scholarly journals High-Grade Inflammation Attenuates Chemosensitivity and Confers to Poor Survival of Surgical Stage III CRC Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Hou-Qun Ying ◽  
Xia-Hong You ◽  
Yu-Cui Liao ◽  
Fan Sun ◽  
Xue-Xin Cheng
Keyword(s):  
Adjuvant Chemotherapy ◽  
Primary Tumor ◽  
Tumor Location ◽  
Stage I ◽  
Stage Iii ◽  
Molecular Characteristics ◽  
Chemotherapy Response ◽  
High Grade ◽  
T4 Stage ◽  
The Right

Background: Heterogeneous clinical and molecular characteristics are reported in colorectal cancer (CRC) with different tumor laterality. However, the outcome of left- and right-sided patients with stage I–III CRC and the role of chronic inflammation in survival differences between them remain unclear.Method: A prospective study including 1,181 surgical patients with stage I–III CRC was carried out to investigate the involvement of circulating fibrinogen-to-pre-albumin (Alb) ratio (FPR) and primary tumor sidedness in the clinical outcome of those patients. We further investigated the effect of FPR on adjuvant chemotherapy response and recurrence in stage III patients.Results: Our study showed that the right tumor location was significantly associated with poor recurrence-free survival (RFS) (p = 0.04, adjusted HR = 1.41, 95% CI = 1.02–1.94) and overall survival (OS) (p = 0.04, adjusted HR = 1.55, 95% CI = 1.01–2.38) only in the stage III disease. In these patients, T4 stage distribution (83.39 vs. 70.94%, p < 0.01) within right-sided cases was significantly higher than left-sided patients. Moreover, preoperative FPR within right-sidedness (p < 0.01), T4 stage (p < 0.05), and large cancer bulk (≥5 cm) (p < 0.05) subgroups was significantly elevated compared to their counterparts, and it was gradually rising following the increased cancer bulk (p trend < 0.01). High-FPR distribution (52.30 vs. 27.00%, p < 0.01) within right-sided patients with the stage III disease was significantly higher than that in the left-sided cases. RFS (plog−rank < 0.01) and OS (plog−rank < 0.01) of the high-FPR patients were extremely inferior to the low-FPR cases, and the significant associations were observed when they were adjusted by other confounders including primary tumor location (p < 0.01, adjusted HR = 1.96, 95% CI = 1.42–2.70 for RFS; p < 0.01, adjusted HR = 2.44, 95% CI = 1.59–3.75 for OS). Additionally, RFS of adjuvant chemotherapy-treated high-FPR patients was superior to the patients without chemotherapy (plog−rank = 0.01) but was inferior to the low-FPR patients undergoing the treatment, especially in the 5-FU- and XELOX-treated subgroup.Conclusion: These findings indicate that chronic high-grade inflammation weakens chemotherapy efficacy and contributes to the poor prognosis of stage III surgical CRC patients.

Impact of primary tumor size/horizontal extent on survival in colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 125-125
Author(s):  
Olatunji B. Alese ◽  
Wei Zhou ◽  
Renjian Jiang ◽  
Katerina Mary Zakka ◽  
Walid Labib Shaib ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Tumor Size ◽  
Primary Tumor ◽  
Survival Rates ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Primary Tumor Size ◽  
The Impact

125 Background: Pathologic staging in colorectal cancer (CRC) is crucial in patient management. Data regarding the impact of size/horizontal tumor extent is limited, contradictory and currently excluded from the American Joint Committee on Cancer (AJCC) staging model. However, a previously published SEER analysis showed that AJCC stages I and IIIA have similar 2- and 5- year survival rates, and worse rates for stage II. Using the largest cohort to date, we report the impact of primary tumor size on CRC survival. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2010 and 2015. Univariate and multivariate analyses were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor/patient characteristics and overall survival (OS). Results: A total of 61,145 patients were identified with a similar gender distribution (M/F:50.9%/49.1%). The mean age was 62.7years (SD+/-14.1) and 82% were non-Hispanic Whites. Majority had colon primary (82.7%) and 82.4% had microsatellite stable (MSS) disease. Distribution across stages I-IV was 20.1%, 32.1%, 34.7% and 13.2% respectively. Among the total study population, AJCC stage correlated closely with OS on multivariate analysis (HR 1.49, 2.29, 8.38 for stages II to IV compared to stage I), while the distinguishing power for tumor size was relatively mild (HR 1.19 and 1.33 for 5-10 cm and >5cm compared to <5cm). Among patients with stage II disease, tumors >10cm were associated with worse survival compared to those <5cm (HR 1.2; 1.03-1.39; p=0.22). Stage III disease also had differential survival rates; patients with tumors 5-10cm (HR 1.21; 1.14-1.28; p<0.001) and >10cm (HR 1.57; 1.37-1.80; p<0.001) had worse survival than those <5cm. Patients with stage II who did not receive adjuvant chemotherapy (CTX) had worse survival outcomes (HR 1.29; 1.08-1.55; p=0.005) compared to stage III disease who did. Accounting for tumor size, there was no statistically significant survival differences between stage I patients and stages II and III patients who received adjuvant chemotherapy. Conclusions: Tumors larger than 10cm have inferior outcomes among patients in the same AJCC stages. Stage II patients without adjuvant CTX did worse than stage III with CTX. Further studies are needed to clarify the role of tumor size in staging models. [Table: see text]

Incidence, timing, and predictors of CNS metastasis in patients (Pts) with clinically localized cutaneous melanoma (CM).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9580-9580
Author(s):  
Merve Hasanov ◽  
Denai R. Milton ◽  
Sapna Pradyuman Patel ◽  
Hussein Abdul-Hassan Tawbi ◽  
Isabella Claudia Glitza ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Cumulative Incidence ◽  
Tumor Location ◽  
Initial Diagnosis ◽  
Stage I ◽  
Acral Lentiginous Melanoma ◽  
Primary Tumor Location ◽  
Cns Metastasis ◽  
Increased Risk

9580 Background: Surveillance for CNS metastasis (mets) is not routinely performed in pts with clinically localized CM. Improved understanding of the incidence, timing and risk factors for the development of CNS metastasis in these pts may inform surveillance strategies. Methods: Under an IRB-approved protocol, demographics, tumor characteristics, and clinical events were collected for pts diagnosed from 1998 to 2019 with AJCC 8th edition stage I or II CM at MD Anderson Cancer Center. Dates of initial diagnosis, regional, distant non-CNS, and CNS mets were recorded. Symptoms and the extent of disease (brain, LMD, both) were recorded for pts with CNS mets. Cumulative incidence of distant mets (CNS and non-CNS) was determined using the competing risks method, including death; pts without CNS mets and alive at last follow-up were censored. Differences in cumulative incidence between groups were assessed using Gray’s test. Associations between measures of interest and cumulative incidence were determined using proportional subdistribution hazards regression models. All statistical tests used a significance level of 5%. Results: 5,179 Stage I-II CM pts were identified. At a median follow up of 82 (0.0-268.8) months, 703 (13.6%) pts were diagnosed with distant mets, including 355 (6.9%) with CNS mets. Cumulative incidence of CNS mets was 0%, 2%, and 5% at 1, 2, and 5 years, respectively. Among pts with distant mets, the first site of distant mets was CNS only for 29 (4%), non-CNS only for 557 (79%), and both for 116 (17%) pts. At initial diagnosis of CNS mets, 195 (55%) pts were asymptomatic, and 46 (13%) had no active extracranial disease. Median time to any distant met was longer for pts who were diagnosed with CNS mets [40.0 (1.9-238.0) months] vs pts diagnosed with non-CNS mets only [31.4 (1.1-185.7) months, p < 0.001]. On multivariable analysis, risk of CNS mets was significantly associated with primary tumor location of scalp [Hazard Ratio (HR) 3.4, 95% Confidence interval (CI) 1.9-5.9], head/neck (HR 3.3, 95% CI 2.0-5.3), or trunk (HR 2.3, 95% CI 1.5-3.5) (vs upper extremity); acral lentiginous melanoma subtype (HR 2.0, 95% CI 1.2-3.6) (vs superficial spreading); increased T category (T2 HR 1.5, 95% CI 1.1-2.2; T3 HR 1.9, 95% CI 1.2-3.0; T4 HR 2.1, 95% CI 1.1-3.8; vs T1), Clark level (CL) (CL4 HR 2.1, 95% CI 1.2-3.7 vs CL2), and mitotic rate (MR) (MR 5-9/mm2 HR 2.1, 95% CI 1.5-3.0; MR > 9/mm2 HR 2.0, 95% CI 1.3-3.0; vs MR 0-4/mm2). While high ( > 9/mm2) MR was associated with increased risk of CNS and non-CNS mets, intermediate (5-9/mm2) was associated with CNS mets only. Conclusions: Primary tumor location, tumor thickness, and MR were strongly associated with risk of CNS mets. MR rate was more strongly associated with risk of CNS than non-CNS mets. Validation in independent cohorts may provide evidence to support CNS surveillance strategies in select pts with stage I-II CM who are deemed high risk for CNS mets.

scholarly journals The effect of adjuvant chemotherapy on survival in patients with FIGO stage I high-grade serous ovarian cancer

2019 ◽  
Vol 153 (3) ◽  
pp. 562-567
Author(s):  
J.O.A.M. van Baal ◽  
K.K. Van de Vijver ◽  
M.D. Algera ◽  
M.A. van der Aa ◽  
G.S. Sonke ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adjuvant Chemotherapy ◽  
Figo Stage ◽  
Stage I ◽  
High Grade ◽  
Serous Ovarian Cancer

Prognostic factors of recurrence of colorectal cancers with microsatellite instability after curative resection: An AGEO retrospective multicenter study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3536-3536 ◽  
Author(s):  
David Tougeron ◽  
Gaelle Sickersen ◽  
Thierry Lecomte ◽  
Aziz Zaanan ◽  
Gaetan Des Guetz ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Lymph Node ◽  
Adjuvant Chemotherapy ◽  
Microsatellite Instability ◽  
Recurrence Rate ◽  
Braf Mutation ◽  
Stage I ◽  
Colorectal Cancers ◽  
T4 Stage

3536 Background: Microsatellite instability (MSI) phenotype is found in approximately 12% of colorectal cancers (CRC). MSI CRC is associated with a low recurrence rate and 5-fluorouracil chemoresistance in adjuvant setting. Clinical and pathological prognostic factors of recurrence are well-identified after surgery of CRC but not in the subgroup of MSI CRC. Methods: This multicenter retrospective study included patients with stage I, II and III MSI CRC. The following prognostic factors were studied: age, sex, perforation, occlusion, tumor location, tumor differentiation, T4 stage, lymph node invasion, VELIPI criteria (vascular emboli, lymphatic invasion and perinervous invasion), BRAF mutation and adjuvant chemotherapy. Disease-free survival (DFS) was calculated using the Kaplan-Meier method. Prognostic factors of DFS were analyzed in multivariate analysis using Cox model. Results: A total of 294 MSI CRC patients were analyzed, including 10%, 49% and 41% stage I, II and III, respectively. Mean age was 67.2 ± 16.0 years. Occlusion was observed in 10% of cases. VELIPI criteria were found in 39%, including 26% with vascular emboli. BRAF mutation was detected in 27% of cases. All in all, 40% of patients received adjuvant chemotherapy, predominantly stage III (74%). Mean follow-up was 39.2 ± 33.2 months. The disease recurrence rate was 3%, 8% and 21% in stage I, II and III patients, respectively. The 3-year DFS rate was 85%. In univariate analysis, age, occlusion, lymph node invasion, T4 stage, vascular emboli and perinervous invasion were associated with decreased DFS (p<0.05). In multivariate analysis, only occlusion (RR=3.0; 95% CI 1.2-7.7, p=0.02) and vascular emboli (RR=4.5; 95% CI 1.6-12.7, p<0.01) were associated with decreased DFS. Recurrence rates for MSI CRC with and without vascular emboli were respectively, 22% versus 5% for stage II and 33% versus 15% for stage III. Conclusions: Occlusion and vascular emboli were independently associated with recurrence of MSI CRC but not lymph node invasion. We advocate vascular emboli analysis in routine clinical practice to facilitate adjuvant chemotherapy decision-making in MSI CRC.

Prognostic impact of preoperative albumin to globulin ratio in curative colon cancer patients.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 647-647
Author(s):  
Yuji Toiyama ◽  
Hiroyuki Fujikawa ◽  
Yasuhiro Inoue ◽  
Hiroki Imaoka ◽  
Masato Okigami ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Early Recurrence ◽  
Stage I ◽  
Stage Iii ◽  
Prognostic Impact ◽  
Stage Iii Colon Cancer ◽  
Albumin To Globulin Ratio

647 Background: Albumin to globulin ratio (AGR) has been reported to predict long term mortality in patients with several cancers. However, prognostic impact of preoperative AGR in colon cancer patients with curative intent has not yet been fully addressed. Therefore, we, for the first time, investigated the association between AGR and clinico-pathological findings including overall survival (OS) and disease free survival (DFS) in stage I-III colon cancer patients. Methods: Clinicopathological findings including preoperative laboratory data (carcinoembryonic antigen [CEA] and AGR) from 251 curative colon cancer patients were assessed as indicators of early recurrence and poor prognosis in this retrospective study. AGR was calculated as [AGR = albumin/ (total protein - albumin)]. The cut-off value of AGR was 1.32 in current study. Results: Several clinicopathological categories related with tumor progression such as lymph node metastasis, T4 tumor, large tumor size, undifferentiated tumor, venous and lymphatic invasion, and high CEA were significantly associated with low AGR level. The patients with low AGR were significantly poorer OS (P = 0.001) and DFS (P = 0.003) than those with high AGR, respectively. In addition, multivariate analyses demonstrated that low AGR was independently associated with early recurrence (HR = 2.87, P = 0.007) and poor prognosis (HR = 2.56, P = 0.008), respectively. On the other hand, sub analysis of survival curves revealed that stage III colon cancer patients with low AGR were significantly poorer OS (P = 0.007) and DFS (P = 0.02) than those with high AGR, respectively. Furthermore, significantly poorer OS and DFS were also shown in stage I-II colon cancer patients with low AGR, respectively (OS: P = 0.02, DFS: P = 0.01). Conclusions: Preoperative AGR was an independent predictor of early recurrence and poor prognosis in curative colon cancer patients. AGR may represent a simple, potentially useful predictive biomarker for selecting stage I-II colon cancer patients who might need adjuvant chemotherapy. Furthermore, AGR may select candidates who are better to introduce more intensive adjuvant chemotherapy after curative operation in stage III colon cancer patients.

Racial/ethnic differences in use of surgery and adjuvant chemotherapy for nonmetastatic colon cancer: Where's the rub?

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 529-529
Author(s):  
J. Yang ◽  
P. Mauldin ◽  
M. Ebeling ◽  
T. Hulsey ◽  
M. B. Thomas ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Medical Oncology ◽  
Stage I ◽  
Stage Iii ◽  
Independent Effect ◽  
Chi Square ◽  
Black Race ◽  
Hispanic Ethnicity

529 Background: Disparities in receipt of recommended medical therapy for colon cancer have been reported. The objective of this study was to determine the independent effect of black race and Hispanic ethnicity on use of surgery/adjuvant therapy in patients (pts) with nonmetastatic colon cancer, controlling for surgical/medical oncology consultation Methods: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified 26,946 pts aged 66 and older with resected stage I-III colon cancer diagnosed between 1999-2004. Surgical/medical oncology consultation and receipt of chemotherapy were ascertained from Medicare claims. The relationships between patient/tumor characteristics, surgical/medical oncology consultation, and use of surgery/adjuvant therapy were analyzed using chi square tests. Odds ratios (OR) of receipt of surgery/chemotherapy were calculated using logistic regression analysis. Results: We identified 23,834 white, 2,022 black, and 1,090 Hispanic pts with stage I (7,088 pts), stage II (9,510 pts), and stage III (7,236 pts) colon cancer. Blacks and Hispanics were more likely to be younger, less educated, of lower income, and have greater comorbidity compared to whites. Rates of surgical resection were lower among blacks than Hispanics (86.6% vs. 88.8% vs. 92.0% in whites, all p < 0.001). Blacks with stage III colon cancer (but not Hispanics) were also less likely to receive adjuvant chemotherapy (48.2% vs. 54.7% in whites, p < 0.001). After controlling for socioeconomic status, comorbidity, and surgical/medical oncology consultation, black race (but not Hispanic ethnicity) was independently associated with underuse of surgery (adjusted OR, 0.68; 95% confidence interval [CI], 0.51-0.89) and adjuvant chemotherapy (adjusted OR, 0.71; 95% CI, 0.60-0.85). Conclusions: Black race, but not Hispanic ethnicity, is a powerful, independent predictor of underuse of surgery and adjuvant chemotherapy in pts with nonmetastatic colon cancer. Qualitative studies are needed to determine whether patient misperceptions about colon cancer surgery/chemotherapy or suboptimal physician-patient interactions may underlie these observations. No significant financial relationships to disclose.

Predictors of survival in pancreatic squamous cell carcinoma (PSCC): An analysis from the National Cancer Database (NCDB).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 399-399
Author(s):  
Anuhya Kommalapati ◽  
Sri Harsha Tella ◽  
Gaurav Goyal ◽  
Amit Mahipal
Keyword(s):  
Surgical Resection ◽  
Primary Tumor ◽  
Multivariable Analysis ◽  
Group Analysis ◽  
Stage Iv ◽  
The United States ◽  
Stage I ◽  
Stage Iii ◽  
Dismal Prognosis ◽  
Stage Iv Disease

399 Background: PSCC is a rare form of exocrine pancreatic malignancy with a dismal prognosis. Using the NCDB, we determined the prognostic factors and survival outcomes of PSCC in the United States. Methods: We performed a retrospective analysis of patients with histologically confirmed PSCC from 2004-2015 using NCDB. Kaplan-Meier method and log-rank test were used to perform overall survival (OS) analysis. Hazard Ratios were calculated using the Cox-proportional hazard method. Results: Of the 654 cases included in our analysis, 46% were female. Median age at diagnosis was 70 years and did not differ by sex (p = 0.19). The proportion of patients with stage I, II, III and IV diseases were 5%, 18%, 12%, and 54%, respectively (10%, unknown stage). Among these, 23% (35 of 150) of stage I and II disease, 10% (8 of 78) of stage III, and 2% (7 of 353) received surgical resection of the primary tumor. The rate of R0 resection was 74% in stage I and II; 38% in stage III; 29% in stage IV disease. Median OS for the entire cohort was 4 months and was significantly higher in patients who received surgical resection of the primary tumor (17 vs. 4 months, p < 0.001). On stage wise sub-group analysis, stage I-II patients had OS benefit from surgery (21 vs. 5 months, p < 0.001) as opposed to stage III (7 vs. 6 months, p = 0.31) and IV disease (5 vs. 3 months, p = 0.17). Adjuvant chemotherapy had no role in prolonging survival in stage I-II disease (20 vs 24 months, p = 0.6). Stage IV patients treated with chemotherapy had a better median OS than those without (5 vs. 2 months, p < 0.0001). On Cox multivariable analysis, stage IV disease (HR: 1.92 CI: 1.46-2.52, p < 0.001) and advanced patient age (HR: 1.02; CI:1.01-1.03, p < 0.001 were associated with poor OS, whereas OS was not dependent on the sex, race, grade, insurance status, surgery, and chemotherapy. Conclusions: This is the largest registry-based study on PSCC to date. PSCC had a diverse OS varied significantly according to increasing age and stage of the disease at presentation. Surgical resection of primary tumor was associated with improved OS in stages I-II, whereas chemotherapy improved OS in stage IV disease. The results of our study may aid the prognostication of patients and in treatment decision making.

Clinical impact of primary tumor location in patients with metastatic colorectal cancer (mCRC) treated with regorafenib or trifluridine/tipiracil as later-line.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 105-105
Author(s):  
Hiromichi Nakajima ◽  
Shota Fukuoka ◽  
Toshikazu Moriwaki ◽  
Toshiki Masuishi ◽  
Atsuo Takashima ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Prognostic Factor ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Tumor Location ◽  
Primary Tumor Location ◽  
The Right ◽  
The Impact

105 Background: In the recent years, primary tumor location (PTL) is considered as an important prognostic and predictive factor in first-line treatment of mCRC. Although regorafenib (REG) and trifluridine/tipiracil (TFTD) have been available recently, the prognostic value of PTL in later-line with these agents is not well understood. TFTD improved survival regardless of PTL in the RECOURSE trial, while REG did not show survival benefit in the patients (pts) with rectal cancer in the CORRECT trial. Methods: We retrospectively evaluated pts with mCRC who were registered in a multicenter observational study (the REGOTAS study). The main inclusion criteria were ECOG PS of 0–2, refractory or intolerant to fluoropyrimidines, oxaliplatin, irinotecan, and anti-VEGF and anti-EGFR therapy (if KRAS wild type), and no prior use of REG and TFTD. The impact of PTL on overall survival (OS) were evaluated using Cox proportional hazards models based on baseline characteristics and propensity score matching. Results: A total of 550 pts (223 pts in the REG group, 327 pts in the TFTD group; 122 pts in the right-sided, 428 pts in the left-sided) were included in this study. Although the right-sided pts was significantly shorter OS compared with the left-sided pts by univariate analysis (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.63-0.99, P = 0.04), multivariate analysis revealed that PTL was not an independent prognostic factor (HR 0.88, 95% CI 0.69-1.1, P = 0.26). The similar results were obtained in each treatment group. In subgroup analysis according to PTL, OS were comparable between REG and TFTD groups regardless of PTL (HR 0.93, 95% CI 0.62-1.39 in the right-sided; HR 1.08, 95% CI 0.83-1.39 in the left-sided [excluding rectum]; and HR 1.01, 95% CI 0.62-1.62 in the rectal cancer pts). These results were similar in sensitivity analysis using propensity score-matching. Conclusions: In the present study, PTL is not a prognostic factor in patient with mCRC treated with either REG or TFTD as later-line. No difference in OS was observed between REG and TFTD groups irrespective of PTL.

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