Spot-Scanning Proton Radiation Therapy for Extra-cranial Chordoma
Reviewer: Christine Hill-Kayser, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 13 de octubre del 2009
Presenter: A Staab
Presenter's Affiliation: Paul Scherrer Institute, Villagen, Switzerland
Type of Session: Scientific
- Chordomas represent a group of rare, locally aggressive tumors, felt to arise from notochord remnants; they most often occur in the regions of the skull base or spinal column
- Although complete resection with or without radiotherapy is the primary treatment, tumor location can often limit the feasibility of surgery. In particular, chordomas near the spine may be unresectable due to proximity to nerve roots and other vital structures.
- Proton radiation is frequently employed for either adjuvant or definitive treatment for chordomas, as the dose distribution allowed through use of particle radiotherapy allows delivery of high doses to tumors, with relative sparing of nearby structures.
- Long-term results have been demonstrated with use of proton radiation in treatment of skull base/paracervical chordomas, with doses of at least 65 CGE (Munzenrider, 1999; Noel, 2003).
- Delivery of such high doses may be complicated for treatment of spinal tumors due to proximity of the spinal cord, as well as organs of the pelvis, abdomen, chest, and mediastinum.
- The study presented here was designed to assess safety and efficacy of proton radiation for extra-cranial chordomas.
Materials and Methods
- This study represents a retrospective review of patients treated with proton radiotherapy for extracranial chordoma at the Center for Proton Radiotherapy at the Paul Scherrer Institute (PSI).
- Forty such patients, treated between 1999 and 2005, were identified.
- Patients had diagnosis of chordoma of the cervical, thoracic, and/or lumbar spine, or sacrum.
- Biopsy and/or maximal surgical resection were performed for all patients.
- 18 of 40 patients had gross residual disease not amenable to further resection (GTV range 13 – 495 mL).
- 21 of 40 patients required surgical stabilization of the axial skeleton.
- All patients received adjuvant or definitive spot-scanning proton radiotherapy, with a median dose of 72 Gy.
- Treatment planning made use of MRI fused with treatment planning CT scan.
- 9 of 40 patients received mixed photon/proton treatment.
- 21 patients received intensity modulated proton treatment.
- Treatment was delivered with standard fractionation (1.8/2.0 Gy/fraction), with treatment delivery four times weekly.
- Median follow-up was 43 months.
- Clinical/ radiologic evaluation was performed every 6 months for two years, and then annually. No patients were lost to follow-up.
- Five-year local control was 62% for the entire study population. Patients were considered in subgroups according to need for surgical stabilization:
- Of 19 patients who did not require surgical stabilization, the local control rate at 5-years was 100%.
- Of 21 patients who had undergone surgical stabilization, 5-year local control was 30% (n = 12, p = 0.0003).
- Five-year overall survival for the entire cohort was 80%.
- Overall survival did not appear to be impacted by differences in local control, although four of six total deaths occurred in patients having undergone surgical stabilization.
- No high-grade neurologic, genitourinary, or gastrointestinal toxicity was observed. Two grade 3 toxicities were observed, one soft tissue necrosis, and one osteonecrosis.
- One patient died of a treatment-related second malignant neoplasm - leiomyosarcoma of the bladder - 49 months after having received mixed photon/proton radiotherapy. The patient’s bladder was noted to be in the photon portal fields, but not the proton portals.
- Multivariate analysis was attempted, but was not possible due to small population.
The authors conclude that spot scanning-based proton radiotherapy after function-preserving surgery is safe and highly effective in patients with extracranial chordoma who have not undergone major surgical instrumentation.
- Although chordomas are rare tumors, they represent both a surgical and radiotherapeutic challenge.
- Due to the relative concentration of proton radiotherapy centers worldwide, only a few have accumulated significant experience treating them.
- Although the role of proton radiotherapy in treatment of skull-based chordomas has been relatively well-established (Ares, 2009), experience with extracranial chordomas is more limited.
- The authors demonstrate that proton radiotherapy for extracranial chordoma may be delivered safely, observing no high-grade neurologic or other toxicity in the treated patients.
- Excellent local control was observed in the subset of patients not requiring surgical stabilization; it must be kept in mind that very late recurrences have been reported in the literature, and that prolonged follow-up of this population will likely be informative (Munzenrider, 1985).
- In addition, based on the data presented here, the presence of extensive surgical procedures appears to negatively impact local control; this may result from disease spread due to surgical instrumentation, altered dose delivery due to presence of surgically placed stabilization devices, delay in treatment due to surgical recovery time, or myriad other factors. Certainly, these findings should be considered carefully during decisions regarding patient care, as they suggest that surgical stabilization may significantly decrease rates of local control.
- Although local control did not appear to impact overall survival in this study, local recurrence of chordoma may be functionally devastating, as recurrent tumors and their treatments may damage nerve roots, spinal cord, and other vital structures. For this reason, avoidance of local recurrence is of utmost importance.
- Further understanding of the impact of extensive surgical procedure on efficacy of radiotherapy in treatment of chordoma may have significant impact on patient care.
- This study represents an important contribution from one of the world’s few centers with significant experience treating extracranial chordomas with proton radiotherapy. As proton radiation becomes more available, larger studies may be possible; however, retrospective data such as that presented here will likely remain clinically important given the rare nature of extracranial chordoma.
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