Impact of Surveillance Imaging in Detecting Local and Metastatic Lung Recurrences Among Patients with Sarcomas of the Extremities: A Systematic Review and Meta-analysis.

BACKGROUND: The surveillance guidelines following treatment completion for patients with high-grade sarcomas of the extremities are based largely upon expert opinions and consensus. In the current meta-analysis, we aim to study the utility of surveillance imaging to diagnose local and metastatic pulmonary relapses among patients with extremity soft tissue sarcomas and primary bone sarcomas. PATIENTS AND METHODS: A meta-analysis was performed to assess the sensitivity, specificity and diagnostic odds ratio (DOR) of surveillance imaging to diagnose local and metastatic pulmonary relapse among patients with sarcoma of the extremities. In addition, impact of surveillance imaging on overall survival was assessed. Heterogeneity among eligible studies was evaluated by I2 statistics. Sensitivity analysis was assessed using influence plots and Baujat plots. RESULTS: Ten studies including 2160 patients with sarcoma were found eligible. For diagnoses of local recurrence based on surveillance imaging (nine studies, 1917 patients), the estimated sensitivity, specificity, and DOR were 13.6%, 99.5%, and 78.15, respectively. Only 16.7% of local recurrences were diagnosed based on imaging. For diagnoses of metastatic pulmonary recurrence (eight studies; 1868 patients), estimated sensitivity, specificity, and DOR were 76.1%, 99.3%, and 1059.9, respectively. A sensitivity analysis showed significant heterogeneity among included studies. None of the included studies showed an overall-survival benefit with the use of surveillance imaging. CONCLUSION: The current meta-analysis challenges the notion of routine use of imaging to detect local relapse, while favoring chest imaging, using either chest radiography or computed tomography scan, for surveillance. Further studies are required to study the ideal surveillance strategy including timing and imaging modality.

Elevated cobalt levels in metal-on-polyethylene knee megaprostheses: a prospective 1-year cohort study of 56 patients with hip and knee megaprostheses.

BACKGROUND AND PURPOSE: Concerns have emerged regarding elevated levels of cobalt and chromium in patients with metal-on-metal megaprostheses. This prospective study aims to identify systemic cobalt and chromium levels in metal-on-polyethylene knee and hip megaprostheses and their associations with other factors. METHODS: 56 patients underwent knee or hip megaprosthesis surgery at 2 sarcoma centers. Serum cobalt and chromium levels were measured preoperatively and thrice within the first year using inductively coupled plasma mass spectrometry. RESULTS: A statistically significant difference in serum cobalt levels (1.4 ppb; 95% confidence interval [CI] 0.0-3.3) was observed 1 year after knee megaprosthesis surgery compared with preoperative levels. In contrast no difference in chromium levels was observed after 1 year compared with preoperative levels (0.05 ppb; CI 0.0-0.8). An association between younger age, higher eGFR, and increased cobalt levels was observed. No significant correlations were found between ion levels and resection length or the number of modular connections. CONCLUSION: We found elevated serum ion levels in metal-on-polyethylene knee megaprostheses in contrast to metal-on-polyethylene hip megaprostheses. Furthermore, a positive correlation between cobalt and chromium levels, and between cobalt and eGFR was identified, along with a negative correlation between cobalt and age. This study highlights the importance of monitoring systemic cobalt and chromium levels in patients with megaprostheses.

Rotationplasty after failed limb salvage: an alternative to amputation.

PURPOSE: Limb salvage procedures for musculoskeletal tumors have inherent complications. Though most complications can be managed with retention of the reconstructions, occasionally salvaging these reconstructions is not possible. We evaluated the outcomes of patients undergoing rotationplasty after multiple failed revisions of limb salvage surgery and document the success rate of this "salvage" technique and the subsequent functional outcome of these patients. METHOD: Between January 1, 1999, and December 31, 2018, 14 patients (12 male and 2 female) with a median age of 24 years (11-51 years) underwent rotationplasty after multiple failed revisions of limb salvage surgery. Indication for rotationplasty was infection (10 patients), failed megaprosthesis (2 patients), unstable biological reconstruction (1 patient) and local recurrence (1 patient). The mean number of surgeries done before the patient underwent rotationplasty was 5 (range 2-7). RESULTS: One patient developed a vascular complication (venous congestion) immediately after rotationplasty and underwent an early amputation. The remaining 13 patients had no surgical complications. Mean Musculo Skeletal Tumor Society score in 13 evaluable patients was 26 (23-30). CONCLUSION: Our study demonstrates the utility of rotationplasty as a "salvage" procedure after multiple failed lower limb salvage surgeries. It offers good success rates, low rates of complications and good functional outcomes in carefully selected cases.

Incidence of SARS-CoV-2 infection among asymptomatic patients undergoing preoperative COVID testing prior to cancer surgery: ASPECT study.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic, with high rate of asymptomatic infections and increased perioperative complications, prompted widespread adoption of screening methods. We analyzed the incidence of asymptomatic infection and perioperative outcomes in patients undergoing cancer surgery. We also studied the impact on subsequent cancer treatment in those with COVID-19. METHODS: All patients who underwent elective and emergency cancer surgery from April to September 2020 were included. After screening for symptoms, a preoperative test was performed from nasopharyngeal and oropharyngeal swabs before the procedure. Patients were followed up for 30 days postoperatively and complications were noted. RESULTS: 2108 asymptomatic patients were tested, of which 200 (9.5%) tested positive. Of those who tested positive, 140 (70%) underwent the planned surgery at a median of 30 days from testing positive, and 20 (14.3%) had ≥ Grade III complications. Forty (20%) patients did not receive the intended treatment; 110 patients were retested in the Postoperative period, and 41 (37.3%) tested positive and 9(22%) patients died of COVID-related complications. CONCLUSION: Routine preoperative testing for COVID-19 helps to segregate patients with asymptomatic infection. Higher complications occur in those who develop COVID-19 in postoperative period. Prolonged delay in surgery after COVID infection may influence planned treatment.

Surgical Site Infections in patients undergoing major oncological surgery during the COVID-19 paNdemic (SCION): A propensity-matched analysis.

BACKGROUND AND OBJECTIVES: There are reports of outcomes of elective major cancer surgery during the COVID-19 pandemic. We evaluated if reinforcement of hand hygiene, universal masking, and distancing as a part of pandemic precautions led to a decrease in the incidence of surgical site infections (SSIs) in major oncologic resections. METHODS: Propensity score matching using the nearest neighbor algorithm was performed on 3123 patients over seven covariates (age, comorbidities, surgery duration, prior treatment, disease stage, reconstruction, and surgical wound type) yielding 2614 matched (pre-COVID 1612 and COVID 1002) patients. Conditional logistic regression was used to identify if SSI incidence was lower amongst patients operated during the pandemic. RESULTS: There was a 4.2% (p = 0.006) decrease in SSI in patients operated during the pandemic. On multivariate regression, surgery during the COVID-19 period (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.61-0.98; p = 0.03), prior chemoradiation (OR = 2.46; CI = 1.45-4.17; p < 0.001), duration of surgery >4 h (OR = 2.17; 95%CI = 1.55-3.05; p < 0.001) and clean contaminated wounds (OR = 2.50; 95% CI = 1.09-2.18; p = 0.012) were significantly associated with SSI. CONCLUSION: Increased compliance with hand hygiene, near-universal mask usage, and social distancing during the COVID-19 pandemic possibly led to a 23% decreased odds of SSI in major oncologic resections. Extending these low-cost interventions in the post-pandemic era can decrease morbidity associated with SSI in cancer surgery.

Percutaneous Radiofrequency Ablation of Appendicular Skeleton Chondroblastoma-an Experience from a Tertiary Care Cancer Center.

PURPOSE: To evaluate safety and long-term efficacy of radiofrequency (RF) ablation in treatment of chondroblastoma. MATERIALS AND METHODS: This retrospective analysis comprised 27 consecutive patients with histopathologically proven chondroblastoma treated by RF ablation. The tumors were located in the proximal humerus (n = 6), proximal tibia (n = 8), proximal femur (n = 6), distal femur (n = 5), acromion process (n = 1), and lunate (n = 1). In 19 patients (70.3%), the tumor was in the weight-bearing area of the bone. Clinical response was assessed by comparing pain scores and functional assessment by Musculoskeletal Tumor Society (MSTS) score before and after ablation. Patients were followed for a minimum of 1 year to rule out complications and recurrence. RESULTS: Technical success rate was 100%. Mean pain score before the procedure was 7.34 (range, 7-9); all patients experienced a reduction in pain, with 25 (92.6%) patients reporting complete pain relief at 6 weeks. Mean MSTS score before the procedure was 15.4, whereas mean MSTS score at 6 weeks after the procedure was 28.6, suggesting significant functional improvement (P < .0001). Two patients developed osteonecrosis and collapse of the treated bone. There were no recurrences. CONCLUSIONS: Percutaneous RF ablation is a safe and effective option for treating chondroblastoma of the appendicular skeleton.

Giant cell tumors of the sacrum: is non-operative treatment effective?

PURPOSE: Giant cell tumors of sacrum in which surgery could endanger important neural components were treated with short term denosumab, angioembolisation and radiotherapy in different combinations to provide a non-operative function preserving treatment option. METHODS: Between April 2013 and April 2017, 13 sacral GCTs [proximal extent of disease-S1 (10), S2 (2) and S3 (1)] were treated. Age ranged from 20 to 50 years. One patient had loss of bladder control at presentation. Treatment protocol included short term denosumab, angioembolisation and radiotherapy in different combinations. Patients were evaluated every 10-12 weeks. If disease ceased to progress no further treatment was advised. In case of progress, patient was advised additional denosumab and/or angioembolisation and/or radiotherapy till disease stopped progressing. RESULTS: 10 patients have non-progressive disease and are asymptomatic, 2 have non-progressive disease with occasional pain, 1 patient died. Follow-up duration (since final non-progression of disease) ranged from 15 to 54 months (mean 31 months). Total number of angio embolisation sessions ranged from 0 to 12 (mean = 4), total number of denosumab doses ranged from 5 to 16 (mean = 9). Five patients did not receive any radiotherapy, 5 received 50.4 Gy and one patient each received 50.4 + 30 + 12 Gy, 50.4 + 30 Gy and 50.4 + 12 Gy. The patient with loss of bladder control at presentation recovered. There were no other long-term complications. CONCLUSION: This study offers a non-surgical management option that provides good mid-term local control while preserving neurological function in these complex lesions.

Outcomes of Elective Major Cancer Surgery During COVID 19 at Tata Memorial Centre: Implications for Cancer Care Policy.

BACKGROUND: Overburdened systems and concerns of adverse outcomes have resulted in deferred cancer surgeries with devastating consequences. In this COVID pandemic, the decision to continue elective cancer surgeries, and their subsequent outcomes, are sparsely reported from hotspots. METHODS: A prospective database of the Department of Surgical Oncology was analysed from March 23rd to April 30th, 2020. FINDINGS: Four hundred ninety-four elective surgeries were performed (377 untested and 117 tested for Covid 19 before surgery). Median age was 48 years with 13% (n = 64) above the age of 60 years. Sixty-eight percent patients were American Society of Anaesthesiology (ASA) grade I. As per surgical complexity grading, 71 (14·4%) cases were lower grade (I-III) and 423 (85.6%) were higher grade complex surgeries (IV - VI).Clavien-Dindo ≥ grade III complications were 5.6% (n = 28) and there were no postoperative deaths. Patients >60 years documented 9.3% major complications compared to 5.2% in <60 years (P = 0.169). The median hospital stay was 1 to 9 days across specialties.Postoperatively, 26 patients were tested for COVID 19 and 6 tested positive. They all had higher grade surgeries but none required escalated or intensive care treatment related to COVID infection. INTERPRETATION: A combination of scientific and administrative rationale contributed to favorable outcomes after major elective cancer surgeries. These results support the continuation of elective major cancer surgery in regions with Covid 19 trends similar to India.

Proximal femur sarcomas with intra-articular disease-Do intra-articular resections provide adequate local control?

BACKGROUND AND OBJECTIVES: Hip preserving (intra-articular) resections for proximal femur sarcoma have better function compared to peri-acetabular (extra-articular) resections, which are more complex and morbid. But, do intra-articular resections in selected cases with intra-articular disease provide adequate local control? METHOD: Extra-articular resection or intra-articular resection in cases without pathologic fracture or away from joint/capsule was classified as a planned safe margin (SM). Circumferential removal of labrum without acetabular resection in cases without gross joint contamination was classified as planned close margins (CM). We analyzed local recurrence-free survival (LRFS) (death as a competing event) for 86 proximal femur resections (SM = 55, CM = 31). RESULTS: The 5 years LRFS was 84% (n = 6/55, 10%) in the SM group and 67% (n = 4/31, 12%) in the CM group. There was no worsening of local recurrence (LR) in the CM group (subdistribution hazard [sH] = 0.69; 95% confidence interval [CI], 0.21-2.29; P = .56). Poor chemotherapy-induced necrosis predicted worse LR (sH = 0.1; 95% CI, 0.01-0.8; P = .03). Overall survival was 16% (SE 8%) at 5 years with LR vs 64% (SE 7%) without LR (P = .0076). CONCLUSION: In proximal femur sarcomas with potential for involvement of the hip joint, a CM in selected cases did not worsen LR; providing an option for avoiding additional morbidity with extra-articular resections.

Compliance and perception about personal protective equipment among health care workers involved in the surgery of COVID-19 negative cancer patients during the pandemic.

BACKGROUND: Health care workers (HCWs) are at risk of getting infected while at work, for example, operating room (OR), hence it is pertinent that they don all the appropriate personal protective equipment (PPE) to minimize the chance of getting infected. METHODS: A COVID-19 specific briefing and debriefing form was created and used in the OR along with the World Health Organization surgical safety checklist to reinforce the use of appropriate PPE. An audit was subsequently done to understand the compliance to PPE use, followed by a survey based on the findings of the audit to understand the issues related to noncompliance. RESULTS: The form was used in 183 out of the 238 (77%) surgeries performed during a months' time. The overall compliance for PPE usage was 96.3%. Noncompliance was seen most often for eye protection (45/567) (P = .01). The survey revealed that this was mostly among surgeons mainly due to discomfort, poor visibility, and frequent fogging. CONCLUSIONS: Our HCW were adapting well to the new normal of donning appropriate PPE in the OR, except for the eye protection due to discomfort and visibility related issues. This is important to know so that necessary changes could be introduced to better the compliance.

Outcomes with nondose-dense chemotherapy for Ewing sarcoma: A practical approach for the developing world.

BACKGROUND: The current multidisciplinary approach in the treatment of Ewing sarcoma has improved cure rates, with contemporary dose-dense chemotherapy attaining 5-year event-free survival (EFS) of 73% in localized cases. Dose-intense and dose-dense chemotherapy is difficult in the majority of resource-limited settings with limited access to optimal supportive care. We report on patients with Ewing sarcoma treated on EFT-2001, a nondose-dense chemotherapy protocol. PROCEDURE: A retrospective analysis was conducted of patients (<15 years) with Ewing sarcoma treated with curative intent during January 2013-June 2017 with an institutional ethics committee-approved nondose-dense protocol (EFT-2001). Local therapy was planned after 9-12 weeks of chemotherapy with metastatic sites addressed with radiotherapy. The study assessed outcomes and prognostic factors. RESULTS: We analysed 200 patients with M:F ratio of 1.27:1 and metastases in 41 patients (20.5%). At a median follow up of 41.5 months (range 4.5-81.8 months), respective 3-year EFS and overall survival (OS) of the whole cohort is 65.3% (95% confidence interval [CI]: 58.1-71.7%) and 79.3% (95% CI: 72.8-84.5%); for localized and metastatic cohort, 70.9% (95% CI: 62.9-77.5%) and 82.8% (95% CI: 75.7-89.0%); and for metastatic cohort, 42.8% (95% CI: 28.0-58.6%) and 65.3% (95% CI: 47.7-78.3%). Presence of residual disease (morphologic/metabolic) on positron emission tomography-computed tomography scan done 3 months post definitive radiotherapy (hazard ratio [HR] 7.92 [95% CI: 3.46-18.14]) and delay in any form of local control >4 months (HR 3.42 [95% CI: 1.32-8.89]) affected outcomes. Nonrelapse mortality during treatment was 6.5%, mainly due to cardiomyopathy (3.0%) and bacterial sepsis (1.5%). Cardiotoxicity was seen in 11.5% of patients. CONCLUSIONS: Nondose-dense chemotherapy provides good outcomes with manageable toxicities in a multidisciplinary treatment approach, while reducing cumulative drug exposures in the developing world where dose-intense or dose-dense chemotherapy could potentially increase toxicity, and hence seems a feasible approach in resource-limited settings. Presence of any residual disease post definitive radiotherapy or delay in local control portends poor outcome.

Is Skeletal Imaging Essential in the Staging Workup for Conventional Chondrosarcoma?

BACKGROUND: Staging of a bone sarcoma before initiating treatment helps orthopaedic oncologists determine the intent of treatment and predicting the prognosis. As per National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) guidelines, there are no exclusive recommendations for chondrosarcoma staging. They are staged similar to other bone sarcomas even though skeletal metastases are extremely rare in chondrosarcomas. QUESTIONS/PURPOSES: We asked: (1) What proportion of patients with a chondrosarcoma present with detectable only skeletal metastasis? (2) What proportion of patients with chondrosarcoma present with skeletal metastasis with or without concurrent pulmonary metastases? METHODS: Between January 2006 to December 2017, 480 patients with histology-proven chondrosarcomas of the extremity, including clavicle, scapula, spine, and pelvis, presented to our institute. Fifty-three patients were excluded due to incomplete details about their staging. The remaining 427 were retrospectively analyzed and included in this study. Their clinical, radiological, and histopathological details were retrieved from patient files and electronic medical records. Of the 427 patients included, 53 had Grade 1 chondrosarcoma, 330 had Grade 2 chondrosarcoma, and 41 had Grade 3 chondrosarcoma. Grade was not available in three patients. All patients were staged with a thoracic CT scan and bone scan or a whole body fluorodeoxyglucose positron-emission tomography/CT (FDG PET/CT). Patients with a suspected or documented metastasis were reviewed again by an experienced radiologist and a nuclear medicine expert for the purpose of this study. A total of 8% (35 of 427) of patients with chondrosarcoma had isolated lung metastases at the time of initial staging. These included 9% (31 of 330) of patients with Grade 2 chondrosarcomas and 10% (4 of 41) of patients with Grade 3 chondrosarcomas. No patient with a Grade 1 chondrosarcoma had detectable lung metastases. The primary study endpoint was the number of patients who had a diagnosis of skeletal or skeletal and lung metastases as identified by the staging modalities. RESULTS: Three patients with Grade 2 chondrosarcoma had only skeletal metastasis. No patients with Grade 1 or Grade 3 chondrosarcoma had detectable bone metastases. Combined lung and bone metastases were seen in only two patients with Grade 2 chondrosarcoma. CONCLUSIONS: Our study found that the incidence of bony metastasis in conventional chondrosarcomas is extremely low. Considering the present results, we believe skeletal scanning may be overused in current staging algorithms. We do not have survival outcomes to know if detecting these few patients with skeletal lesions at initial presentation would be important in the absence of symptoms, but our data suggest that omitting skeletal imaging from the staging work-up of conventional chondrosarcomas should be considered. It may be reserved for patients with documented pulmonary metastases. LEVEL OF EVIDENCE: Level IV, diagnostic study.

Clinicopathologic features of undifferentiated round cell sarcomas of bone & soft tissues: An attempt to unravel the BCOR-CCNB3- & CIC-DUX4-positive sarcomas.

Background & objectives: Certain genetically defined undifferentiated round cell sarcomas, namely BCOR-CCNB3 and CIC-DUX4 positive, have been described. Here we present detailed clinicopathologic features and molecular results in such cases. Methods: Fifty one cases of undifferentiated round cell sarcomas, including 32 cases, tested for BCOR-CCNB3 and CIC-DUX4 fusions, by reverse transcription polymerase chain reaction technique and 44 tumours, for CCNB3 immunostaining, were analyzed. Results: Twenty seven (52.9%) tumours occurred in males and 24 (47%) in females; in soft tissues (38; 74.5%), commonly, trunk and extremities and bones (13; 25.4%), frequently, femur and tibia. Five of 32 (15.6%) tested cases were positive for BCOR-CCNB3 fusion and seven (21.8%) for CIC-DUX4 fusions. Histopathologically, CIC-DUX4-positive sarcomas comprised nodular aggregates of round to polygonal cells, containing hyperchromatic nuclei, prominent nucleoli and moderate cytoplasm, with focal myxoid stroma and variable necrosis, in certain cases. BCOR-CCNB3- positive sarcomas mostly comprised diffusely arranged, round to oval to short spindly cells with angulated nuclei, vesicular chromatin, inconspicuous nucleoli and interspersed vessels. Immunohistochemically, tumour cells were positive for MIC2 in 24 of 49 (48.9%) and CCNB3 in 12 of 44 (27.2%) cases. Four of five BCOR-CCNB3-positive sarcomas showed CCNB3 immunostaining and 6 of 7 CIC-DUX4-positive sarcomas displayed WT1 immunostaining. Most patients (27/37) (72.9%) underwent surgical resection and chemotherapy. Median overall survival was 12 months, and disease-free survival was seven months. Interpretation & conclusions: Undifferentiated round cell sarcomas are rare; mostly occur in soft tissues of extremities, with CIC-DUX4 positive, as these are relatively more frequent than BCOR-CCNB3 positive sarcomas. CCNB3 and WT1 are useful immunostains for triaging such cases for BCOR-CCNB3 and CIC-DUX4 fusion testing, respectively. Overall, these are relatively aggressive tumours, especially CIC-DUX4-positive sarcomas.

A study of 853 high grade osteosarcomas from a single institution-Are outcomes in Indian patients different?

AIMS: To review outcomes of 853 patients of primary high grade osteosarcoma operated with curative intent between January 2006 to December 2013. METHODS: All patients underwent appropriate surgical resection after preoperative chemotherapy (non methotrexate based). Excised specimen was analyzed for margins and response to chemotherapy. We analysed various factors (sex, age, size, site, type of surgery, pathologic fractures, margin status, and chemotherapy induced necrosis) for their impact on outcomes. RESULTS: Five year overall survival (OS) for entire cohort was 49% and event free survival (EFS) was 42%. Seventy hundred thirty-eight non metastatic patients had OS of 53% and EFS of 47% at 5 years. The 3 year OS and EFS of the metastatic patients was 22% and 9%, respectively. Analysis of 738 non metastatic patients demonstrated that chemotherapy induced necrosis, size of tumor (< / >8 cms), type of surgery (limb salvage vs amputation) significantly affected overall survival. Local recurrence was 9%. Site of tumor (long bone vs pelvis), type of surgery and chemotherapy induced necrosis influenced local recurrence. CONCLUSIONS: Our patients appeared to have poorer survival compared to most Western data, possibly attributable to large tumors. In contrast to existing data, males (71%) were predominantly affected and only patients with 100% necrosis qualified as good responders regarding OS.

Reconstructing diaphyseal tumors using radiated (50 Gy) autogenous tumor bone graft.

AIMS: Establish oncologic safety using 50 Gy to sterilize tumor bearing bone before reimplantation in primary diaphyseal high grade extremity tumors, determine extracorporeal radiotherapy (ECRT) graft survival, and analyze factors that affect union at osteotomy sites. MATERIALS AND METHODS: Seventy non metastatic patients underwent reconstruction with intercalary ECRT grafts sterilized with 50 Gy. Diagnosis included osteosarcoma (38) and Ewing's sarcoma (32). At last follow-up-49 patients were alive, 19 had died and 2 were lost to follow up. Survivors had minimum follow up of 3 years (range 39-127 months). RESULTS: Ninty one percent metaphyseal osteotomies united without additional intervention compared to 71% diaphyseal osteotomies. Additional small plate at diaphyseal osteotomy apparently reduced incidence of non-union (17% vs 31%) (P = 0.49). Addition of morsellised allograft did not help union. There were seven (10%) local recurrences, all in soft tissue. Seventeen of 69 patients (25%) needed removal of ECRT graft. Five year survival for ECRT graft (removal for all causes) was 79% and 84% (excluding removal for local recurrence). CONCLUSIONS: Reimplanting sterilized tumor bone using 50 Gy for tumor ablation is an easily applicable, oncologically safe, biological reconstruction option for primary diaphyseal extremity tumors.

Interstitial brachytherapy for pediatric soft tissue sarcoma: Evolving practice over three decades and long-term outcomes.

PURPOSE: Evaluate long-term clinical outcomes, adverse effects, and evolving practice of interstitial brachytherapy (BT) for pediatric soft tissue sarcomas (STS). METHODS: From September 1984 to December 2014, 105 children (median age 10 years) were included. There were 60 males and 45 females. The majority (74%) had primary lesions. Synovial sarcoma (22%) was the most frequent histology. Treatment included wide local excision and BT with or without external beam radiotherapy (EBRT). Eighty-five (81%) received BT alone. RESULTS: After a median follow-up of 65 months, local control (LC), disease-free survival (DFS), and overall survival (OS) at 10 years were 83, 66, and 73%, respectively. On univariate analysis, LC was superior with tumors <5 cm versus >5 cm (93% vs. 75%, P = 0.10), Grade I/II versus Grade III tumors (97% vs. 73%, P = 0.01), nonround cell versus round cell histology (89% vs. 72%, P = 0.03), and trunk/extremity versus head and neck/genitourinary sites (87% vs. 57%, P = 0.0001). On multivariate analysis tumor size (P = 0.03) and location (P = 0.002) retained significance. Children receiving BT alone had comparable LC to those receiving BT and EBRT (84% vs. 80%, P = 0.43). There was no difference in LC between LDR versus HDR BT (86% vs. 83%, P = 0.30). Wound complications were seen in 6%. Subcutaneous fibrosis (25%), limb edema (6%), skeletal abnormalities (3%), and neuropathy (1%) were the late complications. One child (0.9%) developed a second malignancy after 7 years. CONCLUSION: Interstitial BT with or without EBRT results in excellent outcomes. Radical BT alone, when used judiciously, results in excellent local control and function with minimal treatment-related morbidity.

Free fibula flap for lower limb salvage after tumour resection.

CONTEXT: Post-tumour resection lower limb salvage. AIM/INTRODUCTION: Resection of tumours of the femur and tibia around the knee and ankle joints results in large bony defects. Often arthrodesis is an alternative; in case, adequate functional motors cannot be preserved or due to economic constraints. Thus, in an immunocompromised patient, the vascularised fibula is the best form of reconstruction. The vascularised fibular flap (pedicled/free) can be used in combination with an allograft. We refer to such a combination reconstruction as 'allocombo'. The vascularised fibular graft hypertrophies in due course of time, and till that period, the allograft provides the required mechanical strength to allow early ambulation. SUBJECTS AND METHODS: A retrospective study of 24 cases of vascularised fibular graft for lower limb reconstruction was conducted from February 2003 to March 2014. The average defect size was 15.5 cm and the average length of fibula harvested was 24.35 cm. A total of 19 free fibular flaps and 5 pedicled fibula were done. Mean age was 26 years. Fibula was nestled in the allograft obtained from the tissue bank. RESULTS: The mean follow-up time was 52 months. Free flap success rate was 96%. Successful healing was achieved at 45 ends (97.8%). Radiological evidence of union at osteotomy sites occurred at an average of 6.8 months. Eight patients eventually succumbed to disease. At the final follow-up, the mean Musculoskeletal Tumour Society functional score of the evaluable patients was 26 (range 20-30). CONCLUSIONS: Pedicled fibula is a good option if the defect is within 14 cm of the knee joint at the femoral end. The vessels have to curve around the fibular head, thus its removal improves the reach of the pedicle. The flap is easy to harvest with predictable vascular anatomy and it can provide a large amount of vascularised bone and skin paddle. It results in early ambulation, rehabilitation and reduced morbidity. We realised that fixation is easier and chances of vascular injury are less in free as compared to pedicled fibula.

Monogenic and polygenic determinants of sarcoma risk: an international genetic study.

BACKGROUND: Sarcomas are rare, phenotypically heterogeneous cancers that disproportionately affect the young. Outside rare syndromes, the nature, extent, and clinical significance of their genetic origins are not known. We aimed to investigate the genetic basis for bone and soft-tissue sarcoma seen in routine clinical practice. METHODS: In this genetic study, we included 1162 patients with sarcoma from four cohorts (the International Sarcoma Kindred Study [ISKS], 966 probands; Project GENESIS, 48 probands; Asan Bio-Resource Center, 138 probands; and kConFab, ten probands), who were older than 15 years at the time of consent and had a histologically confirmed diagnosis of sarcoma, recruited from specialist sarcoma clinics without regard to family history. Detailed clinical, pathological, and pedigree information was collected, and cancer diagnoses in probands and relatives were independently verified. Targeted exon sequencing using blood (n=1114) or saliva (n=48) samples was done on 72 genes (selected due to associations with increased cancer risk) and rare variants were stratified into classes approximating the International Agency for Research on Cancer (IARC) clinical classification for genetic variation. We did a case-control rare variant burden analysis using 6545 Caucasian controls included from three cohorts (ISKS, 235 controls; LifePool, 2010 controls; and National Heart, Lung, and Blood Institute Exome Sequencing Project [ESP], 4300 controls). FINDINGS: The median age at cancer diagnosis in 1162 sarcoma probands was 46 years (IQR 29-58), 170 (15%) of 1162 probands had multiple primary cancers, and 155 (17%) of 911 families with informative pedigrees fitted recognisable cancer syndromes. Using a case-control rare variant burden analysis, 638 (55%) of 1162 sarcoma probands bore an excess of pathogenic germline variants (combined odds ratio [OR] 1·43, 95% CI 1·24-1·64, p<0·0001), with 227 known or expected pathogenic variants occurring in 217 individuals. All classes of pathogenic variants (known, expected, or predicted) were associated with earlier age of cancer onset. In addition to TP53, ATM, ATR, and BRCA2, an unexpected excess of functionally pathogenic variants was seen in ERCC2. Probands were more likely than controls to have multiple pathogenic variants compared with the combined control cohort group and the LifePool control cohort (OR 2·22, 95% CI 1·57-3·14, p=1·2 × 10(-6)) and the cumulative burden of multiple variants correlated with earlier age at cancer diagnosis (Mantel-Cox log-rank test for trend, p=0·0032). 66 of 1162 probands carried notifiable variants following expert clinical review (those recognised to be clinically significant to health and about which patients should be advised), whereas 293 (25%) probands carried variants with potential therapeutic significance. INTERPRETATION: About half of patients with sarcoma have putatively pathogenic monogenic and polygenic variation in known and novel cancer genes, with implications for risk management and treatment. FUNDING: Rainbows for Kate Foundation, Johanna Sewell Research Foundation, Australian National Health and Medical Research Council, Cancer Australia, Sarcoma UK, National Cancer Institute, Liddy Shriver Sarcoma Initiative.