Tag Archive | metastasis

Large Lytic Defects Produce Spinal Kinematic Instability

With the increasing effectiveness of immunotherapy and chemotherapy, patients with metastatic disease are surviving longer in much higher numbers. For many primary tumors (lung, breast, thyroid), a common site of metastases is the spine, giving rise to concomitant concerns regarding spine stability and the risk of neurologic compromise.

In the May 19, 2021 issue of JBJS, Alkalay et al. report the results of an in vitro study in which they simulated osteolytic defects in 3-level thoracic and lumbar segments of cadaveric spines. The simulations involved 2 patterns of lytic defects previously reported to be associated with increased risk of pathologic vertebral fracture: anterior-column compromise (40% of the vertebral body) and anterior plus middle-column compromise (extension of the model to include the ipsilateral pedicle and facet joint). The spinal segments were kinematically assessed in axial compression and axial compression with a flexion or extension moment, with testing before and after lesion simulation.

The authors concluded that “critical spinal lytic defects result in kinematic abnormalities and lower the compressive strength of the spine.” With greater lytic involvement, significantly higher translational motion along all 3 anatomic axes, and higher torsional and lateral-bending range of motion under axial compression with both flexion and extension moments were demonstrated.

The precision of the model in this cadaveric study was excellent. And the clinical implications of the findings are real: increasing lytic involvement of the vertebral body along with the pedicles could indicate impending instability, with the potential for neurologic injury. These data will be useful for surgeons and patients when formulating decisions regarding the need for intervention with fixation to limit flexion/extension forces in order to reduce pain and neurologic involvement. Future clinical data on the impact of these decisions in terms of pain and functional outcomes will be very valuable as we seek to optimize treatment of our patients with spinal metastatic disease.

Marc Swiontkowski, MD
JBJS Editor-in-Chief

 

Reducing Local Recurrence of Adamantinomas

The international multicenter study by Schutgens et al. in the October 7, 2020 issue of JBJS reports findings from an analysis of >300 cases of patients diagnosed with either classic adamantinomas (ADs) or osteofibrous dysplasia-like adamantinomas (OFD-ADs) who were followed for 7 to >10 years. The mean age at diagnosis was 17 years. The authors conclude that OFD-AD and AD are “parts of a disease spectrum but should be regarded as different entities.” Their findings, they say, also “support reclassification of OFD-AD into the intermediate locally aggressive [but non-metastatic] category” of bone tumors.

Perhaps the most clinically interesting findings in this study are related to local recurrence, which the authors describe as a “multifactorial” phenomenon in both tumor types. They found local recurrence in 22% of the OFD-AD cases and 24% of the AD cases. None of the recurrences in the OFD-AD group progressed to AD, which is a malignant disease with metastatic potential.

The authors found that the unadjusted cumulative incidence of local recurrence was higher if a pathological fracture was reported and if resection margins were contaminated. So, to reduce the risk of local recurrence in both tumor types, Schutgens et al. suggest “preventing pathological fracture after diagnosis and achieving uncontaminated margins with resection.”  The uncontaminated resection should include the periosteum of the involved bone at the time of surgery.

Faster Relief for Patients with Painful Bone Metastases

MR Guided Ultrasound for OBuzz2A technique that combines magnetic resonance (MR) imaging with high-intensity focused ultrasound hyperthermia provides faster pain relief than conventional radiation therapy (RT) for patients with a painful bone metastasis.

In the September 20, 2017 issue of JBJS, Lee et al. report on a matched-pair study of 63 patients with a painful bone metastasis who received either magnetic resonance-guided focused ultrasound (MRgFUS) or RT as first-line treatment. Both modalities were effective overall, yielding response rates of >70% at the three-month follow-up evaluation. However, MRgFUS was more efficient, providing a 71% response rate at 1 week after treatment, compared with 26% for RT at that same time point.

The total treatment time and cost of the two modalities were similar, and neither was associated with adverse events above grade 2. Among MRgFUS patients, there was a 14% rate of positioning-related pain and a 33% rate of sonication-related pain, which typically resolved within 1 day after treatment.

Lee et al. report that the median overall survival of patients in the study was 12.7 months in the MRgFUS group and 9.8 months in the RT group, a statistically nonsignificant difference. But the authors emphasize that the study was more about pain relief than extending life. “Reduc[ing] pain, restor[ing] function, and maintain[ing] quality of life is imperative” for those with bone metastasis, the authors conclude. They also caution that MRgFUS is not appropriate for bone metastases of the skull or most of the spine, or for any lesion that is not at least 1 cm away from “tissues at risk.”

What’s New in Orthopaedic Oncology

Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Here is a summary of selected findings from studies cited in the December 16, 2015 Specialty Update on orthopaedic oncology:

Malignant Primary Bone Tumors

  • A study comparing the efficacy of surgery versus radiation in 465 patients with Ewing sarcoma managed with standardized chemotherapy found lower local failure rates with surgery, but no significant differences in event-free survival, overall survival, or distant metastasis.1
  • A study of 30 long-term survivors of Ewing sarcoma after limb salvage found that, at a mean follow-up of 16 years, 83% of patients were performing athletic activity regularly. Those with pelvic and femoral resections with no reconstruction exercised more hours per week than those with endoprosthetic pelvic reconstruction.2
  • A survival and relapse analysis of 45 locally recurrent osteosarcomas identified a recurrent tumor that was ≥5 cm and metastatic disease at presentation as independent risk factors. Most recurrences were in soft tissues. Early detection and resection with wide negative margins are crucial for optimal outcomes.3
  • A long-term outcome study of 30 patients with recurrent sacral chordoma treated surgically found survival of 89% at two years, 56% at five years, and 19% at ten years. Wide resection gave the best chance of long-term survival, and complete resection of local recurrence gave the best chance of disease control.4

Benign Bone Tumors

  • A study investigating pulmonary metastasis risk factors in 167 patients with giant cell tumor of bone identified local recurrence as the strongest independent predictor of metastasis. Younger patients also had higher metastatic rates.
  • A multicenter study of clinical presentation and outcomes in 126 operatively treated patients with chondroblastoma of the extremities found a local recurrence rate of 4.8% over a minimum two-year follow-up. Findings suggested that local recurrence may be more common in patients with open physes.
  • An investigation of 195 patients with multiple hereditary exostosis found that seven (3.6%) had intraosseous chondroid lesions. Five of those patients developed chondrosarcomas.
  • Curettage, high-speed burring, and bone grafting without other adjuvants in 31 patients with an aneurysmal bone cyst resulted in only one recurrence (3.2%).5

Bone Metastasis and Reconstruction

  • In a study of 125 patients, CT-based structural rigidity analysis of femora to detect impending pathologic fractures had higher sensitivity, specificity, and predictive values than the Mirels classification.6
  • In 111 patients who underwent hemicortical allograft reconstruction of a remaining defect after hemicortical resection of a bone tumor, all of the host bone fractures healed without surgeons having to remove the allograft. The authors recommended hemicortical resections with allograft reconstructions for low- to intermediate-grade tumors.
  • Five-year revision-free survival of conventional total femoral replacements in 40 patients with primary malignant bone tumors was 48%. The most common mechanism of failure was soft-tissue insufficiency.7

References

  1. DuBois SG, Krailo MD, Gebhardt MC, Donaldson SS, Marcus KJ, Dormans J, Shamberger RC, Sailer S, Nicholas RW, Healey JH, Tarbell NJ, Randall RL, Devidas M, Meyer JS, Granowetter L, Womer RB, Bernstein M, Marina N, Grier HE. Comparative evaluation of local control strategies in localized Ewing sarcoma of bone: a report from the Children’s Oncology Group. Cancer. 2015 Feb1;121(3):467-75. Epub 2014 Sep 23.
  2. Hobusch GM, Lang N, Schuh R, Windhager R, Hofstaetter JG. Do patients with Ewing’s sarcoma continue with sports activities after limb salvage surgery of the lower extremity? Clin Orthop Relat Res. 2015 Mar;473(3):839-46.
  3. Takeuchi A, Lewis VO, Satcher RL, Moon BS, Lin PP. What are the factors that affect survival and relapse after local recurrence of osteosarcoma? Clin Orthop Relat Res. 2014 Oct;472(10):3188-95. Epub 2014 Jul 1.
  4. Xie C, Whalley N, Adasonla K, Grimer R, Jeys L. Can local recurrence of a sacral chordoma be treated by further surgery? Bone Joint J. 2015 May;97-B(5):711-5.
  5. Wang EH, Marfori ML, Serrano MV, Rubio DA. Is curettage and high-speed burring sufficient treatment for aneurysmal bone cysts? Clin Orthop Relat Res. 2014Nov;472(11):3483-8. Epub 2014 Jul 22.
  6. Damron TA, Nazarian A, Entezari V, Brown C, Grant W, Calderon N, Zurakowski D,Terek RM, Anderson ME, Cheng EY, Aboulafia AJ, Gebhardt MC, Snyder BD. CT-based structural rigidity analysis is more accurate than Mirels scoring for fracture prediction in metastatic femoral lesions. Clin Orthop Relat Res. 2015 Jul 14.
  7. Sevelda F, Schuh R, Hofstaetter JG, Schinhan M, Windhager R, Funovics PT. Total femur replacement after tumor resection: limb salvage usually achieved but complications and failures are common. Clin Orthop Relat Res. 2015Jun;473(6):2079-87. Epub 2015 Apr 2.