Recurrent Sarcoma Research Articles

Обширная резекция грудной стенки с аллопластикой полимерным материалом Codubix по поводу рецидивной саркомы

A 77-year-old patient was operated on for local recurrence of pleomorphic sarcoma of the left half of the chest wall with the involvement of three ribs in the tumor process. Successful extensive resection of the chest wall with Codubix plastic material made it possible to preserve the skeleton. Periodic accumulation of uninfected exudate can be considered as reactive plervritis, which required periodic evacuation of the contents of the left pleural cavity.

Mixed Endometrioid Adenocarcinoma and Müllerian Adenosarcoma of the Uterus and Ovary: Clinicopathologic Characterization With Emphasis on its Distinction From Carcinosarcoma.

Mullerian adenosarcoma is a biphasic neoplasm composed of benign or atypical Müllerian epithelium and a malignant mesenchymal component that is usually, but not always, of low grade. Focal architectural or cytologic atypia of the epithelial component resembling atypical hyperplasia may uncommonly be present and foci of adenocarcinoma have been rarely reported. Whether the coexistence of these 2 tumor components is a result of independent primaries (collision tumor), adenocarcinoma arising from the epithelial component of the adenosarcoma, an unusual form of carcinosarcoma or some other mechanism is uncertain. To establish the diagnostic criteria and clinical significance of the coexistence of adenocarcinoma in close association with Müllerian adenosarcoma, we conducted a multi-institutional study of these rare tumors. Twenty-six patients were identified with "mixed" adenosarcoma and adenocarcinoma; they ranged in age from 43 to 87 years (median: 66 y). Tumors occurred in the uterine corpus (n=22), ovary (n=2), and the pelvis (n=2). All but 6 had International Federation of Gynecology and Obstetrics (FIGO) stage I disease. All extrauterine tumors were associated with endometriosis. The tumor size ranged from 2 to 25 cm (median: 7.9 cm). The sarcomatous component was of low grade in 18 and high grade in 8 (the majority demonstrating rhabdomyoblastic differentiation); 9 had stromal overgrowth. Twenty-five carcinomas were endometrioid in type (23 FIGO grade 1; 3 FIGO grade 2) and 1 carcinoma was dedifferentiated with FIGO grade 1 endometrioid adenocarcinoma component; 33% of the uterine neoplasms were associated with adjacent endometrial hyperplasia. Next-generation sequencing in 2 tumors identified similar molecular abnormalities in the sarcomatous and carcinomatous components supporting a clonal relationship. Of 10 patients with available follow-up (median: 18 mo), 8 had no evidence of disease and 2 died of recurrent sarcoma at 7 and 8 months. Endometrioid adenocarcinomas that arise in close spatial association with Müllerian adenosarcoma appear to be clonally related to the sarcoma. Unlike carcinosarcomas, these tumors are usually early stage at presentation. The prognosis appears to be driven by the sarcomatous component. These tumors should be distinguished from carcinosarcomas, dedifferentiated endometrial carcinomas, and corded and hyalinized endometrioid carcinomas.

Iatrogenic recurrence of Kaposi sarcoma induced by the pharmacological interaction between periarticular injection of corticosteroids and ritonavir in a HIV ‐infected patient

Iatrogenic recurrence of Kaposi sarcoma induced by the pharmacological interaction between periarticular injection of corticosteroids and ritonavir in a <scp>HIV</scp> ‐infected patient

Histiocytic lymphadenopathy secondary to metallosis following endoprosthetic replacement in osteosarcoma patient – a potential diagnostic pitfall

We present the case of a 43-year old patient with inguinal lymphadenopathy 22 years after distal femoral resection for osteosarcoma with cemented distal femoral replacement reconstruction. Seven years after initial distal femoral resection patient underwent metal on metal hip resurfacing arthroplasty on the affected side. Twenty years after distal femoral replacement and 13 years after metal on metal hip resurfacing procedure, the patient underwent left inguinal lymph­adenectomy for an enlarged mass of inguinal lymph nodes on suspicion for a sarcoma recurrence. On microscopic ex­amination, excised lymph nodes were massively infiltrated with macrophages and multinucleated giant cells with focal asteroid bodies. An examination in polarized light revealed numerous metal particles; immunohistochemical stainings confirmed reactive character of changes, and florid metal-related sinus histiocytosis was finally diagnosed. Microscopic assessment of lymph nodes in the course of malignancy is a standard procedure; we present a rare case of non-neoplastic lymph node enlargement due to the late onset of metallosis, which might be a diagnostic challenge.

Efficacy of hyperthermic isolated limb perfusion in the treatment of locally recurrent high-grade soft tissue sarcoma of the extremities

BackgroundThis novel study compared the use of tumor necrosis factor (TNF)-alpha and melphalan-based isolated limb perfusion (TM-ILP) to the standard treatment of locally recurrent soft tissue extremity sarcoma. The aim was to assess whether TM-ILP positively influences the recurrence-free survival of locally recurrent high-grade soft tissue sarcoma (STS) of the extremities.MethodsWe retrospectively analyzed our clinical database for patients with STS. Variables were analyzed using chi-square test or Mann-Whitney rank-sum test. Furthermore, Kaplan-Meier survival plots were calculated and a proportional hazard regression model was developed.ResultsOut of 448 patients with extraabdominal STS treated between August 2012 and December 2015, 52 cases involving 47 patients had locally recurrent STS. Twenty-eight of these patients were treated with TM-ILP prior to surgical resection (TM-ILP-group), and 24 were treated with standard therapy (without TM-ILP). The 3-year recurrence-free survival for the TM-ILP-group was estimated at 75% (95% confidence interval (CI), 71.5–78.5). Local recurrence-free survival in the standard group was significantly lower (LRFS: 43.4%, 95% CI 38.7–48.1, p = 0.026). Multivariable analysis revealed resection with negative margins, lower number of previous recurrences, and TM-ILP as positive predictors for recurrence-free survival.ConclusionsTM-ILP and consecutive resection of residual tumor with negative resection margins significantly improves local recurrence-free survival for patients with a first local recurrence of high-grade STS in the extremities.

Abstract PO-041: Genome-wide CRISPR/Cas9 screen reveals mitochondrial gene mutation as a driver for drug resistance in Ewing sarcoma

Abstract Ewing sarcoma is a pediatric bone cancer caused by a chromosomal translocation event that generates the pathognomonic fusion protein, EWS/FLI, which acts as aberrant transcription factor. EWS/FLI is responsible for activating and repressing important genes to drive oncogenic transformation and tumorigenesis. EWS/FLI is notoriously difficult to target with small molecule inhibitors based on its lack of enzymatic activity and intrinsically disordered EWS domain, thus rational drug design is presently unfeasible. Other potential therapeutic targets are interacting partners of EWS/FLI, including epigenetic modulators, such as lysine specific demethylase-1 (LSD1). Inhibition of LSD1 by a reversible, non-competitive inhibitor, SP-2509, has been shown to cause extensive changes to gene expression and induce apoptosis in Ewing sarcoma cells. A Phase I clinical trial (NCT03600649) is currently ongoing to study the effect an SP-2509 analog, Seclidemstat (SP-2577), on patients with recurrent or refractory Ewing sarcoma tumors. Thus, understanding potential drug resistance mechanisms is vital to ensure maximal efficacy of Seclidemstat treatment for patients in the present, and in future clinical trials with this targeted therapeutic drug. Preliminary investigation using a genome-wide CRISPR/Cas9 knock-out (GeCKo) screen has revealed that the loss of genes important to mitochondrial function, specifically in the electron transport chain (ETC), play a distinct role in SP-2509 drug-resistance in Ewing sarcoma cells. We validated the GeCKo screen using cell viability assays in an Ewing sarcoma cell line (A673) via knockout (KO) of mitochondrial genes that were identified by the GeCKo screen. Consistent with the screen, we found select mitochondrial genes led to an increase in IC50 values (i.e. drug-resistance) to SP-2509, compared to WT A673 cells. We found that drug resistance could be enhanced even greater by generating monoclonal cell populations containing complete mitochondrial gene KO. We performed RNA-sequencing and metabolomics analyses to examine SP-2509 response differences between WT and our generated drug resistance cell lines. We similarly determined that treating A673 cells with mitochondrial ETC inhibitors recapitulated drug resistance. Currently, the mechanism that links mitochondrial dysfunction in Ewing sarcoma cells and resistance to the epigenetic drug SP-2509 is incompletely understood. However, our ongoing studies aim to uncover this link and ultimately provide consequential information that will help patients overcome Ewing sarcoma. Citation Format: Jack P. Tokarsky, Jesse Crow, Lillian Guenther, Emily Theisen, Kimberly Stegmaier, Stephen Lessnick. Genome-wide CRISPR/Cas9 screen reveals mitochondrial gene mutation as a driver for drug resistance in Ewing sarcoma [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-041.

Advances in the Management of Pediatric Sarcomas.

The prognosis of pediatric patients who present with metastatic or recurrent sarcomas remains poor. In this review, we summarize the advances in the management of metastatic and relapsed pediatric sarcoma by highlighting recent and future clinical trials. Research into the identification of novel therapies for refractory pediatric sarcomas continues to advance. Outcomes have not improved in several decades underlying a need for improved understanding of the biology behind these tumors and the identification of novel therapeutic molecular targets that can be exploited pharmacologically. Multiple challenges remain for novel therapy in sarcomas such as the selection of effective targets, management of toxicities, and the tumor microenvironment. Many unique challenges remain in the treatment of patients with refractory pediatric sarcomas. Multiple strategies and targets are under investigation that hold promise.

Efficacy of palliative SBRT in local control of sarcoma

For patients presenting with recurrent, inoperable, or metastatic sarcoma, treatment options are limited. The inherent low radiosensitivity of many sarcoma histologies can limit effectiveness of palliative radiation for these patients. Stereotactic radiation (SBRT) allows escalation of biologically effective dose while limiting dose to normal tissues, which is particularly important in previously irradiated tissues. In this retrospective cohort study, we examine the efficacy of SBRT in the palliation of sarcoma. A retrospective cohort study was performed of patients treated at a single large tertiary academic medical center with SBRT for management of sarcoma from 2011 through 2016. Details regarding patient demographics, treatment context, tumor histology, treatment parameters, and disease outcomes were recorded. Descriptive statistics and Cox analysis of factors associated with improved local control were examined. Results were available on 22 tumors treated with SBRT in 14 patients. Median follow-up was 6.7 months. Median tumor size was 4.8 cm, with a median total dose and dose per fraction of 27.5 Gy and 6 Gy/fraction, respectively. There were 6 recurrences, with a 1-year local control of 62%. Seventy-nine percent of symptomatic lesions had improvement in their pain. On univariate Cox-analysis, total dose, performance status, and BMI were found to be significantly associated with local control, and dose per fraction was significantly associated with local failure. One-year overall survival was 37%. Our institutional experience provides encouraging evidence of the feasibility of SBRT in the palliation of sarcoma. Poor overall survival is a substantial competing risk in these patients. Further studies will be required to identify the ideal dose and fractionation across histological subtypes. Prospective clinical trials may be warranted.

Intraoperative Localization Using an Implanted Radar Reflector Facilitates Resection of Non-Palpable Trunk and Extremity Sarcoma.

Resecting non-palpable soft tissue tumors presents a unique challenge, particularly with recurrent disease in which surrounding tissue has been surgically manipulated and often irradiated. SAVI SCOUT® is a radar-based localization device that was developed for breast tumor localization and was recently FDA-approved for localization of soft tissue tumors. Application of this technology to soft tissue sarcoma has not been previously reported. We assembled a single-institution retrospective case series of patients with trunk and extremity sarcomas resected by five sarcoma surgeons using SAVI SCOUT® from December 2018 to May 2020. Reflectors were placed preoperatively using image-guidance, and the radar detector was used intraoperatively to localize the target lesion. Clinical variables were abstracted from the electronic medical record including treatment history, pathology, and early oncologic outcomes. Using a focused review, we compared margin status and recurrence rates with previously published cohorts. Ten SAVI SCOUT®-localized sarcoma resections were performed. Eight were for locally recurrent disease, of which seven (83%) had prior radiation. The remaining lesions became non-palpable after neoadjuvant chemotherapy. SAVI SCOUT® facilitated resection in all cases with a margin-negative resection rate (77%) comparable to prior cohorts. In this high-risk population with a median follow-up of 14months, only one patient recurred locally 7.5months after SAVI SCOUT®-localized resection, requiring re-resection. SAVI SCOUT® technology facilitated resection of non-palpable recurrent sarcoma of the trunk and extremities in all ten cases attempted. In a high-risk patient population, the pattern of recurrence has been primarily distant with one instance of local tumor recurrence.

Does ovarian preservation have an effect on recurrence of early stage low-grade endometrial stromal sarcoma?

Surgical treatment of low-grade endometrial stromal sarcoma consists of hysterectomy. The role of oophorectomy is yet to be established. We aimed to examine the effect of preserving the ovaries on the pattern of recurrences in patients with stage I disease. Thirty-four patients with stage I low-grade endometrial stromal sarcoma were retrospectively analysed. Based on ovarian preservation the whole cohort was divided into two groups. Recurrence (liver, lung, groin and bone) was detected in 4 (11.8%) cases. No significant differences in overall survival or disease-free survival (DFS) were observed between the ovarian preservation and bilateral salpingo-oophorectomy (BSO) groups. Subset analysis revealed no significant difference in DFS between the ovarian preservation and BSO groups in the premenopausal arm. And also, the performance of pelvic (n = 2) or para-aortic lymphadenectomy (n = 6) or adjuvant hormonal therapy did not alter DFS significantly. The 5-year DFS rate for the group which received adjuvant radiotherapy was 62.5 and 94.4% for those which did not (p = .014). Preserving the ovaries had no adverse effect on the recurrence of stage I disease. IMPACT STATEMENT What is already known on this subject? Due to the rarity of the disease and the common postoperative diagnosis, only retrospective studies have been reported on low-grade endometrial stromal sarcoma. This disease is commonly diagnosed in premenopausal patients during the early stage. There is no consensus on preserving the ovaries, particularly in young patients, due to the tumour’s hormonal characteristics and the risk of late recurrences. What do the results of this study add? Ovarian preservation had no effect on the recurrence of stage I low-grade endometrial stromal sarcoma. Lymphadenectomy and adjuvant hormonal treatment had no effect on DFS, and adjuvant radiotherapy decreased DFS in the current study. What are the implications of these findings for clinical practice and/or further research? Ovarian preservation should be considered, to prevent the negative effects of surgical menopause, particularly in young patients.

The value of re-staging chest CT at first local recurrence of extremity and trunk soft tissue sarcoma

To determine the prevalence of pulmonary metastases on re-staging chest CT at the time of first local recurrence (LR) of trunk or extremity soft tissue sarcoma (STS). Retrospective review of all patients diagnosed with recurrent STS between May 2007 and April 2018. Data collected included patient age and sex, site of primary STS, time to LR, recurrence site, initial tumour grade, recurrent tumour grade, findings of initial staging chest CT, and prevalence of pulmonary metastases on re-staging chest CT. The study included 109 patients (males = 68, females = 41; mean age 56years, range 9-92years). The commonest tumour sub-types were myxofibrosarcoma (27.5%), undifferentiated pleomorphic/spindle cell sarcoma (20.2%), synovial sarcoma (10.1%), and malignant peripheral nerve sheath tumour (10.1%). Initial staging chest CT demonstrated pulmonary metastases in 1 of 77 (1.3%) patients for whom CT was available for review. The mean time to LR was 30.8months (range 3-224months). Pulmonary metastases were diagnosed on re-staging chest CT in 26 of 109 cases (23.9%), being commonest with grade 3 STS (36.1%). Pleomorphic sarcoma (85.7%) and undifferentiated spindle cell sarcoma (33.3%) were the 2 commonest tumour sub-types associated with pulmonary metastases at first LR. Re-staging chest CT at the time of first LR of STS identified a prevalence of 23.9% pulmonary metastases, which supports the need for chest CT at the time of LR in line with the UK guidelines for the management of bone and soft tissue sarcoma. • Pulmonary metastases were diagnosed in 1.3% of soft tissue sarcomas at presentation. • Pulmonary metastases were identified in ~ 24% of patients at first local recurrence of soft tissue sarcoma, most commonly with pleomorphic sarcoma and Trojani grade tumours. • No patient with a low-grade recurrence had pulmonary metastases.

A novel mutation of the MEN1 gene in a patient with multiple endocrine neoplasia type 1 and recurrent fibromyxoid sarcoma \u2013 a case report

BackgroundMultiple endocrine neoplasia type 1 (MEN1) syndrome is usually accompanied by endocrine tumors, but non-endocrine tumors can occur as well. However, the coexistence of MEN1 syndrome and malignant tumor such as low-grade fibromyxoid sarcoma has not been described in the literature. Moreover, the MEN1 gene mutations have not been identified in patients with fibromyxoid sarcoma, so far.Case presentationWe present a patient with a long-year endocrine follow-up due to multiple endocrine tumors. During his lifespan, he has been surgically treated for pancreatic gastrinoma, parathyroid hyperplasia, atypical pulmonary carcinoid, various benign mesenchymal, and several skin tumors (basocellular tumor, lipomas, and fibromas) which raised a high clinical suspicion of MEN1 syndrome but the patient refused genetic testing. Recently, he developed a novel malignant tumor – recurrent low-grade fibromyxoid sarcoma of the trunk and extremities with multiple subsequent operations. The patient eventually accepted the genetic testing which proved him to be a carrier of a novel mutation in the MEN1 gene.ConclusionsUnlike some other syndromes where a genetic mutation can predict clinical course, there is no genotype-phenotype correlation in MEN1 syndrome. Therefore, these patients require lifelong and multidisciplinary surveillance, not only for typical endocrine and benign non-endocrine tumors but also for diverse and even more malignant forms. The atypical clinical presentation should pose suspicion about new gene mutation and serve as a warning in the further follow-up.

Does iatrogenic tumor rupture during surgery have prognostic implications for the outcome of uterine sarcomas?

ObjectiveTumor rupture during surgery is a risk factor for recurrence of sarcomas in other locations. However, the independent impact of rupture on prognosis is uncertain in uterine sarcomas. The aim...

The Effect of Resection Margin on Local Recurrence and Survival in High Grade Soft Tissue Sarcoma of the Extremities: How Far Is Far Enough?

Simple SummaryIn soft tissue sarcomas the width of surgical margins after resection determines the extent of surgery and the function after resection. But how far is really necessary? 305 patients with deep-seated, G2/3 soft tissue sarcomas of the extremity, the trunk wall, or the pelvis were reviewed. The 5-year local recurrence-free survival (LRFS) was 82%. Overall survival (OS) at 5 years was 66%. Positive (contaminated) margins worsened LRFS and OS. A margin of >10 mm did not improve LRFS and OS as compared to one of >5 mm. A resection margin of <1 mm showed a trend but not significantly better LRFS or OS compared to a contaminated margin. In conclusion the margin should at least be free of tumor, in sound tissue. A margin of >5 mm sound tissue seems to be sufficient. Resecting more tissue does not benefit the patient.Background: The significance of surgical margins after resection of soft tissue sarcomas in respect to local-recurrence-free survival and overall survival is evaluated. Methods: A total of 305 patients with deep-seated, G2/3 soft tissue sarcomas (STS) of the extremity, the trunk wall, or the pelvis were reviewed. The margin was defined according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) classification system (R0-2), the Union Internationale Contre le Cancer (UICC) classification (R + 1 mm) for which a margin <1 mm is included into the R1 group, and in groups of <1 mm, 1–5 mm, >5 mm, or >10 mm. Results: Of these patients, 31 (10.2%) had a contaminated margin, 64 (21%) a margin of <1 mm, 123 (40.3%) a margin of 1–5 mm, 47 (15.4%) a margin of >5 mm, and 40 (13.1%) a margin of >10 mm. The 5-year local recurrence-free survival (LRFS) was 81.6%. Overall survival (OS) at 5 years was 65.9%. Positive margins worsened LRFS and OS. A margin of >10 mm did not improve LRFS and OS as compared to one of >5 mm. Conclusions: A resection margin of <1 mm showed a trend but not significantly better LRFS or OS compared to a contaminated margin. This finding supports use of the UICC classification. A margin of more than 10 mm did not improve LRFS or OS.

1663P Local recurrence and 5-year survival control of primary localized sarcoma of the soft tissues of the extremities and body

1663P Local recurrence and 5-year survival control of primary localized sarcoma of the soft tissues of the extremities and body

Intraoperative ultrasonography-guided surgery for malignant soft tissue tumor.

A clear surgical margin is crucial for preventing the recurrence of soft tissue sarcomas (STSs). Recognizing the tumor border is difficult when the STS is impalpable or ill-defined. Ultrasonography (US) is a widely used diagnostic device that can visualize certain tumors intraoperatively. However, its usefulness for intraoperatively assessing STSs is unclear and was investigated here. Our study comprised 19 patients with STSs that were impalpable, ill-defined, or beneath the fascia. All patients underwent intraoperative US (IOUS), with follow-up times ranging from 5 to 103 months (mean, 49 months). The mean age of the study participants was 56 years (range, 25-83 months). The most common histological diagnosis was undifferentiated pleomorphic sarcoma (UPS) (nine patients). The mean tumor size was 51 mm (range, 7-126 mm). According to the residual tumor classification, 18 tumors were microscopically negative (R0), including seven close to the fascia, and one was microscopically positive (R1). Local recurrence occurred in two cases (both classified as R0). The recurrence-free survival rate was 88.9% in 5 years. IOUS-guided surgery is useful for visualizing STSs. Using this technique, STSs can be precisely localized, evaluated, and excised.

Patterns of recurrence and survival probability after second recurrence of retroperitoneal sarcoma: A study from TARPSWG.

In this series from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), the authors examined longitudinal outcomes of patients with a second recurrence of retroperitoneal sarcoma (RPS) after complete resection of a first local recurrence (LR). Data from patients undergoing resection of a first LR from January 2002 to December 2011were collected from 22 sarcoma centers. The primary outcome was overall survival (OS) after second recurrence. Second recurrences occurred in 400 of 567 patients (70.5%) after an R0/R1 resection of a first locally recurrent RPS. Patterns of disease recurrence were LR in 323 patients (80.75%), distant metastases (DM) in 55 patients (13.75%), and both LR and DM in 22 patients (5.5%). The main subtype among the LR group was liposarcoma (77%), whereas DM mainly were leiomyosarcomas (43.6%). In patients with a second LR only, a total of 200 patients underwent re-resection (61.9%). The 5-year OS rate varied significantly based on the pattern of failure (P<.001): 45.6% for the LR group, 25.5% for the DM group, and 0% for the group with LR and DM. The only factors found to be associated with improved OS on multivariable analysis were both time between second surgery and the development of the second recurrence (32 months vs 8 months: hazard ratio, 0.44 [P<.001]) and surgery for second recurrence (yes vs no: hazard ratio, 3.25 [P<.001]). The 5-year OS rate for patients undergoing surgery for a second LR was 59% versus 18% in the patients not deemed suitable for surgical resection. Survival rates after second recurrence of RPS varied based on patterns of disease recurrence and treatment. Durable disease-free survivors were identified after surgery for second LR in patients selected for this intervention.

Abstract 1984: Investigating circulating tumor DNA as a biomarker of cancer progression and recurrence in sarcoma

Abstract Objective: Circulating tumour DNA (ctDNA) is an active area of research in many types of cancer due to its value as a non-invasive diagnostic tool. Despite making up a small fraction of total cell-free DNA (cfDNA), detection of ctDNA has been made possible given advances in next generation sequencing and Digital Droplet PCR (ddPCR). CtDNA testing has some key advantages compared to tissue biopsy; ease of repetition provides a means of real-time monitoring of treatment response and signs of recurrence in cancer. This has specific relevance in sarcoma, where early detection of recurrence may provide an opportunity for faster intervention and can potentially lead to better prognostic outcomes. The purpose of this study is to determine if ctDNA is detectable in plasma samples collected from sarcoma patients and to validate our pre-analytical procedures and to identify opportunities to optimize our protocols for future use. Methods: 20 ml of blood samples were collected from 270 soft tissue sarcoma and osteosarcoma patients with or without pre-operative adjuvant treatment and processed to separate the plasma. Cf DNA was isolated from 2ml of plasma and the quantity and quality assessment was performed by qRT-PCR and capillary electrophoresis, respectively. Whole exome sequencing (WES) was performed on 6 matched tumor-blood DNA samples to identify tumour specific single nucleotide alterations. Sequence variants identified from WES analysis were used to design primers and probes to detect the tumor specific alterations in the corresponding ctDNA in those 6 cases using ddPCR. Results: Of the 60 patient samples analysed to date, the majority were positive for cfDNA. Quality assessment of 41cfDNA by capillary electrophoresis showed peaks approximately 170 bp in size, characteristic of cfDNA. WES of 6 patients' matched tumor-blood samples identified many tumor specific variants. Six of those sequence variants on SMAD4, COL19A1, DDX3X, ADGRG4, HECW1 and FOXR2 genes (Table 1) were used to design primers and probes to detect the tumour specific alterations in the corresponding ctDNA using dd PCR. We observed the presence tumour specific mutations in all corresponding ctDNAs tested in this study. Table 1:Identification of tumour specific variants by WESCaseGeneSNVSarcoma SubtypeVariant Allele Frequency1SMAD4T1584CMyxofibrosarcoma86%2COL19A1G1252AUndifferentiated pleomorphic sarcoma50%3DDX3XA1038COsteosarcoma54%4ADGRG4T6361CLiposarcoma65%5HECW1C1874AMyxofibrosarcoma25%6FOXR2C130GMyxofibrosarcoma24% Conclusions: Our ongoing study to evaluate the use of ctDNA as a biomarker in sarcoma monitoring shows promise related to the efficiency of our protocols and assays. Further testing is ongoing to assess the clinical value in sarcoma. Citation Format: Nalan Gokgoz, Paige Darville-O'Quinn, Ainaz Malekoltojari, Patrick Prochazka, Peter C. Ferguson, Jay S. Wunder, Irene L. Andrulis. Investigating circulating tumor DNA as a biomarker of cancer progression and recurrence in sarcoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1984.

Analysis of prognostic factors in soft tissue sarcoma: Cancer registry from a single tertiary hospital in Indonesia. A retrospective cohort study

BackgroundSoft tissue sarcoma is one cause of mortality in adult malignancies. This tumor is rare, persistent, and highly-recurrent. Many patients are came in late stage. It is important to identify a prognostic tool that is reliable, easily obtainable, and widely applicable. The aim of this study is to investigate and analyze the prognostic value of clinicopathological and biomarker factors in patients with soft tissue sarcoma. MethodsThis retrospective study extracts data from the musculoskeletal tumor registry from January 2012 to December 2018 in a single tertiary hospital. Eighty patients with diagnosis of soft tissue sarcoma were included. Preoperative modified Glasgow Prognostic Score, Neutrophils/Lymphocytes Ratio, Hemoglobin, serum lactate dehydrogenase data were analyzed along with demographic, clinical, radiological and histopathological data. The relationship between variables on overall survival, distant metastasis, and local recurrence were evaluated using univariate and multivariate Cox regression. ResultsOn univariate analysis, there was significant relationship between hemoglobin, Neutrophils/Lymphocytes Ratio and modified Glasgow Prognostic Score with overall survival (p = 0.031, HR = 1.99; p = 0.04, HR = 1.129; and p = 0.044, HR = 3.89). A significant relationship was found between age and soft tissue sarcoma stage with distant metastasis (p = 0.046, HR = 1.95; and p = 0.00, HR = 3.22). In addition, we also found significant relationship between surgical margin with local recurrence (p = 0.018, OR = 3.44). However, on multivariate analysis the independent prognostic factor for overall survival was only modified Glasgow Prognostic Score (HR = 2.138; p = 0.011). Stage IIIA (HR = 5.32; p = 0.005) and IIIB (HR = 13.48; p = 0.00) were independent prognostic for distant metastasis. Surgical margin was independently associated with local recurrence (HR = 14.84; p = 0.001). ConclusionModified Glasgow Prognostic Score can be used as prognostic tool of overall survival in soft tissue sarcoma patients. Moreover, stage of STS and surgical margin can be used as a prognostic factor for distant metastasis and local recurrence of soft tissue sarcoma respectively.

Long-term multidisciplinary treatment including proton therapy for a recurrent low-grade endometrial stromal sarcoma and pathologically prominent epithelial differentiation: an autopsy case report

BackgroundLong-term follow-up reports of low-grade endometrial stromal sarcoma (LGESS) including its clinical course and pathological data are rare. We previously reported the case of a Japanese woman diagnosed with LGESS, who was treated with multidisciplinary therapy. She had been suffering from uterine cervical tumor diagnosed as cervical polyps, or fibroid in statu nascendi, since 24 years old. The patient had survived for 25 years with the disease. This report presents her progress and pathological change since the previous report.Case presentationAt age 45, the patient experienced a relapse of the remnant LGESS tumor between the right diaphragm and liver. Although chemotherapy was not effective, the tumor was eliminated by proton therapy. At age 46 years, the remnant tumors outside the irradiated field were resected. The disease was originally diagnosed as “neuroendocrine carcinoma (NEC)” using the surgical specimen. Therefore, cisplatin and irinotecan combination chemotherapy were administered to treat the remnant dissemination. After 4 cycles of chemotherapy, the liver metastases had enlarged and were resected surgically. Consequently, no remnant tumor was visible in the abdominal cavity at the end of the surgery. To determine the origin of NEC, we examined the previously resected specimens obtained from her ileum at age 40 years. A boundary between the LGESS and neuroendocrine tumor grade 2 (NET G2)-like lesion was found in the tumor, indicating that the origin of these tumors was LGESS. After less than 2 years of chemotherapy and undergoing surgery, a relapse of the tumor in the liver induced biliary duct obstruction with jaundice, which was treated with endoscopic retrograde biliary drainage. Although pazopanib prolonged her life for 10 months, she died from sepsis at age 49 years, which was caused by the infection that spread to the liver metastatic tumor via the stented biliary ducts. Autopsy revealed adenocarcinoma-like differentiation of the tumor.ConclusionThis LGESS patient has survived for a long time owing to multidisciplinary treatment including proton therapy. The LGESS tumor differentiated to NET G2-like tissue and then further to adenocarcinoma-like tissue during the long-term follow-up.