Particle Therapy for Bone and Soft Tissue Sarcomas: A Retrospective Study

Reviewer: Geoffrey Geiger MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 14 de octubre del 2009

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Presenter: Y. Demizu , M. Murakami, D. Miyawaki, M. Mima, K. Terashima, T. Arimura, Y. Niwa, Y. Hishikawa
Presenter's Affiliation: Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Japan
Type of Session: Scientific

Background

  • Bone and soft tissue sarcomas (BSTSs) represent nearly 10,000 cases of newly diagnosed malignant disease in the United States each year.
  • These tumors have historically been considered radioresistant and the primary modality of treatment has traditionally been complete surgical resection +/- pre- or post-operative radiation.
  • With respect to available modalities of radiation, protons interact more densely with tissue, result in a greater degree of ionization per unit volume, and have a higher radiobiological effect (RBE) than photons.
  • Charged particle beam therapy with protons allows the delivery of higher doses of conformal radiation due to the dose characteristics of proton beam radiotherapy, including finite range and steep dose fall off beyond the Bragg peak.
  • Because of the superior conformality and higher radiobiological effectiveness, charged particle radiation therapy is expected to deliver biologically equivalent doses with superior precision and with less radiation-induced morbidity than conventional photon radiation therapy.
  • Particle therapy using carbon ions or protons, therefore, has the potential to be an alternative to surgery in the treatment of BSTSs.
  • The purpose of this study was to analyze the results of particle therapy using both carbon ion and protons for BSTSs at the Hyogo Ion Beam Medical Center (HIBMC).

Materials and Methods

  • Between January 2005 and August 2007, 25 patients with 27 separate BSTSs were treated with particle therapy at HIBMC.
  • Patient characteristics:
    • Tumor sites: 7 in the thorax, 8 in the pelvis, 5 in the spine, and 7 in the extremities.
    • 56% of patients were male and 44% female.
    • Histological types: 7 chondrosarcomas, 5 malignant fibrous histiocytomas (MFHs), 4 osteosarcomas, (OS), 3 liposarcomas, 3 malignant peripheral nerve sheath tumors (MPNSTs), and 5 others.
    • 11% of the 25 patients had metastatic disease at the time of treatment.
    • 52% of patients had no prior treatment, 37% had a post-operative recurrence, and 11% were felt to be chemotherapy resistant.
  • Particle therapy protocols:
    • Carbon ion therapy of 70.4 CGE (centi Gray equivalents) in 16 fractions was used for 23 lesions, proton therapy of 70.4 CGE/16 fractions for 2 lesions, and proton therapy of 65 CGE/26 fractions was used for 2 lesions.
      • The 70.4 CGE/16 fractions proton regimen was used for tumors felt to be too deep for carbon ions, and the lower proton dose was used for one case where organ at risk (OARs) constraints prevented the use of higher doses.
    • Overall and progression-free survivals, and local control rates were evaluated using the Kaplan-Meier method.
    • Acute and late morbidities were assessed based on the Common Terminology Criteria for Adverse Events (CTCAE) v3.0.

Results

  • The data presented here represent single institution retrospective data collected from the Hyogo Ion Beam Medical Center in Tatsuno, Japan.
  • The median follow-up was 24 months (range, 2-47 months).
  • The 2-year overall survival, progression-free survival, and local control rates were 80%, 55%, and 76%, respectively.
  • Four patients developed local recurrences:
    • 3 occurred within the GTV and one occurred marginally.
    • Histologies of locally recurrent lesions:
      • MFH (2), MPNST (1), and OS (1).
  • Distant metastases occurred in 10 patients:
    • Lung (4 patients), bone (3), soft tissue (3), skull base (1).
  • Observed toxicities:
    • Acute: nine occurrences of grade 2 skin toxicity and seven grade 3 skin toxicities.
    • Late: two grade 3 motor neuropathies, one brachial plexopathy and one incidence of soft tissue necrosis. Five grade 4 late toxicities were observed: 4 episodes of skin toxicity and one fracture requiring hospitalization.

Author's Conclusions

  • Particle therapy for BSTSs demonstrated favorable results with good 2-year overall survival and local control rates, the latter of which was nearly equal to that of the National Institute of Radiological Sciences (Kamada, 2002; Serizawa, 2009) using the same protocol with 70.4 CGE in 16 fractions for the majority of cases.
    • Chondrosarcomas were the most likely lesions to exhibit behavior compatible with local control, and MFHs the least.
  • Patients with good local control were also found to have  increased rates of survival.
  • Acute and late morbidities were considered acceptable, and skin toxicities were the most common acute and long-term side effects.
    • Recently, the group has been attempting to reduce skin dose using additional treatment portals, which is difficult when the tumor is adjacent to the skin surface.
      • In such conditions, the group has employed 70.4 CGE in 32 fractions with good short-term data.
  • Overall, neuropathies and brachial plexopathies were relatively uncommon, although doses to all nervous system structures were felt to be under tolerance during the initial radiation planning sessions.

Clinical/Scientific Implications

  • Charged particle radiotherapy with protons (or alternatively, carbon or helium ions) affords the ability to treat tumors with minimal collateral damage due to the physical properties of charged particles, such as increased dose at the end of the beam range (called the Bragg peak) and a sharp decrease in dose of the radiation beam beyond the target volume.
  • These properties permit highly localized and homogeneous dose distributions and sparing of normal critical structures.
  • Additionally, these data demonstrate the safety and efficacy of high dose particle radiotherapy for the treatment of BSTSs of various histologies.
  • Good local control rates were observed in this single institution study, although detailed information regarding staging, tumor grade, extent of resection, and adjuvant therapies preclude making conclusive assessments regarding efficacy of this treatment regime in the context of larger and more comprehensive studies. Furthermore, it is unclear whether the inclusion of more favorable histologies among the enrolled patients led to improved outcomes.
  • The data presented here appear interesting and promising, with potentially improved results as compared to historical data; however, the retrospective nature of the study, small sample size, and relatively short follow-up time preclude making statements regarding effectiveness in the definitive setting as compared to more readily available multimodality treatment.


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