Introduction: Current treatment of osteosarcoma includes surgical resection of all gross disease in conjunction with systemic chemotherapy to control micro-metastatic disease. This yields a 5-year ...event free survival (EFS) of approximately 70% for patients with localized osteosarcoma while patients with metastatic or recurrent disease fare poorly with overall survival rates of less than 20%.
Areas covered: This review outlines the current and future approach towards the treatment of osteosarcoma. A literature search was performed utilizing PubMed. Several recent clinical trials are reviewed in detail, as is innovative research evaluating novel agents and surgical techniques which hold promise.
Expert commentary: The outcome for patients with osteosarcoma has not changed in several decades. This plateau in survival rates highlights the need for a novel approach towards research. There remains a great deal of interest in utilizing the very high risk population of recurrent osteosarcoma patients to rapidly and sequentially evaluate novel agents to determine if any of these agents hold promise. Several phase II studies are ongoing or in development that offer hope based on intriguing preclinical data. Furthermore, initiatives in obtaining specimens to further explore the genetic and immunological profile behind osteosarcoma will be essential towards identifying novel pathways and targets to exploit.
Chondrosarcoma Weinschenk, Robert C; Wang, Wei-Lien; Lewis, Valerae O
Journal of the American Academy of Orthopaedic Surgeons,
07/2021, Volume:
29, Issue:
13
Journal Article
Peer reviewed
Chondrosarcoma is the second most common primary bone tumor, with >90% of cases representing the primary conventional subtype. In addition to arising de novo, conventional chondrosarcoma can arise ...secondary to a benign underlying lesion, such as enchondroma or osteochondroma. Symptoms are often characterized by focal, dull, aching pain to the affected region. Grade is a well-recognized prognostic factor in these tumors. Grade I lesions/atypical cartilaginous tumors rarely metastasize, rarely recur, and have a 10-year survival rate of >80%. By contrast, grade III lesions are associated with a poor prognosis with the highest local recurrence rates, a lung metastasis rate of >50%, and a 10-year survival rate of <30%. The standard treatment of high-grade conventional chondrosarcoma is complete surgical resection with wide margin. However, low-grade lesions may be amenable to curettage plus or minus adjuvant local treatment. Conventional chondrosarcoma does not respond to chemotherapy or standard radiation doses. Adjuvant treatment can be beneficial for some subtypes such as chemotherapy for dedifferentiated and mesenchymal chondrosarcoma and radiation additionally for mesenchymal chondrosarcoma. Emerging radiation technologies may also play a useful role in treating tumors in anatomically complex areas such as the spine or pelvis.
Orthopaedic surgeons in training and in their careers can experience a lack of confidence and imposter syndrome. Confidence is built early through continuous improvement, accomplishments, support, ...and reinforcement. Although it is normal to lack confidence at times, the goal is to recognize this issue, work on visualizing success, and know when to seek help. Mentors can help mentees to build confidence and to normalize thoughts of insecurity and imposter syndrome. It is critical to develop and to maintain resilience, grit, emotional intelligence, courage, and vulnerability during training and throughout one's entire orthopaedic career. Leaders in the field must be aware of these phenomena, be able to talk about such issues, have methods to combat the harmful effects of imposter syndrome, and create a safe, supportive environment conducive to learning and working. Leading well builds not only confidence in oneself but also self-confidence in others. Leaders who are able to build the confidence of individuals will enhance team dynamics, wellness, and overall productivity as well as individual and organizational success.
Insufficiency of the rotator cuff is a major problem after resections of proximal humeral tumors and can limit shoulder motion despite preservation of the deltoid muscle and axillary nerve. ...Allograft-prosthetic composite reconstruction offers one method to reattach the rotator cuff tendons and has been successful in small studies with short followup. However, data are lacking with regard to implant durability, changes in Musculoskeletal Tumor Society (MSTS) scores over time, and delayed complications with extended followup.
(1) What is the cumulative incidence of allograft-prosthetic composite revision surgery 5 years after the procedure? (2) What are the early- and intermediate-term MSTS scores of allograft-prosthetic composite reconstruction of the shoulder? (3) What are the complications of allograft-prosthetic composite reconstruction?
Twenty-one patients underwent allograft-prosthetic composite reconstruction after tumor resection of the proximal humerus between 2000 and 2015. Six patients who were lost to followup were not included. All patients had malignant or aggressive benign tumors that could be treated with a wide intraarticular approach preserving the deltoid muscle, axillary nerve, and glenoid. Cumulative incidence of implant revision was calculated with death of the patient as a competing risk. Minimum followup was 24 months (with the exception of one patient who died at 22 months), and median followup was 97 months (range, 20-198 months). The upper extremity MSTS score was used to assess function. Various complications were identified from radiographs and charts.
The cumulative risk of implant revision was 10.1% at 5 years (95% confidence interval CI, 1.6%-28.0%). Mean MSTS scores were 86% (± SD 9%) at 1 year and 78% (± SD 13%) at 5 years (mean difference ± SD 9% ± 14%, p = 0.015). Mean active forward elevation was 101° (± SD 33°) at 1 year and 92° (± SD 34°) at 5 years (mean difference ± SD 8° ± 36°, p = 0.41). Notable adverse events included progressive radiographic superior subluxation > 1 cm after 12 months followup (12 of 21 patients), delayed union > 12 months (10 of 21 patients), resorption of the greater tuberosity (nine of 21 patients), and aseptic loosening (three of 21 patients).
At intermediate 5-year followup, allograft-prosthetic composite reconstruction of the proximal humerus has an acceptable overall MSTS score and a low incidence of implant revision, but loss of patients to followup and exclusion from the study likely make the results seem better than they actually are. The MSTS score deteriorates between 1 and 5 years. Decreased active forward elevation is not likely to be the sole reason for worsening MSTS scores. A variety of delayed complications including delayed union, resorption of the greater tuberosity, and superior subluxation occurs frequently and may contribute to overall scores. Future studies that compare allograft-prosthetic composites against other forms of reconstruction should attempt to control for possible selection bias and have sufficiently long followup to detect the deterioration of MSTS scores that occur with time.
Level IV, therapeutic study.
Whatʼs New in Musculoskeletal Oncology Lewis, Valerae O
Journal of bone and joint surgery. American volume,
2009-June-01, Volume:
91, Issue:
6
Journal Article
Limited clinical activity has been seen in osteosarcoma (OS) patients treated with immune checkpoint inhibitors (ICI). To gain insights into the immunogenic potential of these tumors, we conducted ...whole genome, RNA, and T-cell receptor sequencing, immunohistochemistry and reverse phase protein array profiling (RPPA) on OS specimens from 48 pediatric and adult patients with primary, relapsed, and metastatic OS. Median immune infiltrate level was lower than in other tumor types where ICI are effective, with concomitant low T-cell receptor clonalities. Neoantigen expression in OS was lacking and significantly associated with high levels of nonsense-mediated decay (NMD). Samples with low immune infiltrate had higher number of deleted genes while those with high immune infiltrate expressed higher levels of adaptive resistance pathways. PARP2 expression levels were significantly negatively associated with the immune infiltrate. Together, these data reveal multiple immunosuppressive features of OS and suggest immunotherapeutic opportunities in OS patients.
Soft tissue sarcomas are a heterogeneous and rare group of solid tumors of mesenchymal origin that can arise anywhere in the body. Although surgical resection is the mainstay of treatment for ...patients with localized disease, disease recurrence is common and 5-year overall survival is poor (~ 65%). Both radiation therapy and conventional chemotherapy are used to reduce local and distant recurrence. However, the utility of radiation therapy is often limited by disease location (in the case of retroperitoneal sarcomas, for instance) while systemic therapy with conventional lines of chemotherapy offer limited efficacy and are often poorly tolerated and associated with significant toxicity. Within the past decade, major advances have been made in the treatment of other malignancies including melanoma, renal cell carcinoma, and non-small cell lung carcinoma with the advent of immune-checkpoint inhibitors such as ipilimumab (anti-CTLA4), pembrolizumab (anti-PD1), and nivolumab (anti-PD1). The recently published SARC028 (NCT02301039), an open label, phase II, multicenter trial of pembrolizumab in patients with advanced bone and soft tissue sarcomas reported promising activity in select histologic subtypes of advanced STS, including undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.
There is a clear need for novel and effective adjuncts in the treatment of STS. We hypothesize that immune checkpoint blockade will be effective in patients with surgically resectable primary or locally recurrent dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma when administered in the neoadjuvant setting. The primary aim of this phase II, single-center, open label, randomized non-comparative trial is to determine the pathologic response to neoadjuvant nivolumab monotherapy and combination nivolumab/ipilimumab in patients with resectable dedifferentiated liposarcoma of the retroperitoneum or undifferentiated pleomorphic sarcoma of the trunk or extremity treated with concurrent standard of care neoadjuvant radiation therapy.
This study will help define the role of single agent anti-PD1 and combination anti-CTLA4 and anti-PD1 therapy in patients with surgically resectable dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma.
ClinicalTrials.gov NCT03307616 , registered October 12, 2017.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Outcomes of targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) in the oncologic population are limited. We sought to examine the safety and effectiveness of TMR ...and RPNI in controlling postamputation pain in the oncologic population.
A retrospective cohort study of consecutive patients who underwent oncologic amputation followed by immediate TMR and/or RPNI was conducted from November 2018 to May 2022. Primary study outcome was postamputation pain, assessed using the Numeric Pain Scale (NPS), and Patient-Reported Outcomes Measurement Information System (PROMIS ®) for residual limb pain (RLP) and phantom limb pain (PLP). Secondary outcomes included postoperative complications, tumor recurrence, and opioid use.
Sixty-three patients were evaluated with mean follow-up period of 11.3 months. The majority of patients (65.1%) had a history of previous limb salvage. At final follow-up, patients had an average NPS RLP of 1.3 ± 2.2 and PLP 1.9 ± 2.6. The final average raw PROMIS® measures were Pain Intensity 6.2 ± 2.9 (T-score 43.5), Pain Interference 14.6 ± 8.3 (T-score 55.0), and Pain Behavior 39.0 ± 22.1 (T-score 53.4). Patient opioid use decreased from 85.7% preoperatively to 37.7% postoperatively and morphine milligram equivalents (MME) decreased from a mean of 52.4 ± 53.0 preoperatively to 20.2 ± 38.4.
TMR and RPNI in the oncologic population are safe surgical techniques associated with significant reductions in PLP, RLP and improvements in patient-reported outcomes. This study provides evidence for the routine incorporation of TMR and RPNI in the multidisciplinary care of oncologic amputees.
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 .
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