Carbon Ion Radiotherapy for Primary Malignant Bone Tumors of the Sacrum
Reviewer: Geoffrey Geiger, MD
The Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 2 de noviembre del 2010
Authors: T. Kamada, R. Imai, H. Tsuji, T. Imaizumi, H. Tsujii Institution: National Institute of Radiological Sciences, Chiba, Japan
Primary malignant bone tumors of the sacrum are extremely rare, and their management complex because of the proximity of these tumors to sacral nerve roots as well as the important weight bearing function of the spine and sacrum. Furthermore, the limited radiation tolerance of the spinal cord and cauda equina present challenges for the delivery of adequate doses of radiation to the primary tumor without harm to these essential nervous structures.
Surgery has been considered the mainstay of treatment for primary malignant bone tumors of the sacrum, and the definitive en bloc resection of tumor is mandatory to obtain long-term disease free survival.
However, radical surgical intervention has been associated with morbidities including substantial neurological deficits.
Compared to X-rays and more readily available modalities of radiation, carbon ions interact more densely with tissue, result in a greater degree of ionization per unit volume, and have a higher radiobiological effect (RBE) than photons or protons.
Charged particle beam therapy with carbon ions, therefore, allows the delivery of higher doses of conformal radiation due to the dose characteristics of particle beam radiotherapy, including finite range and steep dose fall off beyond the Bragg peak.
Because of its 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 radiation therapy.
In this study, the investigators evaluated the effectiveness and safety of carbon ion radiotherapy in patients with primary malignant bone tumors of the sacrum not suitable for surgical resection.
Materials and Methods
From 1996 to 2009, 175 (male/female: 112/66) patients with primary malignant bone tumors of the sacrum (not suitable for resection) received carbon ion radiotherapy as part of a phase I/II study dose escalation study (1996-2000) or as part of a fixed phase II dose study (2000-2009) at the National Institute of Radiological Sciences at Chiba, Japan.
Ages ranged from 13 to 87 (median 62 years).
All 175 patients were treated at the time of initial diagnosis and no patients were treated for recurrent disease.
Minimum follow-up for survivors was at least 6 months.
The majority of tumors were chordomas and the breakdown of histologies was as follows: chordoma in 123, osteosarcoma in 21, chondrosarcoma in 9, Ewing's tumors in 9, MFH (Malignant fibrous histiocytoma) in 6, MPNST (malignant peripheral nerve sheath tumor) in 3, and other histologies in 7 patients.
All specimens had central pathological review.
Carbon ion radiotherapy was delivered in 16 fractions over 4 weeks in 4 doses per week.
Total doses: 52.8 GyE (3.3 GyE / Fr) in 1, 57.6 GyE (3.6 GyE / Fr) in 2, 64.0 GyE (4.0 GyE / Fr) in 1, 67.2 GyE (4.2 GyE / Fr) in 39, 70.4 GyE (4.4 GyE / Fr) in 123, and 73.6 GyE (4.6 GyE / Fr) in 12 patients. Clinical target volumes ranged between 42 and 1497 cm3 (median 354 cm3).
Median survival time was 37 months (range: 2-131) for all patients and all living patients were followed more than 6 months.
At 5 years, actuarial overall local control (LC) rate and overall survival (OS) rate were 85% and 70%, respectively.
Five-year actuarial LC rate and OS rate in 123 patients with chordoma were 89% and 87%, respectively, and 84% and 36% in 21 patients with osteosarcoma, respectively.
Seven patients experienced grade 3 and/or 4 skin/soft tissue late reactions in this series. There were no GI toxicities beyond grade 2.
This is one of the largest series of primary malignant bone tumors of the sacrum.
Local control and overall survival at 5 years in patients with primary malignant bone tumors of the sacrum treated by carbon ion radiotherapy are similar to those in reported in series of patients treated by surgical resection with/without adjuvant radiotherapy.
Grade 3/4 skin reactions were observed in only 7 patients and no other severe morbidities were observed in this series.
Carbon ion radiotherapy is suggested to be an effective and safe treatment for primary malignant bone tumors of the sacrum especially for which surgical resection is not a viable option, and it appears to represent a promising alternative to surgery.
For tumors requiring high doses of radiation for acceptable local control, adequate doses are traditionally limited by unacceptable doses to OARs.
Particle therapy has a well-established history treating tumors of several histologies, and carbon ion RT combines the physical advantages of a particle beam together with distinct biological features that potentially lead to higher RBE in the tumor than in the surrounding normal tissue.
By using the physical properties of particle therapy, further local dose escalation is possible based on the physical properties of the Bragg peak and the finite range of carbon ion beams, even for tumors closely surrounded by critical structures.
Complete tumor resection can be difficult in primary malignant bone tumors of the sacrum and adjuvant or definitive radiation therapy is frequently needed. In these cases, particle therapy, which takes advantage of the Bragg peak, enables adequate dose to achieve local control.
Overall, the data presented here appear interesting and promising, with potentially improved results as compared to historical data with the use of photon and proton/photon irradiation; however, the nature of the study, small sample size and relatively short follow-up time presented preclude making statements regarding effectiveness as compared to surgical resection.
The data presented here demonstrate that delivery of adequate dose to primary malignant bone tumors of the sacrum is feasible and tolerable with carbon ions, and continued study with reports including longer follow up are warranted.