High-dose Proton-beam Based Radiation Therapy with or without Surgery in the Management of Primary and Recurrent Spine Chordomas: A Retrospective Review of Outcomes and Clinicopathologic Prognostic Factors
The Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 4 de octubre de 2011
Presenter: Ronny Rotundo, MD
Presenter's Affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
- Chordomas are rare, slow-growing, low metastatic potential, but locally aggressive tumors thought to arise from embryonic remnants of primitive notochordal elements.
- These types of tumors most often occur in the skull base and spinal column, particularly the sacrococcygeal region. Despite their slow-growing nature, these tumors can be very disruptive to patients lives due to their tendency to recur locally and cause significant pain and discomfort.
- Aggressive initial therapy consisting of maximal safe surgery as well as radiation has been found to improve overall outcome as salvage therapy portends poor local control.
- Due to the proximity to numerous critical structures, including the spinal cord, treatment can be challenging with complete resection often impossible.
- Although complete resection with or without radiation is the primary treatment, tumor location can often limit the feasibility of surgery. Due to the tendency for incomplete resection, radiation is frequently employed as adjuvant therapy.
- Additionally, due to dose limitations for the nearby critical spinal cord as well as other structures, dose escalation is difficult with photon radiation. Local control rates with surgery and conventional radiation below 60 Gy have been documented to be as low as 27- 0%. With conventional photon-based radiation therapy, doses capable of rendering local control have been difficult, if not impossible, to attain without unacceptable toxicity.
- Even with multimodality therapy, local recurrence remains the most common failure pattern.
- Both proton and carbon ion therapy have been investigated as they potentially allow increased dosage of radiation due to the dose characteristics. Proton beam radiotherapy offers steep dose fall off beyond the Bragg peak, possibly mitigating toxicity.
- An approach using a combination of photon- and proton-based radiotherapy has been utilized at Massachusetts General Hospital (MGH) since 1973 (Hug, 1995) for skull base and spinal cord chordomas.
- A phase II study of high-dose photon/proton radiotherapy in the management of spine sarcomas was published in 2009 (DeLaney, 2009). A total of 50 patients were treated with 48 month median follow-up. Reported 5-year actuarial local control, recurrence-free survival, and overall survival were 78%, 63%, and 87% respectively. 5.6% of patients treated for primary versus 50% for recurrent tumor developed local recurrence (p< 0.001).
- The purpose of the current presentation was to assess outcomes and clinicopathologic prognostic factors in patients undergoing high-dose proton-beam based RT with or without surgery in the management of primary or recurrent spine chordomas.
Materials and Methods
- Between November 1982 and January 2011, 126 patients (127 lesions) were treated with high-dose proton-beam based RT with or without surgery at the Massachusetts General Hospital for primary or recurrent spine CH.
- Patients were categorized according to disease status at presentation (primary vs recurrent) and by type of surgery performed (en bloc vs intralesional), extent of resection (gross total resection (GTR) vs subtotal resection (STR), margin status (R0/R1/R2), and according to RT received, including pre- and/or post-operative RT, as well as definitive RT without surgery for recurrent tumors.
- No cervical lesions were included in the analysis.
- A majority of patients were treated with a combined proton/ photon radiation plan with photons composing approximately 45% of the total dose.
- Seventy-one sacrococcygeal, 40 lumbar, and 16 thoracic chordomas (mean size 7.0 cm, range 1.6 - 21.7) occurring in 79 males and 47 females (mean age at diagnosis, 53.4 years) were analyzed.
- The last surgical intervention was en bloc resection for 61 patients and intralesional resection for 62 patients (n=3 unknown), with 78 patients having had at least one intralesional procedure during the course of their disease management.
- 97 resections were categorized as gross total resections and 30 as subtotal resections (R0 = 34, R1 = 58, R2 = 29).
- Of the 95 primary chordomas, 44 were treated with pre- and post-operative radiation while 51 were treated with post-operative radiation.
- Of the 32 recurrent chordomas, 16 were treated with pre- and post-operative radiation, 9 were treated with post-operative radiation, and 7 were treated with definitive radiation alone.
- The mean total radiation dose was 72.4 Gy RBE (range 46.3 - 83.6).
- With a median follow-up of 41 mos, 5 year outcomes for the entire cohort were the following:
- Overall survival (OS): 81%
- Local control (LC): 62%
- Locoregional (LRC): 60%
- Distant control (DC):77%
- LC for chordoma with primary presentation was 68% vs 49% for recurrent lesions (p=0.058).
- LC for chordoma treated with or without a component of pre-operative RT was 72% vs 54% (p=0.113), respectively.
- Among primary patients only, LC and LRC with vs without pre-operative RT were 85% vs 56% (p=0.019) and 79% vs 56% (p=0.034), respectively.
- Overall LC was significantly improved with en bloc resection vs intralesional resection (72% vs 55%, p=0.016) and there was a trend towards improved LC and LRC for R0 (negative) margin status.
- As the number of prior surgeries increased, the local control significantly declined.
- High-dose proton-based radiation therapy offers an effective treatment option for primary or recurrent chordoma. Among primary chordoma patients, high LC (85%) rates are achievable with the combination of pre-operative and post-operative RT.
- Patients with primary disease had significantly better local control and event free survival than patients with recurrent disease. Patients who underwent en bloc resection had significantly better local control than those with intralesional resection. Surgical resections with negative margins had a trend toward better control than patients with positive margins. Additionally, patients with primary tumors who underwent pre-operative radiation therapy had statistically improved local control than patients with post-operative radiation therapy. Finally, multiple surgeries had significant worse local control than patients with patients effectively treated upon initial presentation.
- Because of their location, biology, and high locoregional recurrence rates, chordomas are tumors that are infrequently amenable to R0 resections and frequently require adjuvant radiation.
- Proton therapy is an attractive treatment option affording the ability for excellent local control with limited acute and long-term toxicities. Proton therapy is at least as effective as historical controls with photon therapy.
- This presentation was a well performed retrospective study reporting outcomes of the largest series of spinal chordomas treated with proton therapy in the current literature. The authors have suggested that definitive treatment with pre-operative radiation followed by maximal safe resection improves local control in this debilitating tumor.
- The data presented here appear promising, with potentially improved results as compared to historical data. These support the data for skull base chordomas, suggesting radiation with dose escalation in additional to surgery improve local control. However, the retrospective nature of the study, small sample size, and relatively short follow-up time presented preclude making statements regarding effectiveness in the definitive setting. Additionally, as this report focused on the outcomes, it would be valuable to discuss the toxicity associated with the treatments.
- It would be very informative to have a prospective, randomized trial evaluating pre-operative vs. post-operative radiotherapy in the treatment of spinal chordoma.