Systemic chemotherapies retain antitumor activity in desmoid tumors independent of specific mutations in CTNNB1 or APC: A multi-institutional retrospective study

PURPOSE: Determine whether specific CTNNB1 or APC mutations in patients with desmoid tumor were associated with differences in clinical responses to systemic treatments. EXPERIMENTAL DESIGN: We established a multi-institutional dataset of previously treated patients with desmoid tumor across four U.S. sarcoma centers, including demographic and clinicopathologic characteristics, treatment regimens, and clinical and radiographic responses. CTNNB1 or APC mutation status was determined from prior pathology records, or archival tissue was requested and analyzed by Sanger sequencing and/or next-generation sequencing. Evaluable patients with mutation results were analyzed to determine clinical progression-free survival (cPFS), RECIST 1.1 PFS (rPFS), time to next treatment (TTNT), and overall survival (OS). Kaplan-Meier analysis and Cox proportional hazards regression were performed to identify differences in cPFS, rPFS, TTNT, and OS by mutation subtype, desmoid tumor location, and treatment regimen. RESULTS: A total of 259 evaluable patients were analyzed for at least one of the survival outcomes, with 177 patients having mutation data. First- and second-line cPFS, rPFS, and TTNT were not significantly affected by mutation subtype; however, APC-mutant desmoid tumors demonstrated nonstatistically significant inferior outcomes. Extremity/trunk desmoid tumor location and treatment with doxorubicin-based, methotrexate/vinca alkaloids and sorafenib regimens were associated with better clinical outcomes compared with surgery or other therapies, including estrogen-receptor blockade and imatinib. OS was significantly worse with APC or CTNNB1 negative/other mutations. CONCLUSIONS: Mutation subtype did not affect responses to specific systemic therapies. APC mutations and nonextremity desmoid tumor locations remain prognostic for worse outcomes, and earlier initiation of systemic therapy for these higher-risk desmoid tumors should be prospectively evaluated. See related commentary by Greene and Van Tine, p. 3911

A global collaboRAtive study of CIC-rearranged, BCOR::CCNB3-rearranged and other ultra-rare unclassified undifferentiated small round cell sarcomas (GRACefUl)

[Background] Undifferentiated small round cell sarcomas (URCSs) represent a diagnostic challenge, and their optimal treatment is unknown. We aimed to define the clinical characteristics, treatment, and outcome of URCS patients.[Methods] URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centres were retrospectively identified. Based on molecular assessment, cases were classified as follows: (1) CIC-rearranged round cell sarcomas, (2) BCOR::CCNB3-rearranged round cell sarcomas, (3) unclassified URCSs. Treatment, prognostic factors and outcome were reviewed.[Results] In total, 148 patients were identified [88/148 (60%) CIC-rearranged sarcoma (median age 32 years, range 7–78), 33/148 (22%) BCOR::CCNB3-rearranged (median age 17 years, range 5–91), and 27/148 (18%) unclassified URCSs (median age 37 years, range 4–70)]. One hundred-one (68.2%) cases presented with localised disease; 47 (31.8%) had metastases at diagnosis. Male prevalence, younger age, bone primary site, and a low rate of synchronous metastases were observed in BCOR::CCNB3-rearranged cases. Local treatment was surgery in 67/148 (45%) patients, and surgery + radiotherapy in 52/148 (35%). Chemotherapy was given to 122/148 (82%) patients. At a 42.7-month median follow-up, the 3-year overall survival (OS) was 92.2% (95% CI 71.5–98.0) in BCOR::CCNB3 patients, 39.6% (95% CI 27.7–51.3) in CIC-rearranged sarcomas, and 78.7% in unclassified URCSs (95% CI 56.1–90.6; p < 0.0001).[Conclusions] This study is the largest conducted in URCS and confirms major differences in outcomes between URCS subtypes. A full molecular assessment should be undertaken when a diagnosis of URCS is suspected. Prospective studies are needed to better define the optimal treatment strategy in each URCS subtype.This work was supported by the Carisbo Foundation Call for Translational and Clinical Medical Research.Peer reviewe

Le livre des tests / Michael Nathenson

Contient une table des matièresAvec mode text

Independant learning in higher education /

Bibliogr.: p. 296-324Comprend des inde

Surgical resection for recurrent retroperitoneal leiomyosarcoma and liposarcoma

Abstract Background Retroperitoneal soft tissue sarcomas (STS) include a number of histologies but are rare, with approximately 3000 cases in the USA per year. Retroperitoneal STS have a high incidence of local and distant recurrence. The purpose of this study was to review the University of Maryland Medical Center’s (UMMC) treatment experience of retroperitoneal STS, where the patient population served represents a diverse socioeconomic and ethnic catchment. Methods IRB approval was obtained. We constructed a de-identified database of patients diagnosed with retroperitoneal liposarcomas (LPS) or leiomyosarcomas (LMS) treated at UMMC between 2000 and 2013. A total of 49 patients (Pts) with retroperitoneal STS met our eligibility criteria. Kaplan-Meier plots were used to graphically portray progression-free survival (PFS) and overall survival (OS). The log-rank test was used to compare time-to-event distributions. Results The median OS for all patients (Pts) was 6.3 years, and the 2-year OS rate was 81%. The median PFS for all Pts was 1.8 years, and the 2-year PFS rate was 45%. There was no difference in OS and PFS among LMS and LPS patients; the median OS for LMS was 3.8 years vs. LPS 6.4 years (p = 0.33), and the median PFS for LMS was 1.2 years vs. LPS 2.5 years (p = 0.28). There was a significant difference between histology and race (p = 0.001). LPS were primarily Caucasian 86% vs. 14% black, whereas LMS were primarily black 52% vs. 33% Caucasian. OS was influenced by functional status, gender, American Joint Committee on Cancer (AJCC) stage, grade, histology, tumor size, and extent of resection. PFS was influenced by AJCC stage, grade, and extent of resection. Neither adjuvant chemotherapy (1 Pt) nor neoadjuvant/adjuvant radiation therapy (18 Pts) influenced OS or PFS. There was a non-significant difference that Pts who could undergo resection of local recurrence had improved 2-year OS, with 100% LMS and LPS compared to 2-year OS of 71% (LMS) and 78% (LPS) not undergoing resection of local recurrence. Conclusions This study suggests a higher incidence of leiomyosarcoma in the African-American population. This study confirms the prognostic importance of grade, tumor size, AJCC stage, histology, and extent of resection in patient outcomes, at a large substantially diverse academic medical center. Future research into the biological features of liposarcoma and leiomyosarcoma Pts imparting these characteristics will be important to define

Treatment of Recurrent or Metastatic Uterine Adenosarcoma

Purpose. This study retrospectively evaluated overall survival (OS) by treatment of recurrent or metastatic uterine adenosarcoma including surgery, radiation, chemotherapy, and hormonal therapy and evaluated OS and progression-free survival (PFS) after 1st line systemic chemotherapy. Methods. 78 patients with recurrent or metastatic adenosarcoma comprised the study population. The Kaplan-Meier method was used to estimate OS and PFS. The log-rank test was performed to test the difference in survival between groups. Results. Median OS from diagnosis of recurrent or metastatic disease was 1.8 yrs. OS was influenced by pathology on recurrence, p=0.035. Median OS differed by surgery for 1st recurrence 26.3 months versus 15.1 months. OS was not influenced by chemotherapy, p=0.58, palliative radiation, p=0.58, or hormonal therapy, p=0.15. The response rate (CR + PR) per RECIST 1.1 for chemotherapy was 31.2% for doxorubicin-based regimens and 14.3% for gemcitabine/docetaxel. OS since 1st line chemotherapy was not significantly different among chemotherapy regimens. However, the median PFS was superior for doxorubicin/ifosfamide (15.4 months) compared to gemcitabine/docetaxel (5.0 months), platinum-based regimens (5.7 mo), or other doxorubicin-based regimens (6.5 months). Conclusion. These results suggest that surgery is an important treatment modality for recurrent or metastatic uterine adenosarcoma, and the most effective chemotherapeutics are doxorubicin/ifosfamide and gemcitabine/docetaxel