Survival In Various Malignancies Research Articles

Prognostic importance of prognostic nutritional index and modified Glasgow prognostic score in advanced lung cancer with targetable mutation

BackgroundInflammation and nutrition are important parameters that significantly affect survival in various malignancies. Prognostic nutritional index (PNI) and modified Glasgow prognostic score (mGPS) can reflect both inflammatory and nutritional conditions. Therefore, we aimed to evaluate the prognostic value of PNI and mGPS in patients who had the targetable mutation and also received targeted therapy.Materials and MethodsAdvanced lung cancer patients with EGFR mutation (mut) and ALK rearrangement were enrolled to study, retrospectively. PNI has with the following formula: 10 × serum albumin (g/dl) + 0.005 × peripheral lymphocyte count (per mm3) and threshold value was accepted as 50. Modified GPS was also calculated using albumin and CRP level and patients were scored as range 0 to 2.ResultsA total of 182 patients enrolled in the study. 132 and 50 of 182 patients had EGFR mut and ALK rearrangement, respectively. PFS was significantly longer in high PNI group in both the EGFR and ALK rearrangement-positive subgroups (P = 0.004 for EGFR mut-positive group; P = 0.017 for ALK rearrangement-positive group). Additionally, PFS was significantly shortened from mGPS 0 to 2 (P = < 0.001 for EGFR mut-positive group; P = 0.016 for ALK rearrangement-positive group).ConclusionBoth PNI and mGPS can be used as a reliable, inexpensive, and easily applicable prognostic index in the advanced lung cancer patients who had the targetable mutation and also received targeted therapy.

Abstract 2480: Treatment of steroid-refractory immune checkpoint inhibitor-associated myocarditis: A case series of 18 patients

Abstract Background: Immune checkpoint inhibitors (ICI) have improved survival in various malignancies but are associated with significant immune-related adverse events (irAE). Up to 2% of patients on ICI develop ICI-myocarditis, which is associated with significant mortality. Treatment guidelines for ICI-myocarditis are limited. The initial treatment starts with high dose glucocorticoids, but the subsequent lines of treatment remain ill-defined. Methods: We retrospectively identified patients at our institution from 2021 onwards who were treated for ICI-myocarditis and who had an inadequate response to steroid treatment (thus steroid refractory). Baseline characteristics, laboratory and imaging data, and outcomes were reviewed. Results: Of the 34 patients diagnosed with ICI-myocarditis, 18 (53%) were steroid refractory. Amongst the 18, 11 were female and 7 were male, with a mean age of 73. Cancer types included head and neck, thoracic, urologic, gynecologic, and gastrointestinal. Patients had received a median of 2 ICI doses prior to myocarditis presentation. Thirteen (72%) patients had prior or concurrent irAE, most commonly neurologic or neuromuscular such as myasthenia gravis/myositis (44%) or hepatitis (33%). For initial treatment, 14 (41%) patients received a max dose of methylprednisolone 1g/day, while 4 (12%) received smaller doses (less than 500mg/day). Following steroids, the most common next treatment was mycophenolate mofetil (MMF) for 9 (50%), IVIG for 6 (33%), and Abatacept for 3 patients (17%). MMF was most often added and uptitrated to wean steroids, with 8 (44%) patients being able to be tapered off after a median duration of 112 days. IVIG was more commonly used for patients with concomitant neurologic symptoms while Abatacept was more commonly used for patients presenting with grade IV toxicities. The most encountered side effects following steroids were hyperglycemia, weight gain, adrenal insufficiency, and myopathy and following MMF were cytopenias and hypertension. The median survival since myocarditis diagnosis was 412 days. The patient with the longest documented survival of 645 days received IVIG and then MMF following steroids. Two patients with severely immunosuppression-resistant myocarditis responded well to tofacitinib, with one patient living 521 days after diagnosis (after methylprednisolone, IVIG, MMF, Abatacept, Tofacitinib) and one still alive more than 400 days after diagnosis (after methylprednisolone, MMF, Abatacept, IVIG, Infliximab, Tofacitinib). Conclusion: Steroid-refractory ICI-associated myocarditis can be responsive to other immunosuppression agents. Our case series, one of the largest studies of this population, highlights their effectiveness and the populations they can cater to. Adjunctive treatments for ICI-myocarditis require further study to identify right doses and order of treatment. Citation Format: Ritujith Jayakrishnan, Samantha Brongiel, Darren Luon, Stephanie Halene, Jennifer M. Kwan. Treatment of steroid-refractory immune checkpoint inhibitor-associated myocarditis: A case series of 18 patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2480.

The cancer survival index-A prognostic score integrating psychosocial and biological factors in patients diagnosed with cancer or haematologic malignancies.

ObjectiveWe aimed to investigate whether (1) psychological and social indicators influence survival in patients diagnosed with cancer or haematologic malignancies when important biological aspects are controlled for, (2) psychological, social and biological indicators can be utilised to design one collated index for survival, usable in clinical practice to identify patients at risk of shorter survival and to improve personalised healthcare provision.MethodsIn this cross‐sectional study, 2263 patients with cancer or haematologic malignancies participated. We analysed 15 biological, psychological and social indicators as risk factors for survival with a Cox proportional hazards model. Indicators significantly associated with survival were combined to compute models for the identification of patient groups with different risks of death. The training sample contained 1122 patients. Validation samples included the remaining 1141 patients, the total sample, as well as groups with different cancer entities.ResultsFive indicators were found to significantly impact survival: Cancer site (HR: 3.56), metastatic disease (HR: 1.88), symptoms of depression (HR: 1.34), female sex (HR: 0.73) and anaemia (HR: 0.48). Combining these indicators to a model, we developed the Cancer Survival Index, identifying three distinct groups of patients with estimated survival times of 47.2 months, 141 months and 198.2 months (p < 0.001). Post hoc analysis of the influence of depression on survival showed a mediating effect of the following four factors, related to both depression and survival: previous psychiatric conditions, employment status, metastatic disease and haemoglobin levels.ConclusionsPsychosocial and biological factors impact survival in various malignancies and can be utilised jointly to compute an index for estimating the survival of each patient individually—the Cancer Survival Index.

IKBKE-driven TPL2 and MEK1 phosphorylations sustain constitutive ERK1/2 activation in tumor cells.

IKBKE have been associated with numerous cancers. As a result, IKBKE have emerged as potential target for cancer therapy. Accumulating evidence support that IKBKE orchestrate tumor cell survival in cancers. Here we evaluated the possible link between IKBKE and ERK phosphorylation. The effects of IKBKE silencing on MAPK activation in tumor vs. normal cells were evaluated via WB and RT-PCR. Ectopically expressed IKBKE, TPL2 or MEK1 constructs were used to examine the possible interactions among them via co-IP. In vitro kinase assays were performed to understand nature of the observed interactions. In tumors, IKBKE regulates MEK/ERK constitutive activations in vitro and in vivo. IKBKE and TPL2 physically interact and this interaction leads to TPL2 phosphorylation. We describe here a novel regulatory link between IKBKE and constitutive ERK1/2 activation in tumor cells. This new circuitry may be relevant for tumor cell survival in various malignancies.

Prognostic value of combined preoperative prognostic nutritional index and neutrophil to lymphocyte ratio in esophageal squamous cell carcinoma

BackgroundPreoperative nutritional status and some inflammatory indexes are associated with survival in various malignancies. Prognostic nutritional index (PNI) or neutrophil to lymphocyte ratio (NLR) was demonstrated associated with survival in patients with esophageal squamous cell carcinoma (ESCC). The purpose of the present study was to investigate whether the combination index of PNI and NLR (PNI-NLR) is superior to either alone in survival prognosis of patients with ESCC.MethodsIn total, 271 patients with ESCC who underwent radical esophagectomy from Qianfoshan Hospital from May 2009 to July 2014 were enrolled. Preoperative PNI and other clinical data were collected and analyzed. Using the 5-year survival rate as an end point, a receiver operating characteristic (ROC) analysis was used to find the best cutoff value for PNI and NLR was 49.1 and 3.14, respectively. And all the enrolled patients were classified into three groups: group 1 (score 0, NLR ≤3.14 and PNI >49.1), group 2 (score 1, NLR >3.14 or PNI ≤49.1) and group 3 (score 2, NLR >3.14 and PNI ≤49.1).ResultsThe combined index of PNI-NLR was a sensitive index in survival prognosis, and patients in the group 1, 2 and 3 had median survival times of 64, 47 and 36 months, respectively. Patients in group1 had significantly longer survival time than those of group 2 and group 3. In multivariate analyses, TNM stage, lymph stage, PNI and PNI-NLR affected the overall survival (OS). PNI was significantly correlated with TNM stage.ConclusionsPreoperative PNI-NLR was an independent predictor of survival of patients with ESCC. The index of PNI-NLR can improve the accuracy of prognoses for patients with ESCC than the index of NLR.

Abstract 4469: Impact of peripheral blood neutrophil lymphocyte ratio on response and survival in various malignancies treated with immunotherapy

Abstract Introduction: Immune check point inhibitors(ICI) have revolutionized the treatment of metastatic malignancies. There is a need for a bio-marker apart from PDL-1 especially in a 2nd line setting in malignancies like metastatic renal cell carcinoma (mRCC), metastatic non small cell lung cancer (mNSCLC). Peripheral blood neutrophil lymphocyte ratio (NLR) is emerging as a prognostic marker. Materials &amp; methods: Ambi-directional retro-prospective study of 100 patients who received ICI between 2016-2019. Peripheral blood NLR of 5 at baseline was used to stratify them into 2 groups. Objective response rate (ORR) and overall survival (OS) was compared between the 2 groups. NLR was also monitored at the 4th cycle. Results: Among the 100 patients, 40 had mRCC, 35 had mNSCLC, 18 had recurrent/metastatic head and neck squamous cell carcinoma (mHNSCC) and 7 had MMR-deficient/MSI high tumors. In patients with mRCC, those with NLR&amp;lt;5 (n=26) had significantly better ORR of 73%, median OS not reached (HR:0.12) as compared to 14.28 % in those with NLR&amp;gt; 5 (n=14) with median OS of only 5 months.4 patients with NLR &amp;lt;5 (15.38%) achieved complete response (CR) and continue to be in CR for 41,39, 30 &amp;21 months respectively. Of 35 mNSCLC patients treated with ICI,18 received it in 2nd line setting. Among these 18 patients, ORR of 37.5% with median OS of 14 months was found in NLR&amp;lt;5 (n=8) as compared to ORR of 20% with median OS of only 6 months in NLR&amp;gt;5 (n=10). In the first line setting of NSCLC, ORR was 69.2 % in NLR &amp;lt;5 (n=13) as compared to 50% in NLR&amp;gt;5(n=4) with median OS not reached in both groups. In mHNSCC(n=18), patients with NLR &amp;lt;5 (n=8) had a ORR of 37.5%,median OS of 10 months (maximum ongoing follow up of 22 and 20 months) as compared to ORR of 30% with median OS of 4 months in those with NLR&amp;gt;5. Among MMR-d/MSI-H tumours (n=7), 3 patients had NLR&amp;gt;5. There was no impact of baseline NLR on response or survival as 6 of 7 patients achieved a partial response with ongoing prolonged survival. There was no significant change in the NLR at 4th cycle across all malignancies in both the groups (p&amp;gt;0.05). However a subset of those with NLR&amp;gt;5 at baseline (5 out of 14 in NSCLC, 2 out of the 10 in mHNC, and all 3 patients of MMR-d/MSI-H tumours) - had reduction in the NLR to &amp;lt;5 after 3 cycles of treatment with ICI and demonstrated an objective response and prolonged survival of 12 months or more as compared to those who did not have significant reduction. Discussion: Patients with low baseline NLR were found to have superior response and survival in various malignancies treated with ICI. A significant reduction in NLR after initiation of treatment with ICI may influence prognosis. Large scale studies need to be done to see if NLR can be used as a marker to guide treatment such as combining ICI with another agent in those with high NLR rather than using it as a single agent. As NLR is cost effective, it maybe of great value for prognostication in resource constrained settings. Citation Format: Nitin Yashas Murthy, Amit Rauthan, Poonam Patil, S.p Somashekhar, Shabber S. Zaveri, Kakoli Lahkar, Kushal Gupta, Gaurav Nigade, Rajshri Ashwath, Prathyush Vundemodalu, Aditi Raghunathan. Impact of peripheral blood neutrophil lymphocyte ratio on response and survival in various malignancies treated with immunotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4469.

Impact of Serum γ-Glutamyltransferase on Overall Survival in Patients with Metastatic Renal Cell Carcinoma in the Era of Targeted Therapy.

γ-Glutamyltransferase (GGT) is a marker of oxidative stress. Elevated serum GGT is linked to poor survival in various malignancies; however, there are no data on metastatic renal cell carcinoma (mRCC). Additionally, GGT expression in cancer tissues remains largely unknown. The present study was designed to determine the prognostic role of serum GGT in patients with mRCC and the association between systemic and local GGT levels. Pretherapeutic serum GGT and other clinicopathological parameters were retrospectively compared with overall survival (OS) in 146 consecutive patients with mRCC receiving tyrosine kinase inhibitor therapy. GGT expression was analyzed in 65 resected specimens using immunohistochemistry. A total of 82 patients (56%) died during the follow-up period (median 34.9months). Median OS was 16.0months and 36.8months in patients with elevated GGT levels and without elevated GGT, respectively (P < 0.001). On multivariable analysis, elevated serum GGT was an independent adverse prognostic factor (hazard ratio [HR] 4.04, P < 0.001), together with high neutrophils (HR 2.06, P = 0.041), low albumin (HR 2.00, P = 0.006), high lactate dehydrogenase (HR 2.68, P < 0.001), and high De Ritis ratio (HR 1.97, P = 0.004). Preoperative serum GGT levels were 29, 48, and 109 U/l in patients whose renal cancer cells showed negative to weak, moderate, and strong GGT expression, respectively (P = 0.004). Elevated serum GGT was an unfavorable prognostic factor in mRCC, and overexpression of GGT in renal cancer cells might be responsible for elevation of serum GGT.

Unmarried men have worse oncologic outcomes after radical cystectomy for nonmetastatic urothelial bladder cancer

BackgroundUnmarried status is an established risk factor for worse cancer control outcomes and survival in various malignancies. We tested the effect of marital status on the rate of nonorgan confined disease as well as on cancer-specific mortality (CSM) in patients who underwent radical cystectomy for nonmetastatic urothelial bladder cancer (UCUB). MethodsWithin the Surveillance, Epidemiology and End Results database (2007-2015), we identified 11,167 patients (8,639 men and 2,528 women) who underwent radical cystectomy for nonmetastatic UCUB. Temporal trend analyses, logistic regression models, cumulative incidence plots, competing-risks regression models and landmark analyses were used. ResultsOverall, 2,454 men (28.4%) and 1,363 women (53.9%) were unmarried. Unmarried men had a higher rate of nonorgan-confined disease at radical cystectomy (OR: 1.24, CI 1.10–1.33; P < 0.001). Moreover, in men, unmarried status was an independent predictor of higher CSM (HR: 1.24, CI 1.12–1.37) In women, unmarried status neither predicted nonorgan-confined disease at radical cystectomy (OR: 1.07, CI 0.91–1.26; P = 0.37) nor was it associated with CSM (HR: 1.13, CI 0.88–1.31; P = 0.14). In 6-month landmark analyses, unmarried status remained an independent predictor of higher CSM in men (HR: 1.20, CI 1.08–1.33). ConclusionsUnmarried men have more advanced tumor stage at radical cystectomy and worse CSM compared to married men. Interestingly, marital status did not affect oncologic outcomes in women. These data suggest a gender-specific effect of marital status in UCUB.

Predictive value of immuno-inflammatory and nutritional measures modulated by neoadjuvant chemotherapy on the response of neoadjuvant chemotherapy and long-term outcomes in patients with esophageal cancer.

It has been reported that immuno-inflammatory and nutritional parameters are associated with long-term survival in various malignancies. However, little is known regarding the associations between alterations of these parameters during neoadjuvant chemotherapy (NAC) and the response to NAC in patients with esophageal cancer. The present study examined the clinical significance of alterations in these parameters during NAC in terms of the response to NAC and the long-term outcomes in patients with esophageal cancer. Various systemic immuno-inflammatory and nutritional measures including the systemic neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP)-to-albumin ratio (CAR) and psoas muscle index (PMI) were examined before and after NAC. Statistical analyses were performed to determine the significance of immuno-inflammatory and nutritional parameters prior to NAC and alterations during NAC regarding the response to NAC and long-term outcomes. The NLR, PMI, neutrophil count and platelet count declined significantly following NAC, whereas no alterations in PLR, CAR, lymphocyte counts, CRP levels and albumin concentration were observed. The decreases in NLR and neutrophil counts following NAC were strongly associated with a favorable overall survival (P=0.006). In conclusion, decreases in NLR and neutrophil counts following NAC were clinically significant predictors of the response to NAC and of survival in esophageal cancer, respectively.

IMPACT of putative chemopreventative agents on prostate cancer diagnosis.

e16553 Background: Prostate cancer (PC) is the most common non-cutaneous cancer in men and the third most common cause of cancer death in males. Several studies have shown that use of commonly prescribed medications, is associated with improved survival in various malignancies, including PC. There has not been any large population-based study, examining the effects of these and other commonly prescribed medications, such as proton pump inhibitors (PPI), on the rate of PC diagnosis, PC advanced disease and PC-specific death. Methods: A retrospective population-based study using data from the institute of clinical evaluative sciences, including all male patients aged 65 and above in Ontario who have had a negative first prostate biopsy between 1994 and 2016. We assessed the impact of commonly prescribed medications on PC outcomes. The analyzed medications included Statins (hydrophilic and hydrophobic), most commonly used diabetes drugs (metformin, insulins, sulfonylureas, and thizolidinedions), PPIs, 5 alpha reductase inhibitors, and alpha blockers. Time dependent Cox regression proportional hazards models were performed to determine predictors of PC diagnosis, PC advanced disease (defined as usage of hormonal therapy), and PC-specific death. Medication exposure was time varying and modelled as “ever” vs. “never” use or as cumulative exposure. Results: A total of 21,562 men were analyzed over a mean (SD) follow-up time of 8.06 (5.44) years. Overall, 5,187 patients (24%) were diagnosed with PC, 7861 (36.5%) had died, and 647 (3%) died of PC. On multivariable analysis usage of hydrophilic statins modelled as “ever vs. never” was associated with a lower diagnosis rate (OR 0.832, 95% CI 0.732-0.946, p = 0.005) and a significantly decreased PC-specific death (OR 0.676, 95% CI 0.528-0.871, p = 0.0024). In contrast, Pantoprazole was associated with a higher rate of advanced PC disease when modelled as cumulative exposure of 6 months (OR 1.03, 95% CI 1.003-1.06, P = 0.031), and PC-specific death, when modeled as “ever vs. never” (OR 1.26, 95% CI 1.02-1.576, p = 0.031). Conclusions: Hydrophilic statins were associated with a clinically and statistically significant lower PC diagnosis and PC-specific death, while pantoprazole was associated with a higher rate of advanced PC disease and PC-specific death.

Combination of the preoperative albumin to globulin ratio and neutrophil to lymphocyte ratio as a novel prognostic factor in patients with triple negative breast cancer.

Background: The pretreatment albumin to globulin ratio (AGR) and neutrophil to lymphocyte ratio (NLR) were the inflammation-associated factors which were related to the disease-free survival in various malignancies. The aim of this study was to evaluate the clinical significance of the pretreatment AGR combined with NLR for patients with triple negative breast cancer (TNBC).Method: This retrospective study included 286 cases of pathologically diagnosed patients with TNBC. The relationships of AGR and NLR with clinicopathologic characteristics and prognosis were analyzed by Kaplan–Meier and Cox regression methods.Results: An AGR of 1.63 and a NLR of 2.93 were identified as the optimal cut-off points for distinguishing patients with good versus poor prognosis. The area under the receiver operating characteristic curves of combined with AGR and NLR (CO-AN) was increased compared with AGR and NLR individually. Kaplan–Meier analysis showed that low AGR/high NLR was related to poor survival. The prognosis of patients can be predicted well by the CO-AN. Univariate and multivariate analyses revealed that high AGR levels, low NLR levels, and CO-AN<1 were significantly and independently associated with favorable disease-free survival.Conclusions: Our study suggested that AGR and NLR levels can be prognostic biomarkers for disease-free survival in patients with TNBC. The CO-AN may have greater predictive value than AGR and NLR in patients with TNBC.

Impact of putative chemopreventative agents on prostate cancer diagnosis.

40 Background: Prostate cancer (PC) is the most common non-cutaneous cancer in Canadian men and the third most common cause of cancer death in Canada. Several studies have shown that use of commonly prescribed medications, including those used for diabetes and hypercholesterolemia, is associated with improved survival in various malignancies, including PC. There has not been any large population-based study, examining the effects of these and other commonly prescribed medications, on the rate of PC diagnosis, over a 20 years follow-up period. Methods: A retrospective population-based study using data from the institute of clinical evaluative sciences, including all male patients aged 65 and above in Ontario who have had a negative first prostate biopsy between 1994 and 2016. We assessed the impact of commonly prescribed medications on PC diagnosis. The medications included Statins (hydrophilic and hydrophobic), diabetes drugs (metformin, insulins, sulfonylureas, and thizolidinedions), proton pump inhibitors, 5 alpha reductase inhibitors, and alpha blockers. Time dependent Cox regression proportional hazards models were performed determine predictors of PC diagnosis. Medication exposure was time varying and modeled as “ever” vs. “never” use or as cumulative exposure for 6 months of usage. A priori variables included in the model included age, ADG comorbidity score, rurality index, index year, and all medications. Results: A total of 51,415 men were analyzed over a mean (SD) follow-up time of 8.06 (5.44) years. Overall, 10,466 patients (20.4%) were diagnosed with PC, 16,726 (32.5%) had died, and 1,460 (2.8%) patients died of PC. On multivariable analysis increasing age and rurality index were associated with higher PC diagnosis rate, while a more recent index year, and usage of hydrophilic statins was associated with a lower diagnosis rate in both “ever” vs. “never” and cumulative models (HR 0.832, 95% CI 0.732-0.946, p = 0.005, HR 0.973 95% CI 0.951-0.995, p = 0.016, respectively). Conclusions: Hydrophilic statins are associated with a clinically significant lower PC diagnosis. To our knowledge this is the first study demonstrating a clear advantage of one group of statins (hydrophilic) over another (hydrophobic) in PC prevention.

An NF90/NF110-mediated feedback amplification loop regulates dicer expression and controls ovarian carcinoma progression.

Reduced expression of DICER, a key enzyme in the miRNA pathway, is frequently associated with aggressive, invasive disease, and poor survival in various malignancies. Regulation of DICER expression is, however, poorly understood. Here, we show that NF90/NF110 facilitates DICER expression by controlling the processing of a miRNA, miR-3173, which is embedded in DICER pre-mRNA. As miR-3173 in turn targets NF90, a feedback amplification loop controlling DICER expression is established. In a nude mouse model, NF90 overexpression reduced proliferation of ovarian cancer cells and significantly reduced tumor size and metastasis, whereas overexpression of miR-3173 dramatically increased metastasis in an NF90- and DICER-dependent manner. Clinically, low NF90 expression and high miR-3173-3p expression were found to be independent prognostic markers of poor survival in a cohort of ovarian carcinoma patients. These findings suggest that, by facilitating DICER expression, NF90 can act as a suppressor of ovarian carcinoma.

Neutrophil-to-lymphocyte ratio in head and neck cancer prognosis: A systematic review and meta-analysis.

Hematologic markers, such as the neutrophil-to-lymphocyte ratio (NLR), characterize the inflammatory response to cancer and are associated with poorer survival in various malignancies. We evaluate the effect of pretreatment NLR on overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC). Using multiple databases, a systematic search for articles evaluating the effect of NLR on OS in patients with HNSCC was performed. An inverse variation, random-effects model was used to analyze the data. A total of 24 of 241 articles, including 6479 patients, were analyzed. The combined hazard ratio for OS in patients with an elevated NLR (range 2.04-5) was 1.78 (confidence interval [CI] 1.53-2.07; P < .0001). The hazard ratios for site-specific cancer: oral cavity 1.56 CI 1.23-1.98 (P < .001), nasopharynx 1.66 CI 1.35-2.04 (P < .001), larynx 1.55 CI 1.26-1.92 (P < .001), and hypopharynx 2.36 CI 1.54-3.61 (P < .001). An elevated NLR is predictive of poorer OS in patients with HNSCC.

Medication use and kidney cancer survival: A population-based study.

Several studies demonstrate that use of commonly prescribed medications is associated with improved survival in various malignancies. Methods of classifying medication use in many of these studies, however, do not account for intermittent or cumulative use. Moreover, there are limited data in kidney cancer. Therefore, we performed a population-based cohort study utilizing healthcare databases in Ontario, Canada. We identified patients aged ≥65 with an incident diagnosis of kidney cancer between 1997 and 2013 and examined use of nine putative anti-neoplastic medications using prescription claims. Cox proportional hazard models evaluated the association of medication exposure on cancer-specific and overall survival. We conducted three separate analyses: the effect of cumulative duration of exposure to the study medications on outcomes, the effect of current exposure (in a binary nature) and the effect of exposure at diagnosis. During the 16-year study period, we studied 9,124 patients. Increasing cumulative use of angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs) and selective serotonin reuptake inhibitors were associated with markedly improved cancer-specific survival; increasing use of NSAIDs was associated with markedly improved overall survival. These results were generally discordant with analyses evaluating the effect of current use and exposure at diagnosis. In conclusion, pharmacoepidemiology studies may be sensitive to the method of analysis; cumulative use analyses may be the most robust as it accounts for intermittent use and supports a dose-outcome relationship. Prospective studies are needed to confirm whether patients diagnosed with kidney cancer should be started on an angiotensin-converting enzyme inhibitor, NSAID or selective serotonin reuptake inhibitor to improve survival.

The prognostic value of inflammation-based scores in advanced hepatocellular carcinoma patients prior to treatment with sorafenib.

Background and AimsThe multikinase inhibitor sorafenib is the only currently approved drug for the indication of advanced hepatocellular carcinoma (HCC). It provides a limited gain in survival time but is frequently associated with adverse events. We currently lack simple prognostic factors in sorafenib-treated HCC patients. Various inflammation-based scores (IBSs) have been evaluated as predictors of tumor recurrence and survival in various malignancies (including HCC). The objective of the present study was to determine the prognostic value of IBSs for overall survival (OS) in advanced HCC patients prior to the initiation of sorafenib therapy.MethodsPatients with Barcelona Clinic Liver Cancer stage C HCC were enrolled retrospectively between October 2007 and September 2015. To identify prognostic factors for OS, bivariate and multivariate analysis were performed using a Cox proportional hazards regression model.Results161 patients (87.0% males; median age: 67; median OS: 9.1 months) were enrolled. A multivariate analysis identified a body mass index <25kg/m2 (hazard ratio (HR)=1.55, p<0.017), macroscopic vascular invasion (HR=1.63, p< 0.001), an AST level >38 U/L (HR=2.65, p<0.001), Child Pugh B stage (HR=2.59, p<0.001) and a systemic immune-inflammation index (SII) ≥600 × 109 (HR 1.72, p=0.002) as independent risk factors for OS in advanced HCC.ConclusionIBSs (such as the SII) are novel, simple, low-cost prognostic indices in patients with advanced HCC. They may be of value in determining whether these patients may benefit from sorafenib therapy.

Clinical Significance of Preoperative Albumin and Globulin Ratio in Patients with Gastric Cancer Undergoing Treatment.

Background. The pretreatment albumin and globulin ratio (AGR) was an inflammation-associated factor which was related to the overall survival in various malignancies. The aim of this study was to evaluate the prognostic value of AGR in patients with gastric cancer. Method. This retrospective study included 862 cases pathologically diagnosed with gastric cancer. All patients were randomly divided into the testing group (431 cases) and validation group (431 cases). The relationships of AGR with clinicopathologic characteristics and prognosis were analyzed by Kaplan-Meier and Cox regression methods. Results. In the testing group, the median overall survival was 26.90 months and the cutoff value of AGR was 1.50 based on R language. Kaplan-Meier analysis showed that lower AGR was correlated with poorer overall survival. Multivariate analysis demonstrated that AGR was an independent prognostic factor for overall survival (HR: 0.584, 95% CI = 0.351–0.973, and p = 0.039). In the validation group, the median overall survival was 24.10 months. Lower AGR (≤1.50) also had a significantly poorer overall survival by Kaplan-Meier analysis. According to multivariate analysis, the AGR was also confirmed to be an independent prognostic factor for overall survival (HR: 0.578, 95% CI = 0.373–0.897, and p = 0.015). Conclusions. Our study suggested that the pretreatment AGR could be a prognostic biomarker for overall survival in patients with gastric cancer.

Abstract 2728: Correlation of p62/ubiquitin IHC expression with clinicopathologic outcome in gastrointestinal carcinomas

Abstract Background:P62 and ubiquitin are small regulatory proteins demonstrated to have implications in the prognosis and survival of various malignancies including: hepatocellular, breast, ovarian, and some gastrointestinal carcinomas. They play a vital role in controlling the process of cell death and survival. In order to understand the roles p62/ubiquitin play in gastrointestinal carcinomas, we carried out immunohistochemical analyses of p62/ubiquitin expression in a cohort of patients with annotated clinicopathologic data. Methods:Tissue microarrays (TMAs) of two 1mm cores each of 130 gastrointestinal carcinomas were immunostained for p62 and ubiquitin expression. Normal gastric, colon and pancreatic tissues were included as negative controls. Subjects were categorized into positive and negative groups based on the 20% cutoff of staining area. The staging of these three types of cancer were classified into early (Stage 0-3A) and advanced stage (equal or more than stage 3B).Chi-square or Fisher's exact test was used for assessing the comparability of cancer staging (pathologic stage, tumor size, lymph node metastases, and distant metastases) between positive and negative groups. A two-sample t-test was used to evaluate the association between log-transformed survival time and the positivity of tumor cells. All the statistical analyses were conducted using SAS statistical software version 9.3 (SAS Institute, Inc.,Cary, NC), and P&amp;lt;0.05 was considered statistically significant. Results:Of 130 carcinoma, there were 45 gastric, 70 colorectal and 15 pancreatic carcinoma. In gastric carcinoma (45), positive p62 nuclear expression was noted in 25 (53%) and cytoplasmic in 26 (57%), while positive ubiquitin was nuclear expressed in 36 (80%), and cytoplasmic in 11 (24%). In colon carcinoma (70), positive p62 nuclear expression was noted in 29 (41%) and cytoplasmic in 48 (68.5%), while positive ubiquitin was nuclear in 40 (57%) and cytoplasmic in 30 (42%). In pancreatic cancer (15), positive p62 nuclear expression was noted in 13 (86%) and cytoplasmic in 9 (60%), while positive ubiquitin was nuclear in 15 (100%) and cytoplasmic in 12 (80%). Normal gastric (6), colon (4) and pancreatic (4) tissues were negative for both p62 and ubiquitin (nuclear and cytoplasmic staining &amp;lt;20%). Ubiquitin high expression was associated with worse pancreatic adenocarcinoma overall survival (1.37 vs 2.26 mos, P = 0.04). P62 and ubiquitin expression did not correlate with clinicopathologic parameters in gastric and colon adenocarcinomas. Conclusion:This study revealed that both p62 and ubiquitin are highly expressed in nuclei and cytoplasm of gastrointestinal carcinomas (gastric, colonic and pancreatic carcinomas). High ubiquitin expression was noted to have an impact on overall survival in patients with pancreatic adenocarcinoma. Citation Format: Amr Mohamed, Ayman AlKhoder, Wang Tengteng, Charles Kovach, Ahmed Kaseb, Momin T. Siddiqui, Cynthia Cohen. Correlation of p62/ubiquitin IHC expression with clinicopathologic outcome in gastrointestinal carcinomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2728. doi:10.1158/1538-7445.AM2015-2728

P62/Ubiquitin IHC Expression Correlated with Clinicopathologic Parameters and Outcome in Gastrointestinal Carcinomas.

P62 and ubiquitin are small regulatory proteins demonstrated to have implications in the prognosis and survival of various malignancies including: hepatocellular, breast, ovarian, and some gastrointestinal carcinomas. Several trials studied the link of their activity to the extrinsic apoptosis pathway and showed that their autophagy modification has a critical stand point in tumorigenesis. These findings explain their vital role in controlling the process of cell death and survival. It has been shown recently that p62 and ubiquitin overexpression in different types of cancers, such as triple negative breast and ovarian cancers, have directly correlated with incidence of distant metastases. We aim to evaluate p62/ubiquitin expression in gastrointestinal carcinomas of gastric, colonic, and pancreatic origin, and correlate with annotated clinicopathologic data. In gastric carcinoma (61), positive p62 nuclear expression was noted in 57% and cytoplasmic in 61%, while positive ubiquitin was nuclear expressed in 68.8%, and cytoplasmic in 29.5%. In colon carcinoma (45), positive p62 nuclear expression was noted in 29% and cytoplasmic in 71%, while positive ubiquitin was nuclear in 58% and cytoplasmic in 44%. In pancreatic cancer (18), positive p62 nuclear expression was noted in 78% and cytoplasmic in 56%, while positive ubiquitin was nuclear in 83% and cytoplasmic in 72%. Normal gastric (6), colon (4), and pancreatic (4) tissues were negative for both P62 and ubiquitin (nuclear and cytoplasmic staining <20%). Ubiquitin high expression was associated with more lymph node metastases in colon (4.14 vs 1.70, P = 0.04), and pancreatic adenocarcinomas (3.07 vs 0.33, P = 0.03). Also, ubiquitin high expression was associated with worse pancreatic adenocarcinoma overall survival (1.37 vs 2.26 mos, P = 0.04). In addition, gastric cancer patients with high p62 expression tend to have more poorly differentiated grade when compared to those with low expression (21 vs 17, P = 0.04) but less lymph node metastases (2.77 vs 5.73, P = 0.01). P62 and ubiquitin expression did not correlate with other clinicopathologic parameters in gastric, colon or pancreatic denocarcinomas. The results suggest that p62 and ubiquitin are highly expressed in gastric, colonic, and pancreatic carcinomas. High ubiquitin expression was noted to have an impact on number of lymph node metastases in patients with colon and pancreatic adenocarcinomas, but on overall survival only in patients with pancreatic adenocarcinoma. Also, P62 high expression is correlated with poor differentiation, but less lymph node metastases, in gastric carcinoma.

Preoperative neutrophil-to-lymphocyte ratio is a prognostic factor for overall survival in patients with gastric cancer.

PurposePreoperative neutrophil-to-lymphocyte ratio (NLR) reflects patients' inflammation status, clinical stage, and survival in various malignancies. However, only a limited amount of information on the clinical importance and prognostic significance of NLR in gastric cancer has been reported. The objective of this study is to assess the prognostic values of preoperative NLR in patients with gastric cancer.MethodsDuring the period between August 1, 2005 and December 31, 2011, we collected data from 601 patients among those who had undergone surgery for gastric cancer at the Department of Surgery, Konkuk University Medical Center. We classified the subjects into high NLR (NLR ≥ 1.7) group and low NLR (NLR < 1.7) group.ResultsThe gender, age, and American Society of Anesthesiologists (ASA) score did not differ in the two NLR groups. The pathologic features (tumor size, histology, number of examined lymph node, T stage, N stage, and TNM stage) did not differ either, except for tumor location (P = 0.006). Multivariate analysis identified TNM stage, NLR, and age as significant prognostic factors. Gender, tumor size, location, and histology did not show their prognostic significance when we applied the Cox proportional hazard model.ConclusionOur study verified that advanced stage, high preoperative NLR (NLR ≥ 1.7), and old age (≥ 70 years) are significant, independent prognostic factor for overall survival in patients with gastric cancer.