High-dose, Spot Scanning Based Proton Therapy For Paraspinal / Retroperitoneal Neoplasms and Small Bowel Tolerance: Dose Distribution Analysis in a Patient Cohort

Reviewer: Samuel Swisher-McClure, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 3, 2010

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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.

Background

  • 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.

Materials/Methods

  • 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

Results

  • 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:

Dosimetric Parameter

Mean Volume of Small Bowel Receiving Specified Dose (Range)

V5 (n=24)

86.5 cc (2.0-237.8 cc)

V20 (n=24)

45.1 cc (0.2-150.6 cc)

V30 (n=22)

35.5 cc (0.1-120.0 cc

V40 (n=20)

27.5 cc (0.2-89.0 cc)

V50 (n=19)

17.7 cc (0.2-59.0 cc)

V60 (n=17)

7.6 cc (0.37-29.0 cc)

V70 (n=12)

2.4 cc (0.04-11.0 cc)

Author's Conclusions

  • 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.

Clinical Implications

  • 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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