Large metastatic lesions of the diaphysis can cause considerable pain and result in difficult surgical challenges. Resection and cemented intercalary endoprosthetic reconstruction offer one solution ...to the problem, but it is an extensive operation that might not be tolerated well by a debilitated patient. The risk of aseptic loosening and revision after intercalary endoprosthetic replacement has varied in previous reports, which have not examined the risk of revision in the context of patient survival.
(1) In a small case series from one institution, what is the survivorship of patients after cemented intercalary endoprosthetic replacement for diaphyseal metastasis, and what is the cumulative incidence of revision for any reason? (2) What are the complications associated with cemented intercalary reconstruction? (3) What is the functional outcome after the procedure as assessed by the MSTS93 score?
We retrospectively studied 19 patients with diaphyseal long bone metastases who were treated with resection and cemented intercalary endoprosthetic reconstruction by five participating surgeons at one referral center from 2006 to 2017. There were 11 men and eight women with a median age of 59 years (range 46 to 80 years). The minimum follow-up required for this series was 12 months; however, patients who reached an endpoint (death, radiographic loosening, or implant revision) before that time were included. One of these 19 patients was lost to follow-up but was not known to have died. The median follow-up was 24 months (range 0 to 116 months). Eight of the 19 patients presented with pathologic fractures. Ten of 19 lesions involved the femur, and nine of 19 were in the humerus. The most common pathologic finding was renal cell carcinoma (in 10 of 19). Survival estimates of the patients were calculated using the Kaplan-Meier method. A competing risks estimator was used to evaluate implant survival, using death of the patient as the competing risk. We also estimated the cumulative incidence of aseptic loosening in a competing risk analysis. Radiographs were analyzed for radiolucency at the bone-cement-implant interfaces, fracture, integrity of the cement mantle, and component position stability. Complications were assessed using record review that was performed by an individual who was not involved in the initial care of the patients. Functional outcomes were assessed using the MSTS93 scoring system.
Patient survivorship was 68% (95% CI 50% to 93%) at 1 year, 53% (95% CI 34% to 81%) at 2 years, and 14% (95% CI 4% to 49%) at 5 years; the median patient survival time after reconstruction was 25 months (range 0 to 116 months). In the competing risk analysis, using death as the competing risk, the cumulative incidence of implant revision was 11% (95% CI 2% to 29%) at 1 year and 16% (95% CI 4% to 36%) at 5 years after surgery; however, the cumulative incidence of aseptic loosening (with death as a competing risk) was 22% (95% CI 6% to 43%) at 1 year and 33% (95% CI 13% to 55%) at 5 years after surgery. Other complications included one patient who died postoperatively of cardiac arrest, one patient with delayed wound healing, two patients with bone recurrence, and one patient who experienced local soft tissue recurrence that was excised without implant revision. Total MSTS93 scores improved from a mean of 12.6 ± 8.1 (42% ± 27%) preoperatively to 21.5 ± 5.0 (72% ± 17%) at 3 months postoperatively (p < 0.001) and 21.6 ± 8.5 (72% ± 28%) at 2 years postoperatively (p = 0.98; 3 months versus 2 years).
Resection of diaphyseal metastases with intercalary reconstruction can provide stability and short-term improvement in function for patients with advanced metastatic disease and extensive cortical destruction. Aseptic loosening is a concern, particularly in the humerus; however, the competing risk analysis suggests the procedure is adequate for most patients, because many in this series died of disease without undergoing revision.
Level IV, therapeutic study .
Osteosarcoma occurs predominantly in children and young adults. High-grade tumors require multidisciplinary treatment consisting of chemotherapy in the neoadjuvant and adjuvant settings, along with ...surgical intervention. Despite this approach, death from respiratory failure secondary to the development and progression of pulmonary metastases remains a significant problem. Here, we identify the IL-11 receptor α subunit (IL-11Rα) as a cell surface marker of tumor progression that correlates with poor prognosis in patients with osteosarcoma. We also show that both IL-11Rα and its ligand, IL-11, are specifically up-regulated in human metastatic osteosarcoma cell lines; engagement of this autocrine loop leads to tumor cell proliferation, invasion, and anchorage-independent growth in vitro. Consistently, IL-11Rα promotes lung colonization by human metastatic osteosarcoma cells in vivo in an orthotopic mouse model. Finally, we evaluate the IL-11Rα–targeted proapoptotic agent bone metastasis-targeting peptidomimetic (BMTP-11) in preclinical models of primary intratibial osteosarcomas, observing marked inhibition of both tumor growth and lung metastases. This effect was enhanced when BMTP-11 was combined with the chemotherapeutic drug gemcitabine. Our combined data support the development of approaches targeting IL-11Rα, and establish BMTP-11 as a leading drug candidate for clinical translation in patients with high-risk osteosarcoma.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Extremity reconstruction in skeletally immature patients presents unique challenges in terms of operative technique, bone healing, and limb function. A variety of insetting techniques have been ...described, with no clearly superior option. The authors hypothesized that vascularized fibula flaps placed in the intramedullary space are associated with shorter union times and better functionality compared with onlay flaps.
In a cohort study, the authors retrospectively reviewed the medical records of all pediatric patients who underwent fibula flap extremity reconstruction at a single center from 2001 through 2018. Comorbidities, complications, and outcomes were analyzed. Complete fibula union was based on radiographic evidence of significant cortical bridging.
Thirty-three patients (mean age, 13.6 years; range, 2 to 18 years) underwent pedicled ( n = 7) or free ( n = 26) fibula flap reconstructions in 12 upper extremities and 21 lower extremities. Median follow-up was 69.5 months (interquartile range, 16.3 to 114.6 months). Onlay and intramedullary fibula position compared with intercalary placement (median, 13.5 and 14.6 months versus 3.4 months; P = 0.002) were associated with longer time to complete bone union. Complications including allograft fracture ( P = 0.02) and hardware removal ( P = 0.018) were also associated with longer time to complete union and eventual conversion to megaprosthesis ( P = 0.02, P = 0.038). Thirty-two patients (97%) achieved full union and a functional reconstruction.
Fibula flap reconstruction is safe and effective for pediatric long-bone reconstruction. Longer fibula union times were associated with onlay and intramedullary fibula placement, allograft fracture, and hardware removal.
Therapeutic, IV.
Background
The perioperative period of major oncologic surgery is characterized by immunosuppression, angiogenesis, and an increased load of circulating malignant cells. It is a window period in ...which cancer cells may seed, invade, and proliferate. Thus, it has been hypothesized that the use of regional anesthesia with the goal of reducing surgical stress and opioid and volatile anesthetic consumption would avoid perioperative immune suppression and angiogenesis and ultimately cancer recurrence.
Questions/purposes
We performed a systematic review of the literature on the use of regional anesthesia and postoperative analgesia to improve cancer-related survival after oncologic surgery. Our primary topic of interest is survival after orthopaedic oncologic surgery, but because that literature is limited, we also have systematically reviewed the question of survival after breast, gastrointestinal, and genitourologic cancers.
Methods
We searched the PubMed and Embase databases with the search terms: “anesthesia and analgesia”, “local neoplasm recurrence”, “cancer recurrence”, “loco-regional neoplasm recurrence”, “disease-free survival”, and “cumulative survival rates”. Our initial search of the two databases provided 836 studies of which 693 were rejected. Of the remaining 143 studies, only 13 articles qualified for inclusion in this systematic review, based on defined inclusion criteria. All these studies had retrospective design. Due to the high heterogeneity among the identified studies and the complete absence of randomized controlled trials from the literature on this topic, the results of a meta-analysis would be heavily confounded; hence, we instead performed a systematic review of the literature.
Results
No eligible studies addressed the question of whether regional anesthesia and analgesia have an impact on survival after musculoskeletal cancer surgery. Only one relevant clinical study was identified on regional breast cancer survival; it suggested a benefit. The literature on gastrointestinal and genitourinary surgery was larger but mixed, although some preliminary studies do suggest a benefit of regional anesthesia on survival after oncologic surgery in those patient populations.
Conclusions
Although basic science studies suggest a potential benefit of regional anesthesia and stress response reduction in cancer formation, we found little clinical evidence to support the theory that regional anesthesia and analgesia improve overall patient survival after oncologic surgery.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Regional lymph node metastasis in extremity and trunk soft tissue sarcoma (ETSTS) is rare with no standardized management. We sought to determine management patterns for regional lymph ...node metastasis in ETSTS.
Methods
A survey regarding the management of ETSTS lymph node metastasis was distributed to the membership of the Musculoskeletal Tumor Society (MSTS) and the Society of Surgical Oncology (SSO) in January 2022. The survey queried the type of training (surgical oncology, orthopedic oncology), details of their practice setting, and management decisions of hypothetical ETSTS scenarios that involved potential or confirmed lymph node metastasis.
Results
The survey was distributed to 349 MSTS members (open rate of 63%, completion rate 21%) and 3026 SSO members (open rate of 55%, completion rate 4.7%) and was completed by 214 respondents, of whom 73 (34.1%) and 141 (65.9%) were orthopedic oncology and surgical oncology fellowship-trained, respectively. The majority of respondents practiced in an academic setting (
n
= 171, 79.9%) and treat >10 extremity sarcoma cases annually (
n
= 138, 62.2%). In scenarios with confirmed nodal disease for clear cell and epithelioid sarcoma, surgical oncologists were inclined to perform lymphadenectomy, while orthopedic oncologists were inclined to offer targeted lymph node excision with adjuvant radiation (
p
< 0.001). There was heterogeneity of responses regarding the management of nodal disease regardless of training background.
Conclusion
Self-reported management of nodal disease in ETSTS was variable among respondent groups with differences and similarities based on training background. These data highlight the variability of practice for nodal disease management and the need for consensus-based guidelines.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The standard preoperative radiotherapy regimen of 50 Gy delivered in 25 fractions for 5 weeks for soft tissue sarcomas results in excellent local control, with major wound complications occurring in ...approximately 35% of patients. We aimed to investigate the safety of a moderately hypofractionated, shorter regimen of radiotherapy, which could be more convenient for patients.
This single-centre, open-label, single-arm, phase 2 trial (HYPORT-STS) was done at a single tertiary cancer care centre (MD Anderson Cancer Center, Houston, TX, USA). We administered preoperative radiotherapy to a dose of 42·75 Gy in 15 fractions of 2·85 Gy/day for 3 weeks (five fractions per week) to adults (aged ≥18 years) with non-metastatic soft tissue sarcomas of the extremities or superficial trunk and an Eastern Cooperative Oncology Group performance status of 0–3. The primary endpoint was a major wound complication occurring within 120 days of surgery. Major wound complications were defined as those requiring a secondary operation, or operations, under general or regional anaesthesia for wound treatment; readmission to the hospital for wound care; invasive procedures for wound care; deep wound packing to an area of wound measuring at least 2 cm in length; prolonged dressing changes; repeat surgery for revision of a split thickness skin graft; or wet dressings for longer than 4 weeks. We analysed our primary outcome and safety in all patients who enrolled. We monitored safety using a Bayesian, one-arm, time-to-event stopping rule simulator comparing the rate of major wound complications at 120 days post-surgery among study participants with the historical rate of 35%. This trial is registered with ClinicalTrials.gov, NCT03819985, recruitment is complete, and follow-up continues.
Between Dec 18, 2018, and Jan 6, 2021, we assessed 157 patients for eligibility, of whom 120 were enrolled and received hypofractionated preoperative radiotherapy. At no time did the stopping rule computation indicate that the trial should be stopped early for lack of safety. Median postoperative follow-up was 24 months (IQR 17–30). Of 120 patients, 37 (31%, 95% CI 24–40) developed a major wound complication at a median time of 37 days (IQR 25–59) after surgery. No patient had acute radiation toxicity (during radiotherapy or within 4 weeks of the radiotherapy end date) of grade 3 or worse (Common Terminology Criteria for Adverse Events CTCAE version 4.0) or an on-treatment serious adverse event. Four (3%) of 115 patients had late radiation toxicity (≥6 months post-surgery) of at least grade 3 (CTCAE or Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme): femur fractures (n=2), lymphoedema (n=1), and skin ulceration (n=1). There were no treatment-related deaths.
Moderately hypofractionated preoperative radiotherapy delivered to patients with soft tissue sarcomas was safe and could therefore be a more convenient alternative to conventionally fractionated radiotherapy. Patients can be counselled about these results and potentially offered this regimen, particularly if it facilitates care at a sarcoma specialty centre. Results on long-term oncological, late toxicity, and functional outcomes are awaited.
The National Cancer Institute.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PURPOSE OF REVIEWTo review recent developments in the molecular pathogenesis of tenosynovial giant cell tumor (TGCT) or pigmented villonodular synovitis (PVNS) and its therapeutic implications.
...RECENT FINDINGSTGCT or PVNS is a benign clonal neoplastic proliferation arising from the synovium characterized by a minor population of intratumoral cells that harbor a recurrent translocation. These cells overexpress CSF1, resulting in recruitment of CSF1R-bearing macrophages that are polyclonal and make up the bulk of the tumor. Inhibition of CSF1R using small molecule inhibitors such as imatinib, nilotinib or sunitinib can result in clinical, radiological and functional improvement in the affected joint.
SUMMARYCurrently, surgery remains the treatment of choice for patients with TGCT/PVNS. Localized TGCT/PVNS is managed by marginal excision. Recurrences occur in 8–20% of patients and are easily managed by re-excision. Diffuse TGCT/PVNS tends to recur more often (33–50%) and has a much more aggressive clinical course. Patients are often symptomatic and require multiple surgical procedures during their lifetime. For patients with unresectable disease or multiple recurrences, systemic therapy using CSF1R inhibitors may help delay or avoid surgical procedures and improve functional outcomes.
Forequarter amputations (FQAs) and extended forequarter amputations (EFQAs) are rare procedures with high morbidity that often require significant soft-tissue or bony reconstruction. The authors ...describe the largest series of oncologic FQAs and EFQAs to date with associated reconstructive and oncologic outcomes.
The authors retrospectively reviewed data from all patients who underwent FQA or EFQA at The University of Texas M. D. Anderson Cancer Center from January 1, 2008, to January 1, 2019. Surgical outcomes, survival, and local recurrence rates were summarized and compared.
Forty-seven patients met the inclusion criteria, including 14 with EFQAs. Most patients (53%) were male; the median age was 58 years (range, 2 to 74). The most common tumor type was sarcoma (79%), and the most common presentation was recurrent (34%). Nineteen patients (40%) had distant metastases. The median defect size was 351 cm 2 ; flap reconstruction was required in 30 patients (64%). Eight patients (17%) experienced immediate complications and 12 (26%) experienced delayed complications. The median overall survival (OS) time was 21 months and the 5-year OS rate was 28.1%. OS and disease-free survival were superior in the EFQA group (69.8% versus 11.6%, P = 0.017; 58.9% versus 9.8%, P = 0.014, respectively). Metastasis at presentation was the most important predictor of survival on multivariate analysis (OR, 3.98; P = 0.004).
Patients with EFQA had better OS and disease-free survival than did patients with FQA, owing to a lower incidence of metastatic disease. This study suggests a benefit to more aggressive resection and reconstruction when disease is locally confined.
Therapeutic, III.
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