What is the impact of local control in Ewing sarcoma : analysis of the first Brazilian collaborative study group – EWING1

Background: Relapse in localized Ewing sarcoma patients has been a matter of concern regarding poor prognosis. Therefore, we investigated the impact of local control modality (surgery, surgery plus radiotherapy, and radiotherapy) on clinical outcomes such as survival and recurrence in patients with non-metastatic Ewing sarcoma treated on the first Brazilian Collaborative Group Trial of the Ewing Family of Tumors (EWING1). Methods: Seventy-three patients with localized Ewing sarcoma of bone aged < 30 years were included. The treating physicians defined the modality of local control based on the recommendations of the coordinating center and the patient and tumor characteristics. Possible associations of local control modality with local failure (LF), disease-free survival (DFS), event-free survival (EFS), overall survival (OS), and clinical characteristics were analyzed. Results: Mean patient age was 12.8 years (range, 2 to 25 years) and median follow-up time was 4.5 years (range, 2. 3 to 6.7 years). Forty-seven patients underwent surgery, 13 received radiotherapy, and 13 received both. The 5-year EFS, OS, and DFS for all patients was 62.1%, 63.3%, and 73.1%, respectively. The 5-year cumulative incidence (CI) of LF was 7.6% for surgery, 11.1% for radiotherapy, and 0% for postoperative radiotherapy (PORT) (p = 0.61). The 5-year EFS was 71.7% for surgery, 30.8% for radiotherapy, and 64.1% for PORT (p = 0.009). Conclusions: There was a significant effect of local control modality on EFS and OS in the study. Surgery and PORT modalities yielded very close results. The group treated with radiotherapy alone had considerably worse outcomes. This may be confounded by greater risk factors in these patients. There was no significant effect of local control modality on the CI of LF and DFS

What is the impact of local control in Ewing sarcoma: analysis of the first Brazilian collaborative study group-EWING1

Background: Relapse in localized Ewing sarcoma patients has been a matter of concern regarding poor prognosis. Therefore, we investigated the impact of local control modality (surgery, surgery plus radiotherapy, and radiotherapy) on clinical outcomes such as survival and recurrence in patients with non-metastatic Ewing sarcoma treated on the first Brazilian Collaborative Group Trial of the Ewing Family of Tumors (EWING1). Methods: Seventy-three patients with localized Ewing sarcoma of bone aged < 30 years were included. The treating physicians defined the modality of local control based on the recommendations of the coordinating center and the patient and tumor characteristics. Possible associations of local control modality with local failure (LF), disease-free survival (DFS), event-free survival (EFS), overall survival (OS), and clinical characteristics were analyzed. Results: Mean patient age was 12.8 years (range, 2 to 25 years) and median follow-up time was 4.5 years (range, 2. 3 to 6.7 years). Forty-seven patients underwent surgery, 13 received radiotherapy, and 13 received both. The 5-year EFS, OS, and DFS for all patients was 62.1%, 63.3%, and 73.1%, respectively. The 5-year cumulative incidence (CI) of LF was 7.6% for surgery, 11.1% for radiotherapy, and 0% for postoperative radiotherapy (PORT) (p = 0.61). The 5-year EFS was 71.7% for surgery, 30.8% for radiotherapy, and 64.1% for PORT (p = 0.009). Conclusions: There was a significant effect of local control modality on EFS and OS in the study. Surgery and PORT modalities yielded very close results. The group treated with radiotherapy alone had considerably worse outcomes. This may be confounded by greater risk factors in these patients. There was no significant effect of local control modality on the CI of LF and DFS.Children's Cancer InstituteRafael Accordi Foundation, Porto Alegre, RS, BrazilHCPA, Serv Orthoped & Traumatol, Rua Ramiro Barcelos 2350, BR-90035903 Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, HCPA, Dept Pediat, Porto Alegre, RS, BrazilPontificia Univ Catolica Rio Grande Sul PUCRS, Dept Pediat, Hosp Sao Lucas, Porto Alegre, RS, BrazilHCPA, Serv Orthoped & Traumatol, Porto Alegre, RS, BrazilUniv Fed Sao Paulo UNIFESP, Support Grp Children & Adolescents Canc GRAACC, Sao Paulo, SP, BrazilHosp Canc Infantojuvenil, Fundacao Pio 12, Barretos, SP, BrazilCtr Hosp Pereira Rossell, Montevideo, UruguayHosp AC Camargo Canc Ctr, Orthoped Serv, Sao Paulo, SP, BrazilSanta Casa Misericordia Porto Alegre, Serv Orthoped & Traumatol, Porto Alegre, RS, BrazilUniv Sao Paulo, Orthoped Trauma Inst, Hosp Clin Sao Paulo, Sch Med, Sao Paulo, SP, BrazilSanta Casa Misericordia Sao Paulo HSCSP, Dept Orthoped & Traumatol, Sao Paulo, SP, BrazilPontificia Univ Catolica Rio Grande Sul PUCRS, Hosp Sao Lucas, Serv Orthoped & Traumatol, Porto Alegre, RS, BrazilUniv Estadual Paulista UNESP, Hosp Clin Botucatu, Sch Med, Botucatu, SP, BrazilInst Canc Infantil, Porto Alegre, RS, BrazilUniv Fed Sao Paulo UNIFESP, Support Grp Children & Adolescents Canc GRAACC, Sao Paulo, SP, BrazilChildren's Cancer InstituteRafael Accordi Foundation, Porto Alegre, RS, BrazilWeb of Scienc

SELNET clinical practice guidelines for bone sarcoma

Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context

SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

Lineage survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development.1,2 Here we show that a peak of genomic amplification on chromosome 3q26.33, found in squamous cell carcinomas (SCCs) of the lung and esophagus, contains the transcription factor gene SOX2—which is mutated in hereditary human esophageal malformations3 and necessary for normal esophageal squamous development4, promotes differentiation and proliferation of basal tracheal cells5 and co-operates in induction of pluripotent stem cells.6,7,8 SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These observations identify SOX2 as a novel lineage survival oncogene in lung and esophageal SCC

What is the impact of local control in Ewing sarcoma: analysis of the first Brazilian collaborative study group – EWING1

Abstract Background Relapse in localized Ewing sarcoma patients has been a matter of concern regarding poor prognosis. Therefore, we investigated the impact of local control modality (surgery, surgery plus radiotherapy, and radiotherapy) on clinical outcomes such as survival and recurrence in patients with non-metastatic Ewing sarcoma treated on the first Brazilian Collaborative Group Trial of the Ewing Family of Tumors (EWING1). Methods Seventy-three patients with localized Ewing sarcoma of bone aged < 30 years were included. The treating physicians defined the modality of local control based on the recommendations of the coordinating center and the patient and tumor characteristics. Possible associations of local control modality with local failure (LF), disease-free survival (DFS), event-free survival (EFS), overall survival (OS), and clinical characteristics were analyzed. Results Mean patient age was 12.8 years (range, 2 to 25 years) and median follow-up time was 4.5 years (range, 2.3 to 6.7 years). Forty-seven patients underwent surgery, 13 received radiotherapy, and 13 received both. The 5-year EFS, OS, and DFS for all patients was 62.1%, 63.3%, and 73.1%, respectively. The 5-year cumulative incidence (CI) of LF was 7.6% for surgery, 11.1% for radiotherapy, and 0% for postoperative radiotherapy (PORT) (p = 0.61). The 5-year EFS was 71.7% for surgery, 30.8% for radiotherapy, and 64.1% for PORT (p = 0.009). Conclusions There was a significant effect of local control modality on EFS and OS in the study. Surgery and PORT modalities yielded very close results. The group treated with radiotherapy alone had considerably worse outcomes. This may be confounded by greater risk factors in these patients. There was no significant effect of local control modality on the CI of LF and DFS

Sarcoma European & Latin American Network (SELNET) recommendations on prioritization in sarcoma care during covid‐19 pandemic

Background COVID‐19 outbreak has resulted in collision between SARS‐CoV‐2‐infected patients and cancer patients on different fronts. Serious SARS‐CoV‐2 cases overwhelmed hospital capacity, especially in intensive care units, causing a domino effect, displacing areas from their primary use. Cancer patient has been impacted by deferral, modification or even cessation of therapy. Adaptive measures to minimize hospital exposure, following the precautionary principle have been proposed for cancer care during COVID‐19 era. We present here a consensus on prioritizing recommendations across the continuum of sarcoma patient care. Material and methods A total of 125 recommendations were proposed in soft‐tissue, bone and visceral sarcoma care. Recommendations were assigned as higher‐ or lower‐priority if they cannot or can be postponed at least 2‐3 months, respectively. The consensus level for each recommendation was classified as “strongly recommended” (SR) if more than 90% of experts agreed, “recommended” (R) if 75‐90% of experts agreed and “no consensus” (NC) if fewer than 75% agreed. Sarcoma experts from 11 countries within the SELNET consortium participated, including countries in the Americas and Europe. The ESMO‐Magnitude of clinical benefit scale was applied to systemic‐treatment recommendations to support prioritization. Results There were 80 SR, 35 R and 10 NC among the 125 recommendations issued and completed by 31 multidisciplinary sarcoma experts. The consensus was higher among the 75 higher‐priority recommendations (85%, 12% and 3% for SR, R and NC, respectively) than in the 50 lower‐priority recommendations (32%, 52% and 16% for SR, R and NC, respectively). Conclusion The consensus on 115 of 125 recommendations indicates a high‐level of convergence among experts. The SELNET consensus provides a tool for sarcoma multidisciplinary treatment committees during the COVID‐19 outbreak. The details of different recommendations and the distinction between two priority levels enables a practical approach for both Latin‐American and other health‐care providers, and sarcoma expert centres. Implications for Practice SELNET consensus on sarcoma prioritization care during the COVID‐19 era, issued 125 pragmatical recommendations distributed as higher or lower priority, to protect critical decisions on sarcoma care during COVID‐19 pandemic. A multidisciplinary team from 11 countries, including countries in the Americas and Europe, reached consensus on 115 recommendations. The consensus was lower among lower‐priority recommendations, which shows reticence to postpone actions even in indolent tumors. The ESMO‐magnitude of clinical benefit scale was applied as support for prioritizing systemic treatment. Consensus on 115 of 125 recommendations indicates a high‐level of convergence among experts. The SELNET consensus provides a practice tool for the guidance in the decisions of sarcoma multidisciplinary treatment committees during the COVID‐19 outbreak.Peer reviewe

SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

Lineage-survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development. Here we show that a peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas (SCCs) of the lung and esophagus contains the transcription factor gene SOX2, which is mutated in hereditary human esophageal malformations, is necessary for normal esophageal squamous development, promotes differentiation and proliferation of basal tracheal cells and cooperates in induction of pluripotent stem cells. SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 here cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC