What’s New in Musculoskeletal Tumor Surgery 2020
Every month, JBJS publishes a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all such OrthoBuzz specialty-update summaries.
This month, author Peter S. Rose, MD summarized the 5 most compelling findings from the 40 studies highlighted in the December 16, 2020 “What’s New in Musculoskeletal Tumor Surgery.”
Primary Bone Tumors
–A retrospective analysis of data from the Euro-EWING99 trial1 is probably the most thorough examination to date of local tumor-control options in Ewing’s sarcoma of the pelvis–a difficult and controversial condition. The authors conclude with a recommendation for aggressive surgery and radiation in many patients, which goes beyond what most North American centers provide.
Metastatic Tumors
–Anderson et al. validate a fracture-risk calculating app2 that provides immediate clinical guidance on the risk of fracture and the role for surgery in patients with skeletal metastases. It is an early example of applying digital technology to provide real-time, individualized clinical guidance.
Phantom Limb Pain
–Alexander et al. provide an excellent early report of a new surgical technique3 (targeted muscle reinnervation) and a focused rehabilitation protocol to decrease phantom limb pain and maximize function after oncologic amputations.
Soft-Tissue Sarcomas
–After analyzing >1,600 patients treated for a soft-tissue sarcoma, Bedi et al. put forth a nomogram4 to predict postoperative wound complications, the single most frequent surgical complication in this population. The finding that BMI, tumor location, and timing of radiation are associated with the risk of wound complications is clinically relevant to all surgeons who treat these patients.
Carcinogenesis from Radiation Exposure
–This thought-provoking study predicted a lifetime fatal cancer risk of 3.5% from medical imaging studies used in the care of polytrauma patients. While the study focused on trauma patients rather than oncology patients, the striking results may have implications for how we use CT imaging to follow tumor patients as well.
References
- Andreou D, Ranft A, Gosheger G, Timmermann B, Ladenstein R, Hartmann W, Bauer S, Baumhoer D, van den Berg H, Dijkstra PDS, Dürr HR, Gelderblom H, Hardes J, Hjorth L, Kreyer J, Kruseova J, Leithner A, Scobioala S, Streitbürger A, Tunn PU, Wardelmann E, Windhager R, Jürgens H, Dirksen U; GPOH-Euro-EWING99 Consortium. Which factors are associated with local control and survival of patients with localized pelvic Ewing’s sarcoma? A retrospective analysis of data from the Euro-EWING99 trial. Clin Orthop Relat Res.2020 Feb;478(2):290-302.
- Anderson AB, Wedin R, Fabbri N, Boland P, Healey J, Forsberg JA. External validation of PATHFx version 3.0 in patients treated surgically and nonsurgically for symptomatic skeletal metastases. Clin Orthop Relat Res.2020 Apr;478(4):808-18.
- Alexander JH, Jordan SW, West JM, Compston A, Fugitt J, Bowen JB, Dumanian GA, Pollock R, Mayerson JL, Scharschmidt TJ, Valerio IL. Targeted muscle reinnervation in oncologic amputees: early experience of a novel institutional protocol. J Surg Oncol.2019 Sep;120(3):348-58. Epub 2019 Jun 13.
- Bedi M, Ethun CG, Charlson J, Tran TB, Poultsides G, Grignol V, Howard JH, Tseng J, Roggin KK, Chouliaras K, Votanopoulos K, Cullinan D, Fields RC, Cardona K, King DM. Is a nomogram able to predict postoperative wound complications in localized soft-tissue sarcomas of the extremity? Clin Orthop Relat Res.2020 Mar;478(3):550-9.
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.
3D-Printed Endoprosthesis Yields Promising Early Results
Tumor resections from the pelvic girdle often pose daunting reconstruction challenges for orthopaedic surgeons. In the September 2, 2020 issue of The Journal of Bone & Joint Surgery, Ji et al. report early results from a series of 80 bone-tumor patients who underwent pelvic reconstruction using a 3D-printed modular hemipelvic endoprosthesis. The 3D-printed interconnected porous component was generated from an electron beam melting process, and the design allowed for the main iliosacral fixation screws to be oriented parallel to the loading axis of the trunk.
The authors detected no acetabular component instability or implant loosening or migration after a mean follow-up of 32.5 months. The mean acetabular tilt on the reconstructed side immediately after surgery was 46.9o, and it was 47.1o at the most recent follow-up. The mean function score (84%, as measured by the Musculoskeletal Tumor Society 93 tool) was higher than the previously reported range of 55% to 72% from recent studies, and the authors say that the 3-month dislocation rate in this series (2.5%) “seems to be the lowest ever reported.” Moreover, histological analysis of specimens from 2 patients who experienced tumor recurrence revealed bone trabeculae extending toward the implant and bone ingrowth within the porous network.
Still, complications occurred in 16 (20%) of the patients, with wound dehiscence being the most prevalent one. Deep infections, relatively common after pelvic reconstruction surgery, occurred in 5 (6.3%) of the patients, which is a lower deep-infection rate than those reported in previous studies.
Despite the stable fixation and “satisfying early functional and radiographic outcomes” with this 3D-printed modular prosthesis, the authors caution that their short-term results “may prove to be insufficient for the assessment of implant viability.” Nevertheless, any innovation that helps address the many surgical challenges in this population of orthopaedic patients is welcome.
Complex Reconstructions Call for Creative Solutions
Metastatic disease around the acetabulum often leads to patients needing total hip arthroplasty (THA), plus supplementary acetabular reconstruction. Traditional methods such as the Harrington reconstruction technique have shown good short-term outcomes, but there are concerns that a cemented acetabular component in this setting is at risk for failure in the longer term. Newer approaches, such as using cementless tantalum acetabular components with augments, have also shown promise. Houdek et al. compared these 2 approaches and report the findings in the July 15, 2020 issue of The Journal.
The authors followed 115 patients who underwent THA for metastatic disease at 2 tertiary sarcoma centers, with a mean 4-year follow-up among surviving patients. They compared the outcomes of 78 Harrington reconstructions with those of 37 tantalum reconstructions, with surgeons at each center exclusively performing 1 of the 2 techniques. The cohorts were comparable at baseline regarding age, sex, severity of systemic disease and acetabular defects, and pelvic discontinuity. Functional outcomes improved in both groups, but there were no significant between-group differences. The main statistical finding of the study was that a higher percentage of patients in the Harrington reconstruction group (27%) needed a reoperation than those in the tantalum group (8%), with a hazard ratio of 4.59 (p=0.003).
Historically, there has been an understandable lack of long-term follow-up in this fragile patient population; 94 of the 115 patients in this study died of systemic disease progression at an average of 16 months after surgery. Overall patient survival was only 34% at 2 years and 15% at 10 years. Despite these grim mortality numbers, Houdek et al. claim that with advances in treatments for metastatic cancer, patients are living longer and therefore may benefit from more durable acetabular reconstructions.
This study leaves unanswered the question of whether the theoretic advantage of bony ingrowth with tantalum is what accounted for the decreased reoperation rates. As Albert Aboulafia, MD notes in his Commentary on this study, the authors did not review radiographs or postmortem histology to look for evidence of osseointegration. But Houdek et al. do present a potential avenue for further investigation. And what remains clear is that metastatic disease around the hip is a complex problem, and that we as surgeons should continue to investigate promising treatment strategies to improve patient outcomes (even if only palliative) and enhance biological fixation.
Click here for a 4-minute video in which co-author Matthew Houdek explains the rationale for this study.
Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media
Amid COVID-19, What Does “Elective” Mean?
As Sarac et al. note in the latest JBJS fast-tracked article, the phrase “elective procedure” is ambiguous, even though it is supposed to identify procedures that are being postponed to help hospitals cope with the COVID-19 pandemic. Guidelines from the Centers for Disease Control and Prevention (CDC) say that operations for “most cancers” and “highly symptomatic patients” should continue, but that leaves much of the ambiguity unresolved. What constitutes an elective procedure in orthopaedics at this unusual time remains unclear.
To help clarify the situation, the authors summarize guidance issued by states and describe the guidelines currently in use for orthopaedic surgery at their institution, The Ohio State University College of Medicine.
Here are the state-related data collected by Sarac et al., as of March 24, 2020:
- 30 states have published guidance regarding discontinuation of elective procedures; 16 of those states provide a definition of “elective” or offer guidance for determining which procedures should continue to be performed.
- 5 states provide guidelines specifically mentioning orthopaedic surgery; of those, 4 states explicitly permit trauma-related procedures, and 4 states recommend against performing arthroplasty.
- 10 states provide guidelines permitting the continuation of oncological procedures.
In the Buckeye State, the Ohio Hospital Association asked each hospital and surgery center to cancel procedures that do not meet any of the following criteria:
- Threat to a patient’s life if procedure is not performed
- Threat of permanent dysfunction of an extremity or organ system
- Risk of cancer metastasis or progression of staging
- Risk of rapid worsening to severe symptoms
Mindful of those criteria, individual surgical and procedural division directors at the authors’ university developed a list of specific procedures that should continue to be performed. Respective department chairs approved the lists, which were then sent to the hospital chief clinical officer for signoff.
The authors tabulate the orthopaedic procedures that continue to be performed at their institution as of March 25, 2020, but they are quick to add that even this list is not without ambiguity. For example, surgery should continue on “select closed fractures that if left untreated for >30 days may lead to loss of function or permanent disability,” but that requires surgeons to judge, in these uncertain and fluid times, which fractures necessitate fixation in the short term.
Sarac et al. emphasize that such lists, however specific they are today, are likely to change as demands on hospitals shift. They suggest that as the pandemic evolves, a further classification of procedures into 2 time-based categories might be helpful: (1) those that need to be performed within 2 weeks and (2) those that need to be performed within 4 weeks. Sarac et al. also remind orthopaedic surgeons to provide patients waiting for surgery that has been postponed with information regarding safe and effective methods of managing their pain.
What’s New in Musculoskeletal Tumor Surgery 2019
Every month, JBJS publishes a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of OrthoBuzz summaries of these “What’s New” articles. This month, author Peter S. Rose, MD selected the most clinically compelling findings from the 40 studies summarized in the December 18, 2019 “What’s New in Musculoskeletal Tumor Surgery.”
Staging Primary Bone Tumors
–The American Joint Committee on Cancer (AJCC) issued new staging criteria for primary bone tumors,1 largely in response to clinician reports that pelvic and spinal bone tumors have adverse clinical outcomes compared with extremity tumors. In the AJCC staging system, different criteria are applied to extremity, pelvic (inclusive of the sacrum), and mobile spinal tumors—an important step toward gathering data to better define the prognosis of these tumors.
Bone Metastases
–The skeletal system is the third most common site of metastatic disease, and the most common location of symptomatic skeletal metastases is about the hip. In a risk-adjusted analysis of US Veterans Administration data, Philipp et al. showed that patients with femoral metastases treated prophylactically have a lower risk of death (hazard ratio, 0.75) than similar patients treated after pathological fracture.2
Post-Resection Reconstruction
–Aponte-Tinao et al. investigated the ≥10-year survival of bulk allografts for the femur and tibia, demonstrating 60% graft survival in 166 patients.3 However, proximal tibial osteoarticular grafts fared poorly.
Soft-Tissue Sarcomas
–An analysis of the impact of obesity on soft-tissue sarcoma presentation and management4 arrived at 3 conclusions. Relative to non-obese patients,
- Obese patients presented with larger tumors (presumably because of difficulty detecting them).
- Obese patients required more complex wound closures.
- Obese patients experienced more complications.
–A retrospective analysis of the value of radiotherapy and chemotherapy in treating different subtypes of soft-tissue sarcomas5 revealed that myxoid liposarcomas, vascular sarcomas, and myxofibrosarcomas had the greatest benefit from radiation in terms of local control rates, although there was no difference in overall survival. Chemotherapy resulted in a 5% survival benefit.
References
- Kniesl JS, Rosenberg AE, Anderson PM, Antonescu C, Bruland O, Cooper K, Horvai A, Holt G, O’Sullivan B, Patel S, Rose P. Bone. In: Amin M.B., Edge S.B., Greene F.L., Byrd D.R., Brookland R.K., Washington M.K., Gershenwald J.E., Compton C.C., Hess K.R., Sullivan D.C., Jessup J.M., Brierley J.D., Gaspar L.E., Schilsky R.L., Balch C.M.,Winchester D.P., Asare E.A., Madera M., Gress D.M., Vega L.M., editors. AJCC cancer staging manual. 8th ed. Springer; 2018. p 471-86.
- Philipp T, Mikula J, Doung Y-C, Gundle K. Is there an association between prophylactic femur stabilization and survival in patients with metastatic bone disease? Clin Orthop Relat Res. 2019 May 17. [Epub ahead of print.]
- Aponte-Tinao L, Ayerza M, Albergo J, Farfalli GL. Do massive allograft reconstructions for tumors of the femur and tibia survive 10 or more years after implantation? Clin Orthop Relat Res. 2019 May 17. [Epub ahead of print.]
- Montgomery C, Harris J, Siegel E, Suva L, Wilson M, Morell S, Nicholas R. Obesity is associated with larger soft-tissue sarcomas, more surgical complications, and more complex wound closures (obesity leads to larger soft-tissue sarcomas). J Surg Oncol. 2018 Jul;118(1):184-91. Epub 2018 Jun 7.
- Callegaro D, Miceli R, Bonvalot S, Ferguson P, Strauss DC, Levy A, Griffin A, Hayes AJ, Stacchiotti S, Le P`echoux C, Smith MJ, Fiore M, Dei Tos AP, Smith HG, Catton C, Casali PG, Wunder JS, Gronchi A. Impact of perioperative chemotherapy and radiotherapy in patients with primary extremity soft tissue sarcoma: retrospective analysis across major histological subtypes and major reference centres. Eur J Cancer. 2018 Dec;105:19-27. Epub 2018 Oct 29.
Factors Affecting Union after Capanna Reconstruction
Resection of long-bone tumors often leaves large skeletal defects. Since the late 1980s, surgeons have used the “hybrid” Capanna technique—a vascularized fibular graft inlaid in a massive bone allograft—to fill those voids, with good functional outcomes reported. In the November 20, 2019 issue of The Journal of Bone & Joint Surgery, Li et al. report on factors influencing union after the Capanna technique.
The authors radiographically evaluated Capanna-technique reconstructions in 60 patients (10 humeral, 33 femoral, and 17 tibial) and correlated allograft-host union time to the following variables:
- Patient age
- Tumor site
- Adjuvant treatment (e.g., chemotherapy)
- Previous surgical procedures
- Defect length
- Fixation method
- Fibular viability (assessed with a bone scan 10 days after reconstruction)
They also histologically analyzed a retrieved specimen from one patient.
Among these 60 reconstructions, the mean defect length was 16 cm, and the mean time to union of the constructs was 13 months. The overall survival rate of the constructs was 93% at the latest follow-up.
Multivariate linear regression revealed no correlation between allograft-host osseous union time and patient age, defect length, tumor site, or fixation method. Conversely, devitalization of the transplanted fibular graft, chemotherapy administration, and a previous surgical procedure were associated with a prolonged union time. Histologically, the allograft-host cortical junction was united by callus from periosteum of both the host bone and the fibular graft.
Li et al. conclude that “ensuring patent vascular anastomoses of the transplanted fibula is crucial to prevent delayed or nonunion.” They also suggest that Capanna-technique patients who have any of the 3 “adverse factors” noted above should be treated with extended postoperative immobilization and delayed weight-bearing.
Whole-Slide View of Rare Orthopaedic Tumor
JBJS Case Connector debuted digital whole-slide images back in 2016, and the February 27, 2019 case report by Lans et al. put that ability to link to and navigate an entire microscope slide to good use again.
The 27-year-old man described in this case report presented with a progressively painful right forearm. Conventional radiographs and MRI led clinicians to suspect a rare desmoplastic fibroma of the proximal aspect of the radius, but it was not until a CT-guided core biopsy was analyzed histologically that the diagnosis could be confirmed. The histologic findings, depicted in a digital whole-slide image, revealed a fibrous to fibro-osseous lesion composed of fibroblast-like cells with varying degrees of hypercellularity.
The patient subsequently underwent a wide-margin resection that preserved the radial head but created an 8.5-cm defect, which surgeons reconstructed with a vascularized fibular autograft. At the 2-year follow-up, the patient’s QuickDASH score was 2.7 and his PROMIS Upper Extremity and Physical Function Short Form score was 42.
For more information about JBJS Case Connector, watch this video featuring JBJS Editor-in-Chief Dr. Marc Swiontkowski.
Giant-Cell Tumor Treatment: Curettage Without Denosumab Is Better
Denosumab is an FDA-approved drug for osteoporosis. It works by binding RANKL, thus inhibiting osteoclastic activity. Denosumab has also been shown to have a favorable impact on tumor response in relatively small, short-term studies among patients with giant-cell tumor of bone (GCTB).
In the March 21, 2018 issue of The Journal, Errani et al. report on a longer-term follow up (minimum 24 months, median 85.6 months) in two cohorts of patients with GCTB who were treated with joint-preserving curettage: those treated with curettage plus denosumab and those treated with curettage alone. The study found that denosumab administration was significantly associated with unfavorable outcomes in patients treated with curettage. Specifically, the local GCTB recurrence rate was nearly 4 times higher (60% vs 16%) in patients treated with denosumab plus curettage, compared to those treated with curettage alone.
Recent in vitro studies have shown that denosumab only slows giant-cell multiplication to some degree. The authors point out that patients treated with denosumab in this cohort study had more severe GCTB disease, which would seem to further confirm that cellular proliferation of giant cells is ineffectively slowed by this RANKL-binding drug. What’s most important about the Errani et al. study is that it’s the first one to look at the longer-term outcomes of denosumab usage before and after curettage for GCTB.
The authors emphasize that while their study shows a strong and independent association between denosumab administration and a high level of local recurrence, “causation could not be evaluated.” Still, at a time when clinicians, payers, and patients are critically evaluating every facet of treatment, it seems difficult to recommend the use of denosumab in addition to curettage for GCTB. The data in this study should encourage the musculoskeletal oncology community to continue to investigate other adjunctive treatments to be used with curettage for this disease process.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
In Spinal-Metastasis Surgery, High-Volume Yields Better Outcomes
In orthopaedics, the connection between a hospital/surgeon performing a surgical procedure many times and improved outcomes has been demonstrated compellingly with total joint replacement. In the October 18, 2017 edition of JBJS, Schoenfeld et al. show that this same volume-outcome relationship holds true in the surgical treatment of spinal metastases.
The study analyzed 3,135 patients treated by 1,488 surgeons at 162 hospitals throughout Florida. Using sophisticated statistics, the authors defined high-volume surgeons as those who had performed ≥49 procedures per year and high-volume hospitals as those at which ≥167 procedures per year had been performed.
Among the entire cohort, the 90-day complication rate was 26% and the readmission rate was 43%. (Rates that high are not unexpected with such risky spinal surgeries.) Here are the findings according to surgeon volume:
- 21% complication rate for patients treated by high-volume surgeons
- 30% complication rate for patients treated by low-volume surgeons
- 37% readmission rate for patients treated by high-volume surgeons
- 47% readmission rate for patients treated by low-volume surgeons
In other words, the relative odds of complications and readmissions following operations performed by low-volume surgeons were approximately 40% higher than those following operations done by high-volume surgeons. A similar percentage difference was found between the odds at low- and high-volume hospitals. In a secondary analysis, the authors found that African Americans and Hispanics were significantly less likely than white patients to receive care from a high-volume surgeon or at a high-volume hospital.
Schoenfeld et al. state that the ideal care for patients facing surgery for spinal metastases comes from a team of experienced surgeons, medical oncologists, radiation oncologists, nurses, and support staff. They conclude that their findings “speak to the need for regionalization of subspecialty spinal oncology care as a means to optimize treatment for this cohort of patients.”
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