scholarly journals Genetic Polymorphisms in the Tumor Necrosis Factor Locus Influence Non-Hodgkin's Lymphoma Outcome

Blood ◽  
1998 ◽  
Vol 91 (10) ◽  
pp. 3574-3581 ◽  
Author(s):  
Krzysztof Warzocha ◽  
Patricia Ribeiro ◽  
Jacques Bienvenu ◽  
Pascal Roy ◽  
Carole Charlot ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Necrosis ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Large Cell ◽  
Rank Test ◽  
Free Survival ◽  
Log Rank Test ◽  
Large Cell Lymphoma ◽  
Necrosis Factor

Systemic release of tumor necrosis factor (TNF) and lymphotoxin-α (LTα) has been found to contribute to the severity of non-Hodgkin's lymphoma (NHL). We investigated whether genetic polymorphisms in the TNF locus, previously shown to influence TNF and LTα genes expression, might contribute to these cytokines production and to the clinical course of NHL. Genomic DNA from 273 lymphoma patients was typed for TNF (−308) polymorphism using an allele-specific polymerase chain reaction (PCR) and for LTα (+252) polymorphism with a PCR-based restriction fragment length polymorphism. The presence of the TNF allele involved in increased TNF gene transcription was associated with higher plasma levels of this cytokine at the time of lymphoma diagnosis (χ2 test, P = .013). An extended haplotype analysis showed that the presence of at least two TNF or LTα high-producer alleles constituted a risk factor for first-line treatment failure (χ2 test, P = .021), shorter progression-free survival (log-rank test, P = .0007), and overall survival (log-rank test, P = .012). In the subgroup of 126 patients with diffuse large-cell lymphoma, the presence of two or more TNF/LTα high producing alleles contributed significantly to a higher rate of relapse and progression (log-rank test, P = .045 and P = .027). In multivariate Cox regression models including the variables of the International Prognostic Index, the TNF/LTα haplotype status was found to be an independent risk factor for progression-free survival (relative risk 2.33, 95% confidence interval [1.17 to 4.64], P = .0053) and overall survival (relative risk 1.92, 95% confidence interval [0.63 to 5.80],P = .081) of large-cell lymphoma patients. These results indicate that genetic polymorphism leading to increased TNF production influences the outcome of NHL and suggest a pathophysiological role for the genetic control of the immune response in lymphoid malignancies.

scholarly journals Genetic Polymorphisms in the Tumor Necrosis Factor Locus Influence Non-Hodgkin's Lymphoma Outcome

Blood ◽  
1998 ◽  
Vol 91 (10) ◽  
pp. 3574-3581 ◽  
Author(s):  
Krzysztof Warzocha ◽  
Patricia Ribeiro ◽  
Jacques Bienvenu ◽  
Pascal Roy ◽  
Carole Charlot ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Necrosis ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Large Cell ◽  
Rank Test ◽  
Free Survival ◽  
Log Rank Test ◽  
Large Cell Lymphoma ◽  
Necrosis Factor

Abstract Systemic release of tumor necrosis factor (TNF) and lymphotoxin-α (LTα) has been found to contribute to the severity of non-Hodgkin's lymphoma (NHL). We investigated whether genetic polymorphisms in the TNF locus, previously shown to influence TNF and LTα genes expression, might contribute to these cytokines production and to the clinical course of NHL. Genomic DNA from 273 lymphoma patients was typed for TNF (−308) polymorphism using an allele-specific polymerase chain reaction (PCR) and for LTα (+252) polymorphism with a PCR-based restriction fragment length polymorphism. The presence of the TNF allele involved in increased TNF gene transcription was associated with higher plasma levels of this cytokine at the time of lymphoma diagnosis (χ2 test, P = .013). An extended haplotype analysis showed that the presence of at least two TNF or LTα high-producer alleles constituted a risk factor for first-line treatment failure (χ2 test, P = .021), shorter progression-free survival (log-rank test, P = .0007), and overall survival (log-rank test, P = .012). In the subgroup of 126 patients with diffuse large-cell lymphoma, the presence of two or more TNF/LTα high producing alleles contributed significantly to a higher rate of relapse and progression (log-rank test, P = .045 and P = .027). In multivariate Cox regression models including the variables of the International Prognostic Index, the TNF/LTα haplotype status was found to be an independent risk factor for progression-free survival (relative risk 2.33, 95% confidence interval [1.17 to 4.64], P = .0053) and overall survival (relative risk 1.92, 95% confidence interval [0.63 to 5.80],P = .081) of large-cell lymphoma patients. These results indicate that genetic polymorphism leading to increased TNF production influences the outcome of NHL and suggest a pathophysiological role for the genetic control of the immune response in lymphoid malignancies.

Nodal Peripheral T-Cell Lymphoma – a Clinical and Epidemiological Analysis at Medicine School of Sao Paulo University

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1706-1706
Author(s):  
Luis Alberto de Padua Covas Lage ◽  
Marianne Castro Goncalves ◽  
Rodrigo Santucci ◽  
Renata Oliveira Costa ◽  
Debora Levy ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
High Risk ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Free Survival ◽  
Large Cell Lymphoma

Abstract Background: Peripheral T-cell lymphoma (PTCL) are a biologically and clinically heterogeneous group of rare diseases arising from mature or activated post-thymic T lymphocytes. Correspond to 10% to 15% of lymphoid malignancies with marked geographical variation in incidence. According to the WHO classification they are divided into nodal, extranodal, primary cutaneous and leukemic or disseminated and encompass 18 distinct entities. The nodal group involves the peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic lymphoma (AITL), anaplastic large cell lymphoma ALK positive (ALCL-ALK+) and anaplastic large cell lymphoma ALK negative (ALCL-ALK-). The literature of PTCL is scarce, especially in our country where data of epidemiology, clinical features and outcomes are usually rarely available. So, to better understand PTCL we performed a retrospective study with patients treated in a reference service for cancer treatment in Brazil. Methods: Eight-seven nodal PTCL patients treated with anthracyclne-based regimen (CHOP or, CHOEP) from January 2000 to June 2014 were evaluated retrospectively at the Medicine School of Sao Paulo University, Brazil. All patients lower than 60 years were consolidated with autologous hematopoietic stem cell transplantation (ASCT) in first CR or PR except that with ALCL-ALK+ diagnosis. Refractory and relapsed patients were salvaged with 3-4 cycles of IVAC (Ifosphamide 1.5 g/m2 i.v D1-D5, etoposide 100mg/m2 i.v D1-D5, aracytin 2g/m2 i.v twice a day D1-D2) regimen and submitted to ASCT. It was performed a central histopathological review and clinical and epidemiological data were obtained from medical records. Patients were evaluated for overall response (OR) including complete response (CR) and partial response (PR), overall survival (OS) and progression free survival (PFS). Statistical analysis was performed using the STATA-3 program using and a p-value ≤ 0.05 was considered statistically significant. Results: Of the 87 patients, 34 (39.08%) cases were classified as ALCL-ALK-, 27 (31.03%) as PTCL-NOS, 16 (18.39%) as ALCL-ALK+, 6 (6.89%) as AITL and in 4 (4.1%) cases the diagnosis could not be performed and an expansion of the immunohistochemical is ongoing. Thirty-six (45.38%) cases were female and 51(54.62%) were male, 59(67.81%) patients were lower than 60 years. Seventy-six (87.35%) patients presented in advanced stage (III or IV) at diagnosis but 73(83.90%) patients presented an ECOG < 2 and 14(16.10%) ≥ 2. Eighteen (20.70%) patients were of low-risk, 26 (29.88%) of low-intermediate risk and 43(49.42%) of high-intermediate and high-risk of international prognostic index (IPI). The CR and PR was obtained for 44(50.57%) and 8(9.19%), respectively with 59.76% OR. Thirty (34.48%) patients were primary refractory and five remain under treatment. In a median of follow of 30 months, ALCL-ALK+ show higher OS (median 140.98 months) than ALCL-ALK- (44.20 months), PTCL-NOS (median 20.62 months) and AITL (median 7.24 months) (p=0.41) (Figure 1A). The median of PFS was 3.84 months for AITL, 23.44 months for ALCL-ALK+, 40.03 months for PTCL-NOS and was not yet reached for ALCL-ALK- (p=0.0006) (Figure 1B). Figure 1: Overall survival (1A) and Progression Free Survival (1B) of nodal PTCL Figure 1:. Overall survival (1A) and Progression Free Survival (1B) of nodal PTCL Figure 2 Figure 2. Conclusion: In this study we showed that ALCL-ALK+ as well as found in the literature presented a better OS in comparison to others nodal T-cell lymphoma as AITL, PTCL-NOS and ALCL-ALK-. Surprisingly the PFS of ALCL-ALK+ was statistically significant lower than of ALCL-ALK-. We thought that this result may be explained because in our service until to perform this analysis we did not indicate ASCT in first CR for ALCL-ALK+, but for all ALCL-ALK-. This hypothesis may be reinforced as the most of our cases presented high-intermediate and high-risk of IPI and that could equalize the favorable effect of ALK expression. In addition, we changed our approach and we are also indicating ASCT in first line for patients with ALCL-ALK+ with intermediate-high and high-risk of IPI . Disclosures No relevant conflicts of interest to declare.

scholarly journals Retrospective Analysis of Peripheral T-Cell Lymphoma Patients: Single Center ‘Real-Life’ Experience

2020 ◽  
Author(s):  
Murat Özbalak ◽  
Metban Mestanzade ◽  
Özden Özlük ◽  
Tarık Onur Tiryaki ◽  
İpek Yonal Hindilerden ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Lymphoma ◽  
Real Life ◽  
Progression Free Survival ◽  
Large Cell ◽  
Survival Times ◽  
Serum Total Protein ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Large Cell Lymphoma

Objective: Peripheral T-cell lymhomas (PTCLs) represent a heterogeous group of diseases, with poor long-term outcomes excluding ALK+ anaplastic large cell lymphoma (ALCL). Method: We represent data of our retrospective analysis of 62 consecutive PTCL cases diagnosed since 2002. Median observation time was 16 months. Results: The overall response rate to first line treatment was 53 percent. Data related to median progression- free survival and overall survival times could not be obtained for ALK+ALCL group whereas median progression- free survival and overall survival times for ALK-negative ALCL group were 1 and 18 months, respectively. Disease progression was frequently observed histologically in ALK-negative group. For ALKnegative ALCL, advanced stage disease was defined as the presence of serum albumin <3.4 g/dl, serum total protein ≤6.2 g/dl, high serum LDH, and serum ferritin >200 ng/ml, presence of B symptoms, and extranodal involvement of more than one site. Risk factors associated with death were serum albumin <3.4 g/dl, serum total protein ≤6.2 g/dl, serum ferritin over 200 ng/ml, and bone marrow involvement at the time of diagnosis. During follow-up 39 patients (64%) died. Most common reasons were progressive disease and infections. Four patients developed secondary malignancies. Conclusion: Our study is a reflection of the ‘real-life’. Three patients died due to disease progression shortly after diagnosis without providing treatment due to aggressiveness of the disease. Alternatives to CHOP-based chemotherapies should be found for the ALK + non-anaplastic large cell lymphoma group.

Survivin Expression Predicts Poorer Prognosis in Anaplastic Large-Cell Lymphoma

2004 ◽  
Vol 22 (9) ◽  
pp. 1682-1688 ◽  
Author(s):  
Ellen J. Schlette ◽  
L. Jeffrey Medeiros ◽  
Andre Goy ◽  
Raymond Lai ◽  
George Z. Rassidakis
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
Survivin Expression ◽  
Large Cell ◽  
Rank Test ◽  
Anaplastic Lymphoma ◽  
Log Rank Test ◽  
Large Cell Lymphoma ◽  
Alk Positive

Purpose Survivin, a member of the inhibitor of apoptosis (IAP) family, is not detected in normal adult tissues but is overexpressed in various cancers, including some types of lymphoma. The frequency and prognostic significance of survivin expression in anaplastic large-cell lymphoma (ALCL) is unknown. Materials and Methods We assessed for survivin expression in 62 ALCL tumors (30 anaplastic lymphoma kinase [ALK]-positive and 32 ALK-negative) obtained before doxorubicin-based chemotherapy. Given that survivin is a target of the STAT3 signaling pathway and STAT3 is activated in ALCL, survivin expression was also correlated with STAT3 activation. Results Survivin was expressed in 34 tumors (55%) and did not correlate with ALK. A significant association between survivin expression and STAT3 activation was observed (P = .007, Fisher's exact test). For the ALK-positive group, the 5-year failure-free survival (FFS) was 34% for patients with survivin-positive ALCL compared with 100% for patients with survivin-negative ALCL (P = .009, log-rank test). For the ALK-negative group, the 5-year FFS was 46% for patients with survivin-positive tumors compared with 89% for patients with survivin-negative tumors (P = .03, log-rank test). Overall survival was similarly worse for patients with survivin-positive tumors in both the ALK-positive and ALK-negative groups. Furthermore, multivariate analysis confirmed the independent prognostic value of survivin expression, along with age older than 60 years and Ann Arbor stage III or IV. Conclusion Survivin is expressed in approximately half of ALCL tumors and independently predicts unfavorable clinical outcome. Modulation of survivin expression or function may provide a novel target for experimental therapy in patients with ALCL.

Anaplastic large cell lymphoma (ALCL) ALK positive and ALCL ALK negative uniformly treated with intensive alternating chemotherapy at a single institution.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18512-e18512
Author(s):  
Joanna Romejko-Jarosinska ◽  
Katarzyna Domanska-Czyz ◽  
Beata Ostrowska ◽  
Ewa Paszkiewicz-Kozik ◽  
Lidia Poplawska ◽  
...  
Keyword(s):  
Survival Time ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Clinical Stage ◽  
Progression Free Survival ◽  
Large Cell ◽  
Bulky Disease ◽  
Free Survival ◽  
Large Cell Lymphoma ◽  
Alk Positive

e18512 Background: Anaplastic large cell lymphoma ALK positive (ALCL ALK+) is frequently referred to as easily curable disease, however, patients with more than 1 IPI risk factors have a poor outcome. ALCL ALK negative (ALCL ALK-) have usually higher IPI score and there is no general consensus on what treatment is the optimal. We evaluated data on 26 consecutive patients with ALCL ALK+ and ALCL ALK- treated uniformly at our institution between July 2004 and April 2011. Methods: 26 patients with ALCL ALK+ or ALCL ALK- were treated according to GMALL B-ALL/NHL 2002 protocol (Hoelzer D et al. Blood 2007; 110: Abstr. 518) without rituximab. Kaplan-Meier method and Cox’s model were used to analyze overall survival time and progression free survival time. Results: ALK protein expression was tested in 26 patients, 19(73%) were positive, 5(27%) were negative. Median age was 33 years (range 16-53). 14 pts (54%) were male, 20 (77%) were in clinical stage (CS) III or IV, 16 (61,5%) had B symptoms, 10(38,5%) had bulky disease, 10 (38,5%) had LDH > N, and 20 (77%) had IPI score >1. The overall response rate (ORR) was evaluated in 23 of 26 patients. The ORR was 87% (20/23 patients). After median follow up of 26 months (range; 6-90) overall (OS) and progression free survival (PFS) at 2 years was 67%: 95% C.I.=[48%, 86%] and 65%: 95% C.I.=[48%, 82%], respectively. On multivariate analysis none of factors: CS III and IV, B symptoms, bulky disease, IPI score>2, LDH>N, ALK expression influenced OS and PFS. The major toxicity was reversible myelosuppression: grade 4 neutropenia occurred after every cycle. Other complications included mucositis and infection. Two toxic deaths (7,6%) from sepsis occurred during neutropenia after first cycle of treatment. Conclusions: These results suggest that GMALL- B-ALL/NHL 2002 protocol is an effective treatment for both ALCL ALK + and ALCL ALK-, however, toxicity is remarkable, with neutropenia and infection being most frequent complications.

Immunohistochemical characterization of anaplastic large cell lymphoma using tissue microarray.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8048-8048
Author(s):  
Poorvi Kirit Desai ◽  
Ling Zhang ◽  
Qianxing Mo ◽  
Lubomir Sokol
Keyword(s):  
Protein Expression ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Rank Test ◽  
Time To Event ◽  
Expression Levels ◽  
Favorable Prognosis ◽  
Log Rank Test ◽  
Large Cell Lymphoma

8048 Background: Anaplastic Large Cell Lymphoma (ALCL) is a subtype of mature T-cell lymphoma comprised of systemic (ALK+ or ALK-) and primary cutaneous (PCALCL) forms. ALK+, usually associated with NPM1-ALK gene, has a favorable prognosis. PCALCL is usually indolent. Despite worse prognosis for ALK-, pts with DUSP22 rearrangement have favorable outcomes similar to ALK+ while those with p63 aberration have poor outcomes. We hypothesize that other genetic alterations in ALCL could aid in diagnosis and prognosis. We compared protein expression levels of selected signaling molecules (JAK1, STAT3, DUSP22, ERBB4/HER4, PRDM1/BLIMP1 and SOCS3) among the subtypes and correlated to outcomes. Methods: Of 50 pts with ALCL at Moffitt (MCC) from 2000-2019, 27 tissue samples (6 ALK+, 10 ALK-, 8 PCALCL, 3 controls) met eligibility criteria. Tissue microarrays (TMAs) were constructed from formalin-fixed, paraffin-embedded lymph node biopsies. Up to 3 replicate cores were taken from each block. Immunohistochemistry was performed with antibodies to the selected proteins. Stained TMA slides were scanned using the Aperio™ ScanScope XT2 to determine % positive biomarker stain within each core per established algorithm. Statistics: ANOVA was used to compared protein expression levels, with pairwise tests when significant. T-test compared PCALCL to systemic ALCL. Boxplots were created for differences in protein expression levels and time to event outcomes (OS and RFS) using Log rank test and Cox proportional hazards models. Kaplan-Meier curves were used for clinical time-to-event outcomes and quartiles of the protein expression levels. Results: The 3 subgroups had a significant difference in SOCS3 expression with mean and std respectively: 42.4% (0.153), 17.4% (0.089), and 21.0% (0.155), p = 0.008. Among all pairs, ALK+ and PCALCL groups were statistically different (P = 0.011). Patients with high BLIMP1 (≥28.5%) across 3 ALCL subgroups were associated with better median OS (not reached) in comparison to pts with lower expression (27.3 mos) (Log rank test p = 0.014, HR = 0.17, 95% CI 0.034-0.829). The same was seen for median RFS (81.1 vs. 12.5 mos). (Log rank test p = 0.009, HR 0.23, 95% CI 0.069-0.755). Conclusions: High BLIMP1 suggests favorable prognosis in ALCL and could potentially be a positive prognostic marker. High SOCS3 appears more prevalent in PCALCL than systemic and could aid in differential. Larger samples should be used to validate results. Secondary markers like Bcl-2 can be considered in the future to correlate expression levels to targeted treatments like venetoclax.

Number of cycles of chemotherapy in patients with advanced non-small cell lung caner: Efficacy and relationship with histology.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18125-e18125
Author(s):  
Eduardo Richardet ◽  
Martin Eduardo Richardet ◽  
Nicolas Castagneris ◽  
Matias Nicolas Cortes ◽  
Perelli Laura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Rank Test ◽  
Test Results ◽  
First Line ◽  
Free Survival ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Number Of Cycles

e18125 Background: Platinum based regimens are standard first-line treatment in patients with advanced non mall cell lung cancer. We intend to evaluate their effectiveness according to the number of cycles administered, and investigate whether histology is a predictor of benefit from a greater number of infusions. Methods: 124 patients with stage IV NSCLC were evaluated retrospectively. They were divided according to whether they made 4 or 6 cycles of chemotherapy. The schemes used were: Cisplatin / Gemcitabine and Carboplatin / Paclitaxel, at standard doses. We studied the efficacy in both groups according to the most common histologies (adenocarcinoma and squamous cell carcinoma). PFS (progression-free survival) and OS (overall survival) were calculated by the Kaplan-Meier curves and compared by the Log Rank Test. Results: Those who underwent 4 cycles had a PFS of 7.77 months and OS of 12.2 months vs. 8.64 and 10.8 months those who received 6 cycles (p = 0.47, p = 0.76). Within the subgroup with squamous histology (n = 43), PFS and OS were 7.38 and 13.38 months respectively in the group that received 4 cycles vs. 7.97 and 9.76 months in those receiving 6 (p = 0.70, p = 0.32 ). Within adenocarcinoma histology (n = 81), those who received 4 cycle, has a PFS of 8.17 months and they lived 11.56 month, vs 8.96 and 10.79 months for those receiving 6 cycles (p = 0.29, p = 0.88) Conclusions: In our population, a greater number of cycles showed no advantages in terms of progression-free survival or overall survival. Histology is not a predictive factor for deciding how many chemotherapy cycles administer.

Long-term survival of de novo stage IV human epidermal growth factor receptor 2 (HER2)-positive breast cancers treated with HER2 targeted therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1021-1021 ◽  
Author(s):  
Yao Wong ◽  
Akshara Singareeka Raghavendra ◽  
Christos Hatzis ◽  
Javier Perez Irizarry ◽  
Teresita Vega ◽  
...  
Keyword(s):  
Overall Survival ◽  
Targeted Therapies ◽  
De Novo ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Rank Test ◽  
Her2 Positive ◽  
Free Survival ◽  
Log Rank Test ◽  
Her 2

1021 Background: An increasing number of metastatic HER2 positive cancers represent de novo stage IV disease as fewer early stage patients relapse. We hypothesize that a subset of these has long progression free survival (PFS) after initial combined modality HER2-targeted therapies. Methods: 483 patients with de novo stage IV HER2 positive breast cancer diagnosed between 1998-2015 were identified through the medical records at Yale and MD Anderson Cancer Centers, respectively. Treatment, clinical variables and survival were extracted and compared between those who achieved “no evidence of disease” (NED) status with initial therapy and those who did not. Results: All patients received trastuzumab and 94 (20%) also received pertuzumab as first line therapy.The median OS was 5.5 years (95% Cl: 4.8-6.2); OS rates at 5 and 10 years were 54% (95% CI: 48%-60.4%) and 18% (95% Cl: 11.4%-28.3%), respectively and PFS were 41% (95% CI: 35%-48%) and 41% (95% CI: 35%-48%). Sixty-three patients (13.0%; 95% CI: 10.2% -16.4%) achieved NED. The PFS and OS at 5 and 10 years were the same 100% and 98% (95% CI: 94.6%-100%), respectively. For patients with no-NED (n = 420), the median OS was 4.7 years (95% Cl: 4.2-5.3), the PFS and OS rates at 5 and 10 years were 12% (95% CI: 4.5%-30.4%) and 0% and 45% (95% CI: 38.4%-52.0%) and 4% (95% CI: 1.3%-13.2%), respectively. NED patients had significantly longer progression free survival (log-rank test p≤0.001) and overall survival (log-rank test p≤0.001), more frequently had single organ site metastasis (76% vs 57%, p = 0.005), and more frequently had surgery for primary tumor (59% vs. 25%, p ≤0.001) than no-NED patients, but there was no significant difference in age, grade, race, year of diagnosis, ER status, treatment distribution, or radiation between the groups. Conclusions: About 13% of de novo, stage IV, HER-2 positive MBC patients achieved NED with HER-2 targeted therapies, all of these patients were progression free at 5 years and overall survival at 10-years was 98% compared to 4% among those with no-NED in our data sets. These results suggest that aggressive multimodality therapy of newly diagnosed stage IV HER2 positive cancers to render them NED may be warranted.

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