Purpose To identify the independent risk factors for developing morbid hypothalamic obesity, to p... more Purpose To identify the independent risk factors for developing morbid hypothalamic obesity, to propose a predictive scoring system for morbid hypothalamic obesity, and to propose an algorithm for management in order to minimize the risk of developing morbid hypothalamic obesity in patients with pediatric craniopharyngioma. Methods A retrospective analysis of all pediatric craniopharyngioma patients diagnosed and treated at Boston Children's Hospital (BCH) between 1985 and 2017. Analysis of the data was conducted using IBM SPSS Statistics. Results We identified 105 patients, 90 (47 males and 43 females) fulfilled the inclusion criteria. The median age of patients at time of diagnosis was 8.4 years. The median follow-up was 10.6 years. Morbid hypothalamic obesity was evident in 28 (31.1%) patients at the last follow-up visit. Age of patients at time of diagnosis > 10 years (P = 0.023), preoperative body mass index (BMI) > 95th percentile (P = 0.006), and preoperative papilledema (P < 0.001) were the independent risk factors for developing morbid hypothalamic obesity. Conclusion We developed a unique predictive scoring system in order to differentiate between patients with and without high risk for developing morbid hypothalamic obesity.
International Journal of Radiation Oncology Biology Physics, Sep 1, 2019
Compared to photon radiotherapy (XRT), proton radiotherapy (PRT) is postulated to improve long-te... more Compared to photon radiotherapy (XRT), proton radiotherapy (PRT) is postulated to improve long-term toxicity for pediatric patients with brain tumors; however, the acute hematologic toxicity of craniospinal irradiation (CSI) in pediatric patients has not been wellcharacterized. We aimed to examine the hematologic side-effects of proton and photon radiotherapy (RT), in pediatric patients with medulloblastoma receiving CSI plus tumor bed or whole posterior fossa boost as part of standard of care. Materials/Methods: Clinical and treatment characteristics were recorded for 97 patients diagnosed with medulloblastoma before 25 years of age who received CSI without concurrent chemotherapy or with concurrent single-agent vincristine from 2007-2017. 60 patients received PRT and 37 received XRT. Patients who received induction chemotherapy before RT were excluded. Clinical and treatment characteristics between the PRT and XRT cohorts were compared using Fisher exact tests or Chi-square tests. Overall survival (OS) was determined by Kaplan-Meier curves with logrank test. Nadir hematologic toxicity during the 6-week course of RT was graded according to the NCI CTCAE v5. Comparisons of blood counts over 6-week course of RT were conducted using multiple t-tests with Bonferroni corrections. Results: Median age of patients receiving proton and photon CSI was 7.5 years (range: 3.5-22.7) and 9.9 years (range: 3.6-19.5), respectively (pZ0.054). Most patients were diagnosed with standard risk medulloblastoma with 86.7% and 89.2% for PRT and XRT cohorts, respectively (p>0.05). Median total dose was 54.0 Gy/CGE and median CSI dose was 23.4 Gy/CGE for both cohorts. 7 patients (11.7%) and 2 patients (5.4%) in PRT and XRT, respectively, did not receive concurrent vincristine (p>0.05). No difference in overall survival was observed. While weekly white blood cell counts did not differ between the PRT and XRT cohorts, patients receiving PRT had significantly higher lymphocyte counts during weeks 1-6 of RT (p<0.01). We also found that 45 patients (76.3%) and all patients (100%) in PRT and XRT cohorts, respectively, had grade 3 lymphopenia (p<0.001). Weekly platelet counts were significantly higher in the proton cohort compared to the photon cohort in weeks 3-6 of RT (p<0.001). 17 patients (28.3%) in the PRT cohort and 17 patients (45.9%) in the XRT cohort had grade 1 thrombocytopenia (pZ0.09). Conclusion: Patients who receive CSI using PRT experience decreased hematologic toxicity compared to those receiving XRT.
International Journal of Radiation Oncology*Biology*Physics, 2017
associated with OS. The actuarial rate of grade !3 necrosis was 7.0% (95% CI Z 3.3-15.0), with me... more associated with OS. The actuarial rate of grade !3 necrosis was 7.0% (95% CI Z 3.3-15.0), with median time of onset of 8.6 months after RT2. Conclusion: Re-irradiation for relapsed pediatric ependymoma results in long-term survival for many patients. Patients with 1q gain are at risk of distant failure. RT2 CSI changes the pattern of failure in patients with local-only failure after RT1, with no distant failures observed. Novel biomarkers to select patients who benefit most from CSI are needed.
International Journal of Radiation Oncology Biology Physics, Oct 1, 2016
Forty-four out of 64 (69%) trial reports included target volume definition. All trials reported t... more Forty-four out of 64 (69%) trial reports included target volume definition. All trials reported total radiation dose and fractionation. Radiation prescription point was mentioned in 11 (17%) trials. In terms of QA, 17 (27%) trials specified undergoing a QA process and 4 (6%) trials specified adherence to the QA process. Only 1 trial reported all six quality measures. Conclusion: The quality of radiotherapy reporting in head and neck cancer RCTs is poor. Future research should focus on how to improve the quality of radiotherapy reporting in order to allow the accurate replication of the radiotherapy technique for all patients undergoing head and neck radiotherapy.
Clinical and Translational Radiation Oncology, 2021
Background and purpose: Magnetic resonance guided radiotherapy (MRgRT) has been successfully impl... more Background and purpose: Magnetic resonance guided radiotherapy (MRgRT) has been successfully implemented for several routine clinical applications in adult patients. The purpose of this study is to map the potential benefit of MRgRT on toxicity reduction and outcome in pediatric patients treated with curative intent for primary and metastatic sites. Materials and methods: Between May and August 2020, a survey was distributed among SIOPE-and COGaffiliated radiotherapy departments, treating at least 25 pediatrics patients annually and being (candidate) users of a MRgRT system. The survey consisted of a table with 45 rows (clinical scenarios for primary (n = 28) and metastatic (n = 17) tumors) and 7 columns (toxicity reduction, outcome improvement, PTV margin reduction, target volume daily adaptation, online re-planning, intrafraction motion compensation and on-board functional imaging) and the option to answer by 'yes/no'. Afterwards, the Dutch national radiotherapy cohort was used to estimate the percentage of pediatric treatments that may benefit from MRgRT. Results: The survey was completed by 12/17 (71% response rate) institutions meeting the survey inclusion criteria. Responders indicated an 'expected benefit' from MRgRT for toxicity/outcome in 7% (for thoracic lymphomas and abdominal rhabdomyosarcomas)/0% and 18% (for mediastinal lymph nodes, lymph nodes located in the liver/splenic hilum, and liver metastases)/0% of the considered scenarios for the primary and metastatic tumor sites, respectively, and a 'possible benefit' was estimated in 64%/46% and 47%/59% of the scenarios. When translating the survey outcome into a clinical perspective a toxicity/outcome benefit, either expected or possible, was anticipated for 55%/24% of primary sites and 62%/38% of the metastatic sites. Conclusion: Although the benefit of MRgRT in pediatric radiation oncology is estimated to be modest, the potential role for reducing toxicity and improving clinical outcomes warrants further investigation. This fits best within the context of prospective studies or registration trials.
1 on the challenges and future approaches to curing patients with primary brain tumours. We congr... more 1 on the challenges and future approaches to curing patients with primary brain tumours. We congratulate Cancer Research UK (CRUK) on convening this group of expert clinicians and scientists, and we applaud the authors' elegant synthesis of multiple complex issues. However, we note that among the disciplines represented by the 26 authors of this article, expertise in radiation oncology is conspicuously absent. The authors assert that CRUK "convened an international panel of brain cancer researchers with interests in neurobiology, preclinical tumour modelling, genomics, pharmaco logy, drug discovery and/or development, neuropathology, neurosurgery, imaging, radiotherapy and medical oncology, with the task of identifying the most important challenges that must be overcome if we are to eventually be in the position to cure all patients with a brain tumour" 1. Aside from radiation oncology, all of the neurooncological subspecialties listed above were represented. Beyond issues of author representation, radiotherapy is only discussed in the context of efforts to reduce the dose of radiation or to eliminate radiotherapy entirely from the treatment of patients with certain disease characteristics. Even in clinical situations in which attempts to reduce the radiation dose have failed (such as medulloblastoma) 2,3 , the authors contend that this is a function of
Developmental Medicine & Child Neurology, 2017
with CP and presenting with CSS was much lower in this study cohort (54.5y). Due to the high prev... more with CP and presenting with CSS was much lower in this study cohort (54.5y). Due to the high prevalence of documented CSS in this adult cohort (7.5%), which is likely an underestimate, we propose active X-ray screening for CSS in patients with CP over 50 years of age. Although our study identified several associations with CSS (depression, benzodizapenes, antispastics, analgesics), further research is necessary to identify the pathophysiology of CSS development and to clarify the risk factors for patients with CP.
International Journal of Radiation Oncology*Biology*Physics, 2014
student t-test was used to identify the significant difference in mean percent agreement between ... more student t-test was used to identify the significant difference in mean percent agreement between novice and experts, and between sets. Results: There was no significant difference in mean agreement with experts opinion by the novice for the two sets (p Z 0.05, Table 1). Conclusions: Study results support the reliable use of HFACS model for the Radiation Oncology-Incident reporting and Learning System. We recognize that there are inherent limitations to this study (e.g. small samples of incidents with unequal representation of all categories and layers of the HFACS model, small number of participants, etc.). Nevertheless, this pilot study is a reasonable first step to provide some confidence that the HFACS can be reliably used for analysis of radiation oncology incidents.
International Journal of Radiation Oncology*Biology*Physics, 1993
To determine the efficacy and safety of subcutaneous administration of recombinant human erythrop... more To determine the efficacy and safety of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) at a dose of 200 units/kg/day to cancer patients undergoing radiotherapy. This is a randomized, open-labeled, Phase II study. Only patients receiving radiotherapy +/- chemotherapy are included. Eligibility is restricted to patients with lung cancer, carcinoma of the uterine cervix, prostatic adenocarcinoma, or adenocarcinoma of the breast. Patients in the control and treatment arms receive radiotherapy with similar policies, and their doses of radiotherapy and treatment volumes are determined by the site and stage of the disease. Patients in the &amp;amp;amp;amp;amp;amp;quot;treatment arm&amp;amp;amp;amp;amp;amp;quot; receive 200 units/kg/day of r-HuEPO, subcutaneously, five times a week with iron (Fe SO4, 325 mg. p.o., t.i.d.) supplements. Complete blood counts are obtained weekly. Quality of life is assessed weekly by the patients themselves by a few simple entries on an analog scale. Twenty-six patients have been entered in the study so far. Twelve patients were placed in the control arm and 14 in the treatment arm. Pre-randomization demographic and laboratory mean values in both arms were comparable, with none of 16 parameters compared reaching statistical significance. Our results can be summarized as follows: (a) Mean hemoglobin, hematocrit, and red blood cell values increased gradually in the treatment arm patients. Week-by-week comparison showed that mean values for these three parameters were significantly higher in the treatment arm than in the control arm. For example, the p values for the differences in hemoglobin mean values for weeks 1-6 were 0.015, 0.002, 0.003, 0.0002, 0.0006, and 0.007, respectively. Similar trends were observed for red blood cells and the hematocrit values. (b) No significant toxicity has been encountered. (c) No significant differences in the mean values of white blood cells and platelet counts were seen between the two arms. The values of these two parameters declined over the course of radiotherapy. (d) The mean weekly increase in hemoglobin levels in the treatment arm was 0.43 gm/dl. (a) The safety and efficacy of r-HuEPO, with 200 units/kg/day of subcutaneous administration, have been confirmed in our study group. (b) However, the rate of increase in hemoglobin levels is not very rapid with the doses used. (c) Dose escalation studies are needed for determination of the feasibility of improving hemoglobin levels by about 1 gm/dl/week. (d) The question whether improvement in hemoglobin with r-HuEPO therapy can improve outcome by improving tumor oxygenation needs to be studied in carcinoma of the uterine cervix and squamous cell carcinoma of the head and neck.
This study aims to identify factors that predict outcome after salvage therapy for patients with ... more This study aims to identify factors that predict outcome after salvage therapy for patients with Hodgkin disease (HD) in first relapse. Between 1969 and 1985, 627 patients with Pathologic Stage IA-IIIB HD were treated at the Joint Center for Radiation Therapy. With a median follow-up time for survivors of 135 months, 138 patients (22%) have experienced relapse. One hundred twenty-seven of these were retreated with curative intent and form the basis of this report. The complete response (CR) rate after retreatment was 79%. The 10-year actuarial freedom from second relapse (FSR) was 53%, and the 10-year survival rate from the time of first relapse was 57%. For patients experiencing relapse after initial radiation therapy (RT) alone (n = 110), the 10-year FSR and overall survival rates were 58% and 62%, respectively. Histologic type was the single most important prognostic factor for second CR rate, FSR, and survival. Patients with nodular sclerosis or lymphocyte predominant (NS/LP) histologic type had a 91% second CR rate, 67% 10-year FSR rate, and 75% 10-year survival rate, compared with 66%, 44%, and 43%, respectively, for patients with mixed cellularity or lymphocyte depleted (MC/LD) histologic type. For patients who experienced relapse after initial combined modality therapy (CMT; n = 17), the 10-year FSR and overall survival rates were 13% and 24%, respectively. This study demonstrates that patients who experience relapse after RT alone can be effectively salvaged with combination chemotherapy. The implications of these results for clinical decision making are discussed.
PURPOSE: To analyze the long-term survival and the pattern and timing of excess mortality in pati... more PURPOSE: To analyze the long-term survival and the pattern and timing of excess mortality in patients with early-stage Hodgkin’s disease. PATIENTS AND METHODS: Between 1969 and 1997, 1,080 patients age 50 or younger were treated for clinical stage IA to IIB Hodgkin’s disease. Overall survival was determined, and prognostic factors were assessed. Relative risk and absolute excess risk (AR) of mortality were calculated for the entire cohort and by prognostic groups (on the basis of B symptoms, mediastinal status, and number of sites, modified from the European Organization for Research and Treatment of Cancer). RESULTS: The median follow-up was 12 years. The 15- and 20-year Kaplan-Meier survival estimates were 84% and 78%, respectively. Cox proportional hazards models showed that number of involved sites (P = .006), mediastinal status (P = .02), and histology (P = .02) were independent predictors of death from all causes. The AR of mortality in patients with a favorable prognosis increased over time, whereas for those with an unfavorable prognosis, the AR peaked in the first 5 years, predominantly from Hodgkin’s disease. The relative risk of mortality from all causes, causes other than Hodgkin’s disease, second tumors, and cardiac disease remained significantly elevated more than 20 years after treatment. CONCLUSION: Patients treated for early-stage Hodgkin’s disease have a sustained excess mortality risk despite good control of the disease. Treatment reduction efforts in patients with early-stage, favorable-prognosis disease should continue, but for patients with an unfavorable prognosis, modified treatment may not be advisable. The excess mortality noted beyond two decades underscores the importance of long-term follow-up care in patients treated for Hodgkin’s disease.
International Journal of Radiation Oncology Biology Physics, Oct 1, 2017
determining propensity for metastatic site (MS) failure (MSF). This retrospective study sought to... more determining propensity for metastatic site (MS) failure (MSF). This retrospective study sought to evaluate the utility of MIBG to identify patients and metastatic sites at highest risk for MSF. Materials/Methods: Seventy-six patients with high-risk neuroblastoma treated on prospective trials at a single institution from 1997 to 2014 were included. Patients received induction chemotherapy, primary site surgery, and myeloablative chemotherapy with autologous stem cell rescue (AuSCR) and maintenance chemotherapy. Primary and metastatic site radiotherapy (RT) was applied according to the specific protocol. CT and I-123 MIBG studies were reviewed to characterize metastatic site location, avidity, response, and failure. MSF1 was progression at a site identified prior to any therapy. MSF2 was progression at a previously undocumented site. Curie scores were calculated for 554 scans completed at diagnosis, post-induction, after AuSCR, and at the time of MSF. Progression-free (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazards frailty regression (cphfR) was used to evaluate the role of MIBG avidity on the hazard for MSF. Results: The median PFS and OS were 24.1 months (95% CI 16.5-38.7) and 61 months (95% CI 42.6-NR). Patients with Curie scores 2 who underwent AuSCR and maintenance chemotherapy had improved 2yr PFS compared to those with Curie scores >2 (90% vs. 76%, P Z 0.1) and displayed a non-significant trend toward reduced Curie score at progression. MSF occurred in 42 (55%) patients at 180 sites. MSF1 was observed at 77 (43%) and MFS2 at 103 (57%) sites. Combined site failure occurred in 14 (18%). Ten patients received consolidative RT to 30 MS. Irradiated MS were avid at diagnosis, post-induction, and after AuSCR in 12, 7, and 11 cases, respectively. MSF1 occurred in post-induction MIBG avid lesions in 68 of 81 (84%) and 12 of 14 (85%) non-RT and RT MS, respectively. The 3 year MSF rate for sites that were avid at diagnosis, post-induction, and after AuSCR was 14%, 26.7%, and 47%, respectively, while the median time to MSF for new sites was 9.6 months (95% CI 7.2-14.3). CphfR showed an increased hazard for MSF1 in MIBG avid sites post-induction (HR 4.9, 95% CI 1.1-20.9, P Z 0.03) and after AuSCR (HR 7.3 95% CI 1.8-30.2, P Z 0.006). Consolidative RT to 23.4 Gy did not modify the hazard for MSF. Conclusion: Curie scoring identified patients with improved survival and reduced disease burden at failure. Progression at previously undocumented sites (MSF2) occurred much earlier relative to sites identified prior to therapy (MSF1). Metastatic lesions that remained MIBG avid following induction chemotherapy and after AuSCR had an increased hazard for MSF. Consolidative site RT to 23.4 Gy did not improve metastatic site control.
Background: Children's Oncology Group study AEWS0031 demonstrated superior 5-year event-free surv... more Background: Children's Oncology Group study AEWS0031 demonstrated superior 5-year event-free survival (EFS) in patients with localized Ewing sarcoma (ES) receiving interval-compressed (IC) chemotherapy (every 2 weeks) compared to standard timing (ST) chemotherapy (every 3 weeks). We assessed the long-term outcome of patients treated on AEWS0031 to determine whether the survival advantage of IC chemotherapy was maintained at 10 years. Methods: AEWS0031 enrolled 568 eligible patients with localized ES. Patients were stratified into four groups by age (<18 years and ≥ 18 years) and primary site (pelvic and non-pelvic), and randomized to receive 14 cycles of alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide given every 3 weeks (ST; Regimen A) vs. every 2 weeks (IC; Regimen B). For this updated report, one patient was excluded due to uncertainty of original diagnosis giving a total of 567 patients in this analysis. Data for tumor measurements and histologic response were collected retrospectively from institutional reports. EFS and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test and Gray's test for cumulative incidence (CI). Results: The 10-year EFS for patients treated with IC chemo was 70% compared to 61% for ST chemo (p = 0.03), and the OS was 76% with IC chemo compared to 69% for ST chemo (p = 0.03). The 10-year CI of second malignant neoplasms (SMNs) for ST chemo was 4.2% [95% confidence interval: 2.4-7.5] compared to 3.2% (95% confidence interval: 1.6-6.3) for IC chemo (p = 0.5). There was a trend towards improved 10-year EFS in those receiving IC chemo both with non-pelvic (N = 477; 71% vs. 64%) and pelvic (N = 90; 67% vs. 43%) primary tumors. Similarly, the 10-year EFS was superior for patients treated with IC chemo in both the < 18 years (N = 500; 73% vs. 64%) and ≥ 18 years (N = 67; 53% vs. 37%) age groups. Among the 184 patients with available histologic response data, the 10-year EFS from the time of local control was 76% for those with < 10% viable tumor and 56% for those with ≥ 10% viable tumor (p = 0.01). Additional analysis comparing patients with any viable tumor vs. no viable tumor (NVT) by treatment regimen demonstrated that patients with NVT who received IC chemo had 10-year EFS and OS from local control of 91% and 97%, respectively. In the 210 patients for whom tumor volume calculations were possible, there was no difference in the 10-year EFS for patients with tumors < 200 mL vs. ≥ 200 mL. Conclusions: With longer term follow-up, IC chemotherapy for localized ES is associated with superior EFS and OS without an increase in SMNs. This study suggests patients ≥ 18 years with poor necrosis or pelvic primary tumors remain at high risk for relapse despite IC chemo, emphasizing the need for alternative treatment strategies to improve their outcomes. Clinical trial information: NCT00006734
OBJECTIVE The goal in this study was to outline unique differences between radiation-induced and ... more OBJECTIVE The goal in this study was to outline unique differences between radiation-induced and nonradiation-induced pediatric meningiomas and to identify independent risk factors of tumor recurrence/progression. METHODS This is a retrospective cohort study of all pediatric meningiomas diagnosed and surgically treated at the authors’ institution between 1993 and 2017. Multivariable Cox regression was applied to identify independent risk factors for tumor recurrence/progression. RESULTS Thirty-five patients were identified. The primary etiology was nonradiation-induced (n = 24: n = 3 with neurofibromatosis type 2) or radiation-induced (n = 11: acute lymphoblastic leukemia [n = 5], medulloblastoma [n = 4], germ cell tumor [n = 1], and primitive neuroectodermal tumor [n = 1]) meningioma. The mean age at time of diagnosis was 10.7 ± 5.7 years for nonradiation-induced and 17.3 ± 3.5 years for radiation-induced meningiomas. Overall, 8/24 patients with nonradiation-induced meningioma expe...
ObjectivesPalliative radiation therapy (pRT) is often used to improve quality of life for pediatr... more ObjectivesPalliative radiation therapy (pRT) is often used to improve quality of life for pediatric patients. Though palliative doses are generally lower than those for cure, pRT may still introduce undesirable effects. The decision to pursue additional therapy for a child may be challenging and depends on parents’ knowledge and expectations. The goal of this study was to explore parental perceptions of pRT.MethodsTwenty‐eight children referred for pRT were enrolled in our prospective study. Parents were counseled regarding the indication and expected outcomes. They then completed a series of questionnaires to assess their understanding of pRT, side effects that their child experienced, and how the outcomes compared to their expectations.ResultsThe majority of parents listed pain relief and addressing new disease as the main indication for pRT. When asked about expectations, the majority chose improvement in quality of life and prolongation of their child's life. Interestingly, ...
Purpose To identify the independent risk factors for developing morbid hypothalamic obesity, to p... more Purpose To identify the independent risk factors for developing morbid hypothalamic obesity, to propose a predictive scoring system for morbid hypothalamic obesity, and to propose an algorithm for management in order to minimize the risk of developing morbid hypothalamic obesity in patients with pediatric craniopharyngioma. Methods A retrospective analysis of all pediatric craniopharyngioma patients diagnosed and treated at Boston Children's Hospital (BCH) between 1985 and 2017. Analysis of the data was conducted using IBM SPSS Statistics. Results We identified 105 patients, 90 (47 males and 43 females) fulfilled the inclusion criteria. The median age of patients at time of diagnosis was 8.4 years. The median follow-up was 10.6 years. Morbid hypothalamic obesity was evident in 28 (31.1%) patients at the last follow-up visit. Age of patients at time of diagnosis > 10 years (P = 0.023), preoperative body mass index (BMI) > 95th percentile (P = 0.006), and preoperative papilledema (P < 0.001) were the independent risk factors for developing morbid hypothalamic obesity. Conclusion We developed a unique predictive scoring system in order to differentiate between patients with and without high risk for developing morbid hypothalamic obesity.
International Journal of Radiation Oncology Biology Physics, Sep 1, 2019
Compared to photon radiotherapy (XRT), proton radiotherapy (PRT) is postulated to improve long-te... more Compared to photon radiotherapy (XRT), proton radiotherapy (PRT) is postulated to improve long-term toxicity for pediatric patients with brain tumors; however, the acute hematologic toxicity of craniospinal irradiation (CSI) in pediatric patients has not been wellcharacterized. We aimed to examine the hematologic side-effects of proton and photon radiotherapy (RT), in pediatric patients with medulloblastoma receiving CSI plus tumor bed or whole posterior fossa boost as part of standard of care. Materials/Methods: Clinical and treatment characteristics were recorded for 97 patients diagnosed with medulloblastoma before 25 years of age who received CSI without concurrent chemotherapy or with concurrent single-agent vincristine from 2007-2017. 60 patients received PRT and 37 received XRT. Patients who received induction chemotherapy before RT were excluded. Clinical and treatment characteristics between the PRT and XRT cohorts were compared using Fisher exact tests or Chi-square tests. Overall survival (OS) was determined by Kaplan-Meier curves with logrank test. Nadir hematologic toxicity during the 6-week course of RT was graded according to the NCI CTCAE v5. Comparisons of blood counts over 6-week course of RT were conducted using multiple t-tests with Bonferroni corrections. Results: Median age of patients receiving proton and photon CSI was 7.5 years (range: 3.5-22.7) and 9.9 years (range: 3.6-19.5), respectively (pZ0.054). Most patients were diagnosed with standard risk medulloblastoma with 86.7% and 89.2% for PRT and XRT cohorts, respectively (p>0.05). Median total dose was 54.0 Gy/CGE and median CSI dose was 23.4 Gy/CGE for both cohorts. 7 patients (11.7%) and 2 patients (5.4%) in PRT and XRT, respectively, did not receive concurrent vincristine (p>0.05). No difference in overall survival was observed. While weekly white blood cell counts did not differ between the PRT and XRT cohorts, patients receiving PRT had significantly higher lymphocyte counts during weeks 1-6 of RT (p<0.01). We also found that 45 patients (76.3%) and all patients (100%) in PRT and XRT cohorts, respectively, had grade 3 lymphopenia (p<0.001). Weekly platelet counts were significantly higher in the proton cohort compared to the photon cohort in weeks 3-6 of RT (p<0.001). 17 patients (28.3%) in the PRT cohort and 17 patients (45.9%) in the XRT cohort had grade 1 thrombocytopenia (pZ0.09). Conclusion: Patients who receive CSI using PRT experience decreased hematologic toxicity compared to those receiving XRT.
International Journal of Radiation Oncology*Biology*Physics, 2017
associated with OS. The actuarial rate of grade !3 necrosis was 7.0% (95% CI Z 3.3-15.0), with me... more associated with OS. The actuarial rate of grade !3 necrosis was 7.0% (95% CI Z 3.3-15.0), with median time of onset of 8.6 months after RT2. Conclusion: Re-irradiation for relapsed pediatric ependymoma results in long-term survival for many patients. Patients with 1q gain are at risk of distant failure. RT2 CSI changes the pattern of failure in patients with local-only failure after RT1, with no distant failures observed. Novel biomarkers to select patients who benefit most from CSI are needed.
International Journal of Radiation Oncology Biology Physics, Oct 1, 2016
Forty-four out of 64 (69%) trial reports included target volume definition. All trials reported t... more Forty-four out of 64 (69%) trial reports included target volume definition. All trials reported total radiation dose and fractionation. Radiation prescription point was mentioned in 11 (17%) trials. In terms of QA, 17 (27%) trials specified undergoing a QA process and 4 (6%) trials specified adherence to the QA process. Only 1 trial reported all six quality measures. Conclusion: The quality of radiotherapy reporting in head and neck cancer RCTs is poor. Future research should focus on how to improve the quality of radiotherapy reporting in order to allow the accurate replication of the radiotherapy technique for all patients undergoing head and neck radiotherapy.
Clinical and Translational Radiation Oncology, 2021
Background and purpose: Magnetic resonance guided radiotherapy (MRgRT) has been successfully impl... more Background and purpose: Magnetic resonance guided radiotherapy (MRgRT) has been successfully implemented for several routine clinical applications in adult patients. The purpose of this study is to map the potential benefit of MRgRT on toxicity reduction and outcome in pediatric patients treated with curative intent for primary and metastatic sites. Materials and methods: Between May and August 2020, a survey was distributed among SIOPE-and COGaffiliated radiotherapy departments, treating at least 25 pediatrics patients annually and being (candidate) users of a MRgRT system. The survey consisted of a table with 45 rows (clinical scenarios for primary (n = 28) and metastatic (n = 17) tumors) and 7 columns (toxicity reduction, outcome improvement, PTV margin reduction, target volume daily adaptation, online re-planning, intrafraction motion compensation and on-board functional imaging) and the option to answer by 'yes/no'. Afterwards, the Dutch national radiotherapy cohort was used to estimate the percentage of pediatric treatments that may benefit from MRgRT. Results: The survey was completed by 12/17 (71% response rate) institutions meeting the survey inclusion criteria. Responders indicated an 'expected benefit' from MRgRT for toxicity/outcome in 7% (for thoracic lymphomas and abdominal rhabdomyosarcomas)/0% and 18% (for mediastinal lymph nodes, lymph nodes located in the liver/splenic hilum, and liver metastases)/0% of the considered scenarios for the primary and metastatic tumor sites, respectively, and a 'possible benefit' was estimated in 64%/46% and 47%/59% of the scenarios. When translating the survey outcome into a clinical perspective a toxicity/outcome benefit, either expected or possible, was anticipated for 55%/24% of primary sites and 62%/38% of the metastatic sites. Conclusion: Although the benefit of MRgRT in pediatric radiation oncology is estimated to be modest, the potential role for reducing toxicity and improving clinical outcomes warrants further investigation. This fits best within the context of prospective studies or registration trials.
1 on the challenges and future approaches to curing patients with primary brain tumours. We congr... more 1 on the challenges and future approaches to curing patients with primary brain tumours. We congratulate Cancer Research UK (CRUK) on convening this group of expert clinicians and scientists, and we applaud the authors' elegant synthesis of multiple complex issues. However, we note that among the disciplines represented by the 26 authors of this article, expertise in radiation oncology is conspicuously absent. The authors assert that CRUK "convened an international panel of brain cancer researchers with interests in neurobiology, preclinical tumour modelling, genomics, pharmaco logy, drug discovery and/or development, neuropathology, neurosurgery, imaging, radiotherapy and medical oncology, with the task of identifying the most important challenges that must be overcome if we are to eventually be in the position to cure all patients with a brain tumour" 1. Aside from radiation oncology, all of the neurooncological subspecialties listed above were represented. Beyond issues of author representation, radiotherapy is only discussed in the context of efforts to reduce the dose of radiation or to eliminate radiotherapy entirely from the treatment of patients with certain disease characteristics. Even in clinical situations in which attempts to reduce the radiation dose have failed (such as medulloblastoma) 2,3 , the authors contend that this is a function of
Developmental Medicine & Child Neurology, 2017
with CP and presenting with CSS was much lower in this study cohort (54.5y). Due to the high prev... more with CP and presenting with CSS was much lower in this study cohort (54.5y). Due to the high prevalence of documented CSS in this adult cohort (7.5%), which is likely an underestimate, we propose active X-ray screening for CSS in patients with CP over 50 years of age. Although our study identified several associations with CSS (depression, benzodizapenes, antispastics, analgesics), further research is necessary to identify the pathophysiology of CSS development and to clarify the risk factors for patients with CP.
International Journal of Radiation Oncology*Biology*Physics, 2014
student t-test was used to identify the significant difference in mean percent agreement between ... more student t-test was used to identify the significant difference in mean percent agreement between novice and experts, and between sets. Results: There was no significant difference in mean agreement with experts opinion by the novice for the two sets (p Z 0.05, Table 1). Conclusions: Study results support the reliable use of HFACS model for the Radiation Oncology-Incident reporting and Learning System. We recognize that there are inherent limitations to this study (e.g. small samples of incidents with unequal representation of all categories and layers of the HFACS model, small number of participants, etc.). Nevertheless, this pilot study is a reasonable first step to provide some confidence that the HFACS can be reliably used for analysis of radiation oncology incidents.
International Journal of Radiation Oncology*Biology*Physics, 1993
To determine the efficacy and safety of subcutaneous administration of recombinant human erythrop... more To determine the efficacy and safety of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) at a dose of 200 units/kg/day to cancer patients undergoing radiotherapy. This is a randomized, open-labeled, Phase II study. Only patients receiving radiotherapy +/- chemotherapy are included. Eligibility is restricted to patients with lung cancer, carcinoma of the uterine cervix, prostatic adenocarcinoma, or adenocarcinoma of the breast. Patients in the control and treatment arms receive radiotherapy with similar policies, and their doses of radiotherapy and treatment volumes are determined by the site and stage of the disease. Patients in the &amp;amp;amp;amp;amp;amp;quot;treatment arm&amp;amp;amp;amp;amp;amp;quot; receive 200 units/kg/day of r-HuEPO, subcutaneously, five times a week with iron (Fe SO4, 325 mg. p.o., t.i.d.) supplements. Complete blood counts are obtained weekly. Quality of life is assessed weekly by the patients themselves by a few simple entries on an analog scale. Twenty-six patients have been entered in the study so far. Twelve patients were placed in the control arm and 14 in the treatment arm. Pre-randomization demographic and laboratory mean values in both arms were comparable, with none of 16 parameters compared reaching statistical significance. Our results can be summarized as follows: (a) Mean hemoglobin, hematocrit, and red blood cell values increased gradually in the treatment arm patients. Week-by-week comparison showed that mean values for these three parameters were significantly higher in the treatment arm than in the control arm. For example, the p values for the differences in hemoglobin mean values for weeks 1-6 were 0.015, 0.002, 0.003, 0.0002, 0.0006, and 0.007, respectively. Similar trends were observed for red blood cells and the hematocrit values. (b) No significant toxicity has been encountered. (c) No significant differences in the mean values of white blood cells and platelet counts were seen between the two arms. The values of these two parameters declined over the course of radiotherapy. (d) The mean weekly increase in hemoglobin levels in the treatment arm was 0.43 gm/dl. (a) The safety and efficacy of r-HuEPO, with 200 units/kg/day of subcutaneous administration, have been confirmed in our study group. (b) However, the rate of increase in hemoglobin levels is not very rapid with the doses used. (c) Dose escalation studies are needed for determination of the feasibility of improving hemoglobin levels by about 1 gm/dl/week. (d) The question whether improvement in hemoglobin with r-HuEPO therapy can improve outcome by improving tumor oxygenation needs to be studied in carcinoma of the uterine cervix and squamous cell carcinoma of the head and neck.
This study aims to identify factors that predict outcome after salvage therapy for patients with ... more This study aims to identify factors that predict outcome after salvage therapy for patients with Hodgkin disease (HD) in first relapse. Between 1969 and 1985, 627 patients with Pathologic Stage IA-IIIB HD were treated at the Joint Center for Radiation Therapy. With a median follow-up time for survivors of 135 months, 138 patients (22%) have experienced relapse. One hundred twenty-seven of these were retreated with curative intent and form the basis of this report. The complete response (CR) rate after retreatment was 79%. The 10-year actuarial freedom from second relapse (FSR) was 53%, and the 10-year survival rate from the time of first relapse was 57%. For patients experiencing relapse after initial radiation therapy (RT) alone (n = 110), the 10-year FSR and overall survival rates were 58% and 62%, respectively. Histologic type was the single most important prognostic factor for second CR rate, FSR, and survival. Patients with nodular sclerosis or lymphocyte predominant (NS/LP) histologic type had a 91% second CR rate, 67% 10-year FSR rate, and 75% 10-year survival rate, compared with 66%, 44%, and 43%, respectively, for patients with mixed cellularity or lymphocyte depleted (MC/LD) histologic type. For patients who experienced relapse after initial combined modality therapy (CMT; n = 17), the 10-year FSR and overall survival rates were 13% and 24%, respectively. This study demonstrates that patients who experience relapse after RT alone can be effectively salvaged with combination chemotherapy. The implications of these results for clinical decision making are discussed.
PURPOSE: To analyze the long-term survival and the pattern and timing of excess mortality in pati... more PURPOSE: To analyze the long-term survival and the pattern and timing of excess mortality in patients with early-stage Hodgkin’s disease. PATIENTS AND METHODS: Between 1969 and 1997, 1,080 patients age 50 or younger were treated for clinical stage IA to IIB Hodgkin’s disease. Overall survival was determined, and prognostic factors were assessed. Relative risk and absolute excess risk (AR) of mortality were calculated for the entire cohort and by prognostic groups (on the basis of B symptoms, mediastinal status, and number of sites, modified from the European Organization for Research and Treatment of Cancer). RESULTS: The median follow-up was 12 years. The 15- and 20-year Kaplan-Meier survival estimates were 84% and 78%, respectively. Cox proportional hazards models showed that number of involved sites (P = .006), mediastinal status (P = .02), and histology (P = .02) were independent predictors of death from all causes. The AR of mortality in patients with a favorable prognosis increased over time, whereas for those with an unfavorable prognosis, the AR peaked in the first 5 years, predominantly from Hodgkin’s disease. The relative risk of mortality from all causes, causes other than Hodgkin’s disease, second tumors, and cardiac disease remained significantly elevated more than 20 years after treatment. CONCLUSION: Patients treated for early-stage Hodgkin’s disease have a sustained excess mortality risk despite good control of the disease. Treatment reduction efforts in patients with early-stage, favorable-prognosis disease should continue, but for patients with an unfavorable prognosis, modified treatment may not be advisable. The excess mortality noted beyond two decades underscores the importance of long-term follow-up care in patients treated for Hodgkin’s disease.
International Journal of Radiation Oncology Biology Physics, Oct 1, 2017
determining propensity for metastatic site (MS) failure (MSF). This retrospective study sought to... more determining propensity for metastatic site (MS) failure (MSF). This retrospective study sought to evaluate the utility of MIBG to identify patients and metastatic sites at highest risk for MSF. Materials/Methods: Seventy-six patients with high-risk neuroblastoma treated on prospective trials at a single institution from 1997 to 2014 were included. Patients received induction chemotherapy, primary site surgery, and myeloablative chemotherapy with autologous stem cell rescue (AuSCR) and maintenance chemotherapy. Primary and metastatic site radiotherapy (RT) was applied according to the specific protocol. CT and I-123 MIBG studies were reviewed to characterize metastatic site location, avidity, response, and failure. MSF1 was progression at a site identified prior to any therapy. MSF2 was progression at a previously undocumented site. Curie scores were calculated for 554 scans completed at diagnosis, post-induction, after AuSCR, and at the time of MSF. Progression-free (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazards frailty regression (cphfR) was used to evaluate the role of MIBG avidity on the hazard for MSF. Results: The median PFS and OS were 24.1 months (95% CI 16.5-38.7) and 61 months (95% CI 42.6-NR). Patients with Curie scores 2 who underwent AuSCR and maintenance chemotherapy had improved 2yr PFS compared to those with Curie scores >2 (90% vs. 76%, P Z 0.1) and displayed a non-significant trend toward reduced Curie score at progression. MSF occurred in 42 (55%) patients at 180 sites. MSF1 was observed at 77 (43%) and MFS2 at 103 (57%) sites. Combined site failure occurred in 14 (18%). Ten patients received consolidative RT to 30 MS. Irradiated MS were avid at diagnosis, post-induction, and after AuSCR in 12, 7, and 11 cases, respectively. MSF1 occurred in post-induction MIBG avid lesions in 68 of 81 (84%) and 12 of 14 (85%) non-RT and RT MS, respectively. The 3 year MSF rate for sites that were avid at diagnosis, post-induction, and after AuSCR was 14%, 26.7%, and 47%, respectively, while the median time to MSF for new sites was 9.6 months (95% CI 7.2-14.3). CphfR showed an increased hazard for MSF1 in MIBG avid sites post-induction (HR 4.9, 95% CI 1.1-20.9, P Z 0.03) and after AuSCR (HR 7.3 95% CI 1.8-30.2, P Z 0.006). Consolidative RT to 23.4 Gy did not modify the hazard for MSF. Conclusion: Curie scoring identified patients with improved survival and reduced disease burden at failure. Progression at previously undocumented sites (MSF2) occurred much earlier relative to sites identified prior to therapy (MSF1). Metastatic lesions that remained MIBG avid following induction chemotherapy and after AuSCR had an increased hazard for MSF. Consolidative site RT to 23.4 Gy did not improve metastatic site control.
Background: Children's Oncology Group study AEWS0031 demonstrated superior 5-year event-free surv... more Background: Children's Oncology Group study AEWS0031 demonstrated superior 5-year event-free survival (EFS) in patients with localized Ewing sarcoma (ES) receiving interval-compressed (IC) chemotherapy (every 2 weeks) compared to standard timing (ST) chemotherapy (every 3 weeks). We assessed the long-term outcome of patients treated on AEWS0031 to determine whether the survival advantage of IC chemotherapy was maintained at 10 years. Methods: AEWS0031 enrolled 568 eligible patients with localized ES. Patients were stratified into four groups by age (<18 years and ≥ 18 years) and primary site (pelvic and non-pelvic), and randomized to receive 14 cycles of alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide given every 3 weeks (ST; Regimen A) vs. every 2 weeks (IC; Regimen B). For this updated report, one patient was excluded due to uncertainty of original diagnosis giving a total of 567 patients in this analysis. Data for tumor measurements and histologic response were collected retrospectively from institutional reports. EFS and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test and Gray's test for cumulative incidence (CI). Results: The 10-year EFS for patients treated with IC chemo was 70% compared to 61% for ST chemo (p = 0.03), and the OS was 76% with IC chemo compared to 69% for ST chemo (p = 0.03). The 10-year CI of second malignant neoplasms (SMNs) for ST chemo was 4.2% [95% confidence interval: 2.4-7.5] compared to 3.2% (95% confidence interval: 1.6-6.3) for IC chemo (p = 0.5). There was a trend towards improved 10-year EFS in those receiving IC chemo both with non-pelvic (N = 477; 71% vs. 64%) and pelvic (N = 90; 67% vs. 43%) primary tumors. Similarly, the 10-year EFS was superior for patients treated with IC chemo in both the < 18 years (N = 500; 73% vs. 64%) and ≥ 18 years (N = 67; 53% vs. 37%) age groups. Among the 184 patients with available histologic response data, the 10-year EFS from the time of local control was 76% for those with < 10% viable tumor and 56% for those with ≥ 10% viable tumor (p = 0.01). Additional analysis comparing patients with any viable tumor vs. no viable tumor (NVT) by treatment regimen demonstrated that patients with NVT who received IC chemo had 10-year EFS and OS from local control of 91% and 97%, respectively. In the 210 patients for whom tumor volume calculations were possible, there was no difference in the 10-year EFS for patients with tumors < 200 mL vs. ≥ 200 mL. Conclusions: With longer term follow-up, IC chemotherapy for localized ES is associated with superior EFS and OS without an increase in SMNs. This study suggests patients ≥ 18 years with poor necrosis or pelvic primary tumors remain at high risk for relapse despite IC chemo, emphasizing the need for alternative treatment strategies to improve their outcomes. Clinical trial information: NCT00006734
OBJECTIVE The goal in this study was to outline unique differences between radiation-induced and ... more OBJECTIVE The goal in this study was to outline unique differences between radiation-induced and nonradiation-induced pediatric meningiomas and to identify independent risk factors of tumor recurrence/progression. METHODS This is a retrospective cohort study of all pediatric meningiomas diagnosed and surgically treated at the authors’ institution between 1993 and 2017. Multivariable Cox regression was applied to identify independent risk factors for tumor recurrence/progression. RESULTS Thirty-five patients were identified. The primary etiology was nonradiation-induced (n = 24: n = 3 with neurofibromatosis type 2) or radiation-induced (n = 11: acute lymphoblastic leukemia [n = 5], medulloblastoma [n = 4], germ cell tumor [n = 1], and primitive neuroectodermal tumor [n = 1]) meningioma. The mean age at time of diagnosis was 10.7 ± 5.7 years for nonradiation-induced and 17.3 ± 3.5 years for radiation-induced meningiomas. Overall, 8/24 patients with nonradiation-induced meningioma expe...
ObjectivesPalliative radiation therapy (pRT) is often used to improve quality of life for pediatr... more ObjectivesPalliative radiation therapy (pRT) is often used to improve quality of life for pediatric patients. Though palliative doses are generally lower than those for cure, pRT may still introduce undesirable effects. The decision to pursue additional therapy for a child may be challenging and depends on parents’ knowledge and expectations. The goal of this study was to explore parental perceptions of pRT.MethodsTwenty‐eight children referred for pRT were enrolled in our prospective study. Parents were counseled regarding the indication and expected outcomes. They then completed a series of questionnaires to assess their understanding of pRT, side effects that their child experienced, and how the outcomes compared to their expectations.ResultsThe majority of parents listed pain relief and addressing new disease as the main indication for pRT. When asked about expectations, the majority chose improvement in quality of life and prolongation of their child's life. Interestingly, ...
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