Overall Survival In Older Patients Research Articles

Clinical outcomes after idecabtagene vicleucel in older patients with multiple myeloma: a multicenter real-world experience

AbstractThe safety and efficacy of chimeric antigen receptor T-cell therapy is not well described in older patients, a population that has higher frailty and comorbidities. In this multicenter retrospective study, we evaluated clinical outcomes along with frailty and geriatric characteristics such as comorbidities, polypharmacy, falls, neuropathy, organ dysfunction, and performance status in younger (aged <65 years) vs older (aged ≥65 years) patients who received commercial idecabtagene vicleucel (ide-cel). A total of 156 patients (n = 75, aged ≥65 years) were infused with ide-cel by data cutoff. In older patients (median age: 69 years; range, 65-83; 66.7% frail; 77.3% did not meet KarMMa eligibility criteria), with a median follow-up duration of 14.2 months, best overall response rate (ORR) was 86.7%, which was comparable with pivotal KarMMa study results (ORR: 73%). Median progression-free survival and overall survival in older patients were 9.1 months and 26.5 months, respectively. Grade ≥3 cytokine-release syndrome and immune effector cell–associated neurotoxicity syndrome were observed in 1% and 4% of older patients, respectively. Compared with younger patients, the older patients had significantly higher prevalence of frailty, geriatric characteristics such as polypharmacy (≥5 drugs; 97%), ≥4 comorbidities (69%), and organ dysfunction (35%; P < .05). The safety and efficacy of ide-cel therapy were similar in younger and older patients. Frailty and geriatric characteristics such as polypharmacy, comorbidities, and organ dysfunction in older patients did not confer an inferior overall outcome.

Intrinsic capacity and survival among older adults with gastrointestinal malignancies: The Cancer and Aging Resilience Evaluation registry.

Intrinsic capacity (IC) was introduced by the World Health Organization (WHO) as a marker of healthy aging, and is defined as the combination of an individual's physical, mental, and psychological capacities. This study aimed to assess IC via a patient-reported geriatric assessment (GA) and evaluate its association with survival among older adults with gastrointestinal (GI) malignancies. Data were used from a single-institution prospective registry of older adults undergoing GA before cancer therapy. Key domains of IC (vitality, locomotion, and sensory [hearing and visual], psychological, and cognitive capacities) were captured via GA, and each was given a score of 0 or 1 (0,impaired) to compute the total IC score (range, 0-6, where 6indicatesno impairment and ≤5indicatesimpairment in ≥1 domains). A frailty index (FI) was measured via the deficit accumulation method. Cox regression models and Kaplan-Meier curves were used to examine the impact of IC impairment on survival. The study included 665 patients; the median age was 68 years, 57.4% were men, and 72.9% were White. The median IC score was 4, and 79.3% of participants showed impairment in ≥1 domains of IC. Most commonly impaired domains were locomotion (48.7%) and vitality (43.9%). IC was inversely associated with FI (Spearman coefficient, -0.75; p<.001). IC impairment was associated with inferior overall survival (score, 4-5: adjusted hazard ratio [aHR], 1.7; 95% CI, 1.11-2.48; score, 2-3: aHR, 1.9; 95% CI, 1.30-2.85; score, 0-1: aHR, 1.9; 95% CI, 1.11-2.48). IC impairment is associated with frailty and reduced overall survival in older patients with GI malignancies. GA can be used to screen for IC impairment as recommended by the WHO. The World Health Organization introduced intrinsic capacity as a marker of healthy aging. Intrinsic capacity is the combination of an individual's physical, mental, and psychological capacities. It contains six key domains: vitality, locomotion, and sensory (hearing and visual), psychological, and cognitive capacities. Older adults with cancer are susceptible to a decrease in intrinsic capacity as a result of cancer and the aging process. In this study, we aimed to assess the intrinsic capacity for patients with gastrointestinal cancer and also identify whether there exists any association of intrinsic capacity with overall survival. We identified that approximately 80% of this population had one or more impaired domains, and more intrinsic capacity impairment was associated with reduced overall survival.

Mathematical modelling of clonal reduction therapeutic strategies in acute myeloid leukemia

Over the years, the overall survival of older patients diagnosed with acute myeloid leukemia (AML) has not significantly increased. Although standard cytotoxic therapies that rapidly eliminate dividing myeloblasts are used to induce remission, relapse can occur due to surviving therapy-resistant leukemic stem cells (LSCs). Hence, anti-LSC strategies have become a key target to cure AML. We have recently shown that previously approved cardiac glycosides and glucocorticoids target LSC-enriched CD34+ cells in the primary human AML 8227 model with more efficacy than normal hematopoietic stem cells (HSCs). To translate these in vitro findings into humans, we developed a mathematical model of stem cell dynamics that describes the stochastic evolution of LSCs in AML post-standard-of-care. To this, we integrated population pharmacokinetic-pharmacodynamic (PKPD) models to investigate the clonal reduction potential of several promising candidate drugs in comparison to cytarabine, which is commonly used in high doses for consolidation therapy in AML patients. Our results suggest that cardiac glycosides (proscillaridin A, digoxin and ouabain) and glucocorticoids (budesonide and mometasone) reduce the expansion of LSCs through a decrease in their viability. While our model predicts that effective doses of cardiac glycosides are potentially too toxic to use in patients, simulations show the possibility of mometasone to prevent relapse through the glucocorticoid’s ability to drastically reduce LSC population size. This work therefore highlights the prospect of these treatments for anti-LSC strategies and underlines the use of quantitative approaches to preclinical drug translation in AML.

Preoperative Myosteatosis and Prognostic Nutritional Index Predict Survival in Older Patients With Resected Biliary Tract Cancer.

Sarcopenia accompanied by systemic inflammation is associated with poor prognosis in patients with cancer. This study evaluated the prognostic significance of sarcopenia (myopenia and myosteatosis) and systemic inflammatory markers in older patients (aged ≥80 years) with resected biliary tract cancer. Patients who underwent resection for biliary tract cancer between July 2010 and January 2023 at the NHO Fukuyama Medical Center were retrospectively reviewed. Preoperative computed tomography measured myopenia and myosteatosis, using the psoas muscle index and modified intramuscular adipose tissue content. Associations between clinicopathological characteristics, inflammation-based prognostic scores, and overall survival were analyzed using Cox proportional hazards models. Univariate analysis revealed low C-reactive protein-to-albumin ratio (<0.125), low prognostic nutritional index (<42), low modified intramuscular adipose tissue content, higher T-stage (T3-4), lymph node metastasis, and postoperative complications associated with worse overall survival in older patients (aged ≥ 80 years) with resected biliary tract cancer (n=48). Multivariate analysis identified low prognostic nutritional index (<42) (p=0.007), low modified intramuscular adipose tissue content (p=0.015), higher T-stage (T3-4) (p<0.001), lymph node metastasis (p=0.001), and postoperative complications (p=0.017) as independent predictors of overall survival. Preoperative myosteatosis and low prognostic nutritional index are independent prognostic factors for overall survival in older patients (aged ≥80 years) with resected biliary tract cancer. These factors may be useful for risk stratification and clinical decision-making. Early interventions, such as nutritional support and physical exercise, may improve outcomes after resection of biliary tract cancer.

Geriatric factors associated with overall survival in older patients with metastatic colorectal cancer

Advanced age in patients with colorectal cancer is a factor of poor prognosis, but little is known about geriatric factors associated with survival and chemotherapy prescription in frail elderly patients. Our research sought to investigate these factors in older patients with metastatic colorectal cancer (mCRC). Patients and methodspatients aged ≥75 years, who were treated for mCRC and have had a Comprehensive Geriatric Assessment (CGA) due to their frailty, were included in this multicenter practice study in the Loire Valley region (France). With initial patient care for mCRC as the starting point, demographic, oncological, geriatric and survival data were collected from the regional cancer database and the medical record of each patient. We analyzed overall survival and chemotherapy prescription, according to the geriatric factors of the CGA. Results108 patients were enrolled (mean age 84.0 +/- 4.5 years; 57.4 % men), among whom 53 (49 %) received at least one line of chemotherapy. The median overall survival [95 %CI] was 8.05 [5.6–12.0] months. In univariate analysis, prescription of chemotherapy was associated with the number of severe co-morbidities, number of co-medications, G8 score, BMI, MMSE score, IADL and ADL scores, Lee index and Balducci criteria. Survival was significantly associated with chemotherapy, ADL and IADL scores, G8 score, repeated falls, number of severe co-morbidities, MMSE score, Lee index and Balducci criteria. In multivariate analysis, only the ADL score (HR [95 %CI]: 0.74 [0.55–0.99], p = 0.04), number of severe co-morbidities (HR [95 %CI]: 1.62 [1.06–2.47], p = 0.03) and repeated falls (HR [95 %CI]: 3.54 [1.70–7.39], p < 0.001) were significantly associated with survival. Conclusionin frail elderly patients with mCRC, dependency, co-morbidities and repeated falls are independent factors associated with survival. As such, there could be merit in taking these into consideration before the choice of oncological treatment is made.

Assessment of geriatric and clinical domains for development and validation of a novel nomogram to predict the prognosis of older patients with breast cancer: a real-world retrospective cohort study

BackgroundBreast cancer is a relatively heterogeneous disease in the older population. Survival in older breast cancer patients is not only affected by tumor-related factors, but also by geriatric assessment domains. How tumor clinical factors and geriatric factors specifically affect the survival rate of older patients and how to combine these two factors to predict the risk of death in older patients with breast cancer remain clinical questions to be addressed.MethodWe used the Peking Union Medical College Hospital database to identify older patients (≥65 years) who were newly diagnosed with breast cancer between January 2013 and December 2019. Of the 641 eligible patients, we retrospectively analyzed the clinical and geriatric data of 556 patients who formed our study population. The primary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors and construct a nomogram to predict the 1-, 3-, and 5-year survival rates. The performance of the constructed nomogram was evaluated using calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA).ResultsMultivariate Cox regression analysis revealed seven independent prognostic factors associated with OS in older patients with breast cancer: age, tumor stage, lymph node stage, intrinsic molecular subtype, functional status, comorbidities, and psychological state. Nomogram based on these seven factors yielded excellent performance, with area under the ROC curve (AUROC) of 0.748. Similarly, the nomogram for BCSS had an AUROC of 0.760. Moreover, the calibration curve and DCA revealed good predictive accuracy between the actual and predicted probabilities.ConclusionIndependent prognostic factors for OS and BCSS in older patients with breast cancer in China were determined in our study. A novel nomogram for predicting the 1-, 3-, and 5-year OS and BCSS in this patient population was developed and validated. The nomogram exhibited good accuracy, indicating its potential for clinical decision making and improving outcomes.

Improvements in Overall Survival in Older Patients with Mantle Cell Lymphoma Are Driven By Improvements across Multiple Lines of Therapy

Introduction Survival rates for people with mantle cell lymphoma (MCL) have improved in recent years. Among the potential factors accounting for this improvement is the approval of multiple new therapies over the past two decades, including bortezomib, bendamustine, ibrutinib, lenalidomide, acalabrutinib, and zanubrutinib. We hypothesized that the availability of multiple agents with non-overlapping mechanisms of action would result in significant improvements in overall survival following first-line therapy. Methods Patients diagnosed with MCL between 2002 and 2017 were identified using the SEER-Medicare linked database. Selected patients were &amp;gt;65 years of age at the time of diagnosis with MCL. Lines of therapy were determined using billing codes, with inpatient/outpatient claims used for traditional agents and Medicare Part D dataset used for oral agents. Next lines of therapy were defined based on claims for new anticancer agents separated from the end of the prior line by some certain number of days. Sensitivity analyses were performed varying the number of days between therapies. Overall survival (OS) was defined as initiation of initial therapy to death, while OS2 was defined as time from initiation of second-line therapy to death. Time to next therapy 1 (TTNT1) was defined as time from start of first-line therapy to death or start of second-line therapy, whichever came first. Cox models and Kaplan-Meier (KM) survival curves were generated for time-to-event analyses. Analyses were stratified by categories of years of first- and second-line therapies corresponding to eras of key drug approvals (e.g., 2002-2005, 2006-2009, 2010-2013, &amp;gt;2013). Results In total, 4,832 patients were included, among whom 3,840 patients (79.5%) had claims for first-line regimens and 1,648 (34.1% of total and 42.9% of patients with first-line regimens) had second-line regimens. Of the 4,832 patients, the majority were male (67.4%), White (94.6%), and non-Hispanic (94.7%), with good performance status (74.8%) and a Charlson Comorbidity Index &amp;lt;2 (64.8%). The median age at diagnosis was 75 (IQR 70-81). Patients with first- and/or second-line regimens did not differ significantly from the entire population of 4,832 patients with MCL in terms of baseline characteristics. In the first-line setting, use of bendamustine-rituximab (BR) increased from 2.3% of patients treated in 2006-2009 to 49.5% in 2014-2017. Similarly, use of single-agent BTK-inhibitors (BTKi) increased from nonexistent in patients treated in 2010-2013 to 13.8% in 2014-2017. In the second-line setting, use of single-agent BTKi similarly increased from 2.6% of those treated in 2010-2013 to 44.9% in 2014-2017. Median OS for the 3,840 patients with fist-line regimens was 4.4 years (95% CI, 4.1-4.5); median OS for those receiving first-line therapy in 2002-2005 was 3.5 years (3.1-3.9), compared to 3.7 (3.4-4.0), 4.5 (4.2-5.0), and not reached (4.8-NR) among those treated in 2006-2009, 2010-2013, and 2014-2017, respectively. Patients treated in 2014-2017 had significantly improved OS compared with those in 2002-2005 (log rank p&amp;lt;0.0001). Median TTNT1 overall was 2.5 years (2.4-2.6); median TTNT1 was 3.2 years (2.9-3.5) vs 2.3 years (2.1-2.6) for patients who received first-line therapy in 2014-2017 compared to 2002-2005 (log rank p&amp;lt;0.0001) ( Figure A). In addition, there was a significant difference across KM curves for OS2 stratified by categories of years of second-line therapy, with median OS2 of 2.5 (2.0-3.2) in patients treated in 2014-2017 compared to median OS2 of 2.1 (1.7-2.5) in 2010-2013 ( Figure B). Discussion In this analysis, we observed improvements survival of MCL patients over time, along with similar improvements in outcomes following first-line therapy, which may correlate with increased BR and BTKi use as first-line agents. Unexpectedly, improvements in survival following first-line therapy were considerably more modest. Potential explanations include lack of data from recent years during which we expect continued increased utilization of oral therapies vs unique impact of repeated therapies in the elderly. Overall, these data support the need for ongoing development of first- and subsequent-line therapies in MCL.

Correlation of the Geriatric Assessment with Overall Survival in Older Patients with Cancer

AimsGlobal guidelines recommend that all older patients with cancer receiving chemotherapy should undergo a geriatric assessment. However, utilisation of the geriatric assessment is often constrained by its time-intensive nature, which limits its adoption in settings with limited resources and high demand. There is a lack of evidence correlating the results of the geriatric assessment with survival from the Indian subcontinent. Therefore, the aims of the present study were to assess the impact of the geriatric assessment on survival in older Indian patients with cancer and to identify the factors associated with survival in these older patients. Materials and methodsThis was an observational study, conducted in the geriatric oncology clinic of the Tata Memorial Hospital (Mumbai, India). Patients aged 60 years and older with cancer who underwent a geriatric assessment were enrolled. We assessed the non-oncological geriatric domains of function and falls, nutrition, comorbidities, cognition, psychology, social support and medications. Patients exhibiting impairment in two or more domains were classified as frail. ResultsBetween June 2018 and January 2022, we enrolled 897 patients. The median age was 69 (interquartile range 65–73) years. The common malignancies were lung (40.5%), oesophagus (31.9%) and genitourinary (12.1%); 54.6% had metastatic disease. Based on the results of the geriatric assessment, 767 (85.4%) patients were frail. The estimated median overall survival in fit patients was 24.3 (95% confidence interval 18.2–not reached) months, compared with 11.2 (10.1–12.8) months in frail patients (hazard ratio 0.54; 95% confidence interval 0.41–0.72, P < 0.001). This difference in overall survival remained significant after adjusting for age, sex, primary tumour and metastatic status (hazard ratio 0.56; 95% confidence interval 0.41–0.74, P < 0.001). In the patients with a performance status of 0 or 1 (n = 454), 365 (80.4%) were frail; the median overall survival in the performance status 0–1 group was 33.0 months (95% confidence interval 24.31–not reached) in the fit group versus 14.4 months (95% confidence interval 12.25–18.73) in the frail patients (hazard ratio 0.50; 95% confidence interval 0.34–0.74, P = 0.001). In the multivariate analysis, the geriatric assessment domains that were predictive of survival were function (hazard ratio 0.68; 95% confidence interval 0.52–0.88; P = 0.003), nutrition (hazard ratio 0.64; 95% confidence interval 0.48–0.85, P = 0.002) and cognition (hazard ratio 0.67; 95% confidence interval 0.49–0.91, P = 0.011). DiscussionThe geriatric assessment is a powerful prognostic tool for survival among older Indian patients with cancer. The geriatric assessment is prognostic even in the cohort of patients thought to be the fittest, i.e. performance status 0 and 1. Our study re-emphasises the critical importance of the geriatric assessment in all older patients planned for cancer-directed therapy.

Long-term impact of sarcopenia in older patients undergoing gastrectomy for gastric cancer: a systematic review and meta-analysis.

Sarcopenia is an inevitable problem in older patients. After gastrectomy, patients often have an inadequate dietary intake and easily fall into sarcopenia. However, the impact of preoperative sarcopenia on long-term outcomes after gastrectomy has not been analyzed. A systematic review was conducted for all relevant articles identified on PubMed, the Cochrane Library, Web of Science, and ClinicalTrials.gov until April 2023. Adjusted hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the fixed or random effects model according to the heterogeneity. The Newcastle-Ottawa Scale was used to quantify study quality. Seven studies involving 1,831 patients aged ≥65 years who underwent gastrectomy for gastric cancer were analyzed. Four hundred twelve patients (22.5%) were diagnosed with sarcopenia. The analysis showed that preoperative sarcopenia was significantly associated with poor overall survival (OS) (HR =1.93; 95% CI:1.60-2.34; P<0.001). Two of the included studies also showed that preoperative sarcopenia was significantly correlated with disease-related survival: one with disease-specific survival (DSS) (HR =4.00; 95% CI: 1.20-13.3, P=0.024) and the other with non-cancer specific survival (HR =3.27; 95% CI: 1.61-6.67; P=0.001). Furthermore, sarcopenic patients experienced more severe complications than non-sarcopenic patients (OR =1.80; 95% CI: 1.10-2.95; P=0.019). This meta-analysis suggested that preoperative sarcopenia is useful as a prognostic factor of impaired OS in older patients after gastrectomy. Preoperative evaluation and intervention for skeletal muscle loss should be considered. Further studies of sarcopenic impact on disease-related survival are required.

Outcome of Philadelphia chromosome-positive chronic myeloid leukemia in the United States since the introduction of imatinib therapy-The Surveillance, Epidemiology, and End Results database, 2000-2019.

Since the introduction of BCR::ABL1 tyrosine kinase inhibitors (TKIs) in 2000, the treatment of Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) has improved significantly. This study aimed to evaluate Ph-positive CML outcomes in the TKI therapy era, considering factors like age, ethnicity, and income. Using the Surveillance, Epidemiology, and End Results (SEER) database, 2857 patients with Ph-positive CML diagnosed from 2000 to 2019 were analyzed. The overall 5-year survival rates in Ph-positive CML increased to above 80%, compared with pre-TKIs historical data reporting 5-year overall survival (OS) rates of less than 50%. The 5-year OS rate was 73% for patients diagnosed in 2000-2004, 82% in 2005-2009, and 78% in 2010-2014; the 4-year OS rate was 83% in 2015-2019. The 5-year OS rate for younger patients (<60years old) was 88% in 2000-2009 and 90% in 2010-2019 (p value .426). In older patients (60+ years old), the 5-year OS rates were 64% and 65%, respectively (p value, .303). Lower household income was associated with inferior survival across the 2000-2019. These results are inferior to European studies where TKIs are universally available and affordable, and relative OS in CML is similar to age-matched normal populations. Although the outcome of Ph-positive CML has improved significantly since 2000, the SEER data still shows differences in outcomes among patient subsets, some anticipated (worse OS in older patients accounted by the relative OS), but others that suggest less than universal access and affordability of this therapy (among poorer patients) in the United States.

Influence of treatment intensity and medical comorbidities in older adults with peripheral T cell lymphoma

We conducted a population-based study of patients >65 years, diagnosed 2008-2017, with peripheral T-cell lymphoma (PTCL) using SEER-Medicare. Associations between PTCL subtype, treatment regimen, comorbidity, and mortality were assessed using the Kaplan-Meier method and multivariable Cox regression. Amongst the 2,546 patients, the median age was 77 years (interquartile range, 71–83). 5-year overall survival (OS) ranged from 22.2% to 37.3% depending on PTCL subtype. The most common frontline regimen was cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). 5-year OS rate was 47.0% for patients treated with etoposide + CHOP (N = 67; CHOEP), 33.7% for those treated with CHOP (N = 732), and 23.8% for patients treated with non-anthracycline-containing regimens (N = 105; p < 0.001). In patients without comorbidities, CHOEP remained independently associated with improved OS (HR 0.52, 95% CI,0.30-0.91). Median OS was 1.2 years from initiation of second-line therapy (N = 228) independent of treatment regimen. Frontline but not second-line treatment regimen is associated with OS in older patients with PTCL.

Abstract P3-05-36: Prognostic factors in non-metastatic hormone receptor-positive HER2-negative mucinous breast cancer: an international multicentre cohort study

Abstract Background: Mucinous carcinoma is the third most common histological subtype of breast cancer after ductal and lobular carcinomas, accounting for approximately 3% of invasive breast cancers. Although considered a favourable subtype with de-escalation of treatment recommended in the National Comprehensive Cancer Network guidelines, recurrence can occur and supporting data is limited. We thus examined prognostic factors of pure mucinous breast cancer (PMBC) in an international multicentre cohort study. Methods: Patients diagnosed between January 2000 to December 2015 with hormone receptor-positive HER2-negative stage I to III PMBC, invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) at 6 centers in Singapore, Taiwan, Korea and Japan were evaluated. Cox proportional hazards regression analyses were used to compare relapse-free survival (RFS), distant relapse-free survival (DRFS) and overall survival (OS) by histological subtypes, and to identify prognostic factors for PMBC. Results: Of 23,105 women eligible for analysis, 20,684 had IDC, 1,475 had ILC and 946 had PMBC. The median follow-up was 6.6 years; 5-year RFS, DRFS and OS for PMBC were 94.6%, 96.5% and 98.1% respectively. On multivariable cox regression analyses, PMBC demonstrated superior RFS (hazard ratio [HR] = 0.70, 95% CI: 0.56 - 0.88), DRFS (HR = 0.69, 95% CI: 0.53 - 0.89) and OS (HR = 0.70, 95% CI: 0.52 - 0.93) compared to IDC, while ILC had comparable survival outcomes as IDC. When restricted to only PMBC, significant independent prognostic factors for RFS included ethnicity (vs Chinese, “Others” [non-Chinese/Japanese/Korean, mainly Malay and Indian]: HR = 2.62, 95% CI 1.23 – 5.57), older age (vs &amp;lt; 40 years, &amp;gt;70 years: HR = 3.53, 95% CI 1.67 – 7.46), tumor size (vs T1, T3-4: HR = 2.79, 95% CI 1.45 – 5.37), positive lymph nodes (HR = 2.04, 95% CI: 1.10 – 3.77), use of radiotherapy (HR = 0.54, 95% CI 0.33 – 0.91) and endocrine therapy (HR = 0.31, 95% CI 0.12 – 0.77). On further analysis, the inferior RFS, DRFS and OS in older patients (&amp;gt;70 years) were driven largely by non-breast cancer deaths rather than relapses. Use of endocrine therapy was also associated with superior DRFS (HR = 0.26, 95% CI 0.09 – 0.73) but not OS. In a subgroup analysis, use of chemotherapy was associated with improved DRFS (HR = 0.25, 95% CI 0.08 – 0.82) and OS (HR = 0.07, 95% CI 0.01 – 0.37) with a trend in RFS (HR = 0.41, 95% CI 0.14 – 1.24) for lymph node-positive PMBC; no differences in outcomes were observed for the lymph node-negative subgroup. Conclusions: Larger tumor size, lymph node positivity and ethnicity were significant factors for RFS in PMBC. Use of endocrine therapy was associated with superior RFS and DRFS, while chemotherapy was associated with better DRFS and OS for lymph-node positive PMBC. Citation Format: Ryan Tan, Whee Sze Ong, Kyung-Hun Lee, Seri Park, Jabed Iqbal, Yeon Hee Park, Jeong-Eon Lee, Jong Han Yu, Ching-Hung Lin, Yen-Shen Lu, Makiko Ono, Takayuki Ueno, Yoichi Naito, Tatsuya Onishi, Geok hoon Lim, Su-Ming Tan, Han-Byoel Lee, Jiwon Koh, Han Suk Ryu, Wonshik Han, Veronique Kiak Mien Tan, Fuh-Yong Wong, Seock-Ah Im, Puay Hoon Tan, Yoon-Sim Yap. Prognostic factors in non-metastatic hormone receptor-positive HER2-negative mucinous breast cancer: an international multicentre cohort study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-36.

Enhanced Recovery Stem-Cell Transplantation: Multidisciplinary Efforts to Improve Outcomes in Older Adults Undergoing Hematopoietic Stem-Cell Transplant.

Older adults have unique risk factors for poor outcomes after hematopoietic stem-cell transplant (HSCT). We sought to determine the impact of our multidisciplinary supportive care program, Enhanced Recovery after stem-cell transplant (ER-SCT), on survival outcomes in patients age 65 years and older who underwent HSCT. In this retrospective study, clinicodemographic data, nonrelapse mortality (NRM), overall survival (OS), and relapse were compared between 64 patients age 65 years and older who underwent allogeneic stem-cell transplant during ER-SCT program's first year, October 2017 through September 2018, and 140 historical controls age 65 years and older who underwent allogeneic HSCT, January 2015 through September 2017. In the ER-SCT cohort, 41% (26 of 64) of patients were women, and the median (range) age was 68 (65-74) years; in the control cohort, 38% (53 of 140) of patients were women, and the median (range) age was 67 (65-79) years. Hematopoietic cell transplant comorbidity index and donor type/cell source were similar between cohorts. The ER-SCT cohort had a lower 1-year NRM rate (13% v 26%, P = .03) and higher 1-year OS rate (74% v 53%, P = .007). Relapse rate did not differ significantly between cohorts. In multivariate analyses, ER-SCT was associated with improved 1-year NRM (hazard ratio, 0.4; 95% CI, 0.2 to 0.9; P = .02) and improved 1-year OS (hazard ratio, 0.5; 95% CI, 0.3 to 0.9; P = .03). A multidisciplinary supportive care program may improve NRM and OS in older patients undergoing allogeneic HSCT. Randomized studies are warranted to confirm this benefit and explore which program components most contribute to the improved outcomes.

A new player in IDH1 mutated myeloid neoplasias

Acute myeloid leukaemia with mutated IDH1 is most frequently found in the European LeukemiaNet intermediate risk group. The incidence of IDH1 mutations increases with age, and older patients (aged >75 years) with IDH1-mutated acute myeloid leukaemia who are ineligible for intensive chemotherapy are highly sensitive to azacitidine combined with venetoclax.1 A randomised phase 3 trial2 showed that the IDH1 inhibitor ivosidenib combined with azacitidine significantly prolonged event-free survival and overall survival of older patients with IDH1 mutated acute myeloid leukaemia compared with placebo and azacitidine.

Hyperglycemia is associated with worse 3-year survival in older patients admitted to the intensive care unit after non-cardiac surgery: Post hoc analysis of a randomized trial.

Hyperglycemia is common in critically ill patients after surgery and is associated with worse perioperative outcomes. Yet, the impact of postoperative hyperglycemia on long-term outcomes remains unclear. We therefore analyzed the association between early postoperative hyperglycemia and 3-year overall survival in older patients who were admitted to the intensive care unit after surgery. This was a post hoc analysis of database obtained from a previous randomized trial and 3-year follow-up. The underlying trial enrolled 700 patients aged 65 years or older who were admitted to the intensive care unit after elective non-cardiac surgery. Early postoperative time-weighted average blood glucose was calculated and was divided into three levels, i.e., <8.0 mmol/L, from 8.0 to 10.0 mmol/L, and >10.0 mmol/L. The primary outcome was 3-year overall survival. The association between time-weighted average blood glucose level and 3-year overall survival was analyzed with Cox proportional hazard regression models. Subgroup analyses were also performed in patients with or without diabetes, and in patients following cancer or non-cancer surgery. A total of 677 patients (mean age 74 years, 60% male sex) were included in the final analysis. Within 3 years after surgery, deaths occurred in 22.1% (30/136) of patients with time-weighted average blood glucose <8.0 mmol/L, compared with 35.7% (81/227) of those from 8.0 to 10.0 mmol/L (unadjusted hazard ratio 1.75, 95% CI 1.15 to 2.67, P = 0.009), and 36.9% (116/314) of those >10.0 mmol/L (unadjusted hazard ratio 1.91, 95% CI 1.28 to 2.85, P = 0.002). After adjustment for confounding factors, the risk of 3-year mortality remained higher in patients with time-weighted average blood glucose from 8.0 to 10.0 mmol/L (adjusted hazard ratio 2.28, 95% CI 1.47 to 3.54, P < 0.001) and in those >10.0 mmol/L (adjusted hazard ratio 2.00, 95% CI 1.29 to 3.10, P = 0.002). Similar results were obtained in the subgroups of patients without diabetes and patients following cancer surgery. For older patients admitted to the intensive care unit after elective non-cardiac surgery, high early blood glucose (time-weighted average blood glucose ≥ 8.0 mmol/L) was associated with poor 3-year overall survival. The impact of moderate glycemic control on long-term survival deserves further investigation.

Are health outcomes in the older colorectal cancer patients treated by curative intent surgery any different to the younger patients?

Colorectal cancer poses a major burden. Its incidence increases with age and older patients with comorbidities have a higher likelihood of major complications. This study investigated the impact of age on health outcomes in colorectal cancer patients treated by surgery. A prospective database of all patients undergoing colorectal cancer surgery with curative intent between 2012 and 2017 was used to identify patients. A retrospective review of existing medical records investigating health-related outcomes in colorectal cancer patients undergoing surgery was performed. Primary outcomes measured were overall survival (OS) and disease-free survival (DFS). Difference in restricted mean survival times (RMST) up to a pre-specified time point of 24 months was used to compare four age groups. Six-hundred and fifty-one patients were divided into four age group categories: ≤65-years (n= 244), 66 to 75-years (n= 213), 76 to 85-years (n= 162) and >85-years (n= 32). Older patients were found to have a higher rate of post-operative medical complications (including confusion) (P= 0.001) and a longer length of stay (LOS) (P= 0.01). There was no difference between the 76 to 85-year age group and >85-year age group in OS and DFS. However, there was a reduced OS in older patients (>65) compared to their younger cohorts (<65) (P= 0.04). Older patients who undergo curative surgery have reduced OS, increased LOS and higher complication rates. Complex older patients may benefit from geriatric assessment and management in the peri-operative period.

Predicting Immunotherapy Outcomes in Older Patients with Solid Tumors Using the LIPI Score.

Simple SummaryThe Lung Immune Prognostic Index (LIPI) is a score that combines pretreatment dNLR (neutrophils/(leukocytes − neutrophils) and lactate dehydrogenase (LDH) and is correlated with outcomes in patients with non-small-cell lung cancer treated with anti PD-(L)1 but has not been validated in an older cohort of patients. LIPI is associated with poorer overall survival in older patients. LIPI is a simple and accessible worldwide tool that could serve as a prognostic factor and can be useful in identifying patients who will not benefit from such treatment.Immunotherapy with immune checkpoint blockers (ICB) represents a valid therapeutic option in older patients for several solid cancer types. However, most of the data concerning efficacy and adverse events of ICB available are derived from younger and fitter patients. Reliable biomarkers are needed to better select the population that will benefit from ICB especially in older patients who may be at a higher risk of developing immune-related adverse events (irAEs) with a greater impact on their quality of life. The Lung Immune Prognostic Index (LIPI) is a score that combines pretreatment dNLR (neutrophils/[leukocytes − neutrophils]) and lactate dehydrogenase (LDH) and is correlated with outcomes in patients treated with ICB in non-small-cell lung cancer. We aimed to assess the impact of LIPI in ICB outcomes in a dedicated cohort of older patients. The primary objective was to study the prognostic role of LIPI score in patients aged 70 years or above in a real-life population treated with anti-programmed death-(ligand)1 (anti PD-(L)1). dNLR and LDH were collected in a prospective cohort of patients aged 70 years or above treated with PD-(L)1 inhibitors with metastatic disease between June 2014 and October 2017 at Gustave Roussy. LIPI categorizes the population into three different prognostic groups: good (dNLR ≤ 3 and LDH ≤ ULN—upper normal limit), intermediate (dNLR > 3 or LDH > ULN), and poor (dNLR > 3 and LDH > ULN). Anti PD-(L)1 benefit was analyzed according to overall survival (OS), progression free survival (PFS), and overall response rate (ORR) using RECIST v1.1. criteria. In the 191 older patients treated, most of them (95%) were ICB-naïve, and 160 (84%) had an ECOG performance status of 0–1 with a median age at ICB treatment of 77 (range, 70–93). The most common tumor types were melanoma (66%) and non-small-cell lung cancer (15%). The median follow-up duration was 18.8 months (95% CI 14.7–24.2). LIPI classified the population into three different groups: 38 (23%) patients had a good LIPI score, 84 (51%) had an intermediate LIPI score, and 43 (26%) had a poor LIPI score. The median OS was 20.7 months [95% CI, 12.6–not reached] compared to 11.2 months [95% CI, 8.41–22.2] and 4.7 months [95% CI, 2.2–11.3] in patients with a good, intermediate, and poor LIPI score, respectively (p = 0.0003). The median PFS was 9.2 months [95% CI, 6.2–18.1] in the good LIPI group, 7.2 months [95% CI, 5.4–13] in the intermediate LIPI group, and 3.9 months [95% CI, 2.3–8.2] in the poor LIPI group (p = 0.09). The rate of early death (OS < 3 months) was 37% in the poor LIPI group compared to 5% in the good LIPI group (<0.001). Poor LIPI score was associated with a poorer outcome in older patients treated with anti PD-(L)1. LIPI is a simple and accessible worldwide tool that can serve as a prognostic factor and can be useful for stratification benefit from ICB.

Evaluating prognostic significance of preoperative C-reactive protein to albumin ratio in older patients with pathological stage II or III colorectal cancer.

This study was performed to evaluate the prognostic value of preoperative C-reactive protein to albumin ratio (CAR) in older patients with colorectal cancer (CRC) undergoing curative resection. We retrospectively analyzed 244 older patients (aged 75 years or higher) with pathological stage II or III CRC who underwent curative surgery between 2008 and 2016. The optimal value of CAR was calculated and its correlation with the clinicopathological factors and prognosis was examined. The optimal cutoff value of the CAR was 0.085. High preoperative CAR was significantly associated with high carcinoembryonic antigen levels (P=0.001), larger tumor size (P<0.001), and pT factor (P=0.001). On multivariate analysis, high CAR was independent prognostic factor for relapse-free survival (P=0.042) and overall survival (P=0.001). Preoperative elevated CAR could be considered as an adverse predictor of both relapse-free survival and overall survival in older patients with CRC undergoing curative surgery.

The elderly prognostic index predicts early mortality in older patients with diffuse large B-cell lymphoma. An ad hoc analysis of the elderly project by the Fondazione Italiana Linfomi.

The Elderly Prognostic Index (EPI) is based on the integration of a simplified geriatric assessment, hemoglobin levels and International Prognostic Index and has been validated to predict overall survival in older patients with diffuse large B-cell lymphoma (DLBCL). In this study, we evaluated the ability of EPI to predict the risk of early mortality. This study included all patients registered in the Elderly Project for whom treatment details and a minimum follow-up of 3months were available. Three main treatment groups were identified based on the anthracycline amount administered: cases receiving >70% of the theoretical anthracyclines dose (Full Dose [FD] group), ≤70% (Reduced Dose [RD]) and palliative therapy (PT; no anthracyclines). The primary endpoint was early mortality rate, defined as death for any cause occurring within 90days from diagnosis. We identified 1150 patients with a median age of 76years (range 65-94). Overall, 69 early deaths were observed, accounting for 19% of all reported deaths. The cumulative rate of early mortality at 90days was 6.0%. Comparing early with delayed deaths, we observed a lower frequency of deaths due to lymphoma progression (42% vs. 75%; p<0.001) and a higher frequency due to toxicity and infections (22% vs. 4%, p<0.001, and 22% vs. 3%, p<0.001, respectively) for early events. A multivariable logistic analysis on 931 patients (excluding PT) confirmed an independent association of high-risk EPI (odds ratio [OR] 3.60; 95% confidence interval [CI] 1.15-11.2) and bulky disease (OR 2.08; 95% CI 1.09-3.97) with the risk of early mortality. The cumulative incidence of early mortality for older patients with DLBCL is not negligible and is mainly associated with non-lymphoma related events. For patients receiving anthracyclines, high-risk EPI and bulky disease are associated with a higher probability of early mortality.

Cancer-specific and net overall survival in older patients with de novo metastatic prostate cancer initially treated with androgen deprivation therapy.

This study aimed to assess survival outcomes in older patients with de novo metastatic prostate cancer who initially received androgen deprivation therapy. The retrospective multicenter study included 2784 men with metastatic prostate cancer who were treated with androgen deprivation therapy between 2008 and 2017. Patients were classified into <75, 75-79, and ≥80 age groups. Propensity score matching was conducted to assess the cancer-specific survival of the groups. The 5-year net overall survival of each group was derived to evaluate relative survival compared with the general population using the Pohar-Perme estimator and the 2019 Japan Life Table. During the follow-up (median, 34 months), 1014 patients died, of which 807 died from metastatic prostate cancer progression. Compared with the <75 group, the cancer-specific survival of the 75-79 group was similar (hazard ratio 1.07; 95% confidence interval 0.84-1.37; P = 0.580), whereas that of the ≥80 group was significantly worse (hazard ratio 1.41; 95% confidence interval 1.10-1.80; P = 0.006). The 5-year net overall survival of the <75, 75-79, and ≥80 age groups were 0.678, 0761, and 0.718, respectively. The 5-year net overall survival of patients aged ≥80 years with low- and high-volume disease were 0.893 and 0.586, respectively, which was comparable with those in patients aged <75 years (0.872 and 0.586, respectively). Older metastatic prostate cancer patients aged ≥80 years had poorer cancer-specific survival compared with younger patients. Conversely, 5-year net overall survival in older patients aged ≥80 years was comparable with that in younger patients aged <75 years.