A prognostic score for patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate post chemotherapy.

70 Background: We aimed to establish a simple prognostic score for men with mCRPC treated with abiraterone following docetaxel and explored incorporation of the neutrophil/lymphocyte ratio (NLR), a marker of host inflammation with prognostic value in many solid tumors. Methods: To develop the model, clinical and laboratory factors for 185 men treated at Royal Marsden were included in a univariable Cox regression analysis. Statistically significant variables were dichotomized using an optimal cut-off chosen by selecting the highest c-index among three potential cut-offs with high Hazard Ratios (HR). All significant variables in univariable analysis were analyzed using multivariable Cox analysis. One risk point was assigned for each variable with a P value of <0.05 in multivariable analysis and the risk points were used to establish three prognostic groups of similar prevalence. The validity of the model is being examined using the large data-set from the abiraterone registration trial (COU-AA-301). Results: Median age was 69 years, 41% had both bone and lymph node metastases (BLN), 15% had visceral disease. Involvement of BLN or visceral disease (HR 1.6, P=0.013), ALP >2.0 x ULN (HR 1.7, P=0.005), LDH >1.5 x ULN (HR 3.4, P<0.001), Hgb <12 g/dL (HR 2.1, P<0.001), and NLR >5 (HR 1.5, P=0.033) were associated with worse OS in the multivariable analysis. Outcomes for three risk groups using these 5 factors are presented in the table. The c-index was 0.73 (95% CI 0.65 - 0.80) for the prognostic score. Patients with NLR >5 at baseline and whose NLR was ≤5 within four weeks of treatment also had longer median survival (15.1 months) than those with NLR >5 at baseline that remained high (median OS 7.6 months, HR 0.48, 95% CI 0.25-0.93, P=0.029). Conclusions: This initial simple risk score provides good prognostic and discriminatory accuracy for men with mCRPC. Data from the validation cohort will be presented. [Table: see text]

Download Full-text

Plasmin(ogen) serves as a favorable biomarker for prediction of survival in advanced high-grade serous ovarian cancer

Biological Chemistry ◽

10.1515/hsz-2016-0282 ◽

2017 ◽

Vol 398 (7) ◽

pp. 765-773 ◽

Cited By ~ 6

Author(s):

Shuo Zhao ◽

Julia Dorn ◽

Rudolf Napieralski ◽

Axel Walch ◽

Sandra Diersch ◽

...

Keyword(s):

Ovarian Cancer ◽

Cox Regression ◽

Multivariable Analysis ◽

Positive Staining ◽

Mrna Levels ◽

High Grade ◽

Serous Ovarian Cancer ◽

Data Set ◽

Cox Regression Analysis ◽

Kaplan Meier

Abstract In serous ovarian cancer, the clinical relevance of tumor cell-expressed plasmin(ogen) (PLG) has not yet been evaluated. Due to its proteolytic activity, plasmin supports tumorigenesis, however, angiostatin(-like) fragments, derived from PLG, can also function as potent anti-tumorigenic factors. In the present study, we assessed PLG protein expression in 103 cases of advanced high-grade serous ovarian cancer (FIGO III/IV) by immunohistochemistry (IHC). In 70/103 cases, positive staining of tumor cells was observed. In univariate Cox regression analysis, PLG staining was positively associated with prolonged overall survival (OS) [hazard ratio (HR)=0.59, p=0.026] of the patients. In multivariable analysis, PLG, together with residual tumor mass, remained a statistically significant independent prognostic marker (HR=0.49, p=0.009). In another small patient cohort (n=29), we assessed mRNA expression levels of PLG by quantitative PCR. Here, elevated PLG mRNA levels were also significantly associated with prolonged OS of patients (Kaplan-Meier analysis; p=0.001). This finding was validated by in silico analysis of a microarray data set (n=398) from The Cancer Genome Atlas (Kaplan-Meier analysis; p=0.031). In summary, these data indicate that elevated PLG expression represents a favorable prognostic biomarker in advanced (FIGO III/IV) high-grade serous ovarian cancer.

Download Full-text

Toxicity and efficacy of salvage paclitaxel chemotherapy in Royal Marsden (RM) oesophagogastric adenocarcinoma (OGA) patients (pts).

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.188 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 188-188

Author(s):

NOELIA TARAZONA ◽

Elizabeth Catherine Smyth ◽

Clare Peckitt ◽

Ian Chau ◽

David J. Watkins ◽

...

Keyword(s):

Cox Regression ◽

Prognostic Score ◽

Significant Proportion ◽

Progression Free Survival ◽

Response Duration ◽

Hematological Toxicity ◽

Cox Regression Analysis ◽

Neutrophil Lymphocyte Ratio ◽

Grade 3

188 Background: Paclitaxel is a standard global salvage therapy for pts with advanced refractory OGA. Western pts may differ from Asian pts with respect to chemotherapy metabolism and cancer behaviour, and the benefits associated with paclitaxel in this setting have not been assessed outside of Asia. We examined the efficacy and toxicity associated with salvage paclitaxel for advanced OGA at RM over a 3 year period. Methods: This was a retrospective observational study. We identified all pts with OGA treated with salvage weekly paclitaxel from 01/06/2011 to 21/02/2014 from the electronic pt record at RM. The following data was collected: demographics, metastatic sites, resection status, response/duration of response to prior chemotherapy, ECOG PS, haemoglobin, albumin, alkaline phosphatase (ALP), neutrophil/lymphocyte ratio, CEA, CA19.9, RM prognostic score, CT response and date of progression, death or last follow up. Toxicity was collected as per NCI Common Toxicity Criteria (v4.0). Overall and progression free survival (OS/PFS) were estimated using the Kaplan-Meier method. Multivariate Cox regression analysis examined the association between clinical and laboratory variables with survival. Results: 57 pts were identified. Pts were 74% male; median age 64y; 66% PS 0-1; 91% 2nd line. Median number cycles 3 (range 1-8). Median follow up 13.6m. Response rate was 18.4% in evaluable pts. OS and PFS were 5.8m (95% CI: 4.8 – 6.8m) and 2.6m (95% CI: 1.9 – 3.2m). 2y and 3y survival from start of 1st line treatment were 26% and 13%. In multivariate analyses PS ≥2 [HR 2.28, p = 0.018], and ALP ≥100 U/L, [HR=2.01, p= 0.033] were independent negative prognostic factors for OS. ≥ Grade 3 nausea, diarrhea and neuropathy were uncommon (<2% each), rate of ≥ grade 3 fatigue was 11%. Grade 3-4 neutropenia, leucopenia and thrombocytopenia occurred in 12%, 11% and 2% pts. Conclusions: Advanced OGA pts treated at RM with salvage paclitaxel have an OS equivalent to pts in clinical trials with less hematological toxicity than seen in Asian patients. This may be due to regional pharmacogenetic profiles. As a significant proportion of pts now survive 2-3y with limited toxicity, therapeutic nihilism is unwarranted.

Download Full-text

SLFN11 expression (exp) in castration-resistant prostate cancer (CRPC) patients (pts) to predict response to platinum-based chemotherapy (PLT).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5065 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5065-5065

Author(s):

Vincenza Conteduca ◽

Loredana Puca ◽

Sheng-Yu Ku ◽

Judy Hess ◽

Megan Kearney ◽

...

Keyword(s):

Cox Regression ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Predictive Biomarker ◽

Median Number ◽

Parp Inhibitors ◽

Castration Resistant Prostate Cancer ◽

Cox Regression Analysis ◽

Platinum Based Chemotherapy

5065 Background: Schlafen family member 11 (SLFN11) sensitizes tumor cells to DNA-damaging agents and has been investigated as a potential predictive biomarker of response to PLT and PARP inhibitors, especially in small cell lung cancer (Lok, CCR 2017; Pietanza, JCO 2018). We aimed to explore the predictive/prognostic role of SLFN11 in PLT-treated CRPC. Methods: We assessed tumor exp of SLFN11 in PLT-treated, metastatic CRPC pts by RNAseq (N=27) and/or CTCs (N=20) (via the Epic Sciences platform). In addition, tumor morphology for neuroendocrine (NE) features and genomic status of select genes (ie, AR, TP53, RB1, BRCA2, BRCA1, ATM) by whole exome sequencing were evaluated. Statistical comparisons used Cox regression analysis and Kaplan Meier method for the association with overall/radiographic progression free survival (OS/rPFS). A dose response curve with PLT was performed in patient-derived organoids using Cell Title Glo according to the manufacturer’s protocol. Results: 41 CRPC (including 20 CRPC-NE) treated with PLT monotherapy (N=3) or PLT combination therapy (N=38) between August 2013 and December 2017 were evaluated. Median age was 67.1 years (range 51-91). Median number of prior therapies was 2 (range 1-7). A longer median rPFS was observed in all SLFN11+ pts treated with PLT (regardless of histology, RB1, TP53, PTEN, or DNA repair status) compared to SLFN11- [5.2 vs 2.3 months, HR 3.5, 95%CI 1.6-7.7, P<0.0001]. No association was reported for OS. On multivariable analysis (Table), SLFN11 was an independent factor associated with rPFS. Organoids derived from patient tumors expressing SLFN11 showed sensitivity to PLT in vitro. Conclusions: SLFN11 exp identifies both CRPC and CRPC-NE pts with a better response to PLT. Patient-derived organoids expressing SLFN11 confirmed increased sensitivity to PLT. Larger prospective evaluation of therapy decisions based on SLFN11 exp is now required. [Table: see text]

Download Full-text

PRAME Expression and Its Clinical Relevance in Hodgkin's Lymphoma

Acta Haematologica ◽

10.1159/000381533 ◽

2015 ◽

Vol 134 (4) ◽

pp. 199-207 ◽

Cited By ~ 8

Author(s):

Vehbi Ercolak ◽

Semra Paydas ◽

Emine Bagir ◽

Melek Ergin ◽

Gulsah Seydaoglu ◽

...

Keyword(s):

Real Time ◽

Real Time Pcr ◽

Hodgkin’S Lymphoma ◽

Cox Regression ◽

Prognostic Score ◽

Disease Free Survival ◽

Risk Groups ◽

Hodgkin's Lymphoma ◽

Rank Test ◽

Cox Regression Analysis

Objectives: Although Hodgkin's lymphoma (HL) is one of the most curable cancers in adult patients, new targets have to be defined in cases resistant to traditional chemotherapy. The preferentially expressed antigen of melanoma (PRAME) is a cancer testis antigen and its expression is very scarce or absent in normal tissues. For this reason PRAME is a promising candidate for tumor immunotherapy. The aim of this study is to understand the correlation of PRAME expression with prognostic factors in HL, to determine the utility of PRAME as a targeted molecule for immunotherapy and to compare real-time polymerase chain reaction (real-time PCR) and immunohistochemistry (IHC) for the detection of PRAME. Methods: In 82 patients, PRAME was studied using real-time PCR and IHC. Data analyses were performed using statistical methods such as t test, Mann-Whitney U test, χ2 test, Kaplan-Meier method, log-rank test and Cox regression analysis. Results: PRAME was detected in 15 (18.3%) patients using IHC and in 8 (9.8%) patients using real-time PCR. A correlation was found between PRAME positivity and higher International Prognostic Score (p = 0.039). PRAME positivity detected using real-time PCR was found to be correlated with shorter disease-free survival (DFS) and overall survival (OS, p = 0.0005). Discussion: The demonstration of PRAME especially in histiocytes and Reed-Sternberg cells may provide guidance for immunotherapy. Although PRAME positivity increases the risk for death (3.56), independent risk factors that affected DFS and OS occurred in advanced age and high-risk groups. Conclusion: Although real-time PCR is sensitive in the detection of PRAME, IHC can be another useful method. Despite the need for studies conducted on larger patient samples, PRAME expression is considered as a poor prognostic parameter in HL.

Download Full-text

Assessment of two prognostic risk group methods to predict outcomes with docetaxel-based therapy in men with metastatic castration-resistant prostate cancer (mCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.185 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 185-185

Author(s):

G. R. Pond ◽

A. J. Armstrong ◽

B. A. Wood ◽

M. Brookes ◽

L. H. Leopold ◽

...

Keyword(s):

Prostate Cancer ◽

Cox Regression ◽

Progression Free Survival ◽

Risk Groups ◽

Prognostic Models ◽

Castration Resistant Prostate Cancer ◽

Discriminatory Ability ◽

Molecular Features ◽

Ecog Ps ◽

Visceral Disease

185 Background: Threeprognosticrisk groups have been identified in men with mCRPC (good [GR]/intermediate [IR]/poor [PR]) based on 0-1, 2 or 3-4 factors (visceral disease, pain, anemia, bone scan progression). Prostate Cancer Working Group (PCWG)-2 defines clinical subtypes with visceral disease, bone metastases ± nodal metastases and nodal disease only. The prognostic ability of risk grouping or PCWG2 subtypes was evaluated in a large, independent phase II trial. Methods: A randomized phase IItrial of 221 men with mCRPC that received docetaxel-prednisone (DP) + AT-101 (Bcl-2 inhibitor) or DP + placebo was retrospectively analyzed using Cox regression and χ2 tests. Additional outcomes, tests and measures of discriminatory ability were assessed and will be presented. Patients from both groups were combined for analysis, as no significant differences in outcomes were observed. Results: 93, 81 and 38 men had GR, IR and PR disease. GR men were more likely than IR/PR men to be ECOG-PS 0 (48%, 27%, 21%) and had a lower median baseline PSA (63, 85, 193 ng/ml). Significant differences between risk groups were observed for progression-free survival (PFS, p=0.009) and overall survival (OS, p<0.001), while PCWG2 subtypes did not discriminate for these outcomes. Both risk groups and PCWG2 subtypes inconsistently predicted PSA declines (table). Conclusions: Prognostic risk groups significantly distinguished between outcomes in men with mCRPC receiving DP-based therapy, while PCWG2 subtypes did not. Risk groups may enhance stratification of patients in randomized trials and enable tailored drug development. Prognostic models that incorporate tumor molecular features may improve discriminatory ability. [Table: see text] [Table: see text]

Download Full-text

Modified Glasgow Prognostic Score (mGPS) for Prognostication of Adult Oncology Patients With Palliative Intent in a Regional Victorian Hospital, Australia

American Journal of Hospice and Palliative Medicine® ◽

10.1177/1049909120958389 ◽

2020 ◽

pp. 104990912095838

Author(s):

Nuttaradee Lojanapiwat ◽

Md Rafiqul Islam ◽

Martin Ridout ◽

Sivakumar Subramaniam

Keyword(s):

Cancer Patients ◽

Median Survival ◽

Cox Regression ◽

Prognostic Score ◽

Glasgow Prognostic Score ◽

P Value ◽

C Reactive Protein ◽

Cox Regression Analysis ◽

Reactive Protein ◽

Modified Glasgow Prognostic Score

Background: Accurate prognostication is essential in caring for palliative patients. Various prognostication tools have been validated in many settings in the past few years. Biomarkers of inflammation (albumin and C-reactive protein) are combined to calculate the modified Glasgow prognostic score (mGPS), which has been found to be a simple prognostic tool in this population. Objective: This retrospective cohort study was to evaluate mGPS as a prognostication tool for cancer patients admitted to an acute hospital in regional Australia. Methods: Adult cancer patients admitted to an acute Australian regional hospital during 2017 who had albumin and C-reactive protein (CRP) tested were included. The mGPS was calculated based on their admission values and discharge values. Based on their score (0-2), groups were compared using univariate and multivariate Cox regression analysis for prognostication. Kaplan-Meier survival plots and median survival time from admission and discharge were constructed. Results: A total of 170 patient records were reviewed of which 95 had admission and discharge mGPS scores available for analysis. Of those, 86 had died at the time of data analysis. The median survival for admission mGPS 0, 1, 2 was 168,156 and 74 days. For discharge mGPS 0, 1, 2 medians were 168,119 and 70 days. On multi variate analysis admission mGPS 2 showed Hazard ratio of 2.29 (95% CI 1.16-4.56, p -0.02) and discharge mGPS 2 of 2.07 (95% CI 0.95-4.50, p value 0.07). Conclusions: In this study, mGPS was able to differentiate cancer patients into various prognostic groups. Further studies in regional acute hospitals could validate this prospectively with a multi-center larger sample size.

Download Full-text

Changes and Prognostic Impact of Inflammatory Nutritional Factors During Neoadjuvant Chemoradiotherapy for Patients with Resectable and Borderline Resectable Pancreatic Cancer

10.21203/rs.3.rs-73604/v1 ◽

2020 ◽

Author(s):

Minoru Oshima ◽

Keiichi Okano ◽

Hironobu Suto ◽

Yasuhisa Ando ◽

Hideki Kamada ◽

...

Keyword(s):

Cox Regression ◽

Prognostic Score ◽

Neoadjuvant Chemoradiotherapy ◽

Glasgow Prognostic Score ◽

Ductal Adenocarcinoma ◽

Prognostic Impact ◽

Borderline Resectable ◽

Nutritional Factors ◽

Cox Regression Analysis ◽

Neutrophil Lymphocyte Ratio

Abstract BackgroundInflammatory nutritional factors, such as the neutrophil/lymphocyte ratio (NLR), Glasgow Prognostic Score (GPS), modified GPS (mGPS), and C-reactive protein/albumin (CRP/Alb) ratio, have prognostic values in many types of cancer. In this study, the prognostic values of inflammatory nutritional scores were evaluated in the patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemoradiotherapy (NACRT).MethodsA total of 49 patients who underwent pancreatectomy after NACRT from September 2009 to May 2016 were enrolled. The NACRT consisted of hypofractionated external-beam radiotherapy (30 Gy in 10 fractions) with concurrent S-1 (60 mg/m2) delivered 5 days/week for 2 weeks before pancreatectomy. Inflammatory nutritional scores were determined before and after NACRT in this series. ResultsThe median NLR increased after NACRT (from 2.067 to 3.302), with statistical difference (p<0.001). In multivariate Cox regression analysis, high pre-NACRT mGPS (2 or 1; p=0.0478) and significant increase in CRP/Alb ratio after NACRT (≧0.077; p=0.0036) were associated with shorter overall survival. All patients were divided into two groups according to the ΔCRP/Alb ratio after NACRT: the group with high ΔCRP/Alb ratio (≧0.077) and the group with low ΔCRP/Alb ratio (<0.077). The group with high ΔCRP/Alb ratio after NACRT (n=13) not only had higher post-NACRT CRP levels (p<0.001) but also had lower post-NACRT Alb levels (p=0.002). Patients in the group with high ΔCRP/Alb ratio lost more body weight during NACRT (p=0.03).ConclusionIn addition to pre-NACRT mGPS, ΔCRP/Alb after NACRT could provide prognostic value in the patients with PDAC treated by NACRT.

Download Full-text

A Prognostic Microenvironment-Related Immune Signature via ESTIMATE (PROMISE Model) Predicts Overall Survival of Patients With Glioma

Frontiers in Oncology ◽

10.3389/fonc.2020.580263 ◽

2020 ◽

Vol 10 ◽

Author(s):

Huaide Qiu ◽

Yongqiang Li ◽

Shupeng Cheng ◽

Jiahui Li ◽

Chuan He ◽

...

Keyword(s):

Immune Cells ◽

Cox Regression ◽

Risk Groups ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Data Sets ◽

Data Set ◽

Cox Regression Analysis ◽

Immune Signature ◽

Genome Atlas

ObjectiveIn the development of immunotherapies in gliomas, the tumor microenvironment (TME) needs to be investigated. We aimed to construct a prognostic microenvironment-related immune signature via ESTIMATE (PROMISE model) for glioma.MethodsStromal score (SS) and immune score (IS) were calculated via ESTIMATE for each glioma sample in the cancer genome atlas (TCGA), and differentially expressed genes (DEGs) were identified between high-score and low-score groups. Prognostic DEGs were selected via univariate Cox regression analysis. Using the lower-grcade glioma (LGG) data set in TCGA, we performed LASSO regression based on the prognostic DEGs and constructed a PROMISE model for glioma. The model was validated with survival analysis and the receiver operating characteristic (ROC) in TCGA glioma data sets (LGG, glioblastoma multiforme [GBM] and LGG+GBM) and Chinese glioma genome atlas (CGGA). A nomogram was developed to predict individual survival chances. Further, we explored the underlying mechanisms using gene set enrichment analysis (GSEA) and Cibersort analysis of tumor-infiltrating immune cells between risk groups as defined by the PROMISE model.ResultsWe obtained 220 upregulated DEGs and 42 downregulated DEGs in both high-IS and high-SS groups. The Cox regression highlighted 155 prognostic DEGs, out of which we selected 4 genes (CD86, ANXA1, C5AR1, and CD5) to construct a PROMISE model. The model stratifies glioma patients in TCGA as well as in CGGA with distinct survival outcome (P<0.05, Hazard ratio [HR]>1) and acceptable predictive accuracy (AUCs>0.6). With the nomogram, an individualized survival chance could be predicted intuitively with specific age, tumor grade, Isocitrate dehydrogenase (IDH) status, and the PROMISE risk score. ROC showed significant discrimination with the area under curves (AUCs) of 0.917 and 0.817 in TCGA and CGGA, respectively. GSEA between risk groups in both data sets were significantly enriched in multiple immune-related pathways. The Cibersort analysis highlighted four immune cells, i.e., CD 8 T cells, neutrophils, follicular helper T (Tfh) cells, and Natural killer (NK) cells.ConclusionsThe PROMISE model can further stratify both LGG and GBM patients with distinct survival outcomes.These findings may help further our understanding of TME in gliomas and shed light on immunotherapies.

Download Full-text

An Analytical Study: Survival Rate of Laryngeal Carcinoma Patients Among Indonesian Population

10.53350/pjmhs211592966 ◽

2021 ◽

Vol 15 (9) ◽

pp. 2966-2970

Author(s):

Putu Aditya Bawa ◽

Nur Akbar Aroeman ◽

Yussy Afriani Dewi

Keyword(s):

Significant Relationship ◽

Laryngeal Carcinoma ◽

Cox Regression ◽

Squamous Metaplasia ◽

Multivariable Analysis ◽

Neck Surgery ◽

P Value ◽

Epithelial Surface ◽

Cox Regression Analysis ◽

Risk Of Death

Introduction: Laryngeal carcinoma is a malignant squamous metaplasia of the overlying epithelial surface of larynx. Several factors are believed to affect the survival of laryngeal carcinoma. This study aims to identify the survival of patients with laryngeal carcinoma. Materials and Methods: This was a retrospective cohort study using Cox Regression analysis for the survival analysis design. Patients were included if they were diagnosed with laryngeal cancer, had radiotherapy, chemotherapy, surgery or combination therapy and had a complete medical record. Data were collected retrospectively from medical records, such as smoking, alcohol consumption, genetic, tumor location, stadium, and therapy. Result: The results shows that from the 149 patients with laryngeal carcinoma who came to Head and Neck Surgery oncology outpatient clinic and had received therapy in the period January 2009 to December 2014, it was founded that smoking, alcohol, genetic, staging, surgery, and chemotherapy had a significant relationship to the laryngeal carcinoma survival (p value <0.05). While the location of the tumor and radiation did not show a significant relationship (p value> 0.05). Based on multivariable analysis of Cox Regression obtained smoking, alcohol, and surgery which provides a significant influence on survival. Patients who smoke have a risk of death 23.9 times. Suffering from consuming alcohol has a risk 2.41 times of death. Patients who do surgery can reduce the risk of death about 54%. Conclusion: The 5-year survival of patients with laryngeal carcinoma is 56.4%. Keywords: Patient Factors, Prognostic Factors, Tumor Factors, Laryngeal Carcinoma, Survival

Download Full-text

Effect of inflammatory and nutritional (IN) status on induction chemotherapy (CT) followed by chemoradiotherapy (CRT) for locally advanced pancreatic cancer (LAPC): An exploratory subgroup analysis of JCOG1106.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.4123 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 4123-4123

Author(s):

Nobumasa Mizuno ◽

Akira Fukutomi ◽

Junki Mizusawa ◽

Hiroshi Katayama ◽

Satoaki Nakamura ◽

...

Keyword(s):

Subgroup Analysis ◽

Cox Regression ◽

Prognostic Score ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Glasgow Prognostic Score ◽

P Value ◽

Treatment Benefit ◽

Cox Regression Analysis ◽

The Impact

4123 Background: JCOG1106 is a randomized selection phase 2 trial to evaluate the efficacy and safety of CRT (S-1 concurrent RT) with (Arm B) or without (Arm A) induction CT of gemcitabine (GEM) for LAPC. In the final analysis, we selected Arm A as a promising regimen due to a poorer 2-year overall survival (OS) of Arm B, in spite of a favorable 1-year OS with crossing of the survival curves around 1-year (Ioka, ESMO2016). Therefore, this study aimed to explore subgroups benefit more from either treatment. IN statuses defined by such as serum C-reactive protein (CRP) and serum albumin (Alb) are recognized as prognostic and predictive factors in patients (pts) with various cancers receiving CT or CRT. We hypothesized that IN status may modify the effect of induction CT. Methods: Subjects were all eligible pts who were enrolled in JCOG1106 (n = 51/49 in Arm A/B). Glasgow Prognostic Score (GPS) was classified by baseline CRP and Alb. Pts with a CRP ≤ 10 mg/L and Alb ≥ 35 g/L were allocated to GPS 0, with a CRP > 10 mg/L or Alb < 35 g/L to GPS 1, and with a CRP > 10 mg/L and Alb < 35 g/L to GPS 2. This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of IN status at baseline on OS. Less than 0.1 of P-value for interaction was regarded as significant. Results: GPS, CRP and Alb showed significant treatment interactions in terms of OS. HRs of Arm B to Arm A were 1.35 (0.82–2.23) and 0.59 (0.24–1.50) in the GPS 0 (n = 44/34 in Arm A/B) and GPS 1/2 group (n = 7/15) ( P-interaction = 0.06). HRs were 2.57 (1.36–4.86) and 0.70 (0.37–1.32) in the low CRP group (≤ 1.35 mg/L, n = 25/25) and high CRP ( > 1.35 mg/L, n = 26/24) ( P= 0.01). HRs were 1.62 (0.77–3.40), 2.70 (1.17–6.23) and 0.52 (0.24–1.13) in the 1st (≤ 0.7 mg/L, n = 16/16), 2nd ( > 0.7, ≤ 3.0 mg/L, n = 20/16), and 3rd tertiary CRP group ( > 3.0 mg/L, n = 15/17) ( P= 0.01). HRs were 2.29 (1.11–4.69) and 0.89 (0.51–1.54) in the high Alb group ( > 40 g/L, n = 23/17) and low Alb (≤ 40 g/L, n = 28/32) ( P= 0.04). Arm B showed better survival in subgroups of GPS 1/2, higher CRP or lower Alb compared to Arm A. Conclusions: Pts with poor IN status may have treatment benefit of induction CT followed by CRT for LAPC. Clinical trial information: UMIN000006811.

Download Full-text