Radiotherapy for retroperitoneal liposarcoma: A report from the Transatlantic Retroperitoneal Sarcoma Working Group.

BACKGROUND: The current study investigated the role of radiotherapy (RT) in patients with primary nonmetastatic retroperitoneal liposarcomas. METHODS: A total of 607 patients with localized retroperitoneal well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS) underwent surgical resection with or without RT at 8 high-volume sarcoma centers (234 patients with WDLPS, 242 patients with grade 1 to 2 DDLPS, and 131 patients with grade 3 DDLPS; grading was performed according to the National Federation of Centers for the Fight Against Cancer [Federation Nationale des Centres de Lutte Contre le Cancer; FNCLCC]). RT was administered in 19.7%, 34.7%, and 35.1%, respectively, of these 3 cohorts. Overall survival (OS) was estimated using the Kaplan-Meier method, and the incidences of local recurrence and distant metastasis (DM) were estimated in a competing risk framework. To account for bias consistent with nonrandom RT assignment, propensity scores were estimated. Cox univariable analysis of the association between RT and oncological endpoints was performed by applying inverse probability of treatment weighting (IPTW) using propensity scores. RESULTS: Age, tumor size, and the administration of chemotherapy were found to be significantly imbalanced between patients who did and did not undergo RT in all cohorts. IPTW largely removed imbalances in key prognostic variables. Although the 8-year local recurrence incidences in patients treated with surgery plus RT versus surgery only were 11.8% and 39.2%, respectively, for patients with WDLPS (P = .011;); 29.0% and 56.7%, respectively, for patients with grade 1 to 2 DDLPS (P = .008); and 29.8% and 43.7%, respectively, for patients with grade 3 DDLPS (P = .025), this significant benefit was lost after IPTW analyses. There were no significant differences noted with regard to DM and OS between irradiated and unirradiated patients across all 3 cohorts. CONCLUSIONS: Perioperative RT was found to be associated with better local control in univariable unadjusted analysis in all 3 cohorts, but not after accounting for imbalances in prognostic variables. RT did not impact on DM or OS. The appropriate selection of RT in this disease remains challenging. The results of the European Organization for Research and Treatment of Cancer (EORTC)-Soft Tissue and Bone Sarcoma Group (STBSG) 62092-22092 prospective randomized trial are awaited.

Postoperative Morbidity After Radical Resection of Primary Retroperitoneal Sarcoma: A Report From the Transatlantic RPS Working Group.

OBJECTIVE: To investigate the safety of radical resection for retroperitoneal sarcoma (RPS). BACKGROUND: The surgical management of RPS frequently involves complex multivisceral resection. Improved oncologic outcomes have been demonstrated with this approach compared to marginal excision, but the safety of radical resection has not been shown in a large study population. METHODS: The Transatlantic Retroperitoneal Sarcoma Working Group (TARPSWG) is an international collaborative of sarcoma centers. A combined experience of 1007 consecutive resections for primary RPS from January 2002 to December 2011 was studied retrospectively with respect to adverse events. A weighted organ score was devised to account for differences in surgical complexity. Univariate and multivariate logistic regression analyses were performed to investigate associations between adverse events and number and patterns of organs resected. Associations between adverse events and overall survival, local recurrence, and distant metastases were investigated. RESULTS: Severe postoperative adverse events (Clavien-Dindo ≥3) occurred in 165 patients (16.4%) and 18 patients (1.8%) died within 30 days. Significant predictors of severe adverse events were age (P = 0.003), transfusion requirements (P < 0.001), and resected organ score (P = 0.042). Resections involving pancreaticoduodenectomy, major vascular resection, and splenectomy/pancreatectomy were found to entail higher operative risk (odds ratio >1.5). There was no impact of postoperative adverse events on overall survival, local recurrence, or distant metastases. CONCLUSIONS: A radical surgical approach to RPS is safe when carried out at a specialist sarcoma center. High-risk resections should be carefully considered on an individual basis and weighed against anticipated disease biology. There appears to be no association between surgical morbidity and long-term oncologic outcomes.

Post-relapse outcomes after primary extended resection of retroperitoneal sarcoma: A report from the Trans-Atlantic RPS Working Group.

BACKGROUND: Despite a radical surgical approach to primary retroperitoneal sarcoma (RPS), many patients experience locoregional and/or distant recurrence. The objective of this study was to analyze post-relapse outcomes for patients with RPS who had initially undergone surgical resection of their primary tumor at a specialist center. METHODS: All consecutive patients who underwent macroscopically complete resection for primary RPS at 8 high volume centers from January 2002 to December 2011 were identified, and those who developed local recurrence (LR) only, distant metastasis (DM) only, or synchronous local recurrence and distant metastasis (LR+DM) during the follow-up period were included. Overall survival (OS) was calculated for all groups, as was the crude cumulative incidence of a second recurrence after the first LR. Multivariate analyses for OS were performed. RESULTS: In an initial series of 1007 patients with primary RPS, 408 patients developed recurrent disease during the follow-up period. The median follow-up from the time of recurrence was 41 months. The median OS was 33 months after LR (n = 219), 25 months after DM (n = 146), and 12 months after LR+DM (n = 43), and the 5-year OS rates were 29%, 20%, and 14%, respectively. Predictors of OS after LR were the time interval to LR and resection of LR, while histologic grade approached significance. For DM, significant predictors of OS were the time interval to DM and histologic subtype. The subgroup of patients who underwent resection of recurrent disease had a longer median OS than patients who did not undergo resection. CONCLUSIONS: Relapse of RPS portends high disease-specific mortality. Patients with locally recurrent or metastatic disease should be considered for resection. Cancer 2017;123:1971-1978. © 2017 American Cancer Society.

External validation of a multi-institutional retroperitoneal sarcoma nomogram.

BACKGROUND: A multi-institutional nomogram for predicting disease-free survival (DFS) and overall survival (OS) in patients with primary retroperitoneal sarcoma (RPS) incorporating relevant prognostic factors not included in the American Joint Committee on Cancer staging system for soft tissue sarcoma has been reported. The authors validated this nomogram with an independent, transatlantic cohort. METHODS: Data from patients with RPS who were undergoing definitive resection at 1 of 6 sarcoma centers in Europe and North America ("validation set") were used to validate a RPS nomogram developed from 3 other centers ("development set"). The nomogram incorporated 6 variables: age, tumor size, grade, histologic subtype, multifocality, and quality of surgery. Nomogram-predicted probabilities were stratified into 6 subgroups and compared with observed outcomes. Discriminative ability was quantified by Harrell C statistics. RESULTS: The validation and development sets included 631 and 523 patients, respectively, all of whom underwent surgical resection at the institutions represented. The 7-year DFS and OS rates for the validation set were 38% (95% confidence interval, 34%-43%) and 58% (95% confidence interval, 53%-63%), respectively. All 6 nomogram variables were found to be independently prognostic. The corrected Harrell C statistics concordance index values for the validation set were 0.69 for DFS and 0.73 for OS, which were similar to those for the development set, suggesting good calibration of the nomogram in the validation cohort. CONCLUSIONS: The RPS nomogram was externally validated using a larger, independent cohort. The nomogram can be generalized to patients undergoing surgery for RPS by specialized sarcoma surgeons at sarcoma centers. The nomogram provides a more individualized and disease-relevant estimation of OS compared with the American Joint Committee on Cancer classification. Cancer 2016;122:1417-1424. © 2016 American Cancer Society.

Variability in Patterns of Recurrence After Resection of Primary Retroperitoneal Sarcoma (RPS): A Report on 1007 Patients From the Multi-institutional Collaborative RPS Working Group.

BACKGROUND: Retroperitoneal sarcomas (RPS) are rare tumors composed of several well defined histologic subtypes. The aim of this study was to analyze patterns of recurrence and treatment variations in a large population of patients, treated at reference centers. METHODS: All consecutive patients with primary RPS treated at 6 European and 2 North American institutions between January 2002 and December 2011 were included. Five, 8, and 10-year overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were calculated. Multivariate analyses for OS, CCI of LR, and DM were performed. RESULTS: In all, 1007 patients were included. Median follow-up was 58 months (first and third quartile range 36-90). The 5, 8, and 10-year OS were 67% [95% confidence interval (CI), 63, 70), 56% (95% CI, 52, 61), and 46% (95% CI, 40, 53). The 5, 8, and 10-year CCI of LR and DM were 25.9 (95% CI, 23.1, 29.1), 31.3 (95% CI, 27.8, 35.1), 35% (95% CI, 30.5, 40.1), and 21% (95% CI, 18.4, 23.8%), 21.6 (95% CI, 19.0, 24.6), and 21.6 (95% CI, 19.0, 24.6), respectively. Tumour size, histologic subtype, malignancy grade, multifocality, and completeness of resection were significant predictors of outcome. Patterns of recurrence varied depending on histologic subtype. Different treatment policies at participating institutions influenced LR of well differentiated liposarcoma without impacting OS, whereas discrepancies in adjuvant systemic therapies did not impact LR, DM, or OS of leiomyosarcoma. CONCLUSIONS: Reference centers are critical to outcomes of RPS patients, as the management strategy requires specific expertise. Histologic subtype predicts patterns of recurrence and should inform management decision. A prospective international registry is under preparation, to further define our understanding of this disease.

Intraparenchymal mesenchymal chondrosarcoma of the frontal lobe--a case report and molecular detection of specific gene fusions from archival FFPE sample.

Mesenchymal chondrosarcoma is a rare tumor of cartilaginous origin characterized by its bimorphic pattern composed of highly undifferentiated small round cells separated by islands of well-differentiated hyaline cartilage. It exhibits higher malignancy and earlier occurrence in comparison to classic chondrosarcomas. Recently identified HEY1-NCOA2 and IRF2BP2-CDX1 gene fusions confirm their distinct molecular origin and pose a promising diagnostic marker. The majority of cases arise from craniofacial bones. In this study, we present a rare case of mesenchymal chondrosarcoma encompassed within the brain parenchyma of the frontal lobe without any dural or bone attachment. We demonstrate histopathological findings and confirm the HEY1-NCOA2 gene fusion in a formalin-fixed paraffin-embedded archival sample using simple reverse transcription polymerase chain reaction (RT-PCR) method. IRF2BP2-CDX1 gene fusion was absent in the analyzed sample. The clinical follow-up is also presented with a review of treatment modalities for this entity.

Palliative Radiotherapy Produced Spectacular Improvement in a Terminally Ill Colorectal Carcinoma Patient With Severe Pain and Duodenal Bleeding.

Colorectal cancer has a devastating effect on the quality of life, and the treatment of active intestinal bleeding in colorectal cancer is a real challenge at the end of life. This case report presents a spectacular effect of an unusual palliative treatment strategy in a middle-aged home hospice patient with severe pain and persistent duodenal bleeding secondary to its neoplastic infiltration. Palliative radiotherapy (RT) significantly improved pain control, terminated the duodenal bleeding, and allowed successful treatment of deep vein thrombosis, previously impossible because of the bleeding. It also made the patient independent of otherwise unavoidable transfusions, thus improving his quality of life. In our patient, RT played a leading role in restoring general fitness and, accordingly, mental state improvement. Our case demonstrates that palliative RT may be a valuable treatment option in cases similar to ours. Still, careful assessment of risks and benefits is always mandatory.

Denosumab treatment of inoperable or locally advanced giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive tumor that rarely metastasizes and typically occurs in the bones. At present, the primary treatment for GCTB is curettage with local adjuvants. Giant cells express receptor activator of nuclear factor-κB ligand (RANKL). Denosumab, a RANKL inhibitor appears to present an effective therapeutic option in advanced cases of GCTB. The aim of the present study was to confirm the efficacy of denosumab in large group of patients with locally advanced GCTB. A total of 35 patients with histologically confirmed GCTB that were treated with denosumab with no participation in clinical trials between May 2013 and September 2015 were included in the present study. Denosumab treatment was administered until complete tumor resection was feasible or tumor progression or unacceptable toxicity had occurred. The mean denosumab treatment duration was 7.4 months. A total of 17 patients received surgery following denosumab treatment: 11 patients underwent wide en bloc resection with prosthesis implantation in 10 cases and 6 patients were treated with intralesional curettage. Tumor progression was observed in 2 patients that underwent intralesional curettage without prosthesis implantation. In addition, tumor progression was observed during denosumab treatment in 2 patients that had previously undergone radiotherapy. The overall 1-year progression-free survival rate was 92.8%. Thus, for patients with advanced, unresectable, progressive or symptomatic pretreated GCTB, denosumab provides a therapeutic option not previously available, which has become the standard therapy in multidisciplinary management of GCTB.