Pazopanib in the advanced and rare subtypes of soft tissue sarcoma: Russian Sarcoma Group study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23528-e23528
Author(s):  
Anastasia Alekseevna Tararykova ◽  
Beniamin Bokhyan ◽  
Andrey A. Konev ◽  
Polina A. Falkina ◽  
Zaur Yu. Kumekhov ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Clear Cell ◽  
Soft Part ◽  
Progression Free Survival ◽  
Myxoid Liposarcoma ◽  
Clear Cell Sarcoma ◽  
Primary Tumors ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Ewing Tumors

e23528 Background: Sarcoma is a heterogeneous group of tumors that arise from connective tissue. The most frequent localizations of primary tumors are soft tissues and bones of the extremities, and the lungs is the most common localization of metastases. Pazopanib is an antineoplastic agent, multi-kinase inhibitor that retards angiogenesis in tumor tissues and has been shown to be effective in the treatment of patients with advanced sarcoma. Median progression-free survival was 4,6 months (95% CI 3,7–4,8) for pazopanib compared with 1,6 months (0,9–1,8) for placebo in the PALETTE clinical trial. This study designed to detect epidemiology data as well as the pazopanib efficiency for rare sarcoma subtypes. Methods: We collected data from 109 cases with 20 different sarcoma histotypes and 15 localizations, at N.N. Blokhin National Medical Research Center of Oncology from 2018 till 2020. Disease was histologically confirmed by a sarcoma pathologist. The average age of patients was 47.8 years and the women and men ratio was about 2:1. Patients received pazopanib 800 mg once daily and passed control examinations every 2 or 3 months (CT/MRI). Treatment response was assessed by RECIST criteria. Results: The most frequent localizations of primary tumors were the soft tissues of the extremities (39.6%), the uterus (16.9%) and the retroperitoneum (13.2%). The main histological subtypes were leiomyosarcoma (33.6%) and synovial sarcoma (14.9%). There were also included such types like a embryonal rhabdomyosarcoma, chondrosarcoma, Ewing tumors, EHE, alveolar soft part sarcoma, PEComa, clear cell sarcoma, adamantinoma, solitary fibrous tumor, epithelioid sarcoma and myxoid liposarcoma. The majority of patients (61%) received more than 2 of therapy. The average duration of therapy was 7.5 months. Best tumor response by RECIST was as follows: complete response 0 (0%), partial response 2 (2%), stable disease 81 (88,3%), progression disease 25 (27,3%) cases. Median progression-free survival was 8 months (95% CI 6,7-9,2) for pazopanib. Median overall survival was not reached. Overall pazopanib was well tolerated, except one case with SAE. Conclusions: In this study we observed pazopanib efficiency in a rare for pazopanib sarcoma subtypes such as myxoid liposarcoma (1 PR), PEComa, adamantinoma, embryonal rhabdomyosarcoma, malignant peripheral nerve sheath tumor and Ewing tumors. Also our study confirms pazopanib long-term disease control in alveolar soft part sarcoma, clear cell sarcoma, leiomyosarcoma, synovial sarcoma and undifferentiated pleomorphic sarcoma which explains median PFS 8 months.

scholarly journals Efficacy and Safety of Trabectedin in Patients with Soft Tissue Sarcoma: A Bicentric Retrospective Analysis.

2021 ◽  
Author(s):  
Chaigneau Loïc ◽  
Jary Marine ◽  
Nerich Virginie ◽  
Hervieu Alice ◽  
Aubry Sébastien ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Progression Free Survival ◽  
Myxoid Liposarcoma ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Heterogenous Group ◽  
End Of Treatment ◽  
Low Toxicity

Abstract Background: Soft tissue sarcomas (STS) are a rare and heterogenous group of tumors, with poor prognostic, judging from their frequency to relapse. Few drugs are available. Since 2007, trabectedin got approval after failure of anthracyclines and ifosfamide, for advanced or metastatic STS.Patients and Methods: This retrospective study describes effects of trabectedin on survival, response, and toxicity, in STS patients. One hundred twenty-nine patients treated between 2002 and 2019 were analysed, from two French centers. All patients were tested for toxicities, and efficacy was assessed in patients exposed to at least 2 cycles of trabectedin.Results: Three median cycles were administered per patient (1-79). Among the 115 patients analysed for efficacy, the median progression free survival was 3.0 months [CI95%: 2.3 – 4.7], with an overall survival of 11.9 months [CI95%: 10.2 – 16.6]. The rate of disease control was 45.2% at the end of treatment. Myxoid liposarcoma (n = 11) was the histology subtype that benefited most from this chemotherapy with median progression free survival and an overall survival of 13.3 months [CI95%: 2.3 – 18.7] and 27.8 months [CI95%: 3.2 – 64.7], respectively. Adverse events were manageable. Conclusion: Efficacy of trabectedin is confirmed in terms of clinical benefit and low toxicity, especially for myxoid liposarcoma.

scholarly journals Cabozantinib in Combination With Atezolizumab for Advanced Renal Cell Carcinoma: Results From the COSMIC-021 Study

2021 ◽  
pp. JCO.21.00939
Author(s):  
Sumanta K. Pal ◽  
Bradley McGregor ◽  
Cristina Suárez ◽  
Che-Kai Tsao ◽  
William Kelly ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
End Point

PURPOSE COSMIC-021 is evaluating cabozantinib plus atezolizumab in patients with solid tumors. We report results from patients with advanced clear cell (cc) and non–clear cell (ncc) renal cell carcinoma (RCC). METHODS This phase Ib study ( NCT03170960 ) enrolled patients age ≥ 18 years with advanced RCC. A dose-escalation stage was followed by expansion cohorts. For cohort expansion, prior systemic therapy was not permitted for ccRCC but allowed for nccRCC. Patients received oral cabozantinib 40 mg once a day (ccRCC and nccRCC) or 60 mg once a day (ccRCC only) plus atezolizumab (1,200 mg intravenously, once every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1; the secondary end point was safety. RESULTS A total of 102 patients were enrolled. Median follow-up was 25.8, 15.3, and 13.3 months for the 40-mg ccRCC, 60-mg ccRCC, and nccRCC groups, respectively. ORR was 53% (80% CI, 41 to 65) in the 40-mg ccRCC group (n = 34) and 58% (80% CI, 46 to 70) in the 60-mg ccRCC group (n = 36), 3% and 11%, respectively, with complete response; median progression-free survival (exploratory end point) was 19.5 and 15.1 months, respectively. In nccRCC (n = 32), ORR was 31% (80% CI, 20 to 44), all partial responses; median progression-free survival was 9.5 months. Grade 3 or 4 treatment-related adverse events (TRAEs) were reported by 71% of patients in the 40-mg ccRCC group, 67% in the 60-mg ccRCC group, and 38% in the nccRCC group; TRAEs leading to discontinuation of both agents occurred in 15%, 6%, and 3% of patients, respectively. There were no grade 5 TRAEs. CONCLUSION The novel combination of cabozantinib plus atezolizumab demonstrated encouraging clinical activity and acceptable tolerability in patients with advanced ccRCC and nccRCC. Disease control was observed across dose levels and histologic subtypes.

Telomerase Expression Predicts Unfavorable Outcome in Osteosarcoma

2004 ◽  
Vol 22 (18) ◽  
pp. 3790-3797 ◽  
Author(s):  
Robert P. Sanders ◽  
Rachid Drissi ◽  
Catherine A. Billups ◽  
Najat C. Daw ◽  
Marcus B. Valentine ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Primary Tumor ◽  
Progression Free Survival ◽  
Outcome Analysis ◽  
Negative Group ◽  
Primary Tumors ◽  
Free Survival ◽  
Positive Group ◽  
Alternative Lengthening ◽  
Group 3

Purpose Osteosarcoma is distinct from most cancers in that the majority of osteosarcomas lack telomerase expression and use the alternative lengthening of telomeres (ALT) mechanism to maintain telomeres. Laboratory studies suggest that compared with ALT, telomerase expression is associated with increased tumor aggressiveness. We evaluated the clinical significance of telomerase expression in human osteosarcoma. Patients and Methods Fifty-six osteosarcomas from 51 patients treated at St Jude Children's Research Hospital between 1982 and 2003 were evaluated for telomerase enzyme activity, mRNA expression of the catalytic component of telomerase (TERT), and presence of the ALT pathway. Results Outcome analysis was based on TERT mRNA expression in the primary tumor samples from 44 patients. Fourteen primary tumors expressed TERT mRNA (32%; eight TERT only, six TERT and ALT) and 30 did not express TERT mRNA (68%; 29 ALT, one no ALT). Progression-free survival (PFS) was inferior in the TERT-positive group compared with the TERT-negative group (3-year estimates, 21.4% ± 9.5% v 63.7% ± 11.1%; P = .014). Likewise, overall survival was inferior in the TERT-positive group compared with the TERT-negative group (3-year estimates, 42.9% ± 12.2% v 70.0% ± 9.9%; P = .031). Among 31 patients with nonmetastatic disease at diagnosis, PFS was lower in the TERT-positive group compared with the TERT-negative group (3-year estimates, 33.3% ± 13.6% v 72.0% ± 11.5%; P = .092). Conclusion Telomerase expression in primary tumor samples is associated with decreased PFS and OS in patients with osteosarcoma. Additional studies are warranted to better define the clinical utility of this molecular marker.

Use of nab-paclitaxel and gemcitabine in pancreatic cancer without granulocyte colony-stimulating factor: A multicenter real-world experience

2021 ◽  
pp. 107815522110386
Author(s):  
Angela Chen ◽  
Vincent H Ha ◽  
Sunita Ghosh ◽  
Carole R Chambers ◽  
Michael B Sawyer
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Free Survival ◽  
Colony Stimulating Factors ◽  
Median Progression Free Survival ◽  
Stimulating Factor

Introduction The metastatic pancreatic adenocarcinoma clinical trial (MPACT) trial established gemcitabine (gem) and nab-paclitaxel (nab) as a standard treatment for pancreatic cancer utilizing granulocyte colony-stimulating factors to manage neutropenia. This was a challenge for jurisdictions that do not use granulocyte colony-stimulating factors in palliative settings. We developed dosage guidelines to dose modify gem and nab without granulocyte colony-stimulating factors. We undertook a retrospective review to determine the efficacy and safety of these dose adjustment guidelines in the real world. Methods A multi-centered, retrospective chart review was performed on pancreatic patients between December 1, 2014, and August 21, 2018. Provincial electronic medical health records were reviewed. Using Log-rank statistics we determined the patient's progression-free survival and overall survival. Results Of 248 patients, 209 met patient selection criteria. Patients were excluded if they were lost to follow-up, on gem alone prior to nab/gem combination therapy or did not receive nab or gem. Patients who received nab/gem as first-line therapy had a median progression-free survival of 6.3 months (95% CI, 5.1–7.4), and median overall survival of 11.1 months (95% CI, 9.5–12.8). Those who received gem/nab in the second line had a median progression-free survival of 4.6 months (95% CI, 2.8–6.5), and median overall survival of 19.3 months (95% CI, 12.6–26.0). Conclusions The patient’s progression-free survival and overall survival taking nab/gem using our dose modification algorithm were equivalent or superior to the MPACT trial's progression-free survival and overall survival. Gem/nab can be given by our dose modification scheme without granulocyte colony-stimulating factor.

scholarly journals NOVEL PLASMA GLYCOPROTEIN BIOMARKERS PREDICT PROGRESSION-FREE SURVIVAL IN SURGICALLY RESECTED CLEAR CELL RENAL CELL CARCINOMA

2022 ◽  
Author(s):  
Daniel Serie ◽  
Amanda A Myers ◽  
Daniela A Haehn ◽  
Alexander Parker ◽  
Essa Bajalia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differential Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Progression Free Survival ◽  
P Value ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival ◽  
Kaplan Meier

Introduction: Limited data exists on utilization of protein post-translational modifications as biomarkers for clear cell renal cell carcinoma (ccRCC). We employed high-throughput glycoproteomics to evaluate differential expression of glycoprotein-isoforms as novel markers for ccRCC progression-free survival (PFS). Methods: Plasma samples were obtained from 77 patients treated surgically for ccRCC. Glycoproteomic analyses were carried out after liquid chromatography tandem mass spectrometry. Age-adjusted Cox proportional hazard models were constructed to evaluate PFS. Optimized Harrells c-index was employed to dichotomize the collective for the construction of Kaplan-Meier curves. Results: The average length of follow-up was 3.4 (range: 0.04-9.83) years. Glycoproteomic analysis identified 39 glycopeptides and 14 non-glycosylated peptides that showed statistically significant (false discovery rate p ≤0.05) differential expression associated with PFS. Five of the glycosylated peptides conferred continuous hazard ratio of > 6 (range 6.3-11.6). These included prothrombin A2G2S glycan motif (HR=6.47, P=9.53E-05), immunoglobulin J chain FA2G2S2 motif (HR=10.69, P=0.001), clusterin A2G2 motif (HR=7.38, P=0.002), complement component C8A A2G2S2 motif (HR=11.59, P=0.002), and apolipoprotein M glycopeptide with non-fucosylated and non-sialylated hybrid-type glycan (HR=6.30, P=0.003). Kaplan-Meier curves based on dichotomous expression of these five glycopeptides resulted in hazard ratios of 3.9-10.7, all with p-value < 0.03. Kaplan-Meyer plot using the multivariable model comprising 3 of the markers yielded HR of 11.96 (p <0.0001). Conclusion: Differential glyco-isoform abundance of plasma proteins may be a useful source of biomarkers for the clinical course and prognosis of ccRCC.

scholarly journals High Expression of GSDMC Is Associated with Poor Survival in Kidney Clear Cell Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yun-Qian Cui ◽  
Fei Meng ◽  
Wen-Li Zhan ◽  
Zhou-Tong Dai ◽  
Xinghua Liao
Keyword(s):  
Potential Role ◽  
Clear Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Renal Clear Cell Carcinoma ◽  
High Expression ◽  
Poor Survival ◽  
Free Survival

This study is aimed at exploring the potential role of GSDMC in kidney renal clear cell carcinoma (KIRC). We analyzed the expression of GSDMC in 33 types of cancers in TCGA database. The results showed that the expression of GSDMC was upregulated in most cancers. We found a significant association between high expression of GSDMC and shortened patient overall survival, progression-free survival, and disease-specific survival. In vitro experiments have shown that the expression of GSDMC was significantly elevated in KIRC cell lines. Moreover, decreased expression of GSDMC was significantly associated with decreased cell proliferation. In summary, we believe that this study provides valuable data supporting future clinical treatment.

Epithelial-Type and Neural-Type Cadherin Expression in Malignant Noncarcinomatous Neoplasms With Epithelioid Features That Involve the Soft Tissues

2002 ◽  
Vol 126 (4) ◽  
pp. 425-431 ◽  
Author(s):  
William B. Laskin ◽  
Markku Miettinen
Keyword(s):  
Malignant Melanoma ◽  
Synovial Sarcoma ◽  
Soft Tissues ◽  
Clear Cell ◽  
Epithelioid Sarcoma ◽  
Clear Cell Sarcoma ◽  
Extraskeletal Myxoid Chondrosarcoma ◽  
Cell Sarcoma ◽  
Myxoid Chondrosarcoma ◽  
Poorly Differentiated

Abstract Context.—Transmembrane adhesion molecules, epithelial-type cadherin (ECAD) and neural-type cadherin (NCAD), help in regulating transformations between epithelial and mesenchymal cells in the developing embryo and in maintaining the epithelioid phenotype. Consequently, the presence of epithelioid cells in certain malignant noncarcinomatous neoplasms raises speculation that the expression of ECAD and NCAD in these neoplasms may have diagnostic significance. Objective.—To investigate the utility of ECAD and NCAD immunoexpression in distinguishing malignant (noncarcinomatous) neoplasms with epithelioid features that involve the soft tissues. Design.—Membranous immunoreactivity of anti-ECAD and anti-NCAD was evaluated on archived cases selected from the files of the Armed Forces Institute of Pathology. Results.—Epithelial-type cadherin was found in biphasic synovial sarcoma (35 of 35 cases), malignant melanoma (13/21), monophasic fibrous synovial sarcoma (13/26), clear cell sarcoma (4/9), poorly differentiated synovial sarcoma (3/13), diffuse mesothelioma (4/20), malignant epithelioid peripheral nerve sheath tumor (1/6), and epithelioid sarcoma (5/62). Neural-type cadherin was observed in chordoma (11/11), biphasic synovial sarcoma (30/35), diffuse mesothelioma (14/20), malignant melanoma (14/25), epithelioid sarcoma (24/63), epithelioid angiosarcoma (1/4), poorly differentiated synovial sarcoma (2/13), clear cell sarcoma (1/10), and monophasic fibrous synovial sarcoma (1/26). Eighteen cases of primary cutaneous squamous cell carcinomas all tested positive for ECAD, whereas NCAD was focally observed in 5 cases. No expression of either molecule was observed in cases of epithelioid hemangioendothelioma (n = 9), alveolar soft part sarcoma (n = 8), and extraskeletal myxoid chondrosarcoma (n = 7). Conclusions.—Epithelial-type and neural-type cadherins are found in a variety of noncarcinomatous neoplasms with epithelioid features that involve the soft tissues and can be utilized, in association with other immunomarkers, in distinguishing chordoma (100% NCAD) from extraskeletal myxoid chondrosarcoma and conventional chondrosarcoma of bone (0% NCAD), squamous cell carcinoma (100% ECAD) from epithelioid sarcoma (8% ECAD), and biphasic synovial sarcoma (100% ECAD) from diffuse mesothelioma (20% ECAD).

NCOG-33. GROWTH DYNAMICS OF INCIDENTAL MENINGIOMAS - A 10-YEAR PROSPECTIVE STUDY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi159-vi159
Author(s):  
Torbjørn Austveg Strømsnes ◽  
Morten Lund-Johansen ◽  
Geir Olve Skeie ◽  
Bente Sandvei Skeie
Keyword(s):  
Growth Rate ◽  
Tumour Growth ◽  
Growth Dynamics ◽  
Progression Free Survival ◽  
Early Observation ◽  
Active Monitoring ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Observation Period

Abstract There is no consensus for the management of incidental meningiomas. To evaluate the natural history, we assessed tumour growth dynamics during 10 years of active monitoring of 62 patients (45 female and mean age 63.9) harbouring 68 tumours. Radiological and clinical data was obtained was obtained biannually for two years, then annually the following eight. Thirty-six patients (38 tumours) were referred to treatment and/or died of unrelated causes (n=5) within 5 years. The remaining were monitored for up to 10 years. Mean overall survival was at 128 months (95% CI: 118.8-136.7). Median progression free survival was 34 months (95% CI: 14.7-53.3). Median time for growth requiring intervention was 46 months (95% CI: 23.5-68.5). All tumours with self-limiting growth at 5 years (57.9 %) were still stable or reducing in size at 10 years. Mean growth rate decreased from 0.27 cm3/year (95% CI: 0.10-0.43) during the early observation period (0-5 years) to 0.09 cm3/year (95% CI: -0.02-0.21) in the late observation period. No tumours were referred to treatment during the late observation period. Two patients, both with verified WHO2 grade meningiomas succumbed to the disease, seven and eight years after diagnosis. No other patients developed symptoms and none other of the 18 total mortalities were meningioma related. Most clinical and radiological events occur within 5 years after diagnosis. Our findings suggests that if tumour growth slows down during the first 5 years of monitoring, this trend will continue. Clinical follow-up should be sufficient when a self-limiting growth pattern has been established.

BIOM-38. THE PROGNOSTIC ROLE OF THE IMMUNOHISTOCHEMICAL MARKERS H3K27me3, SSTR1-5 AND BAP1 IN MENINGIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi19-vi19
Author(s):  
Felix Behling ◽  
Christina Fodi ◽  
Mirjam Renovanz ◽  
Frank Paulsen ◽  
Marco Skardelly ◽  
...  
Keyword(s):  
Tumor Recurrence ◽  
Prognostic Markers ◽  
Somatostatin Receptors ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Potential Candidate ◽  
Primary Tumors ◽  
Free Survival ◽  
Immunohistochemical Markers ◽  
Increased Risk

Abstract Meningiomas are the most common primary tumors of the nervous system. These slow growing tumors arise from the meninges. Most patients can be cured by surgical excision. Yet, approximately 20% of patients suffer tumor recurrence. Prognostic markers are warranted to facilitate the identification of patients with an increased risk of tumor recurrence. Immunohistochemical markers are very interesting candidates in this regard and could be integrated into the routine clinical workflow as an inexpensive tool for prognostication and risk stratification. We analyzed the prognostic impact of the immunohistochemical expression of H3K27me3, somatostatin receptors 1-5 and BAP1 in the Tübingen meningioma cohort including &gt; 1200 meningiomas. We identified an independent negative prognostic impact of the loss of H3K27me3. An increased expression score for SSTR2A was associated with a shorter progression-free survival. Higher expression of SSTR5 indicated a more favorable prognosis. The loss of BAP1 expression in meningioma cells was a negative prognostic factor with a shorter progression-free survival. Taken together, we present potential candidate prognostic markers that could be further investigated in prospective cohorts to determine their clinical utility.

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