Early Axial Growth Outcomes of Pediatric Patients Receiving Proton Craniospinal Irradiation.

Guidelines on proton craniospinal irradiation (p-CSI) target volume selection in children are lacking. We examined the impact of target volume selection on growth of children receiving p-CSI at a institution. Records of 58 patients who received p-CSI were reviewed. Median age at treatment initiation was 8 years (range, 2 to 18 y). Spinal target volumes included whole vertebral body (WVB) in 67% and partial vertebral body (PVB) in 33%. Height z-scores before and after p-CSI were assessed using Centers for Disease Control and Prevention stature-for-age charts. Maximal Cobb angle and height z-score change were compared for WVB versus PVB p-CSI using a t test. Among 93% of patients with detailed data, median follow-up was 19 months (range, 2 to 58 mo) after radiation therapy initiation. Quantitative growth evaluations were available for 64% of patients. Median change in height z-score was -0.5 (range, -2.1 to +0.7) after treatment, representing a decrease (P<0.001) in age-adjusted height. WVB patients had significantly greater reduction in height z-score versus PVB patients (P=0.004) but no difference in Cobb angle change (P>0.05). Despite reluctance surrounding its use in younger patients, PVB p-CSI was associated with similar spinal curvature and less growth suppression as compared with WVB p-CSI; a trial comparing WVB versus PVB in children may be warranted.

Is there a role for conventional MRI and MR diffusion-weighted imaging for distinction of skull base chordoma and chondrosarcoma?

BACKGROUND: Chordoma and chondrosarcoma are locally invasive skull base tumors with similar clinical symptoms and anatomic imaging features as reported in the literature. PURPOSE: To determine differentiation of chordoma and chondrosarcoma of the skull base with conventional magnetic resonance imaging (cMRI) and diffusion-weighted MR imaging (DWI) in comparison to histopathological diagnosis. MATERIAL AND METHODS: This retrospective study comprised 96 (chordoma, n = 64; chondrosarcoma, n = 32) patients with skull base tumors referred to the Paul Scherrer Institute (PSI) for proton therapy. cMRI signal intensities of all tumors were investigated. In addition, median apparent diffusion coefficient (ADC) values were measured in a subgroup of 19 patients (chordoma, n = 11; chondrosarcoma, n = 8). RESULTS: The majority 81.2% (26/32) of chondrosarcomas displayed an off-midline growth pattern, 18.8% (6/32) showed clival invasion, 18.8% (6/32) were located more centrally. Only 4.7% (3/64) of chordomas revealed a lateral clival origin. Using cMRI no significant differences in MR signal intensities were observed in contrast to significantly different ADC values (subgroup of 19/96 patients examined by DWI), with the highest mean value of 2017.2 × 10(-6 )mm(2)/s (SD, 139.9( )mm(2)/s) for chondrosarcoma and significantly lower value of 1263.5 × 10(-6 )mm(2)/s (SD, 100.2 × 10(-6 )mm(2)/s) for chordoma (P = 0.001/median test). CONCLUSION: An off-midline growth pattern can differentiate chondrosarcoma from chordoma on cMRI in a majority of patients. Additional DWI is a promising tool for the differentiation of these skull base tumors.

Whole breast proton irradiation for maximal reduction of heart dose in breast cancer patients.

PURPOSE: In left-sided breast cancer radiotherapy, tangential intensity modulated radiotherapy combined with breath-hold enables a dose reduction to the heart and left anterior descending (LAD) coronary artery. Aim of this study was to investigate the added value of intensity modulated proton therapy (IMPT) with regard to decreasing the radiation dose to these structures. METHODS: In this comparative planning study, four treatment plans were generated in 20 patients: an IMPT plan and a tangential IMRT plan, both with breath-hold and free-breathing. At least 97 % of the target volume had to be covered by at least 95 % of the prescribed dose in all cases. Specifically with respect to the heart, the LAD, and the target volumes, we analyzed the maximum doses, the mean doses, and the volumes receiving 5-30 Gy. RESULTS: As compared to IMRT, IMPT resulted in significant dose reductions to the heart and LAD-region even without breath-hold. In the majority of the IMPT cases, a reduction to almost zero to the heart and LAD-region was obtained. IMPT treatment plans yielded the lowest dose to the lungs. CONCLUSIONS: With IMPT the dose to the heart and LAD-region could be significantly decreased compared to tangential IMRT with breath-hold. The clinical relevance should be assessed individually based on the baseline risk of cardiac complications in combination with the dose to organs at risk. However, as IMPT for breast cancer is currently not widely available, IMPT should be reserved for patients remaining at high risk for major coronary events.

Preservation of Neurocognition after Proton Beam Radiation Therapy for Intracranial Tumors: First Results from REGI-MA-002015.

PURPOSE: Proton beam radiation therapy reduces dose to healthy brain tissue and thereby decreases the risk of treatment-related decline in neurocognition. Considering the paucity of prospective data, this study aimed to evaluate neurocognitive performance in an adult patient population with intracranial tumors. METHODS AND MATERIALS: Between 2017 and 2021, patients enrolled in the MedAustron registry study and irradiated for intracranial tumors were eligible for neurocognitive assessment. Patients with available 1-year follow-up data were included in the analysis. The test battery consisted of a variety of standardized tests commonly used in European Organization for Research and Treatment of Cancer trials. Scores were transformed into z scores to account for demographic effects, and clinically relevant change was defined as a change of ≥1.5 standard deviations. Binary logistic regression analysis and the χ2 test were conducted for clinical parameters and dosimetric hippocampal parameters to evaluate the relationship with overall cognitive decline and changes in memory. RESULTS: One hundred twenty-three patients with mostly nonprogressive, extra-axial tumors and neurocognitive assessment at baseline and treatment end as well as 3, 6, and 12 months after completion of proton beam radiation therapy were analyzed. Overall, 7 test scores revealed stability in neurocognitive function with minimal positive changes 1 year after treatment completion (statistically significant in 6 of 7 tests), whereas the majority had no or minimal baseline deficits. At 1-year follow-up, 89.4% of all patients remained stable in their overall cognitive functioning without clinically relevant deterioration in 2 or more tests. None of them showed disease progression. Of the patients, 8.1% presented with radiation-induced brain lesions and exhibited a higher percentage of overall cognitive deterioration without reaching statistical significance. Multivariate binary logistic regression analysis revealed higher age at baseline as the only independent parameter to be associated with an overall clinically relevant cognitive decline. There was no significant correlation of hippocampal doses and memory functioning. CONCLUSIONS: One year after proton therapy, we observed preservation of cognitive functioning in the vast majority of our patients with intracranial tumors.

Pragmatic, Prospective Comparative Effectiveness Trial of Carbon Ion Therapy, Surgery, and Proton Therapy for the Management of Pelvic Sarcomas (Soft Tissue/Bone) Involving the Bone: The PROSPER Study Rationale and Design.

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy (n = 30), and (3) proton therapy (n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures.

The Majority of United States Citizens With Cancer do not Have Access to Carbon Ion Radiotherapy.

As of December 31, 2020, there were 12 facilities located in Asia and Europe which were treating cancer patients with carbon ion radiotherapy (CIRT). Between June 1994 and December 2020, 37,548 patients were treated with CIRT worldwide. Fifteen of these patients were United States (U.S.) citizens. Using the Surveillance, Epidemiology, and End Results cancer statistics database, the Mayo Clinic in Rochester, MN has conservatively estimated that there are approximately 44,340 people diagnosed each year in the U.S. with malignancies that would benefit from treatment with CIRT. The absence of CIRT facilities in the U.S. not only limits access to CIRT for cancer care but also prevents inclusion of U.S. citizens in phase III clinical trials that will determine the comparative effectiveness and cost effectiveness of CIRT for a variety of malignancies for FDA approval and insurance coverage. Past and present phase III clinical trials have not been able to enroll U.S. citizens due to their unwillingness or inability to travel abroad for CIRT for an extended period. These barriers could be overcome with a limited number of CIRT facilities in the U.S.

A Review of Particle Therapy for Skull Base Tumors: Modern Considerations and Future Directions.

Skull base tumors constitute one of the established indications for particle therapy, specifically proton therapy. However, a number of prognostic factors, practical clinical management issues, and the emerging role of carbon ion therapy remain subjects of active clinical investigation. This review summarizes these topics, assesses the present status, and reflects on future research directions focusing on the management of chordomas, one of the most aggressive skull base tumors. In addition, the role of particle therapy for benign tumors of the skull base, including pituitary adenoma and acoustic neuroma, is reviewed.

Carbon Ion Dose Constraints in the Head and Neck and Skull Base: Review of MedAustron Institutional Protocols.

BACKGROUND: Dose constraints are of paramount importance for the outcome of any radiotherapy treatment. In this article, we report dose-volume constraints as well as currently used fractionation schedules for carbon ion radiotherapy as applied in MedAustron (Wiener Neustadt, Austria). MATERIALS AND METHODS: For fractionation schedules, both German and Japanese regimes were used. From the clinical experience of National Institute of Radiological Sciences (Chiba, Japan) and Heidelberg Ion Therapy (Heidelberg, Germany; formerly GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany) and the work by colleagues in Centro Nazionale Adroterapia Oncologica (Pavia, Italy) recalculating the dose from the microdosimetric kinetic model to the local effect model, we have set the dose constraints for critical organs of the head and neck area. Where no clinical data was available, an educated guess was made, based on data available from photon and proton series. RESULTS: We report the constraints for the optic nerve and chiasm, brainstem, spinal cord, cochlea, brain parenchyma, salivary gland, eye and adnexa, and mandibular/maxillary bone; constraints are grouped based on a fractionation scheme (German versus Japanese) and the risk of toxicity (safe, low to middle, and middle to high). CONCLUSION: We think validation of dose constraints should present a relevant part of the activity of any carbon ion radiotherapy facility, and we anticipate future multicentric, joint evaluations.

Development of a Comprehensive, Contour-Based, Peer Review Workflow at a Community Proton Center.

PURPOSE: Quality assurance and continuing quality improvement are integral parts of any radiation oncology practice. With increasingly conformal radiation treatments, it has become critical to focus on every slice of the target contour to ensure adequate tumor coverage and optimal normal tissue sparing. Proton therapy centers open internationally with increasing frequency, and radiation oncologists with varying degrees of subspecialization apply proton therapy in daily practice. Precise treatment with proton therapy allows us to limit toxicity but requires in-depth knowledge of the unique properties of proton beam delivery. To address this need at our proton therapy center, we developed a comprehensive peer review program to help improve the quality of care that we were providing for our patients. MATERIALS AND METHODS: We implemented a policy of comprehensive peer review for all patients treated at our community proton facility starting in January 2013. Peer review begins at the time of referral with prospective cases being reviewed for appropriateness for proton therapy at daily rounds. There is then biweekly review of target contouring and treatment plans. RESULTS: During a 6-month period from June 2013 to November 2013, a total of 223 new patients were treated. Documentation of peer review at chart rounds was completed for 222 of the 223 patients (99.6%). An average of 10.7 cases were reviewed in each biweekly chart rounds session, with a total of 560 case presentations. The average time required for contour review was 145 seconds (±71 seconds) and plan review was 120 seconds (±64 seconds). Modifications were suggested for 21 patients (7.9%) during contour review and for 19 patients (6.4%) during treatment plan review. An average of 4 physicians were present at each session. CONCLUSIONS: We demonstrated that the implementation of a comprehensive, prospective peer review program is feasible in the community setting. This article can serve as a framework for future quality assurance programs.

Postoperative spot-scanning proton radiation therapy for chordoma and chondrosarcoma in children and adolescents: initial experience at paul scherrer institute.

PURPOSE: To evaluate postoperative spot-scanning proton radiation therapy (PT) and intensity-modulated PT (IMPT) for chordoma and chondrosarcoma in pediatric patients. METHODS AND MATERIALS: Between 2000 and 2005, 10 patients (six male patients, four female patients; six chordomas, four chondrosarcomas), aged 10-20 years (median, 16 years), were treated at our institute. Tumor sites were in the brain (one case), skull base (five cases), cervical (three cases), and lumbar spine (one case). Three children had complete resections. In seven children, resection was incomplete, leaving residual tumor behind (range, 2.3-46.3 mL). PT was delivered using spot scanning, with (three patients) or without (seven patients) IMPT. Total dose was 74.0 cobalt Gray equivalents (CGE) for chordoma, and 63.2-68.0 CGE for chondrosarcoma (median, 66.0), depending on histopathological grading and whether the patient had concurrent chemotherapy. RESULTS: Median follow-up time was 36 months (range, 8-77 months). Radiation treatment was well tolerated. All patients remained failure-free at their last follow-up. Late adverse events were reported in three patients and were mild (neurosensory in one patient; alopecia and hypoaccusis in one patient) to moderate (one patient, Grade 2 pituitary insufficiency). CONCLUSIONS: Postoperative spot-scanning PT, delivered in combination with and without IMPT, for chordoma and chondrosarcoma in children and adolescents was tolerated without unacceptable adverse event and initial outcome is perfectly satisfactory in this small cohort. Longer follow-up time and larger cohort are needed to more fully assess tumor control, adverse events, as well as functional and cosmetic outcome.

Proton Therapy for Primary Breast Cancer.

Proton therapy reduces the integral dose received by normal tissues due to its physical properties of dose deposition in the Bragg peak. In a small but significant percentage of patients requiring adjuvant radiotherapy (RT) for left-sided breast cancer, photon-based RT can lead to cardiac complications during long-term follow-up. The risk of cardiac complications is correlated with the dose to the coronary arteries and to the general 'mean heart dose'. Dosimetric comparison analysis has identified advantages of proton therapy in accomplishing sparing of the heart with increasing target complexity while permitting uncompromised target coverage of the chest wall ± breast plus draining lymphatics. Early clinical data indicate good clinical tolerance to proton therapy without unexpected complications. Several clinical trials are presently ongoing to prospectively confirm a clinical benefit and to identify the subgroup of patients benefitting most from proton therapy for breast cancer.

Spot scanning proton therapy in the curative treatment of adult patients with sarcoma: the Paul Scherrer institute experience.

PURPOSE: To assess the safety and efficacy of spot scanning proton beam therapy (PT) in the curative treatment of soft-tissue sarcoma (STS) in adults patients. PATIENTS AND METHODS: We identified 13 STS patients treated with PT between July 1998 and May 2005 in our institutional database. Tumor histology varied with the most common histologic subtypes including liposarcoma and peripheral nerve sheet tumor. All tumors were located in vicinity of critical structures, such as the spinal cord, optic apparatus, bowel, kidney, or bowel. Of the patients, 6 and 5 patients received PT either as adjuvant therapy for non-R0 resection or for recurrence, respectively. Two patients received radical PT for unresectable disease. The median prescribed dose was 69.4 CGE (CGE = proton Gy x 1.1)-Gy (range, 50.4-76.0) at 1.8 to 2 CGE-Gy (median, 1.9) per fraction. Pre-PT anthracycline-based chemotherapy was delivered to 3 patients only. No patient has been lost to follow-up (median 48.1 months, range, 19.1-100.7 months). RESULTS: Of the 13 patients, all but 2 patients were alive. Local recurrence developed in 3 (23%) patients. The administered dose to these patients was < or =60 Gy-CGE. Distant control was achieved in all but 2 patients (lung metastasis), 1 of whom presented with a concomitant local recurrence. The 4-year local control and metastasis-free survival rates were 74.1% and 84.6%, respectively. Late grade > or =2 toxicity was observed in only 2 patients. CONCLUSIONS: Spot scanning PT is an effective and safe treatment for patient with STS in critical locations. The observed toxicity rate was acceptable.

Dosimetric Comparison of Pencil-Beam Scanning and Photon-Based Radiation Therapy as a Boost in Carcinoma of Cervix.

PURPOSE: Brachytherapy is essential for local treatment in cervical carcinoma, but some patients are not suitable for it. Presently, for these patients, the authors prefer a boost by using intensity-modulated radiation therapy (IMRT). The authors evaluated the dosimetric comparison of proton-modulated radiation therapy versus IMRT and volumetric-modulated arc therapy (VMAT) as a boost to know whether protons can replace photons. PATIENTS AND METHODS: Five patients who received external beam radiation therapy to the pelvis by IMRT were reviewed. Three different plans were made, including pencil beam scanning (PBS), IMRT, and VMAT. The prescribed planning target volume (PTV) was 20 Gy in 4 fractions. The dose to 95% PTV (D95%), the conformity index, and the homogeneity index were evaluated for PTV. The Dmax, D2cc, and Dmean were evaluated for organs at risk along with the integral dose of normal tissue and organs at risk. RESULTS: The PTV coverage was optimal and homogeneous with modulated protons and photons. For PBS, coverage D95% was 20.01 ± 0.02 Gy (IMRT, 20.08 ± 0.06 Gy; VMAT, 20.1 ± 0.04 Gy). For the organs at risk, Dmax of the bladder for PBS was 21.05 ± 0.05 Gy (IMRT, 20.8 ± 0.21 Gy; VMAT, 21.65 ± 0.41 Gy) while the Dmax for the rectum for PBS was 21.04 ± 0.03 Gy (IMRT, 20.81 ± 0.12 Gy; VMAT, 21.66 ± 0.38 Gy). Integral dose to normal tissues in PBS was 14.17 ± 2.65 Gy (IMRT, 25.29 ± 6.35 Gy; VMAT, 25.24 ± 6.24 Gy). CONCLUSIONS: Compared with photons, modulated protons provide comparable conformal plans. However, PBS reduces the integral dose to critical structures significantly compared with IMRT and VMAT. Although PBS may be a better alternative for such cases, further research is required to substantiate such findings.

Acquired Chiari malformation type I following fractionated radiation therapy to the anterior skull base in a 20-month-old boy. Case report.

The authors present the case of a 20-month-old boy who underwent fractionated radiation therapy to the paranasal sinuses and anterior skull base during treatment for nasopharyngeal parameningeal rhabdomyosarcoma. Subsequent magnetic resonance imaging demonstrated progressive development of a Chiari malformation Type I (CM-I) and partial hypoplasia of the posterior fossa. Since the tonsillar herniation was discovered, the child, now 3 years old, remains asymptomatic except for mild, intermittent neck discomfort. For the time being, his family has elected for him to undergo clinical and neuroimaging follow up. The authors believe this is the first report of a progressive acquired CM-I after cranial irradiation in the pediatric population.

Proton Beam Reirradiation for Recurrent Head and Neck Cancer: Multi-institutional Report on Feasibility and Early Outcomes.

PURPOSE: Reirradiation therapy (re-RT) is the only potentially curative treatment option for patients with locally recurrent head and neck cancer (HNC). Given the significant morbidity with head and neck re-RT, interest in proton beam radiation therapy (PBRT) has increased. We report the first multi-institutional clinical experience using curative-intent PBRT for re-RT in recurrent HNC. METHODS AND MATERIALS: A retrospective analysis of ongoing prospective data registries from 2 hybrid community practice and academic proton centers was conducted. Patients with recurrent HNC who underwent at least 1 prior course of definitive-intent external beam radiation therapy (RT) were included. Acute and late toxicities were assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and the Radiation Therapy Oncology Group late radiation morbidity scoring system, respectively. The cumulative incidence of locoregional failure was calculated with death as a competing risk. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were calculated with the Kaplan-Meier method. RESULTS: Ninety-two consecutive patients were treated with curative-intent re-RT with PBRT between 2011 and 2014. Median follow-up among surviving patients was 13.3 months and among all patients was 10.4 months. The median time between last RT and PBRT was 34.4 months. There were 76 patients with 1 prior RT course and 16 with 2 or more courses. The median PBRT dose was 60.6 Gy (relative biological effectiveness, [RBE]). Eighty-five percent of patients underwent prior HNC RT for an oropharynx primary, and 39% underwent salvage surgery before re-RT. The cumulative incidence of locoregional failure at 12 months, with death as a competing risk, was 25.1%. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were 84.0% and 65.2%, respectively. Acute toxicities of grade 3 or greater included mucositis (9.9%), dysphagia (9.1%), esophagitis (9.1%), and dermatitis (3.3%). There was 1 death during PBRT due to disease progression. Grade 3 or greater late skin and dysphagia toxicities were noted in 6 patients (8.7%) and 4 patients (7.1%), respectively. Two patients had grade 5 toxicity due to treatment-related bleeding. CONCLUSIONS: Proton beam re-RT of the head and neck can provide effective tumor control with acceptable acute and late toxicity profiles likely because of the decreased dose to the surrounding normal, albeit previously irradiated, tissue, although longer follow-up is needed to confirm these findings.

Importance of protocol target definition on the ability to spare normal tissue: an IMRT and 3D-CRT planning comparison for intraorbital tumors.

PURPOSE: We selected five intraorbital tumor sites that are frequently found in clinical practice in children diagnosed with orbital rhabdomyosarcoma and performed three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated photon radiotherapy (IMRT) planning. Results of target coverage and doses to critical structures were compared. The goal of this study was to evaluate and to document realistic expectations as to organ-sparing capabilities of modern radiation therapy planning technologies with a focus on lens-sparing irradiation. Furthermore, we investigated potential added benefits of IMRT compared with 3D-CRT and the influence of protocol volume criteria definitions on the ability to obtain normal tissue dose sparing using the orbit as an example of a complex anatomic site. METHODS AND MATERIALS: The five intraorbital tumor sites were placed retrobulbar, temporal, nasal, in the upper inner and upper outer quadrant, the latter two more complex in shape. Gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV) were defined in image-fused computed tomography and magnetic resonance data sets. 3D-CRT and IMRT photon plans, using equal beam angles and collimation for direct comparison, were designed to 45 Gy prescription dose according to Intergroup Rhabdomyosarcoma Study Group-D9602 (IRSG-D9602) protocol (Intergroup Rhabdomyosarcoma Study V [IRS-V] protocol) for Stage I, Clinical Group 3 orbital rhabdomyosarcoma. To compare the impact of changed target definitions in IMRT planning, additional IMRT plans were generated using modified volume and dose coverage criteria. The minimum dose constraint (95%) of the PTV was substituted by a required minimum volume coverage (95%) with the prescribed dose. Dose-volume histograms (DVHs) were obtained, including target volumes, lens, optic nerves, optic chiasm, lacrimal gland, bony orbit, pituitary gland, frontal and temporal lobes. RESULTS: Protocol target volume coverage criteria were fulfilled in all cases (5/5) with 3D-CRT and IMRT. Using the protocol criteria, lens sparing was achieved only for two tumor sites (retrobulbar and lateral position) with either planning technique. Mean lens doses were 8.5 and 10.4 Gy for 3D-CRT and 7.5 and 13.2 Gy for IMRT, respectively. The mean lens doses for the other three tumor locations averaged 26.8 Gy. IMRT plans reduced the lens dose in four of five cases by an average of 2.6 Gy compared with 3D-CRT. Modified target protocol prescription markedly reduced mean lens doses by 23-50% and by as much as 18 Gy. Recorded mean lens doses after protocol modification were 26% lower using IMRT plans compared with 3D-CRT. The cold spot as a result of the relaxed volume coverage requirements was within 2% of the original protocol criteria and located at the edge of the PTV, outside the CTV. Compared with 3D-CRT, IMRT resulted in an increase of brain volume receiving 10% (V10) and 20% (V20) of the prescribed dose. CONCLUSION: Strict adherence to IRS-V protocol criteria prohibits at present lens sparing within compliance criteria for the majority of intraorbital tumor locations because of protocol-specific CTV and PTV target definitions. Changing protocol definitions by prescribing to the volume rather than to a dose constraint, IMRT planning significantly reduced lens doses. This was not accomplished to the same degree with 3D-CRT. Our study underlines the importance of appropriate selection of planning objectives to maximize the specific capabilities and advantages of IMRT in terms of sufficient target coverage and simultaneous sparing of critical structures. Our results can add to the ongoing discussion in the design of future 3D-CRT/IMRT protocols.

Proton radiation therapy for retinoblastoma: comparison of various intraocular tumor locations and beam arrangements.

PURPOSE: To study the optimization of proton beam arrangements for various intraocular tumor locations; and to correlate isodose distributions with various target and nontarget structures. METHODS AND MATERIALS: We considered posterior-central, nasal, and temporal tumor locations, with straight, intrarotated, or extrarotated eye positions. Doses of 46 cobalt grey equivalent (CGE) to gross tumor volume (GTV) and 40 CGE to clinical target volume (CTV) (2 CGE per fraction) were assumed. Using three-dimensional planning, we compared isodose distributions for lateral, anterolateral oblique, and anteromedial oblique beams and dose-volume histograms of CTVs, GTVs, lens, lacrimal gland, bony orbit, and soft tissues. RESULTS: All beam arrangements fully covered GTVs and CTVs with optimal lens sparing. Only 15% of orbital bone received doses > or =20 CGE with a lateral beam, with 20-26 CGE delivered to two of three growth centers. The anterolateral oblique approach with an intrarotated eye resulted in additional reduction of bony volume and exposure of only one growth center. No appreciable dose was delivered to the contralateral eye, brain tissue, or pituitary gland. CONCLUSIONS: Proton therapy achieved homogeneous target coverage with true lens sparing. Doses to orbit structures, including bony growth centers, were minimized with different beam arrangements and eye positions. Proton therapy could reduce the risks of second malignancy and cosmetic and functional sequelae.

Radiotherapy for local control of osteosarcoma.

PURPOSE: Local control of osteosarcoma in patients for whom a resection with satisfactory margins is not achieved can be difficult. This study evaluated the efficacy of radiotherapy (RT) in this setting. METHODS AND MATERIALS: We identified 41 patients in our sarcoma database with osteosarcomas that either were not resected or were excised with close or positive margins and who underwent RT with external beam photons and/or protons at our institution between 1980 and 2002. Patient charts were reviewed to assess local control, progression-free survival, metastasis-free survival, and overall survival. RESULTS: The anatomic sites treated were head/face/skull in 17, extremity in 8, spine in 8, pelvis in 7, and trunk in 1. Of the 41 patients, 27 (65.85%) had undergone gross total tumor resection, 9 (21.95%) subtotal resection, and 5 (12.2%) biopsy only. The radiation dose ranged from 10 to 80 Gy (median 66). Twenty-three patients (56.1%) received a portion of their RT with protons. Chemotherapy was given to 35 patients (85.4%). Of the 41 patients, 27 (65.85%) were treated for localized disease at primary presentation, 10 (24.4%) for local recurrence, and 4 (9.8%) for metastatic disease. The overall local control rate at 5 years was 68% +/- 8.3%. The local control rate according to the extent of resection was 78.4% +/- 8.6% for gross total resection 77.8% +/- 13.9% for subtotal resection, and 40% +/- 21.9% for biopsy only (p < 0.01). The overall survival rate according to the extent of resection was 74.45% +/- 9.1% for gross total resection, 74.1% +/- 16.1% for subtotal resection, and 25% +/- 21.65% for biopsy only (p < 0.001). Patients with either gross or subtotal resection had a greater rate of local control, survival, and disease-free survival compared with those who underwent biopsy only at 5 years (77.7% +/- 7.5% vs. 40% +/- 21% [p <0.001], 73.9% +/- 8.1% vs. 25% +/- 21.6% [p <0.001], and 51.9% +/- 9.1% vs. 25% +/- 21.6% [p <0.01], respectively). Overall survival was better in patients treated at primary presentation (78.8% +/- 8.6% compared with 54% +/- 17.3% for recurrence) p <0.05). No definitive dose-response relationship for local control of tumor was seen, although the local control rate was 71% +/- 9% for 32 patients receiving doses > or =55 Gy vs. 53.6% +/- 20.1% for 9 patients receiving <55 Gy (p = 0.11). Of 15 patients with tumors >5.3 cm, 9 received doses > or =55 Gy and the local control rate was 80% +/- 17.9%, and 6 received doses <55 Gy with a local control rate of only 50% +/- 25% at 5 years (p = 0.16). Among patients who underwent gross total resection, the local control rate was 77.5% +/- 9.95% in 22 patients with negative margins vs 66.7% +/- 27.2% in 3 patients with positive margins (p = 0.54). Two patients had unknown margin status. CONCLUSION: RT can help provide local control of osteosarcoma for patients in whom surgical resection with widely, negative margins is not possible. It appears to be more effective in situations in which microscopic or minimal residual disease is being treated.

Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma--long-term results of phase III RTOG 85-31.

PURPOSE: Radiation Therapy Oncology Group protocol 85-31 was designed to evaluate the effectiveness of adjuvant androgen suppression, using goserelin, in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy (RT). METHODS AND MATERIALS: Eligible patients were those with palpable primary tumor extending beyond the prostate (clinical Stage T3) or those with regional lymphatic involvement. Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and/or seminal vesicle involvement was documented histologically. Stratification was based on histologic differentiation, nodal status, acid phosphatase status, and prior prostatectomy. The patients were randomized to either RT and adjuvant goserelin (Arm I) or RT alone followed by observation and application of goserelin at relapse (Arm II). In Arm I, the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression. RESULTS: Between 1987 and 1992, when the study was closed, 977 patients were entered: 488 to Arm I and 489 to Arm II. As of July 2003, the median follow-up for all patients was 7.6 years and for living patients was 11 years. At 10 years, the absolute survival rate was significantly greater for the adjuvant arm than for the control arm: 49% vs. 39%, respectively (p = 0.002). The 10-year local failure rate for the adjuvant arm was 23% vs. 38% for the control arm (p <0.0001). The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24% vs. 39% (p <0.001) and 16% vs. 22% (p = 0.0052), respectively, both in favor of the adjuvant arm. CONCLUSION: In a population of patients with unfavorable prognosis carcinoma of the prostate, androgen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival. The improvement in survival appeared preferentially in patients with a Gleason score of 7-10.

Proton radiotherapy in management of pediatric base of skull tumors.

PURPOSE: Primary skull base tumors of the developing child are rare and present a formidable challenge to both surgeons and radiation oncologists. Gross total resection with negative margins is rarely achieved, and the risks of functional, structural, and cosmetic deficits limit the radiation dose using conventional radiation techniques. Twenty-nine children and adolescents treated with conformal proton radiotherapy (proton RT) were analyzed to assess treatment efficacy and safety. MATERIALS AND METHODS: Between July 1992 and April 1999, 29 patients with mesenchymal tumors underwent fractionated proton (13 patients) or fractionated combined proton and photon (16 patients) irradiation. The age at treatment ranged from 1 to 19 years (median 12); 14 patients were male and 15 female. Tumors were grouped as malignant or benign. Twenty patients had malignant histologic findings, including chordoma (n = 10), chondrosarcoma (n = 3), rhabdomyosarcoma (n = 4), and other sarcomas (n = 3). Target doses ranged between 50.4 and 78.6 Gy/cobalt Gray equivalent (CGE), delivered at doses of 1.8-2.0 Gy/CGE per fraction. The benign histologic findings included giant cell tumors (n = 6), angiofibromas (n = 2), and chondroblastoma (n = 1). RT doses for this group ranged from 45.0 to 71.8 Gy/CGE. Despite maximal surgical resection, 28 (97%) of 29 patients had gross disease at the time of proton RT. Follow-up after proton RT ranged from 13 to 92 months (mean 40). RESULTS: Of the 20 patients with malignant tumors, 5 (25%) had local failure; 1 patient had failure in the surgical access route and 3 patients developed distant metastases. Seven patients had died of progressive disease at the time of analysis. Local tumor control was maintained in 6 (60%) of 10 patients with chordoma, 3 (100%) of 3 with chondrosarcoma, 4 (100%) of 4 with rhabdomyosarcoma, and 2 (66%) of 3 with other sarcomas. The actuarial 5-year local control and overall survival rate was 72% and 56%, respectively, and the overall survival of the males was significantly superior to that of the female patients (p = 0.002). Of the patients with benign tumors, 1 patient (giant cell tumor) had local failure at 10 months. The other 8 patients continued to have local tumor control; all 9 patients were alive at last follow-up (actuarial 5-year local control and overall survival rate of 89% and 100%, respectively). Severe late effects (motor weakness and sensory deficits) were observed in 2 (7%) of 29 patients. CONCLUSION: Proton RT for children with aggressively recurring tumors after major skull base surgery can offer a considerable prospect of tumor control and survival. Longer follow-up is necessary to assess the real value of protons, in particular with regard to bone growth and cosmetic outcome.