Prognostic factors for spinal chordomas and chondrosarcomas treated with postoperative pencil-beam scanning proton therapy: a large, single-institution experience

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  • 1 Center for Proton Therapy, Paul Scherrer Institute, Villigen;
  • 3 Department of Physics, ETH, Zurich;
  • 4 Radiation Oncology Department, University Hospital of Bern;
  • 5 Radiation Oncology Department, University Hospital of Zurich, Switzerland; and
  • 2 Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland
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OBJECTIVE

The aim of this paper was to evaluate the prognostic factors in surgical and adjuvant care for spinal chordomas and chondrosarcomas after surgery followed by high-dose pencil-beam scanning proton therapy (PBS-PT).

METHODS

From 1997 to 2016, 155 patients (61 female patients; median age 55 years) with spinal (cervical, n = 61; thoracic, n = 29; lumbar, n = 13; sacral, n = 46; pelvic, n = 6) classic chordomas (n = 116) and chondrosarcomas (n = 39; most were low grade) were treated with maximal safe resection followed by PBS-PT (median dose prescribed: 74 Gy [relative biological effectiveness], range 48.6–77 Gy). The majority of patients (n = 153, 98.7%) had undergone at least 1 resection prior to PBS-PT (median 1, range 0–5; biopsy only, n = 2). Fewer than half (45.1%) of the surgeries were rated as gross-total resections (GTRs) prior to PBS-PT. Surgical stabilization (SS) was present in 39% of all patients (n = 60). Ninety-one patients (59%) presented with macroscopic tumor at the start of PBS-PT. The median follow-up duration was 64.7 months (range 12.2–204.8 months).

RESULTS

The 5-year local tumor control, disease-free survival (DFS), and overall survival were 64.9% (95% CI 56.3%–73.5%), 59.4% (95% CI 50.6%–68.2%), and 77.9% (95% CI 70.6%–85.2%), respectively. In total, 63 patients (40.6%) experienced failure during the follow-up period: local only in 32 (20.6%), distal only in 7 (4.5%), local + distal in 19 (12.3%), surgical pathway failure (SPF) only in 2 (1.3%), local + SPF in 2 (1.3%), and distal + SPF in 1 (< 1%). Univariate analysis identified gross residual disease, the presence of SS, and treatment era prior to 2008 as highly significant for worse outcome, with all 3 remaining significant on multivariate analysis. The type of surgery (GTR or subtotal resection/biopsy) and whether GTR was achieved by en bloc or curettage did not show a significant prognostic effect. Surgical complications prior to PBS-PT were present in 42.5% of all surgically treated patients and were seen more commonly in patients with multiple surgical interventions (p = 0.005) and those operated on with the intent of en bloc resection (p = 0.006).

CONCLUSIONS

The extent of resection and metallic stabilization substantially influenced clinical outcomes for patients with spinal chordoma or chondrosarcoma despite high-dose adjuvant PBS-PT. Optimal upfront surgical management of these tumors continues to include GTR, as possible, with prompt adjuvant proton therapy.

ABBREVIATIONS CTCAE = Common Terminology Criteria for Adverse Events; DFS = disease-free survival; GTR = gross-total resection; IMPT = intensity-modulated proton therapy; LC = local control; OS = overall survival; PBS-PT = pencil-beam scanning proton therapy; PSI = Paul Scherrer Institute; PTV = planning treatment volume; PTV1 = PTV subclinical dose; PTV2 = PTV prescription dose; RBE = relative biological effectiveness; SPF = surgical pathway failure; SS = surgical stabilization.

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Contributor Notes

Correspondence Damien C. Weber: Center for Proton Therapy, Paul Scherrer Institute, ETH Domain, Villigen, Switzerland. damien.weber@psi.ch; damiencharles.weber@uzh.ch.

INCLUDE WHEN CITING Published online January 31, 2020; DOI: 10.3171/2019.11.SPINE1927.

Disclosures Dr. Snider: consultant for Siemens Healthineers, Pyrexar, and Varian Medical Systems; and patent holder with ProtonGRID.

  • 1

    Ailon T, Torabi R, Fisher CG, Rhines LD, Clarke MJ, Bettegowda C, : Management of locally recurrent chordoma of the mobile spine and sacrum: a systematic review. Spine (Phila Pa 1976) 41 (Suppl 20):S193S198, 2016

    • Search Google Scholar
    • Export Citation
  • 2

    Amendola L, Cappuccio M, De Iure F, Bandiera S, Gasbarrini A, Boriani S: En bloc resections for primary spinal tumors in 20 years of experience: effectiveness and safety. Spine J 14:26082617, 2014

    • Search Google Scholar
    • Export Citation
  • 3

    Bergh P, Gunterberg B, Meis-Kindblom JM, Kindblom LG: Prognostic factors and outcome of pelvic, sacral, and spinal chondrosarcomas: a center-based study of 69 cases. Cancer 91:12011212, 2001

    • Search Google Scholar
    • Export Citation
  • 4

    Bjornsson J, Wold LE, Ebersold MJ, Laws ER: Chordoma of the mobile spine. A clinicopathologic analysis of 40 patients. Cancer 71:735740, 1993

    • Search Google Scholar
    • Export Citation
  • 5

    Boriani S, Bandiera S, Donthineni R, Amendola L, Cappuccio M, De Iure F, : Morbidity of en bloc resections in the spine. Eur Spine J 19:231241, 2010

    • Search Google Scholar
    • Export Citation
  • 6

    Boriani S, De Iure F, Bandiera S, Campanacci L, Biagini R, Di Fiore M, : Chondrosarcoma of the mobile spine: report on 22 cases. Spine (Phila Pa 1976) 25:804812, 2000

    • Search Google Scholar
    • Export Citation
  • 7

    Boriani S, Gasbarrini A, Bandiera S, Ghermandi R, Lador R: En bloc resections in the spine: the experience of 220 patients during 25 years. World Neurosurg 98:217229, 2017

    • Search Google Scholar
    • Export Citation
  • 8

    Cummings BJ, Hodson DI, Bush RS: Chordoma: the results of megavoltage radiation therapy. Int J Radiat Oncol Biol Phys 9:633642, 1983

  • 9

    DeLaney TF, Kepka L, Goldberg SI, Hornicek FJ, Gebhardt MC, Yoon SS, : Radiation therapy for control of soft-tissue sarcomas resected with positive margins. Int J Radiat Oncol Biol Phys 67:14601469, 2007

    • Search Google Scholar
    • Export Citation
  • 10

    DeLaney TF, Liebsch NJ, Pedlow FX, Adams J, Weyman EA, Yeap BY, : Long-term results of Phase II study of high dose photon/proton radiotherapy in the management of spine chordomas, chondrosarcomas, and other sarcomas. J Surg Oncol 110:115122, 2014

    • Search Google Scholar
    • Export Citation
  • 11

    Holliday EB, Mitra HS, Somerson JS, Rhines LD, Mahajan A, Brown PD, : Postoperative proton therapy for chordomas and chondrosarcomas of the spine: adjuvant versus salvage radiation therapy. Spine (Phila Pa 1976) 40:544549, 2015

    • Search Google Scholar
    • Export Citation
  • 12

    Indelicato DJ, Rotondo RL, Begosh-Mayne D, Scarborough MT, Gibbs CP, Morris CG, : A prospective outcomes study of proton therapy for chordomas and chondrosarcomas of the spine. Int J Radiat Oncol Biol Phys 95:297303, 2016

    • Search Google Scholar
    • Export Citation
  • 13

    Keisch ME, Garcia DM, Shibuya RB: Retrospective long-term follow-up analysis in 21 patients with chordomas of various sites treated at a single institution. J Neurosurg 75:374377, 1991

    • Search Google Scholar
    • Export Citation
  • 14

    Lomax A: Intensity modulation methods for proton radiotherapy. Phys Med Biol 44:185205, 1999

  • 15

    McDonald MW, Linton OR, Moore MG, Ting JY, Cohen-Gadol AA, Shah MV: Influence of residual tumor volume and radiation dose coverage in outcomes for clival chordoma. Int J Radiat Oncol Biol Phys 95:304311, 2016

    • Search Google Scholar
    • Export Citation
  • 16

    Molina CA, Ames CP, Chou D, Rhines LD, Hsieh PC, Zadnik PL, : Outcomes following attempted en bloc resection of cervical chordomas in the C-1 and C-2 region versus the subaxial region: a multiinstitutional experience. J Neurosurg Spine 21:348356, 2014

    • Search Google Scholar
    • Export Citation
  • 17

    Pennicooke B, Laufer I, Sahgal A, Varga PP, Gokaslan ZL, Bilsky MH, : Safety and local control of radiation therapy for chordoma of the spine and sacrum: a systematic review. Spine (Phila Pa 1976) 41 (Suppl 20):S186S192, 2016

    • Search Google Scholar
    • Export Citation
  • 18

    Potluri S, Jefferies SJ, Jena R, Harris F, Burton KE, Prevost AT, : Residual postoperative tumour volume predicts outcome after high-dose radiotherapy for chordoma and chondrosarcoma of the skull base and spine. Clin Oncol (R Coll Radiol) 23:199208, 2011

    • Search Google Scholar
    • Export Citation
  • 19

    Rich TA, Schiller A, Suit HD, Mankin HJ: Clinical and pathologic review of 48 cases of chordoma. Cancer 56:182187, 1985

  • 20

    Rotondo RL, Folkert W, Liebsch NJ, Chen YL, Pedlow FX, Schwab JH, : High-dose proton-based radiation therapy in the management of spine chordomas: outcomes and clinicopathological prognostic factors. J Neurosurg Spine 23:788797, 2015

    • Search Google Scholar
    • Export Citation
  • 21

    Rutz HP, Weber DC, Sugahara S, Timmermann B, Lomax AJ, Bolsi A, : Extracranial chordoma: outcome in patients treated with function-preserving surgery followed by spot-scanning proton beam irradiation. Int J Radiat Oncol Biol Phys 67:512520, 2007

    • Search Google Scholar
    • Export Citation
  • 22

    Schwab JH, Healey JH, Rose P, Casas-Ganem J, Boland PJ: The surgical management of sacral chordomas. Spine (Phila Pa 1976) 34:27002704, 2009

    • Search Google Scholar
    • Export Citation
  • 23

    Snider JW, Schneider RA, Poelma-Tap D, Stieb S, Murray FR, Placidi L, : Long-term outcomes and prognostic factors after pencil-beam scanning proton radiation therapy for spinal chordomas: a large, single-institution cohort. Int J Radiat Oncol Biol Phys 101:226233, 2018

    • Search Google Scholar
    • Export Citation
  • 24

    Stieb S, Snider JW III, Placidi L, Kliebsch U, Lomax AJ, Schneider RA, : Long-term clinical safety of high-dose proton radiation therapy delivered with pencil beam scanning technique for extracranial chordomas and chondrosarcomas in adult patients: clinical evidence of spinal cord tolerance. Int J Radiat Oncol Biol Phys 100:218225, 2018

    • Search Google Scholar
    • Export Citation
  • 25

    Talac R, Yaszemski MJ, Currier BL, Fuchs B, Dekutoski MB, Kim CW, : Relationship between surgical margins and local recurrence in sarcomas of the spine. Clin Orthop Relat Res (397):127132, 2002

    • Search Google Scholar
    • Export Citation
  • 26

    Verlaan JJ, Kuperus JS, Slooff WB, Hennipman A, Oner FC: Complications, secondary interventions and long term morbidity after en bloc sacrectomy. Eur Spine J 24:22092219, 2015

    • Search Google Scholar
    • Export Citation
  • 27

    Weber DC, Malyapa R, Albertini F, Bolsi A, Kliebsch U, Walser M, : Long term outcomes of patients with skull-base low-grade chondrosarcoma and chordoma patients treated with pencil beam scanning proton therapy. Radiother Oncol 120:169174, 2016

    • Search Google Scholar
    • Export Citation
  • 28

    Weber DC, Murray F, Combescure C, Calugaru V, Alapetite C, Albertini F, : Long term outcome of skull-base chondrosarcoma patients treated with high-dose proton therapy with or without conventional radiation therapy. Radiother Oncol 129:520526, 2018

    • Search Google Scholar
    • Export Citation
  • 29

    Wei F, Liu Z, Liu X, Jiang L, Dang G, Passias PG, : An approach to primary tumors of the upper cervical spine with spondylectomy using a combined approach: our experience with 19 cases. Spine (Phila Pa 1976) 43:8188, 2018

    • Search Google Scholar
    • Export Citation
  • 30

    York JE, Berk RH, Fuller GN, Rao JS, Abi-Said D, Wildrick DM, : Chondrosarcoma of the spine: 1954 to 1997. J Neurosurg 90 (1 Suppl):7378, 1999

    • Search Google Scholar
    • Export Citation
  • 31

    Zagars GK, Ballo MT: Significance of dose in postoperative radiotherapy for soft tissue sarcoma. Int J Radiat Oncol Biol Phys 56:473481, 2003

    • Search Google Scholar
    • Export Citation

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