Circulating Tumor Cells are Predictive of Poor Response to Chemotherapy in Metastatic gastric cancer

2015 ◽  
Vol 30 (4) ◽  
pp. 382-386 ◽  
Author(s):  
Su Jin Lee ◽  
Jeeyun Lee ◽  
Seung Tae Kim ◽  
Se Hoon Park ◽  
Joon Oh Park ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Tumor Cells ◽  
Progression Free Survival ◽  
Poor Response ◽  
Metastatic Gastric Cancer ◽  
Negative Group ◽  
Free Survival ◽  
Positive Group ◽  
Response To Chemotherapy

Background The aim of this study was to investigate the impact of number of circulating tumor cells (CTCs) on the treatment outcome for metastatic gastric cancer (GC) following palliative chemotherapy. Methods CTCs were isolated from 7.5 mL of whole blood from 100 patients with metastatic GC by anti-EpCAM antibody coated magnetic particles using the CTC-Profiler (Veridex). Correlations between CTC counts and clinicopathological variables, progression-free survival and overall survival were examined. Results Between January 2010 and August 2010, 100 metastatic GC patients were enlisted. Among 100 patients, 5 or more CTCs (CTC-positive) were detected in 27 of 95 patients (28%). Even though the clinical characteristics of the CTC-positive and CTC-negative groups were not significantly different, the treatment response to cytotoxic chemotherapy in the CTC-positive group was significantly poorer (progressive disease: 23.4% vs. 60.0% in CTC-negative vs. CTC-positive group, respectively; p = 0.004). The median progression-free survival of the CTC-positive group was substantially shorter than that of the CTC-negative group (59 days vs. 141 days; p = 0.004). For overall survival, CTC-positive group had significantly shorter survival than CTC-negative group (median OS, 120 days vs. 220 days; p = 0.030). A multivariate Cox proportional hazards regression model showed that CTC positivity was an independent adverse factor for progression-free survival and overall survival. Conclusions This study suggests CTCs are associated with poor response to chemotherapy in metastatic GC ­patients.

Third- and later-line treatment in advanced or metastatic gastric cancer: a systematic review and meta-analysis

2020 ◽  
Vol 16 (2) ◽  
pp. 4409-4418 ◽  
Author(s):  
Alessandro Rizzo ◽  
Veronica Mollica ◽  
Angela Dalia Ricci ◽  
Ilaria Maggio ◽  
Maria Massucci ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Supportive Care ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Best Supportive Care ◽  
Free Survival

Aim: We performed a systematic review and meta-analysis to investigate the efficacy and safety of third-line (TLT) and salvage treatment (ST) in advanced or metastatic gastric cancer. Materials & methods: Eligible studies included randomized clinical trials assessing TLT and ST versus placebo or best supportive care. Outcomes of interest included: overall survival, objective response rate and disease control rate in TLT; progression-free survival in ST; grade 3–4 adverse events in ST. Results: The use of TLT and ST was superior to placebo or best supportive care in terms of prolonging overall survival and progression-free survival. Hematological toxicities were more frequent in ST. Conclusion: TLT and ST are considerable and tolerable treatment options for patients with advanced or metastatic gastric cancer. Given the substantial heterogeneities affecting the efficacy analyses, these results have to be interpreted cautiously.

Telomerase Expression Predicts Unfavorable Outcome in Osteosarcoma

2004 ◽  
Vol 22 (18) ◽  
pp. 3790-3797 ◽  
Author(s):  
Robert P. Sanders ◽  
Rachid Drissi ◽  
Catherine A. Billups ◽  
Najat C. Daw ◽  
Marcus B. Valentine ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Primary Tumor ◽  
Progression Free Survival ◽  
Outcome Analysis ◽  
Negative Group ◽  
Primary Tumors ◽  
Free Survival ◽  
Positive Group ◽  
Alternative Lengthening ◽  
Group 3

Purpose Osteosarcoma is distinct from most cancers in that the majority of osteosarcomas lack telomerase expression and use the alternative lengthening of telomeres (ALT) mechanism to maintain telomeres. Laboratory studies suggest that compared with ALT, telomerase expression is associated with increased tumor aggressiveness. We evaluated the clinical significance of telomerase expression in human osteosarcoma. Patients and Methods Fifty-six osteosarcomas from 51 patients treated at St Jude Children's Research Hospital between 1982 and 2003 were evaluated for telomerase enzyme activity, mRNA expression of the catalytic component of telomerase (TERT), and presence of the ALT pathway. Results Outcome analysis was based on TERT mRNA expression in the primary tumor samples from 44 patients. Fourteen primary tumors expressed TERT mRNA (32%; eight TERT only, six TERT and ALT) and 30 did not express TERT mRNA (68%; 29 ALT, one no ALT). Progression-free survival (PFS) was inferior in the TERT-positive group compared with the TERT-negative group (3-year estimates, 21.4% ± 9.5% v 63.7% ± 11.1%; P = .014). Likewise, overall survival was inferior in the TERT-positive group compared with the TERT-negative group (3-year estimates, 42.9% ± 12.2% v 70.0% ± 9.9%; P = .031). Among 31 patients with nonmetastatic disease at diagnosis, PFS was lower in the TERT-positive group compared with the TERT-negative group (3-year estimates, 33.3% ± 13.6% v 72.0% ± 11.5%; P = .092). Conclusion Telomerase expression in primary tumor samples is associated with decreased PFS and OS in patients with osteosarcoma. Additional studies are warranted to better define the clinical utility of this molecular marker.

Progression-Free Survival in Children With Optic Pathway Tumors: Dependence on Age and the Quality of the Response to Chemotherapy—Results of the First French Prospective Study for the French Society of Pediatric Oncology

2003 ◽  
Vol 21 (24) ◽  
pp. 4572-4578 ◽  
Author(s):  
Véronique Laithier ◽  
Jacques Grill ◽  
Marie-Cécile Le Deley ◽  
Marie-Madeleine Ruchoux ◽  
Dominique Couanet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Disease Progression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Optic Pathway ◽  
Free Survival ◽  
Factors Associated ◽  
Response To Chemotherapy ◽  
Risk Of Disease

Purpose: To evaluate a strategy aimed at avoiding radiotherapy during first-line treatment of children with progressive optic pathway tumors (OPT), by exclusively administering multiagent chemotherapy during 16 months. Patients and Methods: Between 1990 and 1998, 85 children with progressive OPT were enrolled onto this multicenter nationwide trial. Chemotherapy alternating procarbazine plus carboplatin, etoposide plus cisplatin, and vincristine plus cyclophosphamide was given every 3 weeks. At the time of relapse or progression, second-line chemotherapy was authorized before recourse to radiotherapy. Results: Objective response rate (partial response [PR] + complete response [CR]) to chemotherapy was 42%. Five-year progression-free survival (PFS) and overall survival rates were 34% and 89%, respectively. The 5-year radiotherapy-free survival rate was 61%. In the multivariate analysis of the 85 patients that entered onto the study, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .047) and absence of neurofibromatosis type 1 (P = .035). In the multivariate analysis of the 74 patients that remained on study after the first cycle of chemotherapy, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .0053) and no objective response to chemotherapy (P = .0029). Three-year PFS was 44% in infants ≤ 1 year versus 66% in children older than 1 year. Three-year PFS was 53% in the absence of an objective response to chemotherapy versus 68% after a PR or CR. Conclusion: A significant proportion of children with OPT can avoid radiotherapy after prolonged chemotherapy. Deferring irradiation with chemotherapy protocols did not compromise overall survival of the entire population or visual function.

scholarly journals Hyperprogressive disease during nivolumab or irinotecan treatment in patients with advanced gastric cancer

ESMO Open ◽  
2019 ◽  
Vol 4 (3) ◽  
pp. e000488 ◽  
Author(s):  
Masahiko Aoki ◽  
Hirokazu Shoji ◽  
Kengo Nagashima ◽  
Hiroshi Imazeki ◽  
Takahiro Miyamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Survival Benefit ◽  
Poor Prognosis ◽  
Tumour Growth ◽  
Progression Free Survival ◽  
Free Survival ◽  
Prior Therapy ◽  
Hyperprogressive Disease

BackgroundNivolumab showed a survival benefit for advanced gastric cancer (AGC). However, an acceleration of tumour growth during immunotherapy, (hyperprogressive disease, HPD) has been reported in various cancers. This study reviewed the HPD in patients with AGC treated with nivolumab or irinotecan.MethodsThe subjects of this retrospective study were patients with AGC with measurable lesions, and their tumour growth rates (TGR) during nivolumab or irinotecan were compared with those during prior therapy. HPD was defined as an increase in TGR more than twofold.Results34 and 66 patients received nivolumab and irinotecan in third or later line between June 2009 and September 2018 at our hospital; 22 patients receiving nivolumab had prior treatment with irinotecan, and one patient received irinotecan after nivolumab. Nivolumab and irinotecan showed no differences in disease control rates (38.2% and 34.8%) and in progression-free survival (PFS) (HR 1.1, 95% CI 0.7 to 1.6, p=0.802). The incidence of HPD was slightly higher after nivolumab (29.4%) than after irinotecan (13.5%) (p=0.0656), showing no differences in background between the patients with and without HPD. Compared between HPD and PD other than HPD after nivolumab, the HRs for PFS and overall survival (OS) were 1.1 (95% CI 0.5 to 2.7; p=0.756), and 2.1 (95% CI 0.7 to 5.8; p=0.168), but such clear difference in OS was not observed after irinotecan.ConclusionsHPD was observed more frequently after nivolumab compared with irinotecan, which was associated with a poor prognosis after nivolumab but not so clearly after irinotecan.

Similar Outcomes among African-Americans (AA) and Whites after Autologous Hematopoietic-Cell Transplantation (Auto HCT) for Multiple Myeloma (MM)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 740-740 ◽  
Author(s):  
Parameswaran Hari ◽  
Navneet S. Majhail ◽  
Anna Hassebroek ◽  
Mei-Jie Zhang ◽  
Fareeha Siddiqui ◽  
...  
Keyword(s):  
Overall Survival ◽  
Renal Function ◽  
African Americans ◽  
Progression Free Survival ◽  
Free Survival ◽  
Post Transplant ◽  
Transplant Outcomes ◽  
Remission Status ◽  
Response To Chemotherapy ◽  
White Patients

Abstract MM is the most common hematological malignancy among AA adults and AA have twice the incidence and mortality from MM compared to Whites (SEER data, 2007). Based on CIBMTR registration rates of Auto HCT and incidence rates for MM, AA patients have been shown to have significantly lower likelihood of receiving Auto HCT (age adjusted odds ratio 0.58) compared to White patients with MM. The characteristics of AA patients who undergo Auto HCT for MM and their post transplant outcomes have not been compared to that of White MM patients. We compared characteristics and post-transplant outcomes of AA (N=303) and White (N=1892) patients receiving a first Auto HCT for MM and reporting to the CIBMTR between 1995 and 2005. Recipients of tandem Auto HCT were excluded. Compared to Whites, AA were significantly younger (29% aged <50 yr vs 21%, p=0.002), had better performance status at Auto HCT (69% with KPS score ≥90 vs 61%, p=0.005) and had higher incidence of hypertension (47% vs 25%, p<0.001), diabetes mellitus (17 % vs 9%, p<0.001) and morbid obesity (38% vs 31%, p=0.01). Durie-Salmon stage, immunoglobulin subtype, renal function, number of prior chemotherapy regimens, response to chemotherapy and remission status at transplant were similar in both groups. Transplant was more likely to be performed later (>12 months from diagnosis) in AA (37% vs 28% in Whites, p<0.001). The proportion of AA receiving Auto HCT increased from 7% in 1995 to 17% in 2004. No significant differences were found between AA and Whites in overall survival (52% vs 47%, at 5 years), progression-free survival (19% vs 21%, at 5 years), non-relapse mortality (3% vs 5%, at 1 year), or relapse (72% at 5 years in both groups) after Auto HCT. In multivariate analyses adjusting for patient, disease and transplant-related variables, race did not impact overall survival, progression-free survival, non-relapse mortality, or relapse (Table 1). We conclude that despite increased pre-transplant co-morbidities and transplantation later in the course of disease, post-transplant outcomes are comparable among AA and White patients who undergo Auto HCT for MM. The lower transplant rates in AA and the differences in pre-transplant patient characteristics need further investigation to explore racial differences in patient referral and selection for Auto HCT. Table 1: Multivariate analysis: African-Americans vs. Whites (reference group) Outcome Relative Risk 95% CI P-value Overall survival 0.94 0.78–1.13 0.50 Progression-free survival 0.94 0.81–1.09 0.42 Non-relapse mortality 1.16 0.75–1.80 0.51 Relapse 0.92 0.78–1.08 0.31 Adjusted for age, gender, KPS score at transplant, comorbidities (hypertension, diabetes, obesity, smoking), renal function, immunoglobulin subtype, Durie-Salmon stage, number of previous chemotherapy regimens, response to chemotherapy, remission status, time since diagnosis and year of transplant

Multicenter randomized phase II study of weekly docetaxel alone versus weekly docetaxel plus oxaliplatin as a second-line chemotherapy in patients with advanced gastric cancer: Preliminary response and safety results.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14570-e14570 ◽  
Author(s):  
Jin Young Kim ◽  
Young Rok Do ◽  
Keon Uk Park ◽  
Hun-Mo Ryoo ◽  
Sung Hwa Bae ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Therapy Group ◽  
Progression Free Survival ◽  
Combination Group ◽  
Second Line ◽  
Free Survival ◽  
Weekly Docetaxel ◽  
Line Chemotherapy

e14570 Background: Gastric cancer is a frequent malignancy with worldwide estimated incidence of 990,000 cases, representing 7.8% of all cancers in 2008. There are limited data suggesting a benefit for doublet second-line chemotherapy in advanced gastric cancer. Methods: The eligibility criteria were patients 1) with prior exposure to cisplatin based chemotherapy and advanced or recurrent stomach cancer 2) with pathologically proven gastric adenocarcinoma, 3) with an ECOG performance status 0 to 2, 4) with measurable lesions. Each treatment cycle was consisted of docetaxel 36 mg/m2 in docetaxel mono therapy group and docetaxel 36 mg/m2, oxaliplatin 80 mg/m2 in docetaxel/oxaliplatin doublet therapy group on days 1, 8. The primary end point of this study was response rate, and secondary end points included toxicity, progression free and overall survival. Results: Fifty two patients were enrolled; median age was 63 years; male (n=42) and female (n=10); docetaxel mono therapy (n=27) and docetaxel/oxalliplatin doublet therapy (n=25). The median number of cycles administered was 2.5 (range,1-9). Fourty eight patients were assessable for efficacy. Four partial responses, 7 stable diseases in mono therapy group (RR; 4/27, 14.8%) and 1 complete remission, 4 partial responses, 13 stable diseases in double therapy group (RR; 5/25, 20.0%) were confirmed (p=0.198). Median progression free survival was 1.97 months in the mono therapy group and 4.93 months in doublet therapy group (p=0.007). Median overall survival was 11.57 months in the mono therapy group and 8.13 months in doublet therapy group (p=0.650). Grade 3 or 4 adverse events were reported in 11 of 52 patients; G3 pain were in 2 patients and G3 pneumonia was in 1 patient in mono group, G3/4 neutropenia were 5 patients in the combination group, G3 nausea, vomiting, general weakness was 1 patient each group in combination group. Conclusions: Weekly docetaxel/oxaliplatin doublet therapy showed superior progression free survival to monotherapy group as second line therapy in cisplatin pretreated advanced gastric cancer patients.

Salvage gastrectomy for unresectable advanced gastric cancer after combination chemotherapy with docetaxel, cisplatin, and S-1.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15113-e15113
Author(s):  
Kei Hosoda ◽  
Keishi Yamashita ◽  
Shinichi Sakuramoto ◽  
Hiroaki Mieno ◽  
Katsuhiko Higuchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Advanced Gastric Cancer ◽  
Univariate Analysis ◽  
Pancreatic Head ◽  
Progression Free Survival ◽  
Hematologic Toxicity ◽  
Primary Tumors ◽  
Free Survival

e15113 Background: The prognosis for patients with unresectable advanced gastric cancer treated with chemotherapy alone is extremely poor. We have evaluated the safety and efficacy of salvage gastrectomy following chemotherapy with docetaxel, cisplatin, and S-1 (DCS) in patients with unresectable advanced gastric cancer. Methods: We evaluated 30 patients with unresectable advanced gastric adenocarcinoma whose lesions were down-staged by DCS chemotherapy and who underwent salvage gastrectomy with lymph node dissection from 2006 to 2012, when visible lesions were judged resectable. We retrospectively reviewed their medical records to identify factors that would influence overall survival. Results: Of the 30 patients, 17 had extra-regional lymph node metastases, 5 had liver metastases, 9 had peritoneal dissemination and 6 had pancreatic head invasion prior to DCS chemotherapy. Of the 30 patients, 23, 3, and 4 underwent R0, R1, and R2 resection, respectively. No in-hospital deaths or reoperations occurred. Pathological evaluation of primary tumors revealed grades 3, 2, 1b, 1a, and 0 tumor regression in 4, 9, 7, 7, and 2 patients, respectively. Median progression-free survival was 19 months.Two-year progression-free survival and overall survival rates were 45% and 65%, respectively. Of 17 patients with target tumors, 15 had partial responses, making the overall response rate 88%. The most common grade 3/4 hematologic toxicity was neutropenia (56%); all treatment-related toxicities were resolved, and no patient died of toxicity-related causes. Univariate analysis showed that R1/2 surgery (p<0.001), diffuse type histology (p=0.054), histological grade 0/1a/1b following chemotherapy (p<0.033), ypN3 (p<0.001) and yply2/3 (p=0.003), were significantly prognostic of reduced overall survival. A multivariate proportional hazard model found that ypN3 (p=0.003) was the sole independent prognostic factor. Conclusions: Salvage gastrectomy after DCS chemotherapy was safe and effective in patients with unresectable advanced gastric cancer. Lymph node metastasis after chemotherapy was significantly prognostic of poor prognosis, suggesting the need for further treatment.

scholarly journals Progression-Free Survival as a Surrogate for Overall Survival in Advanced/Recurrent Gastric Cancer Trials: A Meta-Analysis

2013 ◽  
Vol 105 (21) ◽  
pp. 1667-1670 ◽  
Author(s):  
Xavier Paoletti ◽  
Koji Oba ◽  
Yung-Jue Bang ◽  
Harry Bleiberg ◽  
Narikazu Boku ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Free Survival ◽  
Recurrent Gastric Cancer ◽  
Cancer Trials
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