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.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4123-4123
Author(s):  
Nobumasa Mizuno ◽  
Akira Fukutomi ◽  
Junki Mizusawa ◽  
Hiroshi Katayama ◽  
Satoaki Nakamura ◽  
...  

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.

Author(s):  
Nuttaradee Lojanapiwat ◽  
Md Rafiqul Islam ◽  
Martin Ridout ◽  
Sivakumar Subramaniam

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.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4500-4500
Author(s):  
R. T. Shroff ◽  
M. M. Javle ◽  
X. Dong ◽  
V. S. Kumar ◽  
S. Krishnan ◽  
...  

4500 Background: The IGFR pathway is activated in pancreatic cancer and may result in aggressive disease course. The study of single nucleotide polymorphisms (SNPs) involved in this pathway may provide prognostic information and predict response to IGFR directed agents. We investigated IGFR pathway SNPs in patients with LAPC. Methods: We evaluated 39 SNPs from 7 candidate genes in the IGFR pathway (IGF1R, IGF2R, IGF1, IGF2, IRS1, IRS2, IGFBP3) in 105 LAPC patients. DNA extraction from whole blood was performed using the Qiagen Flexigene DNA and Promega Maxwell 16 kits. Genotyping was performed using the Sequenom method. Overall survival was measured from date of diagnosis to date of death or last follow-up. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare survival of patients according to genotype corrected for previously identified prognostic factors, including induction chemotherapy, CA 19–9, albumin, LDH, hemoglobin and Karnofsky performance status (KPS). Results: Median survival time (MST) was 15 months (95% CI 13.3–16.7). Induction chemotherapy, LDH, CA 19–9 level, hemoglobin, and KPS were not significantly associated with survival. Serum albumin and three SNPs of the IGF pathway (IGF1R IVS20–3431A>G, IRS1 G971R, and IGF2 *4352A>G) were significantly associated with prognosis ( Table ). Two of the three genotypes remained as significant predictors for survival in Cox regression analysis when adjusted for clinical factors. A significant combined genotype effect was observed wherein patients with all three deleterious alleles had significantly worse survival than those with only two or one (10 vs. 16.3 vs. 21.3 months, p< 0.0001). Conclusions: These data suggest that SNPs in the IGFR pathway genes may have prognostic value for LAPC patients. This information may identify population subgroups that could benefit from IGFR-targeted agents. [Table: see text] No significant financial relationships to disclose.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 70-70 ◽  
Author(s):  
Arnoud J. Templeton ◽  
Aurelius Gabriel Omlin ◽  
Carmel Jo Pezaro ◽  
Thian San Kheoh ◽  
Raya Leibowitz-Amit ◽  
...  

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]


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21103-21103
Author(s):  
D. Sivasubramaniam ◽  
R. Komrokji ◽  
S. Dhaliwal ◽  
V. Sundarajan ◽  
Z. Nahleh

21103 Background: Complete pathological response (pCR) has been considered a reliable endpoint to assess the benefit of NC. However, different pathological responses ranging from near complete response to resistance would likely indicate different prognostic groups. Method: We studied patients with locally advanced breast cancer (LABC) who received NC between 2001–2006 at the University of Cincinnati. Pathological response to therapy was evaluated. In addition, RCB was quantified according to MD Anderson RCB Calculator index that combines pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size). We examined the correlation between pCR, RCB, event-free survival (EFS) and over all survival (OS) by Cox regression analyses. Result: Pathological slides of 32 patients were analyzed. Median age 52, 38% white and 62% African American. Stage IIB 12% , Stage IIIA 19%, Stage IIIB 53% and Stage IIIC 16% . 72% invasive ducal, 6% invasive lobular and 22% inflammatory cancer. Forty seven percent of tumors were ER +/or PR+ , 53% ER-/PR-, 28% HER-2 /neu + ( IHC 3+ or FISH HER2 gene to chromosome 17 ration > 2.2). Tumor response was as follows: 22% (n=7) achieved pCR , RCB scores ranged between 0- 4.87. By univariate Cox regression analysis, RCB correlated with EFS {Hazard ratio (HR) 1.57 (95% CI 1.04–2.38), p-value 0.018}, and with OS {HR 1.74 (95% CI 0.91 -3.32), p value-0.09}. However, pCR did not seem to correlate with EFS {HR 0 .24 (95%CI 0.03 -1.86–2.38), p-value .172} or OS {HR 0.03 (95% CI 0–89),p value-0.40}. By multivariate Cox regression analysis, RCB was noted to be an independent predictive variable for EFS {HR 1.59 (95% CI 1.04–2.43), p value-0.033} while pCR was not {HR 0.90 (95% CI 0.52–1.57), p value-0.7. Conclusion: RCB was easily quantifiable and appears to be a better predictor of outcome following neoadjuvant chemotherapy in LABC compared to pCR. Higher RCB scores were associated with higher EFS and lower rate of OS. Prospective trials are needed to further evaluate the role of RCB as an endpoint following NC. No significant financial relationships to disclose.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 150-150
Author(s):  
Tatsuya Okuno ◽  
Junki Mizusawa ◽  
Ken Kato ◽  
Masayuki Shinoda ◽  
Hiroshi Katayama ◽  
...  

150 Background: The prognosis of patients (pts) with locally advanced esophageal squamous cell carcinoma (LAESCC) is generally dismal. Definitive chemoradiotherapy (CRT) with cisplatin plus 5-fluorouracil (CF-RT) is the standard treatments especially for the pts with unresectable LAESCC. The aim of this study is to investigate the possible prognostic factors and predictive accuracy of the Glasgow Prognostic Score (GPS) in the pts with unresectable LAESCC treated with CRT. Methods: 142 patients were enrolled to JCOG0303, and assigned to standard CF-RT group and low-dose CF-RT group. 131 pts with sufficient data were used for this analysis. Cox regression model was used for an analysis of prognostic factors of the pts with unresectable LAESCC treated with CF-RT. GPS was classified by baseline CRP and serum albumin. Pts with a CRP ≤ 1.0 mg/dL and albumin ≥ 3.5 g/dL were allocated to GPS0 group. If only CRP was increased or albumin decreased,pts were allocated to the GPS1 and pts in whom CRP was > 1.0 mg/dL and albumin level < 3.5 g/dL were classified as GPS2. Results: The pts background was as follows: median age (range), 62 (37-75), male / female, 119/12; ECOG PS 0/1/2, 64/65/2; clinical stage (UICC 6th) IIB/III/IVA/IVB, 3/75/22/31. As a result of multivariable analysis including all variables, the factors which became statistically significant were shown in the table. In several sensitivity multivariate analyses, only esophageal stenosis was indicated as a common poor prognostic factor. In addition, overall survival tended to decrease according to GPS subgroups (median survival time(m): GPS0/GPS1/GPS2 16.1/14.9/8.7). Conclusions: Presence of stenosis was thought to be one of the candidates for stratification factor in randomized trial for unresectable LAESCC pts. Furthermore, GPS represents a prognostic fator in LAESCC pts treated with CRT. Clinical trial information: 000000861. [Table: see text]


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 21-21
Author(s):  
Ross Dolan ◽  
Elliot Tilling ◽  
Chia Y Kong ◽  
Nicholas James MacLeod ◽  
Stephen Thomas McSorley ◽  
...  

21 Background: The presence of a systemic inflammatory response (SIR) in patients with advanced cancer is an increasingly recognised prognostic domain and is commonly assessed by the Glasgow Prognostic Score (GPS) and modified Glasgow Prognostic Score (mGPS). However, little work has been carried out to evaluate their role in palliative radiotherapy. The aim of the present study was to compare the prognostic value of the GPS/mGPS in patients with advanced oesophageal cancer receiving palliative radiotherapy. Methods: Those patients receiving palliative radiotherapy for oesophageal cancer between 2010 and 2015 were examined (n=194). After exclusions the following demographic data was recorded sex, age, indication for radiotherapy, time from treatment to death/last clinic visit, medical comorbidities, tumour and radiotherapy location/dose, CRP, albumin, and differential blood counts. GPS, mGPS, NLR, PLR and LMR were all calculated and Cox regression analysis carried out in SPSS. Results: Patients who had undergone non-oesophageal/neoadjuvant radiotherapy (n=2) or died within 30 days of treatment administration were excluded (n=22). Of the remaining 170 analysed, 112 (66%) were male and the median age was 72 (Range: 43-91). The most common clinical indications for radiotherapy were dysphagia (n=142), weight loss (n=81) and pain (n=50). Medical comorbidities varied with the most common being hypertension (n=83), ischaemic heart disease (n=46) and COPD (n=42). At the time of analysis, 170 (100%) of the patients were dead with median survival of 6 months (Range: 1-81 month). On univariate six month cancer specific survival analysis, TNM stage (p=0.028), GPS (p<0.001) and mGPS (p<0.001) were significantly associated with poor survival. On multivariate analysis of the significant variables, only mGPS (HR: 2.28, 95%CI 1.29-4.01, p=0.004) and TNM stage (HR: 1.71 95%CI 1.09-2.69, p=0.020) remained independently associated with survival. Conclusions: In the palliative radiotherapy setting, systemic inflammation based scores (GPS/mGPS) had prognostic value and the mGPS had independent prognostic value.


2020 ◽  
Author(s):  
Minoru Oshima ◽  
Keiichi Okano ◽  
Hironobu Suto ◽  
Yasuhisa Ando ◽  
Hideki Kamada ◽  
...  

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.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20641-e20641
Author(s):  
J. P. Plastaras ◽  
J. C. Haynes ◽  
R. Mick ◽  
L. M. Hertan ◽  
A. I. Urdaneta ◽  
...  

e20641 Background: Baseline nutritional status is associated with clinical outcomes in esophageal cancer. Moreover, nutritional support during chemoradiation has been shown to improve outcomes in other disease sites. This retrospective study evaluated the impact of nutritional interventions and baseline nutritional status on outcomes in patients (pts) with locally advanced esophageal cancer. Methods: A retrospective review was performed of 132 pts treated with curative intent using radiation (RT) between 1986 and 2007 at the Hospital of the University of Pennsylvania. The median age of the population was 60 years (range: 33–86). Esophagectomy was performed in 70%, with adjuvant RT in 60% and neoadjuvant RT in 40%. Concurrent chemotherapy was given to 85% of the group. Nutritional counseling was provided to 83% of pts. During RT, oral or enteral nutritional supplements were provided to 77% of pts and intravenous fluids (IVF) were given to 38%. Median follow-up was 14.1 months. Results: Median survival from end of radiation was 1.5 yrs. Median absolute and percentage weight loss during RT were 6.2 lbs and 3.8%, respectively. Median percentage decrease in hemoglobin and albumin were 5.7% and 9.1%, respectively. Univariable Cox regression analysis demonstrated a statistically significant association between weight loss of ≥5 lbs during RT and worse survival (HR 1.74, 95% CI 1.09 - 2.79, p=0.02). Decrease in hemoglobin of 5% or more (HR 1.22, 95% CI 0.59 - 2.54) and decrease in albumin of 10% or more (HR 1.09, 95% CI 0.48 - 2.48) were not associated with survival. Patients who received only nutritional supplements during RT survived significantly longer (p=0.03) than pts who received IVF regardless of nutritional supplementation (HR 2.12, 95% CI 1.12 - 4.01) or pts who received neither nutritional supplements nor IVF (HR 1.8, 95% CI 1.03 - 3.14). Conclusions: Weight loss during RT predicted for worse survival. Nutritional factors before and during RT may be important in outcomes in patients with esophageal cancer and may be modifiable. The use of IVF may be a potential indicator of worse prognosis. Future prospective studies should consider these factors in trial design. No significant financial relationships to disclose.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20628-e20628
Author(s):  
David Eric Cowall ◽  
Veera Holdai

e20628 Background: The intensity of end-of-life (EOL) cancer care in a rural community has been previously reported (Cowall et al: J Oncol Pract 8: 40e-44e, 2012) using a random sample of all cancer deaths from Wicomico County, Maryland for calendar years 2004-2008. We now examine the impact of hospice services on survival in this same population. Methods: Significance (P-value) of diagnosis to death median survivals (MS) between different groups was calculated by log-rank analysis. Hazard ratios (HR) with 95% confidence intervals (CI) were obtained using Cox regression analysis. Results: 179 patients from our sample did not receive hospice services, and 211 were enrolled in hospice at some point during their illness. MS were 6.0 and 9.0 months respectively (P= 0.050, HR 1.222, CI 1.000-1.492). In the lung cancer subset, 54 patients did not receive hospice services and 78 were enrolled in hospice. MS were 5.0 and 7.0 months respectively (P=0.034, HR 1.468, CI 1.030-2.093). Other subsets were too small for analysis. Conclusions: Prolongedsurvival was significantly associated with hospice services in our sample, and that effect was more pronounced with lung cancer patients. The hospice effect on survival may reflect some combination of the following: hospice services result in better symptom management as well as counseling against toxic therapies at EOL and/or the bias of some patients against toxic treatments even before hospice enrollment.


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