Treatment strategy for metastatic colorectal cancer (mCRC) treated with chemotherapy plus biological targeted agent: Is strategy with biological targeted agent based on the primary tumor lesion possible?

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 769-769
Author(s):  
Tamotsu Sagawa ◽  
Kyoko Hamaguchi ◽  
Naomi Uemura ◽  
Fumito Tamura ◽  
Koshi Fujikawa ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Tumor Location ◽  
Wild Type ◽  
Survival Times ◽  
Retrospective Case ◽  
Primary Tumors ◽  
Tumor Lesion ◽  
Targeted Agent ◽  
Early Tumor ◽  
The Impact

769 Background: The data from randomized trials suggested that primary tumor location (PTL) could represent a prognostic and predictive factor in mCRC patients, particularly during treatment with anti- EGFR therapy. However, it remains unclear whether anti-EGFR is effective for right- sided primary tumors (RT). Methods: Single-institution, retrospective, case-control study was reviewed. A total of 110 patients with mCRC were enrolled between January 2011 and December 2016. We evaluated the association between PTL and survival parameters in patients with previously untreated mCRC receiving first-line chemotherapy (FOLFOX/CapeOX or FOLFIRI/IRIS) plus cetuximab(Cmab) or bevacizumab(Bmab). The impact of PTL for Cmab and Bmab groups was analyzed, respectively. Results: 76 patients presented Left-sided primary tumors (LT) and 34 patients RT. Median PFS, median OS, and ORR were numerically superior in our study patients with LT compared with patients with RT (PFS, L vs R, 13.0 vs 6.8 M, p = 0.0040; OS, 36.2 vs 19.0 M, p = 0.002; ORR, 67.1 vs 44.1 %, p = 0.022951). In the Cmab group, LT were significantly superior to RT in terms of OS (L vs R, 56.3 vs11.3 M, p = 0.0057). Likewise, in the Bmab group, OS showed differences between the LT and RT (L vs R, 27.8 vs 19.7 M, p = 0.0116). In LT, Cmab group were significantly superior to Bmab group in terms of the OS (C vs B, 56.3 vs 27.8 M p = 0.0428). Conversely, in RT, the survival times showed no differences between Cmab and Bmab group (C vs B, 11.3 vs 19.7 M, p = 0.6555). Furthermore, while early tumor shrinkage(ETS) was associated with favorable outcome in patients with RT who treated Cmab, non-ETS represented a less favorable survival (ETS vs non-ETS, NR vs 11.3 M, p = 0.0335). ETS was a predictor for survival benefit acquired from Cmab treatment for patients with RT with wild-type KRAS/RAS tumors. Conclusions: Our study suggests the conclusion that patients with LT with KRAS/RAS wild-type should be preferentially treated with Cmab. By contrast, in RT, chemotherapy plus Bmab may be effective, but optimal treatment has yet to be defined and ETS may be able to predictive of benefit acquired from Cmab.

Primary tumor location as a prognostic and predictive factor in metastatic colorectal cancer (mCRC) treated with chemotherapy plus cetuximab: A retrospective analysis.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 711-711 ◽  
Author(s):  
Tamotsu Sagawa ◽  
Kyoko Hamaguchi ◽  
Akira Sakurada ◽  
Fumito Tamura ◽  
Tsuyoshi Hayashi ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Strong Predictor ◽  
Tumor Location ◽  
Molecular Characteristics ◽  
Survival Times ◽  
Retrospective Case ◽  
Primary Tumors ◽  
Primary Tumor Location ◽  
Left And Right ◽  
The Impact

711 Background: Left- and right-sided colon cancers are significantly different in epidemiologic, clinicopathological and molecular characteristics. However, the impact of primary tumor location in mCRC treated biological targeted agent in combination with chemotherapy is unclear. We therefore investigated the prognostic and predictive impact of primary tumor location in mCRC. Methods: Single-institution, retrospective, case-control study was reviewed. A total of 96 patients with mCRC were enrolled between January 2011 and December 2015. We evaluated the association between tumor location and survival parameters in patients with previously untreated mCRC receiving first-line chemotherapy plus cetuximab or bevacizumab. The impact of primary tumor location for cetuximab and bevacizumab groups was analyzed, respectively. Left-sided primary tumors were defined as tumors from rectum to splenic flexure, while right-sided primary tumors were defined as tumors from cecum to the distal part of the transverse colon. Results: 68 patients presented left-sided tumors and 28 patients right-sided primary tumors. In the cetuximab group, left-sided tumors were significantly superior to right-sided tumors in terms of the progression-free survival (PFS) and Overall survival (OS) (PFS, left vs right, 18.3 vs 6.8 M, p = 0.0415; OS, 50.6 vs10.5 M, p = 0.0004). Likewise, in the bevacizumab group, OS showed differences between the left- and right-sided tumors (PFS, left vs right, 11.6 vs 7.3 M, p = 0.1904; OS, 25.7 vs 16.2 M, p = 0.0389). In left-sided tumors, cetuximab group were significantly superior to bevacizumab group in terms of the OS (PFS, cetuximab vs bevacizumab, 18.0 vs 11.6 M, p = 0.1088; OS, 50.6 vs 25.7 m p = 0.0354). Conversely, in right-sided, the survival times showed no differences between cetuximab- and bevacizumab group (PFS, cetuximab vs bevacizumab, 6.8 vs 7.3 M, p = 0.7816; OS, 10.5 vs 16.2 M, p = 0.1088). Conclusions: Our study demonstrates that primary tumor location is an important prognostic factor in previously untreated mCRC. Furthermore, left-sided primary tumor location might be a strong predictor of PFS and OS in cetuximab therapy.

scholarly journals Primary tumor location affects recurrence-free survival for patients with colorectal liver metastases after hepatectomy: A propensity score matching analysis

2020 ◽  
Author(s):  
Yuanping Zhang ◽  
Yongjin Wang ◽  
Yichuan Yuan ◽  
Jiliang Qiu ◽  
Yuxiong Qiu ◽  
...  
Keyword(s):  
Propensity Score ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Colorectal Liver Metastases ◽  
Tumor Location ◽  
Recurrence Free Survival ◽  
Primary Tumors ◽  
Free Survival ◽  
Primary Tumor Location ◽  
Before And After

Abstract Background: Whether primary tumor location of colorectal cancer (CRC) affects survival of patients after resection of liver metastases remains controversial. This study was conducted to investigate the differences in clinicopathological characteristics and prognosis between right-sided CRC and left-sided CRC patients with liver metastases after hepatectomy. Methods: From 2002 to 2018, 611 patients with colorectal liver metastases (CRLM) who underwent hepatectomy at our center were reviewed. Primary tumors located from cecum to transverse colon were defined as right-sided group (n = 141); tumors located from splenic flexure to rectum were defined as left-sided group (n = 470). Patients were compared between two groups before and after a 1:1 propensity score matching (PSM) analysis. Results: Before PSM, median survival time and 5-year overall survival (OS) rate in right-sided group were 77 months and 56.3%, and those in left-sided group were 64 months and 51.1%, respectively. After PSM, median survival time and 5-year OS rate in right-sided group were 77 months and 55.9%, and those in left-sided group were 58.8 months and 47.3%, respectively. The OS rates did not differ between two groups before and after PSM (P = 0.575; P = 0.453). However, significant different recurrence-free survival (RFS) rate was found before and after PSM between right-sided and left-sided group (P = 0.028, P = 0.003). Conclusions: Compared to patients with left-sided primary tumors, patients with right-sided primary tumors had a worse RFS but similar OS. Careful preoperative evaluation, intensive preoperative chemotherapy and frequent follow-up to detect early recurrence might be justified for CRLM patients with right-sided primary tumors.

Contrast enhanced CT (CE-CT) changes and nephrometry down-scoring of unresectable primary renal cell carcinoma (RCC) tumors in patients (Pts) treated with neoadjuvant sunitinib.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 299-299 ◽  
Author(s):  
M. Salem ◽  
S. N. Shah ◽  
L. S. Wood ◽  
P. Elson ◽  
A. Medsinge ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Objective Response ◽  
Sign Test ◽  
Rank Test ◽  
Primary Tumors ◽  
Venous Thrombus ◽  
Nephrometry Score ◽  
Primary Renal Cell Carcinoma ◽  
Contrast Enhanced Ct ◽  
The Impact

299 Background: The impact of neoadjuvant sunitinib on CE-CT parameters and nephrometry score of primary RCC tumors remains unknown. Methods: Retrospective review of baseline and prenephrectomy CE-CT from a prospective phase II trial of neoadjuvant sunitinib (50 mg sunitinib continuous dosing) in unresectable primary RCC tumors with or without metastatic disease. CE-CT parameters and R.E.N.A.L. nephrometry score for each lesion were determined in pts who underwent subsequent surgery. RECIST and MASS criteria were used to assess primary tumor radiographic response. CT changes were analyzed using the sign test and Wilcoxon signed rank test. Results: Twenty nine pts were enrolled, of which 13 pts (85%M; median age 63y) underwent post-sunitinib resection of 16 primary tumors (3 pts had multifocal RCC). Post-therapy, 88% of tumors had decreased long diameter (median 32% decrease, p<0.001 vs. baseline), 88% decreased attenuation (median 30 HU reduction, p=0.006) and 69% increased necrosis (p=0.001). 56% of tumors had a decrease in nephrometry score (median 1 point decrease; 10 to 9, p=004). At baseline, 81% of tumors were highly complex by nephrometry score; following therapy 46% of the highly complex tumors became moderately complex. At baseline 13 tumors abutted renal hilar vital structures, whereas following treatment 4 tumors demonstrated abutment. Adenopathy decreased (range, 23%-83%) in 4/4 patients with enlarged baseline lymph nodes, with complete resolution in 1 patient. RECIST objective response was seen in 38% and SD in 56% of primary tumors; 1 tumor had PD based on size despite > 95% necrosis. MASS criteria response was favorable 38%, intermediate 62%. Two of four pts had reduction in extent of venous thrombus (1 pt from level 0 to resolved and 1 pt from level IV to II). Conclusions: Neoadjuvant sunitinib resulted in decreased size/attenuation, increased necrosis of the primary tumor and reduction in lymphadenopathy and venous thrombus in pts who underwent subsequent surgery. Sunitinib reduced the RENAL nephrometry score and facilitated nephrectomy, notably due to impact on tumor proximity to vital structures in the renal hilum. [Table: see text]

Impact of M1a and M1b staging in patients (pts) with metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3590-3590 ◽  
Author(s):  
Hagen F. Kennecke ◽  
Jason Yu ◽  
Sharlene Gill ◽  
Winson Y. Cheung ◽  
Charles Davic Blanke ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Prognostic Impact ◽  
Primary Tumors ◽  
7Th Edition ◽  
The Impact

3590 Background: In 2009, pts with M1 colorectal cancer were divided into two subsets for the American Joint Committee on Cancer (AJCC) 7th edition. Pts with metastases (mets) confined to one organ or site at initial diagnosis became stage M1a while multiple sites or peritoneal mets became M1b. The objectives of the study are to evaluate the impact of site of mets and M1a/b staging among pts with M1 colorectal cancer. Methods: All pts referred to the BC Cancer Agency from 1999-2007 with newly diagnosed M1 colon or rectal cancer were included. Demographic, treatment, and outcome data were prospectively collected. The prognostic impact of individual sites of mets was assessed by hazard ratio estimates from univariate Cox models. Multivariable Cox proportional-hazards models were used to determine variables associated with overall survival in the entire cohort and in those undergoing resection of their primary tumor. Results: 2,049 pts with M1 disease were included. Median age was 66 years; 71% had colonic origin; 70% had their primary tumor resected; and 69% received chemotherapy. In univariate analysis, solitary mets were associated with improved survival. In multivariable analysis, M1a/b status still had significant prognostic effect. The effect remained significant in the subgroup analysis of pts with resected primary tumors when histology, T and N stage were included. Conclusions: Pts with solitary mets, including peritoneum, have superior overall survival as compared to those with multiple sites of mets. AJCC 7th edition staging that includes M1a/b provides significant prognostic information and should be considered in clinical practice and trials of pts with M1 disease who otherwise have few prognostic factors. [Table: see text]

Primary tumor location and efficacy of second-line therapy after initial treatment with FOLFIRI in combination with cetuximab or bevacizumab in patients with metastatic colorectal cancer- FIRE-3 (AIOKRK0306).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3525-3525 ◽  
Author(s):  
Dominik Paul Modest ◽  
Sebastian Stintzing ◽  
Ludwig Fischer von Weikersthal ◽  
Thomas Decker ◽  
Alexander Kiani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Treatment Duration ◽  
Tumor Location ◽  
Second Line ◽  
Wild Type ◽  
Second Line Therapy ◽  
Primary Tumor Location ◽  
Line Therapy

3525 Background: FIRE3 compared 1st-line therapy with FOLFIRI plus either cetuximab (arm A) or bevacizumab (arm B) in 592 patients (pts) with KRAS exon 2 wild-type metastatic colorectal cancer (mCRC). Second-line therapies appeared more successful in arm A compared to arm B. The impact of primary tumor location on this observation is unclear. Methods: Pts. were stratified for primary tumor site (left- vs. right-sided). Duration of 2nd-line therapy was calculated as time from first to last application. Progression-free survival (PFS2nd) and overall survival (OS2nd) of second-line therapy) were evaluated by Kaplan-Meier method and compared by log rank test as well as Cox regression. All analyses were performed in the RAS wild-type population of the trial and reported according to drug sequences. Results: 272 of 400 pts. (68%) received 2nd-line therapy, of those 206 (109 in arm A, 97 in arm B) pts. presented left-sided, whereas 66 (26 in arm A, 40 in arm B) pts. presented right-sided primaries. PFS2nd was markedly longer in pts. with left-sided as compared to right-sided primary tumors (6.0 (95% CI: 5.5-6.7) vs. 3.4 (95% CI: 3.0-5.8) months, hazard ratio (HR): 0.64 (95% CI: 0.47-0.87), P = 0.005). Differences in PFS2nd between study-arms were evident in pts. with left-sided primaries (arm A: 7.3 (95% CI: 6.4-7.7) vs. arm B: 5.3 (95% CI: 4.3-5.9) months, HR: 0.61 (95% CI: 0.44-0.84), P = 0.002), but not in pts. with right-sided primaries (arm A: 4.0 (95% CI: 3.0-6.3) vs. arm B: 3.3 (95% CI: 2.6-5.8) months, HR: 1.09 (95% CI: 0.62-1.90). Consistent observations were also made for treatment duration and OS2nd. Conclusions: This retrospective analysis indicates that treatment duration and efficacy of second-line therapy are associated with primary tumor location. Efficacy of second-line therapy was significantly greater in pts. with left-sided tumors as compared to right sided tumors. This difference was driven by superior activity of second-line regimens of arm A compared to arm B in left-sided tumors. Our observations confirm the strong prognostic value of primary tumor location in mCRC across treatment lines. Clinical trial information: NCT00433927.

Prognostic impact of PD-L1 and PD-1 expression by primary tumor location in colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 628-628 ◽  
Author(s):  
Jonna Berntsson ◽  
Anna Larsson ◽  
Bjorn Nodin ◽  
Jakob Eberhard ◽  
Karin Jirstrom
Keyword(s):  
Colorectal Cancer ◽  
Immune Cells ◽  
Primary Tumor ◽  
Tumor Location ◽  
Left Colon ◽  
Prognostic Impact ◽  
Full Cohort ◽  
Primary Tumors ◽  
Primary Tumor Location ◽  
Entire Cohort

628 Background: A plethora of studies report abundant expression of programmed death-ligand 1 (PD-L1) on tumors to be associated with poor outcome in several cancer forms, whereas immune cell-specific expression of PD-L1 has been associated with improved prognosis in colorectal cancer. However, none of these studies have investigated the association with prognosis according to primary tumor location. This study aimed to investigate the clinicopathological correlates and prognostic impact of PD-L1 and its receptor PD-1 in colorectal cancer, with particular reference to the anatomical subsite of the primary tumor. Methods: Immunohistochemical expression of PD-L1 and PD-1 was analysed in tissue microarrays with tumors from 557 incident cases of CRC from a prospective population-based cohort. Kaplan-Meier and Cox regression analyses were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. Results: High PD-L1 expression on tumor-infiltrating immune cells correlated significantly with an improved 5-year OS in univariable and multivariable analysis, adjusted for age, sex, TNM stage, differentiation grade, and vascular invasion, in the full cohort (HR = 0.49; 95 % CI 0.35-0.68), and in primary tumors of the right (HR = 0.43; 95 % CI 0.25-0.74) and the left colon (HR = 0.28; 95 % CI 0.13-0.61), but not in rectal cancer. High tumor-specific PD-L1-expression was not significantly associated with prognosis in neither the full cohort nor according to primary tumor location. High expression of PD-1 on tumor-infiltrating immune cells was significantly associated with an improved 5-year overall survival in the entire cohort (HR = 0.42; 95 % CI 0.21-0.87), but not in subsite analysis according to primary tumor location. Conclusions: This study is, to the best of our knowledge, the first to investigate the prognostic impact of PD-L1 and PD-1 expression according to primary tumor site in colorectal cancer. Dense infiltration of PD-L1+ immune cells was found to be an independent favorable prognostic factor in primary tumors of the right and left colon, but not in the rectum.

CD73 expression in primary and metastatic renal cell carcinoma (RCC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 643-643 ◽  
Author(s):  
Abhishek Tripathi ◽  
Sarah E Johnston ◽  
Yan D Zhao ◽  
Oudai Hassan ◽  
Linda F Thompson ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Checkpoint Inhibitors ◽  
Statistical Significance ◽  
Method Comparison ◽  
Rank Test ◽  
Primary Tumors ◽  
Metastatic Tissue ◽  
Pathologic Features ◽  
Cd73 Expression ◽  
The Impact

643 Background: Agents targeting the PD-1 pathway have improved outcomes in RCC. CD73 may be an additional mechanism which tumors can exploit for immune evasion. It is regulated by hypoxia inducible factor (HIF) and converts AMP to adenosine. The resulting increase in extracellular adenosine can inhibit T-cell effector function. We evaluated CD73 expression in primary and metastatic tumor samples in patients with RCC. Methods: A commercial TMA (US Biomax) consisting of 31 primary clear cell RCC samples (2 with sarcomatoid features) with 8 matched and 1 unmatched metastases was used to assess CD73 expression. A genitourinary pathologist (OH) confirmed pathology and grade. Immunohistochemistry (IHC) was performed using a monoclonal anti-CD73 antibody (Cell Signaling; D7F9A). A combined score (CS: % of cells positive x intensity) was employed to quantify CD73 expression. Expression levels between matched primary and metastatic tissue was compared using Wilcoxon signed-rank test. Correlation of CD73 expression (CS > 0) in primary tumor with baseline clinical and pathologic characteristics was assessed using Kruskal-Wallis and Fisher's exact tests. Overall survival (OS) was estimated using the Kaplan-Meier method. Comparison between CD73 expression groups used log rank test. Results: CD73 expression was seen in 19% (n = 6) of primary and 66.7% (n = 6) of metastatic samples. Among matched primary and metastatic samples (n = 8 each), median CS was 25 (Q1-Q3:0-105) in metastatic samples while none of the corresponding primary samples demonstrated CD73 expression (median CS = 0, p = 0.062). CD73 expression in primary tumor samples did not correlate with baseline clinical or pathologic features. Five-year OS was 50% in patients who expressed CD73 in primary tumors compared to 84% in those who did not (p = 0.26). Conclusions: We observed a numerical increase in CD73 expression in metastatic tissue compared to primary RCC samples and worse 5 year OS. The small number of samples has limited statistical significance. Further studies are needed to examine the impact of CD73 expression on outcomes in RCC patients treated with currently approved checkpoint inhibitors and the investigational CD73 antagonists that are in early phases of development.

scholarly journals Impact of Glutamine Transporters on Pneumococcal Fitness under Infection-Related Conditions

2010 ◽  
Vol 79 (1) ◽  
pp. 44-58 ◽  
Author(s):  
Tobias Härtel ◽  
Matthias Klein ◽  
Uwe Koedel ◽  
Manfred Rohde ◽  
Lothar Petruschka ◽  
...  
Keyword(s):  
White Blood Cells ◽  
Survival Rates ◽  
Genomic Analysis ◽  
Infection Model ◽  
Wild Type ◽  
Survival Times ◽  
Reverse Transcription Pcr ◽  
Mouse Infection Model ◽  
The Impact ◽  
Glutamine Uptake

ABSTRACTThe genomic analysis ofStreptococcuspneumoniaepredicted six putative glutamine uptake systems, which are expressed underinvitroconditions, as shown here by reverse transcription-PCR. Four of these operons consist ofglnHPQ, while two lackglnH, which encodes a soluble glutamine-binding protein. Here, we studied the impact of two of these glutamine ATP-binding cassette transporters onS.pneumoniaeD39 virulence and phagocytosis, which consist of GlnQ and a translationally fused protein of GlnH and GlnP. Mice infected intranasally with D39Δgln0411/0412showed significantly increased survival times and a significant delay in the development of pneumococcal pneumonia compared to those infected with D39, as observed in real time using bioluminescent pneumococci. In a mouse sepsis model, the mutant D39Δgln0411/0412showed only moderate but significant attenuation. In contrast, the D39Δgln1098/1099knockout strain was massively attenuated in the pneumonia and septicemia mouse infection model. To cause pneumonia or sepsis with D39Δgln1098/1099, infection doses 100- to 10,000-fold higher than those used for wild-type strain D39 were required. In an experimental mouse meningitis model, D39Δgln1098/1099produced decreased levels of white blood cells in cerebrospinal fluid and showed decreased numbers of bacteria in the bloodstream compared to D39 and D39Δgln0411/0412. Phagocytosis experiments revealed significantly decreased intracellular survival rates of mutants D39Δgln1098/1099and D39Δgln0411/0412compared to wild-type D39, suggesting that the deficiency of Gln uptake systems impairs resistance to oxidative stress. Taken together, our results demonstrate that both glutamine uptake systems are required for full virulence of pneumococci but exhibit different impacts on the pathogenesis of pneumococci underinvivoconditions.

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