Localized Myxofibrosarcoma: A Retrospective Analysis of Primary Therapy and Prognostic Factors in 134 Patients in a Single Institution.

BACKGROUND: Primary therapy of localized myxofibrosarcoma (MFS) remains controversial. Primary resection is complicated by a high rate of local recurrence, and the refractoriness to non-surgical treatment results in a higher risk of metastasis. The aim of the present study was to contribute the findings of a single sarcoma-specialized center and encourage investigating new treatment options. PATIENTS AND METHODS: We analyzed 134 patients treated with localized MFS in our center regarding prognostic factors defining overall survival, local recurrence, and metastasis. We focused on multimodal treatment of localized MFS: surgery, radiation, chemotherapy, hyperthermia, and isolated limb perfusion. RESULTS: The 5-year OS was 74.9%. From a total of 134 patients: 74 (55.2%) stayed disease free, 48 (35.8%) had a local recurrence (LR), and 23 (17.2%) developed a distant metastasis (DM). The 5-year LR-free survival (LRFS) and DM-free survival (DMFS) were 66.1% and 80.8%, respectively. Older age, tumor size (cT) cT ≥ 2, non-extremity localization, and distant metastasis were adverse predictive factors for OS. Performing an incision biopsy, surgery in a sarcoma-center, wide local excision or compartment-oriented excision, negative margins, and radiotherapy were positive predictive factors for LR. Tumor size cT ≥ 3 was a negative predictive factor for DM. Grading was a negative predictive factor for LR (G ≥ 2) and for DM (G3) in the multivariable analysis. CONCLUSION: Adjuvant radiation had a positive impact on LRFS in all localized tumor stages, even in cT1 tumors. Chemotherapy did not have a significant impact on DMFS, regardless of tumor stage. Our findings indicate that myxofibrosarcoma may be a chemotherapy-resistant entity and a much closer monitoring is required, in case of neoadjuvant treatment.

Surgical management of extremity rhabdomyosarcoma: A consensus opinion from the Children's Oncology Group, the European Pediatric Soft-Tissue Sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe.

The treatment of extremity rhabdomyosarcoma remains a challenge due to several adverse prognostic factors frequently associated with this tumor site. The International Soft-Tissue Sarcoma Database Consortium (INSTRuCT) is a collaboration of the Children's Oncology Group Soft-Tissue Sarcoma Committee, the European Pediatric Soft-Tissue Sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe. The INSTRuCT surgical committee developed an internationally applicable consensus opinion document for the surgical treatment of extremity rhabdomyosarcoma. This document addresses surgical management, including biopsy, nodal staging, timing of therapy, resection and reexcision, reconstruction, and surgical approach at relapse.

Clinical and functional outcome after partial or total claviculectomy without reconstruction for oncologic causes.

BACKGROUND: To achieve clear margins in rare malignant clavicular neoplasms, claviculectomy may become necessary. This study aimed to review clinical, functional, and oncologic outcomes following partial or total claviculectomy without reconstruction. METHODS: This study retrospectively included 15 patients from 2 tertiary sarcoma centers (mean age, 42.6 ± 20.3 years; 66.7% male patients). The median length of clinical and oncologic follow-up was 48.0 months (interquartile range [IQR], 24.0-83.5 months). Functional follow-up (Musculoskeletal Tumor Society score and QuickDASH score [short version of the Disabilities of the Arm, Shoulder and Hand questionnaire]) was available in 9 patients at a median of 36.0 months (IQR, 20.0-100.0 months). RESULTS: Of the 15 patients, 7 underwent total claviculectomy; 5, partial lateral claviculectomy; and 3, partial medial claviculectomy. No postoperative complications emerged. The median Musculoskeletal Tumor Society and QuickDASH scores at latest follow-up amounted to 26.0 points (IQR, 24.0-29.0 points) and 18.0 points (IQR, 11.0-22.0 points), respectively. Notably, scores tended to be lower in patients who underwent total claviculectomy (n = 2) in comparison to partial claviculectomy (n = 7). CONCLUSION: Satisfactory clinical and functional results can be achieved following partial or total claviculectomy without reconstruction, with a low complication rate and acceptable mid- to long-term function.

Incidence, treatment and outcome of abdominal metastases in extremity soft tissue sarcoma: Results from a multi-centre study.

BACKGROUND AND OBJECTIVES: Abdominal metastases (AM) from soft tissue sarcoma (STS) are rare and prognosis is poor. The aims of the study were to (a) identify risk factors for the development of AM and to (b) investigate the outcome of AM-patients. METHODS: Seven-hundred-sixty-nine STS-patients with localised disease at diagnosis treated at three tumour centres (2000-2016) were retrospectively included (409 males; mean age, 55.6 years [range, 8-96 years]; median follow-up, 4.1 years [interquartile-range, 2.5-6.6 years]). RESULTS: Two-hundred-two patients (26.3%) developed secondary metastases, and 24 of them AM (3.1%). Ten patients developed first AM (FAM) after a mean of 2.4 years and 14 patients late AM (LAM, after being diagnosed with metastases to other sites) after a mean of 2.0 years. Patients with liposarcoma had a significantly higher risk of developing AM (P = .007), irrespective of grading. There was no difference in post-metastasis-survival (PMS) between patients with AM at any time point and those with metastases to other sites (P = .585). Patients with LAM or FAM showed no difference in post-abdominal-metastasis-survival (P = .884). CONCLUSIONS: Survival in patients with AM is poor, irrespective of whether they develop secondarily to other metastases or not. Patients at high-risk of AM (ie, liposarcoma) may be followed-up regularly by abdominal-ultrasound/CT.

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.

BACKGROUND: Local treatment of pelvic Ewing's sarcoma may be challenging, and intergroup studies have focused on improving systemic treatments rather than prospectively evaluating aspects of local tumor control. The Euro-EWING99 trial provided a substantial number of patients with localized pelvic tumors treated with the same chemotherapy protocol. Because local control included surgical resection, radiation therapy, or a combination of both, we wanted to investigate local control and survival with respect to the local modality in this study cohort. QUESTIONS/PURPOSES: (1) Do patients with localized sacral tumors have a lower risk of local recurrence and higher survival compared with patients with localized tumors of the innominate bones? (2) Is the local treatment modality associated with local control and survival in patients with sacral and nonsacral tumors? (3) Which local tumor- and treatment-related factors, such as response to neoadjuvant chemotherapy, institution where the biopsy was performed, and surgical complications, are associated with local recurrence and patient survival in nonsacral tumors? (4) Which factors, such as persistent extraosseous tumor growth after chemotherapy or extent of bony resection, are independently associated with overall survival in patients with bone tumors undergoing surgical treatment? METHODS: Between 1998 and 2009, 1411 patients with previously untreated, histologically confirmed Ewing's sarcoma were registered in the German Society for Pediatric Oncology and Hematology Ewing's sarcoma database and treated in the Euro-EWING99 trial. In all, 24% (339 of 1411) of these patients presented with a pelvic primary sarcoma, 47% (159 of 339) of which had macroscopic metastases at diagnosis and were excluded from this analysis. The data from the remaining 180 patients were reviewed retrospectively, based on follow-up data as of July 2016. The median (range) follow-up was 54 months (5 to 191) for all patients and 84 months (11 to 191) for surviving patients. The study endpoints were overall survival, local recurrence and event-free survival probability, which were calculated with the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HRs) with their respective 95% CIs were estimated in a multivariate Cox regression model. RESULTS: Sacral tumors were associated with a reduced probability of local recurrence (12% [95% CI 1 to 22] versus 28% [95% CI 20 to 36] at 5 years, p = 0.032), a higher event-free survival probability (66% [95% CI 51 to 81] versus 50% [95% CI 41 to 58] at 5 years, p = 0.026) and a higher overall survival probability (72% [95% CI 57 to 87] versus 56% [95% CI 47 to 64] at 5 years, p = 0.025) compared with nonsacral tumors. With the numbers available, we found no differences between patients with sacral tumors who underwent definitive radiotherapy and those who underwent combined surgery and radiotherapy in terms of local recurrence (17% [95% CI 0 to 34] versus 0% [95% CI 0 to 20] at 5 years, p = 0.125) and overall survival probability (73% [95% CI 52 to 94] versus 78% [95% CI 56 to 99] at 5 years, p = 0.764). In nonsacral tumors, combined local treatment was associated with a lower local recurrence probability (14% [95% CI 5 to 23] versus 33% [95% CI 19 to 47] at 5 years, p = 0.015) and a higher overall survival probability (72% [95% CI 61 to 83] versus 47% [95% CI 33 to 62] at 5 years, p = 0.024) compared with surgery alone. Even in a subgroup of patients with wide surgical margins and a good histologic response to induction treatment, the combined local treatment was associated with a higher overall survival probability (87% [95% CI 74 to 100] versus 51% [95% CI 33 to 69] at 5 years, p = 0.009), compared with surgery alone.A poor histologic response to induction chemotherapy in nonsacral tumors (39% [95% CI 19 to 59] versus 64% [95% CI 52 to 76] at 5 years, p = 0.014) and the development of surgical complications after tumor resection (35% [95% CI 11 to 59] versus 68% [95% CI 58 to 78] at 5 years, p = 0.004) were associated with a lower overall survival probability in nonsacral tumors, while a tumor biopsy performed at the same institution where the tumor resection was performed was associated with lower local recurrence probability (14% [95% CI 4 to 24] versus 32% [95% CI 16 to 48] at 5 years, p = 0.035), respectively.In patients with bone tumors who underwent surgical treatment, we found that after controlling for tumor localization in the pelvis, tumor volume, and surgical margin status, patients who did not undergo complete (defined as a Type I/II resection for iliac bone tumors, a Type II/III resection for pubic bone and ischium tumors and a Type I/II/III resection for tumors involving the acetabulum, according to the Enneking classification) removal of the affected bone (HR 5.04 [95% CI 2.07 to 12.24]; p < 0.001), patients with a poor histologic response to induction chemotherapy (HR 3.72 [95% CI 1.51 to 9.21]; p = 0.004), and patients who did not receive additional radiotherapy (HR 4.34 [95% CI 1.71 to 11.05]; p = 0.002) had a higher risk of death. The analysis suggested that the same might be the case in patients with a persistent extraosseous tumor extension after induction chemotherapy (HR 4.61 [95% CI 1.03 to 20.67]; p = 0.046), although the wide CIs pointing at a possible sparse-data bias precluded any definitive conclusions. CONCLUSION: Patients with sacral Ewing's sarcoma appear to have a lower probability for local recurrence and a higher overall survival probability compared with patients with tumors of the innominate bones. Our results seem to support a recent recommendation of the Scandinavian Sarcoma Group to locally treat most sacral Ewing's sarcomas with definitive radiotherapy. Combined surgical resection and radiotherapy appear to be associated with a higher overall survival probability in nonsacral tumors compared with surgery alone, even in patients with a wide resection and a good histologic response to neoadjuvant chemotherapy. Complete removal of the involved bone, as defined above, in patients with nonsacral tumors may be associated with a decreased likelihood of local recurrence and improved overall survival. Persistent extraosseous tumor growth after induction treatment in patients with nonsacral bone tumors undergoing surgical treatment might be an important indicator of poorer overall survival probability, but the possibility of sparse-data bias in our cohort means that this factor should first be validated in future studies. LEVEL OF EVIDENCE: Level III, therapeutic study.

The Prognostic Impact of Unplanned Excisions in a Cohort of 728 Soft Tissue Sarcoma Patients: A Multicentre Study.

BACKGROUND: Unplanned excisions (UE) of soft tissue sarcomas (STS) carry a high risk for local recurrence (LR) due to marginal/intralesional resections. However, there are reports about improved prognosis for UE patients who have re-resection compared with patients who undergo planned surgery. The present multicentre study was designed to define characteristics of UE patients and to investigate the impact of UE on subsequent therapy and patient outcomes. METHODS: A total of 728 STS patients (376 males, 352 females; mean age: 58 years) who underwent definite surgery at one of three tumour centres were retrospectively included. Time-to-event analyses were calculated with log-rank and Gray's tests, excluding patients with primary metastasis (n = 59). A propensity-score (PS) of being in the UE group was estimated, based on differences at baseline between the UE group and non-UE group. An inverse-probability-of-UE weight (IPUEW) was generated and time-to-event analyses calculated after IPUEW weighting. RESULTS: Before referral, 38.6% of patients (n = 281) had undergone UE. Unplanned excision patients were younger (p = 0.036), rather male (p = 0.05), and had smaller (p < 0.005), superficially located tumours (p < 0.005). Plastic reconstructions (p < 0.005) and adjuvant radiotherapy (p = 0.041) more often were needed at re-resection. In univariable analysis, re-resected patients had improved overall survival (OS; p = 0.027) and lower risk of distant metastasis (DM; p = 0.002) than primarily resected patients, whereas risk of LR was similar (p = 0.359). After weighting for the IPUEW, however, differences in terms of OS (p = 0.459) and risk of DM (p = 0.405) disappeared. CONCLUSIONS: The present study does not support prior findings of improved outcome for UE patients. Unplanned excisions have a major impact on subsequent therapy, yet they do not seem to affect negatively the long-term oncology outcome.

Metastatic Potential of Grade I Chondrosarcoma of Bone: Results of a Multi-institutional Study.

BACKGROUND: Little is known about the metastatic potential of low-grade chondrosarcoma. This study was designed to evaluate the rate of metastasis to identify possible risk factors. METHODS: The files of 225 patients with newly diagnosed, grade I chondrosarcoma of bone treated between 1975 and 2012 were retrospectively analyzed. Median follow-up was 80 months for survivors (range 24-445 months). Nonparametric analyses were performed with the Mann-Whitney U test. Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank test. RESULTS: Fourteen patients developed metastases after a median of 49 months. Metastasis-free survival probability (MFS) was 95 % at 5 years and 92 % at 10 years. Post-metastasis survival probability amounted to 27 % after 5 years. Tumor size at diagnosis (P = 0.698) and surgical margin width (P = 0.514) had no influence on MFS. Patients who developed local recurrences had a significantly lower 10-year MFS than patients without recurrences (69 % vs. 99 %, P < 0.001). Patients with grade I recurrences had a significantly poorer MFS than patients without recurrences (P = 0.013) but a significantly higher MFS than patients with grade II recurrences (P = 0.006). Patients with thoracic wall tumors had a significantly lower 10-year MFS of 66 % compared with patients with tumors of the upper (100 %, P < 0.001) and lower extremity (93 %, P = 0.033). CONCLUSIONS: The biological behavior of low-grade chondrosarcoma appears to be more consistent with the WHO definition of rarely metastasizing bone tumors, rather than the one of locally aggressive neoplasms. Thoracic wall tumors and the development of local recurrences were associated with a higher metastasis rate in this study.

Histological response assessment following neoadjuvant isolated limb perfusion in patients with primary, localised, high-grade soft tissue sarcoma.

PURPOSE: Histological response assessment following neoadjuvant treatment can help identify patients at a higher risk for systemic disease progression. Our goal was to evaluate whether mitotic count and the amount of viable tumour following neoadjuvant isolated limb perfusion (ILP) for primary, locally advanced, non-metastatic, high-grade extremity soft tissue sarcoma correlate with prognosis. PATIENTS AND METHODS: This study is a retrospective analysis of 61 patients who underwent neoadjuvant ILP followed by surgical resection with curative intent between 2001 and 2011. Non-parametric analyses were carried out with the Mann-Whitney U and the Wilcoxon signed-rank test. Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank test. RESULTS: The median follow-up was 44 months for all patients and 55 months for survivors. The amount of viable tumour after ILP had no correlation with overall (OS) (P = 0.227) or event-free (EFS) (P = 0.238) survival probability. Patients with a low mitotic count after ILP had a significantly higher OS (P < 0.001), EFS (P = 0.002) and post-relapse survival probability (P = 0.030) compared to patients with an intermediate or high mitotic count. CONCLUSIONS: The mitotic count following ILP for primary, high-grade, locally advanced, non-metastatic soft tissue sarcoma appears to significantly correlate with prognosis. If these results are validated in a prospective setting, they could provide a rationale for the design of adjuvant systemic chemotherapy trials with the goal of improving the prognosis of patients with an intermediate or high mitotic count after ILP.

Gemcitabine and docetaxel for epithelioid sarcoma: results from a retrospective, multi-institutional analysis.

OBJECTIVE: Epithelioid sarcoma (ES) presents unique clinical features in comparison to other sarcoma subtypes. Data regarding the benefits of chemotherapy are very limited. Combination regimens using gemcitabine and docetaxel (Gem/Doce) have proven to be effective, especially in uterine and nonuterine leiomyosarcoma. Yet, there is no available data on the efficacy of Gem/Doce in ES. METHODS: A retrospective analysis of the three participating institutions was performed. Twenty-eight patients with an ES diagnosis presented at one of the participating institutions between 1989 and 2012. Of this group, 17 patients received chemotherapy. RESULTS: Patients' median overall survival (OS) after the beginning of palliative chemotherapy was 21 months, and the 1-year OS was 87%. Twelve patients received Gem/Doce with a clinical benefit rate of 83%. The median progression-free survival (PFS) was 8 months for all patients receiving Gem/Doce. The best response was complete remission in 1 patient and partial remission in 6 patients. All 6 patients receiving Gem/Doce as a first-line treatment showed measurable responses with a median PFS of 9 months. CONCLUSIONS: In this retrospective study, Gem/Doce was an effective chemotherapeutic regimen for ES. Prospective studies are needed to better assess the effects of this combination drug therapy.

Prognostic relevance of ¹8F-FDG PET uptake in patients with locally advanced, extremity soft tissue sarcomas undergoing neoadjuvant isolated limb perfusion with TNF-α and melphalan.

PURPOSE: The objective of this study was to determine whether (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) can adequately assess the risk of systemic disease progression in patients with primary, localized, high-grade soft tissue sarcomas of the extremities undergoing neoadjuvant isolated limb perfusion (ILP) with tumour necrosis factor and melphalan. METHODS: This was a retrospective analysis of the files of 35 patients who underwent a PET or PET/CT scan prior to and after ILP followed by surgical resection with curative intent between 2006 and 2012. SUVmax1 was defined as the maximum standardized uptake value (SUV) at diagnosis, SUVmax2 as the maximum SUV after ILP and ΔSUVmax as the percentage difference between SUVmax1 and SUVmax2. RESULTS: The median follow-up was 40 months for all patients. The median SUVmax1 amounted to 7.6, while the median SUVmax2 was 4.7. The median ΔSUVmax was -44%. Overall survival (OS) probability at 2 and 5 years amounted to 78 and 70%, respectively, while metastasis-free survival (MFS) probability at 2 and 5 years was 67 and 64%, respectively. Receiver-operating characteristic (ROC) curve analysis showed that both SUVmax2 and ΔSUVmax could predict systemic disease progression, while SUVmax1 could not adequately identify patients who went on to develop metastatic disease. The optimal cut-off value was 6.9 for SUVmax2 and -31 % for ΔSUVmax. Patients with an SUVmax2 <6.9 had a 2-year MFS of 80%, compared to 31 % for patients with an SUVmax2 ≥ 6.9 (p < 0.001). Patients with a ΔSUVmax < -31 %, i.e. patients with a higher metabolic response, had an MFS of 76% at 2 years, compared to 42% for patients with a ΔSUVmax ≥ -31% (p = 0.050). CONCLUSION: SUVmax after ILP for primary, locally advanced, non-metastatic high-grade soft tissue sarcomas of the extremities appears to be significantly correlated with prognosis. Whether patients with a high SUVmax after ILP will benefit from standard or experimental adjuvant systemic treatment options should be evaluated in future studies.

Oncological outcome of primary non-metastatic soft tissue sarcoma treated by neoadjuvant isolated limb perfusion and tumor resection.

BACKGROUND: Isolated limb perfusion (ILP) is an effective limb salvage strategy in patients with advanced soft tissue sarcoma (STS) where surgery alone would result in significant functional morbidity or mandate an amputation. Most previous reports of patients undergoing ILP focus on limb salvage rates rather than local and distant relapse rates. Here, we report the oncological outcome of sarcoma patients treated by ILP and surgery. METHODS: Data were retrieved from prospective ILP databases from two ILP centers following similar ILP techniques and surgical approaches. Only patients with primary, intermediate, or high grade non-metastatic STS were included. RESULTS: The cohort comprised 90 patients. Median follow-up was 39 months (range 3-165 months). Median tumor size was 11 cm (range 5-34). Twenty of 90 (22%) patients underwent prior debulking surgery outside the centers. Twenty-nine of 90 (32%) had postoperative irradiation. Four of 90 underwent amputation either related to local recurrence or irresectability, 4 of 90 underwent amputation for treatment-related complications. Fifteen of 83 (18%) patients had local recurrences after ILP and limb sparing surgery, 39 of 90 (43%) developed metastatic disease. Twenty-two of 90 (24%) died of disease. CONCLUSION: Preoperative ILP and tumor resection resulted in good local control in a cohort of high-risk STS patients.

Paley's multiplier method does not accurately predict adult height in children with bone sarcoma.

BACKGROUND: The majority of patients with osteosarcoma and Ewing's sarcoma are diagnosed before skeletal maturity. Paley's multiplier is used for height prediction in healthy children, and has been suggested as a method to make growth predictions for children with osteosarcoma and Ewing's sarcoma when considering limb salvage options. To our knowledge, no evaluation of this method in this particular patient group has been performed, but a temporary growth deficit has been observed in children undergoing chemotherapy. QUESTIONS/PURPOSES: We asked whether (1) Paley's formula reliably predicts growth in children who received polychemotherapy; (2) chemotherapy impairs growth velocity; and (3) final adult height is impaired in these patients. METHODS: Retrospectively, data for 94 patients with osteosarcoma and Ewing's sarcoma were retrieved from databases of two sarcoma centers. Onset before 14 years of age in girls and 16 years in boys and a minimum followup until 18 years were required (mean, 67 months; range, 31-124 months) criteria. Exclusion criteria were the intake of growth hormones or no chemotherapy. Thirty-three patients (35%) fulfilled all inclusion criteria. Predicted adult heights were compared with actual adult height. The development of a growth deficit was evaluated for 23 children (without chemotherapy for recurrence) using age- and gender-specific standard deviation scores for height (WHO Z-scores). RESULTS: Height prediction using Paley's method showed a high percentage of false predictions (outside ± 1 SD, 70%; outside ± 2 SD, 61%). On average, the mean total height of the patients was overestimated (2.3 cm). The median absolute error of prediction was 5.0 cm (range, -17 to 8). Patients with osteosarcoma and Ewing's sarcoma showed a significant growth impairment during polychemotherapy. A catchup phase in growth before skeletal maturity was observed in patients with osteosarcoma but not with Ewing's sarcoma. CONCLUSIONS: Owing to its lack of reliability in this patient group, methods other than Paley's should be evaluated to predict adult height. Although limited by a small number of patients, our study results indicate a decreased adult height in patients with bone sarcoma after chemotherapy. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Instructions for Authors for complete description of levels of evidence.

Surgical therapy of primary malignant bone tumours and soft tissue sarcomas of the chest wall: a two-institutional experience.

PURPOSE: Primary malignant bone tumours and soft tissue sarcomas of the chest wall are exceedingly rare entities. The aim of this study was a retrospective two-institutional analysis of surgical therapy with respect to the kind and amount of the resection performed, the type of reconstruction and the oncological outcome. METHODS: Between September 1999 and August 2010 31 patients (seven women and 24 men) were treated due to a primary malignant bone tumour or soft tissue sarcoma of the chest wall in two centres. Eight low-grade sarcomas were noted as well as 23 highly malignant sarcomas. The tumours originated from the sternum in six cases, from the ribs in 12 cases, from the soft tissues of the thoracic wall in 11 cases and from a vertebral body and the clavicle in one case each. RESULTS: In 26 cases wide resection margins were achieved, while four were intralesional and one was marginal. In all 31 cases the defect of the chest wall was reconstructed using mesh grafts. At a mean follow-up of 51 months 20 patients were without evidence of disease, three were alive with disease, seven patients had died and one patient was lost to follow-up. One recurrence was detected after wide resection of a malignant triton tumour. CONCLUSIONS: Primary malignant bone tumour or soft tissue sarcoma of the chest wall should be treated according to the same surgical oncological principles as established for the extremities. Reconstruction with mesh grafts and musculocutaneous flaps is associated with a low morbidity.

What Is the Impact of Multimodal Treatment in Patients with Leiomyosarcoma of Bone? A Multicenter Study of 35 Patients with an Ultra-Rare Tumor Entity.

Primary leiomyosarcoma of bone (LMSoB) is extremely rare, comprising only <0.7% of primary malignant bone tumors, and is therefore considered an ultra-rare tumor entity. There is currently no consensus as to whether therapeutic strategies should be based on the biological characteristics of soft tissue leiomyosarcoma or on primary tumor localization in the bone. The use of perioperative chemotherapy and its effectiveness in this rare tumor entity remains unclear. We aimed to evaluate the impact of different treatment approaches in a multicenter setting with a total of 35 patients included. The 5-year overall survival (OS) was 74%. Patients with localized disease undergoing surgery had a significantly higher 5-year OS compared to patients who did not undergo surgical treatment (82% vs. 0%, p = 0.0015). Axial tumor localization was associated with worse event-free survival (EFS) probability (p < 0.001) and OS (p = 0.0082). A high proportion of our patients developed secondary metastases. Furthermore, the perioperative chemotherapy protocols applied to our patients were not associated with an improved EFS or OS. Therefore, the benefit of perioperative chemotherapy in LMSoB needs to be further investigated, and the choice of agents still needs to be clarified.

Osteolytic lesions of the calcaneus: results from a multicentre study.

PURPOSE: Tumours of the calcaneus are exceedingly rare and the correct diagnosis is often missed. X-rays are the standard clinical examination tool and therefore we wanted to discover whether X-rays alone were a sufficient diagnostic tool for these tumours. Diard's classification was applied to define whether different types of lesions were characteristically distributed in the bone and in addition we analysed whether type and/or duration of symptoms were possible indicators of malignancy. METHODS: Ninety-two patients' files (59 men and 33 women) were retrospectively reviewed. Seventy-five patients with a mean age at surgery of 28 years (range five to 78) were surgically treated. Parameters analysed were sex, age at surgery, side, type and duration of symptoms, tentative diagnosis, biopsy prior to surgery, operative procedure, recurrence rate, revision and localisation of the lesion according to Diard. For each lesion the first documented radiological diagnosis and-in cases of malignancy-Enneking's classification was applied. RESULTS: Discrepancies between the radiological and definitive histological diagnosis occurred in 38 (41 %) of 92 cases. In eight (osteosarcoma n = 5, Ewing's sarcoma n = 2, metastases n = 1) of 17 malignant cases radiological examination initially gave no evidence of malignancy, resulting in an unplanned excision ("whoops procedure") in three cases of osteosarcoma. Applying Diard's system trabecular area 6 (radiolucent area) was highly affected in 64 (80 %) of 80 investigated plain X-rays, whereas areas 1 and 5 were affected in nine (11 %) and 16 (20 %) cases only. CONCLUSIONS: In each case of an osteolytic lesion of the calcaneus a malignant tumour must be ruled out, and thus preoperative plain X-rays in two planes alone are not sufficient and should therefore be followed by magnetic resonance imaging. Applying the Diard system different types of lesions are not characteristically distributed in the bone. Increasing pain for more than ten days without previous trauma should always justify further examinations.

The Use of Regional Anesthesia to Reduce Blood Loss in Isolated Limb Perfusion (ILP)-A Novel Approach.

BACKGROUND: Isolated limb perfusion (ILP) for soft tissue sarcomas (STS) is usually performed with tumor necrosis factor alpha (TNF-α) and melphalan. ILP regularly leads to a total blood loss (BLt) of 1.5-2 L/patient. Blood inflow from the central blood circulation to the limb is influenced by unstable pressure gradients and pain reactions after the administration of melphalan. With perioperative regional anesthesia (RA), pain levels can be reduced, and the pressure gradient stabilized resulting in a reduced BLt. The aim of this study was to compare the BLt with and without RA in patients with ILP during circulation of drugs. METHODS: Patients were treated according to the following protocol: After the establishment of limb circulation, ILP was started with the administration of TNF-α. Half the dose of melphalan was given as a bolus after 30 min, and the remaining dose was continuously administered in the following 30 min. The extremity was washed out after 90 min. ILP with perioperative RA (supraclavicular plexus block/peridural catheter) was performed prospectively in 17 patients and compared to a matched retrospective control group of 17 patients without RA. BLt was documented and perioperative anesthesiological data were analyzed for response rates after the application of melphalan (RaM). RESULTS: BLt and RaM tended to be lower for the intervention group with RA if compared to the control group without RA in all analyses. The trend of lower BLt and RaM in ILP with RA was more pronounced for the upper extremity compared to the lower extremity. Results were not statistically significant. CONCLUSION: These findings indicate that the use of RA can help to stabilize hemodynamic anesthetic management and reduce the BLt in ILP, especially during perfusion of the upper extremities.

Pre-operative radiotherapy is associated with superior local relapse-free survival in advanced synovial sarcoma.

PURPOSE: Optimization of local therapies in synovial sarcoma (SS) considered unresectable at diagnosis is needed. We evaluated the effects of neoadjuvant versus adjuvant radiation versus surgery only on long-term outcomes. METHODS: Patients with macroscopic SS tumors before chemotherapy (IRS-group-III) in the trials CWS-81, CWS-86, CWS-91, CWS-96, CWS-2002-P and SoTiSaR-registry were analyzed. Local therapies were scheduled after 3 neoadjuvant chemotherapy cycles. RESULTS: Median age of 145 patients was 14.5 years. 106 survivors had median follow-up of 7.0 years. Tumor site was 96 extremities, 19 head-neck, 16 shoulder/hip, 14 trunk. Tumors were < 3 cm in 16, 3-5 cm in 28, 5-10 cm in 55, > 10 cm in 34 patients. In a secondary resection during chemotherapy, R0-status was accomplished in 82, R1 in 30, R2 in 21 (12 missing). Radiotherapy was administered to 115 (R0 61, R1 29, R2 20, missing 5), thereof 57 before and 52 after tumor resection. 23 were treated with surgery only. For all patients, 5 year event-free (EFS) and overall survival (OS) was 68.9% ± 7.6 (95%CI) and 79.1% ± 6.9. To establish independent significance, tumor site, size, surgical results and sequencing of local therapies were analyzed in a Cox regression analysis. Variables associated with EFS and OS are site, size and sequencing of local therapies. Variables associated with local recurrence are site, surgical results and sequencing of local therapies. The only variable associated with suffering metastatic recurrence is tumor size. CONCLUSION: Differences in sequencing of local therapy procedures are independently associated with outcomes. Best local control is achieved when tumors are irradiated pre-operatively and undergo R0 or R1 resection thereafter.

Developments in the Surgical Approach to Staging and Resection of Rhabdomyosarcoma.

Although survival after rhabdosarcoma treatment has improved over the years, one third of patients still develop locoregional relapse. This review aims to highlight developments pertaining to staging and local treatment of specific RMS tumor sites, including head and neck, chest/trunk, bladder-prostate, female genito-urinary, perianal, and extremity sites.

Effect of radiotherapy on local recurrence, distant metastasis and overall survival in 1200 extremity soft tissue sarcoma patients. Retrospective analysis using IPTW-adjusted models.

BACKGROUND AND PURPOSE: Neoadjuvant (NRTX) and adjuvant radiotherapy (ARTX) reduce local recurrence (LR) risk in extremity soft tissue sarcoma (eSTS), yet their impact on distant metastasis (DM) and overall survival (OS) is less well defined. This study aimed at analysing the influence of NRTX/ARTX on all three endpoints using a retrospective, multicentre eSTS cohort. MATERIALS AND METHODS: 1200 patients (mean age: 60.7 ± 16.8 years; 44.4 % females) were retrospectively included, treated with limb sparing surgery and curative intent for localised, high grade (G2/3) eSTS. 194 (16.2 %), 790 (65.8 %), and 216 (18.0 %) patients had received NRTX, ARTX and no RTX, respectively. For the resulting three groups (no RTX vs. NRTX, no RTX vs. ARTX, NRTX vs. ARTX) Fine&Gray models for LR and DM, and Cox-regression models for OS were calculated, with IPTW-modelling adjusting for imbalances between groups. RESULTS: In the IPTW-adjusted analysis, NRTX was associated with lower LR-risk in comparison to no RTX (SHR [subhazard ratio]: 0.236; p = 0.003), whilst no impact on DM-risk (p = 0.576) or OS (p = 1.000) was found. IPTW-weighted analysis for no RTX vs. ARTX revealed a significant positive association between ARTX and lower LR-risk (SHR: 0.479, p = 0.003), but again no impact on DM-risk (p = 0.363) or OS (p = 0.534). IPTW-weighted model for NRTX vs. ARTX showed significantly lower LR-risk for NRTX (SHR for ARTX: 3.433; p = 0.003) but no difference regarding DM-risk (p = 1.000) or OS (p = 0.639). CONCLUSION: NRTX and ARTX are associated with lower LR-risk, but do not seem to affect DM-risk or OS. NRTX may be favoured over ARTX as our results indicate better local control rates.

Are Postoperative Infections in the First 12 Months after Wide Resection and Megaprosthetic Replacement Associated with the Survival of Osteosarcoma Patients? Results of a Multicenter Study.

Recent retrospective studies suggested that early postoperative infections might be associated with a survival benefit for extremity osteosarcoma patients, but the reported results have been conflicting. The files of 437 patients with a newly diagnosed, high-grade osteosarcoma of the extremities treated at 5 referral centers in Germany and Austria between 1989 and 2016 were retrospectively evaluated. All patients underwent multi-agent chemotherapy and limb-sparing tumor excision, followed by endoprothetic replacement. We used the Kaplan-Meier method to calculate survival curves, which we compared with the log-rank test. With a median follow-up of 100 months (interquartile range, 49-155 months), local recurrence (LR) probability, event-free survival (EFS), and disease-specific survival (DSS) after 5 years in this selected patient cohort amounted to 5%, 67%, and 79%, respectively, and 46 patients (10.5%) developed an early postoperative infection. We found no significant differences in LR, EFS, or DSS between patients with and without early infections, and there were no differences in known prognostic factors between the two groups. However, in subgroup analyses patients with a poor response to neoadjuvant chemotherapy and an early infection had a better DSS compared to patients without early infections (93% vs. 62% after 5 years, p = 0.044). Provided that our findings can be validated in separate patient cohorts, we believe that patient outcome after adjuvant immunomodulatory treatments in osteosarcoma patients should be evaluated and reported separately for good and poor responders to neoadjuvant chemotherapy in future studies.