Opportunities and Challenges in Soft Tissue Sarcoma Risk Stratification in the Era of Personalised Medicine.

OPINION STATEMENT: Soft tissue sarcomas (STS) are a rare and heterogeneous group of cancers. Treatment options have changed little in the past thirty years, and the role of neoadjuvant chemotherapy is controversial. Accurate risk stratification is crucial in STS in order to facilitate clinical discussions around peri-operative treatment. Current risk stratification tools used in clinic, such as Sarculator, use clinicopathological characteristics and may be specific to anatomical site or to histology. More recently, risk stratification tools have been developed using molecular or immunological data. Combining Sarculator with other risk stratification tools may identify novel patient groups with differential clinical outcomes. There are several considerations when translating risk stratification tools into widespread clinical use, including establishing clinical utility, health economic value, being applicable to existing clinical pathways, having strong real-world performance, and being supported by investment into infrastructure. Future work may include incorporation of novel modalities and data integration techniques.

Genetic Predisposition to Sarcoma: What Should Clinicians Know?

OPINION STATEMENT: Pathogenic germline variants in the setting of several associated cancer predisposition syndromes (CPS) may lead to the development of sarcoma. We would consider testing for a CPS in patients with a strong family history of cancer, multiple primary malignancies, and/or pediatric/adolescent/young adult patients diagnosed with other malignancies strongly associated with CPS. When a CPS is diagnosed in a patient with sarcoma, additional treatment considerations and imaging options for those patients are required. This applies particularly to the use of radiation therapy, ionizing radiation with diagnostic imaging, and the use of alkylating chemotherapy. As data and guidelines are currently lacking for many of these scenarios, we have adopted a shared decision-making process with patients and their families. If the best chance for cure in a patient with CPS requires utilization of radiation therapy or alkylating chemotherapy, we discuss the risks with the patient but do not omit these modalities. However, if there are treatment options that yield equivalent survival rates, yet avoid these modalities, we elect for those options. Considering staging imaging and post-therapy evaluation for sarcoma recurrence, we avoid surveillance techniques that utilize ionizing radiation when possible but do not completely omit them when their use is indicated.

Radiation-induced Sarcoma of the Prostate After Treatment for Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is among the most common pediatric solid malignancies. Fusion-negative, embryonal RMS is the predominant histology among prostate and bladder lesions. Management strategies depend on the clinical stage and risk group. Although the optimal strategy continues to evolve, the field has transitioned from radical upfront resection to organ preservation strategies with multi-modal therapy, including chemotherapy, radiation, and surgery. Survivors frequently develop late complications, including impaired fertility and sexual function, bladder dysfunction, and secondary malignancies. Our case describes an 11-year-old male who developed a radiation-induced prostatic sarcoma. We present a novel surgical technique and highlight the importance of multidisciplinary care.

High-Grade Pleomorphic Sarcoma in Postauricular Keloid Scar After Surgical Excision and Radiation.

Keloid scars can cause significant morbidity to the patient including substantial cosmetic disfigurement, particularly in the head and neck region. Surgical excision followed by immediate postoperative radiation therapy has been shown to be more effective than single modality treatment. Radiation therapy increases risk for radiation-induced malignancy, though very few cases have been reported in the treatment of keloids. We report the case of a patient with a large postauricular keloid treated with excision and immediate post-operative radiation who developed a high-grade pleomorphic sarcoma in the scar bed. Laryngoscope, 134:3143-3145, 2024.

Tandem High-Dose Chemotherapy Increases the Risk of Secondary Malignant Neoplasm in Pediatric Solid Tumors.

PURPOSE: This study aimed to investigate the incidence and risk factors for secondary malignant neoplasms (SMN) in pediatric solid tumors, focusing on the effects of tandem high-dose chemotherapy (HDCT). MATERIALS AND METHODS: Patients (aged < 19 years) diagnosed with or treated for pediatric solid tumors between 1994 and 2014 were retrospectively analyzed. The cumulative incidence of SMN was estimated using competing risk methods by considering death as a competing risk. RESULTS: A total of 1,435 patients (413 with brain tumors and 1,022 with extracranial solid tumors) were enrolled. Seventy-one patients developed 74 SMNs, with a 10-year and 20-year cumulative incidence of 2.680±0.002% and 10.193±0.024%, respectively. The types of SMN included carcinoma in 28 (37.8%), sarcoma in 24 (32.4%), and hematologic malignancy in 15 (20.3%) cases. Osteosarcoma and thyroid carcinoma were the most frequently diagnosed tumors. Multivariate analysis showed that radiotherapy (RT) > 2, 340 cGy, and tandem HDCT were significant risk factors for SMN development. The SMN types varied according to the primary tumor type; carcinoma was the most frequent SMN in brain tumors and neuroblastoma, whereas hematologic malignancy and sarcomas developed more frequently in patients with sarcoma and retinoblastoma, respectively. CONCLUSION: The cumulative incidence of SMN in pediatric patients with solid tumors was considerably high, especially in patients who underwent tandem HDCT or in those who received RT > 2,340 cGy. Therefore, the treatment intensity should be optimized based on individual risk assessment and the long-term follow-up of pediatric cancer survivors.

A Sarcoma Masquerading as a Pseudotumor After Total Hip Arthroplasty: A Case Report.

CASE: There is an increasing emphasis on adverse reactions to metal debris around prosthetic hip implants. We present a case report of a patient with increasing pain around a previous total hip arthroplasty and magnetic resonance imaging findings consistent with a pseudotumor. Serum metal ion levels were not elevated and initial biopsy findings inconclusive. The patient was diagnosed with an extraskeletal chondrosarcoma after revision total hip arthroplasty and subsequently underwent external hemipelvectomy with negative margins. CONCLUSION: This report highlights the importance of remaining vigilant for malignant sarcomas presenting as pseudotumors around hip replacements, particularly in the absence of abnormal metal ion levels or definitive biopsy results.

Feline Injection-Site Sarcoma and Other Adverse Reactions to Vaccination in Cats.

Vaccine-associated adverse events (VAAEs), including feline injection-site sarcomas (FISSs), occur only rarely but can be severe. Understanding potential VAAEs is an important part of informed owner consent for vaccination. In this review, the European Advisory Board on Cat Diseases (ABCD), a scientifically independent board of feline medicine experts, presents the current knowledge on VAAEs in cats, summarizing the literature and filling the gaps where scientific studies are missing with expert opinion to assist veterinarians in adopting the best vaccination practice. VAAEs are caused by an aberrant innate or adaptive immune reaction, excessive local reactions at the inoculation site, an error in administration, or failure in the manufacturing process. FISS, the most severe VAAE, can develop after vaccinations or injection of other substances. Although the most widely accepted hypothesis is that chronic inflammation triggers malignant transformation, the pathogenesis of FISS is not yet fully understood. No injectable vaccine is risk-free, and therefore, vaccination should be performed as often as necessary, but as infrequently as possible. Vaccines should be brought to room temperature prior to administration and injected at sites in which FISS surgery would likely be curative; the interscapular region should be avoided. Post-vaccinal monitoring is essential.

Special features of sarcomas developed in patients with Lynch syndrome: A systematic review.

Lynch syndrome (LS) is a genetic predisposition leading to colorectal and non-colorectal tumors such as endometrial, upper urinary tract, small intestine, ovarian, gastric, biliary duct cancers and glioblastoma. Though not classically associated with LS, growing literature suggests that sarcomas might develop in patients with LS. This systematic review of literature identified 44 studies (N = 95) of LS patients who developed sarcomas. It seems that most sarcomas developed in patients with a germline mutation of MSH2 (57 %) exhibit a dMMR (81 %) or MSI (77 %) phenotype, as in other LS-tumors. Although undifferentiated pleomorphic sarcoma (UPS), leiomyosarcoma, and liposarcoma remain the most represented histologic subtype, a higher proportion of rhabdomyosarcoma (10 %, especially pleomorphic rhabdomyosarcoma) is reported. Further studies are required to better characterize this sub-population.

Radiation-induced sarcomas following childhood cancer - A Canadian Sarcoma Research and Clinical Collaboration Study (CanSaRCC).

BACKGROUND: Radiation-induced sarcoma (RIS) is a late toxicity of radiation therapy (RT) usually associated with poor prognosis. Due to ongoing improvements in childhood cancer treatment and patient outcomes, RIS may become more prevalent notwithstanding evolving indications for RT. Due to limited reported studies, we sought to review our experience with RIS in survivors of pediatric cancer. METHODOLOGY: Data were collected on RIS patients following treatment for childhood cancer (initial diagnosis <18 years) identified in the CanSaRCC database. Additionally, details on the protocol guidance at time of treatment were compared with current guidelines for the same disease. RESULTS: Among 12 RIS identified, median age at initial diagnosis was 3.5 years (range 0.16-14) and the latency from RT to RIS diagnosis was 24.5 (range 5.4-46.2) years. Initial diagnoses included neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, Wilms tumor, retinoblastoma and Hodgkin's Lymphoma. RIS histologies included osteosarcoma and soft tissue sarcomas. In comparison to protocols followed at time of diagnosis to current ones (2022), 7/12 (58%) patients would have required RT. RIS treatment included chemotherapy, radiation and surgery in 3/11 (27%), 10/11 (90%), and 7/11 (63%) patients, respectively. With a median follow-up time of 4.7 years from diagnosis of RIS, 8 (66%) patients were alive and 4 (33%) had died of progressive RIS. CONCLUSION: RIS is a serious late effect of radiotherapy in childhood cancer; however, radiation remains an integral component of primary tumor management and requires participation from a specialized multi-disciplinary team, aiming to mitigate RIS and other potential late effects.

Clinical and Pathologic Characterization of 94 Radiation-Associated Sarcomas: Our Institutional Experience.

Radiation-associated sarcomas are an uncommon complication of therapeutic radiation. However, their prevalence has increased with the more widespread use of this treatment modality. The clinical, pathologic and genetic characteristics of radiation-associated sarcomas are not fully understood. In this study we describe the features of 94 radiation-associated sarcomas reviewed at our institution between 1993 and 2018, evaluate their overall survival (OS) and progression-free survival (PFS) outcomes, and compare them with their sporadic counterparts reviewed within the same time period. Histologic subtypes of all radiation-associated sarcomas included 31 (33%) undifferentiated sarcomas, 20 (21%) osteosarcomas, 17 (18%) angiosarcomas, 10 (11%) malignant peripheral nerve sheath tumor (MPNST), 9 (10%) leiomyosarcomas, 4 (4%) myxofibrosarcomas, and 3 (3%) rhabdomyosarcomas. Six patients had a documented cancer predisposition syndrome. The most common preceding neoplasms included adenocarcinoma (47%) and squamous cell carcinoma (19%), with a mean latency of 13 years. Multivariable Cox survival analysis demonstrated that advanced stage at diagnosis based on pT category (AJCC eighth edition) and fragmented resection were associated with worse survival outcomes. In addition, there was a statistically significant difference in PFS between radiation-associated undifferentiated sarcomas and MPNST when compared to their sporadic counterparts using the Kaplan-Meier method and Log-rank analysis. Overall, our study shows that radiation-associated sarcomas comprise a wide clinico-pathologic spectrum of disease, with a tendency for aggressive clinical behavior. This study further delineates the understanding of these uncommon diseases. Future studies are necessary to better understand the genetic and epigenetic changes that drive the differences in behavior between these tumors and their sporadic counterparts, and to offer better treatment options.

Incidence of radiation-associated sarcoma after breast-conserving surgery plus radiation.

BACKGROUND: Radiation-associated sarcoma (RAS) is a rare sequela of radiotherapy. Radiotherapy modalities for breast conservation and radiation treatment (BCT) have changed over time. We sought to determine if the incidence of RAS after BCT has changed over time. METHODS: We identified breast cancer survivors (diagnosed 1988-2012) treated with BCT within the SEER database. We excluded patients with prior cancer, <1-year follow-up/survival, and nonexternal beam radiation (n = 276 301). We identified patients with a subsequent chest sarcoma diagnosis. The primary predictor variable was a 5-year period of breast cancer diagnosis year (1988-1992, 1993-1997, etc.). The incidence of sarcoma was estimated by the Kaplan-Meier method, censoring at sarcoma diagnosis, death, or last follow-up (available through December 2017). Given the known latency of RAS, we used Joinpoint analysis to identify the time point at which RAS incidence significantly increased (start of the analytic window). A log-rank test assessed differences in RAS incidence by diagnosis year. RESULTS: The incidence of RAS was 0.03% at 5 years (95% confidence interval [CI]: 0.03-0.04) and 0.16% at 10 years (95% CI: 0.14-0.18). No statistical difference in RAS incidence by diagnosis year was observed (p = 0.2). CONCLUSIONS: RAS remains a rare but persistent sequela after BCT. As new radiation modalities become more common, ongoing surveillance is necessary to track these rare events.

Primary hyperparathyroidism and sarcoma: A case report and literature review.

ABSTRACT: The relationship between primary hyperparathyroidism (PHPT) and bone sarcoma is debatable, especially after wider use of teriparatide treatment, concerns have intensified on the issue. Extensive search in English literature revealed 10 cases reported having PHPT and sarcomas. Besides, three cases of bone sarcoma occurring after teriparatide treatment had been reported. Hereby, we report a 51-year-old woman with a prolonged history of PHPT. She was diagnosed with chondrosarcoma 9 years after refusal and lack of treatment for PHPT. She was cured surgically for both chondrosarcoma and parathyroid adenoma at 1-year interval. So far, large cohorts did not show an increase in the incidence of bone sarcomas in PHPT. Several case observations, including the current one, as well as data from in vitro and rat studies, pointed out prolonged parathormone exposure, may be a risk for bone sarcomas. Under these circumstances, a safer attitude on individual basis would be the prevention of prolonged parathormone exposures.

Family cancer history and smoking habit associated with sarcoma in a Japanese population study.

Sarcoma is a rare cancer, and little is known about the etiology, lifestyle epidemiology, and actual circumstances of treatment in hospitals in Japan. Understanding these issues is essential for the effective prevention and treatment of sarcoma. We therefore investigated the incidence of a personal and family cancer history in a total of 1320 sarcoma patients at the National Cancer Center Hospital. In addition, obesity, hypertension, dyslipidemia, diabetes mellitus, drinking, smoking, age and sex were compared in a descriptive study of 1159 of these sarcoma patients who were ≥ 20 years of age, and 7738 controls derived from the National Health and Nutrition Examination Survey in Japan. A total of 8% of sarcoma patients had a personal history of another cancer, and 30% of soft tissue sarcoma patients had a family cancer history in a first-degree relative (malignant peripheral nerve sheath tumor, 52%; leiomyosarcoma, 46%). A smoking habit was associated with the development of sarcoma (odds ratio [OR], 2.05; 95% confidence interval, 1.78-2.37; p < 0.01). According to the histology, the ORs for undifferentiated pleomorphic sarcoma (UPS) of bone, UPS of soft tissue, and liposarcoma were 5.71, 3.04, and 2.92, respectively. A family cancer history may be associated with certain soft tissue sarcomas, and a smoking habit was significantly associated with the development of sarcomas; however, further studies are necessary.

Containment Bag Use Among Women Who Undergo Hysterectomy With Laparoscopic Power Morcellation.

OBJECTIVE: To estimate trends in use of laparoscopic power morcellators in women undergoing minimally invasive hysterectomy and to examine use of containment systems in these patients in relation to safety guidance from the U.S. Food and Drug Administration (FDA). METHODS: We examined data that were recorded in the Premier Healthcare Database from patients who underwent laparoscopic supracervical hysterectomy from 2010 to 2018. Patients were stratified based on use of laparoscopic power morcellators. The cohort was further stratified as either pre-FDA guidance (2010 quarter 1-2014 quarter 1) or post-FDA guidance (2014 quarter 2-2018 quarter 2). Interrupted time series analyses were performed to determine the effect of FDA guidance on the use of laparoscopic power morcellators and containment bags. RESULTS: Among 67,115 patients, laparoscopic power morcellator use decreased from 66.7% in 2013 quarter 4 to 13.3% by 2018 quarter 2. The likelihood of laparoscopic power morcellator use decreased by 9.5% for each quarter elapsed in the post-FDA warning period (risk ratio [RR] 0.91, 95% CI 0.90-0.91). Containment bag use rose from 5.2% in 2013 quarter 4 to 15.2% by 2018 quarter 2. The likelihood of containment bag use increased by 3% for each quarter elapsed in the post-FDA warning period (RR 1.03, 95% CI 1.02-1.05). Among women who had laparoscopic power morcellator use, uterine cancers or sarcomas were identified in 54 (0.17%) before the FDA guidance compared with seven (0.12%) after the guidance ( P =.45). Containment bags were used in 11.1% of women with uterine cancers or sarcomas before the FDA guidance compared with 14.3% after the guidance ( P =.12). The perioperative complication rate was 3.3% among women who had laparoscopic power morcellator use without a containment bag compared with 4.5% ( P =.001) in those with a containment bag (aRR 1.35, 95% CI 1.12-1.64). CONCLUSION: Use of laparoscopic power morcellators has decreased over time. Containment bag use increased after the FDA's 2014 guidance; however, most procedures employing laparoscopic power morcellators are still performed without a containment bag.

Investigating the role of signal transducer and activator of transcription 3 in feline injection site sarcoma.

BACKGROUND: Feline injection-site sarcomas (FISSs) are malignant mesenchymal tumors of different histotypes. The pathogenesis of FISS has been correlated with chronic inflammation, resulting in neoplastic transformation. Activation of the Janus kinase-signal transducer and activator of transcription 3 (STAT3) have been demonstrated to play a critical role in tumor development by regulating signaling pathways involved in cell proliferation, survival, metastasis, and angiogenesis in human medicine. To characterize the role of STAT3 in FISS, we first detected STAT3 and phosphorylated STAT3 in formalin-fixed and paraffin-embedded (FFPE) FISS tissues using immunohistochemical staining. RESULTS: STAT3 was detected in 88.9% (40/45) of FISS cases, and phosphorylated STAT3 was detected in 53.3% (24/45) of cases. However, the expression levels of both forms of STAT3 were not correlated with tumor grade. To study the role of STAT3 in tumor survival, two primary cells derived from FISSs of two cats exhibiting consistent immunophenotypes with their parental FFPE tissues were established. A dose-dependent inhibitory effect on cell proliferation was observed in both primary FISS cells treated with the STAT3 inhibitor, 5-hydroxy-9,10-dioxo-9,10-dihydroanthracene-1-sulfonamide. CONCLUSIONS: The STAT 3 may play an important role in the tumorigenesis of FISS and be a potential molecular therapeutic target for FISS.

Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: a phase 2 PEMBROSARC trial cohort.

Immune checkpoint inhibitors (ICIs) show limited clinical activity in patients with advanced soft-tissue sarcomas (STSs). Retrospective analysis suggests that intratumoral tertiary lymphoid structures (TLSs) are associated with improved outcome in these patients. PEMBROSARC is a multicohort phase 2 study of pembrolizumab combined with low-dose cyclophosphamide in patients with advanced STS (NCT02406781). The primary endpoint was the 6-month non-progression rate (NPR). Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety. The 6-month NPR and ORRs for cohorts in this trial enrolling all comers were previously reported; here, we report the results of a cohort enrolling patients selected based on the presence of TLSs (n = 30). The 6-month NPR was 40% (95% confidence interval (CI), 22.7-59.4), so the primary endpoint was met. The ORR was 30% (95% CI, 14.7-49.4). In comparison, the 6-month NPR and ORR were 4.9% (95% CI, 0.6-16.5) and 2.4% (95% CI, 0.1-12.9), respectively, in the all-comer cohorts. The most frequent toxicities were grade 1 or 2 fatigue, nausea, dysthyroidism, diarrhea and anemia. Exploratory analyses revealed that the abundance of intratumoral plasma cells (PCs) was significantly associated with improved outcome. These results suggest that TLS presence in advanced STS is a potential predictive biomarker to improve patients' selection for pembrolizumab treatment.

Subsequent malignant neoplasms in the pediatric age in retinoblastoma survivors in Argentina.

BACKGROUND: Retinoblastoma survivors in low- and middle-income countries are exposed to high-intensity treatments that potentially place them at higher risk of early subsequent malignant neoplasms (SMNs). METHODS: We followed 714 (403 [56.4%] nonhereditary and 311 [43.5%] hereditary) retinoblastoma survivors diagnosed from August 1987 to December 2016, up to the age of 16 years. We quantified risk of SMNs with cumulative incidence (CI) and standardized incidence ratios (SIR) analysis. Multivariate regression Cox model was used to determine the association of treatments and risk of SMNs. RESULTS: Median follow-up was of 9 years (range: 0.18-16.9) and 24 survivors (3.36%) developed 25 SMNs (n = 22 hereditary, n = 2 nonhereditary). SMNs included sarcomas (osteosarcomas, Ewing sarcomas, rhabdomyosarcomas; n = 12), leukemias (n = 5), and central nervous system tumors (CNS; n = 3). All cases of acute myeloid leukemia (AML) and most of Ewing sarcomas occurred within 5 years of retinoblastoma diagnosis. The type of SMN was the main indicator of mortality (five of five patients with leukemias, six of 12 with sarcomas, and zero of three with CNS tumors died). Compared to the general population, radiation increased the risk of Ewing sarcoma in hereditary survivors by 700-fold (95% CI = 252-2422.6) and chemotherapy increased the risk of AML by 140-fold (95% CI = 45.3-436). The CI of SMNs for hereditary survivors was 13.7% (95% CI = 8.4-22.1) at 15 years. CONCLUSION: Retinoblastoma survivors from Argentina are at higher risk of developing SMNs early in life compared to the general Argentinean population, especially those treated with radiation plus chemotherapy. AML and Ewing sarcoma presented within 5 years of retinoblastoma diagnosis are associated with chemotherapy and radiation exposure.

Treatment related factors associated with the risk of breast radio-induced-sarcoma.

BACKGROUND AND PURPOSE: The Radiation Induced Sarcoma (RIS) is a rare but serious adverse event following radiotherapy (RT). Current RT techniques are more precise, but irradiate a larger volume at a low dose. This study aimed to describe radiation characteristics in a large series of patients suffering from RIS. MATERIALS AND METHODS: Patient-representative voxel-based anthropomorphic phantoms were used to reconstruct patient-specific RT fields for 125 patients diagnosed with RIS after primary breast cancer. For each patient, the location of the RIS onset site was determined and transferred onto the phantom as a contour. Using a treatment planning system (TPS), the dose distribution on the RIS in the phantom was calculated. RESULTS: The mean dose (Dmean) received in the area where RIS subsequently developed was 47.8 ± 11.6 Gy. The median dose in the zones where RIS later developed ranged from 11 Gy to 58.8 Gy. The median time from RT to RIS development was 8 years (range 2-32 years). Analysis for predictors of time to radiation-induced sarcoma development highlighted a significant impact of age of patient during the RT whereas in multivariable analysis chemotherapy and hormonotherapy for primary breast cancer were not associated with a significant difference in time to diagnosis of RIS. CONCLUSIONS: This study highlights that the dose received by the tissue in which the RIS developed was almost 47 Gy. These results are encouraging for the use of new RT techniques increasing volumes receiving low doses, without fear of an excess of RIS over the next 10 years.

Total-Body Irradiation Is Associated With Increased Incidence of Mesenchymal Neoplasia in a Radiation Late Effects Cohort of Rhesus Macaques (Macaca mulatta).

PURPOSE: Cancer is a severe delayed effect of acute radiation exposure. Total-body irradiation has been associated with an increased risk of solid cancer and leukemia in Japanese atomic bomb survivors, and secondary malignancies, such as sarcoma, are a serious consequence of cancer radiation therapy. The radiation late effects cohort (RLEC) of rhesus macaques (Macaca mulatta) is a unique resource of more than 200 animals for studying the long-term consequences of total-body irradiation in an animal model that closely resembles humans at the genetic and physiologic levels. METHODS AND MATERIALS: Using clinical records, clinical imaging, histopathology, and immunohistochemistry, this retrospective study characterized the incidence of neoplasia in the RLEC. RESULTS: Since 2007, 61 neoplasms in 44 of 239 irradiated animals were documented (18.4% of the irradiated population). Only 1 neoplasm was diagnosed among the 51 nonirradiated controls of the RLEC (2.0%). The most common malignancies in the RLEC were sarcomas (38.3% of diagnoses), which are rare neoplasms in nonirradiated macaques. The most common sarcomas included malignant nerve sheath tumors and malignant glomus tumors. Carcinomas were less common (19.7% of diagnoses), and consisted primarily of renal cell and hepatocellular carcinomas. Neoplasia occurred in most major body systems, with the skin and subcutis being the most common site (40%). RNA analysis showed similarities in transcriptional profiles between RLEC and human malignant nerve sheath tumors. CONCLUSIONS: This study indicates that total-body irradiation is associated with an increased incidence of neoplasia years following irradiation, at more than double the incidence described in aging, nonirradiated animals, and promotes tumor histotypes that are rarely observed in nonirradiated, aging rhesus macaques.

Role of Virus-Directed Therapy in Soft Tissue Sarcoma.

OPINION STATEMENT: Bone and soft tissue sarcoma are rare cancers of mesenchymal origin with the characteristics of heterogeneity and diversity that account for less than 1% of solid malignant cancers. Conventional chemotherapy remains standard of care with response rates of 10-15% that are usually dependent on histologic subtype as some subtypes are chemotherapy resistant. There remains a large unmet clinical need for new and novel options promoting the development of promising therapeutic options such as immunotherapy. With more than 80 different subtypes, the heterogeneity of sarcoma requires thoughtful clinical trial design. In the sarcoma field, recent breakthroughs have occurred in the context of histology-specific approach based on underlying tumor biology. To that end, immunotherapy approaches will need to take a similar approach. Oncolytic viruses (OVs) have emerged as a promising treatment for many solid tumors and shown encouraging results in sarcoma. This review mainly focuses on collective clinical data highlighting the role of OVs as immunotherapy being used in soft tissue sarcoma (STS) and bone sarcomas. Combining OVs with T cell-activating checkpoint inhibition, adoptive cell therapy or targeted therapies may yield increased potency, improve antitumor efficacy of oncolytic virotherapy, and offer a new prospect for the treatment of sarcoma.