bluuebunny/crossref_metadata_2025 huggingface dataset:
The prevalence of fibroadenoma-like areas in malignant phyllodes tumors of the breast: A retrospective analysis from a referral center.
Authors: Valenza Carmine , Olmeda Edoardo , Porta Francesca Maria , De Pas Tommaso Martino , Gaeta Aurora , Castellano Grazia , Santoro Celeste , Battaiotto Elena , Chiappini Giulia , Trapani Dario , Coppola Sara , Conforti Fabio , Mattar Denise , Gandini Sara , Veronesi Paolo , Guerini Rocco Elena , Pennacchioli Elisabetta , Curigliano Giuseppe
Published: June 2024

e23522

Background: Malignant phyllodes tumors of the breast (B-MPT) are supposed to arise de novo or to derive from a fibroadenoma/benign phyllodes tumor ("secondary"), through a MED12-dependent pathway. Secondary B-MPTs may be associated to better outcomes: both the history of previous fibroadenomas and the presence of MED12 mutations were demonstrated to be associated to improved recurrence-free survival, in small case series. We assessed the prevalence and the prognostic value of fibroadenoma-like areas (FLA) in the context of B-MPTs, which were described as potentially associated with MED12 mutations (Pareja, 2017). Methods: Single-center, retrospective, translational study conducted at European Institute of Oncology. Consecutive patients aged 18 years old or more, with non-metastatic B-MPT, who underwent surgery from Jan 2000 to Dec 2021, were included. FLA were defined as intracanalicular, pericanalicular or myxoid areas of low stromal cellularity, lacking cytologic atypia and mitotic activity. All specimens were reviewed by three pathologists. The endpoints were the cumulative incidences of distant and local recurrences. Results: 89 patients were included (Table). After a median follow-up of 6.4 years, 18 and 14 local and distant recurrences were registered, respectively. The cumulative incidences at 5-years of local and distant recurrences were 19% (95% Confidence Interval [CI], 11–28%) and 11% (95%CI, 5–18%). 47% of tumors had FLA, which were associated with lower ( < 15/10HPF) mitoses (p = 0.05). No pathologic feature was associated with distant or local relapse. The presence of FLA areas was associated with fewer local recurrences, without reaching the statistical significance (p = 0.14); no difference in terms of distant recurrences emerged (p = 0.61). Conclusions: 47% of B-MPTs are characterized by FLAs, which are associated with a lower mitotic count. The association between FLAs and fewer local recurrences did not reach the threshold for statistical significance, probably due to the small number of events. The prognostic role of FLAs needs to be assessed in a larger cohort and may potentially enhance the selection of patients deserving postoperative treatment intensification. [Table: see text]
Epithelioid hemangioendothelioma: Real-world data about a rare entity in a Portuguese tertiary cancer center.
Authors: Cabral Sara , Freitas Rita , Dunões Inês , Santos Miguel , Pereira Carolina , Pereira Patricia M. , Gouveia Emanuel Jose , Ferreira Margarida , Vaz Fatima H
Published: June 2024

e23525

Background: Epithelioid hemangioendothelioma (EHE) is a rare entity of vascular origin, whose malignant potential is uncertain. It can develop in different locations, most commonly bone, liver and lungs. Since there are no specific associated symptoms, the diagnosis is often incidental. Due to its rarity there is no standard treatment. Our aim was to evaluate the demographic characteristics, course of disease and treatment effectivity in EHE patients in our institution in the last 25 years. Methods: We performed a retrospective study of all patients with EHE treated at our institution between January/1997 and September/2023. Statistical analysis was performed using SPSS. Normal distribution was checked using Shapiro-Wilk test. Results: From the 23 patients diagnosed with hemangioendothelioma, 20 were epithelioid (EHE) and 3 were other type. Of note, all the biopsies were centrally reviewed and since 2022 the diagnosis were confirmed with WWTR1 rearrange (3 out of 5 patients were positive). From the total number of EHE, the majority were women (n = 13, 65%). The mean age at diagnosis was 46 ± 22 years-old. Seven (35%) were asymptomatic and 13 (65%) had metastatic disease at diagnosis, all of them with lung metastasis, 2 (10%) with hepatic metastasis and 2 (10%) with bone metastasis. The most frequent primary locations were lungs (n = 5, 25%); soft tissue (n = 5, 25%), and liver (n = 4, 20%), followed by bone (n = 2,10%), stomach (n = 1, 5%), parotid gland (n = 1, 5%), superior vena cava (n = 1, 5%) and one case of unknown primary EHE. The majority of tumors were multifocal (12, 60%). Eight (40%) patients were under active surveillance, 4 (20%) underwent surgery with or without adjuvant radiotherapy, 2 (10%) underwent systemic treatment with tyrosine kinase inhibitor (pazopanib) and 2 (10%) chemotherapy (paclitaxel, doxorubicin). Two (10%) patients received a liver transplant and 2 (10%) patients underwent multiple treatment modalities. With a median follow-up of 30.89 months (3-253), 6 (30%) patients were dead at the time of analysis and mean overall survival was 142.3 months. Patients with an angiosarcoma differentiation had significantly worse mean survival outcomes (p < 0.001), 7.9 ± 4.5 months vs. 158.9 ± 37.2 months. Conclusions: The biological behavior of these tumors remains uncertain. In our cohort, the majority of patients presented with distant metastasis, but the course of the disease was very heterogeneous, regardless of the primary or metastatic site or the treatment modality. Our data emphasizes that this disease should be managed on a case-by-case basis, with a multidisciplinary approach and tailored treatment and surveillance.
Pathologic complete response in patients with localized soft tissue sarcoma treated with neoadjuvant therapy and its correlation with clinical outcomes: A systematic review.
Authors: Kyriazoglou Anastasios , Boulouta Anna , Kotsantis Ioannis , Economopoulou Panagiota , Kirkasiadou Maria , Anastasiou Maria , Pantazopoulos Anastasios , Moutafi Myrto , Gavrielatou Niki , Zazas Evangelos , Nasiadi Chrysanthi , Kavourakis George John , Psyrri Amanda
Published: June 2024

e23529

Background: Soft tissue sarcomas (STS), comprising approximately 1% of adult solid malignancies, are primarily treated with surgery, with the choice of perioperative treatment being a challenging and highly individualized decision. Clinical trials assessing neoadjuvant modalities in STS predominantly use clinical outcomes or radiologic response as endpoints, with pathologic complete response (pCR) typically not being employed as a designated study endpoint. There is a growing inclination towards neoadjuvant treatment for STS. While pCR serves as a crucial marker guiding treatment decisions in other neoplasms like breast cancer and urothelial cancer, it is not yet used in a similar setting for STS. Our systematic review aimed to assess the rates of pCR in clinical trials of different neoadjuvant modalities for STS and its correlation with patient clinical outcomes. Methods: A systematic literature search was conducted, with eligibility criteria being prospective or retrospective, phase I, II or III trials testing neoadjuvant treatments for STS. Neoadjuvant treatments were chemotherapy, radiotherapy, TKIs or combinations of the above. 23 studies were included, from which data regarding rates of pCR with each treatment, as well as the correlation of pCR with clinical outcomes, were retrieved. Results: Of the 23 trials included, seven did not assess pCR. In the remaining 16 trials, pCR was defined by either ≥90% or ≥95% pathologic necrosis in the tumor specimen. The percentage of patients who achieved pCR ranged from 8 to 58%. Most of these trials did not assess an association between pCR and clinical outcomes. However, among those investigating this correlation, a positive association was identified between pCR and both 5-year disease-specific survival (DSS) and 5-year overall survival (OS). Table 1 summarizes the eight trials that sought to correlate rates of pCR with clinical outcomes. Conclusions: Our findings indicate pCR variability across different neoadjuvant treatments for STS and a possible positive correlation with patient outcomes. Consequently, we propose considering pCR as a surrogate endpoint in future prospective trials for STS that might guide further treatment decisions. [Table: see text]
Correlation of ctDNA with hematologic ratios (NLR, MLR, PLR, ELR) in predicting disease progression in soft tissue sarcomas among non-Hispanic Whites and Hispanics: Single-center experience.
Authors: Braat Jonathan , Zamora DIana , Ikram Waleed , Behara Murali Ranjani , Azevedo Chelsea , Dinh Han , Patel Shyamal , Wiseman Jason T. , Gonzalez Velez Miguel
Published: June 2024

e23536

Background: Circulating tumor DNA (ctDNA) has gained prominence as a potential indirect marker for minimal residual disease (MRD) in various cancers, including soft tissue sarcomas (STS). Previous studies have suggested that indirect hematologic ratios – such as Neutrophil-Lymphocyte Ratio (NLR), Monocyte-Lymphocyte Ratio (MLR), Platelet-Lymphocyte Ratio (PLR), and Eosinophil-Lymphocyte Ratio (ELR) may correlate with worse outcomes. We sought to evaluate the correlation of NLR, MLR, PLR and ELR in a real world cohort of Non-Hispanic Whites (NHW) and Hispanics (H) with advanced STS. Methods: We performed a retrospective chart review at Dignity Health Cancer institute using our Electronic Medical Records (EMR) and Signatera™ assay to obtain our data points. Inclusion criteria were STS patients of all ages and stages of disease with complete records. We reviewed 33 patient charts, 14 NHW and 19 H patients. Of the NHW population, 11 were male (M) and 3 females (F). For the H population, 14 were M, and 5 were F. We utilized Spearman's rank correlation coefficient to assess monotonic relationships between ct-DNA levels and the hematologic ratios. ct-DNA was quantified through standardized assays per Protocol, with the resultant values treated as continuous variables in our statistical analyses. Power considerations, based on expected effect sizes and type I error rate adjustments were performed. Results: The Spearman’s correlation coefficients and p-values indicated varied associations across ethnic groups. For NHW, the correlations were generally weak and non-significant (NLR: r = 0.18, p = 0.54; MLR: r = -0.04, p = 0.89; PLR: r = 0.35, p = 0.21; ELR: r = 0.001, p = 1.00). Conversely, in the Hispanic cohort, stronger and statistically significant correlations were observed, particularly with NLR (r = 0.78, p < 0.0001) and MLR (r = 0.70, p < 0.001). Overall, the correlations across the entire study population did not reach statistical significance. Conclusions: This study revealed notable racial variations, particularly in the H population, in the relationship between ctDNA levels and hematologic ratios. The noteworthy associations found with NLR (r = 0.78, p < 0.0001) and MLR (r = 0.70, p < 0.001) highlight the possible usefulness of these ctDNA and these indirect biomarkers in assessing disease status in STS. These findings suggest the possibility of using hematologic ratios, particularly in the Hispanic population, as markers of disease progression similar as ctDNA. Hematologic ratios are more easily accessible to the general population compared to ctDNA in many underserved countries and communities. Future studies with larger cohorts are need to further analyze its validity.
Clinical profile and response to adjuvant treatments in patients with follicular dendritic cell sarcoma in the United States: Insights from SEER analysis.
Authors: Vojjala Nikhil , Yadav Sumeet Kumar , Aldecoa Kim Abbegail Tan , Liu Bolun , Hussein Guleid , Azar Ibrahim , Yadlapalli Sri , Krishnamoorthy Geetha , Goodman Judie R.
Published: June 2024

e23537

Background: Follicular Dendritic Cell Sarcoma (FDCS) is a rare, indolent, low-grade sarcoma known for local recurrences managed primarily by surgery. The role for adjuvant therapy has not been established for either radiation or chemotherapy. We aimed to comprehensively analyze clinical and epidemiological profiles and responses to treatment in these patients. Methods: This is a retrospective study using the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Result (SEER) database. Cases of FDCS between 2001 to 2022 were identified utilizing the International Classification of Diseases for Oncology edition 3 (ICD-O-3) code 9758/3. Only adults > 18 years of age and diagnosed by positive histology or cytology were included. Descriptive statistics were used to describe demographic and tumor characteristics. Logistic regression was used to identify the factors influencing survival. Kaplan-Meier method was used to plot survival based on different treatment regimens and stages. Results: A total of 168 patients with FDCS were identified, with more than 50% of the patients ≥ 50 years of age. The mean age at diagnosis was 52.6 years, 56% were female, and 74.4% were white. Most of the patients had localized disease (63.7%), 17.9% had distant disease, and the remaining had unknown stages. About 90% of the patients underwent surgery, with 41% receiving local tumor excision. In Univariate analysis, older age, and distant disease were found to have poor outcomes. Surgery, irrespective of stage, was found to improve overall Survival (Table 1). While chemotherapy and distant disease had poor outcomes in univariate analysis, they were not statistically significant in multivariate analysis. The majority of the patients who received chemotherapy alone without surgical intervention had distant disease, explaining the poor outcome seen in univariate analysis. Among 107 patients with localized disease, 41 patients (41.1%) underwent only surgery and 43 patients (40.1%) received adjuvant therapy (either chemotherapy or radiation vs both) along with surgery. 5-year overall survival was significantly lower in patients who received adjuvant therapy. (88.4% vs 68.4%, p = 0.001). Conclusions: In conclusion, FDCS has a fair overall 5-year survival with surgery alone. Patients with localized disease, who received adjuvant therapies had poor survival outcomes as compared to the surgery-only group owing to disease burden. Large prospective studies are required to properly evaluate the benefit of adding chemotherapy or radiotherapy in resectable disease.
Real world effectiveness of immunotherapy combined with anti-angiogenic therapy in patients with anthracycline-resistant soft tissue sarcomas.
Authors: He Mengye , Xu Suzhen , Wang Xiaoting , Zhang Xiaochen , Shen Peng
Published: June 2024

e23543

Background: Soft tissue sarcomas are a heterogeneous group of malignant tumors of mesenchymal origin with more than 50 histologic subtypes. They have distinct molecular, genetic and clinical features and account for 1% of adult malignancies, the most common being liposarcoma, undifferentiated pleomorphic sarcoma and leiomyosarcoma. Immune checkpoint inhibitors (ICIs) have limited efficacy in sarcomas compared to other solid tumors; however, they have shown some activity in certain subtypes. The use of immunotherapy in sarcoma faces many challenges due to tumor heterogeneity, scarcity of therapeutic antibodies and chimeric antigen receptors to target antigens in sarcoma subtypes. However, combining ICIs with other therapies seems to improve the therapeutic efficacy to some extent. Antiangiogenic targeted therapy has been recommended by major guidelines as the treatment of choice for second-line soft tissue sarcomas. However, there are limited results from large clinical studies on whether immunotherapy combined with antiangiogenic therapy improves the efficacy. Methods: In this real-world single-center retrospective cohort study conducted at the First Affiliated Hospital of Zhejiang University School of Medicine, the efficacy of immunotherapy combined with antivascular therapy was assessed by progression-free survival (PFS) and overall survival (OS). Safety was assessed using the Common Terminology Criteria for Adverse Events version 5.0. Results: In this study, we enrolled a total of 21 eligible patients, of which 6 were liposarcoma, 4 were leiomyosarcoma, 4 were rhabdomyosarcoma, and 7 were other types. The immunotherapy used in all patients was anti-PD-1 antibody, with bevacizumab as the antivascular therapy drug in four of them and antiangiogenic tyrosine kinase inhibitors in the others. 12(57%) patients had received one-line therapy, 9 (43%) had received ≥ second-line therapy. Median progression-free survival (mPFS) was 5.5 months and median overall survival (mOS) 16.1 months in the total population. mPFS was significantly longer in 2nd-line V.S. ≥3rd-line patients (9.6 months V.S. 3.1 months, P = 0.0007), with a tendency to be prolonged mOS in 2nd-line treatment (16.1 months V.S. 9.3 months), but with no statistically significant difference. The most common grade ≥3 adverse events were hypertension, hand-foot syndrome, and abnormal thyroid function. Conclusions: This study confirms that immunotherapy combined with antiangiogenic therapy is effective and tolerable in anthracycline-resistant soft tissue sarcomas in the real world.It is possible that use in the second line may lead to better efficacy than use in multiple lines, and more clinical studies are expected.
A phase 2 study of regorafenib in metastatic/unresectable, refractory synovial sarcomas.
Authors: Fernandes Sanal Canute , Rastogi Sameer , Shamim Shamim Ahmed , Barwad Adarsh , Panday Rambha , Dhamija Ekta
Published: June 2024

e23551

Background: Current therapeutic options for advanced synovial sarcomas remain limited. Adoptive T-cell therapies against NY-ESO-1 and MAGE-4 benefit a subset of patients, but is of limited value in Asian patients due to the absence of the HLA-A*02 genotype. Methods: The trial had a single arm, Simon two-stage design that included patients with advanced synovial sarcomas who had progressed on 2 lines of therapy, one of which could be an anti-VEGF therapy. Regorafenib was administered orally in a continuous regimen with 80mg and 120 mg doses on alternate days. The primary end point was 3-month progression-free rate (PFR). A 3-month PFR of greater than 40% was taken to be a marker of drug efficacy. Secondary end points included median PFS, OS and safety analysis. Quality of life assessment was carried out at baseline and at 3 months using the EORTC C-30 questionnaire. Radiological responses were assessed using RECIST 1.1 criteria after independent review by 2 radiologists. Results: A total of 22 patients were included in the study during the period from January 2022 to December 2023 with baseline characteristics as shown in Table 1. 18 patients were eligible for assessment of the primary outcome. The 3-month PFR with regorafenib was 57% with an ORR of 5%. At a median follow up of 9 months, the median PFS was 5.0 (2.9-7.0) months, and the median OS was 10.0 (7.8-11.2) months. In an exploratory analysis, the subset of patients previously exposed to pazopanib showed a 3-month PFR of 46% and a median PFS of 3 months. The grade ¾ toxicities seen included HFSR (52%), diarrhea (5%) and oral mucositis (5%). The quality-of-life analysis showed symptom burden to be highest in the fatigue, pain and financial difficulties domain at baseline. No worsening of symptom burden scores was seen over the study period. The global health status score showed a numerical improvement at 3 months. Conclusions: The study had a significant number of patients with poor PS. Regorafenib in the above-mentioned dosing regimen demonstrated meaningful clinical activity in a heavily pre-treated population of patients with synovial sarcoma, including those previously exposed to pazopanib, with a preserved quality of life. The treatment was associated with manageable toxicities and no new safety signals, albeit with higher HFSR rates. [Table: see text]
Clinical features, molecular findings, and clinical outcomes of follicular dendritic cell sarcoma.
Authors: Yi Dongni , Rech Karen , Lester Scott , Breen William , Zanwar Saurabh , Ruan Gordon , Robinson Steven Ian , Okuno Scott H. , Siontis Brittany L. , Garrity James , Kimball Brittany , Ravindran Aishwarya , Shah Mithun Vinod , Bennani Nabila Nora , Goyal Gaurav , Go Ronald S. , Abeykoon Jithma P.
Published: June 2024

e23554

Background: Follicular dendritic cell sarcoma (FDCS) is a low-grade neoplasm arising from follicular dendritic cells. Its diagnosis is challenging due to its extreme rarity, and the optimal management remains unknown. Methods: We conducted a retrospective study of FDCS patients (pts) seen at Mayo Clinic, MN since 2018. Time to event analyses were done from the time of diagnosis. Results: Ten pts with FDCS were identified (Table). The median age was 60 years (range, 38-76) and 5 were males. Abdominal pain was the most common presenting symptom (30%) followed by constitutional symptoms, shortness of breath, and vision change. In 3 pts, the diagnosis was incidental. The 2 most common primary locations were abdomen/pelvis (50%) and mediastinum (30%). Six pts (60%) presented with advanced disease and 3 (30%) had Castleman’s disease. Most (60%) had advanced disease. Six pts had Epstein-Barr virus in situ hybridization and all tested negative. Seven pts had next generation sequencing and 5 (83%) had genetic alterations detected with CDKN2A/B alterations being most frequent (3 pts, all with advanced disease). The median follow up was 4.3 years (range, 0.2-13.3). In the 4 patients with localized disease, 3 underwent complete surgical excision resulting in complete remissions (CRs). The one who received radiation had a partial remission (PR). The median time to progression after 1st line treatment was 4 months (all with advanced disease). All 3 pts who died had advanced disease and 2 had CDKN2A/B alterations. Conclusions: In FDCS, localized diseases managed by surgical excision with or without radiation can achieve long term remissions. Advanced diseases generally do not respond to multimodality therapy including immunotherapy but can have disease stabilization with variable survival. CDKN2A/B mutations were common and potentially associated with a worse outcome. Better understanding of the impact of the FDCS mutational landscape on prognosis may provide novel approaches to therapy. [Table: see text]
Efficacy and safety of anthracycline combined with alkylating agent for treatment of advanced leiomyosarcoma.
Authors: Tan Huijing , Zuo Lijie , Sun Yuting , Chi Yihebali
Published: June 2024

e23558

Background: Leiomyosarcoma(LMS) accounts for 12-14% of all soft tissue sarcomas(STSs) and this STS subtype has high metastatic potential. We evaluated the efficacy and safety of epirubicin combined with temozolomide(EPI-TMZ) for treatment of advanced LMS. Methods: Oral TMZ(200 or 300 mg) was administered each day on days 1-5, and intravenous EPI(60 mg/m2) was administered on days 1-4, with even distribution over these 96h within a 21‐day cycle. After 8 cycles of intensive chemotherapy, monodrug maintenance therapy consisted of TMZ alone(dosing as in the primary therapy, most choices, stop taking medication after 1 year control), and two-drug maintenance therapy consisted of TMZ with thalidomide(only 3 patients). All patients-initiated EPI-TMZ treatment between January 2018 and January 2024. Results: We examined 31 patients who received EPI-TMZ. There were 25 females and 6 males, with average age 50.5 years old. All were unresectable patients derived from abdominal retroperitoneum, uterus, inferior vena cava, mesentery, small intestine, stomach, thighs, elbows, wrists, pancreas, nasal cavity, meantime with distant metastasis. Average Ki67 is above 40%. This was a first-line treatment in 16 patients, a second- or third-line in 13, and a fourth-line in 2. At the time of data cutoff (January 31, 2024), the median PFS was 12.6 months, 1 patient had cCR, 9 PR and 20 SD. The ORR was 32.3%(10/31) and DCR was 96.8%(30/31). The only patient who progressed after two cycles of medication had PMS2 deficiency, and studies have reported that it may have a primary resistance mechanism. Even the shortest disease control period is also 5 months, indicating this regime has significant clinical benefit. Some patients have undergone tumor reduction surgery to improve quality of life after achieving significant tumor relief. The current longest PFS is 42 months up to now and under continuous tumor control. Previous retrospective studies indicated the best mPFS was 9.2 months and the best ORR was 30.9%. 2023 ESMO declared prospective doxorubicin with trabectedin obtained mPFS of 12.19 months. The most common treatment-related adverse effects were leukopenia, neutropenia, thrombocytopenia, anemia, nausea, vomiting, fatigue, and oral mucositis. Two patients had severe febrile neutropenia, but there were no treatment-related deaths, survival data follow-up. Conclusions: EPI-TMZ is potentially effective for treatment of advanced LMS, and the adverse effects appear tolerable. EPI-TMZ may provide better outcomes than reported in previous studies of other treatments for advanced LMS, worth further prospective research.
Characterizing the transformation and diagnosis of atypical lipomatous tumors to dedifferentiated liposarcoma: Single-institutional outcomes.
Authors: Yu Austin , Honore Lesly , Timmermann Anne Patricia , Demetrious Matthew , Gitelis Steven , Miller Ira , Blank Alan T.
Published: June 2024

e23560

Background: Atypical lipomatous tumor (ALT) is a locally aggressive, benign adipocytic tissue mass with risk of transformation into dedifferentiated liposarcoma (DDLS), a mixed-grade, non-lipogenic tumor with increased risk for metastasis and mortality. Studies have evaluated the dedifferentiation rate of DDLS but seldom report the methodology of obtaining their diagnosis, which is crucial due to their heterogeneous architecture and relatively low core needle biopsy (CNB) accuracy. We included a longitudinal cohort of ALT/DDLS patients characterizing how and when patients received their diagnoses. Methods: 168 patients diagnosed with ALT-only (n = 129), DDLS-only (n = 22), or both (n = 17) were included. Among DDLS patients, the presence of a prior ALT diagnosis along with time between their ALT and DDLS diagnosis was measured. Histology, location, results, and methods of each diagnosis were recorded including, CNB, surgical resection, or both. Disease-specific survival (DSS) and recurrence free-survival (RFS) were calculated with univariate/multivariate analysis for risk factors. Results: Among patients who received a diagnosis with CNB consistent with ALT, 7 were subsequently diagnosed with DDLS after surgical resection, representing 4.8% of ALT patients. Mean time between diagnoses was 2.3 months (STD 2.0). 5 (3.4%) patients were diagnosed with a DDLS recurrence after initial ALT diagnosis confirmed with CNB and surgical resection. Median time between diagnoses was 37.0 months (IQR 16.0, 63.0). 5 (3.4%) had tumors with a heterogeneous composition on initial surgical resection, described as an ALT with dedifferentiated components. 22 DDLS patients had no prior ALT diagnosis. 9 were diagnosed from both CNB and surgical resection, and 13 were diagnosed from surgical resection directly after clinical suspicion and imaging concerning for sarcoma. DSS in the DDLS was significantly lower than ALT-only DSS (p < 0.0001). There was no significant difference in RFS. Conclusions: DDLS may arise after an extended period of time after ALT resection or simultaneously with an ALT diagnosis. Due to its varied diagnostic timeline and appearance, caution is advised when evaluating and treating ALT. [Table: see text]
An NCDB analysis of patient treatment trends in soft tissue angiosarcoma.
Authors: Chaddha Jasleen Kaur , Samuel Maya Mary , Saldhi Prachi , Silberstein Peter T. , Braaten Marco
Published: June 2024

e23563

Background: Angiosarcoma is a rare subtype of soft tissue sarcoma associated with a generally poor prognosis and high mortality rate. Median survival of patients with angiosarcoma typically ranges from 15 to 24 months, with a 5-year survival of 12-33%. Angiosarcomas have a high propensity for local recurrence, metastasis, and multiple organ involvement as they originate from vascular endothelial cells. Though surgical excision currently plays a central role in the treatment of angiosarcoma, no significant study has analyzed NCDB for treatment trends in these patients. This study aims to characterize the effect of different treatment modalities on overall survival of angiosarcoma patients. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with angiosarcoma from 2004 to 2020 using histology code 9120 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA, Chi-Square, Cox Proportional Hazards and Logistic Regression tests were performed, and data were analyzed using SPSS version 29. Statistical significance was set at α = 0.05. Results: 3560 patients with angiosarcoma of the soft tissue were queried. The most common primary site for a tumor was the head, neck, or face (920 patients, 31.3%). Of the initial sample, 1889 ( 53.1%) patients received surgery alone, 450 ( 12.6%) patients received adjuvant chemotherapy, 55 ( 1.54%) received adjuvant radiation, and 30 ( 0.84%) patients received adjuvant chemoradiation. Surgery alone conferred the greatest median survival; no surgery conferred the least ( 31.4 months vs. 7.2 months; p < 0.001). In the crude and adjusted logistic regression models, combined chemoradiation (OR = .210; 95% CI:.100-.400) and surgery alone were associated with the lowest odds of death (OR = .271; 95% CI: .224-.329) relative to no surgical procedure of the primary site. This finding persisted once the model was adjusted for age, stage, and tumor size. Surgery alone conferred the lowest hazard ratio (HR = .352; 95% CI: .323-.384) relative to no surgery. Conclusions: In angiosarcoma patients, surgical excision at the primary site alone was associated with the greatest median survival and the lowest hazard ratio. Additionally, angiosarcoma patients who did not receive surgery had the least median survival. Surgery with adjuvant chemoradiation and surgery alone had the lowest odds of death. These findings affirm that surgical excision at the site of the primary tumor plays a key role in increasing the survival of angiosarcoma patients. Further research is necessary in characterizing treatment trends in angiosarcoma patients to supplement current standardized treatment protocols and improve the mortality of this lethal cancer.
The efficacy of immune checkpoint inhibitors as a part of multimodality treatment in soft tissue and bone sarcoma in an academic community setting.
Authors: Zarifa Abdulrazzak , Britto Michele , Brockstein Bruce
Published: June 2024

e23564

Background: Prior studies have shown response to immune checkpoint inhibitors (ICI) in a variety of sarcoma subtypes, however, much is still unknown about ICI use in specific sarcoma subtypes due to disease rarity. Patients (pts) are often treated with these agents as part of clinical trials, and real world data in the community setting is lacking. The aim of this study is to report real world efficacy and safety of ICI in sarcoma either alone or with radiation (RT) and/or surgery. Methods: A retrospective cohort review was conducted to identify pts with soft tissue and bone sarcoma who were administered ICI at Kellogg Cancer Center at NorthShore University HealthSystem/Endeavor Health. Pts who received ICI as part of a clinical trial were excluded. Results: A total of 29 pts receiving ICI were identified. Pts had a median of 1 prior systemic therapy. ICI included pembrolizumab (n = 23), nivolumab (n = 5), and ipilimumab/nivolumab (n = 1). Treatment was discontinued in 28 pts due to disease progression (n = 18), toxicities (n = 3), death (n = 2), and maximal response (n = 5). One patient is still undergoing treatment. Median progression-free survival (PFS) was 4.9 months. Median overall survival (OS) was 14 months. Overall response rate (ORR) is 31%. Median duration of response was not reached (44+ months). Complete response (CR) (n = 5) reported in 3 pts with undifferentiated pleomorphic sarcoma (UPS), 1 pt with SMARCA4 deficient undifferentiated sarcoma, and 1 pt with dedifferentiated chondrosarcoma. Partial response (PR) (n = 4) reported in 1 pt with UPS, 1 pt with dedifferentiated liposarcoma, 1 pt with high grade spindle sarcoma of bone, and 1 pt with malignant peripheral nerve sheath tumor. Of those pts with a CR, 2 patients received only pembrolizumab, 1 pt was administered concomitant RT, and 2 pts had administered concomitant surgery. Of the pts who had PR, 3 were also treated with concomitant RT. Grade 3 immune related adverse effects were reported in 5 of the 29 patients. Of these patients, 2 had documented CR and 3 documented PR. Conclusions: This study expands on the real world efficacy of ICI in a variety of sarcoma subtypes. CR and PR rates in this setting were high, and responses were durable, although selection bias for treatment may have played a role. This data supports the treatment of metastatic sarcoma with ICI, especially with concomitant RT and surgery, in a variety of subtypes.
Use of immunotherapy with check point inhibitors in soft tissue sarcoma: Analysis from single institution.
Authors: Pachika Pranali Santhoshini , Kalantri Shreyas , Kumar Rohit
Published: June 2024

e23566

Background: Traditional treatments for soft tissue sarcomas include surgery, chemotherapy, and radiation. Effectiveness of Check point inhibitors for sarcoma has been unsatisfactory thus far. Major clinical trials PEMBROSARC and SARC028 revealed median PFS of 2 and 4.5 months, respectively. The FDA has approved three immunotherapy (IO) therapies for sarcoma. Atezolizumab was approved for alveolar soft part sarcoma. Dostarlimab is approved for sarcoma with DNA mismatch repair deficiency (dMMR), Sarcoma patients with high microsatellite instability (MSI-H), dMMR, or tumor mutational burden can receive pembrolizumab. A single-institution analysis of soft tissue sarcoma patients with IO is presented in this paper. Methods: All soft tissue sarcoma patients who have received IO from January 2021 to now have been included. At our institute, a total of seven patients received IO for soft tissue sarcoma. Observations were made regarding their fundamental characteristics and the progression free survival (PFS). The data was not statistically examined due to the small sample size and the heterogeneity of the data. Results: 2 of 7 trial patients were lost to follow-up. Recurrent autoimmune hepatitis terminated IO for another patient. Most of the patients are elderly with the median age of 78. Given their comorbidities and age, IO was chosen as the first line for 5 patients. Median PFS was 5.8 months. High PDL1 ( > / = 5%) patients had a median PFS of 5.6 months, while low PDL1 patients had 4.5 months. However, one patient with low PDL1 had PFS of 7 months. 5/7 patients didn’t have IO related side effects. Two patients developed Autoimmune (AI) hepatitis. Conclusions: The limited sample size prevented definitive conclusions from being drawn. Despite the unsatisfactory outcomes, it is worth mentioning that IO provided a certain degree of PFS in older patients with comorbidities who are not suitable candidates for chemotherapy. Based on limited data, patients with high PDL1 status appear to benefit more. IO alone has not shown promising results. In clinical trials, IO is being tested with chemotherapy and Tyrosine kinase inhibitors. The findings from these trials will provide valuable insights into the potential benefits of combination therapy. [Table: see text]
Preoperative and postoperative platelet-lymphocyte ratio as a prognostic marker for patients with soft tissue sarcoma treated with curative resection.
Authors: Lee Inhee , Na Jihyun , Lee Soo Jung
Published: June 2024

e23568

Background: In cancer development and progression, systemic inflammation has been implicated. Inflammatory markers have been identified as prognostic indicators in numerous malignancies. In this study, we explored the prognostic relevance of initial and postoperative systemic inflammatory markers (neutrophil -lymphocyte ratio, platelet -lymphocyte ratio) on relapse-free survival (RFS) and overall survival (OS) in patients with soft -tissue sarcoma (STS) who underwent curative resection. Methods: We included a total of 89 patients with STS who underwent extensive and radical resection at the Kyungpook National University Chilgok Hospital (Daegu, Korea,) between 2004 and 2018. Kaplan-Meier curves and RFS and OS were calculated using multivariate Cox proportional models. Results: The median age of the patients was 55 years (range 27 - 86) and the ratio of male-to-female ratio was approximately 1:1. A total of 67 (75.3%) patients demonstrated a high initial neutrophil-lymphocyte ratio(NLR) (≥4.1) and 65 (75.3%) showed a high initial platelet-lymphocyte ratio(PLR) (≥231). After curative resection, the number of patients with high NLR and PLR was 16(18.0%) and 17 (29.3%). In both the NLR and PLR groups, including the postoperative NLR and postoperative PLR subgroups, no significant differences were observed in terms of age, sex, histologic type, tumor site, tumor size, tumor depth, or American Joint Committee on Cancer staging when stratified into high and low subgroups. In the univariate and multivariate analyses, an elevated initial PLR ratio was significantly associated with a decreased RFS (hazard ratio[HR]: 2.120; 95% confidence interval[CI]: 1.021 - 4.883, p = 0.017) and OS (HR: 5.073; 95% CI: 1.731 - 14.87, p = 0.003). Patients with a high PLR (PLR > 231) had a median RFS of 24 months, whereas those with a low PLR (PLR ≤231) had a median RFS of 96 months. The median OS was 50 and 298 months for the high PLR and low PLR groups, respectively. Furthermore, a high postoperative PLR ratio was significantly associated with a decreased RFS (HR: 3.921; 95% CI: 1.738 - 8.845, p = 0.001) and OS (HR: 5.702; 95% CI: 1.099 -29.576, p = 0.038). Conclusions: The present results suggest that the preoperative and postoperative PLR ratio can be used as a cost- effective prognostic marker for oncologic outcomes in patients with STS who underwent surgery.
Detection and surveillance of circulating tumor cells in sarcoma for predicting therapy response and prognosis.
Authors: Zhang Qing , Wang Zhe , Yang Yongkun , Deng Zhiping , Yu Feng , You Xia , He Peng
Published: June 2024

e23573

Background: Generally sarcomas are categorized as soft tissue and bone sarcomas and represent heterogenous group of malignancies with more than 70 distinct histologic subtypes. Due to their rarity and heterogeneity, sarcomas present particular challenges for accurate diagnosis, prognosis, and treatment. The presence and persistence of circulating tumor cells (CTCs) in the peripheral blood are believed to be associated with poor prognosis and distant metastases. A blood-based CTCs test is thus greatly needed for monitoring disease progression and predicting clinical outcomes. Methods: In this study, we developed a CTCs test for the detection and surveillance of sarcoma patients’ CTCs, and subsequently explored its clinical value. 123 patients with sarcomas were enrolled as the cohort for serial CTCs tests. Dynamic CTCs counting, in combination with therapy evaluation and post-treatment follow-up, was used to explore predicting pre- and post-chemotherapy evaluation and prognosis. Results: Quantification of CTCs demonstrated a significant increase in sarcoma patients compared to healthy individuals. Furthermore, patients in stage III-IV had a higher CTC count than those in stage I-II (p<0.01), suggesting a correlation between CTCs and disease development. Remarkably, there was variation in the quantity of CTCs among different types of sarcomas. The highest number of CTCs was observed in undifferentiated small round cell sarcoma, followed by soft tissue tumor, while bone tumors had the lowest number. In addition, the number of CTCs in patients with positive PD-L1 expression was considerably greater than in those with negative expression (p<0.01). The count of CTCs shown a substantial decrease following neoadjuvant chemotherapy treatment. There was a decline in the number of CTCs both before and after postoperative adjuvant chemotherapy treatment, however, there was no significant statistical discrepancy. The number of CTCs at the baseline was shown to be considerably larger in the group of patients with progressive disease or stable disease (PD+SD) compared to the group with partial response or complete response (PR+CR) (p<0.05). This difference was particularly pronounced for interstitial-type CTCs (p<0.01). Conclusions: The rate of presence of CTCs in the peripheral blood of sarcoma patients is high, and patients with an increased percentage of CTCs after treatment have a poor treatment effect. The dynamic monitoring of changes in CTCs counts after treatment has clinical significance for the timely detection of recurrence or metastasis. CTCs also showed a clinical value in prediction of therapy efficiency or prognosis, and may be clinically valuable for the whole course management of patients.
A multicohort platform trial to improve drug access for pediatric cancer patients in Japan: The PARTNER trial (NCCH2220).
Authors: Miyazaki Bunpei , Shirakawa Nami , Sugiyama Minako , Arakawa Ayumu , Ando Yayoi , Anjo Kenta , Kai Yoko , Hoshina Yukari , Mizusawa Junki , Shibata Taro , Fukuda Haruhiko , Okita Natsuko Tsuda , Nakamura Kenichi , Ogawa Chitose
Published: June 2024

TPS10079

Background: In Japan, there are no pediatric regulations that encourage drug development for pediatric cancer, such as Pediatric Investigation Plans (PIPs) which are mandated in Europe, or the RACE Act in the U.S. Therefore, there are fewer early-phase clinical trials and approved drugs for pediatric cancer than in Western countries. In addition, because there is no rapid compassionate use program, there are delays when using an unapproved drug. According to a report from the Japanese cancer genome profiling (CGP) testing data center, C-CAT, 51.3% of pediatric patients with solid tumors had targetable genetic abnormalities. However, only 5.8% of them had access to the recommended molecular targeted therapy (Tanimura K. et al., presented at the Japanese Society of Pediatric Hematology and Oncology annual meeting 2022). Thus, Japanese pediatric patients with relapsed or refractory solid tumors have limited access to novel drugs, even if they have druggable mutations. Therefore, we designed a platform study (NCCH2220, PARTNER trial) to rapidly deliver molecularly targeted drugs based on CGP testing. Methods: This study has two objectives: first, to administer some drugs to pediatric patients that are not approved for pediatric cancer in Japan. These drugs have been shown to be safe in pediatric patients in foreign countries and are expected to be effective. Second, to evaluate the safety and efficacy of the drug in Japanese pediatric patients and, if necessary, its pharmacokinetics. These data will be used for potential future regulatory filings. This is an open-label, multicenter, multicohort study. Eligible patients are aged 0–29 years with diseases having no standard therapy, which are refractory, or when there is intolerance to standard therapy. The study drug must be recommended for the patient by CGP testing or approved for pediatric use for their disease in the U.S. or Europe, or approved in Japan for use in adults only. The drugs are used as monotherapy in the study. The study schedules follow a master protocol. Up to 30 patients can be enrolled in each cohort. The primary endpoint is the incidence of dose-limiting toxicity in each cohort. The secondary endpoints are the incidence of adverse events, the overall response rate, and, if necessary, the pharmacokinetics in each cohort. As of January 2024, the study had five treatment cohorts with the following agents: imatinib, pazopanib, ruxolitinib, trametinib, and atezolizumab. Additional cohorts will be added. We started planning the study in November 2022, and enrollment began on January 18, 2024. This platform trial has enabled us to deliver drugs to patients more quickly and efficiently than by conducting individual early-phase trials for each drug. Clinical trial information: jRCTs031230544 .
Blood-based colorectal cancer (CRC) screening implementation into clinical practice in the outpatient clinical setting in the Appalachian highlands.
Authors: Talari Mridula Preetham , Haynes William , Elmore Karen , Jastan Rasmiyah , Mays Charles E , Chirculescu Camelia , Adada Haytham
Published: June 2024

TPS10622

Background: Maximizing colorectal cancer (CRC) screening participation relies on tests that are acceptable, accessible, and patient-centered. While colonoscopy or stool-based tests have traditionally been the standard of care (SOC), they often present challenges related to timely completion and patient adherence. Blood-based tests (BBTs) detecting circulating tumor DNA (ctDNA) offer a quicker, less invasive alternative to previous methods of screening. While the BBTs exhibit comparable sensitivity and specificity to the existing noninvasive SOC, their user-friendly nature holds the potential to enhance adherence. This study aims to explore the implementation of a BBT and its impact on patient acceptability and adherence to CRC screening. The study focuses on the Appalachian population, known for higher CRC incidence1 and mortality rates2 compared to the general US population. Methods: The trial is being conducted at two primary care clinics. It consists of two phases over a 6-month period, aiming to enroll over 300 patients. Participants aged 45-84 years, identified as average risk for CRC according to USPSTF guidelines, and who have opted to be screened for CRC and are willing to participate in the study will be eligible. Exclusion criteria consist of higher-than-average risk for CRC according to the USPSTF standards. During Phase 1 (control period), patients meeting inclusion criteria will be offered SOC (colonoscopy and/or stool-based test) for 3 months followed by Phase 2 (intervention period) where a BBT in addition to SOC will be offered for another 3 months. Informed consent will be obtained prior to any study procedures. The BBT used for the study has a sensitivity of 83% and specificity of 90%. Patients who agree to BBT will undergo a single blood draw of 40 mL. Phase 1 has concluded with enrollment of 75 patients, while Phase 2 is currently ongoing and actively recruiting participants. Upon completion of study, an EMR review will be conducted on participants to evaluate screening rates before and after implementing the BBT and to assess adherence. The primary endpoint of the study involves calculating the total number of consented patients who opted for and completed either BBT or SOC during the interventional period compared to the total number of patients who opted for SOC during the control period. Final data analysis is expected by July 2024. References: 1. Wilson RJ, Ryerson AB, Singh SD, King JB. Cancer Epidemiol Biomarkers Prev. 2016;25(2):250-258. doi:10.1158/1055-9965.EPI-15-0946; 2. Siegel RL, Miller KD, Jemal A. CA Cancer J Clin. 2017;67(1):7-30. doi:10.3322/caac.21387. Clinical trial information: NCT06119425 .