scholarly journals C-Reactive Protein to Albumin Ratio Predicts Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib: A Multicenter Analysis

Author(s):  
Toshifumi Tada ◽  
Takashi Kumada ◽  
Atsushi Hiraoka ◽  
Masashi Hirooka ◽  
Kazuya Kariyama ◽  
...  

Abstract We investigated the impact of C-reactive protein to albumin ratio (CAR) on predicting outcomes in 522 patients with unresectable hepatocellular carcinoma (HCC) treated with lenvatinib. We determined the optimal CAR cutoff value with time-dependent receiver operating characteristic curve analysis. Additionally, we clarified the relationship between CAR and liver function or HCC progression. Median overall survival was 20.0 (95% confidence interval (CI), 17.2–22.6) months. The optimal CAR cutoff value was determined to be 0.108. Multivariate analysis showed that high CAR (≥0.108) (hazard ratio (HR), 1.915; 95% CI, 1.495–2.452), Eastern Cooperative Oncology Group performance status ≥1 (HR, 1.429), and α-fetoprotein ≥400 ng/mL (HR, 1.604) were independently associated with overall survival. Cumulative overall survival differed significantly between patients with low versus high CAR (p<0.001). Median progression-free survival was 7.5 (95% CI, 6.7–8.1) months. Multivariate analysis showed that age, CAR ≥0.108 (HR, 1.644; 95% CI, 1.324–2.043), and non-hepatitis B, non-hepatitis C etiology (HR, 0.726) were independently associated with progression-free survival. Cumulative progression-free survival differed significantly between patients with low versus high CAR (p<0.001). CAR values were significantly higher as Japan Integrated Staging score increased (p<0.001). In conclusion, CAR can predict outcomes in patients with unresectable HCC treated with lenvatinib.

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582093129
Author(s):  
Qinfen Xie ◽  
Lidong Wang ◽  
Shusen Zheng

Background: This meta-analysis explored the correlation between the C-reactive protein to albumin ratio (CAR) and survival outcomes and clinicopathological characteristics in patients with pancreatic cancer. Methods: PubMed, Embase, Web of Science, and Cochrane Library databases were comprehensively searched through October 17, 2019. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate the association between CAR and overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) in pancreatic cancer. Results: The meta-analysis included 11 studies comprising 2271 patients. The pooled results showed that a high CAR was predictive of worse OS (HR = 1.84, 95% CI = 1.65-2.06, P < .001), PFS (HR = 1.53, 95% CI = 1.27-1.85, P < .001), and DFS (HR = 1.77, 95% CI = 1.30-2.41, P < .001). An elevated CAR was also associated with male sex (OR = 1.38, 95% CI = 1.10-1.74, P = .006). Conclusion: Elevated pretreatment CAR effectively predicts inferior survival outcomes in patients with pancreatic cancer and may be a powerful prognostic indicator for these patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kenro Tanoue ◽  
Shingo Tamura ◽  
Hitoshi Kusaba ◽  
Yudai Shinohara ◽  
Mamoru Ito ◽  
...  

AbstractAlthough the neutrophil to lymphocyte ratio (NLR) was reported to be a predictive biomarker for clinical outcomes in various types of cancer, including recurrent or metastatic head and neck cancer (R/M HNSCC) treated with nivolumab, the usefulness of the pretreatment C-reactive protein/albumin ratio (CAR) as a prognostic marker remains to be clarified. This study aimed to analyze the clinical usability of the CAR in comparison with that of the NLR. 46 R/M HNSCC patients treated with nivolumab were retrospectively analyzed. The optimal cutoff value for the CAR was calculated using receiver operating characteristic curve analysis. The optimal cutoff value for the CAR was set to 0.30. On multivariate analyses, a high CAR was significantly associated with poor overall survival (adjusted HR, 2.19; 95% CI, 1.42–3.47; p < 0.01) and progression-free survival (adjusted HR, 1.98; 95% CI, 1.38–2.80; p < 0.01). The overall response rate and disease control rate for the high CAR patients were lower than for the low CAR patients. The CAR had significantly higher area under the curve values than the NLR at 2 and 4 months. The pretreatment CAR might be an independent marker for prognosis and efficacy in R/M HNSCC patients treated with nivolumab.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lei Dai ◽  
Xingchen Cai ◽  
Joseph Mugaanyi ◽  
Yelei Liu ◽  
Shuqi Mao ◽  
...  

AbstractImmune checkpoint inhibitor therapy has shown promising results in patients with unresectable hepatocellular carcinoma. This study aimed to evaluate the effectiveness and safety of sintilimab, a programmed cell death protein-1 (PD-1) blockade, combined with sorafenib and transhepatic arterial chemotherapy and embolization in this patient population, compared with sintilimab monotherapy and sintilimab-sorafenib duotherapy. This was a 22 months single center retrospective cohort study in China. 80 patients with unresectable hepatocellular carcinoma were included, with diagnosis confirmed by either histologic, cytologic or diagnostic imaging analysis. The patients were divided into three groups based on therapeutic regimen: sintilimab monotherapy (sintilimab group, n = 22), sintilimab-sorafenib duotherapy (duplex group, n = 23), sintilimab-sorafenib and transcatheter arterial chemoembolization combined therapy (triple group, n = 35). The principal evaluation criteria were overall survival and progression free survival in the population, assessed according to response evaluation criteria in solid tumors, version 1.1 (RECIST 1.1). Secondary evaluation criteria were safety, objective response rate and disease control rate. From March 1st, 2019 to December 31, 2020, 80 patients with unresectable hepatocellular carcinoma were included and divided into three treatment groups (22 received sintilimab monotherapy, 23 received sintilimab-sorafenib duotherapy, and 35 received sintilimab-sorafenib combined with transcatheter arterial chemoembolization). The median overall survival of all patients was 11.0 months (95% CI 7.7–14.3). Median overall survival was 13.0 months (95% CI NE–NE), 9.0 months(95% CI 6.3–11.7)and 3.0 months (95% CI 1.9–4.1, p < 0.0001) in the triple therapy, duplex and sintilimab groups respectively, while the corresponding median progression-free survival were 5.0 months (95% CI 2.9–7.1, p < 0.001), 4.0 months (95% CI 2.8–5.2) and 2.0 months (95% CI 1.7–2.3). Disease control and clinical benefits rates were higher in the triple therapy group (80%, 95% CI 63.1–91.6, p < 0.001; 54.3%, 95% CI 36.6–71.2, p < 0.01) compared to the sintilimab group. Median duration of disease control was 4.0 months (95% CI NE–NE, p < 0.01) in the triple therapy group, longer than that of the duplex group (2.0 months, 95% CI 0.9–3.1) and sintilimab group (2.0 months, 95% CI 0.8–3.2). Grade 3 or 4 treatment-related adverse events occurred in 26.3% of 80 patients with hypertension was the most common event observed (38, 47.5%), however, other severe toxic effects were infrequent. Sintilimab combined with sorafenib and transcatheter arterial chemoembolization might have more beneficial effects on overall and progression-free survival and on the duration of disease control outcomes than both sintilimab monotherapy and sintilimab-sorafenib duotherapy in patients with unresectable hepatocellular carcinoma. This triple therapy model might represent an innovative and effective option for inoperable liver cancer.


2021 ◽  
Author(s):  
Lei Dai ◽  
Xingchen Cai ◽  
Joseph Mugaanyi ◽  
Yelei Liu ◽  
Shuqi Mao ◽  
...  

Abstract PurposeImmune checkpoint inhibitor therapy has shown promising results in patients with unresectable hepatocellular carcinoma. This study aimed to evaluate the effectiveness and safety of sintilimab, a programmed cell death protein-1 (PD-1) blockade, combined with sorafenib and transhepatic arterial chemotherapy and embolization in this patient population, compared with sintilimab monotherapy and sintilimab-sorafenib duotherapy.MethodsThis was a 22 months single center retrospective cohort study in China. 80 patients with unresectable hepatocellular carcinoma were included, with diagnosis confirmed by either histologic, cytologic or diagnostic imaging analysis. The patients were divided into three groups based on therapeutic regimen: sintilimab monotherapy (sintilimab group, n=22), sintilimab-sorafenib duotherapy (duplex group, n=23), sintilimab-sorafenib and transcatheter arterial chemoembolization combined therapy (triple group, n=35). The principal evaluation criteria were overall survival and progression free survival in the intention-to-treat population, assessed according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). Furthermore, safety, objective response rate, disease control rate and so on were analyzed.ResultsFrom March 1st, 2019 to December 31, 2020, 80 intend-to-treat patients with unresectable hepatocellular carcinoma were included into three treatment groups (22 received sintilimab monotherapy, 23 received sintilimab-sorafenib duotherapy, and 35 received sintilimab-sorafenib combined with transcatheter arterial chemoembolization). The median overall survival of all patients was 11.0 months (95% CI, 7.7-14.3). Median overall survival was 13.0 months (95% CI, NE-NE), 9.0 months(95% CI,6.3-11.7)and 3.0 months (95% CI,1.9-4.1, p < 0.0001) in the triple therapy, duplex and sintilimab groups respectively, while the corresponding median progression-free survival were 5.0 months (95% CI,2.9-7.1 , p < 0.001), 4.0 months (95% CI,2.8-5.2) and 2.0 months (95% CI,1.7-2.3). Disease control and clinical benefits rates were higher in the triple therapy group (80%, 95% CI, 63.1-91.6, p < 0.001; 54.3%, 95% CI, 36.6-71.2, p < 0.01) compared to the sintilimab group. Median duration of disease control was 4.0 months (95% CI, NE-NE, p < 0.01) in the triple therapy group, longer than that of the duplex group (2.0 months, 95% CI, 0.9-3.1) and sintilimab group (2.0 months, 95% CI, 0.8-3.2). Grade 3 or 4 treatment-related adverse events occurred in 26.3% of 80 patients with hypertension was the most common event observed (38, 47.5%), however, other severe toxic effects were infrequent. ConclusionsSintilimab combined with sorafenib and transcatheter arterial chemoembolization might have more beneficial effects on overall and progression-free survival and on the duration of disease control outcomes than both sintilimab monotherapy and sintilimab-sorafenib duotherapy in patients with unresectable hepatocellular carcinoma. This triple therapy model might represent an innovative and effective option for inoperable liver cancer.


Oncology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Kensuke Naruto ◽  
Tomokazu Kawaoka ◽  
Kei Amioka ◽  
Yutaro Ogawa ◽  
Kikukawa Chihiro ◽  
...  

<b><i>Introduction:</i></b> This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma. <b><i>Methods:</i></b> In this retrospective cohort study, 48 patients were treated with regorafenib for unresectable hepatocellular carcinoma. Thirty-five and 13 patients were initiated on 2nd- and 3rd-line therapy, respectively. We assessed the responses to and safety of the therapy. <b><i>Results:</i></b> There were no statistically significant differences in clinical characteristics at the start of 2nd- or 3rd-line regorafenib therapy. The overall response rate of 2nd- and 3rd-line regorafenib was 20 and 8%, respectively. The disease control rate was 57 and 54%, respectively. Median overall survival (mOS) from the start of 2nd-line regorafenib was 17.5 months. mOS from the start of 3rd-line regorafenib was not obtained. Median progression-free survival of 2nd- and 3rd-line regorafenib was 4.9 and 2.3 months, respectively. mOS from 1st-line therapy with tyrosine kinase inhibitor plus sorafenib-regorafenib-lenvatinib was 29.5 months; that with lenvatinib-sorafenib-regorafenib was not obtained. Patients on 3rd-line therapy tended to have better Child-Pugh scores and tumor factors at the start of 1st-line therapy than other patients. <b><i>Conclusion:</i></b> Patients on 2nd- and 3rd-line regorafenib showed favorable responses. Good Child-Pugh scores and tumor factors may be associated with a better response rate and OS.


Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 403
Author(s):  
Chih-Wei Luan ◽  
Hsin-Yi Yang ◽  
Yao-Te Tsai ◽  
Meng-Chiao Hsieh ◽  
Hsin-Hsu Chou ◽  
...  

The C-reactive protein-to-albumin ratio is a proven prognostic predictor of nasopharyngeal carcinoma. However, the role of the C-reactive protein-to-albumin ratio in other head and neck cancers remains unclear. This meta-analysis explored the prognostic value of the C-reactive protein-to-albumin ratio in head and neck cancers. A systematic search was conducted. Outcomes of interest included overall survival, disease-free survival, and distant metastasis–free survival. The hazard ratio with 95% confidence interval was pooled using a random-effects model. A total of 11 publications from the literature were included, allowing for the analysis of 7080 participants. Data pooling demonstrated that pretreatment C-reactive protein-to-albumin ratio had a hazard ratio of 1.88 (95% CI: 1.49−2.37, p < 0.001) for predicting overall survival, 1.91 (95% CI: 1.18−3.08, p = 0.002) for disease-free survival, and 1.46 (95% CI: 1.08−1.96, p = 0.001) for distant metastasis–free survival. Subgroup analysis showed that the C-reactive protein-to-albumin ratio is a significant prognostic marker for various head and neck cancers. An elevated pretreatment C-reactive protein-to-albumin ratio predicts a worse prognosis for patients with head and neck cancers. Therefore, the C-reactive protein-to-albumin ratio could serve as a potential prognostic biomarker facilitating treatment stratification.


2021 ◽  
pp. 78-81
Author(s):  
Devashish Kaushal ◽  
Rajeev Sood

Introduction: Studies on the effects of chemotherapy in Indian Castration-Resistant Prostate Cancer (CRPC) patients are very limited and world data is inconsistent. The purpose of the present study is to assess the effects of Docetaxel therapy in CRPC in Indian patients in terms of survival benet, both progression-free survival, and overall survival. This study also analyzes the effects of various factors on the survival of CRPC patients. Methodology: This is a single institutional prospective observational study. CRPC patients were treated with Docetaxel and followed till death as the primary endpoint or till the end of the study. Survivals were calculated with the Kaplan Meier method. Factors affecting survival were analyzed with univariate and multivariate analysis by log-rank t-test and Cox proportion hazard regression analysis. Result: Out of enrolled 101 patients, 78 were treated with Docetaxel. A decline in PSA (>50% reduction) was observed in 61.54%. Radiological response of regression noted in 40 % Nuclear Bone Scan and 19.23% CT/MRI by RECIST criteria. Progression-free survival and overall survival with Docetaxel (n=78) were 11.8 and 21 months respectively. Hemoglobin less than 11 gm%, Alkaline phosphatase more than 115 IU/dl, PSAmore than 14 ng/ml, Gleason score more than 7 and duration from diagnosis of carcinoma prostate to CRPC less than 24 months, the number of chemotherapy cycles less than 6 were all found to be signicantly associated with poor overall survival in univariate analysis while only Hemoglobin (P=0.0159) showed an independent association with overall survival in multivariate analysis. Conclusion: Overall and progression-free survival of CRPC patients with Docetaxel is 21 & 11.8 months respectively. Hemoglobin, Alkaline phosphatase, PSA, Gleason score, Docetaxel cycle, and duration from diagnosis of carcinoma prostate to CRPC were found to be signicantly associated with poor overall survival.


2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.


Author(s):  
Jiahui Zhou ◽  
Wene Wei ◽  
Hu Hou ◽  
Shufang Ning ◽  
Jilin Li ◽  
...  

Background: Emerging evidence suggests that inflammatory response biomarkers are predictive factors that can improve the accuracy of colorectal cancer (CRC) prognoses. We aimed to evaluate the prognostic significance of C-reactive protein (CRP), the Glasgow Prognostic Score (GPS), and the CRP-to-albumin ratio (CAR) in CRC.Methods: Overall, 307 stage I–III CRC patients and 72 colorectal liver metastases (CRLM) patients were enrolled between October 2013 and September 2019. We investigated the correlation between the pretreatment CRP, GPS, and CAR and the clinicopathological characteristics. The Cox proportional hazards model was used for univariate or multivariate analysis to assess potential prognostic factors. A receiver operating characteristic (ROC) curve was constructed to evaluate the predictive value of each prognostic score. We established CRC survival nomograms based on the prognostic scores of inflammation.Results: The optimal cutoff levels for the CAR for overall survival (OS) in all CRC patients, stage I–III CRC patients, and CRLM patients were 0.16, 0.14, and 0.25, respectively. Kaplan–Meier analysis and log-rank tests demonstrated that patients with high CRP, CAR, and GPS had poorer OS in CRC, both in the cohorts of stage I–III patients and CRLM patients. In the different cohorts of CRC patients, the area under the ROC curve (AUC) of these three markers were all high. Multivariate analysis indicated that the location of the primary tumor, pathological differentiation, and pretreatment carcinoembryonic antigen (CEA), CRP, GPS, and CAR were independent prognostic factors for OS in stage I–III patients and that CRP, GPS, and CAR were independent prognostic factors for OS in CRLM patients. The predictors in the prediction nomograms included the pretreatment CRP, GPS, and CAR.Conclusions: CRP, GPS, and CAR have independent prognostic values in patients with CRC. Furthermore, the survival nomograms based on CRP, GPS, and CAR can provide more valuable clinical significance.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21107-e21107
Author(s):  
Tyler Fugere ◽  
Ples Spradley ◽  
Ahmad Mazen Safar

e21107 Background: C-Reactive Protein (CRP) is a non-specific inflammatory marker and reflects tissue destruction seen in metastatic cancer (ca). We have observed a tight correlation with CRP trends mirroring ca activity, hence it may prove to be a valuable marker to monitor response to Immuno-Oncology (IO) in non-small cell lung cancer (NSCLC) patients (pts). Once CRP levels stabilized, IO discontinuation was offered, and consenting pts were closely observed. This strategy resulted in shortened IO duration and impressive treatment-free progression-free survival (tf-PFS). We sought to examine the validity of this strategy using the rate of return to any form of ca therapy within 6 months after stopping IO. Methods: We analyzed all pts of a single provider since 2016 with stage IV NSCLC who had CRP checked while on IO, totaling 23 pts. We excluded pts who stopped IO for reasons besides stable CRP values (5 progressed on IO, 3 died while on IO, 1 had side effects, 1 stopped for a clinical trial, 1 opted to complete 2 years of IO, and 2 are still on IO). Of the remaining 10 patient cohort, all pts were males treated at the VA with ages between 56-75 years at diagnosis. 50% of the cohort had adenocarcinoma and 50% had squamous cell carcinoma. Results: Using the CRP trend to shorten the duration of IO resulted in durable drug-free holidays with none of the cohort returning to any form of ca therapy within 6 months and comparable rates of overall survival (OS) despite shorter IO duration. In KEYNOTE-042, the median OS for pts on the pembrolizumab arm was 16.7 months in the overall population and 20 months in the TPS ≥50% subgroup. Pts were treated for up to 35 months. In our cohort, median OS was 38 months, with all pts currently still alive, and median number of doses of IO was 9 cycles, or approximately 7 months. Our pts had ongoing progression free survival (PFS) after stopping treatment, which we report as tf-PFS. The median tf-PFS of our cohort was 23.5 months. Conclusions: In pts with stage IV NSCLC treated with IO, CRP appears promising as a marker to tailor IO therapy addressing tumor and clinical heterogeneity. Responding pts with stable CRP levels can be safely taken off IO. CRP should be monitored with stable values indicating continued PFS. tf-PFS rather than PFS may serve as a surrogate for cure and carries significant impact for pts financially, socially, and psychologically. [Table: see text]


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