PROGNOSTIC VALUE OF N-MYC GENE AMPLIFICATION IN PATIENTS WITH NEUROBLASTOMA

This work presents the results of studying the prognostic value of the N-MYC gene amplification in patients with neuroblastoma treated according to the European protocol NB-2004. A retrospective analysis of 140 patients who were diagnosed with neuroblastoma from 2013-2019 was carried out at the SCP and PS. When collecting data from 140 patients with neuroblastoma, amplification of the N-MYC gene was found in 26 patients, of which 19 patients died (73%), 7 patients are alive (survival rate -27%). Amplification of the NMYC gene occurred with the same frequency in boys and girls, 50% in each group. In children under one year old, there were 6 children (23.1%), 1-2 years old 12 patients (46.2%), 2-5 years old 5 children (19.2%), over 5 years old 3 patients (11.5%). In 13 (50%) children, the primary tumor was localized in the adrenal glands, in 11 (42%) - in the retroperitoneal space and in 2 (7.7%) in the mediastinum. In 21 (80.8%) patients with amplification of the N-MYC gene, the disease was diagnosed at stage IV, in 2 cases (7.7%) with stage IVs, and 1 (3.8%) case at I, II, III stage of the disease. Thus, patients with N-MYC gene amplification were more often detected at stage IV of the disease and had an unfavorable outcome.The fact of the negative impact of amplification of the N-MYC gene is confirmed in our study. The therapeutic protocol is ineffective in the presence of N-MYC gene amplification (survival - 27%). Keywords: Neuroblastoma, NMYC gene amplification, prognosis, children.

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Phase II study of pemetrexed (Pem) and cisplatin (Cis) plus cetuximab (Cet) followed by Pem and Cet maintenance therapy in patients (Pts) with advanced nonsquamous non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.7554 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 7554-7554

Author(s):

Gerald Schmid-Bindert ◽

Vittorio Gebbia ◽

Frank Mayer ◽

Edurne Arriola ◽

Diego Marquez-Medina ◽

...

Keyword(s):

Survival Rate ◽

Performance Status ◽

Objective Response ◽

Stage Iv ◽

Study Drug ◽

Progression Free Survival ◽

Free Survival ◽

Secondary Endpoints ◽

Grade 3 ◽

One Year

7554 Background: A prospective, nonrandomized, multicenter study was conducted to assess the effect of adding cet to pem and cis in pts with advanced nonsquamous NSCLC. Methods: 113 Caucasian performance status 0-1 pts received 1st line pem (500 mg/m2) and cis (75 mg/m2) on day 1 (21d cycle) for 4-6 cycles and cet (400 mg/m2 loading dose followed by 250 mg/m2) weekly. Non-progressive pts received pem 500 mg/m2 on day 1 (21d cycle) plus cet (250mg/m2 weekly) until progression. Pts received vitamin B12/folic acid and dexamethasone. Primary endpoint was objective response rate (ORR) (RECIST 1.0). Secondary endpoints were progression free survival (PFS), 1 year survival rate, translational research (TR) and safety. Results: Pts’ characteristics: median age 59.7 years, 64% male, 50% PS 0, 92% stage IV, and 78% adenocarcinoma. All pts completed ≥ 1 cycle of induction therapy and 45% and 43% completed ≥ 1 cycle of maintenance with pem and cet, respectively. ORR (n=109) was 38.5% (80% CI 32.2-45.1), all partial responses. Disease control rate (response/stable disease) was 59.6% (80% CI: 53.1-65.9). Median PFS was 5.82 months (80% CI: 4.40-6.70). One year survival rate was 0.45 (80% CI: 0.39-0.51). Significant associations were seen between high EGFR by IHC and increased PFS (cytoplasm: HR=0.46, p=0.035; membrane: HR=0.41, p=0.008), and between high nuclear TTF-1 and increased ORR (OR=7.73, p=0.021) / PFS (HR=0.21, p<0.001) / OS (HR=0.25, p=0.035). Of 113 pts evaluated for safety, 73 (64.6%) pts had drug related CTC Grade 3/4 adverse events (AE): most frequent were neutropenia (14.2%), rash (15%), and vomiting (8.8%). Drug related serious AEs were reported in 27.4% pts: most frequent were anemia (5.3%), neutropenia (5.3%), vomiting (3.5%), and rash, renal failure, diarrhea and fatigue (1.8% each). There were 2 potential on-study drug related deaths (sudden death and large intestinal perforation). Conclusions: Pem, cis and cet appeared efficacious and tolerable. These results support further evaluation in a randomized trial. The TR outcomes are hypothesis generating given the study’s size and nonrandomized nature.

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Prognostic Value of Primary Tumor Sidedness for Unresectable Stage IV Colorectal Cancer: A Retrospective Study

Annals of Surgical Oncology ◽

10.1245/s10434-019-07209-x ◽

2019 ◽

Vol 26 (5) ◽

pp. 1358-1365 ◽

Cited By ~ 9

Author(s):

Dai Shida ◽

Taro Tanabe ◽

Narikazu Boku ◽

Atsuo Takashima ◽

Takefumi Yoshida ◽

...

Keyword(s):

Colorectal Cancer ◽

Retrospective Study ◽

Primary Tumor ◽

Prognostic Value ◽

Stage Iv ◽

Stage Iv Colorectal Cancer ◽

Unresectable Stage

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Prognostic Value of Resection of Primary Tumor in Patients with Stage IV Colorectal Cancer: Retrospective Analysis of Two Randomized Studies and a Review of the Literature

Annals of Surgical Oncology ◽

10.1245/s10434-011-1951-5 ◽

2011 ◽

Vol 18 (12) ◽

pp. 3252-3260 ◽

Cited By ~ 104

Author(s):

Sabine Venderbosch ◽

Johannes H. de Wilt ◽

Steven Teerenstra ◽

Olaf J. Loosveld ◽

Aart van Bochove ◽

...

Keyword(s):

Colorectal Cancer ◽

Retrospective Analysis ◽

Primary Tumor ◽

Prognostic Value ◽

Stage Iv ◽

Review Of The Literature ◽

Stage Iv Colorectal Cancer ◽

Randomized Studies

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Randomized phase II study of three doses of the integrin inhibitor cilengitide versus docetaxel as second-line treatment for patients (pts) with stage IV non-small cell lung cancer (NSCLC)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.8014 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 8014-8014

Author(s):

C. Manegold ◽

J. Vansteenkiste ◽

F. Cardenal ◽

W. Schütte ◽

P. Woll ◽

...

Keyword(s):

Survival Rate ◽

Tumor Progression ◽

Phase Ii ◽

Phase Ii Study ◽

Stage Iv ◽

Progression Free Survival ◽

Open Label ◽

Randomized Phase Ii ◽

Grade 3 ◽

One Year

8014 Background: Cilengitide (EMD 121974) is the most advanced compound in clinical development of a new class of oncology drugs, the integrin inhibitors. Integrins (heterodimeric transmembrane receptors) play key roles in cell interactions. Cilengitide selectively inhibits the cell-surface integrins αVβ3 and αVβ5 on activated endothelial cells during angiogenesis and on tumor cells. Methods: Multicenter, open-label, randomized, phase II study in 140 pts with relapsed stage IV NSCLC. Pts received 1 of 3 cilengitide doses (240 [n=35], 400 [n=35], or 600 [n=36] mg/m2) twice weekly or docetaxel 75 mg/m2 (n=34) once every 3-week cycle for 6 months. Responding pts could continue cilengitide for up to 1 year. Primary endpoint: progression-free survival (PFS). Results: Median age (range) was 60 (33–80) years; 94 pts were male (67%); 83% of pts had KPS ≥80%. Median PFS (95% CI) was 54 (43–64), 63 (53–66), 63 (42–67), and 67 (61–123) days for cilengitide 240, 400, 600, and docetaxel 75 mg/m2, respectively. Median OS (95% CI) was 173 (81–197), 117 (92–209), 181 (90–326), and 194 (135–298) days, respectively. One-year survival rate (95% CI) was 13% (1–24%), 13% (0–26%), 29% (12–37%), and 27% (10–43%), respectively. Survival was similar with cilengitide 600 mg/m2 and docetaxel 75 mg/m2: median OS 181 versus 194 days and 1-year survival rate (95% CI) 29% (12–37%) versus 27% (10–43%). Five docetaxel pts (15%) had a partial response. Most pts (98%) had ≥1 adverse event (AE). Most common AEs were dyspnea (33%), nausea (30%), tumor progression (29%), and cough (23%). Dyspnea and tumor progression were more common with cilengitide than with docetaxel. Grade 3/4 treatment-related AEs were more common with docetaxel (n=13, 41%) than cilengitide 240 (n=2, 6%), 400 (n=4, 11%), or 600 (n=4, 11%) mg/m2. For cilengitide, these were nausea, chest pain, dyspnea, and fatigue. Conclusions: PFS in the docetaxel group was greater than that of cilengitide at all doses. However, cilengitide monotherapy at a dose of 600 mg/m2 showed similar OS to docetaxel and better tolerability. Combination studies with standard chemotherapy and cilengitide are warranted. [Table: see text]

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EGFR-activating mutations and treatment with tyrosine-kinase inhibitors (TKI) to revert poor-prognosis (PP) associated with liver metastases (LM) in stage IV non-small cell lung cancer (NSCLC) patients (pts).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e19106 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e19106-e19106

Author(s):

Eduardo Castanon ◽

Maria D. Lozano ◽

Juan Pablo Fusco ◽

Estefania Arevalo ◽

Omar Esteban Carranza ◽

...

Keyword(s):

Survival Rate ◽

Clinical Outcome ◽

Kinase Inhibitors ◽

Stage Iv ◽

Egfr Mutations ◽

Wild Type ◽

Molecular Alterations ◽

Activating Mutations ◽

One Year ◽

Egfr Tki

e19106 Background: LM appear in 20-30% of pts diagnosed with NSCLC and they confer PP. However, whether the clinical outcome of NSCLC pts with LM harboring molecular alterations in EGFR, KRAS and EML4-ALK genes is substantially different depending on their distinct status is still unknown. Methods: A total of 268 consecutive stage IV NSCLC pts were included. The tumor molecular analysis for EGFR, KRAS and EML4-ALK was available in 205 pts (76.5%), 136 pts (50.7%) and 31 pts (11.6%), respectively. An EGFR mutation was observed in 32 pts (15.6%), KRAS was mutated in 28 pts (20.6%) and EML4-ALK gene rearrangement was observed in 3 pts (9.6%). We aimed to determine whether the molecular status of EGFR, KRAS and EML4-ALK has an impact on the clinical outcome of stage IV NSCLC pts. Results: Most of the pts were men (71.3%). The most common histology was adenocarcinoma (59.3%). Overall, 34% of the pts showed LM at any time of the disease course. Among the whole cohort, median OS for LM pts was 16 months vs 42 months for pts with metastases other than LM (p<0.001). Among pts with LM and EGFR mutations, the one-year survival rate was 85.7% vs 54.3% for pts with LM and EGFR wild-type (p=0.03). We analyzed whether pts received EGFR TKI or standard chemotherapy (SC). For the subgroup of pts carrying EGFR mutations and receiving TKI, the 18-month survival rate was 75% for those showing LM vs 80% (p=0.44) for those without LM. In contrast, for the subgroup of EGFR wild-type pts receiving SC, the 18-month survival rate was 32.4% for those showing LM vs 74.9% for those without LM (p<0.001). No impact of KRAS or EML4-ALK molecular alterations on OS of pts with LM was observed. Conclusions: The presence of LM at any time of the disease curse negatively impacts on the clinical outcome of NSCLC pts. However, the presence of EGFR activating mutations significantly improves the OS of those with liver spread, reaching a similar OS to subjects with no LM. Pts with EGFR mutations and LM may revert the PP associated to LM when an EGFR TKI is prescribed.

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