Outcomes of postoperative treatment with concurrent chemoradiotherapy (CRT) in high risk resected oral cavity squamous cell carcinoma (OCSCC): A multi-institutional collaboration.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6080-6080 ◽  
Author(s):  
Jessica Lyn Geiger ◽  
Neil McIver Woody ◽  
C. Jillian Tsai ◽  
Ahmed I. Ghanem ◽  
Neal Dunlap ◽  
...  
Keyword(s):  
High Risk ◽  
Demographic Data ◽  
Disease Free Survival ◽  
Total Sample ◽  
Postoperative Treatment ◽  
High Dose ◽  
P Values ◽  
Administration Schedule ◽  
7Th Edition ◽  
Pathologic Features

6080 Background: Adjuvant CRT with high-dose cisplatin remains standard treatment for OCSCC with high risk pathologic features of positive surgical margins (SM+) and/or extranodal extension (ENE). High-dose cisplatin is associated with significant toxicities, and alternative dosing schedules or treatments are used. We evaluated outcomes associated with different systemic therapies concurrent with RT and the effect of cumulative dosing of cisplatin. Methods: An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I-IVB AJCC 7th edition) treated with primary surgical resection between 1/1/2005 and 1/1/2015 with or without adjuvant therapy was established from 6 academic institutions. Pts were categorized by systemic therapy received, and resultant groups compared for demographic data, pathologic features, and outcomes by t-test and Chi-squared tests. Kaplan-Meier curves, log-rank p-values, and multivariate analysis (MVA) for disease free survival (DFS) and freedom from metastatic disease (DM). Results: From a total sample size of 1282 pts, 196 pts were identified with high risk features (SM+, ENE) who were treated with adjuvant CRT. Median age was 56 years, 63.3% of pts were men, 81.1% were Caucasian, 70.9% had significant tobacco history. 35.7% of pts had SM+, 82.7% ENE, 65.3% with perineural invasion (PNI), 49% had lymphovascular space invasion (LVSI). There was a trend associating higher cisplatin dose delivered with improved locoregional control, DM, and overall survival (OS) (p-values 0.131, 0.084, and 0.187, respectively). DFS was significantly better with higher cisplatin dose (HR = 0.95 per 100 mg/m2 increase in cisplatin). Administration schedule of cisplatin (weekly versus high-dose) was not significantly associated with DFS. On MVA, PNI and higher cisplatin dose remained statistically significant for DFS (p < 0.001 and 0.007). Median OS by cisplatin dose was 10.5 ( < 200 mg/m2) vs. 20.8 months ( > / = 200 mg/m2). Conclusions: This multi-institutional analysis demonstrated cumulative cisplatin dose > / = 200 mg/m2 was associated with improved DFS in high risk resected OCSCC pts. It remains unclear by this analysis if cisplatin administration schedule has any prognostic implication. Further study is warranted to elucidate the optimal cisplatin schedule for this population.

scholarly journals Outcomes of Post-Operative Treatment with Concurrent Chemoradiotherapy (CRT) in High-Risk Resected Oral Cavity Squamous Cell Carcinoma (OCSCC): A Multi-Institutional Collaboration

2021 ◽  
Vol 28 (4) ◽  
pp. 2409-2419
Author(s):  
Arslan Babar ◽  
Neil M. Woody ◽  
Ahmed I. Ghanem ◽  
Jillian Tsai ◽  
Neal E. Dunlap ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Demographic Data ◽  
Disease Free Survival ◽  
Total Sample ◽  
High Dose ◽  
Pathologic Features

Adjuvant chemoradiation (CRT), with high-dose cisplatin remains standard treatment for oral cavity squamous cell carcinoma (OCSCC) with high-risk pathologic features. We evaluated outcomes associated with different cisplatin dosing and schedules, concurrent with radiation (RT), and the effect of cumulative dosing of cisplatin. An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I–IVB AJCC 7th edition) treated with primary surgical resection between January 2005 and January 2015, with or without adjuvant therapy, was established from six academic institutions. Patients were categorized by cisplatin dose and schedule, and resultant groups compared for demographic data, pathologic features, and outcomes by statistical analysis to determine disease free survival (DFS) and freedom from metastatic disease (DM). From a total sample size of 1282 pts, 196 pts were identified with high-risk features who were treated with adjuvant CRT. Administration schedule of cisplatin was not significantly associated with DFS. On multivariate (MVA), DFS was significantly better in patients without perineural invasion (PNI) and in those receiving ≥200 mg/m2 cisplatin dose (p < 0.001 and 0.007). Median DFS, by cisplatin dose, was 10.5 (<200 mg/m2) vs. 20.8 months (≥200 mg/m2). Our analysis demonstrated cumulative cisplatin dose ≥200 mg/m2 was associated with improved DFS in high-risk resected OCSCC pts.

Outcomes of post-operative treatment with concurrent systemic therapy and radiotherapy (RT) in intermediate (INT) risk resected oral cavity squamous cell carcinoma (OCSCC): A multi-institutional collaboration.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17567-e17567
Author(s):  
Jessica Lyn Geiger ◽  
Neil McIver Woody ◽  
C. Jillian Tsai ◽  
Ahmed I. Ghanem ◽  
Neal Dunlap ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Surgical Resection ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Total Sample ◽  
7Th Edition ◽  
Extranodal Extension ◽  
Kaplan Meier ◽  
Improved Outcomes ◽  
Pathologic Features

e17567 Background: Patients (pts) with adverse pathologic factors in resected OCSCC excluding positive surgical margins or extranodal extension represent a group of INT risk disease. Though not standard of care, adjuvant CRT is often used in INT pts. We conducted a multi-institutional study to evaluate factors associated with improved outcomes in INT pts treated with or without chemotherapy. Methods: An IRB-approved collaborative database of patients with primary OCSCC (Stage I-IVB AJCC 7th edition) treated with primary surgical resection between 1/1/2005 and 1/1/2015 with or without adjuvant therapy was established from 6 academic institutions. Pts were categorized by pathologic features and adjuvant therapy. Kaplan Meier curves, log-rank p-values and multivariate analysis (MVA) were used to describe outcomes by treatment including locoregional control (LRC) and disease free survival (DFS). Results: From a total sample size of 1270 patients, 455 INT risk pts were treated with primary surgical resection and adjuvant therapy; 95 received CRT, 274 received RT alone, and 86 received RT without recorded chemotherapy. 49% of pts had perineural invasion (PNI), 24.8% lymphovascular space invasion, 21.5% poorly differentiated histology, 47.3% with pT3/4 disease, and 27.9% with > 2 lymph node positive (LN+). 55.8% of CRT pts were treated with cisplatin. > 2 LN+ was the only significant predictor of LRC (HR 1.49, p= 0.049). PNI and > 2 LN+ were significant predictors of DFS (HR 1.52, p= 0.003 and HR 1.76, p< 0.001). On MVA, after adjusting for > 2 LN+, treatment with cisplatin-RT was borderline significant for LRC (HR 0.52, p= 0.08). 3 year LRC in pts with > 2 LN+ was 84.4% in pts treated with cisplatin-RT compared with 64.9% for RT alone. Conclusions: The addition of cisplatin-based CRT to INT risk pts is controversial but among pts with > 2 LN+ there was a trend toward benefit. This study is limited by small numbers of pts treated with CRT, though these results highlight the need for further investigation in this population to identify INT pts who would benefit from adjuvant therapy intensification.

Double-Unit Cord Blood Transplantation (DCBT) for Acute Leukemia: High Disease-Free Survival in Adults and Children with Comparable Survival in European and Minority Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3080-3080
Author(s):  
Juliet N Barker ◽  
Doris M Ponce ◽  
Anne Marie R Gonzales ◽  
Marissa N Lubin ◽  
Hugo Castro-Malaspina ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Leukemia ◽  
Conflicts Of Interest ◽  
Cord Blood Transplantation ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
European Ancestry ◽  
High Dose ◽  
Free Survival ◽  
Disease Free

Abstract Abstract 3080 As compared to single-unit CBT, DCBT may improve engraftment and protect against relapse. Therefore, we have adopted DCBT for both children and adults with acute leukemia, myelodysplasia (MDS), and myeloproliferative diseases (MPD). However, determinants of disease-free survival (DFS) have yet to be fully established. Furthermore, whether DFS after DCBT is comparable in patients of European and non-European ancestry is of special interest. Therefore, we analyzed the DFS of 75 DCBT recipients with acute leukemia in morphologic remission or aplasia (n = 69), and MDS/MPD with ≤ 5% blasts (n = 6) transplanted from 10/2005-4/2011. Nearly all patients had high-risk disease. Children 0–15 years (n = 23) had the following characteristics: median age 9 years (range 0.9–15); median weight 37 kg (range 7–72); 30% European; and 26% CMV sero-positive. Diagnoses were 43% AML (or biphenotypic), 52% ALL, and 4% MDS/MPD, and all received high-dose conditioning. The children received grafts with a median infused TNC × 107/kg of 3.3 (larger unit) and 2.6 (smaller unit), and 2% of units were 6/6 HLA-A, -B antigen, -DRB1 allele matched, 63% 5/6, and 35% 4/6. Adults ≥ 16 years (n = 52) had the following characteristics: median age 41 years (range 16–69); median weight 69 kg (range 47–105); 48% European; 69% CMV sero-positive; and diagnoses were 63% AML (or biphenotypic), 27% ALL, and 10% MDS/MPD. Fifty percent received high-dose and 50% reduced intensity conditioning. Their units had a median infused TNC/kg of 2.7 and 1.9, and 3% were 6/6 HLA-matched, 47% 5/6, and 50% 4/6. All patients (pediatric and adult) received calcineurin-inhibitor/ mycophenolate mofetil immunosuppression, and none received anti-thymocyte globulin. Sustained donor neutrophil engraftment was seen in 91% of children and 94% of adults at medians of 20 and 26 days, respectively. The incidence of grade II-IV acute GVHD by day 180 was 44% in children and 58% in adults. Day 100 transplant-related mortality (TRM) was 9% in children and 19% in adults. The 2-year relapse incidence was 9% in children and 6% in adults. With a median follow-up of survivors of 26 months (range 4–70), 2-year Kaplan-Meier estimate of DFS was 78% in children and 64% in adults (Figure). Differences in survival by age did not reach significance. Univariate analysis of variables potentially influencing 2-year DFS (with log rank estimates of significance) in all patients is shown in the Table. There were no differences in 2-year DFS according to ancestry, remission status, and conditioning intensity. There was also no difference in 2-year DFS according to engrafting unit-recipient HLA-match (4-6/6 or 10 allele), or engrafting unit infused TNC dose/kg. However, patients who were CMV seronegative had a higher 2-year DFS (85% vs 55%, p = 0.018). Multivariate analysis revealed recipient CMV serostatus was a predictor of DFS independent of patient age, and its effect was mediated by an influence on TRM. We have previously shown that DCBT extends transplant access to minority patients. We now demonstrate that DCBT can achieve high and comparable DFS in both European and non-European pediatric and adult patients with acute leukemia and MDS/MPD. While these are very encouraging results further investigation in racial/ethnic sub-groups is needed. Nonetheless, our findings support DCBT as an immediate alternative therapy for high-risk acute leukemia in patients without suitable unrelated volunteer donors, especially given the very low incidence of relapse. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Minimal Disseminated Disease in Nonmetastatic Retinoblastoma With High-Risk Pathologic Features and Association With Disease-Free Survival

2016 ◽  
Vol 134 (12) ◽  
pp. 1374 ◽  
Author(s):  
Viviana E. Laurent ◽  
Ana Vanesa Torbidoni ◽  
Claudia Sampor ◽  
Daniela Ottaviani ◽  
Valeria Vazquez ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Free Survival ◽  
Free Survival ◽  
Pathologic Features ◽  
Minimal Disseminated Disease ◽  
Disseminated Disease ◽  
Disease Free

scholarly journals Neoadjuvant Chemotherapy in High-Risk Soft Tissue Sarcomas: Final Results of a Randomized Trial From Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) Sarcoma Groups

2020 ◽  
Vol 38 (19) ◽  
pp. 2178-2186 ◽  
Author(s):  
Alessandro Gronchi ◽  
Emanuela Palmerini ◽  
Vittorio Quagliuolo ◽  
Javier Martin Broto ◽  
Antonio Lopez Pousa ◽  
...  
Keyword(s):  
High Risk ◽  
Soft Tissue ◽  
Neoadjuvant Chemotherapy ◽  
Soft Tissue Sarcomas ◽  
Disease Free Survival ◽  
Phase Iii ◽  
High Dose ◽  
Nerve Sheath Tumor ◽  
Open Label ◽  
Cox Models

PURPOSE To determine whether the administration of histology-tailored neoadjuvant chemotherapy (HT) was superior to the administration of standard anthracycline plus ifosfamide neoadjuvant chemotherapy (A+I) in high-risk soft tissue sarcoma (STS) of an extremity or the trunk wall. PATIENTS AND METHODS This was a randomized, open-label, phase III trial. Patients had localized high-risk STS (grade 3; size, ≥ 5 cm) of an extremity or trunk wall, belonging to one of the following five histologic subtypes: high-grade myxoid liposarcoma (HG-MLPS); leiomyosarcoma (LMS), synovial sarcoma (SS), malignant peripheral nerve sheath tumor (MPNST), and undifferentiated pleomorphic sarcoma (UPS). Patients were randomly assigned in a 1:1 ratio to receive three cycles of A+I or HT. The HT regimens were as follows: trabectedin in HG-MLPS; gemcitabine plus dacarbazine in LMS; high-dose prolonged-infusion ifosfamide in SS; etoposide plus ifosfamide in MPNST; and gemcitabine plus docetaxel in UPS. Primary and secondary end points were disease-free survival (DFS) and overall survival (OS), estimated using the Kaplan-Meier method and compared using Cox models adjusted for treatment and stratification factors. The study is registered at ClinicalTrials.gov (identifier NCT01710176 ). RESULTS Between May 2011 and May 2016, 287 patients (UPS: n = 97 [33.8%]; HG-MLPS: n = 65 [22.6%]; SS: n = 70 [24.4%]; MPNST: n = 27 [9.4%]; and LMS: n = 28 [9.8%]) were randomly assigned to either A+I or HT. At the final analysis, with a median follow-up of 52 months, the projected DFS and OS probabilities were 0.55 and 0.47 (log-rank P = .323) and 0.76 and 0.66 (log-rank P = .018) at 60 months in the A+I arm and HT arm, respectively. No treatment-related deaths were observed. CONCLUSION In a population of patients with localized high-risk STS, HT was not associated with a better DFS or OS, suggesting that A+I should remain the regimen to choose whenever neoadjuvant chemotherapy is used in patients with high-risk STS.

Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial

Blood ◽  
2006 ◽  
Vol 107 (12) ◽  
pp. 4614-4622 ◽  
Author(s):  
Donald W. Milligan ◽  
Keith Wheatley ◽  
Timothy Littlewood ◽  
Jenny I. O. Craig ◽  
Alan K. Burnett ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Relapse Rate ◽  
Myeloid Leukemia ◽  
Remission Rate ◽  
Disease Free Survival ◽  
High Dose ◽  
Standard Chemotherapy ◽  
All Trans Retinoic Acid ◽  
Acute Myeloid

AbstractThe optimum chemotherapy schedule for reinduction of patients with high-risk acute myeloid leukemia (relapsed, resistant/refractory, or adverse genetic disease) is uncertain. The MRC AML (Medical Research Council Acute Myeloid Leukemia) Working Group designed a trial comparing fludarabine and high-dose cytosine (FLA) with standard chemotherapy comprising cytosine arabinoside, daunorubicin, and etoposide (ADE). Patients were also randomly assigned to receive filgrastim (G-CSF) from day 0 until neutrophil count was greater than 0.5 × 109/L (or for a maximum of 28 days) and all-trans retinoic acid (ATRA) for 90 days. Between 1998 and 2003, 405 patients were entered: 250 were randomly assigned between FLA and ADE; 356 to G-CSF versus no G-CSF; 362 to ATRA versus no ATRA. The complete remission rate was 61% with 4-year disease-free survival of 29%. There were no significant differences in the CR rate, deaths in CR, relapse rate, or DFS between ADE and FLA, although survival at 4 years was worse with FLA (16% versus 27%, P = .05). Neither the addition of ATRA nor G-CSF demonstrated any differences in the CR rate, relapse rate, DFS, or overall survival between the groups. In conclusion these findings indicate that FLA may be inferior to standard chemotherapy in high-risk AML and that the outcome is not improved with the addition of either G-CSF or ATRA.

Y-Box–Binding Protein YB-1 Identifies High-Risk Patients With Primary Breast Cancer Benefiting From Rapidly Cycled Tandem High-Dose Adjuvant Chemotherapy

2009 ◽  
Vol 27 (36) ◽  
pp. 6144-6151 ◽  
Author(s):  
Oleg Gluz ◽  
Karin Mengele ◽  
Manfred Schmitt ◽  
Ronald Kates ◽  
Raihana Diallo-Danebrock ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Binding Protein ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
High Dose ◽  
Primary Tumors ◽  
Multifunctional Protein ◽  
Conventional Dose

Purpose To investigate the potential of Y-box–binding protein YB-1, a multifunctional protein linked to tumor aggressiveness and multidrug resistance, to identify patients with breast cancer likely to benefit from dose-intensified chemotherapy regimens. Patients and Methods YB-1 was immunohistochemically determined in 211 primary tumors from the prospective, randomized West German Study Group WSG-AM-01 trial in high-risk (≥ 10 involved lymph-nodes) breast cancer (HRBC). Predictive impact of YB-1 was assessed by multivariate survival analysis, including time-varying factor-therapy interactions. Results At median follow-up of 61.7 months, patients receiving rapidly cycled tandem high-dose therapy (HD; two cycles [2×] epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 every 14 days, followed by 2× epirubicin 90 mg/m2, cyclophosphamide 3,000 mg/m2, and thiotepa 400 mg/m2 every 21 days) had better disease-free survival (DFS; hazard ratio [HR] = 0.62; 95% CI, 0.44 to 0.89) and overall survival (OS; HR = 0.59; 95% CI, 0.4 to 0.89) than those receiving conventional dose-dense chemotherapy (DD; 4× epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2, followed by 3× cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 every 14 days). High YB-1 was associated with aggressive tumor phenotype (negative steroid hormone receptor status, positive human epidermal growth factor receptor 2 and p53 status, high MIB-1, unfavorable tumor grade) and poor OS (median 78 v 97 months; P = .01). In patients with high YB-1, HD yielded a 63-month median DFS (P = .001) and a 46-month median OS advantage (P = .002) versus DD. In multivariate models, patients with high B-1 receiving HD (v DD) had one third the hazard rate after 20 months for DFS and one sixth after 40 months for OS. Conclusion In a randomized prospective cancer therapy trial, for the first time, a strong predictive impact of YB-1 on survival has been demonstrated: enhanced benefit from HD (v DD) therapy occurs in HRBC with high YB-1. Future trials could therefore address optimal chemotherapeutic strategies,taking YB-1 into account.

Disease-Free Survival in Adult Patients with Acute Leukemia and Advanced CML Supports Use of Double-Unit Cord Blood Grafts As an Immediate Alternative to 8/8 HLA-Matched Unrelated Donors (URD)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2588-2588
Author(s):  
Doris M. Ponce ◽  
Patrick Hilden ◽  
Sean M. Devlin ◽  
Molly Maloy ◽  
Marissa N Lubin ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
High Risk ◽  
Acute Leukemia ◽  
Cord Blood ◽  
Acute Gvhd ◽  
Disease Free Survival ◽  
Adult Patients ◽  
High Dose ◽  
Free Survival ◽  
Disease Free

Abstract Background: Double-unit cord blood transplantation (DCB-T) is a rapidly available alternative to unrelated donor transplantation (URD-T) for patients with high-risk acute leukemia or advanced CML. Retrospective analyses in adult DCB-T suggest that double-unit CB grafts may be associated with improved disease-free survival (DFS). However, the prioritization of URD-T vs DCB-T is controversial. Methods: We evaluated 175 consecutive adult allograft recipients (120 URD-T and 55 DCB-T) aged 16-60 years transplanted 10/2005-11/2012 for acute leukemia in morphologic remission or aplasia (113 AML/ biphenotypic, 50 ALL), or advanced CML (n = 12). URD grafts were 7-8/8 HLA-matched (74 8/8, 46 7/8). CB grafts were 4-6/6 donor-recipient HLA-matched (4 6/6, 51 5/6, 55 4/6). All patients received either high dose or reduced intensity myeloablative conditioning. The majority of URD-T recipients (n = 111, 93%) received T-cell depleted (TCD) grafts with rabbit ATG, whereas GVHD prophylaxis for DCB-T was calcineurin-inhibitor/mycophenolate mofetil. Results: The median ages of URD-T (43 years) and DCB-T (42 years) recipients were similar (p = 0.713). Distributions of gender, recipient CMV positivity, HCT-CI scores, time from diagnosis or relapse to transplant, diagnoses, disease risk, and percentage of patients with minimal residual disease pre-transplant were also similar. Neutrophil engraftment was slower in DCB-T (95%, median 24 days) than URD-T (100%, median 11 days) (p <0.001). While the incidence of grade II-IV acute GVHD at day 100 was lower in TCD URD-T recipients (15%) than in unmodified URD-T (56%) and DCB-T (55%), p = 0.002, the incidence of day 100 grade III-IV acute GVHD was similar in TCD URD-T, unmodified URD-T, and DCB-T recipients (p = 0.794). With a comparable survivor follow-up [URD-T median 51 months (range 15-99) vs DCB-T median 46 months (range 15-92)], transplant-related mortality was similar (3-year estimates: URD-T 25% vs DCB-T 24%, p = 0.838) whereas the relapse risk was decreased after DCB-T (3-year estimates: URD-T 23% vs DCB-T 9%, p = 0.008). Overall, the 3-year DFS after URD-T was 52% and 68% after DCB-T (p = 0.056). When split into 3 groups, the 3-year DFS was 59% in 8/8 URD-T, 40% in 7/8 URD-T, and 68% in DCB-T, p = 0.043 (Figure). Multivariate analysis was performed to determine risk factors for disease relapse or death in the 175 patients (Table). Female gender (HR 1.65, p = 0.029), diagnosis of ALL (HR 2.11, p = 0.002), and mismatched URD-T (HR 1.97, p = 0.027) were each significantly associated with treatment failure. Conclusions: DCB-T can achieve favorable DFS in adults with acute leukemia and CML with low relapse rates. In this series, multivariate analysis demonstrated that mismatched URD-T was independently associated with lower DFS. Our findings support use of DCB-T as an immediate alternative for high-risk acute leukemia and advanced CML in adult patients without a readily available 8/8 allele HLA-matched unrelated volunteer donor. This could have the additional benefit of speeding time to transplant in high-risk patients. Table Variable MultivariateHR (95% CI) P-value Male Female Reference 1.65 (1.05-2.59) 0.029 Recipient CMV Negative Recipient CMV Positive Reference 1.34 (0.85-2.12) 0.201 HCT-CI score 0-2 HCT-CI score > 3 Reference 1.56 (0.98-2.47) 0.059 AML/CML ALL Reference 2.11 (1.30-3.41) 0.002 DCB-T 8/8 URD-T 7/8 URD-T Reference 1.32 (0.72-2.41) 1.97 (1.08-3.60) - 0.365 0.027 Figure Figure. Disclosures No relevant conflicts of interest to declare.

Prognostic role of MRP1 in localized high-risk soft tissue sarcoma (STS): Translational research associated to randomized phase III trial (ISG-STS 1001).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11543-11543
Author(s):  
Javier Martin Broto ◽  
David Silva Moura ◽  
Rafael Ramos ◽  
Luca Braglia ◽  
Paola Collini ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Value ◽  
Disease Free Survival ◽  
Phase Iii ◽  
High Dose ◽  
Prognostic Role ◽  
Phase Iii Trial ◽  
Group A ◽  
Group B ◽  
Worse Prognosis

11543 Background: The ceiling-drug effect seen for most active drugs in STS could be related, partially, to multidrug resistance mechanisms (MDRM). We previously reported the independent prognostic role for RFS and OS of MRP1 in high-risk localized STS of limbs and trunk-wall treated with epirubicin and ifosfamide (Mol Cancer Ther.2014 13(1):249-59). A translational study was carried out within the randomized phase III trial of epirubicin plus ifosfamide vs histotype-tailored neoadjuvant chemotherapy (NCT01710176), to investigate MRP1 prognostic value using the trial population as validation set. Methods: Patients enrolled in the trial were invited to participate, through the informed consent, to this analysis. IHC used QCRL-1 (Santa Cruz biotechnology) MRP1 monoclonal antibody. TMAs were built on the highest-grade area of each tumor, being the procedure blinded for clinical data. MRP1 expression was grouped as low (≤ 25% positive cells) vs high ( > 25% positive cells) expression. For data analysis, patients were grouped as A) epirubicin plus ifosfamide control arm and B) histotype-tailored experimental arm. Drugs used in group B were: gemcitabine-docetaxel (UPS), gemcitabine-DTIC (LMS), trabectedin (High-grade (HG) myxoid LPS), ifosfamide-etoposide (MPNST) and high-dose ifosfamide (SS). Prognostic value of MRP1’s extension was analyzed using Cox’s proportional hazard regression. A p-value < 0.05 was considered statistically significant. Results: 175 patients were analyzed (median age 49; males 61%) with median follow-up of 4.66 y. Group A (n = 88) included HG-myxoid LPS (27%), SS (25%), UPS (24%), LMS (12%) MPNST (10%) and others (2%); group B (n = 87) included UPS (38%), SS (24%), HG-myxoid LPS (20%), LMS (10%) and MPNST (8%). MRP1 high extension was distributed as follows: 48% (A) and 57% (B). High MRP-1 expression showed significantly worse prognosis for disease-free survival (DFS) (HR 2.71 (1.31-5.62) p = 0.007) and a trend towards worse OS (HR = 2.75 (0.97-7.81) p = 0.058) in group A. No correlation was seen between MRP-1 expression and DFS (p = 0.384) or OS (p = 0.665), in group B. Conclusions: MRP1 overexpression was related to significant worse prognosis in 2 prospective randomized series of high-risk, localized, STS treated with neoadjuvant epirubicin and ifosfamide. These agents are both substrate of MRP1; this could add rationale for a possible predictive role, as MDRM, for the two most active drugs in STS. A trial combining epirubicin, ifosfamide and MRP1 inhibitor is currently under design.

The Role of Irradiation of the Internal Mammary Lymph Nodes in High-Risk Stage II to IIIA Breast Cancer Patients After High-Dose Chemotherapy: A Prospective Sequential Nonrandomized Study

2003 ◽  
Vol 21 (14) ◽  
pp. 2713-2718 ◽  
Author(s):  
Salomon M. Stemmer ◽  
Shulamith Rizel ◽  
Izhar Hardan ◽  
Adamous Adamo ◽  
Avivit Neumann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Electron Beam ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cox Regression ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
Stage Ii ◽  
High Dose ◽  
Internal Mammary

Purpose: This phase II single-institution prospective, nonrandomized trial investigates high-dose adjuvant chemotherapy and locoregional radiotherapy in patients with breast cancer. We compared the outcome of patients in this study treated with radiotherapy fields including the internal mammary nodes (IMN) to a group of patients who did not receive IMN irradiation. Patients and Methods: 100 patients with high-risk stage II–III breast cancer received doxorubicin-based adjuvant chemotherapy followed by high-dose chemotherapy, stem-cell support, and locoregional radiotherapy. The radiotherapy included electron-beam irradiation to the IMN. For 20 months during the study, no electron-beam facility was available and we were unable to deliver the IMN irradiation as planned to 33 patients. The remaining 67 patients (32 treated before and 35 treated after this period) received IMN irradiation. Patients with receptor-positive tumors received tamoxifen for 5 years. Results: At a median follow-up of 77 months for all of the patients, disease-free survival (DFS) was significantly prolonged in patients receiving IMN radiation compared to those without IMN radiation (73% v 52%; P = .02). A trend was seen for overall survival (OS; 78% v 64%; P = .08). Cox regression multivariate analysis found IMN radiotherapy to be significant both for DFS and OS. Estrogen receptor positivity was also significant for DFS. There was no treatment related mortality. Conclusion: In patients with high-risk stage II to III breast cancer, the inclusion of the IMN in the radiotherapy field was associated with a statistically significant increase in DFS and a borderline increase in OS.

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