Authors: R. A. Schneider, V. Vitolo, F. Albertini, T. Koch, C. Ares, A. Lomax, G. Goitein, E. B. Hug. Affiliations: Paul Scherrer Institute, Villigen PSI, Switzerland. Fondazione CNAO, Pavia, Italy. University of Zurich, Zurich, Switzerland.
Mesenchymal tumors require high doses of radiation when treated either in the adjuvant or definitive setting.
Small bowel dose constraints have historically restricted dose delivery to paraspinal targets and moderate doses to large abdominal volumes carry the risk of long term morbidity.
Pre-clinical comparisons of proton radiation therapy (PT) vs. photon radiotherapy (RT) have suggested a reduction in integral dose to normal tissues by PT for a number of tumor types.
A previously published series of patients with skull base chordomas treated with spot scanning PT at PSI (Hug et al. IJROBP 2009) reported a 5 year local control rate of 81% after treatment to 73.5 Gy (RBE). These observed outcomes compare favorably with those observed with conventional photon irradiation.
Spot scanning technique was developed at the Paul Scherrer Institute (PSI) and has been in use since 1996.
This study correlated target coverage with small bowel dose-volume histograms as well as clinical tolerance.
This study was a retrospective observational cohort study.
Between 1997 and 2008, 31 patients underwent spot-scanning based PT at PSI for paraspinal/retroperitoneal tumors.
PT was used to deliver a mean total dose of 72.3 Gy(RBE) [range 64-76 Gy(RBE)] delivered at 1.8-2 Gy(RBE) fraction dose. The estimated RBE used was 1.1.
Patients were all positioned prone and immobilized using individual custom vacuum molds.
Treatment was delivered most commonly with posterior and oblique fields.
None of the patients in this analysis received concurrent chemotherapy.
Based on the original CT therapy plans small bowel dose distributions were re-analyzed.
Actual small bowel loops were outlined, and the small bowel was defined at axial CT-levels 2 cm above and below the planning target volumes.
Toxicity was graded according to CTCAE version 4.0
Characteristics of the Study Population:
The mean patient age was 52.1 years (Range 10-76 years).
Patient included in this analysis had been diagnosed with chordoma (81%), sarcoma (17%) and meningioma (3%)
Tumors were localized at either the lumbar region (17 pts.) or at the sacrum (14 pts.).
The 31 patients included in the analysis had previously undergone a total of 54 surgical procedures related to their diagnosis. However, a detailed account of the extent of tumor resection was not provided.
The mean follow-up was 3.5 years (Range 0.9-8.7 years).
The reported 3 year actuarial local control (LC) rate was 72%, and 3 year actuarial overall survival (OS) rate was 77%.
Mean high-dose target volume was 560.22 cc (range, 6.3-1720 ccs) and 95% volume was covered by 90% prescription dose.
Treatment related toxicities:
Two patients (6%) experienced Grade I acute small bowel toxicity and no patient ? Grade II acute toxicity.
No patient experienced ? Grade 2 small bowel late adverse events.
In clinical practice, the composite dose distribution at the distal edge resulted in a dose fall-off from the 60 to 20 Gy (RBE) isodose within 2 cm.
In 7 patients, PT was accomplished without significant radiation dose to the small bowel (V5 = 0).
Among the remaining 24 patients, the mean Dmax to the small bowel was 64.1 Gy (RBE). Despite target doses of 70 Gy(RBE), small bowel received a maximum dose of 50 Gy (RBE) in 61% of patients, and 60 Gy (RBE) in 54% of patients.
Dose-volume relationships for the small bowel are provided in further detail below:
Mean Volume of Small Bowel Receiving Specified Dose (Range)
86.5 cc (2.0-237.8 cc)
45.1 cc (0.2-150.6 cc)
35.5 cc (0.1-120.0 cc
27.5 cc (0.2-89.0 cc)
17.7 cc (0.2-59.0 cc)
7.6 cc (0.37-29.0 cc)
2.4 cc (0.04-11.0 cc)
PT for posterior targets results in an excellent dose fall-off within the abdominal cavity, allowing for target doses > 70 Gy (RBE) to be delivered safely.
Non-circumferential, small volumes of small bowel can tolerate doses > 60 Gy (RBE).
In addition, PT allows for lower integral dose to the small bowel when treating paraspinal/retroperitoneal tumors.
Almost complete absence of small bowel toxicity confirms that PT is an excellent tool to limit the small bowel dose when treating paraspinal/retroperitoneal mesenchymal tumors with high dose radiation.
This is a retrospective observational study that analyzes dosimetric and clinical outcomes of patients receiving spot scanning PT for paraspinal and retroperitoneal mesenchymal tumors.
Mean doses in excess of 70 Gy (RBE) were delivered safely and with minimal treatment related toxicity.
PT offers marked potential advantages in improving the therapeutic index for such patients.
Reduction of treatment related toxicities may be particularly advantageous when considering combined modality therapy for selected patients.
Limitations of the current study include:
Toxicities other than small bowel toxicity are not reported but were presumably minimal.
Minimal amounts of details are provided regarding the extent of resection each patient received and this makes it difficult to interpret the observed LC rates and compare to other studies.
While the authors treated target volumes to a mean dose of 72.3 Gy (RBE) with minimal toxicity, the observed local control rates were 72% at 3 years. The optimal dose for these tumors remains unknown and ultimately should be evaluated in a prospective clinical trial.
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