scholarly journals Clinical Features, Treatment, and Outcome in 102 Adult and Pediatric Patients with Localized High-Grade Synovial Sarcoma

Sarcoma ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
H. Al-Hussaini ◽  
D. Hogg ◽  
M. E. Blackstein ◽  
B. O'Sullivan ◽  
C. N. Catton ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Synovial Sarcoma ◽  
Surgical Resection ◽  
Pediatric Patients ◽  
Response Rate ◽  
High Grade ◽  
En Bloc ◽  
Positive Surgical Margins ◽  
Response To Neoadjuvant Chemotherapy

Background. There remains controversy on the routine use of chemotherapy in localized SS.Methods. The records of 87 adult (AP) and 15 pediatric (PP) patients with localized SS diagnosed between 1986 and 2007 at 2 centres in Toronto were reviewed.Results. Median age for AP and PP was 37.6 (range 15–76) and 14 (range 0.4–18) years, respectively. 65 (64%) patients had large tumours (>5 cm). All patients underwent en bloc surgical resection resulting in 94 (92.2%) negative and 8 (7.8%) microscopically positive surgical margins. 72 (82.8%) AP and 8 (53%) PP received radiotherapy. Chemotherapy was administered to 12 (13.8%) AP and 13 (87%) PP. 10 AP and 5 PP were evaluable for response to neoadjuvant chemotherapy, with response rate of10%and40%, respectively. 5-year EFS and OS was69.3±4.8%and80.3±4.3%, respectively, and was similar for AP and PP, In patients with tumors >5 cm, in whom chemotherapy might be considered most appropriate, relapse occurred in 9/19 (47%) with chemotherapy, compared to 17/46 (37%) In those without.Conclusions. Patients with localized SS have a good chance of cure with surgery and RT. Evidence for a well-defined role of chemotherapy to improve survival In localized SS remains elusive.

Outcome of leiomyosarcoma of bone: A single center experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e21502-e21502
Author(s):  
Rajeev Rajendra ◽  
Seth Pollack ◽  
Eve T. Rodler ◽  
Ernest U. Conrad ◽  
Darin J Davidson ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Neoadjuvant Chemotherapy ◽  
Surgical Resection ◽  
Treatment Strategies ◽  
Recurrence Time ◽  
Low Grade ◽  
High Grade ◽  
Response To Chemotherapy

e21502 Background: Leiomyosarcoma (LMS) of bone is a very rare sarcoma subtype. These tumors are managed akin to osteosarcoma, with neoadjuvant chemotherapy followed by surgery. The precise role of chemotherapy remains to be defined. Methods: Patients treated with primary bone LMS at the University of Washington between 2002 and 2012 were included. Patients with high grade tumors were treated with neoadjuvant chemotherapy and surgery; whereas those with low grade tumors were treated with surgical resection alone. Chemotherapy consisted of doxorubicin and ifosfamide x 2 cycles. Treatment details included: initial treatment (surgery versus chemo), surgical and pathological margins, and timing of chemotherapy. Follow-up data included: time to local recurrence, time to metastasis, time to last follow up if alive, or time to death. Results: Ten patients were identified, 4 male and 6 female. Median age at diagnosis: 52 years (range 29 - 91). The primary site was the distal femur in 5 patients, and the hemipelvis, acetabulum, proximal femur, distal clavicle and mid-shaft of femur in 1 patient each. Median tumor size at diagnosis was 8 cm. Five were high-grade tumors; 3 were intermediate and 2 were low grade. Four of 10 patients received neoadjuvant chemotherapy, with the following histological response; 70%, 30%, 15% and <5%. None of these patients had a dimensional radiological response to chemotherapy. Of the patients treated with surgery alone, one developed a local recurrence and another developed metastatic disease. Of the patients treated with chemotherapy and surgery, 1 died from an unrelated cause. Median follow-up was 9 months (range 0 - 83). Median DFS was 9 months (range 0 - 83). OS has not yet been reached. Conclusions: Surgical resection remains the mainstay of management of LMS of bone. The role of neoadjuvant chemotherapy requires further evaluation. Larger collaborative studies and biomarker analyses are essential to evaluate optimal treatment strategies for this rare disease.

Study of the expression of integrin pathway's proteins as predictive markers of response to neoadjuvant chemotherapy in pretreatment biopsies of patients with high-grade osteosarcoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10076-10076
Author(s):  
Elizabeth Laurence Cohen-Jonathan Moyal ◽  
Sophie Le Guellec ◽  
Thomas Filleron ◽  
Marie-Bernadette Delisle ◽  
Christine Chevreau ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Surgical Resection ◽  
Preoperative Chemotherapy ◽  
Poor Response ◽  
Conservative Surgery ◽  
High Grade ◽  
Pre Treatment ◽  
Gsk 3Β ◽  
High Grade Osteosarcoma ◽  
Response To Neoadjuvant Chemotherapy

10076 Background: Up to now, chemosensitivity to neoadjuvant chemotherapy performed for patients with osteosarcoma is evaluated on the surgical resection by the evaluation of the percentage of necrotic cells. No predictive profile of chemotherapy has been described yet. Because we have previously shown that integrin pathway controls genotoxic-induced cell death and hypoxia via ILK, FAK and RhoB, we hypothesized that the expression of the proteins involved in this pathway in pre-treatment biopsies could be associated with sensitivity to chemotherapy in osteosarcoma. Methods: We studied by immunohistochemistry β1, β3, β5, integrins, ILK, FAK, GSK-3β, RhoB and Ang-2 expression in 36 osteosarcomas biopsies of patients obtained before treatment. All the patients were treated by the SFOP OS94 chemotherapy protocol and underwent wide conservative surgery. Response to preoperative chemotherapy was assessed on the surgical resection by the Rosen’s protocol. An immunoreactive score (IRS) was assessed, combining the percentage of positive tumour cells and staining intensity. We evaluated the correlation of the selected markers expression with response to preoperative chemotherapy and clinical outcome. Results: FAK expression was statistically linked with ILK expression (rho=0.43; p=0.020), β1integrin expression with FAK expression (rho=0.51); p=0.003), RhoB with ILK expression (rho=0.55; p=0.002), and β1 with β3integrin expression (rho=0.70; p<.001), suggesting that a regulation of the integrin pathway that we studied might exist in high grade osteosarcoma. Moreover, the combination of β5 integrin, FAK and GSK-3β discriminated good and poor responder to chemotherapy (89.9%; 95% CI= [77.4;1.00], yielding a sensitivity of 94.1%, a specificity of 85.7% and a diagnostic accuracy of 90.3%. Conclusions: We report for the first time a protein expression profile on pre-treatment biopsies associating β5 integrin FAK and GSK-3β related with a poor response to neoadjuvant chemotherapy. This profile could help to select patients for clinical trials using inhibitors of this pathway in association with chemotherapy.

Molecular response to neoadjuvant chemotherapy in high-grade serous ovarian carcinoma

2016 ◽  
Vol 141 ◽  
pp. 151-152
Author(s):  
R.C. Arend ◽  
Z.C. Dobbin ◽  
D.K. Crossman ◽  
B.K. Erickson ◽  
J.D. Boone ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Ovarian Carcinoma ◽  
Molecular Response ◽  
High Grade ◽  
Serous Ovarian Carcinoma ◽  
Response To Neoadjuvant Chemotherapy

Is there a role for neoadjuvant chemotherapy in the management of non-carcinoid epithelial neoplasms of the appendix?

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15115-15115
Author(s):  
M. H. Katz ◽  
P. F. Mansfield ◽  
C. Eng ◽  
R. A. Wolff ◽  
P. Diaz ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Standard Of Care ◽  
Low Grade ◽  
High Grade ◽  
Appendiceal Neoplasms ◽  
Tertiary Center ◽  
Standardized Treatment ◽  
Crs And Hipec ◽  
Epithelial Neoplasms

15115 Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) are considered the standard of care for patients with pseudomyxoma peritonei (PMP) and carcinomatosis of appendiceal origin. The role of neoadjuvant chemotherapy (CTX) in the management of these patients is unknown. Methods: Retrospective analysis of all patients evaluated for the treatment of appendiceal epithelial neoplasms at a tertiary center between 1992 and August 2006. All diagnoses were confirmed pathologically and classified by a single group of pathologists. Patients with carcinoid tumors or metastases to the appendix were excluded. Tumor histology, stage, peritoneal-based disease, and the potential for complete cytoreduction dictated treatment. Results: 250 consecutive patients were evaluated, 140 of whom had low grade disease. 114 underwent CRS and HIPEC. Median follow-up was 24 mos from referral. Average time to referral was 13 mos after diagnosis (range 0–243); 85% had undergone prior surgical therapy (median 1.3 operations, range 1–4); 22% had previous CTX consisting of many different regimens. 5- and 10-year survival for patients with low grade tumors treated with CRS and HIPEC alone (n=80) were 84% and 68%, respectively. 21 patients with low grade tumors had CTX prior to CRS and HIPEC. There was no effect on overall survival (p = 0.61). 5-and 10-year survival of 39 patients with low grade histology who did not receive CRS and HIPEC was 55% and 30%, respectively (p = 0.009). 83 patients with intermediate and high-grade disease who received CTX but not CRS and HIPEC had a 5- year survival of 27%. 5-year survival for patients with intermediate or high grade disease who underwent CRS and HIPEC (n=13) was 67%. Conclusions: Patients with peritoneal-based disease from non-carcinoid epithelial neoplasms of the appendix who undergo CRS and HIPEC have a more favorable survival. Currently there is no survival advantage to the use of CTX before CRS and HIPEC for low grade appendiceal neoplasms. The role of neoadjuvant CTX and biologic agents for patients with high grade neoplasms needs to be determined. Early referral to a peritoneal malignancy center will help standardized treatment for these patients. No significant financial relationships to disclose.

Effect on response to neoadjuvant chemotherapy in high-grade serous ovarian cancer by inhibiting the GAS6/AXL pathway and inducing homologous recombination deficiency.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6080-6080
Author(s):  
Mary M Mullen ◽  
Elena Lomonosova ◽  
Michael Driscoll Toboni ◽  
Hollie M Noia ◽  
Danny Wilke ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Homologous Recombination ◽  
Neoadjuvant Chemotherapy ◽  
Mouse Models ◽  
Poor Response ◽  
Tumor Burden ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Response To Neoadjuvant Chemotherapy

6080 Background: Less than 10% of patients with high grade serous ovarian cancer (HGSC) have a complete pathologic response to neoadjuvant chemotherapy. We aimed to identify a biomarker predictive of response to neoadjuvant chemotherapy and to determine if GAS6/AXL inhibition with AVB500 (AVB) could increase platinum response. Methods: AVB was supplied by Aravive Biologics. HGSC tumor samples were obtained pre- and post-neoadjuvant chemotherapy. GAS6 expression was measured by tissue immunohistochemistry (IHC) and serum ELISA. Four HGSC cell lines were used for all experiments. Immunofluorescent (IF) assays targeting ɣH2AX for DNA damage, RAD51, BRCA1, and BRCA2 for homologous recombination (HR) and 53BP1 for non-homologous end joining (NHEJ) were performed. Flow cytometry was used to evaluate RPA binding. DNA fiber assays were performed. In vitro clonogenic assays were done on chemoresistant ovarian tumor cells treated with carboplatin (carbo) +/- AVB and olaparib +/- AVB. Synergy assays were analyzed using Combenefit software. Mouse models were used to evaluate the combination of carboplatin + AVB and olaparib + AVB on tumor burden. Results: Patients with high pretreatment tumor GAS6 IHC expression ( > 85%) or serum GAS6 concentrations ( > 25ng/mL) were more likely to have a poor response to neoadjuvant chemotherapy than those with low GAS6 (P = 0.002). Additionally, high GAS6 concentration was associated with decreased overall survival (24.4 months versus undefined, P = 0.009). Carbo + AVB resulted in decreased clonogenic colonies compared to carbo alone (p < 0.05). In vivo tumor mouse models treated with chemotherapy + AVB had significantly less tumor burden than those treated with chemotherapy alone (50mg vs 357mg, P = 0.003). We identified an induction in HR deficiency by a decrease in RAD51, BRCA1, and BRCA2 foci and RPA binding in cells treated with carbo + AVB compared to carbo (P < 0.05). There was increase in ɣH2AX and 53BP1 foci as well as replication fork slowing in tumor cells treated with carboplatin + AVB (P < 0.01). We also AVB and carboplatin were synergistic. Olaparib + AVB resulted in decreased clonogenic colonies (P < 0.05) and decreased tumor burden in mouse models (76mg vs 171mg, P = 0.03) compared to olaparib alone. Conclusions: GAS6 is a potential biomarker predictive of poor response to neoadjuvant chemotherapy in HGSC. Inhibition of this GAS6/AXL pathway with AVB improves sensitivity to traditional neoadjuvant chemotherapy by inducing a homologous recombination deficiency.

scholarly journals The role of carboplatin in the neoadjuvant chemotherapy treatment of triple negative breast cancer

2017 ◽  
Author(s):  
Aurelio Bartolome Castrellon ◽  
Ihor Pidhorecky ◽  
Vicente Valero ◽  
Luis Estuardo Raez
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Response Rate ◽  
Pathologic Response ◽  
Chemotherapy Treatment ◽  
Improved Outcomes ◽  
Selection Of Patients ◽  
Selection Of ◽  
Made In

Triple negative breast (TNBC) cancer constitutes a heterogeneous group of disease with histologic and molecular differences. Complete pathologic response to neoadjuvant chemotherapy (NACT) in TNBC is associated with improved outcomes. Efforts have been made in identifying drug combinations that will increase the response rate to preoperative chemotherapy. In this review we present recent studies that have incorporated carboplatin (Cb) in the NACT of TNBC. We discuss the homologous recombination deficiency score and the somatic or germline mutation for BRCA as potential biomarkers for future selection of patients that could benefit from the addition of Cb to NACT.

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