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Title: SU-F-T-221: An Assessment of the Potential for Improved Local Control of Skull- Base Chordomas Via Reduction of the Proton Beam Range Uncertainty

Abstract

Purpose: The beam range uncertainty presents a special challenge for proton therapy. Novel technologies currently under development offer strategies to reduce the range uncertainty [1,2]. This work quantifies the potential advantages that could be realized by such a reduction for dosimetrically challenging chordomas at the base of skull. Therapeutic improvement was assessed by evaluating tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP). Methods: Treatment plans were made for a modulated-scanned proton delivery technique using the Eclipse treatment planning system. The prescription dose was 7920 cGy to the CTV. Three different range uncertainty scenarios were considered: 5 mm (3.5% of the beam range + 1 mm, representing current clinical practice, “Curr”), 2 mm (1.3%), and 1 mm (0.7%). For each of 4 patients, 3 different PTVs were defined via uniform expansion of the CTV by the value of the range uncertainty. Tumor control probability (TCP) and normal tissue complication probabilities (NTCPs) for organs-at-risk (OARs) were calculated using the Lyman-Kutcher-Burman[3] formalism and published model parameters [ref Terahara[4], quantec S10, Burman Red Journal v21 pp 123]. Our plan optimization strategy was to achieve PTV close to prescription while maintaining OAR NTCP values at or better than the Curr plan. Results: Themore » average TCP values for the 5, 2, and 1 mm range uncertainty scenarios are 51%, 55% and 65%. The improvement in TCP for patients was between 4 and 30%, depending primarily on the proximity of the GTV to OAR. The average NTCPs for the brainstem and cord were about 4% and 1%, respectively, for all target margins. Conclusion: For base of skull chordomas, reduced target margins can substantially increase the TCP without increasing the NTCP. This work demonstrates the potential significance of a reduction in the range uncertainty for proton beams.« less

Authors:
; ; ; ; ; ;  [1]
  1. University of Pennsylvania, Philadelphia, PA (United States)
Publication Date:
OSTI Identifier:
22648838
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; NEOPLASMS; PLANNING; PROTON BEAMS; RADIATION DOSES; RADIOTHERAPY; TCP

Citation Formats

Muller, L, Soldner, A, Kirk, M, Fager, M, Solberg, T, Robert, L, and Dolney, D. SU-F-T-221: An Assessment of the Potential for Improved Local Control of Skull- Base Chordomas Via Reduction of the Proton Beam Range Uncertainty. United States: N. p., 2016. Web. doi:10.1118/1.4956360.
Muller, L, Soldner, A, Kirk, M, Fager, M, Solberg, T, Robert, L, & Dolney, D. SU-F-T-221: An Assessment of the Potential for Improved Local Control of Skull- Base Chordomas Via Reduction of the Proton Beam Range Uncertainty. United States. doi:10.1118/1.4956360.
Muller, L, Soldner, A, Kirk, M, Fager, M, Solberg, T, Robert, L, and Dolney, D. 2016. "SU-F-T-221: An Assessment of the Potential for Improved Local Control of Skull- Base Chordomas Via Reduction of the Proton Beam Range Uncertainty". United States. doi:10.1118/1.4956360.
@article{osti_22648838,
title = {SU-F-T-221: An Assessment of the Potential for Improved Local Control of Skull- Base Chordomas Via Reduction of the Proton Beam Range Uncertainty},
author = {Muller, L and Soldner, A and Kirk, M and Fager, M and Solberg, T and Robert, L and Dolney, D},
abstractNote = {Purpose: The beam range uncertainty presents a special challenge for proton therapy. Novel technologies currently under development offer strategies to reduce the range uncertainty [1,2]. This work quantifies the potential advantages that could be realized by such a reduction for dosimetrically challenging chordomas at the base of skull. Therapeutic improvement was assessed by evaluating tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP). Methods: Treatment plans were made for a modulated-scanned proton delivery technique using the Eclipse treatment planning system. The prescription dose was 7920 cGy to the CTV. Three different range uncertainty scenarios were considered: 5 mm (3.5% of the beam range + 1 mm, representing current clinical practice, “Curr”), 2 mm (1.3%), and 1 mm (0.7%). For each of 4 patients, 3 different PTVs were defined via uniform expansion of the CTV by the value of the range uncertainty. Tumor control probability (TCP) and normal tissue complication probabilities (NTCPs) for organs-at-risk (OARs) were calculated using the Lyman-Kutcher-Burman[3] formalism and published model parameters [ref Terahara[4], quantec S10, Burman Red Journal v21 pp 123]. Our plan optimization strategy was to achieve PTV close to prescription while maintaining OAR NTCP values at or better than the Curr plan. Results: The average TCP values for the 5, 2, and 1 mm range uncertainty scenarios are 51%, 55% and 65%. The improvement in TCP for patients was between 4 and 30%, depending primarily on the proximity of the GTV to OAR. The average NTCPs for the brainstem and cord were about 4% and 1%, respectively, for all target margins. Conclusion: For base of skull chordomas, reduced target margins can substantially increase the TCP without increasing the NTCP. This work demonstrates the potential significance of a reduction in the range uncertainty for proton beams.},
doi = {10.1118/1.4956360},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = 2016,
month = 6
}
  • Purpose: To evaluate effectiveness and safety of spot-scanning-based proton radiotherapy (PT) in skull-base chordomas and chondrosarcomas. Methods and Materials: Between October 1998 and November 2005, 64 patients with skull-base chordomas (n = 42) and chondrosarcomas (n = 22) were treated at Paul Scherrer Institute with PT using spot-scanning technique. Median total dose for chordomas was 73.5 Gy(RBE) and 68.4 Gy(RBE) for chondrosarcomas at 1.8-2.0 Gy(RBE) dose per fraction. Local control (LC), disease specific survival (DSS), and overall survival (OS) rates were calculated. Toxicity was assessed according to CTCAE, v. 3.0. Results: Mean follow-up period was 38 months (range, 14-92 months).more » Five patients with chordoma and one patient with chondrosarcoma experienced local recurrence. Actuarial 5-year LC rates were 81% for chordomas and 94% for chondrosarcomas. Brainstem compression at the time of PT (p = 0.007) and gross tumor volume >25 mL (p = 0.03) were associated with lower LC rates. Five years rates of DSS and OS were 81% and 62% for chordomas and 100% and 91% for chondrosarcomas, respectively. High-grade late toxicity consisted of one patient with Grade 3 and one patient with Grade 4 unilateral optic neuropathy, and two patients with Grade 3 central nervous system necrosis. No patient experienced brainstem toxicity. Actuarial 5-year freedom from high-grade toxicity was 94%. Conclusions: Our data indicate safety and efficacy of spot-scanning based PT for skull-base chordomas and chondrosarcomas. With target definition, dose prescription and normal organ tolerance levels similar to passive-scattering based PT series, complication-free, tumor control and survival rates are at present comparable.« less
  • Purpose: The aim of this study was to evaluate the effectiveness and toxicity of carbon ion radiotherapy in chordomas of the skull base. Methods and Materials: Between November 1998 and July 2005, a total of 96 patients with chordomas of the skull base have been treated with carbon ion radiation therapy (RT) using the raster scan technique at the Gesellschaft fuer Schwerionenforschung (GSI) in Darmstadt, Germany. All patients had gross residual tumors. Median total dose was 60 CGE (range, 60-70 CGE) delivered in 20 fractions within 3 weeks. Local control and overall survival rates were calculated using the Kaplan-Meier method.more » Toxicity was assessed according to the Common Terminology Criteria (CTCAE v.3.0) and the Radiation Therapy Oncology Group (RTOG) / European Organization for Research and Treatment of Cancer (EORTC) score. Results: Mean follow-up was 31 months (range, 3-91 months). Fifteen patients developed local recurrences after carbon ion RT. The actuarial local control rates were 80.6% and 70.0% at 3 and 5 years, respectively. Target doses in excess of 60 CGE and primary tumor status were associated with higher local control rates. Overall survival was 91.8% and 88.5% at 3 and 5 years, respectively. Late toxicity consisted of optic nerve neuropathy RTOG/EORTC Grade 3 in 4.1% of the patients and necrosis of a fat plomb in 1 patient. Minor temporal lobe injury (RTOG/EORTC Grade 1-2) occurred in 7 patients (7.2%). Conclusions: Carbon ion RT offers an effective treatment option for skull-base chordomas with acceptable toxicity. Doses in excess of 75 CGE with 2 CGE per fraction are likely to increase local control probability.« less
  • Purpose: Intracranial chordomas and chondrosarcomas are histologically low-grade, locally invasive tumors that infiltrate the skull base. Currently, consensus therapy includes surgical resection and adjuvant radiotherapy. Radiation delivery is typically limited by the proximity of these tumors to critical skull base structures. Methods: This is a retrospective review of 13 cases of chordomas and 2 cases of chondroid chondrosarcomas of the skull based treated with linear accelerator stereotactic radiotherapy (SRT, n = 10) or stereotactic radiosurgery (SRS, n = 5). The average time to the most recent follow-up visit was 4.5 years. The tumor characteristics, treatment details, and outcomes were recorded.more » Each radiation plan was reviewed, and the dosage received by the brainstem, optic apparatus, and pituitary was calculated. Results: Of the 10 patients treated with SRT, 6 were found to have unchanged or decreased tumor size as determined from radiographic follow-up. Of the 5 patients treated with SRS, 3 were found to have stable or unchanged tumors at follow-up. The complications included 1 SRT patient who developed endocrinopathy, 2 patients (1 treated with SRS and the other with SRT), who developed cranial neuropathy, and 1 SRS patient who developed visual deficits. Additionally, 1 patient who received both SRS and SRT within 2 years for recurrence experienced transient medial temporal lobe radiation changes that resolved. Conclusions: Where proton beam therapy is unavailable, linear accelerator-based SRT or radiosurgery remains a safe option for adjuvant therapy of chordomas and chondrosarcomas of the skull base. The exposure of the optic apparatus, pituitary stalk, and brainstem must be considered during planning to minimize complications. If the optic apparatus is included in the 80% isodose line, it might be best to fractionate therapy. Exposure of the pituitary stalk should be kept to <30 Gy to minimize endocrine dysfunction. Brainstem exposure should be limited to <60 Gy in fractions.« less
  • Purpose: To report on a universal bolus (UB) designed to replace the range shifter (RS); the UB allows the treatment of shallow tumors while keeping the pencil beam scanning (PBS) spot size small. Methods and Materials: Ten patients with brain cancers treated from 2010 to 2011 were planned using the PBS technique with bolus and the RS. In-air spot sizes of the pencil beam were measured and compared for 4 conditions (open field, with RS, and with UB at 2- and 8-cm air gap) in isocentric geometry. The UB was applied in our clinic to treat brain tumors, and the plansmore » with UB were compared with the plans with RS. Results: A UB of 5.5 cm water equivalent thickness was found to meet the needs of the majority of patients. By using the UB, the PBS spot sizes are similar with the open beam (P>.1). The heterogeneity index was found to be approximately 10% lower for the UB plans than for the RS plans. The coverage for plans with UB is more conformal than for plans with RS; the largest increase in sparing is usually for peripheral organs at risk. Conclusions: The integrity of the physical properties of the PBS beam can be maintained using a UB that allows for highly conformal PBS treatment design, even in a simple geometry of the fixed beam line when noncoplanar beams are used.« less
  • Purpose: We evaluated patient and treatment parameters correlated with development of temporal lobe radiation necrosis. Methods and Materials: This was a retrospective analysis of a cohort of 66 patients treated for skull base chordoma, chondrosarcoma, adenoid cystic carcinoma, or sinonasal malignancies between 2005 and 2012, who had at least 6 months of clinical and radiographic follow-up. The median radiation dose was 75.6 Gy (relative biological effectiveness [RBE]). Analyzed factors included gender, age, hypertension, diabetes, smoking status, use of chemotherapy, and the absolute dose:volume data for both the right and left temporal lobes, considered separately. A generalized estimating equation (GEE) regression analysis evaluatedmore » potential predictors of radiation necrosis, and the median effective concentration (EC50) model estimated dose–volume parameters associated with radiation necrosis. Results: Median follow-up time was 31 months (range 6-96 months) and was 34 months in patients who were alive. The Kaplan-Meier estimate of overall survival at 3 years was 84.9%. The 3-year estimate of any grade temporal lobe radiation necrosis was 12.4%, and for grade 2 or higher radiation necrosis was 5.7%. On multivariate GEE, only dose–volume relationships were associated with the risk of radiation necrosis. In the EC50 model, all dose levels from 10 to 70 Gy (RBE) were highly correlated with radiation necrosis, with a 15% 3-year risk of any-grade temporal lobe radiation necrosis when the absolute volume of a temporal lobe receiving 60 Gy (RBE) (aV60) exceeded 5.5 cm{sup 3}, or aV70 > 1.7 cm{sup 3}. Conclusions: Dose–volume parameters are highly correlated with the risk of developing temporal lobe radiation necrosis. In this study the risk of radiation necrosis increased sharply when the temporal lobe aV60 exceeded 5.5 cm{sup 3} or aV70 > 1.7 cm{sup 3}. Treatment planning goals should include constraints on the volume of temporal lobes receiving higher dose. The EC50 model provides suggested dose–volume temporal lobe constraints for conventionally fractionated high-dose skull base radiation therapy.« less