Metastasiertes nicht kleinzelliges Lungenkarzinom: Operation vor zielgerichteter Therapie mit EGFR-TKI

2021 ◽  
pp. 1-2
Author(s):  
Tobias Rachow ◽  
Susanne M. Lang
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Kleinzelliges Lungenkarzinom ◽  
Free Survival ◽  
Resection Group ◽  
Metastatic Burden ◽  
The Impact ◽  
Egfr Tki

<b>Objectives:</b> The characteristics and efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in advanced <i>EGFR</i>-mutant lung adenocarcinoma patients with primary tumor resection (PTR) is not yet clear. <b>Methods:</b> We enrolled advanced <i>EGFR</i>-mutant lung adenocarcinoma patients with EGFR-TKI as first-line therapy to access the impact of PTR on the outcomes. <b>Results:</b> A total of 466 patients were enrolled with 76 patients (16.3%) undergoing PTR; 59 patients recurred after curative surgery, while 17 patients underwent surgery as diagnostic purposes. PTR patients displayed a better performance status, a lower metastatic burden, and much less measurable diseases (30.3 vs. 97.4%, <i>p</i> &#x3c; 0.001). PTR patients experienced a significantly longer progression-free survival (25.1 [95% CI 16.6–33.7] vs. 9.4 [95% CI 8.4–10.4] months; aHR 0.40 [95% CI 0.30–0.54], <i>p</i> &#x3c; 0.001) and overall survival (56.8 [95% CI 36.3–77.2] vs. 31.8 [95% CI 28.2–35.4] months; aHR 0.57 [95% CI 0.39–0.84], <i>p</i> = 0.004). Survival advantage was still observed while comparing PTR patients with the better performance and lower metastatic burden subgroup found within the non-resection group. Moreover, the progression-free survival and overall survival of 11 patients who were found having pleural metastases during surgery and underwent PTR plus pleural biopsy, were also longer than those with pure N0–1/M1a-malignant pleural effusion disease in the non-resection group (<i>n</i> = 19) (<i>p</i> &#x3c; 0.001 and <i>p</i> = 0.002, respectively). <b>Conclusion:</b> PTR was associated with significantly better outcomes in advanced lung adenocarcinoma patients treated with EGFR-TKI. Further studies are needed to evaluate the biological role of PTR among these patients.

EGFR-mutiertes Adenokarzinom der Lunge: Wachsender Stellenwert der multimodalen Therapie

2021 ◽  
pp. 1-2
Author(s):  
Khosro Hekmat
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitor ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Free Survival ◽  
Resection Group ◽  
Metastatic Burden ◽  
The Impact ◽  
Egfr Tki

<b>Objectives:</b> The characteristics and efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in advanced <i>EGFR</i>-mutant lung adenocarcinoma patients with primary tumor resection (PTR) is not yet clear. <b>Methods:</b> We enrolled advanced <i>EGFR</i>-mutant lung adenocarcinoma patients with EGFR-TKI as first-line therapy to access the impact of PTR on the outcomes. <b>Results:</b> A total of 466 patients were enrolled with 76 patients (16.3%) undergoing PTR; 59 patients recurred after curative surgery, while 17 patients underwent surgery as diagnostic purposes. PTR patients displayed a better performance status, a lower metastatic burden, and much less measurable diseases (30.3 vs. 97.4%, <i>p</i> &#x3c; 0.001). PTR patients experienced a significantly longer progression-free survival (25.1 [95% CI 16.6–33.7] vs. 9.4 [95% CI 8.4–10.4] months; aHR 0.40 [95% CI 0.30–0.54], <i>p</i> &#x3c; 0.001) and overall survival (56.8 [95% CI 36.3–77.2] vs. 31.8 [95% CI 28.2–35.4] months; aHR 0.57 [95% CI 0.39–0.84], <i>p</i> = 0.004). Survival advantage was still observed while comparing PTR patients with the better performance and lower metastatic burden subgroup found within the non-resection group. Moreover, the progression-free survival and overall survival of 11 patients who were found having pleural metastases during surgery and underwent PTR plus pleural biopsy, were also longer than those with pure N0–1/M1a-malignant pleural effusion disease in the non-resection group (<i>n</i> = 19) (<i>p</i> &#x3c; 0.001 and <i>p</i> = 0.002, respectively). <b>Conclusion:</b> PTR was associated with significantly better outcomes in advanced lung adenocarcinoma patients treated with EGFR-TKI. Further studies are needed to evaluate the biological role of PTR among these patients.

Primary Tumor Resection Is Associated with a Better Outcome among Advanced EGFR-Mutant Lung Adenocarcinoma Patients Receiving EGFR-TKI Treatment

Oncology ◽  
2020 ◽  
Vol 99 (1) ◽  
pp. 32-40
Author(s):  
Jeng-Sen Tseng ◽  
Kuo-Hsuan Hsu ◽  
Zhe-Rong Zheng ◽  
Tsung-Ying Yang ◽  
Kun-Chieh Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Primary Tumor ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Primary Tumor Resection ◽  
Free Survival ◽  
Resection Group ◽  
Metastatic Burden ◽  
Egfr Tki

<b><i>Objectives:</i></b> The characteristics and efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in advanced <i>EGFR</i>-mutant lung adenocarcinoma patients with primary tumor resection (PTR) is not yet clear. <b><i>Methods:</i></b> We enrolled advanced <i>EGFR</i>-mutant lung adenocarcinoma patients with EGFR-TKI as first-line therapy to access the impact of PTR on the outcomes. <b><i>Results:</i></b> A total of 466 patients were enrolled with 76 patients (16.3%) undergoing PTR; 59 patients recurred after curative surgery, while 17 patients underwent surgery as diagnostic purposes. PTR patients displayed a better performance status, a lower metastatic burden, and much less measurable diseases (30.3 vs. 97.4%, <i>p</i> &#x3c; 0.001). PTR patients experienced a significantly longer progression-free survival (25.1 [95% CI 16.6–33.7] vs. 9.4 [95% CI 8.4–10.4] months; aHR 0.40 [95% CI 0.30–0.54], <i>p</i> &#x3c; 0.001) and overall survival (56.8 [95% CI 36.3–77.2] vs. 31.8 [95% CI 28.2–35.4] months; aHR 0.57 [95% CI 0.39–0.84], <i>p</i> = 0.004). Survival advantage was still observed while comparing PTR patients with the better performance and lower metastatic burden subgroup found within the non-resection group. Moreover, the progression-free survival and overall survival of 11 patients who were found having pleural metastases during surgery and underwent PTR plus pleural biopsy, were also longer than those with pure N0--1/M1a-malignant pleural effusion disease in the non-resection group (<i>n</i> = 19) (<i>p</i> &#x3c; 0.001 and <i>p</i> = 0.002, respectively). <b><i>Conclusion:</i></b> PTR was associated with significantly better outcomes in advanced lung adenocarcinoma patients treated with EGFR-TKI. Further studies are needed to evaluate the biological role of PTR among these patients.

scholarly journals The Impact of Sequence of Chemotherapy and EGFR-TKI Treatment on DifferentEGFRMutation Lung Adenocarcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-8
Author(s):  
Fu-Tsai Chung ◽  
Ming-Yun Ho ◽  
Yueh-Fu Fang ◽  
Meng-Heng Hshieh ◽  
Tsai-Yu Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Prospective Design ◽  
Free Survival ◽  
Epidermal Growth ◽  
Tki Treatment ◽  
The Impact ◽  
Egfr Tki ◽  
Line Chemotherapy

Objectives. Chemotherapy as first-/second-line treatment in different epidermal growth factor receptor (EGFR) mutation lung adenocarcinoma remains controversial.Methods. Consecutive patients were collected between 2009 and 2012. Patients were divided into two groups (1st-line chemotherapy:n= 56 and 2nd-line chemotherapy:n= 55). Their outcomes profiles were analyzed.Results. The overall survival (OS) of all patients (390 versus 662 days,p< 0.0001), as well as both progression-free survival (PFS, 151 versus 252 days,p= 0.0001) and OS (308 versus 704 days,p= 0.0001) of patients withL858Rmutation (n= 63), who received 2nd-line chemotherapy, was significantly poor. By univariate and multivariate analysis, 2nd-line chemotherapy, andL858Rmutation were significantly related to poor PFS and OS.Conclusion. In advanced lung adenocarcinoma,L858Rmutation and 2nd-line chemotherapy caused a poor outcome. It is a consideration to choice of 1st-line chemotherapy in these subjects. A prospective design is warranted to confirm this finding.

scholarly journals Surgical Resection of Primary Tumors Provides Survival Benefits for Lung Cancer Patients With Unexpected Pleural Dissemination

2021 ◽  
Vol 8 ◽  
Author(s):  
Liwen Fan ◽  
Haitang Yang ◽  
Ke Han ◽  
Yang Zhao ◽  
Wen Gao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Tumor Size ◽  
Primary Tumor ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Sublobar Resection ◽  
Free Survival ◽  
Resection Group ◽  
Nsclc Patients

Background: Surgery is not generally recommended for non-small cell lung cancer (NSCLC) patients with malignant pleural dissemination (PD). However, in some cases, PD is found unexpectedly during surgery. There is no consensus on whether surgical intervention can provide survival benefit for them. We investigated the role of surgery in NSCLC patients with unexpected PD by a cohort study.Methods: Clinical data of consecutive patients who intended to undergo radical surgery for NSCLC between January 2010 and December 2015 at Shanghai Chest Hospital and Huadong Hospital were collected from a lung cancer database. Patients diagnosed with unexpected malignant pleural nodules intraoperatively were enrolled in this retrospective study.Results: A total of 181 NSCLC patients were diagnosed with unexpected malignant PD intraoperatively and confirmed with postoperatively histological examinations. Out of these, 80 (44.2%) patients received pleural nodule biopsies alone, and 101 (55.8%) received primary tumor resection (47 with sublobar resection and 54 with lobectomy). The median progression-free survival and overall survival for all patients were 13 and 41 months respectively. Patients in the resection group had significantly better progression-free survival (19.0 vs. 10.0 months, P &lt; 0.0001) and overall survival (48.0 vs. 33.0 months, P &lt; 0.0001) than patients in the biopsy group. In the resection group, there was no statistical difference between patients with sublobar resection and lobectomy (P = 0.34). Univariate and multivariate analyses identified primary tumor resection, targeted adjuvant therapy, and tumor size (≤ 3 cm) as independent prognostic factors.Conclusions: NSCLC patients with unexpected intraoperative PD potentially benefited from surgical resection of the primary tumor and multidisciplinary targeted therapy, particularly when tumor size did not exceed 3 cm. Our data demonstrated that the resection type was not associated with survival differences, which remains to be defined with a larger sample size.

scholarly journals Low-grade astrocytoma: surgical outcomes in eloquent versus non-eloquent brain areas

2013 ◽  
Vol 71 (1) ◽  
pp. 31-34 ◽  
Author(s):  
André de Macedo Bianco ◽  
Flavio Key Miura ◽  
Carlos Clara ◽  
Jose Reynaldo W. Almeida ◽  
Clemar Correa da Silva ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Subtotal Resection ◽  
Low Grade ◽  
Brain Areas ◽  
Free Survival ◽  
Eloquent Areas ◽  
Eloquent Area ◽  
Extent Of Surgical Resection

A retrospective study of 81 patients with low-grade astrocytoma (LGA) comparing the efficacy of aggressive versus less aggressive surgery in eloquent and non-eloquent brain areas was conducted. Extent of surgical resection was analyzed to assess overall survival (OS) and progression- free survival (PFS). Degree of tumor resection was classified as gross total resection (GTR), subtotal resection (STR) or biopsy. GTR, STR and biopsy in patients with tumors in non-eloquent areas were performed in 31, 48 and 21% subjects, whereas in patients with tumors in eloquent areas resections were 22.5, 35 and 42.5%. Overall survival was 4.7 and 1.9 years in patients with tumors in non-eloquent brain areas submitted to GTR/STR and biopsy (p=0.013), whereas overall survival among patients with tumors in eloquent area was 4.5 and 2.1 years (p=0.33). Improved outcome for adult patients with LGA is predicted by more aggressive surgery in both eloquent and non-eloquent brain areas.

scholarly journals Could Primary Tumor Resection Improve Survival in Metastatic Breast Cancer?

2021 ◽  
Vol 9 (07) ◽  
pp. 422-428
Author(s):  
Rafaela Aparecida Dias de Oliveira ◽  
Lyvia Aparecida Dias de Oliveira ◽  
Marília Davoli Abella Goulart ◽  
Maria Clara Faustino Linhares
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Systemic Therapy ◽  
Primary Tumor ◽  
Tumor Resection ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Primary Tumor Resection ◽  
Free Survival

Introduction: In advanced breast cancer, local treatment is considered palliative. However, although there are some polemic opinions about the surgical treatment, some of the latest studies have emphasized that in advanced cases primary tumor resection (PTR) is related to better outcomes. This review aims to evaluate how resection of the original tumor impacts women with metastatic breast cancer, considering the most recent studies about this subject. Methods: The search was performed in MEDLINE, Scopus, PMC, Current Contents and Wiley Online Library databases; 23 articles - from 2016 to 2019 - were selected and 11 were included in this review. As inclusion criteria were considered: studies presenting outcomes about resection of the primary tumor, comparison between chemotherapy/ hormone therapy/ targeted cancer therapies and surgical intervention, studies published from 2016 to 2019 and available in English, Spanish or Portuguese. We excluded those which did not approach PTR, did not present outcomes of interest (progression-free survival comparison between PTR and systemic therapy) or only discussed systemic therapy, as well as those published before 2016. Results: It was reported in 6 studies that progression-free survival is better on those who underwent surgery. PTR was also related to longer median overall survival in women submitted to surgery, up to 16 months higher when compared to the ones who were not. Enhanced survival even pertained to surgical groups regardless of tumor size.  Conclusion: Based in the analysis, PTR in metastatic breast cancer can be related to higher overall survival.

scholarly journals Pharmacogenetic score predicts overall survival, progression-free survival and platinum sensitivity in ovarian cancer

2020 ◽  
Vol 21 (14) ◽  
pp. 995-1010
Author(s):  
Sara Gagno ◽  
Michele Bartoletti ◽  
Chiara Romualdi ◽  
Elena Poletto ◽  
Simona Scalone ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Germ Line ◽  
Risk Group ◽  
Prognostic Score ◽  
Progression Free Survival ◽  
High Risk Group ◽  
Free Survival ◽  
Estrogen Activity ◽  
The Impact

Aim: To define the impact of polymorphisms in genes involved in platinum-taxane and estrogen activity in the outcome of platinum-based treated ovarian cancer patients (OCP). Patients & Methods: Two hundred and thirty OCP were analyzed for 124 germ-line polymorphisms to generate a prognostic score for overall survival (OS), progression-free survival (PFS) and platinum-free interval (PFI). Results: ABCG2 rs3219191D>I, UGT1A rs10929302G>A and UGT1A rs2741045T>C polymorphisms were significantly associated with all three parameters (OS, PFS and PFI) and were used to generate a score. Patients in high-risk group had a poorer OS (hazard ratio [HR]: 1.8; 95% CI: 1.3–2.7; p = 0.0019), PFS (HR: 2.0; 95% CI: 1.4–2.9; p < 0.0001) and PFI (HR: 1.9; 95% CI: 1.4–2.8; p = 0.0002) compared with those in low-risk group. Conclusion: The prognostic-score including polymorphisms involved in drug and estrogen pathways stratifies OCP according to OS, PFS and PFI.

High Levels of Donor Chimerism Early after Non-Myeloablative Transplantation Predictive of Overall and Progression Free Survival but Not Risk of Acute Graft Versus Host Disease for Patients with AML or MDS.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 185-185
Author(s):  
Edwin P. Alyea ◽  
Shuli Li ◽  
Haesook Kim ◽  
Vincent T. Ho ◽  
Corey Cutler ◽  
...  
Keyword(s):  
Overall Survival ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Early Stage ◽  
Progression Free Survival ◽  
Free Survival ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor Chimerism ◽  
The Impact

Abstract Non-myeloablative (NST) transplantation is increasingly used in the treatment of patients with AML and MDS who are not candidates for myeloblative transplant. Relapse of disease remains a major cause of treatment failure after NST. Predictive factors to identify patients at high risk of relapse are needed to identify patients who would benefit from additional interventions. Attainment of a high degree of donor engraftment achieved early after transplantation may indicate the presence of a more significant allo-immune effect. We have performed a retrospective analysis of 64 patients with AML and MDS receiving NST, assessing the impact of donor chimerism when measured early after transplantation on outcome. Overall survival (OS), progression free survival (PFS) and risk of graft versus host disease (GVHD) were compared for patients achieving ≥90 % or <90% donor derived hematopoiesis when measured 1 month after transplant. All patients received fludarabine 30 mg/m2/day x 4 days and intravenous busulfan (Busulfex)0.8 mg/kg/day x 4 days for conditioning. All patients received calcineurin-inhibitor based GVHD prophylaxis. All patients received PBSC with G-CSF at 5 mcg/kg beginning day 1 after transplantation. Chimerism was measured using FISH for sex mismatched patient donor pairs or by STR analysis. 37 patients had ≥90% donor derived hematopoiesis, 27 patients had <90% donor derived hematopoiesis after transplantation. The two groups had similar characteristics with a median age of 57 yrs (range 21–70) for patients ≥90% and 58 yrs (range 32–69) for patients <90%. Of patients achieving ≥90%, 23 patients had AML and 14 MDS. Of patients <90%, 13 had AML and 14 with MDS. 7 of 16 (44%) patients with early stage disease(AML in CR1 or early stage MDS) achieved ≥90% donor hematopoiesis, while 30 of 48 (63%) patients with advanced disease achieved ≥90%. 17 of 29 (59%) patients with unrelated donors achieved ≥90% donor derived hematopoiesis, while 20 of 33 (61%) patients with matched related donors achieved ≥90% donor derived hematopoiesis. 21 of 32 (66%) patients with donor-recipeint sex mismatch achieved ≥90% while 16 of 32 (50%) patients with same sex donors were ≥90%. The median follow-up for surviving patients achieving ≥90% donor chimerism was 12 months and 15 months for those <90%. Patients achieving ≥90% donor chimerism had a significantly improved 1-year (71% versus 41%) and 2-year (39% versus 19%) OS (p=0.05). Similarly, for patients achieving ≥90% donor chimerism, there was a trend toward an improved PFS at 1-year (49% versus 30%) and 2-years (32% versus 19%) (p=0.08). There was no difference in the risk of developing stage 2–4 acute GVHD, 19% for both patients above and below 90%. Achieving high levels of donor chimerism when measured early after NST predicts for an improved overall survival and there is a trend toward an improved progression free survival. This may represent the presence of an enhanced graft versus leukemia effect in these patients. The degree of donor chimerism does not predict the development of acute GVHD. These results suggest that patients with <90% donor derived hematopoiesis may be candidates for strategies to enhance donor chimerism.

Similar Outcome of Non-Myeloablative and Myeloablative Allogeneic Hematopoietic Cell Transplantation for Patients Greater Than Fifty Years of Age.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 300-300
Author(s):  
Edwin P. Alyea ◽  
Haesook Kim ◽  
Corey Cutler ◽  
Vincent T. Ho ◽  
John Gribben ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Transplantation ◽  
Progression Free Survival ◽  
Advanced Age ◽  
Myeloablative Conditioning ◽  
Early Stage Disease ◽  
Free Survival ◽  
Transplant Patients ◽  
Cd34 Cells ◽  
The Impact

Abstract Advanced age is a relative contraindication to myeloablative allogeneic transplantation due to the increased incidence of treatment related complications seen in older patients. Therefore, non-myeloablative stem cell transplantation (NST) is increasingly utilized in this population. The impact of the shift from myeloablative to NST upon relapse, transplant complications, and outcome has yet to be examined. We performed a retrospective analysis of 152 patients older than age 50 receiving either NST or myeloablative transplantation over a 5 years period. The decision to pursue non-myeloablative as opposed to myeloablative conditioning during this period was based on patient and physician preference. Seventy-one patients received non-myeloablative conditioning, fludarabine (30 mg/m2/day x 4) and intravenous busulfan (0.8 mg/kg/d x 4). Eighty-one patients received myeloablative conditioning, primarily cyclophosphamide and TBI. All patients received pharmacologic prophylaxis to prevent GVHD with the majority of patients receiving FK 506 and methotrexate in both groups (78% NST, 96% myeloablative) with the remainder receiving cyclosporine and prednisone. 93% of NST patients received mobilized PBSC, the median CD34+ cell count infused was 6.4 x 106 CD34+ cells/kg (range 1.0 to 31.0 x 106 CD34+ cells/kg). 80% of myeloablative patients received marrow. The median age was 58 (range 51–70) years for patients receiving NST and 54 (range 51–66) years for patients receiving myeloablative transplantation. Major disease groups included acute leukemia and MDS (51% NST, 41% myeloblative). Ten percent of non-myeloablative transplant patients were in CR1 or had early stage disease at transplantation compared with 40% of myeloablative transplant patients. Primary indications for NST were advanced age (56%) and prior myeloablative transplant (24%). The median follow-up is 18 months (range 6 to 34 months) for patients receiving non-myeloablative transplantation and 46 months (range 3 to 73 months) for patients receiving myeloablative transplantation. NST patients were more likely to have unrelated donors (58% vs. 36%, p=0.009), prior transplant (25% vs. 4%, p=&lt;0.0001), and active disease at transplantation (85% vs. 59%, p=&lt;0.001). Despite the adverse characteristics, overall survival was improved in the NST group at 1 (51% vs. 39%) and 2 (39% vs. 29%) years (p = 0.056). There was no difference in progression free survival (2 year, 27% vs. 25%, p =0.24). Incidence of 2–4 GVHD was similar, (28% vs. 27%). Non-relapse mortality was lower for NST patients (32% vs. 50%, p=0.01), but relapse was higher (46% vs. 30%, p=0.052). A subset analysis was performed assessing overall and progression free survival in patients with advanced leukemia (beyond CR1) and advanced MDS. This demonstrated marginally improved overall survival and progression free survival for patients receiving NST. Our experience suggests that, in patients over age 50, NST with fludarabine and low dose busulfan leads to an overall outcome at least as good as myeloablative therapy.

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