Clinical characteristics of KRAS mutations in NSCLC and their impact on outcomes to first-line chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7588-7588
Author(s):  
Mohit Butaney ◽  
Jennifer Porter ◽  
Neal Ian Lindeman ◽  
Pasi A. Janne ◽  
Michael S. Rabin ◽  
...  
Keyword(s):  
Smoking Status ◽  
Egfr Mutations ◽  
Limited Information ◽  
Wild Type ◽  
First Line ◽  
Kras Mutations ◽  
Response To Chemotherapy ◽  
Significant Difference ◽  
The Impact ◽  
Line Chemotherapy

7588 Background: KRAS is one of the most commonly mutated oncogenes in non-small cell lung cancer (NSCLC). While the impact of EGFR mutations and EML4-alk translocations has been well-described, there is limited information about the impact of these somatic mutations on response to chemotherapy. Methods: We retrospectively reviewed the demographics and clinical outcomes of patients with KRAS mutations and compared these to patients who were KRAS wild-type (WT). Eligible pts received 1st-line IV chemo for stage IV NSCLC at DFCI and had known information about both KRAS and EGFR status. Since the biology and impact of EGFR mutations on response to chemo is well-described, we excluded such pts from the analysis. The primary endpoint was progression-free survival (PFS) with first-line chemo; secondary endpoints included radiographic response rate (RR) and overall survival (OS). Results: Between 2/05 and 8/11, there were 63 eligible KRAS pts and 97 eligible WT pts. The groups were similar in age (median 65yrs in both groups), % female (K 62, WT 54) race (K 89% white/6% black, 5% other; WT 86% white,/6% black/8% other), histology (K 90%adeno/8% NSCLC NOS; WT 86% adeno/9%NSCLC NOS), and % of pts receiving 1/2/3 agents in 1st line (K 11/56/33; WT 18/53/30). KRAS pts were less likely to be never or light smokers (4% vs 33% for WT). Nonsmokers were more likely to harbor KRAS transition rather than transversion mutations (3 transition, 1 transversion), while the converse held for smokers (51 transversions, 8 transitions). Median PFS was similar for KRAS vs WT (K .65 vs WT 4.8 months, p=0.81). RR (29% for both groups), disease control rates (K 73% vs WT 78%), and median OS (K 13.5 vs WT 12.1 months, p=.525) were also similar. Outcomes of KRAS pts to 2nd line chemotherapy (PFS 2.2, OS 8.6) are similar to those seen for WT patients in this setting. There was no significant difference in outcomes based on gender, smoking status, drug received (pemetrexed-based vs taxane based), or specific KRAS genotype. Conclusions: Pts with KRAS mutations experience similar outcomes to standard chemotherapy as those who are wild-type for EGFR and KRAS. Going forward, these data can serve as a reference for control arms of KRAS-specific randomized trials.

Impact of gemcitabine (G) on the activity of first-line chemotherapy in non-small cell lung cancer (NSCLC): A meta-analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7138-7138
Author(s):  
G. L. Pappagallo ◽  
O. Belvedere ◽  
O. Vinante ◽  
F. Grossi
Keyword(s):  
Meta Analysis ◽  
Performance Status ◽  
Objective Response ◽  
Response To Treatment ◽  
Third Generation ◽  
First Line ◽  
Significant Difference ◽  
Nsclc Patients ◽  
The Impact ◽  
Line Chemotherapy

7138 Background: A two-drug platinum-based regimen in which cisplatin or carboplatin is combined with a third-generation agent (i.e. paclitaxel, vinorelbine, docetaxel, or G) is the standard first-line treatment for NSCLC patients with good performance status. Encouraging results have recently been reported for nonplatinum regimens composed of two third-generation drugs. Methods: To assess the impact of G on the activity of first-line chemotherapy in NSCLC, we carried out a meta-analysis on data from 4,362 NSCLC patients who were enrolled in 11 randomized trials comparing a G-containing vs. G-free new generation regimens. We constructed 2x2 tables using response to treatment data. For trials with more than one eligible G-free comparator arm, individual comparisons between the G-based treatment arms and each of the comparator arms were analyzed. A general variance-based method was used to estimate the pooled odds ratio (OR) and 95% confidence interval (CI). We assessed for heterogeneity among the trials based on standard methods. Results: Sixteen comparisons contributed to this analysis. G-containing regimens included: G+cisplatin (894), G+docetaxel (565), G+paclitaxel (200 patients), G+vinorelbine (157), G+carboplatin (49). G-free regimens included: vinorelbine+cisplatin (866), carboplatin+paclitaxel (539), docetaxel+cisplatin (494), cisplatin+paclitaxel (439), vinorelbine+carboplatin (159). Comparing G-containing vs. G-free regimens, the OR for progression was 0.867 (CI 95% 0.770–0.977; p = 0.019), with heterogeneity chi-square 11.639 (p = 0.71). No significant difference was observed for complete (OR 0.909, CI 95% 0.556–1.487; P = 0.707) and overall (complete + partial) response (OR 0.987, CI 95% 0.881–1.106; P = 0.819). Conclusions: These data demonstrate that the progression of disease is more likely in patients treated with G-free doublets. Further analyses are required to address whether disease control (objective response + stable disease) is associated with a survival benefit and may therefore be used as a surrogate end point for survival in chemotherapy trials of NSCLC. No significant financial relationships to disclose.

Association of plasma EGFR mutations with response to first-line chemotherapy and prognosis in Chinese patients with advanced non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19017-e19017
Author(s):  
M. N. Wu ◽  
J. Zhao ◽  
H. Bai ◽  
M. L. Zhuo ◽  
S. H. Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Wild Type ◽  
Small Cell Lung ◽  
First Line ◽  
Nsclc Patients ◽  
Line Chemotherapy

e19017 Background: To investigate associations of plasma EGFR mutations of advanced non-small cell lung cancer (NSCLC) patients with response to the first-line chemotherapy and prognosis. Methods: Plasma EGFR mutations from 145 chemotherapy-naive patients with advanced or metastatic NSCLC were examined by using denaturing high- performance liquid chromatography (DHPLC), and associations of EGFR mutations with tumor response to chemotherapy and clinical outcomes were evaluated. Results: 37.2% (54/145) of the patients was detected to have EGFR mutations in their plasma DNA. The response rate of mutated EGFR carriers to the chemotherapy was 37% (20/54), similar to that of 31.9% (29/91) of wild-type EGFR carriers to the chemotherapy (P= 0.323). Stage IV NSCLC patients with mutated EGFR had a longer PFS than those with wild-type EGFR (4 vs 3 months, P=0.043) after the first-line chemotherapy. The median survival time and 1-, 2- year survival rate for the patients with EGFR mutations (24 months and 85.7%,43.7%) were increased than those with wild-type EGFR (18 months and 65.7%,25.9%) (p=0.0468). Cox multivariate regression analysis showed that clinical stage (IV vs IIIb), response to the first-line chemotherapy (PR vs PD), and EGFR mutations were independent prognostic factors (P=0.008, 0.000 and 0.000 respectively). Conclusions: We conclude that plasma EGFR mutations in the Chinese patients with advanced NSCLC were not associated with response to the first-line chemotherapy, but Stage IV NSCLC patients with mutated EGFR had a longer PFS after the chemotherapy. No significant financial relationships to disclose.

Frequency of KRAS mutations in female colorectal cancer (CRC) patients: Findings of a Brazilian cohort of 8,234 cases.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14101-e14101
Author(s):  
Carlos G. M. Ferreira ◽  
Mariano Zalis ◽  
Ilana Zalcberg-Renault ◽  
Martin H Bonamino ◽  
Marcos Barcelos de Pinho ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Kras Mutation ◽  
Direct Sequencing ◽  
Reference Laboratory ◽  
Wild Type ◽  
Kras Mutations ◽  
Significant Difference ◽  
Exon 1 ◽  
The Impact ◽  
Brazilian Cohort

e14101 Background: Although major advances in the last decades, there are still important gaps in our understanding of CRC carcinogenesis, particularly whether sex-linked factors play any role. Some groups, including ours, observed that KRAS mutation may be more frequent in female than male (Ferreira C.G. et al. J Clin Oncol 28: 2010 suppl abstr 3614; Uetake H. et al. J Clin Oncol 29: 2011 suppl abstr 3605). Methods: Between July 2008 and July 2011, we analyzed 8,234 consecutive patient samples sent to a reference laboratory for KRAS genotyping as a screening for cetuximab use. DNA was extracted from paraffin-embedded tissue, exon 1 was amplified by PCR and submitted to direct sequencing. Codons 12 and 13 were analyzed. Results: The median age was 59 years and well balanced according to gender with 51.9% of male and 48.1% female patients. The percentage of wild-type and mutated KRAS was 66.4 and 33.6%, respectively. Corroborating previous findings a significant difference in the percentage of mutated KRAS patients was observed between female and male (34.8% versus 32.5%, p = 0.03). However there were no differences in the distribution of any specific KRAS mutation according to gender. Among the 2,626 mutated cases, 83% were in codon 12 versus 17% in codon 13. Mutation Gly12Asp was the most common being detected in 36% of the mutated cases. Conclusions: This is one of the largest cohorts of KRAS genotyping in CRC patients. In line with previous data our present findings indicate that KRAS-mutations are more frequent in female than male. Further research is required to better address the impact of gender differences and/or hormones as potential drivers of CRC carcinogenesis.

Is conventional chemotherapy effective in advanced sarcomatoid lung cancers?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18102-e18102 ◽  
Author(s):  
Thibault Vieira ◽  
Aurelie Cazes ◽  
Bonnette Pierre ◽  
Leila Zemoura ◽  
Isabelle Monnet ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Advanced Disease ◽  
Smoking Status ◽  
Univariate Analysis ◽  
First Line ◽  
Conventional Chemotherapy ◽  
Lung Cancers ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
Line Chemotherapy

e18102 Background: Sarcomatoid lung cancers (SC) are associated with poor prognosis. A few studies suggest that these tumors are resistant to platinum-based chemotherapy. Methods: Between January 1994 and October 2011, all consecutive patients with SC were screened from six French centers. Patients with advanced disease and treated with first-line chemotherapy were included in this study. Clinical data, staging (TNM 2009 classification), drugs and response to chemotherapy (RECIST 1.1) at first tumor assessment were reported. Factors associated with progressive disease (PD) in univariate (p<0.2) were included in multivariate analysis. Results: 111 patients with SC were screened. 51 had advanced stage and were treated by a first-line chemotherapy. Among them, 27 (53%) had initial advanced disease and 24 (47%) had relapse after radical surgery or radiotherapy. Patients were 60.7±3 years old, 69% were male, 86% smokers and 86% were symptomatic. PS was 0 (57%), 1 (39%) 2 (4%). Stages at the diagnosis were I (15.5%), II (13.5%), IIIA (20%), IIIB (6%), IV (45%). Histological subtype were pleomorphic (70%), pure sarcoma-like (20%) unspecified (6%), carcino-sarcoma (4%). 38 (75%) received a platinum based-combination and 13 (25%) a monotherapy. Drug given alone or combined with platin were gemcitabine (23%), navelbine (16%), placlitaxel (16%), docetaxel (12%), pemetrexed (9.8%), ifosfamide (9.8%), vepeside (4%) and others (11%). At first tumor assessment, PD and disease control rates were 71% and 29%, respectively. Median progression free survival was 2 months IC95% [1.3, 2.7]. Median overall survival was 6 months [3.2, 8.8]. In univariate analysis, age, gender, smoking status, numbers of metastatic locations, histological subtypes, monotherapy vs platin-based combinations, relapse after radical treatment vs initial advanced disease were not associated with PD. In multivariate analysis, initial advanced disease was the only independent factor of PD (OR 4.59 [1.17, 18] p=0.03). Conclusions: Our series confirm that advanced SC are refractory to conventional chemotherapy. Molecular characterizations are needed to improve therapeutic strategy.

Evaluation of the prognostic/predictive role of tumor EGFR and KRAS mutations in Greek metastatic non-small cell lung cancer patients treated with first-line chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19048-e19048
Author(s):  
Helena Linardou ◽  
Paris A. Kosmidis ◽  
Vassiliki Kotoula ◽  
Vasilios Karavasilis ◽  
Anastasia G Eleftheraki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Wild Type ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Predictive Role ◽  
Nsclc Patients ◽  
Line Chemotherapy

e19048 Background: KRAS mutations are reported in 20-25% of non-small cell lung cancer (NSCLC). Little is known about the prognostic/predictive role of KRAS in advanced NSCLC, with conflicting results among small studies. Recent evidence showed that KRAS mutations could predict for worse outcome in patients treated with platinum-based adjuvant chemotherapy. Methods: KRAS and EGFR genotypes were evaluated in 414 NSCLC patients with available clinical data, diagnosed from March 2000 to December 2012 (tissue blocks from the HeCOG tumor repository). KRAS and EGFR mutations were associated with clinicopathological parameters (mutated vs. wild-type). Outcome comparisons were performed in 214 metastatic patients with treatment data available, following 1st-line chemotherapy without tyrosine kinase inhibitors. Results: The majority of the patients were male (80%), current smokers (53%), with adenocarcinoma (AC) histology (65%). EGFR mutations were found in 10% and KRAS mutations in 17% of all histological types, while in AC they were 14% and 21%, respectively. Most EGFR mutations were classical (79%), while most common KRAS mutations were p.G12C (39%), p.G12D (30%) and p.G12V (15%). Two tumors had concurrent EGFR and KRAS mutations. EGFR mutations were significantly associated with female gender, AC histology and non-smoking status, as previously described. KRAS mutations were associated with AC histology and younger age (<60). At a median follow-up of 31 months, EGFR status did not show any significant associations with OS or PFS, while KRAS mutations were prognostic for worse OS compared to KRAS and EGFR wild-type tumors (HR=1.67, CI=1.08-2.59, p=0.021). This effect was also significant (p=0.022) in the presence of treatment type, with platinum-based therapy being a positive prognostic factor for OS (HR=0.62, CI=0.4-0.92, p=0.019). The association of KRAS mutations with PFS was not significant. Conclusions: EGFR and KRAS genotype incidences are presented for the first time for Greek metastatic NSCLC patients. In this setting, the presence of KRAS mutations significantly increases and platinum 1st-line treatment decreases the risk of death.

TTF1 status as a better predictor of benefit to erlotinib (E) in metastatic non-small cell lung cancer (NSCLC) than sex, histology, and smoking status.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19110-e19110
Author(s):  
Charalambos Haris Charalambous ◽  
Charis Charalambous ◽  
Dimitrios Vomvas ◽  
Nikos Katodritis ◽  
Marios P. Decatris
Keyword(s):  
Cox Regression ◽  
Smoking Status ◽  
Performance Status ◽  
Univariate Analysis ◽  
Egfr Mutations ◽  
Striking Difference ◽  
X Rays ◽  
First Line ◽  
Line Therapy ◽  
Significant Difference

e19110 Background: Erlotinib (E) is currently indicated as first line therapy in patients with EGFR mutations, and as second and third line treatment for patients with advanced metastatic NSCLC. In Cyprus comprehensive EGFR testing started in January 2011. In this study we reviewed all the patients that received E between 2007-2010, without having undergone EGFR mutation testing, looking at predictive factors for benefit. Methods: 100 consecutive patients are included. 3 patients received this as 1st line, 49 patiens as 2nd line and 48 patients as 3rd line and beyond. Previous treatments gemcitabine platinum doublet as first line, and either pemetrexed or docetaxel as 2nd line therapy. Patients had regular Chest x-rays (every 2-3 months) and CT scans (every 4-6 months). Results: 40 female and 60 male, with 9 patients still alive and on treatment. Median age is 66 years (range 32-79). 45 patients were WHO performance status (PS) 0-1, 47 PS 2-3, 8 patients PS not recorded. Median progression-free survival (PFS) for all patients was 95 days( 95% CI 68-118). Median overall survival (OS) from starting E was 144 days (95% CI 103-185). Ten (10) patients had a partial response and 34 stable disease. Subset analyses were undertaken based on smoking status, sex, histology type and TTF1. Univariate analysis for PFS using KM plots showed a statistically significant difference for sex, smoking and TTF1. On Cox regression only gender and TTF1 were statistically significant (0.007 and 0.006). There was a striking difference in both median PFS and median OS between patients with TTF1-ve tumours (33 days) and TTF1 +ve tumours (149 days). Conclusions: TTF1 is a better predictor of benefit to E than histology, sex and smoking status. The very low median PFS and OS for patients with TTF1 –ve tumors would suggest that such patients derive little or no benefit from E. [Table: see text]

Survival outcomes in patients with IDC and ILC breast cancer: A well matched single institution study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13056-e13056
Author(s):  
Michael Grimm ◽  
Bhuvaneswari Ramaswamy ◽  
Maryam B. Lustberg ◽  
Robert Wesolowski ◽  
Sagar D. Sardesai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Her2 Status ◽  
Single Institution ◽  
First Line ◽  
Response To Chemotherapy ◽  
Significant Difference

e13056 Background: Invasive lobular carcinoma (ILC) accounts for only 10-15% of all invasive breast cancers but has distinct clinicopathologic characteristics and genomic profiles. In particular, metastatic lobular cancers (mILC) have unique sites of metastasis and it is unclear if the response to initial endocrine therapy differs from metastatic ductal cancers (mIDC). Therefore we have undertaken a single-institution, retrospective analysis to compare overall outcomes and response to initial endocrine therapy (ET) in patients (pts) with metastatic ILC and IDC. Methods: An IRB approved retrospective review of medical records was conducted evaluating pts treated for metastatic IDC and ILC at The Ohio State University Comprehensive Cancer Center from January 1, 2004 to December 31, 2014. Pts diagnosed with mIDC were matched on age, year of diagnosis, estrogen receptor/progesterone receptor and HER2 status and site of metastasis 2:1 to patients diagnosed with mILC. Overall survival (OS) was defined as the time from metastasis to death or last known follow-up. Progression-free survival (PFS) was defined as time from metastasis to progression on first-line ET. Time to chemotherapy (TTC) was defined as time from starting ET for metastasis to initiation of chemotherapy. Kaplan Meier (KM) methods were used to calculate median OS, PFS and TTC. Results: A total of one hundred sixty one pts with metastatic breast cancer were included in this analysis. The demographic features between the two groups were well balanced and included in the table below. The median OS was 2.6 yrs (95% CI: 1.55, 3.22) for mILC and 2.2 yrs (95% CI: 1.95, 2.62) for mIDC. A subset of 111 patients who started on endocrine therapy were used in the PFS and TTC analyses. The median PFS following first-line ET was 2.2 yrs (95% CI: 0.1.0, 2.7) for mILC and 1.4 yrs (95% CI: 0.91, 1.90) for mIDC. Median TTC was 2.1 yrs (95% CI: 1.71, 4.92) for mILC and 2.4 yrs (95% CI: 1.90, 4.77) for mIDC. There was no statistically significant difference in outcomes between the two groups. Conclusions: Outcomes in patients with ILC and IDC have been varied, with several studies reporting that patients with ILC have worse outcomes and response to chemotherapy. Our retrospective study examining outcomes in mILC in comparison with mIDC showed no difference in OS. Given the concern of resistance to conventional therapies in patients with lobular cancers, it is reassuring to see that the median PFS on first line ET and TTC was similar to metastatic ductal cancers.[Table: see text]

Impact of KRAS mutational status on outcomes in patients with pancreatic cancer (PDAC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4142-4142
Author(s):  
Lucy Xiaolu Ma ◽  
Gun Ho Jang ◽  
Amy Zhang ◽  
Robert Edward Denroche ◽  
Anna Dodd ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Advanced Disease ◽  
Cox Proportional Hazards ◽  
Prognostic Impact ◽  
First Line ◽  
Kras Mutations ◽  
Kaplan Meier ◽  
Mutational Status ◽  
Translational Research Program ◽  
The Impact

4142 Background: KRAS mutations (m) (KRASm) are present in over 90% of pancreatic adenocarcinomas (PDAC) with a predominance of G12 substitutions. KRAS wildtype (WT) PDAC relies on alternate oncogenic drivers, and the prognostic impact of these remains unknown. We evaluated alterations in WT PDAC and explored the impact of specific KRASm and WT status on survival. Methods: WGS and RNAseq were performed on 570 patients (pts) ascertained through our translational research program from 2012-2021, of which 443 were included for overall survival (OS) analyses. This included 176 pts with resected and 267 pts with advanced PDAC enrolled on the COMPASS trial (NCT02750657). The latter cohort underwent biopsies prior to treatment with first line gemcitabine-nab-paclitaxel or mFOLFIRINOX as per physician choice. The Kaplan-Meier and Cox proportional hazards methods were used to estimate OS. Results: KRAS WT PDAC (n = 52) represented 9% of pts, and these cases trended to be younger than pts with KRASm (median age 61 vs 65 years p = 0.1). In resected cases, the most common alterations in WT PDAC (n = 23) included GNASm (n = 6) and BRAFm/fusions (n = 5). In advanced WT PDAC (n = 27), alterations in BRAF (n = 11) and ERBB2/3/4 (n = 6) were most prevalent. Oncogenic fusions (NTRK, NRG1, BRAF/RAF, ROS1, others) were identified in 9 pts. The BRAF in-frame deletion p.486_491del represented the most common single variant in WT PDAC, with organoid profiling revealing sensitivity to both 3rd generation BRAF inhibitors and MEK inhibition. In resected PDAC, multivariable analyses documented higher stage (p = 0.043), lack of adjuvant chemotherapy (p < 0.001), and the KRAS G12D variant (p = 0.004) as poor prognostic variables. In advanced disease, neither WT PDAC nor KRAS specific alleles had an impact on prognosis (median OS WT = 8.5 mths, G12D = 8.2, G12V = 10.0, G12R = 12.0, others = 9.2, p = 0.73); the basal-like RNA subtype conferred inferior OS (p < 0.001). A targeted therapeutic approach following first line chemotherapy was undertaken in 10% of pts with advanced PDAC: MMRd (n = 1), homologous recombination deficiency (HRD) (n = 19), KRASG12C (n = 1), CDK4/6 amplification (n = 3), ERBB family alterations (n = 2), BRAF variants (n = 2). OS in this group was superior (14.7 vs 8.8 mths, p = 0.04), mainly driven by HRD-PDAC where KRASm were present in 89%. Conclusions: In our dataset, KRAS G12D is associated with inferior OS in resected PDAC, however KRAS mutational status was not prognostic in advanced disease. This suggests that improved OS in the WT PDAC population can only be achieved if there is accelerated access to targeted drugs for pts.

scholarly journals Management of neuroblastoma: a study of first- and second-line chemotherapy responses, a single institution experience

2012 ◽  
Vol 6 (1) ◽  
pp. 3 ◽  
Author(s):  
Emmad E. Habib ◽  
Amr T. El-Kashef ◽  
Ezzat S. Fahmy
Keyword(s):  
External Beam Radiotherapy ◽  
Second Line ◽  
First Line ◽  
Actuarial Survival ◽  
Term Survival ◽  
Second Line Chemotherapy ◽  
Significant Difference ◽  
Grade Malignancy ◽  
Chemotherapy Patients ◽  
Line Chemotherapy

Neuroblastoma is a high-grade malignancy of childhood. It is chemo- and radio-sensitive but prone to relapse after initial remission. The aim of the current study was to study the results of the first- and second-line chemotherapy on the short-term response and long-term survival of children, and to further describe the side effects of treatment. Ninety-five children with advanced neuroblastoma were included in the study, divided into two groups according to the treatment strategy: 65 were treated by first-line chemotherapy alone, and 30 children who were not responding or relapsed after first-line chemotherapy were treated by second-line chemotherapy. External beam radiotherapy was given to bone and brain secondary cancers when detected. Staging workup was performed before, during and after management. Response was documented after surgery for the primary tumor. Median follow up was 32 months (range 24-60 months). Chemothe rapy was continued until toxicity or disease progression occurred, indicating interruption of chemotherapy. Patients received a maximum of 8 cycles. Toxicity was mainly myelo-suppression, with grade II-III severity in 60% of the firstline and 70% of the second-line chemotherapy patients. Median total actuarial survival was nearly 51 months for the first-line chemotherapy group and 30 months for the second-line line group, with a statistically significant difference between the two groups (P&lt;0.01).

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