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Background: Samarium-153 ethylenediaminetetramethylene phosphonic acid ((153)Sm-EDTMP) has been used to treat patients with high-risk osteosarcoma. The purpose of the current study was to determine the maximally tolerated dose of (153)Sm-EDTMP that permits hematopoietic recovery within 6 weeks.Methods: Patients with recurrent or refractory osteosarcoma with bone metastases were enrolled in this study. Subjects were treated with increasing doses of (153)Sm-EDTMP, beginning with 1.0 millicuries (mCi)/kg and followed initially with 40% increment dose level escalations, using a continual reassessment method for dose escalation and de-escalation with a target dose-limiting toxicity (DLT) rate of 30%. Complete blood counts were monitored weekly, and the primary DLT was defined as failure to achieve an absolute neutrophil count >750/mm(3) and a platelet count >75,000/mm(3) within 6 weeks of treatment. In addition to assessing toxicity, dosimetry measurements were made to estimate the radiation dose delivered to target lesions.Results: The maximally tolerated dose of (153)Sm-EDTMP was 44.8 megabecquerel (MBq)/kg (1.21 mCi/kg). DLTs were confined to hematologic toxicities, particularly delayed platelet recovery in 2 patients treated at a dose of 51.8 MBq/kg (1.4 mCi/kg). Grade 2 and 3 pulmonary toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) as reported in 2 patients (at administered activities of 44.8 MBq/kg and 51.8 MBq/kg) was attributable to progressive pulmonary disease. No other significant nonhematologic toxicities were observed.Conclusions: Patients with osteosarcoma who have previously been heavily treated with chemotherapy can be safely administered (153)Sm-EDTMP with rapid hematologic recovery. The data from the current study support the development of a future trial to assess the efficacy of combining targeted radiotherapy with cytotoxic chemotherapy as a treatment option for patients with high-risk osteosarcoma. [ABSTRACT FROM AUTHOR]

Background: Radiation oncologists closely monitor patients during weekly on-treatment visits (OTVs). This study examines whether routine patient-reported outcome measures (PROMs) during OTVs change physicians' perceptions of treatment-toxicity and inform symptom-management., Patient and Methods: IMPROVE is a single-arm prospective multicenter trial, conducted from 2020 to 2023. Patients with locally-advanced or oligometastatic thoracic or gastrointestinal cancers receiving definitive-intent radiation, with or without chemotherapy, and their physicians enrolled. Patients completed a 14-question disease-specific PROM in clinic prior to OTVs. Physicians rated their patient's global toxicity-burden based on clinical data/assessments, then re-rated their patient's toxicity-burden and reported management-changes after PROM review. At radiotherapy end, physicians completed a Feedback Form. PROMs and outcome-data collection used electronic or paper forms. We report any change in physician-assessed burden-score and symptom-management due to PROMs., Results: The 100 patients enrolled (49 academic, 51 community-based) were 70 years old (median), 51% female, 81% Caucasian, 95% ECOG 0-1, and 94% received concurrent chemotherapy. The median radiation dose was 60 Gy, delivered over 6 weeks. PROMs were available for review for 607/629 (97%) OTVs: full 433/629 (69%), partial 174/629 (28%). For 75/100 patients (75%; 95% CI:65%-83%), PROM review resulted in any change in physician-reported burden-score, and for 50/100 patients (50%; 95% CI:40%-60%) any change in patients' on-treatment management. Rates of burden-score and management-changes were similar between academic and community-based practices (78% vs. 73%; 53% vs. 47%, respectively). For 78/100 patients with Feedback Forms, physicians agreed/strongly agreed that PROMs improved patients' quality-of-care (91%)., Conclusions: PROM review changes radiation oncologists' on-treatment toxicity assessment in 75% and care delivery in 50% of their patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KRV has received consulting fees from AstraZeneca; CH has received consulting fees from Johnson & Johnson and D1 Medical Technology; RH has received honoraria from AstraZeneca; JM has project support from Boston Scientific and royalties from Springer and UpToDate; TM has royalties/licenses and a leadership/fiduciary role in Oncospace Inc.; JW has leadership roles in American Society of Radiation Oncology (ASTRO) Clinical Affairs and Quality Committee; AM has research support from Nanocan Therapeutics Corporation and Flavocure Biotech;,SL has received consulting fees from PTC Therapeutics. CS has project support from Pfizer and Genentech, personal consulting fees from Shionogi and Janssen (via Health Outcomes Solutions), and is Principal Investigator of the PROTEUS Consortium (Patient-Reported Outcomes Tools: Engaging Users & Stakeholders)., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Radiation oncology peer review evaluates case-specific qualitative treatment planning decisions. We sought to understand interdisciplinary perspectives on peer review to identify factors affecting stakeholder engagement and implementation of recommendations., Materials and Methods: Semistructured interviews and Likert surveys (scaled, 0-10) with radiation oncology peer review participants were audio-recorded and transcribed. Two independent coders utilized a grounded theory approach to extract dominant themes., Results: Participants included 6 academic and 3 community radiation oncologists, 2 residents, 2 medical physicists, 2 radiation therapists, 4 dosimetrists, and 1 industry representative. Thematic priorities of peer review included adherence to institutional guidelines, clinical background to inform decision-making, detection of rare errors, and education. Key facilitators included pretreatment peer review, clear planning guidelines, and feedback on peer recommendations. Barriers to recommendation adoption included resource limitations and a lack of prospective data guiding qualitative recommendations. Participants perceived benefits of peer review were assessed with Likert surveys with higher values placed on reducing practice variation (8.0) and education (7.6) and a lower value placed on the detection of medical errors (7.4) and reduction of treatment delivery incidents (6.9). When comparing Likert scores by participant role, nonphysicians rated the overall importance of peer review (mean, 9.8 vs 6.5, P = .03) and education (mean, 9.0 vs 6.7, P = .02) significantly higher than physicians., Conclusion: Participants in radiation oncology acknowledged the importance of peer review, but there was significant variation in the perceived benefits. A higher value was placed on the alignment of clinical practice and nonphysician participant education. Future processes to improve communication and prospective plan review were identified as beneficial to peer review-mediated plan changes., Competing Interests: None., (© 2025 The Authors.)

Purpose: We assessed clinical outcome and long-term tumor control after fractionated stereotactic radiotherapy (FSRT) for unilateral schwannoma., Methods and Materials: Between 1995 and 2007, 496 patients were treated with fractionated stereotactic radiotherapy at Johns Hopkins Hospital (Baltimore, MD); 385 patients had radiologic follow-up that met the inclusion criteria. The primary endpoint was treatment failure. Secondary endpoints were radiologic progression and clinical outcome. Logistic regression analysis assessed the association of age, race, tumor side, sex, and pretreatment symptoms., Results: In 11 patients (3%) treatment failed, and they required salvage (microsurgical) treatment. Radiologic progression was observed in 116 patients (30.0%), including 35 patients (9%) in whom the treatment volume more than doubled during the follow-up period, although none required surgical resection. Tumors with baseline volumes of less than 1 cm(3) were 18.02 times more likely to progress than those with tumor volumes of 1 cm(3) or greater (odds ratio, 18.02; 95% confidence interval, 4.25-76.32). Treatment-induced neurologic morbidity included 8 patients (1.6%) with new facial weakness, 12 patients (2.8%) with new trigeminal paresthesias, 4 patients (0.9%) with hydrocephalus (1 communicating and 3 obstructive), and 2 patients (0.5%) with possibly radiation-induced neoplasia., Conclusions: Although the rate of treatment failure is low (3%), careful follow-up shows that radiologic progression occurs frequently. When reporting outcome, the "no salvage surgery needed" and "no additional treatment needed" criteria for treatment success need to be complemented by the radiologic data., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Effective cancer treatment generally requires combination therapy. The combination of external beam therapy (XRT) with radiopharmaceutical therapy (RPT) requires accurate three-dimensional dose calculations to avoid toxicity and evaluate efficacy. We have developed and tested a treatment planning method, using the patient-specific three-dimensional dosimetry package 3D-RD, for sequentially combined RPT/XRT therapy designed to limit toxicity to organs at risk., Methods and Materials: The biologic effective dose (BED) was used to translate voxelized RPT absorbed dose (D(RPT)) values into a normalized total dose (or equivalent 2-Gy-fraction XRT absorbed dose), NTD(RPT) map. The BED was calculated numerically using an algorithmic approach, which enabled a more accurate calculation of BED and NTD(RPT). A treatment plan from the combined Samarium-153 and external beam was designed that would deliver a tumoricidal dose while delivering no more than 50 Gy of NTD(sum) to the spinal cord of a patient with a paraspinal tumor., Results: The average voxel NTD(RPT) to tumor from RPT was 22.6 Gy (range, 1-85 Gy); the maximum spinal cord voxel NTD(RPT) from RPT was 6.8 Gy. The combined therapy NTD(sum) to tumor was 71.5 Gy (range, 40-135 Gy) for a maximum voxel spinal cord NTD(sum) equal to the maximum tolerated dose of 50 Gy., Conclusions: A method that enables real-time treatment planning of combined RPT-XRT has been developed. By implementing a more generalized conversion between the dose values from the two modalities and an activity-based treatment of partial volume effects, the reliability of combination therapy treatment planning has been expanded., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Samarium-153 ethylenediamine tetramethylene phosphoric acid (153Sm-EDTMP) is a radiopharmaceutical that has been used to treat osteosarcoma. The authors conducted a phase 2 study to test safety and response of high-risk osteosarcoma to tandem doses of 153Sm-EDTMP and to determine correlation between radiation delivered by low and high administered activities., Methods: Patients with recurrent, refractory osteosarcoma detectable on standard 99mTc bone scan received a low dose of 153Sm-EDTMP (37.0-51.8 MBq/kg), followed upon count recovery by a second, higher dose (222 MBq/kg). Fourteen days later, patients were rescued with autologous hematopoietic stem cells. The authors assessed response to therapy, performed dosimetry to determine the relationship between administered activity and tumor absorbed dose, and investigated whether changes in 2-(fluorine-18) fluoro-2-deoxy-d-glucose (18F-FDG) tumor uptake upon hematologic recovery reflected disease response., Results: Nine patients were given tandem doses of 153Sm-EDTMP; 2 received only the initial dose because of disease progression. Six patients experienced radiographic disease stabilization, but this was not considered a response, so the study was terminated early. There was a linear relationship between administered activity and tumor absorbed dose, but there was no correlation between change in 18F-FDG positron emission tomography tumor uptake and tumor absorbed dose or time to progression. The median time to progression for the entire group was 79 days., Conclusions: Tandem doses of 153Sm-EDTMP were safe for this cohort of heavily pretreated patients with very high-risk disease. The strong correlation between absorbed dose and administered activity within each evaluable patient provides a methodology to individually tailor tandem doses of this agent., (Copyright © 2010 American Cancer Society.)

To characterize a population of pediatric high-grade astrocytoma (HGA) patients by confirming the proportion with a correct diagnosis, and determine prognostic factors for survival in a subset diagnosed with uniform pathologic criteria. Sixty-three children diagnosed with HGA were treated at the Johns Hopkins Hospital between 1977 and 2004. A single neuropathologist (P.C.B.) reviewed all available histologic samples (n = 48). Log-rank analysis was used to compare survival by patient, tumor, and treatment factors. Median follow-up was 16 months for all patients and 155 months (minimum 54 months) for surviving patients. Median survival for all patients (n = 63) was 14 months with 10 long-term survivors (survival >48 months). At initial diagnosis, 27 patients were grade III (43%) and 36 grade IV (57%). Forty-eight patients had pathology slides available for review, including seven of ten long-term surviving patients. Four patients had non-HGA pathology, all of whom were long term survivors. The remaining 44 patients with confirmed HGG had a median survival of 14 months and prognostic analysis was confined to these patients. On multivariate analysis, five factors were associated with inferior survival: performance status (Lansky) <80% (13 vs. 15 months), bilaterality (13 vs. 19 months), parietal lobe location (13 vs. 16 months), resection less than gross total (13 vs. 22 months), and radiotherapy dose <50 Gy (9 vs. 16 months). Among patients with more than one of the five adverse factors (n = 27), median survival and proportion of long-term survivors were 12.9 months and 0%, compared with 41.4 months and 18% for patients with 0-1 adverse factors (n = 17). In an historical cohort of children with HGA, the potential for long term survival was confined to the subset with less than two of the following adverse prognostic factors: low performance status, bilaterality, parietal lobe site, less than gross total resection, and radiotherapy dose <50 Gy. Pathologic misdiagnosis should be suspected in patients who are long term survivors of a pediatric high grade astrocytoma.

Purpose: The objective of this study was to report our experience with stereotactic radiosurgery performed with the Gamma Knife (GK) in the treatment of patients with brain metastases and to compare survival for those treated with radiosurgery alone with survival for those treated with radiosurgery and whole-brain radiotherapy., Methods and Materials: Prospectively collected demographic and clinical characteristics and treatment and survival data on 237 patients with intracranial metastases who underwent radiosurgery with the GK between 2003 and 2007 were reviewed. Kaplan-Meier and Cox proportional hazards regression analyses were used to compare survival by demographic and clinical characteristics and treatment., Results: The mean age of the patient population was 56 years. The most common tumor histologies were non-small-cell lung carcinoma (34.2%) and breast cancer (13.9%). The median overall survival time was 8.5 months from the time of treatment. The median survival times for patients with one, two/three, and four or more brain metastases were 8.5, 9.4, and 6.7 months, respectively. Patients aged 65 years or greater and those aged less than 65 years had median survival times of 7.8 and 9 months, respectively (p = 0.008). The Karnofsky Performance Score (KPS) at the time of treatment was a significant predictor of survival: those patients with a KPS of 70 or less had a median survival of 2.9 months compared with 10.3 months (p = 0.034) for those with a KPS of 80 or greater. There was no statistically significant difference in survival between patients treated with radiosurgery alone and those treated with radiosurgery plus whole-brain radiotherapy., Conclusions: Radiosurgery with the GK is an efficacious treatment modality for brain metastases. A KPS greater than 70, histology of breast cancer, smaller tumor volume, and age less than 65 years were associated with a longer median survival in our study.

Purpose: We describe a computerized (or virtual) model of a stereotactic head frame to enable planning prior to the day of radiosurgery. The location of the virtual frame acts as a guide to frame placement on the day of the procedure., Methods and Materials: The software consists of a triangular mesh representation of the essential frame hardware that can be overlaid with any MR scan of the patient and manipulated in three dimensions. The software calculates regions of the head that will actually be accessible for treatment, subject to the geometric constraints of the Leksell Gamma Knife hardware. DICOM-compliant MR images with virtual fiducial markers overlaid onto the image can then be generated for recognition by the treatment planning system., Results: Retrospective evaluation of the software on 24 previously treated patients shows a mean deviation of the position of the virtual frame from the actual frame position of 1.6 +/- 1.3 mm. Initial clinical use on five patients indicates an average discrepancy of the virtual frame location and the actual frame location of <1 mm. MR images with virtual fiducial markers can be imported into radiosurgical treatment planning software and used to generate an initial treatment plan., Conclusions: The virtual frame provides a tool for prospective determination of lesion accessibility, optimization of the frame placement, and treatment planning before the day of the procedure. This promises to shorten overall treatment times, improve patient comfort, and reduce the need for repeat treatments due to suboptimally placed frames.

Soft tissue sarcomas in children are rare. Approximately 850 to 900 children and adolescents are diagnosed each year with rhabdomyosarcoma (RMS) or a non-RMS soft tissue sarcoma (NRSTS). RMS is more common in children 14 years old and younger and NRSTS in adolescents and young adults. Infants get NRSTS, but their tumors constitute a distinctive set of histologies. Surgery is a major therapeutic modality and radiation plays a role. RMS is treated with adjuvant chemotherapy, whereas chemotherapy is reserved for the NRSTS that are high grade or unresectable. This review discusses the etiology, biology, and treatment of pediatric soft tissue sarcomas.

Radiotherapy is integral in the multidisciplinary approach to patients with musculoskeletal neoplasms. Multiple studies have established a role for radiotherapy as a definitive local treatment of unresectable lesions or when surgery might yield unacceptable functional outcomes, such as in Ewing's tumor or base of skull chondrosarcoma. Radiotherapy is also used as an adjuvant treatment after surgery with close or positive margins. In the metastatic setting, external beam radiotherapy and bone-seeking intravenous radioisotopes are used on a case-by-case basis for palliation. As radiotherapy and its delivery techniques have evolved, so has its role in treating tumors such as Ewing's sarcoma, chordoma and chondrosarcoma, osteosarcoma, primary lymphoma of bone, malignant fibrous histiocytoma of bone, and vascular tumors. Radiation can also be successfully used to treat unresectable or recurrent benign tumors, such as giant cell tumor and aneurysmal bone cyst. This article reviews the indications for radiotherapy for various bone tumors and summarizes some of the important data supporting its use.

Allopurinol, an inhibitor of xanthine oxidase, increases myofilament calcium responsiveness and blunts calcium cycling in isolated cardiac muscle. We sought to extend these observations to conscious dogs with and without pacing-induced heart failure and tested the prediction that allopurinol would have a positive inotropic effect without increasing energy expenditure, thereby increasing mechanical efficiency. In control dogs (n=10), allopurinol (200 mg IV) caused a small positive inotropic effect; (dP/dt)(max) increased from 3103+/-162 to 3373+/-225 mm Hg/s (+8.3+/-3.2%; P=0.01), but preload-recruitable stroke work and ventricular elastance did not change. In heart failure (n=5), this effect was larger; (dP/dt)(max) rose from 1602+/-190 to 1988+/-251 mm Hg/s (+24.4+/-8.7%; P=0.03), preload-recruitable stroke work increased from 55.8+/-9.1 to 84. 9+/-12.2 mm Hg (+28.1+/-5.3%; P=0.02), and ventricular elastance rose from 6.0+/-1.6 to 10.5+/-2.2 mm Hg/mm (P=0.03). Allopurinol did not affect myocardial lusitropic properties either in control or heart failure dogs. In heart failure dogs, but not controls, allopurinol decreased myocardial oxygen consumption (-49+/-4.6%; P=0. 002) and substantially increased mechanical efficiency (stroke work/myocardial oxygen consumption; +122+/-42%; P=0.04). Moreover, xanthine oxidase activity was approximately 4-fold increased in failing versus control dog hearts (387+/-125 versus 78+/-72 pmol/min. mg(-1); P=0.04) but was not detectable in plasma. These data indicate that allopurinol possesses unique inotropic properties, increasing myocardial contractility while simultaneously reducing cardiac energy requirements. The resultant boost in myocardial contractile efficiency may prove beneficial in the treatment of congestive heart failure.