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Introduction The present work is an observational study of a series of variables regarding overall survival and disease-free survival in patients diagnosed with primary liposarcoma. Methods The study is prospective with retrolective data collection that includes all patients with primary liposarcoma referred to Hospital Son Espases University Hospital, Palma de Mallorca, Spain from January 1990 to December 2019. Results The study includes 50 patients and the compartment surgery was performed in 18 patients (36%) of cases. The mean overall survival of the sample was 15.57 years (95% CI: 12.02–19.12) and the mean disease-free survival was 6.70 years (95% CI: 4.50–8.86). Conclusion Compartment surgery has not shown benefits in terms of overall survival and disease-free survival. The ASA classification (≥3) predicts a poor prognosis in both overall survival and disease-free survival. Resection with free margins, described on the pathological results and defined in this work as R0, show better disease-free survival.

Background The Spanish Melanoma Group (GEM) developed a national registry of patients with melanoma infected by SARS-CoV-2 ( GRAVID ).Methods The main objective was to describe the COVID-19 fatality rate in patients with melanoma throughout the pandemic, as well as to explore the effect of melanoma treatment and tumor stage on the risk of COVID-19 complications. These are the final data of the register, including cases from February 2020 to September 2021.Results One hundred-fifty cases were registered. Median age was 68 years (range 6-95), 61 (40%) patients were females, and 63 (42%) patients had stage IV. Thirty-nine (26%) were on treatment with immunotherapy, and 17 (11%) with BRAF-MEK inhibitors. COVID-19 was resolved in 119 cases, including 85 (57%) patients cured, 15 (10%) that died due to melanoma, and 20 (13%) that died due to COVID-19. Only age over 60 years, cardiovascular disorders, and diabetes mellitus increased the risk of death due to COVID-19, but not advanced melanoma stage nor melanoma systemic therapies. Three waves have been covered by the register: February-May 2020, August-November 2020, and December 2020-April 2021. The first wave had the highest number of registered cases and COVID-19 mortality.Conclusion Tumor stage or melanoma treatments are non-significant prognostic factors for COVID-19 mortality. During the pandemic in Spain there was a downward trend in the number of patients registered across the waves, as well as in the severity of the infection.

e21529 Background: Previous reports proved the feasibility of immunotherapy (IT) discontinuation in advanced melanoma (MEL) patients (pts) in case of CR. We aimed to investigate clinical characteristics of pts with sustained CR after elective discontinuation of the 1st line anti-PD1 monotherapy in the real world setting. Methods: This is a multicenter retrospective cohort study. Eligible pts ≥ 18 years with unresectable locally advanced or metastatic primary cutaneous (PC) or unknown primary (UP) MEL with at least one measurable lesion per RECIST version 1.1 at baseline, treated with nivolumab (NIVO) o pembrolizumab (PEMBRO) monotherapy with no previous IT were included. All pts achieved CR to the treatment confirmed by computed tomography (CT) or positron emission tomography (PET-CT) and had at least one imaging study in the follow-up (FU). IT discontinuation was at the discretion of the treating physician. Pts with CR who stopped IT due to toxicity grade (G) 3 and/or 4 were excluded. Information regarding baseline characteristics, survival and immune related adverse events (irAEs) was obtained from patients´ charts. Data cut-off was February 10th 2022. Results: 36 pts treated in 12 hospitals in Spain between October 8th 2015 and October 27th 2021 were identified. Mean age was 66.8 years and mean BMI was 27.4. Twenty eight (77.8%) pts were males and 35 (97.2%) had ECOG PS 0-1. PC melanoma was observed in 33 (91.7%) pts, UP in 3 (8.3%). 35 pts (97.2%) had metastatic disease, with 11 (30.6%) pts with ≥3 metastatic sites. There were 21 (58.4%) pts with stage M1a-M1b disease; only 3 (8.3%) had liver and 2 (5.6%) had brain metastases. Baseline LDH was within normal limits in 28 (77.8%) pts and 31 (86.1%) pts had baseline neutrophil to lymphocyte ratio ≤3. Treatment received: PEMBRO 21 (58.3%), NIVO 15 (41.7%) pts. CR to treatment was confirmed by PET-CT in 27 (75.0%) pts. Median duration of anti-PD1 IT was 23.5 months (range 1.3 - 50.5) and median time to CR was 12.0 months (range 2.2 - 50.2). With the median FU time off treatment of 24.1 months (95% CI 19.4 – 28.8), median progression free survival (PFS) after IT discontinuation has not been reached: estimated PFS at 1 and 2 years were 94.1% and 89.2%, respectively. Estimated overall survival from start of IT at 3 and 4 years were 97.2% and 93.5%, respectively. irAEs G 1-2 were observed in 30 (83.3%) pts and the most common were: vitiligo 8 (22.2%), pruritis 4 (11.1%), other skin toxicity 8 (22.2%), hypothyroidism 5 (13.9%), pneumonitis 3 (8.3%), colitis 5 (13.9%), hepatitis 3 (8.3%), arthralgia 5 (13.9%) and nephritis 3 (8.3%). Conclusions: Our study confirms sustained CR after elective 1st line anti-PD1 monotherapy discontinuation in a cohort of advanced PC and UP MEL pts with favorable established prognostic factors for MEL at baseline. Frequency of irAEs was concordant with previous reports on IT.

Background: Covid-19 pandemic by the new coronavirus SARS-Cov-2 has produced devastating effects on the health care system, affecting also cancer patient care. Data about COVID-19 infection in cancer patients are scarce, and they point out a higher risk of complications due to the viral infection in this population. Moreover, cancer treatments could increase viral complications, specially those treatments based on the use of immunotherapy with checkpoints antibodies. There are no clinical data about the safety of immune check point antibodies in cancer patients when they become infected by SARS-CoV-2. As checkpoint inhibitors, mainly anti PD-1 and anti CTLA-4 antibodies, are an effective treatment for most melanoma patients, avoiding their use during the pandemic could lead to a decrease in the chances of curing melanoma. Methods: In Spain we have started a national registry of melanoma patients infected by SARS-Cov-2 since April 1st, 2020. A retrospective analysis of patients included in the Spanish registery has been performed weekly since the activation of the study. Interim analysis shows unexpected findings about cancer treatment safety in SARS-Cov-2 infected melanoma patients, so a rapid communication to the scientific community is mandatory Results: Fifty patients have been included as of May 17th, 2020. Median age is 69 years (range 6 to 94 years), 27 (54%) patients are males and 36 (70%) patients have stage IV melanoma. Twenty-two (44%) patients were on active anticancer treatment with anti PD-1 antibodies, 16 (32%) patients were on treatment with BRAF plus MEK inhibitors and 12 (24%) patients were not on active cancer treatment. COVID-19 episode has been resolved in 43 cases, including 30 (70%) patients cured, four (9%) patients that have died due to melanoma progression, and nine (21%) patients that have died from COVID-19. Mortality rates from COVID-19 according to melanoma treatment type were 16%, 15% and 36% for patients on immunotherapy, targeted drugs, and for those that were not undergoing active cancer treatment, respectively. Conclusion: These preliminary findings show that the risk of death in those patients undergoing treatment with anti PD-1 antibodies does not exceed the global risk of death in this population. These results could be relevant in order to select melanoma therapy during the COVID-19 pandemic

A broad spectrum of diseases can be included in the differential diagnosis of neck masses. We report a case of extraosseous Ewing sarcoma that presented as a neck mass in a 70-year-old man. To the best of our knowledge, this is the first reported case of extraosseous Ewing sarcoma of the supraclavicular fossa. Published cases of extraosseous Ewing sarcoma in the neck have been described in other age groups, but those tumors were confined to the parapharyngeal space. Also, there have been reported cases in patients older than 70 years in which Ewing sarcoma affected other structures such as the larynx and the pelvis, but none in the soft tissues of the neck. This case adds extraosseous Ewing sarcoma as a possible diagnosis to consider when evaluating a neck mass in the supraclavicular fossa.

Background: The COVID-19 pandemic has produced devastating effects on the health care system, also affecting cancer patient care. When the pandemic reached Spain by the end of February 2020, the scarce data about COVID-19 infection in cancer patients pointed out a higher risk of complications due to cancer diagnosis and also to cancer therapies. These conjectures led to concerns about hospital follow-up and cancer therapies of cancer patients. More recent studies have included a higher number of patients, but heterogeneous according to cancer type and tumor stage, with few melanoma patients recorded. Given that different tumor types are associated with specific comorbidities that have a known impact on COVID-19 evolution, analysis of COVID-19 by cancer types is mandatory. Similarly, analysis by tumor stage is relevant, as advanced cases could have different responses to viral infection due to tumor-related immunosuppression and general condition deterioration. Methods: In Spain we have completed a national registry of melanoma patients infected by SARS-Cov-2 since April 1st, 2020 to June 8th, 2020. Patients with a previous diagnosis of melanoma, presenting with Sars-Cov-2 infection to our network of hospitals, were eligible for enrollment. A prospective observational study with a case registry followed by a retrospective analysis of patient data has been performed. Results: 64 patients have been included. Median age is 68 years (range 6 to 95 years), 22 (34%) patients are females, and 35 (55%) patients have stage IV melanoma. Twenty-one (33%) patients were on active anticancer treatment with anti PD-1 antibodies, 19 (30%) patients with BRAF plus MEK inhibitors, and 24 (37%) patients were not on active treatment. Asymptomatic/paucisymptomatic evolution was recorded in 19 (30%) patients and mild severity in 13 (20%) patients, not requiring hospital admission by COVID-19. Serious and life-threatening complications were recorded in 18 (28%) and 14 (22%) patients, respectively, including 28 (44%) patients who required oxygen therapy and 3 (5%) patients who had ICU admission. COVID-19 episode is resolved in 55 cases, including 34 (53%) patients cured, eight (12%) patients who have died due to melanoma progression, and 13 (20%) patients due to COVID-19. The median age of patients who died from COVID-19 was 74 years (range 49 to 91), while for those cured it was 64 years (range 6 to 95); 85% of patients who died were males, while this rate decreased to 62% for those cured. The mortality rate from COVID-19 was 20% for both stage IV and localized melanoma, while according to melanoma treatment it was 21%, 16%, and 21% for immunotherapy, BRAF plus MEK inhibitors, and for those who were not undergoing active cancer treatment, respectively. Conclusion: Our results show that the risk of death in melanoma patients is higher in males and older patients, and it is similar according to tumor stage and melanoma therapy. The impact of cancer diagnosis and treatments on COVID-19 evolution is lower than previously expected. Citation Format: Maria Gonzalez-Cao, Cristina Carrera, Juan Francisco Rodriguez Moreno, Pedro Rodriguez-Jiménez, Mónica Antoñanzas Basa, Marta Feito Rodríguez, Teresa Puertolas, Eva Muñoz, José Luis Manzano, Ivan Marquez-Rodas, Juan Martín-Liberal, Ainara Soria, Pilar Lopez Criado, Almudena García Castaño, Aram Boada, Pablo Ayala de Miguel, Susana Puig, Guillermo Crespo, Pablo Luna Fra, Cristina Aguayo Zamora, Jesús Gardeazabal, Cayetana Maldonado Seral, Ana Drozdowskyj, Mariano Provencio, Alfonso Berrocal. COVID-19 in melanoma patients: Spanish register [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-059.

11514 Background: Myxoid liposarcoma (ML) exhibits especial sensitivity to trabectedin (T). In prospective series, T showed responses in 44% of patients (pts) with ML. ML is also sensitive to radiation therapy (RT) and preclinical data suggested radiosensitizing properties of T. Preoperative short-course of T with concurrent low-dose RT was conducted in a multicenter, European, phase I/II trial. We present here the data from the phase II part in pts with centralized diagnosis of locally advanced, resectable ML. Methods: Pts received 3 cycles (C) of T in combination with RT (45 Gy) in 25 fractions (1.8Gy/fraction). The phase I part of the study had the classic 3+3 design. Dose Levels for T were: -1 (1.1 mg/m2), 1 (1.3 mg/m2) and 2 (1.5 mg/m2) Results were already reported (EClincalMedicine 2019;9:35-43) and the dose selected for the phase 2 part was 1.5 mg/m2. RECIST responses were evaluated preoperatively at week 10. Surgical specimens were processed for histologic changes and residual tumor. Results: From July 2016 to September 2019, 47 pts (M/F 31/16) with median age 43y (18-77) and median tumor size 11 cm (3-25 cm), 20 low and 24 high grade (3 not available) were enrolled in the phase II part of the study. The major grade 3/4 toxicities were neutropenia (21.3%), ALT (14.9%), GGT (8.5%) and AST (8.5%) elevation. There were no deaths due to toxicity. 43/47 patients received the planned 3 pre-operative T cycles. All pts completed RT. 1 patient started RT before the first cycle of T and was excluded from the analysis. All pts were evaluable for response: 14 achieved PR (30%), 32 SD (70%). All pts underwent surgery (37 [86%] R0/ 5 [12%] R1/ 1 [2%] R2/ 3 not available). Median viable residual tumor was 10% (0-90) with 23/43 pts (53%) with ≤ 10% viable remaining tumor. Of them 6/43 (14%) had complete responses. At a median FU of 18 months (3-41) one pt developed local recurrence and 2 distant metastases. No deaths were observed. The corresponding 2-yr disease-free survival and overall survival were 97% (95% confidence interval 95-100) and 100%. Conclusions: T in combination with RT was feasible and well tolerated in the preoperative setting. The activity of the combination compares favorably with the administration of T/RT alone. This regimen could potentially become an alternative to anthracycline+ifosfamide concurrent to RT in high risk localized ML. Clinical trial information: NCT02275286 .

11067 Background: GEIS 30 was a phase II study showing moderate activity of pazopanib in well-differentiated/dedifferentiated LPS (cohort A:37 pts, Progression free Survival (PFS) at 12 weeks (w) 43.2%) and no activity in Myxoid/round cell LPS (cohort B: 15 pts, PFS at 12w 13.3%). The present study aims to identify tumor and plasma biomarkers that are differently expressed in long responders (LRs) PFS > 24 w. Methods: Serum samples and paraffin-blocks at diagnosis were collected for 28 pts in cohort A and 11 in B. A total of 13 pts were LRs. Serum samples were obtained at baseline, after 3 w of treatment and at progression. A panel of 15 cytokines and growth factors were evaluated using Luminex technology (Millipore). Paraffin-blocks were evaluated for microvessel density (MVD) by CD31 immunostaining and Image Pro-Plus 7.0 Image Analysis System (Media-Cybernetics). For RNA expression analysis, the Oncology Biomarker Panel with probes for 2559 transcripts was used (HTG Molecular Diagnostics). Results: Serum cytokines showed that expression of angiopoietin (AGO) and BMP9 decreases during treatment, whereas GCSF increases. In addition, AGO and BMP overexpression at baseline was associated with worse prognosis in arm A (p = 0.09) and B (p = 0.01) respectively. No differences between study arms and outcome were appreciated by MVD. Gene expression revealed differences in some immunomodulators: PDL-1 was correlated with serum cytokines VEGFD (p = 0.04) and LEPTIN (p = 0.02); and PD-1 with VEGFD (p = 0.04), LEPTIN (p = 0.02), VEGFA (p = 0.02) and ANGIO (p = 0.03). PD1, in addition,was overexpressed in LRs (p = 0.05). Interestingly, three groups were identified in cohort A according to gene expression: Cluster 1, characterized by short-responder patients with the shortest overall survival, whereas cluster 3 (40% LRs) and 2 (63.6% LRs) showed longer survival rates (14.3%, 45.5% and 30% respectively) (p = 0.001). Conclusions: Gene expression profiling unveils three WD/DD-LPS biotypes according to their response to pazopanib, which could be potentially used to select pts for treatment

11544Background: Patients (pts) with advanced STS who require tumor shrinkage beyond first line, have very limited options since the approved drugs exhibit less than 10% of RECIST response. Trabect...

9533 Background: Uveal melanoma is the most common primary intraocular malignant tumor in adults. Overall Survival (OS) at 5 years(y) is 62% due high incidence of liver metastasis, fatal within 4-9 months(m) from diagnosis. No standard treatment exists for MUM. NIVO+IPI combination has shown efficacy in metastatic cutaneous melanoma. However, MUM pts were excluded in these trials. Methods: GEM1402 is a phase-2 trial evaluating NIVO+IPI in untreated adult pts with MUM; is being conducted in 10 centers in Spain, leading by the Spanish Melanoma Group. Eligible pts had histologically-confirmed MUM, ECOG-PS 0/1, and no prior systemic treatment for MUM. Treatment consisted in NIVO (1mg/kg, iv, q3 weeks [wk]) and 4 doses of IPI (3mg/kg iv q3wk) followed by NIVO (3mg/kg q2wk) until progressive disease (PD), toxicity or withdrawal. Primary endpoint is OS and secondary progression free survival (PFS), Overall Response Rate (ORR) (per RECIST 1.1) and safety. Radiologic evaluations q6wk. Interim analysis (n = 19) was planned per protocol to assess safety and ORR. Intention to treat analysis includes pts with PD at first radiological evaluation. Safety population includes all pts receiving at least one dose of study treatment. Results:19 pts enrolled from April to July 2016: Median age 62y (43y-82y), 63% male, liver M1 84% pts and extra-liver M1 42% pts, 31% elevated baseline LDH. 11 pts completed cycle 2 and 8 pts stopped after 1 dose (6 PD, 2 toxicity). Treatment-related adverse events were reported in 12 pts and lead to end of treatment in 2 pts. Grade ≥3 toxicities were seen in 7 pts (36.8%): diarrhea, transaminitis, dermatological events, anemia, acute thyroiditis. All G3/4 were resolved following the toxicity guideline. One G5 acute thyroiditis related to NIVO+IPI was reported. ORR was observed in 15.8% and disease stabilization in 47.4%. With a median follow-up of 4.6m, PFS was 4.99m. Median OS was not reached at time of this analysis. Conclusions: Combination of NIVO+IPI is feasible for MUM. In this INTERIM ANALYSIS, ORR did not reach yet 20%, but PFS seems promising. The clinical trial is ongoing. Final results will be updated. Clinical trial information: 2015-004429-15.

11039Background: Pazopanib, a multitarget TKI, has been approved as second or later line treatment for advanced non-adipocytic soft-tissue sarcoma. This open-label, phase II clinical trial was desi...

10079 Background: Genes involved in cell cycle checkpoints and chromosome stability seem to be relevant in distant metastases appearance in STS. CUL4A is an E3 ubiquitin ligase that has been related to both p16 activation and maintenance of genomic stability. Expression of CUL4A has been scarcely described in some tumors with divergent outcome and there are no publications regarding its expression in STS patients. We previously showed that protein underexpression of CUL4A in metastatic STS was related to poor survival. Methods: The expression level of CUL4A was determined by quantitative qPCR and was retrospectively performed in a subset of 39 high-risk (grade 3, deep tumours and > than 5 cm) localized STS of limbs or trunk wall patients for which histological material and clinical data were available. Patients of this series were enrolled prospectively into a randomized clinical trial conducted by the Italian and Spanish sarcoma groups (ISG-GEIS 0101) comparing 3 vs 5 cycles of epirrubicin and ifosfamide. Differences in PFS, RFS, and OS were calculated using log-rank test Results: The median age was 51 years with a median follow-up of 52 months. The pathologic subtypes were undifferentiated pleomorphic sarcoma (35.3%), synovial sarcoma (23.5%) and mixed subtypes (41.2%). Location was distributed as inferior limbs (66.6%), upper limbs (25.5%) and trunk wall (7.9%). No relationship was seen between CUL4A expression and clinical variables (histologic types, location, size or response to neoadjuvant treatment). The expression level of CUL4A was significantly associated with events of progression, 65% vs 32%, p =0.037, for expression values under and over the median respectively. Regarding 4 y actuarial survival, there was a significant worse PFS and RFS for patients underexpressing CUL4A (p=0.041 and 0.009 respectively) and a trend towards worse OS (p=0.056). Conclusions: Expression of CUL4A gene shows a prognostic role in sarcomas within this high risk localized subset of STS patients. The outcome of this exploratory analysis is aligned with our hypothesis that genes implicated in cell cycle regulation and chromosome stability could play a relevant prognostic role in STS.

10530 Background: There are few reports focusing on systemic treatment in osteosarcoma (OS) patients progressing after most active drugs. Preclinical data showed activity of rapamycin in xenograft ...

11038 Background: SFT is a ubiquitous uncommon soft tissue sarcoma with a pronounced hemangiopericytoma-like vascular pattern, exhibiting rich VEGF (tumor and endothelial cells) and VEGFR1/2 (endothelial cells) expression. Pathologists distinguish typical SFT (T-SFT) and malignant SFT (M-SFT) based on mitosis (≤4 vs > 4), pleomorphism or necrosis. Yet, not clear boundaries are always seen between both subtypes. We have recently published a phase II trial exploring the activity of pazopanib (P) in M-SFT (Lancet Oncol Dec 2018). Here, we present the outcome of the T-SFT cohort of the same trial. Methods: Most relevant inclusion criteria were: unresectable or metastatic, T-SFT (tumor tissue from diagnostic time) confirmed by central pathology review before accrual, with evidence of STAT6 overexpression (IHC and FISH and/or NGS), ≥18 years, ECOG 0-2, progressive, measurable disease and no previous antiangiogenic agents. Main endpoint was response rate according to Choi criteria. Central radiological assessment was mandatory. P was administered at 800 mg/d continuously till progression or toxicity. Results: From June 2014 to December 2018, 34 patients were enrolled in this cohort. The median age was 64 y (31-81). At baseline, ECOG 0/1/2 was distributed as 16/15/3; whereas, locally advanced/metastatic distribution was 11 (32%) and 23 (68%) respectively. At the time of the present analysis, 24 patients were deemed eligible and evaluable for response. Response rates according to local and central assessment were PR 6 (25%), SD 15 (62%), PD 3 (12%) and PR 12 (50%), SD 11 (46%), PD 1 (4%). With a median follow-up of 21 months, the median PFS following local and central assessment were 18.4 (6.6-30.1) and 9.8 (7.5-12.2) months respectively, both were clearly superior to that previously published in M-SFT cohort (5.57 m). The median of OS was 49.8 months. High tumor burden at baseline > 116 mm, ECOG 1-2 vs 0, and PD by local or central response assessment showed significantly worse OS. Metastatic vs locally advanced patients had a similar outcome regarding OS. Conclusions: T-SFT cohort exhibited clearly longer PFS than previous reported M-SFT cohort to pazopanib treatment, and pazopanib showed to improve the historical outcome obtained with chemotherapy in advanced SFT. Clinical trial information: NCT02066285.