Patterns of Care and Outcomes of Patients with Small Gastrointestinal Stromal Tumors at a High-Volume Sarcoma Center.

BACKGROUND: The course of subclinical gastrointestinal stromal tumors (GISTs) is variable. The management of small GISTs is not well-defined. METHODS: Records of patients presenting with small GISTs with documented follow-up appointment at our institution between 2016 and 2022 were identified and reviewed. Comparative univariate analysis to compare patient and tumor characteristics and outcomes was performed. RESULTS: Eighty-six patients were followed for a median of 3.7 years (range 0.1-20 years). The median size at presentation was 1.7 (range 0.1-2.5) cm. A total of 51.2% (n = 44) underwent surgery before or immediately after initial presentation for pain (18.2%), bleeding (15.9%), or patient preference (6.8%). Another 17.4% (n = 15) had delayed surgery for tumor growth (40%), patient preference (2.7%), bleeding (6.7%), or pain (6.7%). The remaining 31.4% (n = 27) of patients never underwent surgery for reasons that included no growth/stability (44.4%), concomitant cancer diagnosis/treatment (29.6%), comorbidities (14.8%), and patient preference (3.7%). Patients who underwent surveillance without intervention compared with those who had delayed surgery were older (71.1 vs. 60.8 years, p < 0.001) with multiple comorbidities or a concurrent cancer diagnosis (70.3% vs. 20%, p = 0.005). There were no differences in survival or rate of distant metastases. Average time to surgery in the delayed group was 2 (range 0.1-10.3) years, and 86% of these patients underwent surgery by 5.5 years after diagnosis. CONCLUSIONS: In older patients with comorbidities or concurrent cancer diagnoses, opting out of surgery does not affect survival. Conversely, younger patients, free from significant comorbidities or other diagnoses, may consider surgery or active surveillance for up to 5 years, with comparable outcomes.

Moderately hypofractionated, preoperative radiotherapy in patients with soft tissue sarcomas (HYPORT-STS): Updated local control, late toxicities, and patient-reported outcomes.

BACKGROUND: Moderately hypofractionated, preoperative radiotherapy in patients with soft tissue sarcomas (HYPORT-STS; ClinicalTrials.gov identifier NCT03819985) investigated a radiobiologically equivalent, moderately hypofractionated course of preoperative radiotherapy (RT) 15 × 2.85 Gy in patients with soft tissue sarcoma (STS). Here, the authors report longer term follow-up to update local control and report late toxicities, as well as functional and patient-reported outcomes. METHODS: HYPORT-STS was a single-center, open-label, single-arm, prospective phase 2 clinical trial that enrolled 120 eligible adult patients with localized STS of the extremities or superficial trunk between 2018 and 2021. Patients received a 3-week course of preoperative RT followed by surgery 4-8 weeks later. End points and follow-up were analyzed from the date of surgery. RESULTS: The median follow-up was 43 months (interquartile range, 37-52 months), and the 4-year local recurrence-free survival rate was 93%. Overall RT-related late toxicities improved with time from local therapy (p < .001), and few patients had grade ≥2 toxicities (9%; n = 8 of 88) at 2 years. These included: 2% grade ≥2 skin toxicity, 2% fibrosis, 3% lymphedema, and 1% joint stiffness. Four patients (3%) had bone fractures. Both functional outcomes, as measured by the Musculoskeletal Tumor Society Rating Scale (p < .001), and quality of life, as measured by the Functional Assessment of Cancer Therapy-General (p < .001), improved with time from treatment, and both measures were better in follow-up at 2 years compared with baseline. CONCLUSIONS: Long-term follow up suggests that moderately hypofractionated preoperative RT for patients with STS is safe and effective. Higher grade late toxicities affect a minority of patients. Late toxicities decrease over time, whereas functional outcomes and health-related quality of life seem to improve with more time from combined modality treatment.

Clinical Variables Influencing Outcomes in Patients with Atypical Intradermal Smooth Muscle Neoplasms (Formerly Cutaneous Leiomyosarcomas): Single-Institution Study of 95 Surgical Patients.

BACKGROUND: Atypical intradermal smooth muscle neoplasm, also commonly termed cutaneous leiomyosarcoma, is a soft tissue tumor with a low risk of aggressive behavior. These lesions arise in the dermis with possible superficial subcutaneous extension, demonstrate cytologic atypia, and often show mitotic activity. METHODS: A retrospective review of patient demographics, tumor characteristics, and treatment methods was conducted in a consecutive series of patients presenting to MD Anderson Cancer Center (MDACC) from 2002 to 2021 (n = 95). All pathology was reviewed by MDACC pathologists and determined to be atypical intradermal smooth muscle neoplasm. RESULTS: Median age at diagnosis was 58 years (range 22-86), and 74% were male. Ninety-five percent (n = 90) of patients identified as White, non-Hispanic. Most tumors were slow-growing, solitary, and painless nodules. Tumors were in the lower extremities (44.2%), followed by the upper extremity (28.4%), trunk (22.1%), and head and neck (5.2%). All patients (n = 44, 46.3%) who had a punch/incisional biopsy for diagnostic purposes had a subsequent tumor excision. Unplanned excision or excisional biopsy was performed on the remaining 46 (48%) patients. Of this subset, 41 of the 46 aforementioned patients (89%) had positive margins and underwent re-excision. Final pathology in 25/38 (66%) re-excision specimens was negative for residual tumor despite an initial positive margin. Two patients in the cohort had local recurrence 2 and 3 years after initial surgery. Both patients had positive margins, underwent excision of the recurrent tumor, and remain free of disease. After median follow-up of 6.9 years (range 1 day-18 years), 5-year recurrence-free survival was 96% and overall survival (OS) of the entire cohort was 78%. CONCLUSION: In this study of consecutive patients presenting with atypical intradermal smooth muscle neoplasm, we found good OS and local control after definitive surgical excision with negative margins, including excisional biopsy with close margins. Atypical intradermal smooth muscle neoplasm is unlikely to metastasize and has an excellent prognosis. Guidelines to determine optimal surveillance strategies for these patients should be revisited.

Antitumor Effects of Resveratrol Opposing Mechanisms of Helicobacter pylori in Gastric Cancer.

Gastric cancer is an aggressive and multifactorial disease. Helicobacter pylori (H. pylori) is identified as a significant etiological factor in gastric cancer. Although only a fraction of patients infected with H. pylori progresses to gastric cancer, bacterial infection is critical in the pathology and development of this malignancy. The pathogenic mechanisms of this bacterium involve the disruption of the gastric epithelial barrier and the induction of chronic inflammation, oxidative stress, angiogenesis and metastasis. Adherence molecules, virulence (CagA and VacA) and colonization (urease) factors are important in its pathogenicity. On the other hand, resveratrol is a natural polyphenol with anti-inflammatory and antioxidant properties. Resveratrol also inhibits cancer cell proliferation and angiogenesis, suggesting a role as a potential therapeutic agent against cancer. This review explores resveratrol as an alternative cancer treatment, particularly against H. pylori-induced gastric cancer, due to its ability to mitigate the pathogenic effects induced by bacterial infection. Resveratrol has shown efficacy in reducing the proliferation of gastric cancer cells in vitro and in vivo. Moreover, the synergistic effects of resveratrol with chemotherapy and radiotherapy underline its therapeutic potential. However, further research is needed to fully describe its efficacy and safety in treating gastric cancer.

Inhibition of glycolysis and Src/Akt signaling reduces Caveolin-1-enhanced metastasis.

Metastasis is the leading cause of cancer-related deaths, making the development of novel, more effective therapies imperative to alleviate patient suffering. Metabolic switching is a hallmark of cancer cells that facilitates metastasis. Cancer cells obtain most of their energy and intermediate metabolites, which are required to proliferate and metastasize, through aerobic glycolysis. Previous work from our laboratory has shown that Caveolin-1 (CAV1) expression in cancer cells promotes glycolysis and metastasis. Here, we sought to determine if limiting glycolysis reduced CAV1-enhanced metastasis and to identify the mechanism(s) involved. We evaluated the effects of the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) in metastatic melanoma and breast cancer cell lines expressing or not CAV1. Non-cytotoxic concentrations of 2-DG (1 mM) inhibited the migration of B16-F10 melanoma and MDA-MB-231 breast cancer cells. CAV1-mediated activation of Src/Akt signaling was required for CAV1-enhanced migration and was blocked in the presence of 2-DG. Moreover, inhibition of Akt reduced CAV1-enhanced lung metastasis of B16-F10 cells. Collectively, these findings highlight the importance of CAV1-induced metabolic reprogramming for metastasis and point towards possible therapeutic approaches to prevent metastatic disease by inhibiting glycolysis and Src/Akt signaling.

A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS.

High Community-Level Social Vulnerability is Associated with Worse Recurrence-Free Survival (RFS) After Resection of Extremity and Truncal Soft Tissue Sarcoma.

BACKGROUND: Although social vulnerability has been associated with worse postoperative and oncologic outcomes in other cancer types, these effects have not been characterized in patients with soft tissue sarcoma. This study evaluated the association of social vulnerability and oncologic outcomes. METHODS: The authors conducted a single-institution cohort study of adult patients with primary and locally recurrent extremity or truncal soft tissue sarcoma undergoing resection between January 2016 and December 2021. The social vulnerability index (SVI) was measured on a low (SVI 1-39%, least vulnerable) to high (60-100%, most vulnerable) SVI scale. The association of SVI with overall survival (OS) and recurrence-free survival (RFS) was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. RESULTS: The study identified 577 patients. The median SVI was 44 (interquartile range [IQR], 19-67), with 195 patients categorized as high SVI and 265 patients as low SVI. The median age, tumor size, histologic subtype, grade, comorbidities, stage, follow-up time, and perioperative chemotherapy and radiation utilization were similar between the high and low SVI cohorts. The patients with high SVI had worse OS (p = 0.07) and RFS (p = 0.016) than the patients with low SVI. High SVI was independently associated with shorter RFS in the multivariate analysis (hazard ratio, 1.64; 95% confidence interval, 1.06-2.54) but not with OS (HR, 1.47; 95% CI 0.84-2.56). CONCLUSION: High community-level social vulnerability appears to be independently associated with worse RFS for patients undergoing resection of extremity and truncal soft tissue sarcoma. The effect of patient and community-level social risk factors should be considered in the treatment of patients with extremity sarcoma.

Practice Pattern Variability in the Management of Regional Lymph Node Metastasis in Extremity and Trunk Soft Tissue Sarcoma: A Survey of the Society of Surgical Oncology and Musculoskeletal Tumor Society Membership.

BACKGROUND: Regional lymph node metastasis in extremity and trunk soft tissue sarcoma (ETSTS) is rare with no standardized management. We sought to determine management patterns for regional lymph node metastasis in ETSTS. METHODS: A survey regarding the management of ETSTS lymph node metastasis was distributed to the membership of the Musculoskeletal Tumor Society (MSTS) and the Society of Surgical Oncology (SSO) in January 2022. The survey queried the type of training (surgical oncology, orthopedic oncology), details of their practice setting, and management decisions of hypothetical ETSTS scenarios that involved potential or confirmed lymph node metastasis. RESULTS: The survey was distributed to 349 MSTS members (open rate of 63%, completion rate 21%) and 3026 SSO members (open rate of 55%, completion rate 4.7%) and was completed by 214 respondents, of whom 73 (34.1%) and 141 (65.9%) were orthopedic oncology and surgical oncology fellowship-trained, respectively. The majority of respondents practiced in an academic setting (n = 171, 79.9%) and treat >10 extremity sarcoma cases annually (n = 138, 62.2%). In scenarios with confirmed nodal disease for clear cell and epithelioid sarcoma, surgical oncologists were inclined to perform lymphadenectomy, while orthopedic oncologists were inclined to offer targeted lymph node excision with adjuvant radiation (p < 0.001). There was heterogeneity of responses regarding the management of nodal disease regardless of training background. CONCLUSION: Self-reported management of nodal disease in ETSTS was variable among respondent groups with differences and similarities based on training background. These data highlight the variability of practice for nodal disease management and the need for consensus-based guidelines.

Re-excision After Unplanned Excision of Soft Tissue Sarcoma is Associated with High Morbidity and Limited Pathologic Identification of Residual Disease.

BACKGROUND: Patients with unplanned excision (UPE) of trunk and extremity soft tissue sarcoma (STS) present a significant management challenge for sarcoma specialists. Oncologic re-resection has been considered standard practice after UPE with positive or uncertain margins. A strategy of active surveillance or "watch and wait" has been suggested as a safe alternative to routine re-excision. In this context, the current study sought to evaluate short-term outcomes and morbidity after re-resection to better understand the risks and benefits of this treatment strategy. METHODS: A retrospective, single-institution study reviewed patients undergoing oncologic re-resection after UPE of an STS during a 5-year period (2015-2020), excluding those with evidence of gross residual disease. Short-term clinical outcomes were evaluated together with final pathologic findings. RESULTS: The review identified 67 patients undergoing re-resection after UPE of an STS. Of these 67 patients, 45 (67%) were treated with a combination of external beam radiation therapy (EBRT) and surgery. Plastic surgery was involved for reconstruction in 49 cases (73%). The rate of wound complications after re-resection was 45 % (n = 30), with 15 % (n = 10) of the patients experiencing a major wound complication. Radiation therapy and plastic surgery involvement were independently associated with wound complications. Notably, 45 patients (67%) had no evidence of residual disease in the re-resection specimen, whereas 13 patients (19 %) had microscopic disease, and 9 patients (13%) had indeterminate pathology. CONCLUSION: Given the morbidity of re-resection and limited identification of residual disease, treatment plans and discussions with patients should outline the expected pathologic findings and morbidity of surgery.

Clinical Impact of External Beam Radiotherapy for Surgically Resected Primary Retroperitoneal Liposarcoma.

INTRODUCTION: EORTC-62092 (STRASS) was a phase 3, randomized study that compared surgery alone versus surgery plus neoadjuvant radiotherapy (RT) for retroperitoneal sarcomas. RT was not associated with improved abdominal recurrence-free survival, the primary outcome measure, although on subanalysis, there may have been benefit for well-differentiated (WD) liposarcoma. This study investigated the real-world use and outcomes of RT (neoadjuvant and adjuvant) for the management of retroperitoneal liposarcoma. METHODS: We queried the National Cancer Database (NCDB) (2004-2017) for patients with nonmetastatic, primary retroperitoneal liposarcoma treated with resection with or without RT (n = 3911). Patients were stratified by treatment type and histology [WD (n = 2252), dedifferentiated (DD) (n = 1659)]. Propensity score (PS) matching was used before comparison of treatment groups. Overall survival (OS) was the primary outcome measure. RESULTS: Median follow-up time was 4.1 years, and median OS was 10.7 years. There was no association between RT and OS for either WDLPS or DDLPS cohorts. We performed a subgroup analysis of neoadjuvant RT only, similar to STRASS. For WDLPS after PS matching (n = 208), neoadjuvant RT was not associated with OS (hazard ratio [HR] 1.01, p = 0.0523) but was associated with longer postoperative hospital stay (p = 0.012). For DDLPS after PS matching (n = 290), neoadjuvant RT was not associated with OS (HR 1.02, p = 0.889). For both WD-LPS and DD-LPS, utilization of neoadjuvant RT was associated with treatment at high-volume (≥ 10 cases/year) and academic/network facilities. CONCLUSIONS: For primary retroperitoneal liposarcoma treated with surgical resection, radiotherapy was not associated with an overall survival benefit in this propensity-matched, adjusted analysis of the NCDB.

Hypofractionated, 3-week, preoperative radiotherapy for patients with soft tissue sarcomas (HYPORT-STS): a single-centre, open-label, single-arm, phase 2 trial.

BACKGROUND: The standard preoperative radiotherapy regimen of 50 Gy delivered in 25 fractions for 5 weeks for soft tissue sarcomas results in excellent local control, with major wound complications occurring in approximately 35% of patients. We aimed to investigate the safety of a moderately hypofractionated, shorter regimen of radiotherapy, which could be more convenient for patients. METHODS: This single-centre, open-label, single-arm, phase 2 trial (HYPORT-STS) was done at a single tertiary cancer care centre (MD Anderson Cancer Center, Houston, TX, USA). We administered preoperative radiotherapy to a dose of 42·75 Gy in 15 fractions of 2·85 Gy/day for 3 weeks (five fractions per week) to adults (aged ≥18 years) with non-metastatic soft tissue sarcomas of the extremities or superficial trunk and an Eastern Cooperative Oncology Group performance status of 0-3. The primary endpoint was a major wound complication occurring within 120 days of surgery. Major wound complications were defined as those requiring a secondary operation, or operations, under general or regional anaesthesia for wound treatment; readmission to the hospital for wound care; invasive procedures for wound care; deep wound packing to an area of wound measuring at least 2 cm in length; prolonged dressing changes; repeat surgery for revision of a split thickness skin graft; or wet dressings for longer than 4 weeks. We analysed our primary outcome and safety in all patients who enrolled. We monitored safety using a Bayesian, one-arm, time-to-event stopping rule simulator comparing the rate of major wound complications at 120 days post-surgery among study participants with the historical rate of 35%. This trial is registered with ClinicalTrials.gov, NCT03819985, recruitment is complete, and follow-up continues. FINDINGS: Between Dec 18, 2018, and Jan 6, 2021, we assessed 157 patients for eligibility, of whom 120 were enrolled and received hypofractionated preoperative radiotherapy. At no time did the stopping rule computation indicate that the trial should be stopped early for lack of safety. Median postoperative follow-up was 24 months (IQR 17-30). Of 120 patients, 37 (31%, 95% CI 24-40) developed a major wound complication at a median time of 37 days (IQR 25-59) after surgery. No patient had acute radiation toxicity (during radiotherapy or within 4 weeks of the radiotherapy end date) of grade 3 or worse (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) or an on-treatment serious adverse event. Four (3%) of 115 patients had late radiation toxicity (≥6 months post-surgery) of at least grade 3 (CTCAE or Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme): femur fractures (n=2), lymphoedema (n=1), and skin ulceration (n=1). There were no treatment-related deaths. INTERPRETATION: Moderately hypofractionated preoperative radiotherapy delivered to patients with soft tissue sarcomas was safe and could therefore be a more convenient alternative to conventionally fractionated radiotherapy. Patients can be counselled about these results and potentially offered this regimen, particularly if it facilitates care at a sarcoma specialty centre. Results on long-term oncological, late toxicity, and functional outcomes are awaited. FUNDING: The National Cancer Institute.

Functional genomic analysis of epithelioid sarcoma reveals distinct proximal and distal subtype biology.

BACKGROUND: Metastatic epithelioid sarcoma (EPS) remains a largely unmet clinical need in children, adolescents and young adults despite the advent of EZH2 inhibitor tazemetostat. METHODS: In order to realise consistently effective drug therapies, a functional genomics approach was used to identify key signalling pathway vulnerabilities in a spectrum of EPS patient samples. EPS biopsies/surgical resections and cell lines were studied by next-generation DNA exome and RNA deep sequencing, then EPS cell cultures were tested against a panel of chemical probes to discover signalling pathway targets with the most significant contributions to EPS tumour cell maintenance. RESULTS: Other biologically inspired functional interrogations of EPS cultures using gene knockdown or chemical probes demonstrated only limited to modest efficacy in vitro. However, our molecular studies uncovered distinguishing features (including retained dysfunctional SMARCB1 expression and elevated GLI3, FYN and CXCL12 expression) of distal, paediatric/young adult-associated EPS versus proximal, adult-associated EPS. CONCLUSIONS: Overall results highlight the complexity of the disease and a limited chemical space for therapeutic advancement. However, subtle differences between the two EPS subtypes highlight the biological disparities between younger and older EPS patients and emphasise the need to approach the two subtypes as molecularly and clinically distinct diseases.

Sentinel Lymph Node Biopsy and Formal Lymphadenectomy for Soft Tissue Sarcoma: A Single Center Experience of 86 Consecutive Cases.

BACKGROUND: Lymph node metastases (LNMs) are rare in patients with soft tissue sarcoma (STS), and there is limited evidence to guide clinical management. We describe our experience with sentinel lymph node biopsy (SLNB) and lymphadenectomy in STS patients. METHODS: A single-center, retrospective review was performed for patients with STS treated with SLNB and/or lymphadenectomy from 1994 to 2018. Clinicopathologic characteristics, multimodality treatment, regional/distant recurrence-free survival (RFS), and overall survival (OS) were examined. RESULTS: Eighty-six patients underwent SLNB (n = 34) and/or lymphadenectomy (n = 60) for STS. The most frequent histologic subtypes were epithelioid, clear cell, and undifferentiated pleomorphic sarcoma. Eight of 34 (23.5%) patients had a positive SLNB with 5-year OS of 71.4% compared with 71.9% for those with a negative SLNB. Eight of the 26 SLN-negative patients (30.8%) eventually developed nodal recurrence (n = 2) and/or (n = 6) distant metastasis with an estimated 5-year OS of 50%. Of patients undergoing lymphadenectomy, estimated 5-year OS was 44.6% and median RFS was 12 months. Eight (13.3%) had distant disease at time of lymphadenectomy, 20 (33.3%) developed distant recurrence after lymphadenectomy, and 6 (10%) developed regional-only recurrence. Patients with regional-only recurrence after lymphadenectomy had an estimated 5-year OS of 66.7% compared with 29.1% for those who recurred distantly. CONCLUSIONS: Patients with positive SLNB had similar survival to those with negative SLNB. Lymphadenectomy for isolated nodal disease is associated with poor RFS but reasonable 5-year OS when recurrence is regional-only. In STS, regional disease appears clinically distinct from distant metastatic disease and has better outcomes.

Experimental models of undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumor.

Undifferentiated pleomorphic sarcoma (UPS) and malignant peripheral nerve sheath tumor (MPNST) are aggressive soft tissue sarcomas that do not respond well to current treatment modalities. The limited availability of UPS and MPNST cell lines makes it challenging to identify potential therapeutic targets in a laboratory setting. Understanding the urgent need for improved treatments for these tumors and the limited cellular models available, we generated additional cell lines to study these rare cancers. Patient-derived tumors were used to establish 4 new UPS models, including one radiation-associated UPS-UPS271.1, UPS511, UPS0103, and RIS620, one unclassified spindle cell sarcoma-USC060.1, and 3 new models of MPNST-MPNST007, MPNST3813E, and MPNST4970. This study examined the utility of the new cell lines as sarcoma models by assessing their tumorigenic potential and mutation status for known sarcoma-related genes. All the cell lines formed colonies and migrated in vitro. The in vivo tumorigenic potential of the cell lines and corresponding xenografts was determined by subcutaneous injection or xenograft re-passaging into immunocompromised mice. USC060.1 and UPS511 cells formed tumors in mice upon subcutaneous injection. UPS0103 and RIS620 tumor implants formed tumors in vivo, as did MPNST007 and MPNST3813E tumor implants. Targeted sequencing analysis of a panel of genes frequently mutated in sarcomas identified TP53, RB1, and ATRX mutations in a subset of the cell lines. These new cellular models provide the scientific community with powerful tools for detailed studies of tumorigenesis and for investigating novel therapies for UPS and MPNST.

Sarculator is a Good Model to Predict Survival in Resected Extremity and Trunk Sarcomas in US Patients.

BACKGROUND: Sarculator is an online validated nomogram that predicts overall survival of patients with resected, primary extremity sarcomas. However, its ability to accurately predict outcomes in US patients with sarcoma is unknown. PATIENTS AND METHODS: Patients from the National Cancer Data Base (NCDB) (2006-2016) with resected stage I-III primary extremity or trunk sarcoma were included. Predicted overall survival (pOS) was calculated using the Sarculator algorithm, which includes patient age, tumor size (cm), grade (1-3), and histology, and compared with actual overall survival (aOS). Harrell's C-index was calculated to determine the discriminatory ability of Sarculator (0.7 = good, 0.8 = strong, 1.0 = perfect model), and calibration plots were created. RESULTS: In total, 9738 patients were included. Five-year pOS was 73.7% compared with aOS of 68.9%. The C-index for the entire cohort was 0.726. By stage, the C-index was 0.730 for stage I, 0.708 for stage II, and 0.679 for stage III. By histology, C-indices were highest for leiomyosarcoma (0.745), myxofibrosarcoma (0.722), and other histologies (0.721). By sociodemographic variables, Sarculator performed better for patients < 50 years (C-index 0.722), of other/unknown race (C-index 0.781), with private insurance (C-index 0.715), treated at a center other than a community cancer programs (C-index > 0.7), and with no comorbidities (C-index 0.716). Outcomes by zip code educational attainment and income were not markedly different (all C-indices > 0.7). CONCLUSIONS: Sarculator is overall a good predictor of aOS and useful tool for clinicians to aid in survival prognostication. However, clinicians should be aware of populations for whom Sarculator's predictions may be less accurate. Future work could focus on enhancing the Sarculator algorithm specifically for US patients by including demographic variables.