Lymphocyte-to-Monocyte Ratio Is a Predictive Biomarker of Response to Treatment with Nivolumab for Gastric Cancer

Oncology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Shigeo Tokumaru ◽  
Tomonobu Koizumi ◽  
Yasushi Sekino ◽  
Nobumichi Takeuchi ◽  
Shinji Nakata ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Treatment Response ◽  
Systemic Inflammation ◽  
Characteristic Curve ◽  
Objective Response ◽  
Response To Treatment ◽  
Lymphocyte To Monocyte Ratio ◽  
Recurrent Gastric Cancer

<b><i>Introduction:</i></b> Patients with unresectable or recurrent gastric cancer who have an objective response (OR) to nivolumab monotherapy are expected to have a good long-term prognosis. However, the OR rate for nivolumab treatment is low at 11%, and there is a need for biomarkers to predict the treatment response. This study aimed to analyze the significance of systemic inflammation-related variables and clinicopathologic characteristics as predictive markers of response to nivolumab monotherapy in patients with advanced gastric cancer. <b><i>Methods:</i></b> In this retrospective cohort study, we enrolled 71 consecutive patients who received nivolumab monotherapy for unresectable or recurrent gastric cancer. Receiver operating characteristic curve analysis was performed to determine the cutoff values of systemic inflammation-related variables, predictors of treatment response, and other prognostic factors related to nivolumab therapy. We focused on systemic inflammation-related variables measured before nivolumab induction and 2 weeks after its first administration and performed multivariate analysis to assess whether they could be used as prognostic factors. <b><i>Results:</i></b> Multivariate analysis revealed that a lymphocyte-to-monocyte ratio (LMR) of ≤3.28 after 2 weeks of initial nivolumab treatment (2wLMR) is a statistically significant predictor of treatment response (<i>p</i> = 0.012). The progression-free survival (PFS) rate of patients with liver metastasis was significantly worse than that of the other patients (1-year PFS: 0.0 vs. 24.4%, respectively; <i>p</i> = 0.005). The overall survival (OS) of patients with a low 2wLMR was significantly longer than that in patients with a high 2wLMR (1-year OS: 37.4 vs. 18.9%, respectively; <i>p</i> = 0.022). <b><i>Conclusions:</i></b> Thus, the 2wLMR could be a useful biomarker to predict response to nivolumab treatment and the prognosis of unresectable and recurrent gastric cancer.

The prognostic factors and the cause of death in patients with advanced or recurrent gastric cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 215-215
Author(s):  
Sang Woo Lee ◽  
In Keun Choi ◽  
Chang Min Lee ◽  
Seung Young Kim ◽  
Jong Jin Hyun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Bone Metastasis ◽  
Advanced Gastric Cancer ◽  
Causes Of Death ◽  
Palliative Surgery ◽  
Peritoneal Seeding ◽  
Recurrent Gastric Cancer

215 Background: The purpose of this study is to evaluate significant prognostic factor and compare the cause of death in patients with advanced or recurrent gastric cancer. Methods: We reviewed the medical records of 170 patients who had been diagnosed as advanced or recurrent gastric cancer between January 2006 and September 2013. The patients were divided into two groups. One group (advanced gastric cancer: AC) included 104 patients had undergone chemotherapy for advanced gastric cancer, and the other group (recurrent gastric cancer: RC) 66 for recurrence after surgical treatment. The causes of death and overall survival were compared between two groups, and the significant prognostic factors were investigated by multivariate analysis. Also, subgroup analysis was performed for 18 patients with gastrectomy for curative intent, and they were proved to have unresectable gastric cancer after surgery (non-palliative surgery for advanced gastric cancer: NS). Results: In the comparison for the causes of death, two groups showed no statistical difference, but AC group had more tendency to die because of bleeding ( p = 0.054) and infection ( p = 0.075). Overall survival of AC group did not differ from that of RC ( p = 0.901). In multivariate analysis, bone metastasis ( p = 0.013, HR = 1.923), peritoneal seeding ( p = 0.001, HR = 2.182) and the frequency of chemotherapy ( p < 0.001, HR = 0.887) were significantly associated with the overall survival. In a subgroup analysis, the overall survival of NS was significantly higher than AC ( p = 0.032). Conclusions: In the patients with advanced or recurrent gastric cancer, AC might have more possibility to die because of bleeding and infection than RC. Additionally, the prognosis of patients with advanced or recurrent gastric cancer was affected by the presence of bone metastasis, peritoneal seeding and frequency of chemotherapy. Non-palliative surgery for gastric cancer might show the better prognosis than AC in the specific conditions.

scholarly journals Germline Mutations in Other Homologous Recombination Repair-Related Genes Than BRCA1/2: Predictive or Prognostic Factors?

2021 ◽  
Vol 11 (4) ◽  
pp. 245
Author(s):  
Laura Cortesi ◽  
Claudia Piombino ◽  
Angela Toss
Keyword(s):  
Prognostic Factors ◽  
Homologous Recombination ◽  
Pancreatic Adenocarcinoma ◽  
Objective Response ◽  
Metastatic Breast ◽  
Germline Mutations ◽  
Response To Treatment ◽  
Homologous Recombination Repair ◽  
Dna Breaks ◽  
Recombination Repair

The homologous recombination repair (HRR) pathway repairs double-strand DNA breaks, mostly by BRCA1 and BRCA2, although other proteins such as ATM, CHEK2, and PALB2 are also involved. BRCA1/2 germline mutations are targeted by PARP inhibitors. The aim of this commentary is to explore whether germline mutations in HRR-related genes other than BRCA1/2 have to be considered as prognostic factors or predictive to therapies by discussing the results of two articles published in December 2020. The TBCRC 048 trial published by Tung et al. showed an impressive objective response rate to olaparib in metastatic breast cancer patients with germline PALB2 mutation compared to germline ATM and CHEK2 mutation carriers. Additionally, Yadav et al. observed a significantly longer overall survival in pancreatic adenocarcinoma patients with germline HRR mutations compared to non-carriers. In our opinion, assuming that PALB2 is a high-penetrant gene with a key role in the HRR system, PALB2 mutations are predictive factors for response to treatment. Moreover, germline mutations in the ATM gene provide a better outcome in pancreatic adenocarcinoma, being more often associated to wild-type KRAS. In conclusion, sequencing of HRR-related genes other than BRCA1/2 should be routinely offered as part of a biological characterization of pancreatic and breast cancers.

Retrospective Analysis of the Prognostic Factors That Influence Treatment Response and Survival of Patients with Cancer of Unknown Primary

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Zeinab Abdlelhafeez ◽  
Dina Ragab ◽  
Nervana Hussien ◽  
Fatma El – Tabakh
Keyword(s):  
Prognostic Factors ◽  
Treatment Response ◽  
Retrospective Analysis ◽  
Clinical Oncology ◽  
Cancer Registries ◽  
Cancer Of Unknown Primary ◽  
Response To Treatment ◽  
Unknown Primary ◽  
University Hospitals ◽  
Patients With Cancer

Abstract Background Cancers of unknown primary site (CUPs) are heterogeneous group of metastatic tumors for which a standardized diagnostic work-up could not recognize the site of origin at the time of diagnosis. Cancer registries around the world report the incidence of CUP in the range of 3%–5% of all malignancies, worldwide the overall age-standardized incidence per 100.000 people per year is 4–19 cases. CUP therefore ranks among the top 10 commonest malignancies. CUP occurs equally in both males and females, at average age 60 years old. Incidence of CUP in Egypt is 6.1%in males and 5.5% in females. Aim of the Work to retrospectively identify the prognostic factors that influence treatment outcome and survival of patients diagnosed with cancer of unknown primary treated patients at Clinical Oncology departments at Ain Shams University Hospitals (ASUH) and Helwan University Hospitals by retrospective analysis. Patients and Methods At the department of clinical oncology, Ain Shams University, 102 patients with cancer of unknown primary were identified in the period between January 2012 and December 2017, all patients data was collected and reviewed. The primary end point of this study is to identify different prognostic factors that influence treatment response and OS in 102 patients with CUP in the period from January 2012 to December 2017. Results Patients with PS 1, with no comorbidities showed better treatment response, also Patients younger than 65year, presented with PS1, with no comorbidity had longer survival. Conclusion CUP has a poor prognosis. Some prognostic factors that affect response to treatment and survival in these patients, which may be identified.

scholarly journals Prognostic role of lymphocyte-to-monocyte ratio in pancreatic neuroendocrine neoplasms

2020 ◽  
Vol 9 (4) ◽  
pp. 289-298 ◽  
Author(s):  
Wentao Zhou ◽  
Tiantao Kuang ◽  
Xu Han ◽  
Wenqi Chen ◽  
Xuefeng Xu ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Systemic Inflammation ◽  
Lymphocyte Count ◽  
Neuroendocrine Neoplasms ◽  
Inflammation Markers ◽  
Clinical Value ◽  
Term Survival ◽  
Pancreatic Neuroendocrine Neoplasms ◽  
Lymphocyte Ratio ◽  
Lymphocyte To Monocyte Ratio

Objectives Systemic inflammation markers have been demonstrated to be associated with prognosis in various tumors. In this study, we aimed to assess the value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index and the counts of lymphocyte, monocyte and neutrophil in predicting prognosis among patients with resected pancreatic neuroendocrine neoplasms (pNENs). Methods A total of 174 patients were included in the study. Univariate and multivariate analyses were performed to evaluate the predictive roles of inflammation markers for relapse-free survival (RFS) and overall survival (OS) in pNEN patients. Results The optimal cut-off values of NLR, LMR and lymphocyte count were 1.9, 5.0 and 1.4 × 109/L, respectively, determined by the X-tile software. RFS was found to be significantly longer in patients with NLR ≤1.9 (P = 0.041), LMR >5.0 (P < 0.001) and lymphocyte count >1.4 × 109/L (P = 0.002) in comparison to those with NLR >1.9, LMR ≤5.0 and lymphocyte count ≤1.4 × 109/L, respectively. Multivariate analysis revealed that LMR (hazard ratio 0.30, 95% CI 0.11–0.85, P = 0.023) was an independent predictor for RFS, but not NLR or lymphocyte count. For long-term survival analysis, patients with NLR ≤1.9 (P = 0.016) were found to be associated with favorable OS, but NLR was not an independent factor validated by multivariate analysis. Conclusions Preoperative LMR is an independent systemic inflammation marker to predict relapses in pNEN patients who underwent curative resections, whose clinical value needs to be verified in further large sample-based prospective studies.

scholarly journals Clinical and pathological study of borrmann 4 type gastric cancer and multivariate analysis of its prognostic factors.

1988 ◽  
Vol 21 (7) ◽  
pp. 1946-1952
Author(s):  
Michio KATO ◽  
Masato FUNASAKA ◽  
Etsuji SHIMADA ◽  
Keizo KIKKAWA ◽  
Takeshi NAKAMURA ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Pathological Study

Weekly Irinotecan in Patients with Metastatic Colorectal Cancer Failing 5-Fluorouracil-Based Chemotherapy: Efficacy and Prognostic Factors

2003 ◽  
Vol 89 (2) ◽  
pp. 141-145 ◽  
Author(s):  
Aziz Karaoğrlu ◽  
Suayib Yalcin ◽  
Gülten Tekuzman ◽  
Ayse Kars ◽  
Ismail Çelik ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Objective Response ◽  
Response Duration ◽  
Response To Treatment ◽  
Time To Progression ◽  
Median Response ◽  
Poor Prognostic Factor ◽  
Histologic Subtype

Aims and background We evaluated the efficacy and tolerability of weekly irinotecan as a second-line treatment in patients with colorectal cancer failing 5-fluorouracil-based chemotherapy and searched for predictive and prognostic factors. Methods A total of 36 patients were included. Median age was 53 years (range, 33-72). One treatment cycle consisted of irinotecan, 100 mg/m2 weekly, for 4 weeks followed by a 2-week rest. Gender, age, primary site, number of metastatic sites, histologic subtype, differentiation, pretreatment CEA, CA 19-9 and lactate dehydrogenase levels and marker response to treatment were investigated as predictive factors for response to treatment and as prognostic factors in the overall survival and time to progression of the patients. Results A total of 120 cycles (median, 3 cycles) was delivered. An overall 14% objective response rate (1 complete and 4 partial responses) was achieved. The median response duration was 4 months (range, 2-7). Another 36% of the patients had stable disease for a median duration of 4 months (range, 2-8). Median time-to-disease progression was 4 months and overall median survival was 12 months (95% confidence interval, 9-15). Pretreatment serum CA 19-9 level and marker response to two courses of treatment were found to be clinically significant in time to progression and overall survival. Younger age (≤45 years) was a poor prognostic factor associated with a shorter time to progression. The major toxicity was grade 3-4 diarrhea, which occurred in 28% of the patients, and treatment was discontinued in 3 (8%) patients due to toxicity. Other hematological and non-hematological toxicities were mild and manageable. Conclusions We concluded that weekly irinotecan at the dose of 100 mg/m2 is an effective and tolerable treatment option, with a 50% disease control rate, for patients with colorectal cancer failing previous 5-fluorouracil-based chemotherapy.

scholarly journals Clinicopathological Characteristics and Prognosis of Proximal and Distal Gastric Cancer during 1997–2017 in China National Cancer Center

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Lulu Zhao ◽  
Huang Huang ◽  
Dongbin Zhao ◽  
Chengfeng Wang ◽  
Yantao Tian ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Tumor Location ◽  
Clinicopathological Characteristics ◽  
Survival Outcome ◽  
Cancer Center ◽  
Poor Survival ◽  
Node Metastasis ◽  
Distal Gastric Cancer

Background. The prognostic relevance of gastric tumor location has been reported and debated. Our study was conducted to examine the differences in clinicopathological features, prognostic factors, and overall survival (OS) between patients with proximal gastric cancer (PGC) and distal gastric cancer (DGC). Patients and Methods. Patients with PGC or DGC were identified from the China National Cancer Center Gastric Cancer Database (NCCGCDB) during 1997–2017. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models. Results. We reviewed 16,119 cases of gastric cancer patients, including 6,479 of PGC and 9,640 of DGC. PGC patients presented as older patients (61.5 versus 56.4 years, P<0.001) and more males (82.9% versus 68.2%, P<0.001). Compared with DGC, PGC was more likely to be in later pT stage (pT3 and pT4, 65.0% versus 52.8%, P<0.001) and lymph node metastasis (54.8% versus 50.9%, P<0.001). In univariate analysis, PGC patients had a worse survival outcome in stage I (Hazard ratio [HR] = 2.04, 95% CI: 1.42-2.94) but a better prognosis in stage IV (HR = 0.85, 95% CI: 0.73-0.98) when compared to DGC patients. However, multivariate analysis demonstrated that PGC was not an independent predictor for poor survival (HR = 1.07, 95% CI: 1.00-1.14). Results from multivariate analysis also revealed that pT4, lymph node metastasis, distant metastasis, no gastrectomy, and Borrmann IV were independent predictors associated with poor survival for both PGC and DGC patients. Additional prognostic factors for PGC patients included underweight (BMI < 18.5) (HR = 1.29, 95% CI: 1.06-1.58), linitis plastica (HR = 2.13, 95% CI: 1.25-3.65), and overweight (23 ≤ BMI <27.5) (HR = 0.80, 95% CI: 0.71-0.90). During the 20-year study period, the 5-year OS increased significantly for both PGC and DGC, with the increase rate of 91.7% and 67.7%, respectively. Conclusion. In China, PGC significantly differed from DGC in clinicopathological characteristics and prognostic factors. However, there was no significant relationship between survival outcome and gastric tumor location.

scholarly journals Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study

2019 ◽  
Vol 6 (1) ◽  
pp. e000298 ◽  
Author(s):  
Thitima Benjachat Suttichet ◽  
Wonngarm Kittanamongkolchai ◽  
Chutipha Phromjeen ◽  
Sirirat Anutrakulchai ◽  
Thanachai Panaput ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Treatment Response ◽  
Induction Therapy ◽  
Characteristic Curve ◽  
Predictive Performance ◽  
Complete Response ◽  
Early Response ◽  
Response To Treatment ◽  
Urine Protein ◽  
Spot Urine

BackgroundTNF-like weak inducer of apoptosis (TWEAK) is a proinflammatory molecule that plays a key role in active inflammation of lupus nephritis (LN). Urine TWEAK (uTWEAK) levels were found to be associated with renal disease activity among patients with LN. Here, we determined whether serial measurements of uTWEAK during induction therapy could predict treatment response or not.MethodsSpot urine samples were collected from patients with biopsy-proven active LN at time of flare, and 3 and 6 months after flare to assess the uTWEAK levels. All patients received standard immunosuppressive therapy and treatment response was evaluated at 6 months. The performance of uTWEAK as a predictor for treatment response was compared with clinically used biomarkers for patients with LN.ResultsAmong 110 patients with LN, there were 29% complete responders (CR), 34% partial responders (PR) and 37% non-responders (NR). On average, uTWEAK level was consistently low in CR, trended down by 3 months in PR and persistently elevated in NR. uTWEAK levels at month 3 were able to predict complete response at month 6 (OR adjusted for age, sex and creatinine=0.34 [95% CI 0.15 to 0.80], the area under the receiver operating characteristic curve [ROC-AUC]=0.68, p=0.02). The optimal threshold for uTWEAK level at month 3 was 0.46 pg/mgCr, discriminating complete response with 70% sensitivity and 63% specificity. Combining uTWEAK and urine protein at month 3 improved predictive performance for complete response at 6 months (ROC-AUC 0.83, p<0.001).ConclusionsIn addition to urine protein, uTWEAK level at 3 months after flare can improve the accuracy in predicting complete response at 6 months of induction therapy.

Survival analysis of treatment with S-1, alone or in combination with CDDP (SP), in elderly patients with advanced gastric cancer: A 10-year retrospective cohort study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15170-e15170
Author(s):  
Akitaka Makiyama ◽  
Tatsuhiro Kajitani ◽  
Hisanobu Oda ◽  
Chinatsu Fujimoto ◽  
Taito Esaki
Keyword(s):  
Gastric Cancer ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Clinical Practice ◽  
Advanced Gastric Cancer ◽  
Cancer Patients ◽  
Patient Characteristics ◽  
The Elderly ◽  
Metastatic Site ◽  
Gastric Cancer Patients

e15170 Background: In Japan, the elderly population is increasing, and steadily increase the number of deaths in the elderly gastric cancer patients. However, the standard treatment of elderly gastric cancer has not been established, either treatment of S-1 or SP is carried out in the clinical practice, while SP is considered as standard therapy in the young people. Now, we investigated the impact of S-1 and SP on survival time in clinical practice. Methods: Between 2003 and 2012, advanced gastric cancer patients over 70 years of age received S-1 or SP as first line therapy were retrospectively reviewed to investigate clinical outcomes. Patient characteristics analyzed included age, gender, performance status (PS), tumor histology, renal function and metastatic site. In addition, we have analyzed prognostic factors in multivariate analysis. Results: Among 93 patients (pts), 67 pts (72%) received S-1 and 26 pts (28%) received SP. Patient characteristics between the two groups showed no significant differences in gender, histology, metastatic site, or creatinine clearance level, but did show an imbalance in PS (tended with better at SP group) and age (tended with younger at SP group), significantly. Even though the background factors were favorable results in SP group, there were no significant differences in median progression-free survival (median 139 vs. 102 days; p = 0.96) and overall survival (median 330 vs. 263 days; p = 0.55) between S-1 and SP group, respectively. Grade 3-4 neutropenia (10 vs. 27%, p < 0.05) , fatigue (3 vs. 15%, p < 0.05) and Grade 1-2 creatinine increased (9 vs. 31%, p < 0.01) were more frequent in the SP group than in the S-1 group, respectively. According to the multivariate analysis, exposure to CDDP was not independently associated with a better prognosis. Conclusions: Despite the obvious limitations of this analysis, there does not appear to be a benefit for the addition of CDDP in the elderly gastric cancer patients due to the increase of toxicity. A randomized controlled trial in this age group is warranted. We will also report the results of clinically meaningful prognostic factors associated with the primary treatment at annual meeting.

The comparison of the usefulness of nab-paclitaxel and paclitaxel for advanced or recurrent gastric cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 217-217
Author(s):  
Yasue Kimura ◽  
Tetsuya Kusumoto ◽  
Eiji Kusumoto ◽  
Masahiko Sugiyama ◽  
Mitsuhiko Ohta ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Data ◽  
Tumor Response ◽  
Objective Response ◽  
Dose Intensity ◽  
The Other ◽  
Second Line ◽  
Recurrent Gastric Cancer ◽  
Other Hand ◽  
Grade 3

217 Background: For patients who do not respond to S-1-based treatment in Japan, weekly paclitaxel (PTX) therapy is more frequently used as second-line chemotherapy. On the other hand, the agent could not be used for alcohol hypersensitivity in some cases. Nab-Paclitaxel (N-PTX), which is the protein-bound paclitaxel, has recently been introduced in Japan. The purpose of this study was to retrospectively determine the more preferable agent, N-PTX or PTX, following the S-1-containing chemotherapy in patients with advanced or recurrent gastric cancer (ARGC). Methods: We conducted a retrospective review of the data for 40 patients with ARGC, who received either N-PTX monotherapy for 5 patients or PTX monotherapy for 35 patients. N-PTX was used as the second-line for all patients in this group. On the other hand, in the PTX group, 4, 28 and 3 patients received PTX monotherapy as the 1st-, 2nd- and 3rd-line, respectively. N-PTX was administered intravenously at a dose of 260 mg/m2 repeated triweekly. PTX was administered intravenously at a dose of 80 mg/m2repeated weekly (on days 1, 8 and 15) every four weeks. The objective response rate (ORR), adverse events, progression-free survival (PFS) were compared between the two groups. Results: For tumor response, in the N-PTX group, CR/PR/SD/PD were 0/3/1/1, respectively for an ORR of 60% and a DCR of 80%; in the PTX group, CR/PR/SD/PD were 0/3/15/13, respectively for an ORR of 10% and a DCR of 58%. The ORR of the N-PTX group was higher, which might result from the higher dose intensity in the group, compared with the PTX group. For the adverse toxicity, in the both group, events of grade ≥ 3 were not observed. Serious neurotoxicity (≥grade 3), as commonly described for treatment with paclitaxel, was not observed in this study. The survival data showed that the PFS was 253 days in the N-PTX group, compared with 176 days in the PTX group, which were not significantly different. Conclusions: We suggest the application of N-PTX in place of PTX after S-1 containing chemotherapy for ARGC, only from the perspective of the tumor response. Further data accumulation is required for overall survival.

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