Factors Influencing the Outcome of Patients with Primary Ewing Sarcoma of the Sacrum.

Pineoblastoma: prognostic factors and survival outcomes in young children.

11529 Background: Maximum tumor dimension > 8 cm. and large tumor volume have been reported to be adverse prognostic factors in patients with ES but have not been prospectively evaluated in the context of a phase 3 clinical trial with interval compressed chemotherapy. Methods: COG AEWS1031 (NCT01231906) was a randomized phase 3 clinical trial comparing interval compressed chemotherapy regimens in patients with newly diagnosed localized ES of bone and soft tissue. A correlative objective of AEWS1031 was to evaluate tumor size and volume as prognostic factors. Institution-reported dimensions of the primary tumor from baseline imaging were prospectively collected. For inclusion in this analysis, patients had to have at least 1 tumor dimension reported for tumor size analyses and dimensions in 3 axes for tumor volume analyses. Maximum dimension was dichotomized as less than vs. > / = 8cm. Tumor volume was dichotomized as less than vs. > / = 200 mL. Event-free (EFS) and overall survival (OS) from enrollment were calculated using Kaplan-Meier methods and compared between groups using a two-sided log-rank test. Hazard ratios (HR) and confidence intervals (CI) were calculated using the Cox model. Results: The 5-year EFS and OS of the 629 eligible patients was 78% (95% CI: 75-81%) and 87% (95% CI: 84-90%) respectively and there was no significant difference in both EFS and OS between the randomized interval compressed chemotherapy arms of AEWS1031. 590 of 629 (94%) patients were evaluable for maximum tumor dimension and 307 (52%) had tumors > / = 8 cm. Patients with tumors > / = 8 cm were at significantly increased risk for EFS events (p = 0.016) with estimated 5-year EFS of 73.7% (95% CI: 68.1 vs.78.4%) vs. 82.9% (95% CI 77.7-87.1%) for patients with tumors < 8 cm [HR: 1.53 (1.08-2.17)]. For tumor volume, 586 of 629 patients (93%) were evaluable and 180 (31%) had tumors > / = 200 mL. Patients with tumor volume > / = 200 mL were at significantly increased risk for EFS events (p = 0.003) with estimated 5-year EFS of 70% (95% CI: 62.3-76.4%) vs. 81.6% (95% CI: 77.2-85.2%) for patients with tumors < 200 mL [HR: 1.69 (1.2-2.39)]. Conclusions: Maximum tumor dimension and tumor volume as defined are both prognostic in patients with newly diagnosed localized ES treated with interval compressed chemotherapy. Clinical trial information: NCT01231906 .

Impact of Thromboembolism on Overall and Event-Free Survival in Children with Acute Lymphoblastic

Outcome of relapsed/refractory acute promyelocytic leukaemia in children, adolescents and young adult patients - a 25-year Italian experience.

No Association of EBV or Immunosuppression Status with Outcomes in US Patients with Diffuse Large B-Cell Lymphoma Treated in the Immunochemotherapy Era

Objective: To study factors affecting outcomes such as overall survival (OS) and locoregional control (LRC), in patients with squamous cell carcinomas of oropharynx treated with definitive radiation therapy (RT), with or without concurrent chemotherapy. Method: Retrospective analysis of 83 patients with squamous cell carcinoma of oropharynx treated with definitive radiation therapy at University of Mississippi Medical Center. All patients were treated to 70 Gy utilizing intensity-modulated radiation treatment. Stage III and IV patients also received concurrent chemotherapy with weekly cisplatin. Chi-square test was used to test the goodness of fit, OS and LRC comparing races were generated by using log rank test and Kaplan-Meier method. The covariables associated with the OS and LRC were determined by multivariate Cox regression model. Hazards ratio (HR) was used to estimate time to event outcome with associated 95% confidence intervals (CIs) and P values. Median follow-up for the entire group was 39 months. Results: Of the total 83 eligible patients 51.8% were black, 48.5% were white, and 2.4% wee other. Stage distribution (per American Joint Committee on Cancer-AJCC 7th Ed) between blacks vs. whites for Stage I and II was 50% vs. 50%; for Stage III, 41.6% vs. 58.3%; and for Stage IV, 55.2% vs. 41.8%. In the univariate analysis, insurance, HPV/p16, body mass index (BMI), and race are the variables that affected the outcomes. In the multivariate analysis, HPV/p16, BMI, race, and tonsil subsite are shown to be significant. Age, gender, income level, employment, distance from facility, smoking, alcohol, and marital status are not shown to be significant. LRC for black patients was 49% vs. 72% in white patients (P = 0.022). Three-year OS for black patients was 49.2% vs. 66% for white patients (P = 0.010). HR for black patients was 0.13 with 95% CI 0.03- 0.61 (P= 0.009); HR for white patients was 0.24 with 95% CI 0.56- 1.06 (P= 0.061). OS for Stage IV black patients was 28% vs. 82% for white patients (P=0.006). In this cohort, HPV/p16 black positive patients were 75%, black negative 33%, white positive 87%, and white negative 50%, respectively. HR for HPV/p16 positive was 0.23 with 95% CI 0.07-0.71(P = 0.01). HR for tonsil subsite was 0.37 with 95% CI 0.15-0.91 (P=0.031). HR for BMI was 5.27 with 95% CI 1.79-15.5 (P = 0.003). The race, HPV/p16, BMI, and tonsil subsite were all independently associated with worse OS on multivariate analysis. HR for black patients was 0.16 with 95% CI 0.03-0.73 (P= 0.019), HR for HPV/p16 positive was 0.24 with 95% CI 0.07-0.73 (P = 0.013), HR for tonsil subsite was 0.41 with 95% CI 0.17-0.99 (P = 0.048), and HR for BMI was 5.59 with 95% CI 1.90-16.39 (P= 0.002). Race, HPV/p16, BMI, and tonsil subsite were all independently associated with worse locoregional failure on multivariate analysis. Conclusion: Among all the covariables examined, race, HPV/p16 status, BMI, and tonsil subsite were shown to be affecting the locoregional and overall survival outcomes. Racial factor appears to be more significant in patients with Stage IV disease. Citation Format: Mary R. Nittala, Eldrin Bhanat, Srinivasn Vijayakumar, Madhava R. Kanakamedala. Factors affecting outcomes in patients with squamous cell carcinoma of oropharynx [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B21.

Objective: To describe the clinical and epidemiological characteristics, and to determine the prognostic factors, event-free survival (EFS) and overall survival (OS) of patients with Ewing Sarcoma family of tumors (ESFT). Materials and methods: retrospective study carried out in patients under 18 years of age with TFSE, seen at the Pediatric and Adolescent Oncology Unit of the Edgardo Rebagliati Hospital between 2006 and 2016. The descriptive analysis was performed by frequency distribution. Kaplan-Meier curves were used for the analysis of SLE and OS. Univariate and multivariate analysis was performed according to Cox regression model for demographic, clinical and surgical variables, and prognostic factors. The measure of strength of association was expressed as hazard ratio (HR) and 95% confidence interval (95% CI), and p<0.05 was considered for significant differences. Results: Twenty-nine cases of TFSE were presented. The median age was 9 years (range 2-17), 55% were male. The most frequent location was the pelvis (31%). Fifty-nine percent had metastases at diagnosis. The 3-year EFS in localized ESFT was 40.4% (±14.4 ES) and with metastases, 14.6% (±12.2, ES). The 3-year OS in localized TFSE was 53.9% (±17.8 ES) and in metastatic disease, 15.1% (±9.7, ES). Tumor size ≥5cm (HR 14.84, p=0.01) and the presence of metastases at debut (HR 3.23, p=0.01) were independent prognostic factors for worse OS. There was no significant difference in relation to prognosis according to sex, age, histologic type, surgical edge involvement or tumor location. Conclusions: ESFTs are highly aggressive. Prognostic factors contributing to lower EFS and OS are the presence of metastases at disease debut and tumor size ≥5cm.

Results of the ECOG E1900 Trial in Younger Adults with AML Using an Event Free Survival Endpoint Are Concordant with Results Based on Overall Survival: Potential for a Surrogate Endpoint to Facilitate Rapid Approval of Therapies in AML

Effect of Radiotherapy Dose on Outcome in Nonmetastatic Ewing Sarcoma

Clinical Impact of Additional Cytogenetic Aberrations and Complex Karyotype In Pediatric 11q23/MLL-Rearranged AML: Results from an International Retrospective Study

PurposePediatric-type sarcomas such as rhabdomyosarcoma (RMS), Ewing sarcoma (EWS), primitive neuroectodermal tumor (PNET), and desmoplastic small round-cell tumor (DSRCT) are rare in adults, with limited studies on their prognosis and optimal treatment strategies. We aimed to examine the outcome of children and adult patients with RMS, EWS, PNET, and DSRCT and relevant prognostic factors.Materials and MethodsWe retrospectively reviewed 220 pediatric-type sarcoma patients at a single institution between 1985 and 2011. Comparisons were made in order to examine differences in demographics, disease characteristics, and survival. Survival analyses were performed using the Kaplan-Meier method with log-rank tests and Cox proportional hazards models.ResultsA total of 220 consecutive patients were identified at our institute. Median age was 15.6 years (range, 0 to 81 years) and there were 108 children (49%) and 112 adult patients (51%). According to histological classification, 106 patients (48.2%) had RMS, 60 (27.3%) had EWS, 50 (22.7%) had PNET, and 4 (1.8%) had DSRCT. With a median follow-up period of 6.6 years, the estimated median overall survival (OS) of all patients was 75 months (95% confidence interval [CI], 27.2 to 122.8 months) and median event-free survival (EFS) for all patients was 11 months (95% CI, 8.8 to 13.2 months). No significant difference in OS and EFS was observed between adults and children. In multivariate analysis, distant metastasis (hazard ratio [HR], 1.617; 95% CI, 1.022 to 2.557; p=0.040) and no debulking surgery (HR, 1.443; 95% CI, 1.104 to 1.812; p=0.012) showed independent association with worse OS.ConclusionMetastatic disease and no surgical treatment are poor prognostic factors for OS among pediatric-type sarcomas for both adults and children.

The prognostic significance of having extraskeletal (EES) versus skeletal Ewing sarcoma (ES) in the setting of modern chemotherapy protocols is unknown. The purpose of this study was to compare the clinical characteristics, biologic features, and outcomes for patients with EES and skeletal ES. Patients had localized ES and were treated on two consecutive protocols using five-drug chemotherapy (INT-0154 and AEWS0031). Patients were analyzed based on having an extraskeletal (n = 213) or skeletal (n = 826) site of tumor origin. Event-free survival (EFS) was estimated using the Kaplan-Meier method, compared using the log-rank test, and modeled using Cox multivariate regression. Patients with extraskeletal ES (EES) were more likely to have axial tumors (72% vs. 55%; P < 0.001), less likely to have tumors >8 cm (9% vs. 17%; P < 0.01), and less likely to be white (81% vs. 87%; P < 0.001) compared to patients with skeletal ES. There was no difference in key genomic features (type of EWSR1 translocation, TP53 mutation, CDKN2A mutation/loss) between groups. After controlling for age, race, and primary site, EES was associated with superior EFS (hazard ratio = 0.69; 95% confidence interval: 0.50-0.95; P = 0.02). Among patients with EES, age ≥18, nonwhite race, and elevated baseline erythrocyte sedimentation rate were independently associated with inferior EFS. Clinical characteristics, but not key tumor genomic features, differ between EES and skeletal ES. Extraskeletal origin is a favorable prognostic factor, independent of age, race, and primary site.

Unrelated Donors below 35 Years of Age Should be Preferred over HLA-Matched Sibling Donors Older Than 50 Years for Patients with Myeloid Malignancies

Simple SummaryAlthough oligometastatic disease is common, present in up to 25% of patients with stage IV non-small cell lung cancer, management of it remains challenging. Numerous other studies have shown promising results in patients who undergo local treatment of both the primary tumor and the metastases. In this, the largest single-institution analysis of patients undergoing primary tumor surgical resection for oligometastatic disease, we have demonstrated encouraging long-term event-free survival, overall survival, and postrecurrence survival, with the greatest benefit in patients who undergo neoadjuvant therapy and those with limited intrathoracic disease. Therefore, in carefully selected patients, surgical resection of the primary tumor can be an important component of multimodal management for advanced-stage non-small cell lung cancer.Stage IV non-small cell lung cancer (NSCLC) accounts for 35 to 40% of newly diagnosed cases of NSCLC. The oligometastatic state—≤5 extrathoracic metastatic lesions in ≤3 organs—is present in ~25% of patients with stage IV disease and is associated with markedly improved outcomes. We retrospectively identified patients with extrathoracic oligometastatic NSCLC who underwent primary tumor resection at our institution from 2000 to 2018. Event-free survival (EFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Factors associated with EFS and OS were determined using Cox regression. In total, 111 patients with oligometastatic NSCLC underwent primary tumor resection; 87 (78%) had a single metastatic lesion. Local consolidative therapy for metastases was performed in 93 patients (84%). Seventy-seven patients experienced recurrence or progression. The five-year EFS was 19% (95% confidence interval (CI), 12–29%), and the five-year OS was 36% (95% CI, 27–50%). Factors independently associated with EFS were primary tumor size (hazard ratio (HR), 1.15 (95% CI, 1.03–1.29); p = 0.014) and lymphovascular invasion (HR, 1.73 (95% CI, 1.06–2.84); p = 0.029). Factors independently associated with OS were neoadjuvant therapy (HR, 0.43 (95% CI, 0.24–0.77); p = 0.004), primary tumor size (HR, 1.18 (95% CI, 1.02–1.35); p = 0.023), pathologic nodal disease (HR, 1.83 (95% CI, 1.05–3.20); p = 0.033), and visceral-pleural invasion (HR, 1.93 (95% CI, 1.10–3.40); p = 0.022). Primary tumor resection represents an important treatment option in the multimodal management of extrathoracic oligometastatic NSCLC. Encouraging long-term survival can be achieved in carefully selected patients, including those who received neoadjuvant therapy and those with limited intrathoracic disease.

11505 Background: Children’s Oncology Group study AEWS0031 demonstrated superior 5-year event-free survival (EFS) in patients with localized Ewing sarcoma (ES) receiving interval-compressed (IC) chemotherapy (every 2 weeks) compared to standard timing (ST) chemotherapy (every 3 weeks). We assessed the long-term outcome of patients treated on AEWS0031 to determine whether the survival advantage of IC chemotherapy was maintained at 10 years. Methods: AEWS0031 enrolled 568 eligible patients with localized ES. Patients were stratified into four groups by age (&lt;18 years and ≥ 18 years) and primary site (pelvic and non-pelvic), and randomized to receive 14 cycles of alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide given every 3 weeks (ST; Regimen A) vs. every 2 weeks (IC; Regimen B). For this updated report, one patient was excluded due to uncertainty of original diagnosis giving a total of 567 patients in this analysis. Data for tumor measurements and histologic response were collected retrospectively from institutional reports. EFS and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test and Gray’s test for cumulative incidence (CI). Results: The 10-year EFS for patients treated with IC chemo was 70% compared to 61% for ST chemo (p = 0.03), and the OS was 76% with IC chemo compared to 69% for ST chemo (p = 0.03). The 10-year CI of second malignant neoplasms (SMNs) for ST chemo was 4.2% [95% confidence interval: 2.4-7.5] compared to 3.2% (95% confidence interval: 1.6-6.3) for IC chemo (p = 0.5). There was a trend towards improved 10-year EFS in those receiving IC chemo both with non-pelvic (N = 477; 71% vs. 64%) and pelvic (N = 90; 67% vs. 43%) primary tumors. Similarly, the 10-year EFS was superior for patients treated with IC chemo in both the &lt; 18 years (N = 500; 73% vs. 64%) and ≥ 18 years (N = 67; 53% vs. 37%) age groups. Among the 184 patients with available histologic response data, the 10-year EFS from the time of local control was 76% for those with &lt; 10% viable tumor and 56% for those with ≥ 10% viable tumor (p = 0.01). Additional analysis comparing patients with any viable tumor vs. no viable tumor (NVT) by treatment regimen demonstrated that patients with NVT who received IC chemo had 10-year EFS and OS from local control of 91% and 97%, respectively. In the 210 patients for whom tumor volume calculations were possible, there was no difference in the 10-year EFS for patients with tumors &lt; 200 mL vs. ≥ 200 mL. Conclusions: With longer term follow-up, IC chemotherapy for localized ES is associated with superior EFS and OS without an increase in SMNs. This study suggests patients ≥ 18 years with poor necrosis or pelvic primary tumors remain at high risk for relapse despite IC chemo, emphasizing the need for alternative treatment strategies to improve their outcomes. Clinical trial information: NCT00006734.