Neck Soft Tissue Sarcomas Research Articles

Head and Neck Soft Tissue Sarcoma Patient: Age and Tumor Region Are Predictive in Disease-Free Survival and Overall Survival

Head and neck soft tissue sarcoma (HNSTS), rare and heterogeneous malignancies, are treated primarily treated with surgery. However, prognostic indicators that might guide HNSTS management are poorly defined. Main purpose of this study is to find variables linked to HNSTS patients' prognosis. Assessment of the Tumor, Node, Metastatis (TNM) system is the secondary purpose. This study is a retrospective cohort performed on HNSTS patients who received surgery at the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital School of Medicine, Shanghai Jiao Tong University from January 1, 2006, to December 31, 2014. Strict inclusion criteria were applied. The predictor variable was a set of heterogenous risk factors and were grouped into the following categories: demographic (age and gender), clinical (primary tumor, tumor region, tumor size, and TNM stage), and treatment (surgical margin, treatment therapy). The primary outcome variables were time to 5-year disease-free survival (DFS) and 5-year overall survival (OS). The secondary outcome variables were time to 5-year tumor local recurrence and metastasis. Not applicable. Descriptive statistical analysis was carried out. Pearson χ2 test was employed in univariate analysis. Cox regression was modified for multiple variable analysis with components that had significant P values in univariate analysis or variables with potential prognostic value. Log-rank test was applied to compare survival situations under various variables. P value less than .05 was statistically significant. The sample was composed of 100 subjects with a mean age of 43.47 (standard deviation: 16.15) years old and 56 (56%) were male. The 5-year DSF and OS were 59 and 60%, respectively. Variables associated with poor DFS and OS were age > 60years (P=.003, hazard ratio [HR]: 4.95, 95% confidence interval [CI]: 1.71,14.1; P=.005, HR: 4.48, 95% CI: 1.57,12.8) and non-primary tumors (P＜.001, HR: 8.41, 95% CI: 2.85,24.8; P=.002, HR: 6.90, 95% CI: 2.46,19.4), respectively. Maxilla and skull base cancers had local recurrence (12/18, 66.7%) more common. T2 (TNM) tumor displayed higher tendency in DFS(P=.009, HR: 4.20, 95% CI: 1.42,12.4) and metastasis(P=.09, HR: 3.51, 95% CI: 0.82,15.0) than T1 (TNM) tumors. Poor prognosis is associated with maxilla and skull base tumors as well as patients over 60years. TNM stage appeared to have limited prognostic significance.

An analysis of the effectiveness of differential diagnosis and surgical treatment of neck soft-tissue sarcomas in children

We conducted a retrospective sample study with prospective collection of follow-up data. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. In the time period from January 2013 to August 2020 (92 months), 126 patients with head and neck soft-tissue sarcomas (STS) received treatment at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. We included 25 patients who had undergone surgery for neck STS and divided them into 4 groups (rhabdomyosarcoma (RMS), non-RMS-like STS, RMS-like STS, IRS-IV STS – with distant metastasis at baseline). The median age at the time of correct diagnosis was 2.6 (0.5; 5.0). The median time from symptom onset to the verification of the correct pathomorphological diagnosis was 3.2 (1.6; 4.9) months. We discovered a significant number (13/25, 52%) of cases of biopsy that was performed improperly (excessive/non-diagnostic biopsy, fine-needle aspiration biopsy) at a general inpatient facility. The correct pathomorphological diagnosis was clinically and statistically much more often made at a reference center (20/25, 80%; p = 0.003). Moreover, more than half of pathomorphological diagnoses (8/13, 62%) made at a general inpatient facility were later changed at a reference center. Radical resection was achieved in 17/20 (85%) survivors. In 3/20 (15%) cases, a repeat surgery was not needed because of the patients' complete response to protocol-based treatment. Radiotherapy was carried out in 11/25 (44%) cases. Protocol-based treatment was completed in 19/25 (76%) patients, 18/25 (72%) patients achieved complete response, 2/25 (8%) patients were considered incurable, and 4/25 (16%) children died before the completion of therapy. Post-operative complications of varying severity were observed in 10/25 (40%) cases and were dependent on the degree of STS extension and the severity of the condition of the patients undergoing intensive protocol-based treatment. The median time of patient observation since diagnosis verification was 33.2 (15.6; 74.2) months. The five-year overall survival (OS) was 76.3% (95% confidence interval (CI) 51.8; 89.5), the five-year event-free survival without local disease progression – 73.9% (95% CI 41.8–90.1). Even though there weren't many patients with IRS-IV in our study (4/25, 16%), their exclusion from the analysis resulted in a higher 5-year OS rate: 88.2% (95% CI 60.2; 96.9). This study revealed significant problems in the differential diagnosis of neck STSs in children. In most patients receiving optimal protocol-based treatment, neck tumors can be radically removed at a specialized healthcare facility without mutilating surgery, which results in high 5-year OS and event-free survival rates in patients without distant metastasis. Our findings require further investigation in a larger sample of patients.

1958P Head and neck soft tissue sarcoma: Evaluation of the 8th AJCC as a prognostic tool for patients treated with curative intent in a multidisciplinary cancer center

1958P Head and neck soft tissue sarcoma: Evaluation of the 8th AJCC as a prognostic tool for patients treated with curative intent in a multidisciplinary cancer center

Dawn of Staging for Head and Neck Soft Tissue Sarcoma: Validation of the Novel 8th Edition AJCC T Classification and Proposed Stage Groupings

After decades of stagnation, the 8th edition TNM (TNM8) introduced a new T classification for head and neck (HN) soft tissue sarcomas (STS). New size cutoffs of 2 and 4 cm define T1-3, and a novel T4 category is defined by local invasion of adjoining structures. These size cutoffs had been chosen arbitrarily to advance data collection in this unique disease site since literature showed approximately 70% of HN STS did not reach the previous size threshold (5 cm) for the existing T1 category. The definition of the TNM8 T categories also align with mucosal HN cancers. No stage grouping for HN STS was defined since this new classification required more data collection to derive stage groups. This study aims to validate the TNM8 T classification and to propose stage groupings. Clinical data of all adult (>16 years) HN STS patients treated from 1988 - 2019 with curative intent in our tertiary cancer center were retrieved from a prospective database, and supplemented with chart review. As per TNM8, cutaneous angiosarcoma, embryonal and alveolar rhabdomyosarcoma, Kaposi sarcoma, and dermatofibrosarcoma protuberans were excluded due to their different behavior. Multivariate analysis (MVA) identified prognostic factors for overall survival (OS). Adjusted hazard ratios (AHR) and recursive partitioning analysis (RPA) were used to derive stage groupings. Stage grouping performance for OS was assessed and also compared against the existing TNM8 groups for non-HN STS. A total of 221 patients (N1: 2; M1: 2) were included. Of the 219 M0 patients, 63% were males; median tumor size was 3.0 cm (range: 0.3-14.0); the proportion of TNM8 T1-T4 were 35%, 34%, 26%, and 5%, respectively. Median follow up was 5.9 years. Five-year OS was 79%. MVA confirmed the prognostic value of T category (T4 HR 7.73, 95% CI 3.62-16.5) and grade (G2/3 vs G1 HR 3.7, 95% CI 1.82-7.53), in addition to age (HR 1.03, 95% CI 1.01-1.04) (all p<0.001) for OS. AHR model derived T1-3_Grade 1 as stage 1; T1-3_Grade 2/3 as stage II; and T4_any Grade or any T_N1 as stage III (Table 1); the corresponding 5-year OS was 93%, 73%, and 38%, respectively. Both patients with M1 died within 1.5 years after diagnosis and M1 disease was designated stage IV. The AHR-grouping outperformed the RPA and non-HN TNM8 stage grouping for hazard consistency, hazard discrimination, percent variance explained, hazard difference, and sample size balance. The novel T4 category introduced in TNM8 is associated with a >7 fold increased risk of death. Grade continues to be a critical prognostic factor in HN STS. The TNM8 HN STS T classifications have been validated, and the proposed new stage groupings with TNM8 incorporating grade have excellent performance for OS.

Outcomes for Patients with Head and Neck Sarcoma Treated Curatively with Radiation Therapy and Surgery

Soft tissue sarcomas (STS) of the head and neck are rare and diverse entities that are challenging to manage. Definitive treatment requires surgery, often with radiation therapy (RT). We sought to describe the outcomes of patients treated curatively with surgery and RT for head and neck STS. We performed a retrospective review of patients treated at a tertiary cancer center for non-metastatic STS of the head and neck between 1968 and 2020; over half were treated in the modern era defined as 2005 or after. Patients with rhabdomyosarcomas or cutaneous angiosarcoma were excluded. The Kaplan-Meier method was used to estimate actuarial overall survival (OS), disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVA) were conducted using Cox proportional hazards model. Median follow-up was 82 months. Of the 192 patients, the majority were male (n = 111, 58%), White (n = 158, 82%), and median age was 49.5 [IQR 32.5-64]. The highest proportion of tumors were in the neck (n = 50, 26%), paranasal sinuses (n = 36, 19%), or face (n = 23, 12%). The most common histology was sarcoma, not otherwise specified (n = 44, 23%), followed by undifferentiated pleomorphic sarcoma (n = 32, 17%), and neurogenic sarcoma (n = 15, 8%). Most patients were treated with postoperative RT (n = 134, 70%). Patients treated with preoperative RT were older (median 56.5 yrs vs post-op 44 yrs, p = 0.009). Post-op RT doses were higher (median 60 Gy, pre-op 50 Gy, p<0.001), and margins were more likely to be negative in those treated with pre-op RT (n = 39, 67%, post-op 69, 51%, p = 0.02). 5-year LC, DSS, and OS for the entire cohort was 76% (95% CI 69-82), 74% (67-80), and 71% (64-77), respectively. LC was not affected by treatment sequence (pre-op RT 78% (63-88), post-op RT 75% (66-82), p = 0.48). Patients with negative margins had improved 5-yr LC (86% (77-92), positive/uncertain 65% (53-74), p = 0.003). On MVA, positive/uncertain margin was the only variable associated with LC (HR 2.54 (1.34-4.82), p = 0.004). Poorer 5-yr DSS was associated with higher grade (grade 3 75% (63-84), grade 1-2 89% (75-94), p = 0.02), and treatment era (pre-2005 68% (57-76), on/after 2005 80% (70-87), p = 0.04). These both remained significant on MVA (grade 3 HR 2.39 (1.07-5.36), p = 0.034; pre-2005 HR 2.31 (1.03-5.21), p = 0.043). Sixteen patients (8%) developed a late RT toxicity, including fibrosis (n = 4, 2%), necrosis (osteoradionecrosis n = 2, brain necrosis n = 1, soft tissue necrosis n = 1), and eye dryness (n = 2, 1%). Neither the timing of RT nor dose was found to be associated with developing a late RT toxicity. Head and neck STS continues to have relatively poorer local control than STS of the trunk or extremities. Timing of RT did not impact oncologic or long-term RT-related toxicity outcomes. However, more data are needed to ascertain whether preoperative RT may impact acute surgical toxicities. These data contribute to multidisciplinary care planning for patients with STS in these challenging anatomic locations.

36 Dawn of Staging for Head and Neck Soft Tissue Sarcoma: Validation of the Novel 8th Edition AJCC T Classification and Proposed Stage Groupings

36 Dawn of Staging for Head and Neck Soft Tissue Sarcoma: Validation of the Novel 8th Edition AJCC T Classification and Proposed Stage Groupings

Comparative analysis between the 8th and 7th AJCC as a prognostic tool for patients diagnosed with nonmetastatic head and neck soft-tissue sarcoma.

e23550 Background: Head and neck soft-tissue sarcoma (HN-STS) is a rare entity for which a new prognostic risk stratification has been proposed in the 8th AJCC. The tumor size 2cm and 4cm have been adopted as cutoffs for T1 to T3 classification and the invasion of surrounding structures denotes T4. In opposite, in the 7th edition the primary tumor size of 5 cm determines T1 and T2 classification. This study aimed to compare the 8th and 7th AJCC as a prognostic tool for HN-STS. Additionally, we sought to investigate prognostic factors in this group of patients. Methods: This is a single Tertiary Hospital study approved by the institutional ethical review committee from the AC Camargo Cancer Center. We retrospectively evaluated patients with non-metastatic HN-STS whose histology subtypes are included in the 40th chapter of the 8th AJCC version. We compared the AJCC 7th and 8th T staging with Cohen’s kappa coefficient using inter-rater agreement analysis. The Kaplan-Meier (KM) estimator was used to calculate median survival times; differences in time-to-event outcomes were assessed using the log-rank test. Cox proportional hazard model was used to assess the effect of features in overall survival (OS). Results: Ninety-five HN-STS treated with curative intent from 2005 from 2021 patients diagnosed were evaluated. Surgical resection (94.7%), radiotherapy (48.4%) and chemotherapy (23.1%) were the employed therapeutic approaches. Leiomyosarcoma and liposarcoma (10 of each subtype) were the most common histology subtypes; High grade disease was present in 66.3%. Kappa coefficient of inter-rater agreement was 0.46 with statistical significance (p = 0.03), which indicates poor agreement between AJCC 7th and 8th T staging system. Regarding OS stratified by T size in the AJCC 7th (T1 and T2) and 8th (T1, T2, T3 and T4) was not statistically different between groups (P = 0.83 and P = 0.21, respectively). Patients with T4 (47.6% vs 78.7%, P = 0.04) and high grade (64.0% vs 96.2%, P = 0.003) had worst 5-years OS. In Cox multivariate analysis, patients with 8th edition T4 and high grade had 3.15- and 4.16-fold increased risk of death, respectively. Conclusions: In our series of patients with HN-STS, neither 7th nor 8th AJCC T size category groups discriminated prognosis. Tumor with local invasion (8th AJCC T4) and high grade were all associated with increased risk of mortality.

Comparison of Definitive Radiotherapy-Based Treatment and Surgical-Based Treatment for Locally Advanced Head and Neck Soft Tissue Sarcoma.

Background: Head and neck soft-tissue sarcomas are rare but aggressive malignancies. Definitive radiotherapy might be an alternative treatment choice in patients unfit for surgery with preservation of organ function and facial morphology. Whether definitive radiotherapy is comparable with surgery has not been fully demonstrated. In this study, we compared the prognosis of patients with radiotherapy-based treatment and with surgery-based treatment. Methods: From May 2014 to February 2021, patients with locally advanced head and neck soft-tissue sarcoma treated with either definitive radiotherapy-based treatment or radical surgery-based treatment were retrospectively enrolled. Clinical outcomes including tumor response, patients' survival and acute treatment-related toxicities were evaluated. Kaplan-Meier curves with log-rank test were used to compare survival data. Cox regression analysis was used to explore prognostic factors. Results: A total of 24 patients (12 males and 12 females, 3 to 61 years old) were eligible for analysis. The median follow-up time was 49 (range: 6-96) months. In 16 patients receiving definitive radiotherapy-based treatment, 6 reached complete response. The survival curve showed that there was no statistically significant difference in overall survival (OS), distant metastasis-free survival (DMFS), loco-regional relapse-free survival (LRRFS) and progression-free survival (PFS) between the two groups of patients (p = 0.35, p = 0.24, p = 0.48, p = 0.1, respectively). COX regression analysis showed that older age was associated with poor DMFS. There was no significant difference in grade 3-4 toxicities between the two groups. Conclusions: In cases of contradictions to surgery, refusal to surgery or failure to complete resection, chemoradiotherapy might be an alternative treatment option.

Skin lesions on a man's face and scalp

An 87-year-old male patient was admitted to our Clinic for diagnostic evaluation and treatment of extensive, confluent erythematous-livid areas that affected almost the entire skin of his face, scalp, and neck Figure (1). The patient also showed left eyelid ectropion and a palpable subcutaneous, painless nodule in the left mandibular region the size of an apple that bled easily. The patient had been treated for undiagnosed erythematous papules on his left cheek 2 years before and reported that his condition had dramatically worsened over the last few weeks. The patient was otherwise healthy and was only being treated for hypertension and hyperlipemia. Multiple computed tomography (CT) scans were performed which showed an extensive disease affecting the skin and subcutaneous tissue of almost the entire face, scalp and neck, with occasional involvement of muscle tissue as well. Numerous secondarily altered lymph nodes of the neck and multiple tumour infiltrates in the liver were also seen. A skin biopsy from the scalp was performed Figure (2). Histopathology showed a tumoral lesion composed of irregular, anastomosing vascular spaces and an increased number of surrounding endothelial cells with hyperchromatic, atypical nuclei. The clinical and pathological features corresponded to a typical presentation of angiosarcoma (AS). The patient had an inoperable disseminated disease and palliative chemotherapy with paclitaxel was initiated. After three cycles of therapy, the patient's general condition worsened, and was admitted to a palliative care facility. cAS is a rare vascular malignant tumour that has a high risk of both local and distant metastatic dissemination despite aggressive therapy. It is classified into primary AS that occurs sporadically, usually in the scalp or face, and secondary AS that is most often related to a history of radiation treatment and chronic lymphedema.1 This malignant tumour resembles a “spreading bruise” that varies from blue to red in colour. The diagnosis of cAS is often delayed due to its subtle initial clinical appearance as it is often mistaken for an ecchymosis or haematoma, especially in elderly patients on anticoagulants. Most patients are asymptomatic although some may present with bleeding, oedema, and/or ulceration. Diagnosis is based on clinical examination and histopathological and immunohistochemical analysis. The extent of the disease may be assessed with magnetic resonance imaging or CT.1, 2 AS represents less than 0.1% of all head and neck malignancies but is associated with the highest rate of lymphatic dissemination among all head and neck soft tissue sarcomas.3, 4 AS shows aggressive behaviour and carries a poor prognosis, thus early diagnosis is crucial. The optimal treatment is surgery followed by wide-field radiotherapy. Clear surgical margins are of paramount importance and correlate with better outcome, but the disease is often so extensive at the time of diagnosis that it is not possible to excise.5, 6 Despite inconsistent data regarding chemotherapy, this is usually employed for patients with metastatic or inoperable disease. Doxorubicin-based regimens are most recommended, but recent use of paclitaxel has shown better efficacy compared with doxorubicin.6, 7 Though involvement of the face and scalp is common in cAS, the extent of disease in our case was striking. AS should be considered in the differential diagnosis of violaceous or ecchymotic lesions on the head or scalp in the elderly. All authors contributed to the manuscript conception, design, and writing. All authors read and approved the final manuscript. The authors have not declared a specific grant from any funding agency in the public, commercial or not-for-profit sectors. The authors declare no conflict of interest. This article did not require the approval of the Ethics committee. The patient in this manuscript has given written informed consent to the publication of his case details. Due to privacy and ethical concerns, neither the data nor the source of the data can be made available.

Prognostic Utility of Nutritional Risk Index in Patients with Head and Neck Soft Tissue Sarcoma.

The nutritional risk index (NRI) is an excellent indicator of nutritional status and a significant prognostic factor in several malignancies, but the relationship between NRI and the prognosis of head and neck soft tissue sarcoma (HNSTS) patients remains unclear. The aim of this study was to investigate the role of NRI in patients with HNSTS. We retrospectively reviewed patients with HNSTS between 1990 and 2021. In order to determine the optimal cut-off value of NRI, the Maximally selected log-rank statistic was performed. We evaluated the effect of NRI on overall survival (OS) and progression-free survival (PFS) by using the Kaplan-Meier method and Cox regression analysis. Then, OS and PFS nomograms based on NRI were constructed. In total, 436 HNSTS patients were included in this study. The optimal cut-off value of NRI was 99.34. Patients with low-NRI showed significantly worse OS and PFS than patients with high-NRI, respectively (5-year OS rate of 43.0 vs. 70.8%, 5-year PFS rate of 29.0 vs. 45.0%, all p < 0.05). In the multivariate analysis, distant metastasis, deep tumor depth, tumor grade, and NRI were prognostic factors for both PFS and OS, and treatment modality was associated with OS but not PFS. The concordance indexes (C-indexes) of OS and PFS nomograms were 0.794 (95% CI, 0.759-0.829) and 0.663 (95% CI, 0.626-0.700), respectively, which also performed well in the validation set. NRI is an independent predictor of OS and PFS in HNSTS patients. The validated nomograms based on NRI provide useful predictions of OS and PFS for patients with HNSTS.

The inflammatory-nutritional score and nomogram for R0 resected head and neck soft tissue sarcoma.

To explore the predictive value of inflammatory-nutritional score (INS) and a nomogram for survivals in head and neck soft tissue sarcoma (HNSTS) patients with negative resection margins (R0). Clinical characteristics and hematological features of 315 HNSTS patients underwent R0 surgery were analyzed. The 5-year overall survival (OS) rate, 3-year recurrence-free survival rate and disease-free survival (DFS) rate were 77.3%, 61.0% and 55.4%, respectively. High INS was associated with a deep tumor location (p < 0.001), high tumor grade (p < 0.001), and advanced AJCC stage (p < 0.001). The low-risk group (INS 0) exhibited a higher 5-year OS rate and 3-year DFS rate than others (87.6% vs. 81.3% vs. 53.3%, p < 0.001; 62.2% vs. 56.9% vs. 37.9%, p=0.007). The INS (p=0.023), tumor depth (p < 0.001), pT classification (p=0.022), pN classification (p < 0.001) and tumor grade (p < 0.001) were independent survival predictors. Moreover, a novel nomogram for predicting OS was generated and assessed by the concordance index, exhibiting a better performance than the p7TNMG classification alone (p < 0.001). For R0 resected HNSTS patients, the oncological outcomes can be predicted using the INS system and a specific nomogram.

Time to Local Recurrence as a Predictor of Survival in Adult Head and Neck Soft Tissue Sarcoma.

We sought to evaluate the impact of the time interval from surgical resection to local recurrence (TTLR) on clinical outcomes in head and neck soft tissue sarcoma (HNSTS). A total of 401 patients who underwent R0 resection for primary HNSTS were included in this study. Patients with local recurrence as the first event after their initial resection were divided into early local recurrence (ELR) or late local recurrence (LLR) groups according to TTLR. Multiple survival analyses were performed to identify the independent prognostic predictors of overall survival (OS) and survival after local recurrence (SAR). Two hundred and nine of the 401 patients (52.1%) developed local recurrence during a median follow-up period of 134.6 months. Patients in the ELR group had a shorter median OS time (35.0 vs. 120.6, p < 0.001) and lower 5-year OS rate (47.7% vs. 80.9%, p < 0.001) than those in the LLR group. Moreover, the ELR group exhibited worse SAR (p=0.001) than the LLR group, and multivariate analyses demonstrated TTLR as an independent prognostic factor for SAR (p=0.048) and OS (p=0.004). Additionally, re-resection significantly prolonged SAR than other salvage interventions or no treatment (p < 0.001). In patients with HNSTS, ELR after R0 resection presents adverse effects on OS and SAR than those with LLR, and TTLR could serve as a promising predictor for survival. Salvage therapies, especially the re-resection could improve SAR and should be recommended when there are surgical indications after recurrence. 3 Laryngoscope, 133:2174-2182, 2023.

Soft Tissue Sarcomas of the Head and Neck Region with Skull Base/Intracranial Invasion: Review of Surgical Outcomes and Multimodal Treatment Strategies: A Retrospective Case Series.

Soft tissue sarcomas (STS) invading the skull base are rare with little data to guide surgical management. Here we aimed to determine the factors affecting tumor control rates and survival in patients with T4 stage head and neck STS involving the skull base. A retrospective review of STS patients, surgically treated at our institution between 1994 and 2017 was conducted. Variables were collected and assessed against progression-free survival. Tumors were graded using the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system. A total of 51 patients (mean age of 35) were included, of whom 17 (33.3%) patients were FNCLCC grade 1, 8 (15. 7%) were FNCLCC grade 2 and 26 (51%) were FNCLCC grade 3. The median PFS was 236.4 months while the 5- and 10-year PFS rates were 44% and 17%, respectively. Recurrence occurred in 17 (33.3%) patients. Local recurrence occurred in 10 (58.8%). Univariate analysis revealed R0 resection had a near-significant impact on tumor control in radiation-naïve patients. Otherwise, prior radiation (HR 6.221, CI 1.236–31.314) and cavernous sinus involvement (HR 14.464, CI 3.326–62.901) were negative predictors of PFS. The most common cause of treatment failure was local recurrence. In T4 stage head and neck STS with skull-base involvement, FNCLCC grade, radiation status, and anatomic spread should be considered in determining the overall treatment strategy.

Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as retroperitoneal/intra-abdominal STS, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis and treatment of retroperitoneal/intra-abdominal STS, outlines treatment recommendations, and reviews the evidence to support the guidelines recommendations.

Abstract 2761: FT573: Preclinical development of multiplexed-engineered iPSC-derived NK cells expressing a novel camelid nanobody chimeric antigen receptor (CAR) targeting pan-cancer antigen B7-H3

Abstract Introduction: B7-H3 (CD276) has gained significant clinical interest as a pan-tumor target antigen for development of various immuno-oncology agents. Due to its broad expression on a wide variety of solid tumors and minimal expression on normal tissues, B7-H3 is an ideal tumor antigen target. Additionally, high levels of B7-H3 are found on “immunologically cold” tumors such as glioblastoma multiforme, prostate cancer, head and neck cancer and soft tissue sarcomas, which typically have poor response to approved immune therapies. To effectively target B7-H3 with an off-the-shelf cellular therapy, we describe here the development of camB7-H3 CAR-NK cell utilizing our iPSC platform to engineer multiple modalities into a clonal iPSC line, which can serve as the starting cell source for mass production of off-the-shelf, iPSC-derived CAR-NK cells (CAR-iNK cells). Methods: A camelid nanobody specific for human B7-H3 (camB7-H3) was discovered using a phage display library and validated in functional assays. camB7-H3 CAR-iNK cells were designed to 1) express membrane-bound IL-15/IL-15 receptor fusion for enhanced persistence, 2) have a CD38 knockout to improve metabolic fitness, 3) express a high-affinity non-cleavable CD16 to maximize ADCC when combined with a therapeutic antibody, and 4) express an anti-camB7-H3 CAR optimized for NK cell signaling. As the initial preclinical study, camB7-H3 CAR-iNK cells were assessed using flow cytometry-based functional assays evaluating CD107a and IFNγ or xCelligence target killing assays against B7-H3 transgenic or naturally expressing tumor cell lines. Results: The camelid single domain B7-H3 initially tested in CAR-T exhibited B7-H3 specific binding and specific activity against several solid tumor cell lines (breast, ovarian, prostate, lung). We next produced camB7-H3 CAR-iNK cells and demonstrated superior B7-H3-specific target elimination compared to untransduced iNK cells. These results were seen across multiple tumor lines representing various solid tumor indications. Further enhancement of anti-tumor efficacy was seen when combined with therapeutic antibodies, including trastuzumab and cetuximab. Conclusions: We have successfully produced and validated the specificity and function of an engineered camB7-H3 CAR-iNK cell exhibiting robust target killing and on-target specificity. To our knowledge, this is the first camelid nanobody antigen recognition domain reported in a CAR-NK cell to be used as an off-the-shelf immunotherapy. The combining camB7-H3 CAR-NK with monoclonal antibodies targeting HER2 and EGFR as a dual targeting approach will add additional tumor specificity, further increase the efficacy of tumor cell elimination and prevent antigen escape. Additional camB7-H3 CAR-iNK cell preclinical studies are in process and will be discussed. Citation Format: Nicholas Zorko, Frank Cichocki, John Goulding, Bryan Hancock, Robert Blum, Mochtar Pribadi, Bjoern Gaertner, Tom Lee, Martin Felices, Ryan Bjordahl, Bahram Valamehr, Jeffrey S. Miller. FT573: Preclinical development of multiplexed-engineered iPSC-derived NK cells expressing a novel camelid nanobody chimeric antigen receptor (CAR) targeting pan-cancer antigen B7-H3 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2761.

Primary epithelioid sarcoma of the oral cavity: Review of literature and presentation of a rare entity

AbstractBackgroundEpithelioid sarcoma (ES) is a rare malignancy when diagnosed within the oral cavity. Currently, only four cases of primary ES of the oral cavity have been reported in the literature. The diagnosis of ES is difficult and requires differentiation from other sarcomas, benign inflammatory processes and squamous cell carcinoma.MethodsHerein, we have described a primary ES of the lateral oral tongue in a young female. This is the third case of primary ES of the tongue to be reported.ResultsA young female underwent partial glossectomy and post‐operative radiation for definitive treatment of a primary ES of the lateral oral tongue with no recurrence at 18 months.ConclusionEpithelioid sarcoma is a clinically aggressive sarcoma with poor overall survival. Treatment is primarily based on evidence from limited case reports and treatment of non‐head and neck soft tissue sarcomas. Treatment requires a multimodal approach including surgical excision and often postoperative radiation therapy, and close follow‐up.

High Local Control Following Pre-Operative Radiotherapy for Adult Deep Soft Tissue Sarcoma of the Head and Neck

<h3>Purpose/Objective(s)</h3> Local control (LC) of head and neck (HN) soft tissue sarcoma (STS) is generally lower than the > 90% rate expected in extremity STS. We report outcomes of high-risk adult HN STS [defined as requiring surgery and radiotherapy (RT) after joint in-person assessment by a HN surgeon and radiation oncologist with expertise in sarcoma management] using pre-operative (Pre-op) RT to reduce target volumes adjacent to optic or other vulnerable anatomy. <h3>Materials/Methods</h3> A prospective series of newly diagnosed adult HN STS patients who underwent Pre-op RT between 1989-2019 was analyzed. Angiosarcoma, fibromatosis, and embryonal/alveolar rhabdomyosarcoma were not included due to natural history requiring different management paradigms; other histologies were excluded due to the anticipated favorable control rates in these subtypes (i.e., dermatofibrosarcoma protuberans, HN sinonasal solitary fibrous tumor/hemangiopericytoma). Actuarial rates of LC, distant control (DC), and overall survival (OS) were analyzed by resection margin status. Important wound complications, defined according to a published randomized trial evaluating Pre-op RT in extremity STS, were also reported. <h3>Results</h3> Eligibility comprised 59 cases arising from neck/supraclavicular (n = 23), sinonasal (n = 16), oral (n = 11), parapharyngeal (n = 7), and scalp (n = 2) regions. UICC/AJCC TNM-8 cT-categories were: T1 (n = 10), T2 (n = 20), T3 (n = 20), and T4 (n = 9). Neoadjuvant chemotherapy was given to 3 patients (2 rhabdomyosarcomas and 1 synovial sarcoma). Pre-op RT included: 50 Gy in 25 fractions over 5 weeks (n = 53) or 60 Gy in 30 fractions over 6 weeks (n = 6). Median interval from pre-op RT to surgery was 7.3 weeks (range: 2.9-19.6). Four patients (6.7%) had wound complications considered important according to the defined criteria. One healed following flap debridement and the remainder only required conservative management. Resection margins were grossly positive (gross+) in 4 (7%), microscopically positive (micro+) in 16 (27%), and negative in 39 (68%) patients. Six received a post-op boost of 10 Gy in 5 fractions (1 for micro+ and 5 for < 10 mm resection margins). Median follow-up was 6.5 years (0.8-28.6 years). Local failure occurred in 1/39 negative, 2/16 micro+, and 4/4 gross+ resection margin groups. Five-year LC, DC and OS for negative vs micro+ vs gross+ resection margin groups were: 97% vs 93% vs 25% (<i>P</i> < 0.001, micro+ vs negative: <i>P</i> = 0.083); 78% vs 75% vs 75% (<i>P</i> = 0.97), 83% vs 87% vs 25% (<i>P</i> < 0.001). No patient developed significant toxicity (e.g., blindness) related to RT. <h3>Conclusion</h3> HN STS patients requiring combined modality local management with moderate dose Pre-op RT in a sarcoma-focused multidisciplinary clinic setting have excellent LC and functional outcomes that parallel extremity cases, but with less wound complications. Micro+ margins without postop boost RT does not seem to compromise LC when managed within a collaborative environment.

Assessment of Prognostic Factors and Adjuvant Treatment Modalities in Adult Head and Neck Soft Tissue Sarcoma Patients Treated With Upfront Surgery

ObjectivesHead and neck soft tissue sarcomas (HNSTSs) are a heterogeneous group of rare tumors. Surgical resection with negative margins remains the standard primary treatment for patients with HNSTS. The role of chemotherapy (CT) and radiotherapy (RT) remains controversial. In this multicenter study, we aimed to demonstrate the real-world assessing prognostic factors and the effect of adjuvant treatment modalities in adult patients with HNSTS treated with upfront surgery.MethodsWe included a total of 47 patients who underwent curative-intent resection of a primary HNSTS between 2000 and 2019.ResultsThe median follow-up was 29 months. The median age of patients was 51 years, and 66% of patients were male. The median relapse-free survival (RFS) of the study population was 31 months (range: 1.0-61.1 months), and the median overall survival (OS) was 115 months (range: 60.8-169.2 months). The univariable analysis revealed that treatment modalities showed a significant impact on RFS (p = 0.021); however, no difference was found in its impact on OS (p = 0.137). R0 resection did not showed impact on RFS (p = 0.130), but a significant association was found with OS (p = 0.004). In multivariable analysis, T stage of the tumor (hazard ratio [HR]: 3.834; 95% CI: 1.631-9.008; p = 0.002) and treatment with surgery and sequential RT and CT (HR: 0.115; 95% CI: 0.035-0.371; p < 0.001) were independent factors associated with RFS. R0 resection was independently associated with OS (HR: 4.902; 95% CI: 1.301-18.465; p = 0.019).ConclusionOur study revealed that R0 resection improved OS, and T3-4 stage of tumor was a negative independent factor for RFS in surgically resected HNSTS patients. The use of sequential CT and RT after resection was associated with a better RFS, which emphasizes the importance of multidisciplinary evaluation of the treatment of HNSTS. Randomized prospective studies are needed

Evaluation of head and neck soft tissue sarcoma 8th edition pathologic staging system and proposal of a novel stage grouping system.

The AJCC 8th edition issued a dedicated staging system for head and neck soft tissue sarcomas (HN-STS) with 2 and 4cm tumor cut-off points, as well as a T4 classification based on invasion of adjacent structures. Stage groupings were not provided due to a paucity of data. We identified HN-STS patients undergoing primary surgery without neoadjuvant therapy patients in the Surveillance, Epidemiology, and End Results (SEER) database. We used multivariable analysis to examine adverse prognosticators. Then, using, recursive partitioning analysis (RPA), we established a stage grouping system that was externally validated in the National Cancer Database (NCDB). Multivariable analysis in the SEER cohort (N=546) demonstrated worsened survival with tumors invading adjacent structures (P<0.001) and increasing de-differentiation (P<0.001). There was no prognostic difference based on size for T1-3 tumors; however, when assessed as a continuous variable, a 5cm tumor size cut-off point was predictive of outcome. RPA generated a stage grouping system with the following five-year overall survival: RPA Stage I (pT1-3N0-1G1-2M0) 71.2%, RPA Stage II (pT4abN0-1G1-2M0/pT1-3N0-1G3-4M0) 53.4%, and RPA Stage III (pT4abN0-1G3-4M0) 17.5%. This was successfully externally validated in the NCDB cohort (P<0.001). We confirm the importance of structural invasion and grade and demonstrate that the currently used size cut-off points are not prognostic. We propose a novel stage grouping system. A 5cm tumor size cut-off point for tumor stage should be further evaluated.

Radiation Therapy in Adult Soft Tissue Sarcoma-Current Knowledge and Future Directions: A Review and Expert Opinion.

Simple SummaryRadiation therapy (RT) is an integral part of the treatment of adult soft-tissue sarcomas (STS). Although mainly used as perioperative therapy to increase local control in resectable STS with high risk features, it also plays an increasing role in the treatment of non-resectable primary tumors, oligometastatic situations, or for palliation. This review summarizes the current evidence for RT in adult STS including typical indications, outcomes, side effects, dose and fractionation regimens, and target volume definitions based on tumor localization and risk factors. It covers the different overall treatment approaches including RT either as part of a multimodal treatment strategy or as a sole treatment and is accompanied by a summary on ongoing clinical research pointing at future directions of RT in STS.Radiation therapy (RT) is an integral part of the treatment of adult soft-tissue sarcomas (STS). Although mainly used as perioperative therapy to increase local control in resectable STS with high risk features, it also plays an increasing role in the treatment of non-resectable primary tumors, oligometastatic situations, or for palliation. Modern radiation techniques, like intensity-modulated, image-guided, or stereotactic body RT, as well as special applications like intraoperative RT, brachytherapy, or particle therapy, have widened the therapeutic window allowing either dose escalation with improved efficacy or reduction of side effects with improved functional outcome. This review summarizes the current evidence for RT in adult STS including typical indications, outcomes, side effects, dose and fractionation regimens, and target volume definitions based on tumor localization and risk factors. It covers the different overall treatment approaches including RT either as part of a multimodal treatment strategy or as a sole treatment, namely its use as an adjunct to surgery in resectable STS (perioperative RT), as a primary treatment in non-resectable tumors (definitive RT), as a local treatment modality in oligometastatic disease or as palliative therapy. Due to the known differences in clinical course, general treatment options and, consequently, outcome depending on lesion localization, the main part of perioperative RT is divided into three sections according to body site (extremity/trunk wall, retroperitoneal, and head and neck STS) including the discussion of special applications of radiation techniques specifically amenable to this region. The review of the current evidence is accompanied by a summary on ongoing clinical research pointing at future directions of RT in STS.