Overall Survival In Elderly Patients Research Articles

The Synergy of Vitamin C with Decitabine Activates TET2 in Leukemic Cells and Significantly Improves Overall Survival in Elderly Patients with Acute Myeloid Leukemia

Background: Decitabine is widely used in the treatment of acute myeloid leukemia (AML) in elderly patients. Low-dose ascorbic acid (Vitamin C) has also been indicated to induce DNA demethylation at the cellular level. Our previous study demonstrated its combined effect and safety with low-dose decitabine prior to aclarubicin andcytarabine (DCAG) in elderly patients with AML, in which it appeared to achieve a complete remission (CR) rate of 76.3% and a median overall survival of 10 months. Pharmacological concentrations of Vitamin C (10-1,000μM) induced a time- and dose-dependent increase in 5-hmC. However, little is known whether low-dose Vitamin C has a synergistic effect with decitabine in clinic. Methods: The effect of combined low-dose Vitamin C and decitabine on cell proliferation, the cell cycle, apoptosis and the expression level and activity of TET2 was investigated in HL-60 and NB-4 human leukemic cells. Additionally, we analyzed the clinical outcomes of 73 elderly AML patients who received A-DCAG (intravenous Vitamin C [IVC] plus DCAG [ n=39]) or DCAG (n=34) treatment. Patients received one of the two induction courses: DCAG or A-DCAG. DCAG consisted of 15mg/m2 of decitabine (intravenously, days 1-5) and 300 μg/day of granulocyte colony-stimulating factor (G-CSF, days 0-9) for priming its combination with 10 mg/m2 of cytarabine (q12h, days 3-9), 8 mg/m2 of aclarubicin (days 3-6, DCAG), or IVC (50-80 mg/kg/day, days 0-9; A-DCAG). The G-CSF priming was discontinued when white blood count (WBC) was ≥20×109/L. Results: We found that low-dose Vitamin C and decitabine has a synergistic efficacy on proliferation, apoptosis and TET2 activity, compared to drug-alone treatment in HL60 and NB4 cell lines in vitro . In clinic, feasibility and safety evaluations revealed that patients who received A-DCAG regimen have a higher complete remission (CR) rate than those who received the DCAG regimen (79.92 % vs. 44.11%; P=0.004) after one cycle of chemotherapy. IVC admission decision appeared to beat the discretion of attending physicians. The median overall survival (OS) was better in the A-DCAG group compared with the DCAG group (15.3 months vs. 9.3 months, P=0.039). Patients with adverse cytogenetics did benefit from CR. There was no clinically significant additional toxicity observed with the addition of IVC. Conclusion: On the basis of these results, the addition of IVC at low doses to DCAG appeared to improve CR and prolong OS, compared with DCAG, in elderly patients with AML. DisclosuresNo relevant conflicts of interest to declare.

High resection rate improves overall survival in elderly patients with pancreatic head cancer – A cohort study

BackgroundThere is evidence that a high hospital volume of pancreaticoduodenectomy improves short- and long-term outcomes, but there are few population-based studies on the effect of a high resection rate in the population. The aim of this national, observational study was primarily to investigate differences in overall survival among elderly patients with cancer in the pancreatic head between high and low resection rate groups and secondarily to determine if counties with high resection rates of pancreaticoduodenectomy had more severe complications after surgery. Materials and methodsAll patients in the Swedish National Registry for tumours in the pancreatic and periampullary region diagnosed between 2010 and 2018 with pancreatic head cancer were included in this retrospective cohort study. Patients were divided into low and high resection rate groups according to the yearly resection rates in the respective counties. For operative outcomes, all patients who had undergone pancreaticoduodenectomy were included regardless of diagnosis. The primary outcome of the study was overall survival among patients aged ≥70 years with pancreatic head cancer. ResultsAmong 13 933 patients in the registry, 7661 were 70 years or older, of whom 3006 had pancreatic head cancer. Overall survival was longer in high resection rate groups for patients aged ≥70 years, as for the age subgroups 70–79 years and ≥80 years (all p < 0.001). Among patients who had undergone pancreaticoduodenectomy aged ≥80 years the high resection rate counties showed an increased rate of severe complications, but no increase in 90-day mortality. ConclusionHigh resection rate groups show a significantly longer overall survival among elderly patients with pancreatic head cancer in Sweden. This implies that there could be a survival benefit from increasing resections in low resection rate groups.

Association of the Geriatric 8 with treatment intensity and prognosis in older patients with diffuse large B-cell lymphoma.

Because of the heterogeneity among older patients with diffuse large B-cell lymphoma (DLBCL), the establishment of an easy-to-use geriatric assessment tool is an unmet need. We verified the impact of the Geriatric 8 (G8) on treatment stratification and overall survival (OS). We conducted a retrospective, multicentre analysis of older patients (≥65years) with DLBCL. The primary endpoint was OS. The total average relative dose intensity (tARDI) was defined as the average delivered dose intensity divided by the planned dose intensity through all cycles. A total of 451 patients were diagnosed with DLBCL from 2007 to 2017, and 388 patients received standard regimens. A multivariate Cox model confirmed that the G8 was a significant predictor of OS (hazard ratio 0·88, 95% confidence interval 0·828-0·935). A Cox model with restricted cubic spline showed a linear association between the G8 and the mortality risk. The G8 had a significant impact on OS in elderly patients with DLBCL. The upper limit of tARDI for standard regimens to improve OS might be appropriate at ≥80% for patients with high G8 scores and 60% for patients with low G8 scores. However, the standard regimens should be given to all patients regardless of the G8 score to improve OS.

Effect of timing of surgical resection of primary hepatocellular carcinoma on survival outcomes in elderly patients and prediction of clinical models

BackgroundThe effect of time delay from diagnosis to surgery on the prognosis of elderly patients with liver cancer is not well known. We investigated the effect of surgical timing on the prognosis of elderly hepatocellular carcinoma patients undergoing surgical resection and constructed a Nomogram model to predict the overall survival of patients.MethodsA retrospective analysis was performed on elderly patients with primary liver cancer after hepatectomy from 2012 to 2018. The effect of surgical timing on the prognosis of elderly patients with liver cancer was analyzed using the cut-off times of 18 days, 30 days, and 60 days. Cox was used to analyze the independent influencing factors of overall survival in patients, and a prognostic model was constructed.Results A total of 232 elderly hepatocellular carcinoma patients who underwent hepatectomy were enrolled in this study. The cut-off times of 18, 30, and 60 days were used. The duration of surgery had no significant effect on overall survival. Body Mass Index, Child-Pugh classification, Tumor size Max, and Length of stay were independent influencing factors for overall survival in the elderly Liver cancer patients after surgery. These factors combined with Liver cirrhosis and Venous tumor emboli were incorporated into a Nomogram. The nomogram was validated using the clinical data of the study patients, and exhibited better prediction for 1-year, 3-year, and 5-year overall survival.ConclusionsWe demonstrated that the operative time has no significant effect on delayed operation in the elderly patients with hepatocellular carcinoma, and a moderate delay may benefit some patients. The constructed Nomogram model is a good predictor of overall survival in elderly patients with hepatectomy.

High Expressions of Notch and Survivin in Elderly Patients with Glioma Contribute to an Unfavorable Prognosis

Gliomas account for 24% of all primary brain and central nervous system tumors. To date, elderly patients constitute 10-25% of patients with a diagnosis of glioblastoma multiforme, but limited attention has been put on their optimal treatment, largely due to a very poor expected survival (only 4-6 months). Unraveling the molecular mechanism of gliomas provides an opportunity to develop novel biomarkers and therapeutic targets. In this study, we collected fasting blood samples from elderly patients diagnosed with glioma and who received treatment in our hospital between May 2016 and May 2019 and determined the expression levels of Notch and Survivin proteins in different clinical stages and their relationship with patient survival. A total of 68 healthy volunteers in this hospital during the same period served as healthy controls. Compared with the healthy controls, the expressions of Notch 1, Notch 2, Notch 3, and Survivin protein in the serum of elderly glioma patients were remarkably increased ( P &lt; 0.05 ), but the expression of caspase-3 protein declined ( P &lt; 0.05 ). As the clinical stage of the patient advanced, the expressions of Notch 1, Notch 2, Notch 3, and Survivin increased, and this increase was statistically significant ( P &lt; 0.05 ). It was observed that high expressions of serum Notch 1, Notch 2, Notch 3, and Survivin were associated with poor overall survival of elderly patients with glioma. We used γ-secretase inhibitor MRK-003 and specific ligand Jagged1 to alter the Notch pathway in U251 cells. It was revealed that MRK-003 incubation effectively suppressed the mRNA expression of Survivin in U251 cells, but Jagged1 stimulation significantly promoted the mRNA expression of Survivin in U251 cells. Results of MTT and transwell migration assays revealed reduced U251 cell viability and migration following MRK-003 treatment and enhanced cell viability and migration following Jagged1 stimulation. In conclusion, the finding obtained from these results supports that Notch and Survivin proteins contribute to the development of glioma in elderly patients and could serve as prognostic factors.

Preoperative skeletal muscle index and visceral-to-subcutaneous fat area ratio are associated with long-term outcomes of elderly gastric cancer patients after gastrectomy.

Sarcopenia is a risk factor of severe surgical complications, short-term outcomes, and long-term outcomes for patients with gastric cancer. Several computed tomography (CT) measurements have been performed to diagnose sarcopenia. However, the optimal CT measurements for determining long-term outcomes have not been revealed. A retrospective review of gastric cancer patients with clinical stage I, II, or III who underwent gastrectomy at age 75 years or more at Shizuoka General Hospital from 2007 to 2015 was performed. Using preoperative CT, skeletal muscle index (SMI), total psoas area, intramuscular adipose tissue content in multifidus muscle, morphologic change of psoas muscle, and visceral-to-subcutaneous adipose tissue area ratio (VSR) were measured in the third lumbar section. A Cox regression analysis was used to explore prognostic factors for overall survival. A total of 257 patients were reviewed. There were 171, 53, and 33 patients with clinical stages I, II, and III, respectively. A multivariate analysis indicated that, in addition to age, performance status, clinical stage, and types of resection, which are known prognostic factors, SMI and VSR are prognostic factors (p = 0.016, 0.046, respectively). The prognostic score, which was the frequency of positive SMI and VSR values within the cutoff, also indicates overall survival. The five-year OS rates of patients with prognostic scores of 0, 1, and 2 were 90.9%, 62.3%, and 52%, respectively (p < 0.001). Preoperative SMI and VSR were prognostic factors for the overall survival of elderly patients with gastric cancer after gastrectomy.

Survival benefit of adjuvant chemotherapy in elderly patients with colon cancer: a systematic review and meta-analysis.

Adjuvant chemotherapy after curative resection is established as a standard therapy for colon and rectal cancer. Although the efficacy of adjuvant chemotherapy has been shown by pooled analyses from randomized controlled trials, elderly patients still receive adjuvant chemotherapy less frequently than younger patients. In this systematic review and meta-analysis, we aimed to assess the survival benefit of adjuvant chemotherapy in elderly patients based on observational studies in which the elderly patients would likely be representative of those encountered in real-world clinical settings. A comprehensive literature search was conducted using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. Observational studies that investigated the survival benefit of adjuvant chemotherapy after curative resection in elderly patients (age ≥ 70years) with colon or rectal cancer were included. The 5-year overall survival (OS) rate and OS were assessed. Risk of bias was assessed using the ROBINS-I tool. Eleven studies in elderly patients with colon cancer were included. No relevant study was identified for rectal cancer. Elderly patients who received adjuvant chemotherapy had a significantly higher 5-year OS rate than those who did not (risk ratio 1.51, 95% confidence interval 1.29-1.76, P < 0.001). There was also a significant improvement in OS in elderly patients who received adjuvant chemotherapy (hazard ratio 0.59, 95% confidence interval 0.53-0.66, P < 0.001). The overall risk of bias was judged to be critical for both outcomes. Adjuvant chemotherapy provides a survival benefit for elderly patients with colon cancer, although the quality of evidence is low.

Impact of Timing of Chemotherapy for Pancreatic Cancer in the Elderly: A National Cancer Database Study

Background: Recent data favor neoadjuvant chemotherapy for pancreatic adenocarcinoma (PDAC). The aim of this study is to evaluate the effect of timing of chemotherapy on overall survival of elderly patients undergoing pancreatic surgery for PDAC. Methods: The NCDB was reviewed from 2004 to 2016. The effect of chemotherapy in elderly patients (≥75) was studied. Three major groups were analysed: adjuvant (ADJ), neoadjuvant (NEO) and neoadjuvant with adjuvant (BOTH). Results: A total of 380,524 patients were diagnosed with PDAC. Of these, 130,039 were ≥75 years of age, and 18,291 patients (7.1%) underwent surgery. Chemotherapy was provided as follows: 5,640 underwent ADJ, 888 NEO and 345 BOTH. A majority being diagnosed at stage II patients in NEO (48%) and BOTH (53%) . The 3 year survival was 31.9% in BOTH (95% CI: 26.4 - 38.6), 24.7% in NEO (95% CI: 21.6 - 28.3) and 25.0% in ADJ (95% CI: 23.8-26.3). Univariate Cox regression shows a significantly improved survival in BOTH in comparison to ADJ (p=0.0081) and a trend in improvement in comparison to NEO (p=0.079). There was a tendency to improved survival when elderly patients that received only neoadjuvant vs those receiving adjuvant chemotherapy (p=0.23). On multivariate analysis comorbidities were identified as an independent factor negatively impacting survival. Chemotherapy given as BOTH was independently associated with improved survival (figure 1). Conclusion: Elderly surgical patients undergoing BOTH neoadjuvant and adjuvant chemotherapy had improved survival. Therefore, BOTH should be given elderly patients if tolerated.

Impact of Immune Checkpoint Inhibitor on the Survival in Elderly Patients with Non-Small Cell Lung Cancer

Purpose: We analysed the relationship between a history of immune checkpoint inhibitor (ICI) and overall survival in elderly patients with non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of the data of patients with NSCLC aged ≥70-year-old who had received systemic anticancer therapy between 2015 and 2019. Results: The analysis included the data of a total of 63 patients. Multivariate analysis revealed a significant association between a history of treatment with ICI and the overall survival. A significant interaction was also observed between a history of treatment with an ICI and the tumor histology. Conclusion: A significant association between history of ICI therapy and the overall survival was detected in elderly NSCLC patients aged ≥70-year-old in a clinical practice setting. Our results also suggested that the impact of ICI therapy on the survival differed depending on the tumor histology.

Associations of Postoperative Complications Assessed by Clavien-Dindo Classification and Comprehensive Complication Index with Long-Term Overall Survival in Elderly Patients after Radical CRC Resection.

BackgroundAdvancing age is associated with high incidence of colorectal cancer (CRC) and high rates of postoperative complications (POCs). However, the impact of of POC severity — evaluated by Clavien–Dindo classification (CDC) or comprehensive complication index (CCI) — on long-term overall survival (OS) in elderly patients after radical CRC resection is not clear.MethodsElderly patients aged 65 years or more with CRC undergoing radical resection were retrospectively recruited. POC details were collected and evaluated using CDC grades and the CCI, blinded to patients’ other information. Risk factors for CDC grade ≥II POCs were analyzed by multivariate logistic regression. Effects of CDC grade II–IV POCs on long-term OS were analyzed via propensity-score matching (PSM) analysis followed by Kaplan–Meier curve plotting and multivariate Cox proportional-hazard regression adjusted for all potential confounders. The prognostic value of the CCI was also explored and compared with CDC grades.ResultsA total of 614 elderly patients were identified, of which 20, 106, 25, 11, and 13 cases experienced CDC grade I, II, III, IV, and V POCs, respectively. Higher age, female sex, coronary heart diseases, family history of tumors, preoperative anemia, high amount of bleeding during operation, and high positive dissected lymph–node ratio were found to be risk factors for CDC grade II–V POCs. After PSM analyses, CDC grade II–IV POCs were identified to be associated with poor long-term OS, which was also verified in the entire cohort. The CCI was also found to be significantly associated with decreased long-term OS and showed prognostic values similar to CDC grades.ConclusionBoth CDC grades and the CCI can be used to evaluate POCs and are associated with long-term OS in elderly patients undergoing radical CRC resection.

Impact of provider volume on front-line chemotherapy guideline compliance and overall survival in elderly patients with advanced ovarian cancer

PurposeWe sought to evaluate whether provider volume or other factors are associated with chemotherapy guideline compliance in elderly patients with epithelial ovarian cancer (EOC). MethodsWe queried the SEER-Medicare database for patients ≥66 years, diagnosed with FIGO stage II-IV EOC from 2004 to 2013 who underwent surgery and received chemotherapy within 7 months of diagnosis. We compared NCCN guideline compliance (6 cycles of platinum-based doublet) and chemotherapy-related toxicities across provider volume tertiles. Factors associated with guideline compliance and chemotherapy-related toxicities were assessed using logistic regression. Overall survival (OS) was compared across volume tertiles and Cox proportional-hazards model was created to adjust for case-mix. Results1924 patients met inclusion criteria. The overall rate of guideline compliance was 70.3% with a significant association between provider volume and compliance (64.5% for low-volume, 72.2% for medium-volume, 71.7% for high-volume, p = .02). In the multivariate model, treatment by low-volume providers and patient age ≥ 80 years were independently associated with worse chemotherapy-guideline compliance. In the survival analysis, there was a significant difference in median OS across provider volume tertiles with median survival of 32.8 months (95%CI 29.6, 36.4) low-volume, 41.9 months (95%CI 37.5, 46.7) medium-volume, 42.1 months (95%CI 38.8, 44.2) high-volume providers, respectively (p < .01). After adjusting for case-mix, low-volume providers were independently associated with higher rates of mortality (aHR 1.25, 95%CI: 1.08, 1.43). ConclusionsIn a modern cohort of elderly Medicare patients with advanced EOC, we found higher rates of non-compliant care and worse survival associated with treatment by low-volume Medicare providers. Urgent efforts are needed to address this volume-outcomes disparity.

Preoperative geriatric nutritional risk index is a useful prognostic indicator in elderly patients with gastric cancer.

Background: The geriatric nutritional risk index (GNRI) was developed to evaluate the prognosis in elderly hospitalized patients at risk of malnutrition and related morbidity and mortality. This study aimed to evaluate the relationship between preoperative GNRI and long-term outcomes in elderly gastric cancer patients.Materials and Methods: We retrospectively reviewed 297 consecutive patients aged ≥ 65 years who underwent laparoscopic gastrectomy with R0 resection and evaluated their overall survival (OS) and cancer-specific survival (CSS).Results: In the univariate analyses, OS was significantly associated with the American Society of Anesthesiologists Physical Status (ASA-PS), tumor size, tumor differentiation, pathological stage, carcinoembryonic antigen (CEA), C-reactive protein, postoperative complications, and GNRI, whereas in the univariate analyses of CSS, ASA-PS, tumor size, tumor differentiation, pathological stage, CEA, postoperative adjuvant chemotherapy, and GNRI were significantly associated with poor prognosis. In the multivariate analysis, ASA-PS, tumor differentiation, pathological stage, and GNRI were significant independent prognostic factors of OS, whereas ASA-PS, pathological stage, and CEA were significant independent prognostic factors of CSS.Conclusions: GNRI is significantly associated with OS and CSS in elderly gastric cancer patients and is an independent predictor of OS. It is a simple, cost-effective, and promising nutritional index for predicting OS in elderly patients.

VATS lobectomy outcomes in octogenarian patients: a retrospective series

: The proportion of octogenarian patients is growing over years. Nowadays video-assisted thoracoscopic surgery (VATS) permits to treat old age patients, even with limited pulmonary function, not otherwise suitable for surgery. The aim of our study is to analyse the factors influencing short and long terms outcome of the octogenarian patients underwent VATS lobectomy. Between January 2013 and March 2019 we performed 292 VATS lobectomies of which 26 patients were octogenarian. The patients’ population were divided in two groups according to patient’s age (group 1: patient younger than 80 years old; group 2: older than 80 years old). The octogenarian patients had higher post-operative complication (POC) rate and hospital stay than the younger patients. Surgeon’s learning curve was significantly associated to higher POC in both group of patients (group 1: P<0.002, group 2: P<0.001). Patients of both groups who underwent VATS lobectomy performed by resident surgeon supported by a skilled tutor had a significantly lower risk of POC (group 1 and group 2: P<0.001). Right upper lobectomy was significantly associated to higher risk of POC in both groups [group 1: P<0.008, relative risk (RR) =1.7 and group 2: P<0.032, RR =1.5] whereas left lower lobectomy showed higher risk of POC only in group 1 (P<0.03, RR =1.9). Hospital stay was significantly influenced by POC (group 1: P<0.001, group 2: P<0.03) and by post-operative atrial fibrillation in octogenarian group (P<0.04). Overall survival was influenced by lung cancer’s stage but not by age and POC in both groups. In conclusion octogenarian patients should undergo surgery after a completed pre-operative assessment due to their comorbidities. Post-operative outcome and overall survival of elderly patients are comparable with younger patients.

Survival outcomes of elderly patients with pathological stages II and III gastric cancer following curative gastrectomy.

AimSurvival outcomes in elderly patients with pathological stages (pStages) II and III gastric cancer remain inadequately elucidated. We retrospectively analyzed outcomes of elderly and nonelderly patients who underwent curative gastrectomy for this cancer and considered clinical results of the Estimation of Physiologic Ability and Surgical Stress (E‐PASS) scoring system for prediction.MethodsAmong 1041 patients who underwent gastrectomy for pStages II and III gastric cancer between 2008 and 2013 consecutively, 898 patients were enrolled. Of these, 158 patients (17.6%) were elderly and 740 patients (82.4%) were nonelderly.ResultsDisease‐specific survival (DSS) in the elderly group with pStage III cancer was significantly worse than that in the same stage nonelderly group (P = .001), while there was no difference in DSS for pStage II cancer between the groups (P = .45). Overall survival (OS) was significantly worse in elderly patients for both pStages II and III. Elderly patients with pStage II cancer had larger survival gaps between OS and DSS compared with those with pStage III cancer. OS for elderly patients with comprehensive risk score (CRS) > 0.159 was significantly worse than that for elderly patients with CRS ≤ 0.159 in pStage II cancer.ConclusionsCompared with nonelderly patients, different characteristics were observed in the survival outcomes of elderly patients between pStages II and III gastric cancer. The survival gap between OS and DSS of elderly patients was larger in pStage II cancer than in pStage III cancer. The E‐PASS scoring system could be a relatively useful predictor in elderly patients.

Estimates of Overall Survival in Patients With Cancer Receiving Different Treatment Regimens

The Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database may provide insights into the comparative effectiveness of oncological treatments for elderly individuals who are underrepresented in clinical trials. To evaluate the suitability of SEER-Medicare data for assessing the effectiveness of adding a drug to an existing treatment regimen on the overall survival of elderly patients with cancer. This comparative effectiveness study analyzed SEER-Medicare data from 9549 individuals who received a new diagnosis of stage II colorectal cancer (2008-2012) and 940 patients who received a new diagnosis of advanced pancreatic adenocarcinoma (2007-2012), with follow-up to December 31, 2013 (SEER-Medicare data released in 2015). Two (hypothetical) target trials were designed and emulated based on 2 existing randomized clinical trials: (1) adjuvant fluorouracil after curative surgery for individuals with stage II colorectal cancer and (2) erlotinib added to gemcitabine for individuals with advanced pancreatic adenocarcinoma. Data were analyzed January 2018 to March 2019. The following treatment strategies were compared: (1) fluorouracil initiation vs no initiation within 3 months of tumor resection and (2) erlotinib initiation vs no initiation within 12 weeks of gemcitabine initiation. All-cause mortality within 60 months of baseline for the fluorouracil trial and within 72 weeks for the erlotinib trial. Compared with 3293 individuals in the existing fluorouracil trial, 9549 eligible individuals included in the present analyses were more likely to have colon cancer (8565 [90%] vs 2291 [71%]) and were older (median [interquartile range], 79 [73-84] vs 63 [56-68] years). The 5-year risk difference for initiation vs noninitiation of fluorouracil after surgery was -3.8% (95% CI, -14.8% to 12.6%), and the mortality hazard ratio (HR) was 0.95 (95% CI, 0.85-1.04). Compared with 569 individuals in the existing erlotinib trial, 940 eligible patients included in the present analysis were older (median [range], 74 [66-93] vs 64 [36-92] years) and more likely to be male (547 [58%] vs 298 [52%]). The 1-year risk difference for initiation vs noninitiation of erlotinib was 4.7% (95% CI, -9.4% to 18.0%), and the corresponding mortality HR was 1.04 (95% CI, 0.86-1.42). In naive analyses, the mortality HR estimate was 1.14 (95% CI, 0.95-1.36) for the fluorouracil emulation and 0.68 (95% CI, 0.54-0.87) for the erlotinib emulation. The present estimates were similar to those from randomized clinical trials that studied adding the same cancer drugs to existing regimens. The published HR was 1.02 (95% CI, 0.70-1.48) in the fluorouracil trial for individuals aged 70 or older and 0.96 (95% CI, 0.74-1.24) in the erlotinib trial for individuals aged 65 years or older. The SEER-Medicare database may be adequate for studying the real-world effectiveness of adding a drug to treatment regimens used for elderly individuals with cancer.

The Clinical Impact of the Post-progression Survival on the Overall Survival in Elderly Patients or Those with a Poor Performance Status and Extensive-disease Small-cell Lung Cancer

The Clinical Impact of the Post-progression Survival on the Overall Survival in Elderly Patients or Those with a Poor Performance Status and Extensive-disease Small-cell Lung Cancer

Impact of timing of chemotherapy for pancreatic cancer in the elderly: A national cancer database study

Presenter: Neha Lad MD | Miami Cancer Institute Background: Recent reports have confirmed that chemotherapy improves overall survival in patients with pancreatic cancer. The aim of this study is to specifically evaluate the effect of timing of chemotherapy on overall survival of elderly patients undergoing pancreatic surgery for pancreatic adenocarcinoma (PDAC). Methods: The NCDB was reviewed from 2004 to 2016. The effect of chemotherapy in elderly patients (≥75) was studied. Three major groups were analysed: adjuvant (ADJ), neoadjuvant (NEO) and neoadjuvant with adjuvant (BOTH). Chi-square test was used to find differences in patient characteristics between groups. Log rank test and multivariable Cox proportional regression models were used to find factors associated with survival. Results: A total of 380,524 patients were diagnosed with pancreatic adenocarcinoma during the study period. Of these, 130,039 were ≥75 years of age, which included 18,291 patients (7.1%) who underwent surgical treatment. Chemotherapy was provided as follows: 5,640 underwent adjuvant chemotherapy (ADJ), 888 neoadjuvant chemotherapy (NEO) and 345 received at least 2 cycles before, but also received chemotherapy after (BOTH). There was a significant difference in the proportion of patients with Stage I to IV between groups, with a majority being diagnosed at stage II patients in NEO (48%) and BOTH (53%) . Demographics and Charlson-Deyo comorbidity score were similar across the groups. The 3 year survival rate was 31.9% in BOTH (95% CI: 26.4 - 38.6), 24.7% in NEO (95% CI: 21.6 - 28.3) and 25.0% in ADJ (95% CI: 23.8-26.3). Univariate Cox regression shows a significantly improved survival in BOTH in comparison to ADJ (p=0.0081) and a trend in improvement in comparison to NEO (p=0.079). There was a non significant tendency to improved survival when comparing elderly patients that received only neoadjuvant vs those that received only adjuvant (p=0.23). On multivariate analysis comorbidities were identified as an independent factor negatively impacting survival. Chemotherapy given as BOTH was independently associated with improved survival (figure 1). Conclusion: Elderly surgical patients undergoing BOTH neoadjuvant and adjuvant chemotherapy had improved survival when compared to patients receiving chemotherapy only in an adjuvant setting. Therefore, BOTH should not be withheld in elderly patients just because of their age.

The Relationship Between the Prognostic Nutritional Index and Overall Survival in Elderly Patients with Epithelial Ovarian Cancer

The Relationship Between the Prognostic Nutritional Index and Overall Survival in Elderly Patients with Epithelial Ovarian Cancer

A Predictive Model for Early Death after Frontline Hypomethylating Agents in Elderly Unfit Acute Myeloid Leukemia Patients: Results from the Pethema Group

INTRODUCTION: A sizable proportion of elderly acute myeloid leukemia (AML) patients receive frontline hypomethylating agents (HMAs), namely azacitidine (AZA) and decitabine (DAC), as they are deemed unfit for intensive chemotherapy (ICT) by their treating physicians. A foreseeable high early death (ED) rate and lack of overall survival (OS) benefit under ICT are the main drivers for this decision. Several groups have published different predictive tools for ED or OS in elderly patients receiving ICT but, since ED in patients treated by HMAs is lower, the research activity has been restricted to OS in this population. METHODS: 415 elderly AML patients (264 M, 152 F) aged 61-90 receiving frontline HMAs (AZA 297, DAC 118), either in daily practice or within clinical trials (AZA 27, DAC 17), with complete relevant clinical information (see Table I) were available from the PETHEMA epidemiologic AML registry (NCT02006004). We analyzed the predictive value for ED (8wk) of the prognostic factors for OS/ED in AML included in the Walter, MRC/LRF, ALFA and ALMA scoring systems, namely age, WBC count, performance status (PS), MRC 2010 cytogenetics, platelet count and secondary disease, as well as the type of HMA. The potential predictors were categorized following previous published models (Walter, MRC/LRF, ALFA, ALMA). Cumulative early death rate at 8 weeks was calculated by the life-time method and the relevant strata were tested for univariate significance by the Wilcoxon test. All significant covariates were included in a Cox multivariate regression model and those significant for death at 8wk were included in a new predictive tool (HMA-EDS). Patients were assigned randomly in a 1:1 ratio to a training cohort (TC) and a validation cohort (VC). The different scoring systems (Walter, MRC/LRF, ALFA, ALMA, HMA-EDS) were checked for their prognostic impact on ED. Finally the 95% CI for the expected death rate at 8wk for the different strata of the new model was calculated for the full patient series. RESULTS: 51 patients out of 415 died and 13 were lost to follow-up before day 56 (cumulative ED rate at 8wk 13%, 95%CI 9-17%). Age, cytogenetics, secondary AML, platelet count and type of HMA were not significantly associated to ED. PS and WBC count strata confirmed their prognostic utility both in univariate and multivariate analysis (Table II). We developed the HMA-EDS by adding WBC (cutoffs 10 and 50, scores 1/2/3) and PS (0-1/2-4, scores 0/1) that classified patients in low-risk (score 1-2/ 84.6% of patients) and high risk (3-4/ 15.4% of patients) strata. When the prognostic utility for ED in the TC and the VC for the different scoring AML systems were checked, only HMA-EDS predicted ED in both cohorts (see Table III). The new EDS discriminates 2 different strata for ED at 8wk in unfit AML patients treated by HMA (see Figure 1 &amp; Table III), namely a lower-risk group (ED rate 10%, 95% CI 6-14) and a high-risk group (ED rate 26%, 95% CI 14-38). CONCLUSIONS: WBC count and PS are the main predictors for ED in unfit AML patients treated by HMAs. A new tool (HMA-EDS) discriminates two different risk groups and supersedes other previously published prognostic systems (Walter's, Wheatley's MRC/LRF, ALFA and ALMA) for this purpose. This score could be useful to select patients for front-line HMA or even HMAs-based combination therapies, given that several cycles are usually needed to achieve a clinical response. We suggest that other patient-related covariates such as geriatric assessment be checked in future studies. Disclosures Ramos: Daiichi Sankyo: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria; Abbvie: Honoraria. Fernandez:Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Surgery for elderly patients with resectable pancreatic cancer, a comparison with non-surgical treatments: a retrospective study outcomes of resectable pancreatic cancer

BackgroundWe designed a retrospective study to compare prognostic outcomes based on whether or not surgical resection was performed in elderly patients aged(≥75 years) with resectable pancreatic cancer.MethodsWe retrospectively analyzed 49 patients with resectable pancreatic cancer (surgery group, resection was performed for 38 cases; no surgery group, resection was not performed for 11 cases) diagnosed from January 2003 to December 2014 at the National Cancer Center, Korea.ResultsThere was no significant difference in demographics between the two groups. The surgery group showed significantly better overall survival after diagnosis than the no surgery group (2-year survival rate, 40.7% vs. 0%; log-rank test, p = 0.015). Multivariate analysis revealed that not having undergone surgical resection [hazard ratio (HR) 2.412, P = 0.022] and a high Charlson comorbidity index (HR 5.252, P = 0.014) were independent prognostic factors for poor overall survival in elderly patients with early stage pancreatic cancer.ConclusionsIn the present study, surgical resection resulted in better prognosis than non-surgical resection for elderly patients with resectable pancreatic cancer. Except for patients with a high Charlson comorbidity index, an aggressive surgical approach seems to be beneficial for elderly patients with resectable pancreatic cancer.