hearing that was associated with a right intracanalicular mass on magnetic resonance imaging (MRI). She underwent a middle fossa craniotomy only to reveal a facial nerve tumor rather than an acoustic neuroma that was not resected due to the high risk of facial paralysis. Following surgery, her facial function worsened and was associated with tumor enlargement on MRI. She was referred for FSRT and received 54 Gy in daily 1.8-Gy fractions with a prescription isodose line of 90%. RESULTS: Three months after treatment she had no worsening of her pretreatment symptoms, and at the 1-year follow-up, she experienced facial weakness improvement accompanied by an absence of tumor growth on MRI. These clinical and imaging findings persisted at 48 months of follow-up. CONCLUSION: In the first report of a facial nerve neuroma treated with FSRT, this treatment resulted in excellent long-term (4-year) tumor control with improvement of pretreatment symptomatology and absence of morbidity. This report demonstrates the potential for using FSRT to treat facial nerve neuromas of the cerebellopontine angle that could otherwise be associated with significant operative morbidity.

Role of Consolidative Radiation Therapy After Autologous Hematopoietic Cell Transplantation for the Treatment of Relapsed or Refractory Hodgkin Lymphoma.

PURPOSE: To evaluate the role of the addition of consolidative radiation therapy after high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT) for relapsed or refractory Hodgkin lymphoma (HL). METHODS AND MATERIALS: Medical records were reviewed from a total of 80 consecutive patients who underwent high-dose chemotherapy with AHCT treated under a single protocol at University of Minnesota between November 2005 and January 2014. Of these, 32 patients received radiation therapy after AHCT as planned consolidation. RESULTS: At a median follow-up of 25 months, the 2-year overall survival (OS) and progression-free survival (PFS) for the entire cohort was 96% and 52%, respectively. Consolidative radiation therapy was found to significantly improve the 2-year PFS (67% vs 42%, P<.01) without a significant change in OS (100% vs 93%, P=.15). On subgroup analysis, consolidative radiation therapy was shown to improve PFS in patients with bulky disease (62% vs 39%, P=.02), B-symptoms (48% vs 28%, P=.05), primary refractory disease (47% vs 32%, P=.02), and those with a partial response on pretransplant imaging (47% vs 32%, P=.02). The improvement seen on 2-year PFS with consolidative radiation therapy remained significant on multivariate analysis (hazard ratio 4.64, 95% confidence interval 1.98-10.88). Minimal toxicity was observed among the patients receiving radiation therapy. CONCLUSIONS: The addition of consolidative radiation therapy after high-dose chemotherapy and AHCT demonstrated a significant improvement in 2-year PFS and no impact on OS. Radiation therapy was well tolerated, with minimal toxicity. Our study supports a role of consolidative radiation therapy in patients with HL treated with AHCT.

Fractionated stereotactic radiotherapy for pediatric patients with retinoblastoma.

In this report we discuss the application of a modified Gill-Thomas-Cosman (GTC) relocatable head frame to enable fractionated stereotactic radiotherapy (SRT) of infants under anesthesia. This system has been used to treat two infants, ages 12 and 18 months for bilateral retinoblastoma on a Varian 6/100 linear accelerator. The GTC head frame was used to reproduceably position and treat the orbits of these children to between 2520 and 3960 cGy in 180 cGy fractions. A standard head and neck tray, with accompanying thermoplastic mask, was adapted to mount to the head frame to enable these treatments. We found the maximum average deviation in the repeat fixations, as compared with the initial fitting data, to be +/- 2 mm. The overall average difference and standard deviation in measurement was 0.47 +/- 0.63 mm for the first case, and 0.19 +/- 0.94 mm for the second case with a combined average of 0.35 +/- 0.79 mm overall from a total of 381 point measurements. The stereotactic treatment plan (Radionics) incorporated a single isocenter for each orbit and 3-4 arcs per isocenter. Inter-comparisons have been made between this technique and a standard lateral field technique, designed using the SRS planning system. Dose-volume histograms and corresponding normal tissue complication probabilities (NTCP) based on pediatric bone growth inhibition have been calculated for each method for the orbital bone areas. We have found that the NTCP is reduced from 95-100% in the standard treatment method to 16% or less with SRT. Use of the modified head frame provides excellent setup reproducibility, facilitates access to patients for anesthesia and reduces the chances of a poor cosmetic result in these growing children.

Fast Megavoltage Computed Tomography: A Rapid Imaging Method for Total Body or Marrow Irradiation in Helical Tomotherapy.

PURPOSE: Megavoltage computed tomographic (MVCT) imaging has been widely used for the 3-dimensional (3-D) setup of patients treated with helical tomotherapy (HT). One drawback of MVCT is its very long imaging time, the result of slow couch speeds of approximately 1 mm/s, which can be difficult for the patient to tolerate. We sought to develop an MVCT imaging method allowing faster couch speeds and to assess its accuracy for image guidance for HT. METHODS AND MATERIALS: Three cadavers were scanned 4 times with couch speeds of 1, 2, 3, and 4 mm/s. The resulting MVCT images were reconstructed using an iterative reconstruction (IR) algorithm with a penalty term of total variation and with a conventional filtered back projection (FBP) algorithm. The MVCT images were registered with kilovoltage CT images, and the registration errors from the 2 reconstruction algorithms were compared. This fast MVCT imaging was tested in 3 cases of total marrow irradiation as a clinical trial. RESULTS: The 3-D registration errors of the MVCT images reconstructed with the IR algorithm were smaller than the errors of images reconstructed with the FBP algorithm at fast couch speeds (2, 3, 4 mm/s). The scan time and imaging dose at a speed of 4 mm/s were reduced to 30% of those from a conventional coarse mode scan. For the patient imaging, faster MVCT (3 mm/s couch speed) scanning reduced the imaging time and still generated images useful for anatomic registration. CONCLUSIONS: Fast MVCT with the IR algorithm is clinically feasible for large 3-D target localization, which may reduce the overall time for the treatment procedure. This technique may also be useful for calculating daily dose distributions or organ motion analyses in HT treatment over a wide area. Automated integration of this imaging is at least needed to further assess its clinical benefits.

BRAF Mutation Is Associated with Improved Local Control of Melanoma Brain Metastases Treated with Gamma Knife Radiosurgery.

OBJECTIVES: Evidence has implicated a possible role of tumor mutation status on local control (LC) with radiotherapy. BRAF is a proto-oncogene that is mutated in approximately 50% of patients with melanoma. We sought to analyze the influence of BRAF status on LC of melanoma brain metastases (MBM) following Gamma Knife radiosurgery (GK). METHODS: Among 125 patients treated with GK for MBM at our institution between 2006 and 2015, we identified 19 patients with 69 evaluable metastases whose BRAF mutation status was known and follow-up imaging was available. LC of individual metastases was compared based on BRAF mutation status using statistical techniques to control for measurements of multiple metastases within each patient. CNS progression was defined as either local failure or development of new lesions. RESULTS: Of the 69 metastases, BRAF was mutated in 30 and wild-type in 39. With a median follow-up of 30 months for all patients and a median follow-up of 5.5 months for treated lesions, 1-year LC was significantly better among metastases with mutated vs. wild-type BRAF (69 vs. 34%, RR = 0.3, 95% CI = 0.1-0.7, p = 0.01). BRAF mutation was found to be a significant predictor of LC after stereotactic radiosurgery (SRS) in both univariate [RR = 0.3 (95% CI 0.1-0.7, p = 0.01)] and multivariate [RR = 0.2 (95% CI 0.1-0.7, p = 0.01)] analyses. There was also a trend toward improved CNS progression free survival (PFS) at 1 year (26 vs. 0%, p = 0.06), favoring BRAF-mutated patients. CONCLUSION: In this retrospective study, MBM treated with GK had significantly improved LC for patients with BRAF mutation vs. wild-type. Our data suggest that BRAF mutation may sensitize tumors to radiosurgery, and that BRAF wild-type tumors may be more radioresistant.