Survival Benefit In Elderly Patients Research Articles

Abstract PS13-08: Chemotherapy in geriatric patients with early stage HER2+ breast cancer: A National Cancer Database analysis

Abstract Background Breast cancer (BC) incidence increases with age and women ≥ 65 years account for almost half of BC related mortality. Life expectancy has increased in the US due to improvements in medical care, and therefore the number of older patients with a BC diagnosis is also expected to increase. The population of individuals ≥ 80 years in the US is growing and now comprises more than 9 million. Approximately 15% of BC are human epidermal growth factor receptor 2 amplified (HER2+). The combination of chemotherapy with trastuzumab +/- pertuzumab compared with trastuzumab alone has been shown to be cost-effective in patients 70 years and older but trastuzumab monotherapy could be considered as an option in certain patients. Nevertheless, there is limited guidelines on how to properly care for the geriatric population with HER2+ BC. Methods We conducted a retrospective analysis of data collected from the National Cancer Database (NCDB). NCDB is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. Women ≥65 years with stage I, II and III HER2+ BC were included in the analysis. Patients were categorized into three treatment groups – those who did not receive chemotherapy or monoclonal antibodies (no-CT/mAbs), those who received chemotherapy in combination with monoclonal antibodies (CT/mAbs) and those who received monoclonal antibodies alone (mAbs). Using the Logrank P value, we explored the age cut off for which survival rates were not significantly different between treatment groups. Two comparisons were done: no-CT/mAbs vs CT/mAbs and CT/mAbs vs mAbs. The main outcome of this study was all-cause mortality. RESULTS: For the first comparison, a total of 9,924 HER2+ early-stage BC patients were included. Of these, 3,052 (30.8%) received no-CT/mAbs, while 6,872 (69.2%) received CT/mAbs. Kaplan Meier curves comparing mortality by treatment in the whole sample showed that those in the CT/mAbs group had significantly improved survival, compared to the no-CT/mAbs group (Logrank P < 0.001). The 1-year and 3-year survival rates were significantly higher in the CT/mAbs, compared to no-CT/mAbs. Cox proportional regression analysis showed that in the whole sample all-cause mortality was significantly lower among patients in the CT/mAbs group, compared to those in the no-CT/mAbs group (hazard ratio [HR], 0.48; CI: 0.41-0.57). However, the Logrank P values showed that there was no age cut off over which CT/mAbs did not improve survival compared to No-CT/mAbs. For the second comparison, a total of 7,457 patients were included. Of these 6,872 (92.2%) receive CT/mAbs and 585 (7.8%) received mAbs. The 1-year and 3-year survival rates were significantly higher in the CT/mAbs compared to the mAbs. The Logrank P values showed that there was no age cut off over which CT/mAbs did not improve survival compared to mAbs. Conclusion Chemotherapy in combination with HER2 directed monoclonal antibodies showed a survival benefit in elderly patients, irrespective of age, when compared to no-CT/mAb and mAb alone. These data highlight the importance of individualizing treatment recommendations and not forgoing standard therapy based merely on age. Limitations of the analysis include lack of available information on BC specific mortality. Also, the benefit that we identified could be secondary to selection bias. Additional studies are needed to improve the treatment in elderly patients with HER2+ BC. Table 1. Logrank P values for survival comparison between those who received CT/mAbs and No-CT/mAbs by age cut-off. Citation Format: Ana Sandoval-Leon, Yolcar Chamorro, Muni Rubens, Mukesh Roy, Lauren Carcas, Naomi Dempsey, Manmeet Ahluwalia, Reshma Mahtani. Chemotherapy in geriatric patients with early stage HER2+ breast cancer: A National Cancer Database analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS13-08.

Target versus sub-target dose of renin-angiotensin system inhibitors on survival in elderly patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis.

The efficiency of the target versus sub-target dose of renin-angiotensin system inhibitors (RASIs) in elderly patients with heart failure (HF) with reduced ejection fraction (HErEF) remains unclear. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from database inception through March 2022 for randomized controlled trials (RCTs) and observational studies considering the effect of the target versus sub-target dose of RASIs on survival in elderly patients (≥ 60 years) with HErEF. The primary outcome was all-cause mortality. The secondary outcomes were cardiac mortality, HF hospitalization, and the composite endpoint of mortality or HF hospitalization. A meta-analysis was conducted to generate combined hazard ratio (HR) and 95% CI. Seven studies (two RCTs and five observational studies) enrolling 16,634 patients were included. A pooled analysis suggested that the target versus sub-target dose of RASIs led to lower rates of all-cause mortality (HR = 0.92, 95% CI: 0.87-0.98, I2 = 21%) and cardiac mortality (HR = 0.93, 95% CI: 0.85-1.00, I2 = 15%) but not reduced rates of HF hospitalization (HR = 0.94, 95% CI: 0.88-1.01, I2 = 0) and the composite endpoint (HR = 1.03, 95% CI: 0.91-1.15, I2 = 51%). However, the target dose of RASIs was associated with a similar primary outcome (HR = 0.85, 95% CI: 0.64-1.14, I2 = 0) in a subgroup of very elderly patients > 75 years of age. Our analysis suggests that the target dose of RASIs has a better survival benefit in elderly patients with HFrEF compared to the sub-target dose of RASIs. However, the sub-target dose of RASIs is associated with a similar mortality rate in very elderly patients > 75 years of age. Future high-quality and adequately powered RCTs are warranted.

Prognostic role of radiotherapy in low-risk elderly breast cancer patients after breast-conserving surgery: a cohort study.

Previous research suggested that radiotherapy (RT) had a small absolute benefit in patients with low-risk breast cancer over the age of 65. To reduce the patient's treatment burden and cost, as well as the damage to normal tissue, this study sought to explore the prognostic role of RT after breast-conserving surgery (BCS) in elderly patients. Patients who were aged ≥65 years, stage T1N0M0, and estrogen receptor/progesterone receptor positive (ER+/PR+) were included in this study. Age, marital status, histology, race, grade, human epidermal growth factor receptor 2 (HER2), subtype, treatment method, and survival were also collected from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. We compared overall survival (OS) and breast cancer-specific survival (BCSS) before and after propensity score matching (PSM) in the patients who underwent BCS with or without RT. Kaplan-Meier method and Cox proportional hazards regression analyses were used in our study. The data of 3,623 patients were analyzed in this study. Among them, 2,851 (78.69%) patients had received RT. The multivariate analyses before PSM showed that RT resulted in better OS [hazard ratio (HR) 0.51, 95% confidence interval (CI): 0.42-0.62, P<0.001], and BCSS (HR 0.40, 95% CI: 0.27-0.58, P<0.001). The multivariate analyses after PSM (n=1,538) confirmed that patients who received RT (n=769) had a longer survival time than those who did not (n=769) (OS: HR 0.73, 95% CI: 0.57-0.95, P=0.018; and BCSS: HR 0.57, 95% CI: 0.35-0.93, P=0.025). The survival analysis showed that patients receiving RT had a better OS (P=0.028) and BCSS (P=0.016) than those who did not receive RT. However, there were no significant differences in patients' OS and BCSS with or without RT across the different age subgroups (P>0.05). In our study, patients who received RT had a longer survival time. However, the age subgroup analysis showed that RT did not have any survival benefit in elderly patients with T1N0M0 and ER+/PR+ breast cancer. Furthermore, at the age of 65-69 years, the P value for OS approached 0.05, which suggests that the decision to administer RT in this patient group should be made based on each patient's condition.

Outcomes in Elderly Patients Undergoing Liver Transplantation Compared with Liver-Directed Ablative Therapy in Early-Stage Hepatocellular Carcinoma.

Orthotopic liver transplantation (OLT) is the accepted treatment in patients with unresectable, early-stage hepatocellular carcinoma (HCC) in the setting of cirrhosis. Due to increasing waitlist demand for OLT, determining optimal groups for transplant is critical. Elderly patients are known to have poorer postoperative outcomes. Considering the effectiveness of liver-directed therapies for HCC, we sought to determine whether elderly patients received survival benefit from OLT over liver-directed therapy alone. The National Cancer Database participant use file was used to analyze data between 2004 and 2017. Only patients ≥70 years of age who received OLT or liver-directed therapy alone were included. Patients with alpha-fetoprotein >500 ng/mL or missing alpha-fetoprotein values were excluded. Baseline demographic variables, model for end-stage liver disease score, and overall survival from time of diagnosis were collected. Descriptive statistics, Kaplan-Meier survival, Cox proportional hazards model, and propensity score matching were used. A total of 2,377 patients received ablative therapy alone, and 214 patients received OLT. Multivariable analysis and Kaplan-Meier showed that OLT conferred a significant survival benefit compared to liver-directed therapy alone. Age was also associated with a yearly 3% increase in risk of mortality. Propensity-matched analysis adjusting also demonstrated a significant survival benefit for elderly patients receiving OLT compared to liver-directed therapy alone. Despite increased age and associated comorbidities being factors associated with poor outcomes, OLT confers a survival advantage compared to liver-directed ablative therapies alone in selected elderly patients with HCC. OLT should be offered in medically appropriate elderly patients with HCC.

The Affects of Adjuvant Radiotherapy on Survival in Elderly Patients with Advanced Head & Neck Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> For locally advanced head and neck squamous cell carcinoma (HNSCC), adjuvant radiotherapy (RT) following definitive surgical resection has been widely shown to confer a survival benefit. However, the presence of this survival benefit for elderly patients has not been clearly demonstrated. Given the numerous morbidities associated with RT, we sought to investigate the difference in overall survival (OS) associated with adjuvant therapy in elderly patients (80+). <h3>Materials/Methods</h3> The National Cancer Database (NCDB) was queried for all cases of HNSCC between 2004-2016 using ICD-O-3 histology and morphology codes. Those with advanced disease, defined as pathologic T3/T4 and/or N2b or greater, were selected for inclusion. Exclusion criteria included those with HPV-positive disease, distant metastasis, positive surgical margins, and/or death within 30 days of surgery. Patients who received neoadjuvant treatment and/or systemic therapy were additionally excluded. Patients treated with surgical resection alone were compared to those treated with surgery + adjuvant RT. OS was compared between these groups in patients younger than 80 and separately for those 80+ using Kaplan meier analysis. Odds ratios (OR) were assessed using Cox proportional hazards to account for differences in patient characteristics, primary site, and HNSCC stage. <h3>Results</h3> NCDB identified 16,504 cases meeting inclusion criteria with 7,375 (44.7%) treated with surgery alone and 9,129 (55.3%) receiving adjuvant RT. The mean age was 63.8 years (SD = 12.0) with 89.0% of patients aged <80 and 11.0% aged 80+. In the younger cohort, adjuvant RT was associated with a significant increase in OS relative to surgery alone when assessed at 1 year (88.4% vs. 83.8%, p=<0.001), 3 years (64.0% vs. 59.2%, p=<0.001) and 5 years (52.8% vs 47.2%, p=<0.001). In the elderly cohort, there was no significant difference in OS between adjuvant RT and surgery alone when measured at 1 year (73.4% vs. 74.8%, 0.296), 3 years (45.8% vs. 41.8%, p=0.465), or 5 years (28.2% vs. 27.7% p=0.759). Cox regression was utilized to assess the OR for 5-year OS associated with adjuvant RT after accounting for differences in primary site, T-stage, and N-stage. In patients under 80, surgery alone remained a significant predictor of 5-year mortality with an OR of 1.32 (95% CI 1.25-1.39, p=<0.001). In the elderly cohort, there was no significant difference between groups with surgery alone carrying an OR of 1.10 (95% CI 0.96-1.25, p=0.169). <h3>Conclusion</h3> In elderly patients undergoing definitive surgical treatment of locally advanced HSNCC, adjuvant RT may not provide a similar overall survival benefit relative to younger patients. Further research is needed to explore differences in disease-specific survival and quality of life to guide shared decision making in this patient population.

Bilateral internal thoracic artery coronary grafting: risks and benefits in elderly patients.

Whether bilateral internal thoracic artery (BITA) grafting benefits elderly patients in coronary artery bypass grafting (CABG) remains unclear since they tend to have a limited life expectancy and severe comorbidities. We aim to evaluate the outcomes of BITA vs. single internal thoracic artery (SITA) grafting in elderly patients. A meta-analysis was performed by database searching until May 2021. Studies comparing BITA and SITA grafting among elderly patients were included. One randomized controlled trial, nine propensity score matching, and six unmatched studies were identified, with a total of 18146 patients (7422 received BITA grafting and 10724 received SITA grafting). Compared with SITA grafting, BITA grafting had a higher risk of deep sternal wound infection (DSWI) [odds ratio: 1.67; 95% confidence interval (CI): 1.22-2.28], and this risk could not be significantly reduced by the skeletonization technique. Meanwhile, BITA grafting was associated with a higher long-term survival [hazard ratio: 0.83; 95% CI: 0.77-0.90], except for the octogenarian subgroup. Reconstructed Kaplan-Meier survival curves revealed 4-year, 8-year, and 12-year overall survival rates of 85.5%, 66.7%, and 45.3%, respectively, in the BITA group and 79.3%, 58.6%, and 34.9%, respectively, in the SITA group. No significant difference was observed in early mortality, perioperative myocardial infarction, perioperative cerebral vascular accidents, or re-exploration for bleeding. Compared with SITA grafting, BITA grafting could provide a long-term survival benefit for elderly patients, although this benefit remained uncertain in octogenarians. Meanwhile, elderly patients who received BITA were associated with a higher risk of DSWI and such a risk could not be eliminated by the skeletonization technique.

Clinicopathological characteristics and prognosis of brain metastases in elderly patients with esophageal carcinoma.

BackgroundBrain metastases (BM) from esophageal carcinoma (EC) is clinically rare and has not yet been reported in elderly patients. This study aimed to investigate the clinicopathological characteristics, outcomes and prognostic factors of BM in elderly patients with EC, in order to provide guidance for clinical practice.MethodsA total of 20 EC patients older than 65 years who were diagnosed with BM were identified from the fourth Hospital of Hebei Medical University between January 1, 2009 and December 31, 2018. Survival was evaluated by the Kaplan–Meier method and Cox proportional hazards models.ResultsThe median time from diagnosis of EC to BM was 11.8 months (0–249.2 months). The median overall survival (OS) was 4.8 months (1.13–23.3 months), with 20% of patients achieving the 1‐year survival rate. Patients with KPS score of ≥70 had a significantly better OS than those with KPS score<70 (8.4 vs. 3.9 months, p = 0.033). Compared to patients without brain radiotherapy, patients with brain radiotherapy showed better outcomes in both median OS (8.4 vs. 2.9 months) and 1‐year survival rate (23.1% vs. 14.3%, p = 0.043). The median OS of patients with radiotherapy combined with chemotherapy and/or targeted therapy and radiotherapy alone was 9.7 months (3.4–23.3 months) and 7.2 months (1.7–18.4 months), respectively, with no significant difference between the two groups (p = 0.215).ConclusionsBrain radiotherapy provided clinically meaningful survival benefit for elderly patients with BM from EC. Thus, active treatments for those patients might be required.

PL03.1.A Surgery for glioblastomas in the elderly: an ANOCEF trial (CSA)

Abstract BACKGROUND The role of surgery for the treatment of malignant gliomas in patients 70 years of age or older is unsettled. We conducted a randomized trial that compared surgical resection of the tumor and biopsy only, both followed by standard therapy, in such patients. MATERIAL AND METHODS Patients aged 70 years and older, with a KPS of at least 50, presenting with a radiological suspicion of an operable glioblastoma (GBM) were randomly assigned between tumor resection and biopsy. Subsequently, they underwent standard radiotherapy during the first years of the trial (2008–2017), with the adjunction of concomitant and adjuvant temozolomide when this regimen became standard (2017–2019). The primary end point was survival; secondary endpoints were progression free survival (PFS), cognitive status (MMS), autonomy (KPS), quality of life (EORTC QLQ C30 and BN20), and perioperative morbidity/ mortality. RESULTS From 2008 to 2019, 107 patients from 9 centers were enrolled in the study, of whom 101 were evaluable for analysis because the diagnosis of GBM was histologically confirmed (50 patients in the “surgery” arm and 51 patients in the “biopsy” arm). There was no statistically significant difference of median survival between the “surgery” arm (9.37 mo) and the “biopsy” arms (8.96 mo, p=0.36). However, the surgery group had increased PFS (5.06 mo vs 4.02 mo; p=0.034; p=0.002 on multivariate analysis) and better QOL (e.g. physical and cognitive functioning, motor dysfunction, fatigue) and KPS score evolution as compared to the “biopsy” group. Surgery was not associated with increased mortality or morbidity. CONCLUSION This study suggests that optimal debulking surgery does not provide a significant survival benefit in elderly patients suffering from newly diagnosed malignant glioma, but resection improves QOL and autonomy with a significant though modest improvement of PFS.

Five-Year Experience in the Surgical Treatment of Endometrial Cancer: Comparing Laparotomy with Robotic and Minimally Invasive Hysterectomy

To compare surgical and oncological outcomes in the treatment of endometrial cancer between laparotomy and minimally invasive surgery. The secondary objective was to determine which MIS approach was the most beneficial. This was a single-centre retrospective review of all endometrial cancer surgeries performed between November 1, 2012 and October 31, 2017 in a gynaecologic oncology unit of a university hospital. Descriptive statistics were used to compare histopathologic results and oncological outcomes, and Kaplan-Meier estimates were used to compare survival. A total of 735 cases were reviewed. The majority of patients (77%) underwent either laparotomy (35%) or robotic-assisted hysterectomy (42%); the remaining patients underwent total laparoscopic hysterectomy (12%) or a laparoscopic-assisted vaginal hysterectomy (8.7%). There was a statistically significant overall survival benefit (P=0.02), a shorter hospital stay (P < 0.0001), and fewer early surgical complications (<30 d; P=0.0002), as well as a survival benefit in elderly patients (>70 y) in the robotic-assisted hysterectomy group (P=0.043) than the laparotomy group. Operating time was shorter in the laparotomy group (P < 0.0001). Recurrence rates in stage 1 low-risk disease were similar between groups. Minimally invasive surgical approaches, particularly robotic surgery, do not compromise oncologic outcomes, especially for early-stage low-risk disease. In addition, these approaches are associated with fewer early surgical complications and shorter hospital stay, with significantly more same-day discharges. Overall survival and survival in a subgroup of elderly patients were significantly better in the robotic-assisted hysterectomy group.

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.

Efficacy and safety of immune checkpoint inhibitor monotherapy in pretreated elderly patients with non-small cell lung cancer

Immune checkpoint inhibitors (ICIs) are an effective subsequent-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, it remains unclear whether the efficacy and safety of subsequent-line ICI monotherapy in elderly patients (aged ≥ 75years) are similar to that in non-elderly patients. Therefore, we aimed to investigate the efficacy and safety of ICI monotherapy in pretreated elderly patients with NSCLC. Between January 2016 and February 2018, 131 elderly patients with advanced NSCLC who received subsequent-line ICI monotherapy at 13 Japanese institutions were enrolled in this study. Baseline characteristics, the efficacy of ICI treatment, and adverse events were evaluated. Ninety-eight men and 33 women (median age 77 [range 75-87] years) were enrolled. Among those who received subsequent-line ICI monotherapy, the overall response, disease control rates, median progression-free survival (PFS), and overall survival (OS) were 27.4%, 61.8%, 4.5months, and 16.0months, respectively. Adverse events such as anorexia, fatigue, pneumonitis, and hypothyroidism were observed. There were two treatment-related deaths due to pneumonitis and thrombocytopenia. Subsequent-line ICI monotherapy in patients with good performance status (PS), receiving steroids for immune-related adverse events (irAEs), and exhibiting partial response (PR) was associated with improved PFS, as well as OS in patients with good PS and PR. Subsequent-line ICI monotherapy in elderly patients, with previously treated NSCLC, was effective, safe and showed outcomes equivalent to those in non-elderly patients. Immunotherapy provides a survival benefit for elderly patients, who exhibit its efficacy and a favorable general condition.

From Evidence to Practice: Are Low-Risk Breast Cancer Patients still Enduring Unnecessary Costs of Radiation?

Radiation is routinely recommended after conservative surgery for breast cancer, despite long-standing Level I evidence showing no survival benefit for elderly patients with favorable disease using endocrine therapy. We sought to evaluate radiation use and costs in patients eligible for omission of radiation. A retrospective single-institution review from 2005 to 2017 was performed of women aged ≥70 years, with cT1N0M0, who were ER/PR positive and HER-2 negative, and receiving breast-conserving surgery. Patient, tumor, and treatment characteristics were compared by use of radiation. Cost estimates used Medicare's 2019 fee schedule. Of 84 patients meeting the study criteria, 72.6 per cent received radiation and 56 per cent received endocrine therapy, with four recurrences (4.9% radiated and 4.4% not radiated, P = 0.9). Early and late grade I radiation toxicities occurred in 67.2 per cent and 26.2 per cent of radiated patients, respectively. Younger age (P = 0.01), receipt of endocrine therapy (P < 0.0001), and axillary surgery (P < 0.0001) were significantly associated with radiation use. There were no significant differences in radiation use based on race/ethnicity, language, comorbidities, BMI, or pathologic tumor size. Estimated total radiation cost was $646,426. Radiation remains overused and endocrine therapy, underused in breast cancer patients eligible to avoid radiation. As gatekeepers for radiation oncology referrals, surgeons can diminish both physical and financial costs of radiation in eligible patients.

Survival Benefit of Adjuvant Radiotherapy in Elderly Patients with WHO Grade III Meningioma

The benefit of adjuvant radiotherapy (RT) is uncertain in elderly patients diagnosed with World Health Organization (WHO) grade III meningiomas. The US National Cancer Database was used to identify elderly patients (aged over 60) with histologically confirmed WHO grade III meningiomas who underwent surgery with or without adjuvant external beam RT. Overall survival (OS) was evaluated by Kaplan-Meier analysis, multivariable Cox proportional hazard models, and propensity score-matched analysis. Among the 254 patients who met inclusion criteria, 151 (58.4%) underwent surgery followed by RT and103 (41.6%) surgery without RT. The 5-year relative survival rate was 57.8% (95% confidence interval [CI], 38.7%-85.4%) in the adjuvant RT group and 38.1% (95% CI, 21.9%-55.9%) in the group without RT when compared with age- and gender-matched US population. Adjuvant RT was associated with longer OS on both univariate (P= 0.011) and multivariable analyses (adjusted hazard ratio [AHR],0.663; 95% CI, 0.449-0.978; P= 0.038). However, adjuvant RT did not significantly improve OS in a propensity score-matched analysis (P= 0.271) after matching the 2 cohorts on age, race, comorbidity, extent of resection, and tumor size. In patients who underwent subtotal resection or biopsy (n= 106), adjuvant RT significantly benefited OS on univariate analysis (P=0.023), but did not show statistically significant benefit on multivariate analysis (AHR, 0.594; 95% CI, 0.337-1.046; P= 0.071). Adjuvant RT was not associated with improved OS in the elderly patients who underwent gross total resection (AHR, 0.764; 95% CI, 0.434-1.344; P=0.350). Adjuvant external beam RT may not provide any survival benefit for elderly patients with WHO grade III meningioma after gross total resection.

P3.04-19 Do Advanced Lung Cancer Patients Derive Similar Survival Benefits from Immunotherapy? A Systematic Review and Meta-Analysis

Checkpoint inhibitors targeting the programmed death-1 (PD-1)/PD-ligand 1 (L1) pathway have become a standard treatment in advanced non-small cell lung cancer (NSCLC) in the first and second line setting. Yet, subgroup analyses from randomized trials have shown inconsistent results regarding survival benefit in elderly patients (> 65 years old), never-smokers and patients with PD-L1 (-) expressing tumors (<1%). We conducted a systematic review and meta-analysis to assess the efficacy of checkpoint inhibitors in these pre-defined subgroups of patients. The electronic databases PubMed and EMBASE, were searched for relevant randomized trials between January 2005 and December 2017. Pooled hazard ratios (HR) for overall survival (OS) and progression free survival (PFS) were meta-analyzed using the generic inverse variance method. To account for between-studies heterogeneity, random-effect models were used to compute pooled estimates. Subgroup analyses compared patients treated in the first versus second line setting. Seven studies were included. Compared to chemotherapy, a significant reduction in the risk of death was seen with the use of checkpoint inhibitors in the second line independent of PD-L1 expression (4 studies, 2,364 participants, HR=0.79, 95%CI 0.66-0.96 and HR=0.66, 95%CI 0.57-0.78 in PD-L1 (–) and (+) patients respectively). Yet, a PFS benefit was only seen in patients with PD-L1 (+) tumors (2 studies, 852 participants, HR=0.69, 95%CI 0.55-0.88). Similarly, an OS benefit was seen in patients independent of age (5 studies, 3,651 participants, HR=0.77, 95%CI 0.64-0.92 and HR=0.75, 95%CI 0.6-0.94 in elderly and non-elderly patients respectively). Conversely, an OS benefit was only seen in ever-smokers (5 studies, 2,905 participants, HR=0.76, 95%CI 0.63-0.92 in ever-smokers and HR=0.83, 95%CI 0.64-1.08 in never-smokers) and a detrimental effect on PFS in never-smokers (3 studies, 1,426 participants, HR=1.68, 95%CI 1.07-2.63). In subgroup analyses, with the use of checkpoint inhibitors, elderly patients derived an OS benefit only in the second line setting (HR=0.69, 95%CI 0.59-0.81). Furthermore, never-smokers had no OS benefit in the first or second line (HR=1.02, 95%CI 0.54-1.93 and HR=0.79, 95%CI 0.59-1.07 respectively) and worse PFS particularly in the first line (HR=2.3, 95%CI 1.23-4.3). In the second line setting, patients with advanced NSCLC derive a survival benefit from checkpoint inhibitors independent of tumor PD-L1 expression and age. However, never-smokers do not benefit from these drugs particularly in the first line. Caution should be exercised when offering checkpoint inhibitors to elderly patients with advanced NSCLC in the first line and further research is needed to define their role in never-smokers.

Meta-analysis of molecular targeted agents in the treatment of elderly patients with metastatic colorectal cancer: Does the age matter?

Patients aged 65 years and older are often underrepresented in clinical trials of metastatic colorectal cancer (mCRC) and probably undertreated in clinical practice. We performed a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy of molecular targeted agents (MTAs) in this population. A comprehensive literature search for studies published up to December 2014 was performed. The endpoints were overall survival (OS) and progression-free survival (PFS). The pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Eleven RCTs involving 8,488 patients were ultimately identified. The pooled analysis demonstrated that the use of MTAs in elderly patients with mCRC significantly improve OS (HR 0.84, 95% CI: 0.76-0.92, P < 0.001) and PFS (HR 0.78, 95% CI: 0.64-0.96, P = 0.017) when compared to MTAs-free therapies. Similar results of OS were observed in subgroup analysis according to treatment line, therapy regimes, and approval status of MTAs. No publication bias was detected by Begg's and Egger's tests. The introduction of MTAs to therapies offered a survival benefit in elderly patients with mCRC. Further studies aimed at this specific patient population were still needed to watchfully monitor potential treatment-related toxicities to optimize the use of these drugs.

Chemotherapy and survival benefit in elderly patients with advanced gastric cancer.

45 Background:There is little evidence if chemotherapy (CT) offer survival benefit for elderly patients (EP) with advanced gastric cancer (AGC). Methods: This was a single-centre retrospective study. A total of 118 patients with AGC were hospitalized at our hospital from April 2012 to June 2016. Of them, EP older than 75 years with AGC were eligible for inclusion in the study. Basically, the treatment strategy, chemotherapy (CT) or best supportive care (BSC) were comprehensively decided according to their background. We evaluate the risk factors for survival using the Cox proportional hazard model and explored the optimal indication for CT for EP. Results: Of 118 patients with AGC, 47 patients were enrolled as EP [63% men; mean age, 81 years]. Of EP, 26 patients (55%) received CT and 21 patients received BSC. As first-line CT, 13 patients received S1 monotherapy, the others treated with combination agents. The median overall survival time (MST) was 138 days. There was no significant difference between CT and BSC group (172 vs. 118 days, p = 0. 1087). Univariate analysis revealed the following 5 factors for poor prognosis were significant (defined as p-value &lt; 0.1): Performance status (PS) 3a 2 (HR3.7, 95% CI: 1.5-8.5), C-reactive protein levels 3a 1mg/dL (HR4.0, 95% CI: 1.8-9.4), albumin level &lt; 3g/dL (HR2.1, 95% CI: 1.1-4.3), neutrophil/lymphocyte ratio (NLR) 3a 4 (HR3.7, 95% CI: 1.7-8.5), and diffuse type (HR1.8, 95% CI: 0.9-3.8). As each poor risk factor of 5 and age factor 3a 80 years represents point 1, we calculated total points (0-6) for each patient. Median total points of CT and BSC were 2 and 4, respectively (p = 0.0196). Therefore, we set cut-off point of 3. Then, EP with a total point of 3 and more were classified as high risk group (HR: N = 25) and the others were as low risk group (LR: N = 22). There was significantly longer MST in LR than HR (all EP; 457 vs 105 days, HR: 0.23, p = 0.0002 and EP with CT; 232 vs 113 days, HR:0.26, p = 0.0085). Conclusions: Our findings using the scoring system including 6 factors suggest that EP with a total point 3 and more, were poor prognosis and may not receive benefit from CT for AGC. When judging indication for CT in EP with AGC, this scoring system may be useful, and in case of LR (total point 0-2) may be considered an indication for CT.

Observation versus thyroidectomy for papillary thyroid microcarcinoma in the elderly

To compare the effectiveness of non-surgical versus surgical therapy in elderly patients with papillary thyroid microcarcinoma. The study cohort included 2323 elderly patients (aged 65 years and over) diagnosed with papillary thyroid microcarcinoma between 1988 and 2009, identified in the Surveillance, Epidemiology, and End Results 18 database of the National Cancer Institute. The five-year overall survival rate was 23 per cent for non-surgical patients compared with 91 per cent for surgical patients (p < 0.0001). Unadjusted analysis revealed significantly improved survival in surgical patients compared with non-surgical patients (hazard ratio = 0.06; p < 0.0001). Propensity score analysis also revealed significantly improved survival in surgical patients compared with non-surgical patients (hazard ratio = 0.11; p < 0.0001). Thyroidectomy appears to provide a survival benefit for elderly patients with papillary thyroid microcarcinoma. High-quality prospective studies are needed to better evaluate the comparative effectiveness of immediate thyroidectomy versus observation for elderly patients with papillary thyroid microcarcinoma.

Meta-analysis of molecular targetted agents in the treatment of elderly patients with metastatic colorectal cancer: does the age matter?

Aim: Patients aged 65 years and older are often under-represented in clinical trials of metastatic colorectal cancer (mCRC) and probably undertreated in clinical practice. We performed a meta-analysis of randomized controlled trials to assess the efficacy of molecular targetted agents (MTAs) in this population. Methods: A comprehensive literature search for studies published up to December 2014 was performed. The endpoints were overall survival (OS) and progression-free survival (PFS). The pooled hazard ratio (HR) and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: Eleven randomized controlled trials involved 8,488 patients were ultimately identified. The pooled analysis demonstrated that the use of MTAs in elderly patients with mCRC significantly improved OS (HR 0.84, 95% CI: 0.76–0.92, p < 0.001) and PFS (HR 0.78, 95% CI: 0.64–0.96, p = 0.017) when compared to MTAs-free therapies. Similar results of OS were observed in sub-group analysis according to treatment line and regimes. No publication bias was detected by Begg's and Egger's tests. Conclusions: The introduction of MTAs to therapies offers a survival benefit in elderly patients with mCRC. Further studies aimed at this specific patient population are still needed to monitor potential treatment-related toxicities to optimize the use of these drugs.

Curative treatments and survival benefit in elderly patients with hepatocellular carcinoma: A SEER population-based analysis.

355 Background: Transplant, resection, and ablation are potentially curative treatments for hepatocellular carcinoma (HCC) with limited outcome data in young-old (65-74) and older (≥75) patients. Methods: We evaluated curative treatment and relative survival (RS) outcomes in patients with HCC in 3 age groups (&lt;65 years, 65-74 years, and ≥75 years). Patients with HCC diagnostic codes (histology 8,170-8,175, morphology C22) were identified in the SEER 18 database from 2000 to 2011. Treatments included curative (transplant, resection, radiofrequency ablation (RFA), and other ablations) and palliative therapies. Primary outcome was 5 year RS. Statistical analysis was performed using Kaplan-Meier and Chi-Square tests. Results: We identified 29,654 cases. The mean age was 62 years with almost 40% of HCC cases in patients over 65 years old. Potentially curable, localized stage rates were similar in all age groups, 46%, 48% and 46%, respectively. As a result of less resection and rare transplant use, fewer cases underwent curative treatments in the group 75 years and older in comparison to all other age groups (15% vs. 27%, p = 0.001). Five-year RS in all 3 age groups (&lt;65 years, 65-74 years, and ≥75 years) was better after resection relative to RFA (47% vs. 35% p&lt;0.0001, 44% vs. 37%, p=0.0093, and 43% vs. 28% p=0.0002). The highest survival was seen after liver transplant. Interestingly, among transplanted patients with HCC, 13% were 65-75 years old. Five-year RS was similar in transplanted patients 65-75 vs. those under 65 (76% vs 74% p=0.65). Conclusions: The use of curative treatments for HCC significantly decreases with age, yet there are clear survival benefits in elderly patients receiving such. Even when considering transplant, the data shows that outcome is as good in elderly patients as in younger patients. The benefit of hepatic resection appears to be superior compared to RFA in all age groups, in our analysis. [Table: see text]

669P - The Role of Adjuvant Chemotherapy for Elderly Patients with Gastric Cancer After a Gastrectomy in Korea

ABSTRACT Aim: Adjuvant chemotherapy is recommended for gastric cancer after a gastrectomy with D2 dissection. However, its survival benefit in elderly patients is unclear. Here, we investigated the use of adjuvant chemotherapy in patients ≥70 years old with stage II or III gastric cancer to identify its impact on survival. Methods: Patients ≥70 years old diagnosed with stage II or III gastric cancer at Ulsan University Hospital from 2008–2012 were identified. A retrospective analysis of electronic and paper patient records was performed to identify baseline characteristics, chemotherapy used, toxicity, and survival. Results: From 2008–2012, 277 patients ≥70 years old underwent gastrectomy with D2 dissection. Of these patients, 94 were pathologically diagnosed with stage II or III gastric cancer; 55 of these patients (58.5 %) received adjuvant chemotherapy and 39 received regular check-ups without chemotherapy. Fluoropyrimidine-alone regimens, including TS-1 (n = 26) and didox (n = 22), were more commonly used than fluoropyrimidine-platinum combination regimens (n = 7). With a median follow-up of 30.9 (range, 0.8–65.5) months, the median relapse-free survival of patients with adjuvant chemotherapy or regular follow-up only was 35.5 and 20.4 months, respectively (p = 0.030). Multivariate analysis revealed that adjuvant chemotherapy is associated with longer relapse-free survival (hazard ratio, 0.50; 95 % confidence interval, 0.27–0.96). There was a trend toward an improved overall survival in the adjuvant chemotherapy group compared with the follow-up only group (p = 0.242). Conclusions: Although well-designed prospective studies are required, adjuvant chemotherapy may confer a potential survival benefit in elderly patients (aged 70 or older) with stage II or III gastric cancer after a gastrectomy with D2 dissection. Disclosure: All authors have declared no conflicts of interest.