Localized Sarcoma Research Articles

Analysis of Local Control Outcomes and Clinical Prognostic Factors in Localized Pelvic Ewing Sarcoma Patients Treated with Radiation Therapy: A Report from the Children's Oncology Group

<h3>Purpose/Objective(s)</h3> To identify potential clinical prognostic factors associated with a higher risk of local recurrence in localized pelvic Ewing Sarcoma (ES) patients treated with radiation therapy. <h3>Materials/Methods</h3> Data for 101 patients treated with definitive radiotherapy (RT) or both surgery and radiation (S+RT) on INT-0091, INT-0154, and AEWS0031 were analyzed. Radiation and imaging data was reviewed at IROC QARC. Imaging data for patients who did not receive radiation was not available, so surgery only patients were excluded. Tumor size was classified as </≥ 8 cm in maximum dimension and </≥ 200 mL volumetrically. Pelvic subsites were categorized as sacrum, iliac/buttock, or ischiopubic-acetabulum. Five-year cumulative incidence of local failure was defined as standard. <h3>Results</h3> The most common primary pelvic subsite was sacrum, 44.6%. Median tumor size at diagnosis was 9.7 cm (range: 2.4-16.0 cm) in maximum dimension and 215.9 mL (range: 3.7-1400.0 mL) volumetrically. RT was utilized in 68% of patients and S+RT in 32%. There was no statistically significant difference in local therapy modality employed based on tumor subsite or size. The five-year cumulative incidence of local failure for the entire cohort was 19.0% (95% CI, 12.7-28.5%). RT was associated with a higher incidence of local failure at 25.0% compared to 6.3% for S+RT (p=0.046). There was no difference in local failure outcomes by tumor size </≥ 8 cm in maximum dimension or </≥ 200 mL volumetrically. A higher incidence of local failure was seen with each additional 100 mL of tumor at diagnosis for all patients (p=0.04) and for RT only patients (p=0.005). Tumors originating in the ischiopubic-acetabular region were associated with the highest local failure incidence of 37.5%, compared to 20.0% for iliac-buttock and 11.4% for sacrum (p=0.02). Ischiopubic-acetabulum tumors treated with RT alone had the highest local failure rate in the cohort (50.0%, p=0.06). Multivariable analysis demonstrated RT alone (HR 5.1, p=0.04), tumor subsite (particularly ischiopubic-acetabulum tumors, HR 4.6, p=0.02), and increasing volume per 100 mL (HR 1.2, p=0.01) were associated with a higher incidence of local recurrence. <h3>Conclusion</h3> Patients with pelvic ES selected for S+RT had lower rates of local failure compared to patients selected for definitive RT. Tumors involving the ischiopubic-acetabular region and increasing tumor volume at diagnosis likely correlate with inferior local tumor control outcomes, especially for RT only patients, indicating local therapy intensification may be warranted for this cohort. Tumor characteristics did not correlate with choice of local therapy modality suggesting an opportunity to develop best local therapy practices guidelines for future studies based on tumor features.

Analysis of Local Control Outcomes and Clinical Prognostic Factors in Localized Pelvic Ewing Sarcoma Patients Treated With Radiation Therapy: A Report From the Children's Oncology Group

To identify potential clinical prognostic factors associated with a higher risk of local recurrence in patients with localized pelvic Ewing sarcoma treated with radiation therapy. Data for 101 patients treated with definitive radiation therapy (RT) or both surgery and radiation (S+RT) to primary pelvic tumors on INT-0091, INT-0154, and AEWS0031 were analyzed. Imaging data for patients who did not receive radiation were not available for central review; therefore, patients with surgery alone were not included. Cumulative incidence rates for local failure at 5 years from time of local control were calculated accounting for competing risks. The most common pelvic subsite was sacrum (44.6%). RT was used in 68% of patients and S+RT in 32%. The local failure rate was 25.0% for RT and 6.3% for S+RT (P=.046). There was no statistically significant difference in local control modality by tumor characteristics. Tumors originating in the ischiopubic-acetabulum region were associated with the highest local failure incidence, 37.5% (P=.02, vs sacrum and iliac/buttock tumors), particularly those treated with RT (50.0%, P=.06). A higher incidence of local failure was seen with each additional 100 mL of tumor at diagnosis (P=.04). Multivariable analysis demonstrated RT alone (hazard ratio [HR], 5.1; P=.04), tumor subsite (particularly ischiopubic-acetabulum tumors; HR 4.6; P=.02), and increasing volume per 100 mL (HR, 1.2; P=.01) were associated with a higher incidence of local recurrence. Combination surgery and RT is associated with improved local control in patients with pelvic Ewing sarcoma compared with definitive RT. Tumors involving the ischiopubic-acetabulum region and increasing tumor volume at diagnosis are associated with inferior local control. Tumor characteristics did not correlate with choice of local therapy modality suggesting an opportunity to develop best local therapy practices guidelines for future studies based on tumor features.

Primary vaginal sarcoma in a single center (143)

<b>Objectives:</b> Primary vaginal sarcomas are rare, easily recurrent tumors with an unknown etiology. We aimed to investigate the clinical characteristics and prognosis of primary vaginal sarcoma. <b>Methods:</b> A retrospective analysis was conducted on patients with primary vaginal sarcoma treated at our center from 2000 to 2020. <b>Results:</b> A total of 15 patients were identified. Of these, nine (60.0%) patients had leiomyosarcoma, two (13.3%) patients had Ewing's sarcoma, two (13.3%) patients had rhabdomyosarcoma, one (6.7%) patient had undifferentiated sarcoma, and one (6.7%) patient had malignant peripheral schwannoma. The median age of the patients was 48 years (range: 29-66 years). Nine patients presented with vaginal mass which was the most common primary symptoms. Eleven patients received their primary surgery at our institution or an outside institution, seven of them received postoperative adjuvant chemotherapy or radiation therapy. The remaining four patients received initial chemotherapy and/or radiotherapy because of advanced-stage disease. The FIGO 2009 distribution by stage was: stage I in ten patients, stage II in one patient, stage III in two patients, and stage IV in two patients. The median follow-up was 43.7 months (range: 10.1-137.5 months). Thirteen patients had disease extent during follow-up, with 12 developed local relapse or adjacent organ metastases, the remaining one patient developed liver metastases during follow up. Ten of them relapsed within two years after diagnosis. Eight patients with local recurrence received a secondary surgery treatment, and only two of them relapsed again. Five patients died during follow-up; 2-year OS and 5-year OS were 80.0% and 66.7%, respectively. Patients with leiomyosarcoma or other sarcomas had the same 5-year OS (74.1% vs 66.7%, <i>p</i>=0.307). <b>Conclusions:</b> Primary vaginal sarcomas are aggressive neoplasms with different presenting characteristics. Surgery is the main treatment for primary vaginal sarcoma and local relapse vaginal sarcoma.

Ultrasound-Guided Trans-Uterine Cavity Core Needle Biopsy of Uterine Myometrial Tumors to Differentiate Sarcoma from a Benign Lesion—Description of the Method and Review of the Literature

Uterine sarcomas are rare, aggressive tumors with poor prognosis that can be further negatively affected by inadequate surgical approaches such as morcellation. There are no clinical and radiologic criteria for differentiating leiomyoma from malignant uterine tumors. However, some ultrasonography and magnetic resonance imaging findings may be informative. We present a technique of ultrasound-guided trans-uterine cavity (UG-TUC) core needle biopsy for uterine lesions. As the procedure is an in-organ biopsy, there is no risk of needle canal contamination. The technique also enables the biopsy of lesions inaccessible by the transvaginal tru-cut biopsy. The core needle of the automatic biopsy system is inserted via the cervical canal into the uterine cavity and is directed and activated at the myometrial lesion under ultrasound control. The standard local treatment of localized uterine sarcomas is en bloc total hysterectomy; for fibroids, there are multiple options including conservative management or tumorectomy and tumor morcellation using minimally invasive techniques. Fragmentation of the sarcoma significantly worsens oncologic outcomes and should therefore be avoided. The UG-TUC core needle biopsy of uterine lesions can complement imaging to obtain sufficient material for histologic and molecular analyses of suspected or undetermined lesions, thus facilitating treatment planning and decreasing the risk of unsuspected sarcomas.

New Approaches Promise to Improve Local Ewing Sarcoma Results.

The study by Whelan and colleagues showed that addition of busulfan and melphalan conditioning and autologous stem cell rescue to conventional EURO-E.W.I.N.G STUDY chemotherapy in local nonmetastatic Ewing sarcoma improves prognosis. However, almost 30% of these study patients will have relapsed before this stage of therapy is reached, and 78% of his patients were at high risk because of inadequate response to the initial chemotherapy given. Further improvement could be achieved by the integration of other novel advances with this approach. Ash and colleagues have shown that the separation of such cases into high- and low-risk groups by using CD56 negativity of the tumor cells is an improvement over current methods with a 100% 10-year progression-free survival in CD56- nonpelvic local isolated Ewing sarcoma patients. Their patients were treated on the SCMCIE 94 protocol, associated with no relapses before 30 months in 24 consecutive patients independent of the CD status. Integration of these novel approaches in diagnosis and treatment would allow truly high-risk patients, who would benefit from the procedure, to reach the busulfan and melphalan stage of therapy and delineate those patients who can be cured without such therapy. Details of the SCMCIE 94 protocol are given and the possible reasons for the different relapse patterns are discussed.

Composite reconstruction of right ventricle and tricuspid valve for cardiac angiosarcoma

Composite reconstruction of right ventricle and tricuspid valve for cardiac angiosarcoma

A rare primary localized extranodal histiocytic sarcoma of oral mucosa: a case report

<h3>Background</h3> Histiocytic sarcoma is a rare hematopoietic malignancy which typically involves extranodal sites, mainly of the gastrointestinal tract. Of the small number of reported cases in the head and neck region, only one case was localized to the oral cavity. The disease may present as a solitary lesion or disseminated process secondary to other hematopoietic malignancies. Histopathologically, the tumors can be mistaken for other lymphoprolifera- tive disorders. Immunohistochemistry shows tumor cells expressing one or more of the histiocytic markers CD163, CD68, or lysozyme. Surgery with or without chemotherapy or radiotherapy are the mainstays of treatment. Even though histiocytic sarcoma has clinically aggressive behavior with poor response to therapy, studies show that a subset of the patients with localized disease and small tumor size have more favorable outcome with surgery alone. We present a case with localized extranodal histiocytic sarcoma of oral mucosa. <h3>Case Description</h3> A 31-year-old, fe- male with onemonth duration of a 10 × 8 × 2 mm smooth-surfaced, well circumscribed, firm soft tissue enlargement at buccal vestibule of #11/12. Biopsy shows a diffuse population of pleomorphic cells with atypical mitoses and fine granular cytoplasm within fibrocollagenous connective tissue. Immunohistochemical studies demonstrated tumor cells positive to CD163, CD68, CD45, CD43, CD4, muramidase, SOX10, S100, NSE and vimentin with a diagnosis of his- tiocytic sarcoma. Surgical excision with uninvolved margins was performed. The diagnosis of histiocytic sarcoma was confirmed with hematopathology consultation. There was no evidence of tumor recurrence after 3 months fol- low up. <h3>Conclusion</h3> To the best of our knowledge, this is the second case of primary localized extranodal histiocytic sarcoma of oral cavity. Surgery alone was the treatment modality for our case. However, due to the rarity/limited number of reported cases, treatment outcomes of a localized disease is limited. The treatment protocol may become more evident as newer studies emerge.

Prognostic Factors and Nomogram Construction for First Local Recurrent Retroperitoneal Sarcoma Following Surgical Resection: A Single Asian Cohort of 169 Cases.

ObjectiveThis study aimed to explore the prognostic factors for first local recurrent retroperitoneal soft tissue sarcoma (FLR-RPS) and construct predictive nomograms in the Asian population.MethodsIn a single Asian sarcoma center, data of patients with FLR-RPS were retrospectively analyzed from January 2011 to September 2020. We developed and internally validated prognostic factors determined by the Cox regression model, as well as nomograms for predicting recurrence-free survival (RFS) and overall survival (OS). The concordance index and calibration curve were used to determine the nomogram’s discriminative and predictive ability.ResultsWith 169 patients, the median follow-up duration was 48 months and the 5-year OS rate was 60.9% (95% confidence interval (CI), 51.9%–69.9%). OS was correlated with chemotherapy at the time of initial surgery and tumor grading. The 5-year cumulative local recurrence rate and distant metastasis rate were 75.9% (95% CI, 67.5%–84.3%) and 10.1% (95% CI, 4.2%–16.0%), respectively, and the length of the disease-free interval following the primary operation was associated with disease recurrence. The 6-year OS and cumulative recurrence rate after surgery in our cohort were comparable with those in the TARPSWG cohort, but the proportion of local recurrence was higher (80.4% vs. 59.0%), and distant metastasis was less common (10.1% vs. 14.6%). In this study, two nomogram prediction models were established, which could predict the 1-, 2-, and 5-year OS and RFS, and the concordance indices were 0.74 and 0.70, respectively. The calibration plots were excellent.ConclusionsFor the FLR-RPS patients, some can still achieve an ideal prognosis. The treatment of FLR-RPS in Asian populations can be aided by the predictive model established in this study.

Management of sarcoma recurrence after megaprosthesis of the knee

BackgroundThe management of local sarcoma recurrence about the knee (at the distal femur or proximal tibia) is challenging. The objective of this study was to describe the locations of local sarcoma recurrences about knee megaprostheses, the treatments used for each type of recurrence, and the outcomes according to the treatment used. HypothesisThe strategy for treating a local sarcoma recurrence about the knee must be based on the topography of tumour involvement. Materials and methodsWe included 13 patients who had local sarcoma recurrence about a knee megaprosthesis and were followed up for at least 2 years. The diagnosis was osteosarcoma in 10 patients and chondrosarcoma in 3 patients. The distal femur was involved in 11 patients and the proximal tibia in 2 patients. We classified the patients into two groups based on whether the tumour involved important structures or was at a distance within the soft tissues. ResultsThe recurrence was a nodule at a distance of important structures in 8 (57%) patients, in whom the mean time to recurrence was 15 months (range, 2–34 months). The remaining 5 (38.5%) patients had involvement of important structures in the popliteal fossa and a mean time to recurrence of 42 months (range, 16–80 months). Surgery was performed in 10 patients; the other 3 patients received palliative care due to rapid metastatic dissemination. Of the 6 patients who had surgery for a recurrence at a distance from important structures, 5 (83.3%) underwent isolated tumour resection with the goal of salvaging the limb and 1 (16.7%) underwent transfemoral amputation. Transfemoral amputation was performed in all 3 patients who had surgery for popliteal recurrences. Lung metastases were detected in 10 (77%) patients, 2 at the time of initial sarcoma diagnosis and 8 at the time of the local recurrence. At last follow-up, 5 patients were alive, including 2 (33.3%) of the 6 patients with recurrences at a distance from important structures and all 3 patients with popliteal recurrences. Of the 5 survivors at last follow-up, 2 had metastases. ConclusionIn patients with local recurrence of knee sarcoma, three presentations can be distinguished. When the local recurrence coincides with distant recurrence, failure to control the disease is likely and the local treatment should be designed as a component of palliative care. When no metastases are detected but the local recurrence is in contact with important structures, amputation is advisable at present given the complexity of limb-salvage surgery and high risk of further local recurrence. Finally, when no metastases are detected and the local recurrence is at a distance from important structures, limb-salvage surgery deserves consideration. Level of evidenceIV, retrospective observational study.

When Should High-dose Chemotherapy and Autologous Stem Cell Transplantation Be Performed in a Pediatric Local High-Risk Ewing Sarcoma A Case Report

When Should High-dose Chemotherapy and Autologous Stem Cell Transplantation Be Performed in a Pediatric Local High-Risk Ewing Sarcoma A Case Report

Considerations for Optimal Implementation of Radiation Therapy Into Multidisciplinary Care for Patients With Sarcoma

Radiation therapy (RT) plays an important role in reducing the risk of local recurrence associated with localized soft-tissue sarcoma (STS) treated with resection alone. The use of image guidance and intensity modulated RT has allowed for excellent local control after wide resection, even with positive margins, with an improved toxicity profile compared with historical strategies used in the literature. However, optimal implementation of RT into multidisciplinary care remains a challenge. Tumors can arise anywhere in the body and exhibit a wide range of behavior, so individualized use of RT is difficult. Data regarding RT for STS are also limited, so making evidence-based decisions is difficult. The American Society for Radiation Oncology recently commissioned a multidisciplinary task force, led by radiation oncologist chair and cochair Drs Kilian Salerno and Ashleigh Guadagnolo. Through 5 key questions (KQs), the recommendations address the most important topics for consideration when discussing RT use with a multidisciplinary treatment team. For patients with localized extremity sarcoma, the authors generally recommend delivering RT for patients at a high risk of recurrence (ie, patients with large, high-grade tumors, especially those expected to have positive margins after surgery). KQ2 and KQ3 recommend that most patients undergo preoperative intensity modulated RT using small clinical target volumes that have been associated with excellent local control in prospective studies. The final KQ discusses the role of preoperative RT in the management of patients with retroperitoneal sarcoma, which is controversial. Overall, the guidelines offer evidence-based expert consensus recommendations that can be used today as a starting point for a multidisciplinary recommendations about RT for patients at your clinic. I look forward to future versions of this guideline, which will consider the results of ongoing work aimed at further improving the value of RT for patients with STS.

Double approach for internal hemipelvectomy: Pararectal and Kocher Langenbeck incision

Background: Internal hemipelvectomy is the preferred treatment option for localized pelvic sarcoma if good functionality is expected in the remaining limb. Wide exposure is crucial for identifying major neurovascular structures in proximity of the tumor. The utilitarian approach and its modifications are the standards to achieve this goal, unfortunately associated with a 35% risk of wound problems and flap ischemia. The pararectal incision provides excellent access to the pelvis, retroperitoneum and even the femoral region.

Extraosseous Ewing sarcoma in children and adolescents: A retrospective series from a referral pediatric oncology center.

Extraosseous Ewing sarcoma is a rare entity and less is known about its clinical behavior and optimal treatment than for its counterpart in bone. This study is a retrospective analysis on a cohort of patients <21years treated according to a "soft tissue sarcoma approach." The "extraosseous" origin of the tumor was established on radiological findings, based on the lack of any bone involvement. Patients were treated using a multimodality approach including surgery, radiotherapy, and chemotherapy. All patients received chemotherapy with alkylating agents and anthracyclines for 25weeks (nine courses). Radiotherapy (45-54.8Gy) was required for all cases except those who had an initial R0 resection of tumors smaller than 5cm. Fifty-seven patients (age 2-20years, median 14) were treated from 1990 to 2020. Ten-year event-free survival (EFS) and overall survival (OS) were 77.5% and 85.5% in patients with localized disease, and 11.1% and 29.6% in those with metastatic disease (p<.001) (follow-up 5-349months, median 107months). In patients with localized disease, the most recent IVADo-IVE regimen achieved excellent survivals, that is, 10-year EFS 95.5%. Our study showed that satisfactory results were achieved in patients with localized extraosseous Ewing sarcoma treated with a tailored approach derived from soft tissue sarcoma protocols, which was less intensive and shorter as compared to the standards utilized for the management of bone Ewing sarcoma. Our study suggests that the extraskeletal site might be considered as a variable to stratify patients and modulate treatment intensity accordingly in Ewing sarcoma protocol.

Postoperative Outcomes of Distal Pancreatectomy for Retroperitoneal Sarcoma Abutting the Pancreas in the Left Upper Quadrant.

BackgroundEn bloc resection of the tumor with adjacent organs is recommended for localized retroperitoneal sarcoma (RPS). However, resection of the pancreas is controversial because it may cause serious complications, such as pancreatic fistula or bleeding. Thus, we evaluated the outcomes of distal pancreatectomy (DP) in pancreas-abutting RPS of the left upper quadrant (LUQ).MethodsWe retrospectively reviewed all consecutive patients who underwent surgery for RPS between September 2001 and April 2020. We selected 150 patients with all or part of their tumor located in the LUQ on preoperative computed tomography. Eighty-six patients who had tumors abutting the pancreas were finally enrolled in our study.ResultsFifty-three patients (53/86; 61.6%) were included in the non-DP group, and 33 patients (33/86; 38.4%) were included in the DP group. Total postoperative complications and complication rates for those Clavien–Dindo grade 3 or higher were similar between the non-DP group and DP group (p = 0.290 and p = 0.550). In the DP group, grade B pancreatic fistulae occurred in 18.2% (6/33) of patients, but grade C pancreatic fistulae were absent, and microscopic pancreatic invasion was noted in 42.4% (14/33) of patients. During multivariate analysis, microscopic pancreatic invasion was deemed a risk factor for local recurrence (p = 0.029). However, there were no significant differences on preoperative computed tomography findings between the pancreatic invasion and non-invasion groups.ConclusionDP is a reasonable procedure for pancreas-abutting RPS located at the LUQ when both complications and complete resection are considered.

Outcome in dogs with curative-intent treatment of localized primary pulmonary histiocytic sarcoma.

Primary pulmonary histiocytic sarcoma (PHS) is a rare form of dendritic cell or macrophage neoplasia originating within the pulmonary parenchyma. There is limited literature describing prognosis in dogs with PHS receiving curative-intent treatment consisting of surgical excision and adjuvant chemotherapy. The primary objective of this study was to report outcomes in dogs with localized PHS treated with standardized local and systemic therapy. A secondary objective was to identify prognostic factors in this population. A multi-institutional retrospective study was performed and medical records including all surgical and histopathologic reports were retrospectively reviewed. For inclusion, dogs were required to have confirmed localized PHS and they must have undergone curative-intent surgery with resection of all gross primary tumour and enlarged tracheobronchial lymph nodes; additionally, they must have received curative-intent treatment with adjuvant single-agent CCNU chemotherapy. Twenty-seven dogs from six veterinary teaching hospitals and five private practices treated from 2008-2019 were included. The overall median survival time was 432 days. Higher CCNU dose was demonstrated to have a negative impact on survival on univariate, but not multivariable, analysis. Factors that were not found to be associated with survival on univariate analysis included body weight, breed, clinical signs at the time of diagnosis, hypoalbuminaemia, tumour size, lung lobe affected, lymph node metastasis, surgical margins and CCNU dose reductions. This study supports a favourable prognosis for dogs diagnosed with localized PHS treated with curative-intent surgery in addition to adjuvant CCNU chemotherapy and suggests that multimodal treatment may be advisable to attempt to prolong survival.

Clinical analysis of multimodal treatment for localized synovial sarcoma: A multicenter retrospective study

IntroductionSeveral prognostic factors for survival in synovial sarcoma have been proposed, but the role of adjuvant chemotherapy and radiotherapy is a matter of debate. The study aim was to clarify the effect of high-dose ifosfamide-containing chemotherapy and adjuvant radiotherapy for patients with localized synovial sarcoma. Materials and methodsFive tertiary musculoskeletal oncology hospitals participated in this retrospective study. The records of the patient diagnosed with synovial sarcoma without metastasis at diagnosis from 1990 to 2011 have been collected and reviewed. Overall, distant failure-free, and local failure-free survivals were calculated, and prognostic factors for each survival were evaluated by performing univariate and multivariate analyses. ResultsA total of 162 patients were enrolled in this study with a median follow-up period of 67 months (range, 5–267 months) for all surviving patients. The 5-year overall, distant failure-free, and local failure-free survival rates were 79.7%, 66.3%, and 98.4%, respectively. Univariate analyses demonstrated that high-dose ifosfamide-containing chemotherapy was significantly associated with better overall (p = 0.014) and distant failure-free survival (p = 0.0043) than that of low-dose or no ifosfamide-containing chemotherapy if we analyzed only patients with tumors >5 cm in size. Addition of radiotherapy was not a significant prognostic factor for overall survival in the univariate and multivariate analyses, but it did improve the overall survival of the patients with R1 resection (p = 0.053). ConclusionPatients with localized synovial sarcoma >5 cm in size had better overall and distant failure-free survival after receiving adjuvant chemotherapy containing high-dose ifosfamide comparing to low-dose or no ifosfamide-containing chemotherapy. The addition of adjuvant radiotherapy was beneficial for the patients who received R1 resection. Alternatively, adjuvant radiotherapy could be avoided for patients who achieved an R0 margin.

Pleuropneumonectomy as Salvage Therapy in Children Suffering from Primary or Metastatic Sarcomas with Pleural Localizations.

Simple SummaryPediatric sarcoma patients with pleuropulmonary lesions have a dismal prognosis because the impossibility to achieve local control. Local therapy with radiotherapy, whether in combination with chemotherapy, appears to be insufficient to eliminate the tumor cells. The aim of this study was to determine if pleuropneumonectomy (PP) could be a therapeutic option. We retrospectively reviewed nine patients who underwent PP for pleuropulmonary localization of primary localized sarcoma or metastatic recurrence. Surgery and complications were analyzed, pulmonary function tests were conducted, and quality of life was determined. Outcome is variable, four patients died within 14 months after PP, one patient suffered from local recurrence, and four patients are in long-lasting remission. This extended operation is quite well tolerated. Lung function seems preserved, and quality of life is generally good. Because it gives improvement of survival in patients with pleural lesions, PP can be considered as effective salvage therapy in selected patients.Pediatric sarcoma patients with pleuropulmonary lesions have a dismal prognosis because the impossibility to obtain local control. The aim of this study was to determine if pleuropneumonectomy (PP) could be a therapeutic option. We retrospectively reviewed nine patients who underwent salvage PP for pleuropulmonary localization of primary localized sarcoma or metastatic recurrence. Surgery and complications were analyzed, pulmonary function tests were conducted, and quality of life was determined with EORTC-QLQ-C30 questionnaire. At the time of PP age was between 9–17 years. Underlying disease included metastatic osteosarcoma (n = 5), Ewing sarcoma (two metastatic, one primary), and one primary undifferentiated sarcoma. Early complications occurred in three patients. Mean postoperative hospitalization stay was 14.5 days. Pulmonary function test showed 19–66% reduction of total lung capacity which led to mild exercise intolerance but did not affect daily life. Four patients died of multi-metastatic relapse <14 months after PP, one patient had a local recurrence, and four patients are in complete remission between 1.5 and 12 years after PP. In conclusion, in this small patient group treated with a pleuropneumonectomy for primary or metastatic lesions, outcome is variable; however, this extended surgical technique was generally quite well tolerated. Postoperative lung function seems well preserved, and it seems to lead to at least an extension of life with good quality and therefor can be considered as salvage therapy.

TP53 Mutation as a Prognostic and Predictive Marker in Sarcoma: Pooled Analysis of MOSCATO and ProfiLER Precision Medicine Trials.

Simple SummarySarcomas have a high recurrence rate and no validated genomic marker to guide decisions of peri-operative systemic treatments. We pooled two precision oncology trials in order to identify genomic markers prognostic and/or predictive of response to treatment with anthracyclines in sarcoma patients. Molecular analysis consisted of targeted next generation sequencing and comparative genomic hybridization array. TP53 mutations were the most frequent alteration, found in 20% of sarcomas. Disease-free survival of localized sarcomas was shorter in TP53 mutated sarcomas, both in our cohort and in The Cancer Genome Atlas database. Objective response rate to anthracycline-based chemotherapy was increased in TP53 mutated sarcomas, in localized and advanced settings in this pooled analysis. Post-validation, TP53 mutations may serve as a biomarker to assist decision of peri-operative anthracycline prescription.(1) Background: locally resected high-grade sarcomas relapse in 40% of cases. There is no prognostic or predictive genomic marker for response to peri-operative chemotherapy. (2) Methods: MOSCATO and ProfiLER are pan-tumor prospective precision medicine trials for advanced tumors. Molecular analysis in both trials comprised targeted next-generation sequencing and comparative genomic hybridization array. We investigated if molecular alterations identified in these trials in sarcomas were associated with disease-free survival (DFS) and response to anthracyclines. (3) Results: this analysis included 215 sarcomas, amongst which 53 leiomyosarcomas, 27 rhabdomyosarcomas, 20 undifferentiated pleomorphic sarcomas, and 17 liposarcomas. The most frequently altered gene was TP53 (46 mutations and eight deletions). There were 149 surgically resected localized sarcomas. Median DFS in TP53 wild type (WT), deleted, and mutated sarcomas was 16, 10, and 10 months, respectively (p = 0.028; deletions: HR = 1.55; 95% CI = 0.75–3.19; mutations: HR = 1.70; 95%CI = 1.13–2.64). In multivariate analysis, TP53 mutations remained associated with shorter DFS (p = 0.027; HR = 2.30; 95%CI = 1.10–4.82). There were 161 localized and advanced sarcomas evaluable for response to anthracyclines. Objective response rates were 35% and 55% in TP53 WT and mutated sarcomas, respectively (OR = 2.24; 95%CI = 1.01–5.03; p = 0.05). In multivariate analysis, TP53 mutations remained associated with increased response (OR = 3.24; 95%CI = 1.30–8.45; p = 0.01). (4) Conclusions: TP53 mutations are associated with shorter DFS and increased response to anthracyclines. Post-validation, these findings could assist in decision-making for peri-operative treatments.

Paediatric non-rhabdomyosarcoma soft tissue sarcomas: the prospective NRSTS 2005 study by the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG)

A standardised approach to treatment of paediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS), which account for about 4% of childhood cancers, is still lacking. We report the results of the NRSTS 2005 protocol developed specifically by the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) to determine a risk-adapted multimodal standard of care for this group of tumours. The EpSSG NRSTS 2005 study included two prospective, non-randomised, historically controlled trials (one on localised adult-type NRSTS and the other on localised synovial sarcoma) done at 100 academic centres and hospitals in 14 countries. Patients younger than 21 years with a pathologically proven diagnosis of synovial sarcoma or an adult-type NRSTS, no evidence of metastatic disease, no previous treatment other than primary surgery, and diagnostic specimens available for pathological review were included. Patients were stratified by surgical stage, tumour size, nodal involvement, tumour grade (for adult-type NRSTS), and tumour site (for synovial sarcoma). Patients were then divided into four treatment groups: surgery alone, adjuvant radiotherapy, adjuvant chemotherapy (with or without radiotherapy), or neoadjuvant chemotherapy (with or without radiotherapy). The main chemotherapy regimen was ifosfamide (3·0 g/m2 intravenously per day for 3 days) plus doxorubicin (37·5 mg/m2 intravenously per day for 2 days); only ifosfamide (3·0 g/m2 intravenously per day for 2 days) was given concomitantly with radiotherapy (delivered with three-dimensional conformal external beam technique, using conventional fractionation [1·8 daily fractions, 5 days per week] at a dose of 50·4 Gy or 54·0 Gy, to a maximum of 59·4 Gy). The number of chemotherapy cycles ranged from three to seven depending on the stage of the disease. The primary outcomes were event-free survival and overall survival. This study has been completed, and is registered under EudraCT, 2005-001139-31. Between May 31, 2005, and Dec 31, 2016, 1321 patients were enrolled, of whom 569 (206 with synovial sarcoma and 363 with adult-type NRSTS), with a median age of 12·6 years (IQR 8·2-14·9), were included in this analysis. With a median follow-up of 80·0 months (IQR 54·3-111·3) for the 467 patients alive, 5-year event-free survival was 73·7% (95% CI 69·7-77·2) and 5-year overall survival was 83·8% (95% CI 80·3-86·7). 5-year event-free survival was 91·4% (95% CI 87·0-94·4) and 5-year overall survival was 98·1% (95% CI 95·0-99·3) in the surgery alone group (n=250); 75·5% (46·9-90·1) and 88·2% (60·6-96·9) in the adjuvant radiotherapy group (n=17); 65·6% (54·8-74·5) and 75·8% (65·3-83·5) in the adjuvant chemotherapy group (n=93); and 56·4% (49·3-63·0) and 70·4% (63·3-76·4) in the neoadjuvant chemotherapy group (n=209). Reported severe adverse events included one case of generalised seizures (probably related to ifosfamide) and six cases of secondary tumours. Findings from the EpSSG NRSTS 2005 study help to define the risk-adapted standard of care for this patient population. Adjuvant treatment can be safely omitted in the low-risk population (classified here as the surgery alone group). Improving the outcome for patients with high-risk, initially resected adult-type NRSTS and those with initially unresectable disease remains a major clinical challenge. Fondazione Città della Speranza.

Extraskeletal Ewing sarcoma in children, adolescents, and young adults. An analysis of three prospective studies of the Cooperative Weichteilsarkomstudiengruppe (CWS).

We have analyzed the outcome of patients with localized extraskeletal Ewing sarcoma (EES) treated in three consecutive Cooperative Weichteilsarkomstudiengruppe (CWS) soft tissue sarcoma (STS) studies: CWS-91, CWS-96, and CWS-2002P. Patients were treated in CWS-91 with four- (vincristine, dactinomycin, doxorubicin, and ifosfamide [VAIA] or cyclophosphamide [VACA II]) or five-drug (+etoposide [EVAIA]) cycles, in CWS-96 they were randomly assigned to receive VAIA or CEVAIE (+carboplatin and etoposide), and in CWS-2002P with VAIA III plus optional maintenance therapy (MT) with cyclophosphamide and vinblastine. Local therapy consisted of resection and/or radiotherapy (RT). Two hundred forty-three patients fulfilled the eligibility criteria. The 5-year event-free survival (EFS) and overall survival (OS) were 63% (95% confidence interval [CI] 57-69) and 73% (95% CI 67-79), respectively. The 5-year EFS by study was 64% (95% CI 54-74) in CWS-91, 57% (95% CI 48-66) in CWS-96, and 79% (95% CI 67-91) in CWS-2002P (n.s.). The 5-year OS was 72% (95% CI 62-82) in CWS-91, 70% (95% CI 61-79) in CWS-96, and 86% (95% CI 76-96) in CWS-2002P (n.s.). In CWS-96, 5-year EFS and OS in the VAIA arm versus the CEVAIE were 65% (95% CI 52-81) versus 55% (95% CI 39-76) log-rank p=.13, and 85% (95% CI 75-96) versus 61% (95% CI 45-82), log-rank p=.09. Our analysis provides interesting information on the treatment and specificities of EES, which can be useful for a better understanding of this rare entity and should be considered in the development of future clinical trials for Ewing sarcoma defined as FET-ETS fusion positive tumors.