Elderly Non-small Cell Lung Cancer Patients Research Articles

Prognostic Value of Sarcopenia in Elderly Patients with Metastatic Non-Small-Cell Lung Cancer Undergoing Radiotherapy

Background: Sarcopenia, a syndrome characterized by age-related loss of muscle mass and function, lacks universally accepted diagnostic criteria, particularly for its role as a prognostic factor in elderly patients with non-small-cell lung cancer (NSCLC). This study aimed to evaluate the prognostic significance of sarcopenia, assessed by psoas muscle size on baseline CT scans, in patients over 70 years of age with metastatic NSCLC. Methods: We retrospectively analyzed 85 elderly patients undergoing palliative radiation therapy between August 2022 and July 2024. Using morphometric analysis of psoas size, we investigated its correlation with overall survival (OS) and progression-free survival (PFS). Results: Our results showed that decreased psoas size was significantly associated with shorter OS and PFS, with median OS of 10 months and PFS of 4 months in sarcopenic patients compared to longer survival times in non-sarcopenic patients. Median survival of non-sarcopenic vs. sarcopenic patients was 21 ± 7 months (muscle area > median) versus 5 ± 2.3 months (muscle area < median). Multivariate analysis confirmed that psoas size, along with ECOG performance status and treatment of primary NSCLC, was a significant predictor of survival. Discussion: These findings suggest that psoas muscle size is a valuable prognostic marker for elderly NSCLC patients, potentially guiding treatment decisions and patient management. Further research is needed to validate these results and refine prognostic models for this population.

Optimizing lung cancer surgery in the elderly: sublobar resection versus lobectomy for early-stage non-small cell lung cancer patients aged 80 and above

The optimal surgical approach for elderly patients with early-stage non-small cell lung cancer (NSCLC) remains a topic of debate. A retrospective analysis was conducted on patients who underwent pulmonary resection for early-stage NSCLC at our single institution between January 2018 and December 2022. Propensity score matching was used to balance baseline characteristics between the sublobar resection and lobectomy groups. Perioperative outcomes, pulmonary function recovery, postoperative quality of life, and survival were compared between the two groups. A total of 151 patients were included, with 42 undergoing sublobar resection and 109 undergoing lobectomy. After propensity score matching, baseline characteristics were well-balanced between the two groups. Sublobar resection was associated with shorter operative time (125.83 ± 33.56 min vs. 161.14 ± 61.54 min, p = 0.048), less intraoperative blood loss [65 (30, 75) ml vs. 120 (70, 170) ml, p < 0.001], shorter drainage duration [3 (2, 5) days vs. 5 (3, 6) days, p < 0.001], shorter hospital stay [6 (4, 8) days vs. 10 (7, 13) days, p < 0.001], and fewer postoperative complications (11.9% vs. 47.6%, p < 0.001), compared to lobectomy. Moreover, sublobar resection led to better pulmonary function recovery and higher postoperative quality of life scores, with no significant difference in overall and disease-free survival between the groups. Sublobar resection in patients aged 80 and above with early-stage NSCLC offered comparable oncological outcomes to lobectomy while preserving more lung function and providing better postoperative recovery and long-term quality of life. These findings have important implications for treatment decision-making in elderly NSCLC patients.

Efficacy and Tolerance of First-Line Afatinib in Elderly NSCLC Patients with EGFR Mutations in Vietnam: A Multicenter Real-World Study.

Afatinib, a second-generation epidermal growth factor receptor(EGFR) tyrosine kinase, has proven effective for non-small-cell lung cancer (NSCLC) patients with EGFR mutations through randomized controlled trials and real-world studies. Elderly patients exhibit unique characteristics in terms of physical condition and comorbidities, leading to differences in clinical practice for selecting the initial dosage and making dose adjustments compared to younger patients. This study aims to evaluate the effectiveness and adverse effects of first-line Afatinib treatment in elderly patients with NSCLC harboring EGFR mutations in Vietnam in a real-world context. We conducted a retrospective analysis of 135 patients, aged 65 years and older, across nine cancer centers in Vietnam. These patients, who harbored drug-sensitive EGFR mutations (excluding de novo T790M), received first-line Afatinib treatment between April 2018 and June 2022. The primary endpoints, time to treatment failure (TTF), and overall survival (OS) were assessed using the Kaplan-Meier method, and comparisons were conducted using the log-rank test. Secondary endpoints included the overall response rate (ORR) according to RECIST 1.1 and adverse effects as classified by CTCAE 4.0. The median age was 71.2 years (SD ± 5.3). Comorbidities included cardiovascular disease (20.7%), diabetes (5.2%), chronic obstructive pulmonary disease (2.2%), and hepatitis B (0.7%). Common mutations constituted 71.9% of cases, with uncommon mutations representing 28.1%. Brain metastases were observed in 24.4% of patients. Initial treatment doses were 40 mg for 35.6% of patients and 30 mg for 62.2%. With a median follow-up of 34.3 months, the median TTF was 16.3 months (95% CI: 15.4-19.5), and the median OS was 32.9 months (95% CI: 28.9-37.5). Factors associated with decreased OS included poor performance status, current smoking, and the presence of uncommon mutations. The ORR was 77.8%, with a complete response of 11.1% and a disease control rate of 94.1%. The most common toxicities were dermatologic and mucosal, including diarrhea (55.6%), rash (48.9%), and stomatitis (40.7%), predominantly in grades 1 and 2. Initiating treatment at doses below 40 mg significantly reduced most toxicities compared to the 40 mg dose. The presence of brain metastases did not significantly affect ORR, TTF, or OS. Starting treatment at doses below 40 mg significantly lowered the response rate but did not impact TTF or OS. First-line treatment with Afatinib in elderly patients with NSCLC and EGFR mutations demonstrates significant efficacy and manageable toxicity in a Vietnamese multicenter real-life setting. The effectiveness of Afatinib was confirmed, with known and well-controlled adverse effects, supporting its use in this patient population.

Extended 73-month survival in an elderly patient with BRAF V600E-mutated lung adenocarcinoma: A case report.

BRAF is a mediator that activates the mitogen-activated protein kinase pathway. A mutation in BRAF can cause abnormal pathway activation, leading to cell proliferation. In a Phase II study, the combination therapy of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib was found to be effective in non-small cell lung cancer (NSCLC) patients with the BRAF mutation. However, this study has limited efficacy and safety data for elderly patients. We present a case of a patient who started treatment at 87 years old and showed a good prognosis, remaining alive 73 months from the start of treatment with no significant adverse events. The patient also maintained a partial response (PR) according to RECIST 1.1 at the last follow-up. This case suggests that the dabrafenib and trametinib combination therapy is safe and effective for elderly NSCLC patients with the BRAF mutation.

The Geriatric Nutritional Risk Index as a prognostic factor in patients treated with immune checkpoint inhibitors with non-small-cell lung cancer.

Globally, non-small cell lung cancer (NSCLC) is a leading factor in cancer-related mortality. Additionally, the Geriatric Nutritional Risk Index (GNRI) has been assessed as a predictive and prognostic indicator in various types of carcinomas. Our study aims to assess the prognostic importance of GNRI computed at diagnosis in NSCLC patients receiving immune checkpoint inhibitors (ICIs). The study evaluated 148 patients who underwent immunotherapy for NSCLC from January 1, 2018, through December 31, 2021, retrospectively. Patients combined with other malignant tumors or severe comorbidities were excluded from the study. The receiver operating characteristic (ROC) curve was employed in regulating the ideal cutoff worth of GNRI. Survival outcomes were evaluated through Kaplan-Meier analysis. Following this, both univariate and multivariate analyses were conducted utilizing Cox regression analysis to identify any potential factors that may influence the survival outcomes. The cutoff point for GNRI was 108.15 [area under the curve (AUC) =0.575, P=0.048]. Further analysis using the Kaplan-Meier method demonstrated that individuals in the high GNRI group had significantly longer progression-free survival (PFS) and overall survival (OS) compared to those in the low GNRI group (P=0.02, P=0.01). The further stratified study showed that GNRI had greater predictive value in tumor node metastasis (TNM) stage II-III and elderly (age ≥65 years) NSCLC patients undergoing ICI therapy. The multivariate Cox regression analysis indicated that GNRI [hazard ratio (HR): 0.536, P=0.03], obesity (HR: 16.283, P<0.001), and surgical history (HR: 0.305, P<0.001) were associated with poorer survival rates. Among patients undergoing ICI therapy for NSCLC, GNRI is an effective independent prognostic indicator, and a high GNRI at diagnosis is substantially related with longer PFS and OS. The incorporation of GNRI in pre-treatment evaluations within clinical settings is beneficial.

Upfront Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy in Elderly Patients with Brain Metastases from Non-small cell lung cancer: A Retrospective Analysis of a 10-Year Bi-Institutional Experience.

Stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) are increasingly used as initial therapies for brain metastases (BM). We aimed to assess the outcomes of SRS/FSRT in patients aged ≥65 years who had 1-10 BM from non-small cell lung cancer (NSCLC). We retrospectively reviewed 91 elderly NSCLC patients with 222 BM who were treated with SRS/FSRT at two institutions between 2010 and 2020. The primary endpoint was overall survival (OS) after SRS/FSRT. In addition, in-field local control (IFLC) within the treated field was evaluated. Statistical analysis was performed to identify the prognostic factors affecting OS and IFLC. During a median follow-up of 18 months, the median OS was 32 months. The 1- and 2-year survival rates were 69.8 and 56.1%, respectively. In multivariate analysis, the NSCLC-specific graded prognostic assessment (GPA) score (p=0.007) and administration of systemic therapy (p=0.039) were defined as prognosticators affecting OS. The median IFLC period was 31 months, and the 1- and 2-year IFLC rates were 75.9 and 57.6%, respectively. The total BM volume (p=0.042) significantly affected IFLC. No severe adverse events were reported after SRS/FSRT. SRS/FSRT is an effective upfront treatment option for BM arising from NSCLC in elderly patients, with a good OS without severe side effects. Higher GPA score and active systemic treatment were associated with improved OS, indicating that elderly patients are significant candidates for SRS/FSRT.

Early Changes in Nutritional Status of Elderly Patients with Lung Cancer Undergoing Chemotherapy Are Positively Related with Symptoms of Depression: A Prospective Follow-Up Study

This study aims to assess early effects of chemotherapy on symptom alleviation, nutritional status, and mental health in elderly patients with advanced non-small-cell lung cancer (NSCLC). This prospective study included 45 NSCLC patients (32 males, 13 females) aged 65–82 years (mean age 70.0 ± 4.5 years) with good performance status. Assessments were conducted immediately after diagnosis and after two chemotherapy cycles, focusing on nutritional status (assessed with MNA questionnaire), quality of life (QoL, based on FACT-L and FACT-TOI questionnaires), lung cancer-related symptoms (based on LCSS), and mental health (based on PHQ-9 questionnaire). Despite significant alleviation of symptoms like cough, dyspnea, and body weight loss, there was no significant correlation between changes in symptoms burden and changes in nutritional status (r 2 = 0.122, P = 0.427), and change of patients’ mental condition (r 2 = –0.141, P = 0.255). No significant QoL changes were noted, but a decrease in severe depression frequency was observed. The improvement of patients’ mental condition was related strictly to the improvement of nutritional status (r 2 = -0.589, P < 0.001). The study highlights the vital link between nutritional status and mental health in elderly NSCLC patients, emphasizing the need for integrated care approaches that address both aspects to enhance treatment effectiveness and patient well-being.

Benefits of adjuvant chemotherapy in elderly patients with stage IB-IIIB non-small cell lung cancer: a propensity-matched analysis.

Adjuvant chemotherapy (ACT) is a well-recognized and well-established treatment for surgically resected non-small cell lung cancer (NSCLC), but its suitability for elderly patients remains controversial. Further investigation is warranted to guide ACT decisions in this demographic. We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on patients aged 70 years or older who underwent surgical resection for stage IB, II, or III NSCLC as per the 7th edition of the American Joint Committee on Cancer staging system (AJCC 7th edition). Propensity score matching (PSM), Kaplan-Meier analysis, and Cox regression were employed for statistical analyses. There were 503 participants received ACT in this study of 2,000 patients aged 70 or older with stage IB-IIIB NSCLC who underwent surgical resection without preoperative chemotherapy. Overall, ACT did not significantly correlate with extended overall survival (OS) (P=0.07) compared to non-ACT. After 2:1 PSM, the matched cohort comprised 317 non-ACT and 206 ACT recipients. Post-PSM, the ACT group exhibited improved OS (P=0.044) compared to the non-ACT group. Cox regression analysis identified gender, primary tumor site, histologic grade, N stage, and ACT as independent predictors of OS (P<0.05). Subgroup analysis indicated amplified ACT benefits in individuals aged 70-79 years, male, with N1 stage, or those without radiotherapy. ACT may confer benefits to elderly stage IB-IIIB NSCLC patients, particularly those aged 70-79 years, male, and with N1 stage.

Investigation of age and smoking in NSCLC patients with uncommon EGFR mutations.

In addition to the two common epidermal growth factor receptor (EGFR) mutations, there are many uncommon mutations. Due to the high number of uncommon types, as well as the rarity of patients, there is lack of information regarding patient demographics, especially age distribution and smoking status. Against this background, we conducted an analysis to clarify the background of patients with uncommon EGFR mutations, especially considering their age distribution and smoking status. We retrospectively reviewed the medical records of non-small cell lung cancer (NSCLC) patients diagnosed in a multicenter clinical practice from 2002 to 2023. Patients included all cases of non-advanced and advanced NSCLC with uncommon EGFR mutations. Information on 158 patients with uncommon EGFR mutation was collected. Median age was 72 years, with the age distribution showing that most patients were in their 70s. There was a significant difference between the proportion of patients aged up to 59 years and the proportion aged 75 years or older. In 88 patients with a smoking habit history, a significant correlation was found between smoking index and age. Among non-smokers, there was a peak between ages 70 and 74, which was older than the peak among smokers. Even in elderly patients and NSCLC patients with a history of smoking, although it is unclear whether EGFR mutation is common or uncommon, EGFR gene testing should be performed considering the possibility of these patients being EGFR-positive.

Current Status and Prospect of PD-1/PD-L1 Immune Checkpoint Inhibitor Therapy in Elderly Patients with Advanced NSCLC

The incidence of cancer is closely correlated with age, as 75% of non-small cell lung cancer (NSCLC) patients are aged at least 65 years. The availability of immune checkpoint inhibitors (ICIs) has altered the available NSCLC therapeutic pattern. Limited studies on elderly patients have demonstrated that ICIs as monotherapy provide substantial benefits for patients aged 65-75 years, showing no significant difference compared to younger patients. This benefit is also observed in combination with immune-combined chemotherapy or radiotherapy. For individuals older than 75 years, the survival effect was not evident, though. Immune-related adverse events (irAEs) with ICIs alone were similar in incidence across age categories. Immune-combination chemotherapy resulted in a higher incidence of irAEs than chemotherapy alone, and patients ≥75 years of age were more likely to experience higher-grade irAEs. Besides the fact that immunosenescence in older patients influences the immune milieu in a multifaceted manner, which in turn impacts the effectiveness of immunotherapy, the prognosis is also influenced by the Eastern Cooperative Oncology Group performance status (ECOG PS) score, among other factors. For certain individuals aged ≥75 years or in poor physical health, immunotherapy combined with low-intensity chemotherapy has emerged as a viable treatment option. However, there are fewer related studies, so there should be a conscious effort to increase the number of elderly patients enrolled in the trial and a comprehensive assessment to explore individualized treatment options. To provide additional references and guidance for immunotherapy in elderly NSCLC patients and to propose new therapeutic perspectives in combination with their characteristics, this review aims to summarize and analyze the pertinent studies on the application of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors in these patients. .

Enhanced recovery after surgery in elderly patients with non-small cell lung cancer who underwent video-assisted thoracic surgery

BACKGROUND This study was designed to investigate the clinical outcomes of enhanced recovery after surgery (ERAS) in the perioperative period in elderly patients with non-small cell lung cancer (NSCLC). AIM To investigate the potential enhancement of video-assisted thoracic surgery (VATS) in postoperative recovery in elderly patients with NSCLC. METHODS We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS (the ERAS group) and 327 elderly NSCLC patients who received routine care (the control group) after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017. After propensity score matching of baseline data, we analysed the postoperative stay, total hospital expenses, postoperative 48-h pain score, and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection. RESULTS After propensity score matching, ERAS significantly reduced the postoperative hospital stay (6.96 ± 4.16 vs 8.48 ± 4.18 d, P = 0.001) and total hospital expenses (48875.27 ± 18437.5 vs 55497.64 ± 21168.63 CNY, P = 0.014) and improved the satisfaction score (79.8 ± 7.55 vs 77.35 ± 7.72, P = 0.029) relative to those for routine care. No significant between-group difference was observed in postoperative 48-h pain score (4.68 ± 1.69 vs 5.28 ± 2.1, P = 0.090) or postoperative complication rate (21.2% vs 27.1%, P = 0.371). Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection. CONCLUSION ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.

Abstract 3729: Association between clinical characteristics and treatment outcome of immune checkpoint inhibitor with or without chemotherapy in elderly non-small cell lung cancer patients with high PD-L1 expression

Abstract Background and Aim: The proportion of elderly patients diagnosed with advanced stage lung cancer has been increasing owing to the aging of the population. Thus, formulating a treatment strategy for elderly non-small cell lung cancer (NSCLC) patients is essential. For NSCLC with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≧ 50%, both immune checkpoint inhibitor monotherapy (ICI mono) and combination therapy of ICI and chemotherapy (ICI/Chemo) have been established as standard treatment options. However, evidence based on the clinical trials specifically for elderly patients is limited, and it is not clear whether ICI mono or ICI/Chemo should be used in elderly NSCLC patients with PD-L1 TPS ≧ 50%. This study aimed to clarify which clinical population will benefit from ICI/Chemo in elderly NSCLC patients with PD-L1 TPS ≧ 50%. Method: We retrospectively analyzed 199 NSCLC patients aged ≧ 70 years of Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 with PD-L1 TPS ≧ 50% who were treated with ICI mono or ICI/Chemo. We analyzed the association between treatment outcome and baseline patient characteristics in each group. Comparing the treatment outcome, propensity score matching was used to reduce bias. Results: Of the 199 patients, 131 received ICI mono, and 68 received ICI/Chemo. The median overall survival (OS; 25.0 vs. 42.2 months, P = 0.116) and median progression-free survival (PFS; 10.9 vs. 11.8 months, P = 0.231) did not significantly differ between the ICI mono and ICI/Chemo groups. Multivariate analysis revealed the factors independently associated with OS: smoking history in the ICI mono group (smoking history/non-smoking history, hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.16-0.78, P = 0.048), and ECOG PS (ECOG PS 1/PS 0, HR 3.84, 95% CI 1.44-10.20, P = 0.007) and histology type in the ICI/Chemo group (Non-squamous cell carcinoma/squamous cell carcinoma, HR 0.17, 95% CI 0.06-0.44, P &amp;lt; 0.001). For patients with ECOG PS 0 (OS: 26.1 months vs. not reached, P = 0.0031, PFS: 6.5 vs. 21.7 months, P = 0.0436) or non-squamous cell carcinoma (OS: 23.8 months vs. not reached, P = 0.0038, PFS: 10.9 vs. 17.3 months, P = 0.0383) in the ICI/Chemo group, PFS and OS were significantly longer than in the ICI mono group. Discussion and Conclusion: In elderly NSCLC patients with high PD-L1 expression, this study suggested that ECOG PS and histological type may be predictive clinical factor when choosing ICI mono or ICI/Chemo treatment. Citation Format: Hayato Kawachi, Shota Takei, Tadaaki Yamada, Motohiro Tamiya, Yoshiki Negi, Yasuhiro Goto, Akira Nakao, Shinsuke Shiotsu, Takayuki Takeda, Asuka Okada, Taishi Harada, Koji Date, Yusuke Chihara, Isao Hasegawa, Nobuyo Tamiya, Takashi Kijima, Koichi Takayama. Association between clinical characteristics and treatment outcome of immune checkpoint inhibitor with or without chemotherapy in elderly non-small cell lung cancer patients with high PD-L1 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3729.

Effectiveness of Roy Adaptation Model-Based Cognitive Stimulation Therapy in Elderly Patients with Non-Small Cell Lung Cancer Undergoing Curative Resection.

This study aimed to investigate the effects of a Roy adaptation model (RAM)-based cognitive stimulation therapy (CST) intervention on elderly patients diagnosed with primary non-small cell lung cancer (NSCLC) undergoing curative resection. A total of 280 patients diagnosed with primary NSCLC were randomized into RAM-based CST group and control group. Outcomes were assessed at three intervals: pre-surgery, discharge, and one-month post-discharge. Cognitive function was evaluated using Mini-Cognitive test. Postoperative delirium prevalence was determined within 48 hours post-surgery using Nursing Delirium Screening Scale. The Hospital Anxiety and Depression Scale evaluated anxiety and depression symptoms, while Quality of Life (QoL) was assessed via Short Form-36 (SF36) Health Survey. The RAM-based CST group demonstrated significantly higher Mini-Cog test scores than the control group upon discharge and post-intervention. Patients with RAM-based CST exhibited a decrease in postoperative delirium compared to the control group. The RAM-based CST intervention yielded an improvement in anxiety and depression at discharge and 1-month post-discharge compared to preoperative levels. Additionally, the RAM-based CST group exhibited substantial enhancements in SF36 subcategory scores at 1-month post-discharge compared to pre-surgery. At post-intervention, the RAM-based CST group demonstrated significantly higher scores than the control group across various health-related domains, including role limitations due to emotional problems, mental health, general health perception, bodily pain, and role limitations due to physical problems. The RAM-based CST intervention in elderly NSCLC patients undergoing curative resection yielded significant enhancements in cognitive function, reduced delirium incidence, improved emotional well-being, and better QoL postoperatively.

Risk factors influencing chemotherapy compliance and survival of elderly patients with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) has high degree of malignance and proneness to recurrence and metastasis. The aim of this study was to analyse the risk factors influencing the chemotherapy compliance and survival status of elderly NSCLC patients. The clinical data of 110 patients admitted from January 2014 to March 2018 were retrospectively analysed. They were assigned to non-chemotherapy (n=25), partial chemotherapy (n=30) and complete chemotherapy (n=55) groups according to chemotherapy compliance, and followed up until March 2021. Their clinicopathological characteristics were investigated by univariate analysis and then multivariate Cox regression analysis. The survival rates were compared by Kaplan-Meier survival curve and log-rank test. Among the 110 NSCLC patients, 25 did not receive chemotherapy, 30 underwent partial chemotherapy and 55 received complete chemotherapy. Educational level, pathological tumor-node-metastasis (TNM) stage, pathological type, surgical approach, place of residence, payment mode and chemotherapy stage were independent risk factors influencing the chemotherapy compliance (P<0.05). Particular attention should be paid to improving the chemotherapy compliance of patients with low educational level, late TNM stage, medical history of squamous cell carcinoma, history of thoracotomy, living in rural areas and no medical insurance, and those in the recurrence period or consolidation period of chemotherapy.

Efficacy and safety analysis of immune checkpoint inhibitors plus angiogenesis inhibitors for treatment of advanced driver-negative NSCLC in elderly patients: A retrospective study.

e21044 Background: Immune checkpoint inhibitors (ICIs) combined with antiangiogenic drugs may have synergistic effects in elderly patients with advanced driver-gene wild-type non-small cell lung cancer (NSCLC), but its true efficacy remains unclear. In addition, the chemotherapy tolerance of elderly NSCLC patients is poor, and the precise identification of the population who can benefit from ICIs combined with angiogenesis inhibitors is also the focus of current research. Methods: We retrospectively compared the clinical efficacy and safety of ICIs combined with or without antiangiogenic agents in elderly patients with advanced driver-gene negative NSCLC who were ≥65 years old in the Cancer Center of the Affiliated Suzhou Hospital of Nanjing Medical University. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR), and immune-related adverse events (irAEs). Results: A total of 36 patients in the IA group（Immune checkpoint inhibitors plus angiogenesis inhibitors group) and 43 patients in the NIA group（Immune checkpoint inhibitors without angiogenesis inhibitors group) were enrolled in the study between January 1, 2019 and December 31, 2021. The median follow-up time for patients in IA group and NIA group was 18.2 months (95%CI: 14 - 22.5 months) and 21.4 months (95%CI: 16.7 -26.1 months), respectively. The median PFS and median OS were longer in the IA group compared to the NIA group（8.1 months vs 5.3 months；HR for PFS: 0.778, 95%CI: 0.474-1.276, P = 0.32; NA vs 30.9 months; HR for OS: 0.795, 95%CI: 0.396-1.595, P = 0.519). Subgroup analysis showed that patients in the IA group had significantly longer PFS in the subgroup with PD-L1 expression ≥50% (P = 0.017), and the relationship between treatment regimens and outcomes was still discrepant in different PD-L1 expression levels (P for interaction = 0.002). There was no significant difference in ORR between the two groups (23.3% vs 30.5%, P = 0.465). The incidence of adverse events in IA group was lower than that in NIA group (39.5% vs 19.4%, P = 0.05), and the cumulative incidence of treatment interruptions due to adverse events was significantly reduced (P = 0.045). Conclusions: In elderly patients with advanced driver-gene wild-type NSCLC, the addition of antiangiogenic agents to ICIs therapy did not provide significant clinical benefit, but the incidence of treatment interruptions due to adverse events was significantly reduced. In the subgroup analysis, we found that the clinical benefit of this combination therapy was observed in patients with PD-L1 expression ≥50%, which warrants further exploration. Clinical trial information: NCT05688046 .

Real‐world data on the efficacy and safety of immune‐checkpoint inhibitors in elderly patients with non‐small cell lung cancer

Immune-checkpoint inhibitors (ICIs) are effective against advanced non-small cell lung cancer (NSCLC). However, whether the efficacy and safety of ICI treatment in elderly patients are similar to those in younger patients is unclear. This study was designed to address this question. We enrolled patients who received ICI monotherapy in Japan between December 2015 and December 2017; those ≥75 years of age comprised the elderly group. We compared the efficacy and safety of ICI monotherapy in elderly patients with those in younger patients and explored prognostic factors in elderly patients. We enrolled 676 patients; 137 (20.3%) were assigned to the elderly group. The median age of the elderly and younger groups was 78 (range, 75-85) and 66 (range, 34-74) years. The median progression-free survival (4.8 months vs. 3.3 months, p = 0.1589) and median overall survival (12.3 months vs. 13.0 months, p = 0.5587) were similar between the elderly and younger groups. Multivariate analysis revealed that a significantly better OS in the elderly group was associated with better responses to first- or second-line ICI treatment (p = 0.011) and more immune-related adverse events (irAEs) (p = 0.02). IrAEs that led to ICI discontinuation occurred in 34 of 137 patients (24.8%) in the elderly group, and their survival was significantly higher than that in those who did not have irAEs. ICI is also effective in elderly NSCLC patients, and treatment discontinuation due to irAEs may be a good prognostic marker.

Evaluating the potential of immunotherapy and chemoimmunotherapy in the treatment of elderly non-small cell lung cancer patients: A real-world study

BackgroundImmune checkpoint inhibitor (ICI) has become the standard therapy for metastatic non-small cell lung cancer (NSCLC) patients. However, no robust evidence on the efficacy and safety of ICI in elderly NSCLC patients has been established. Materials and MethodsThis retrospective study aimed to assess the efficacy and safety of ICI in elderly NSCLC patients. NSCLC patients treated with ICI monotherapy or chemoimmunotherapy (CIT) between 2016 and 2022 were divided into two cohorts according to the age: the Elderly cohort (patients aged ≥ 75 years) and the Nonelderly cohort (patients aged < 75 years). The progression-free survival (PFS), tumor response, and frequency of immune-related adverse events (irAEs) were compared between the two cohorts. ResultsA total of 111 NSCLC patients were included in this study (41 patients in the Elderly cohort and 70 patients in the Nonelderly cohort). The PFS (5.6 months vs. 6.3 months, P = 0.98), response rate (36.6% vs. 44.9%, P = 0.51), and disease control rate (80.5% vs. 76.8%, P = 0.83) were not significantly different between the two cohorts. In a subgroup analysis, stratified according to PD-L1 expression (low vs. high) and ICI treatment mode (ICI monotherapy vs. CIT), the PFSs of both cohorts were also not significantly different, regardless of PD-L1 expression. Moreover, the frequency of irAEs did not significantly differ between elderly and nonelderly NSCLC patients (21/41 [51.2%] vs. 38/70 [54.3%], P = 0.91). ConclusionThe efficacy and safety of ICI in elderly NSCLC patients were not inferior to those in younger patients.

Razlika serumskih tumorskih markera u različitim kliničkim stadijumima starijih pacijenata sa nesitnoćelijskim karcinomom pluća i procena dijagnostičke vrednosti

Background: To explore the difference and diagnostic value evaluation of serum tumor markers in different clinical stages of elderly non-small cell lung cancer (NSCLC) patients. Methods: Select 100 elderly NSCLC patients admitted to our hospital from June 2018 to June 2021, collect the general data, pathology data and imaging data of the patients, and the patients were divided into I-IV clinical stages according to the International Union Against Cancer (UICC) 8th edition lung cancer TNM staging standard. Detect the subjects' peripheral serum tumor markers, serum carcinoembryonic antigen (CEA), cytokeratin fragment 21-1 (CYFRA21-1), squamous cell carcinoma-associated antigen (SCCA), carbohydrate antigen 125 (CA125) and sugar Class antigen 199 (CA199). Compare the differences of serum CEA, CYFRA21-1, SCCA, CA125, CA199 levels in different clinical stages of elderly NSCLC patients, and the diagnostic value of the above indicators for elderly NSCLC patients was analyzed by receiver operating characteristic curve (ROC curve) and area under the curve (AUC). Results: The smoking history, differentiation degree, lymph node metastasis and tumor diameter of elderly NSCLC patients with different clinical stages are significantly different; with the increase of NSCLC disease progression, the levels of serum CEA, CYFRA21-1, SCCA, CA125, and CA199 continue to increase, in serum. There is a significant correlation between the markers; serum CEA, CYFRA21-1, SCCA, CA125, CA199 have diagnostic value for the clinical staging of elderly NSCLC patients. Conclusion: The elevation of serum CEA, CYFRA21-1, SCCA, CA125 and CA199 in elderly NSCLC patients is positively correlated with the degree of tumor malignancy. The detection of the above indicators is of great value for the early diagnosis and disease monitoring of elderly NSCLC.

Clinical Pathological Characteristics and Prognosis of Multigene Co-Mutations in Elderly Patients With Non-Small Cell Lung Cancer: A Retrospective Analysis.

With the development and wide application of next-generation sequencing (NGS), multiple-gene mutations related to lung cancer are detected using this technology. Notably, even multigene concomitant mutations (co-mutations), which occur at a relatively low incidence, can be detected more effectively using NGS. It is well-known that the percentages of non-small cell lung cancer (NSCLC) in the elderly lung cancer population are also gradually increasing, while its prognosis is hard and the quality of long-term survival is poor. This study aimed at investigating the common clinicopathologic features of multigene co-mutations for better evaluating the prognosis of elderly NSCLC patients. A total of 464 NSCLC patients were divided into 3 groups according to the types of gene mutation, whose clinical data were retrospectively analyzed. In total, 38.36% (178/464) of NSCLC patients were in the nonmutation group, 50% in the single-gene mutation group, and 11.64% in the multigene co-mutation group. Nonmutation, single-gene mutation, and co-mutation groups were all prone to occur in male adenocarcinoma patients (P < .05). EGFR gene mutation rates were the highest in the single-gene mutation and co-mutation groups (54.31% and 24.35%). In the co-mutation group, the incidence of EGFR/PIK3CA, LK/KRAS, and EGFR/MET co-mutations was the highest (16.67%, 11.11%, and 7.41%). ALK/HER2/MET, EGFR/HER2/MET, and EGFR/HER2/MET/ROS1 multiple-gene co-mutations were, respectively, found in 1 case, and the multigene co-mutation patients commonly had a worse median progression-free survival (PFS) than that of single-gene mutation (7.13 vs 12.34 months, P = .013). With the application of NGS, the detectable rates of gene co-mutation are increasingly high in elderly patients with NSCLC, which mainly occurs in male adenocarcinoma patients commonly with poor PFS. It will be critically necessary to conduct multigene detections by NGS for directing targeted therapy of elderly NSCLC patients.

The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R): Real-World Data on Stage III Non-Small Cell Lung Cancer Patients Treated With Curative Chemoradiation

IntroductionChemoradiotherapy (CRT) is the standard of care in inoperable non–small-cell lung cancer (NSCLC) patients, favoring concurrent (cCRT) over sequential CRT (seqCRT), with adjuvant immunotherapy in responders. Elderly and frail NSCLC patients have generally been excluded from trials in the past. In elderly patients however, the higher treatment related morbidity of cCRT, may outweigh the possible lower tumor control of seqCRT. For elderly patients with locally advanced NSCLC real-world data is essential to be able to balance treatment toxicity and treatment outcome. The aim of this study is to analyze acute toxicity and 3-month mortality of curative chemoradiation (CRT) in patients with stage III NSCLC and to analyze whether cCRT for elderly stage III NSCLC patients is safe. MethodsThe Dutch Lung Cancer Audit-Radiotherapy (DLCA-R) is a national lung cancer audit that started in 2013 for patients treated with curative intent radiotherapy. All Dutch patients treated for stage III NSCLC between 2015 and 2018 with seqCRT or cCRT for (primary or recurrent) stage III lung cancer are included in this population-based study. Information was collected on patient, tumor- and treatment characteristics and the incidence and severity of acute non-hematological toxicity (CTCAE-4 version 4.03) and mortality within 3 months after the end of radiotherapy. To evaluate the association between prognostic factors and outcome (acute toxicity and mortality within 3 months), an univariable and multivariable analysis was performed. The definition of cCRT was:radiotherapy started within 30 days after the start of chemotherapy. ResultsOut of all 20 Dutch departments of radiation oncology, 19 centers participated in the registry. A total of 2942 NSCLC stage III patients were treated with CRT. Of these 67.2% (n = 1977) were treated with cCRT (median age 66 years) and 32.8% (n = 965) were treated with seqCRT (median age 69 years). Good performance status (WHO 0-1) was scored in 88.6% for patients treated with cCRT and in 71.0% in the patients treated with seqCRT. Acute nonhematological 3-month toxicity (CTCAE grade ≥3 or radiation pneumonitis grade ≥2) was scored in 21.9% of the patients treated with cCRT and in 17.7% of the patients treated with seqCRT. The univariable analysis for acute toxicity showed significantly increased toxicity for cCRT (P = .008), WHO ≥2 (P = .006), and TNM IIIC (P = .031). The multivariable analysis for acute toxicity was significant for cCRT (P = .015), WHO ≥2 (P = .001) and TNM IIIC (P = .016). The univariable analysis for 3-month mortality showed significance for seqCRT (P = .025), WHO ≥2 (P < .001), higher cumulative radiotherapy dose (P < .001), higher gross tumor volume total (P = .020) and male patients (p < .001). None of these variables reached significance in the multivariable analysis for 3-month mortality. ConclusionIn this national lung cancer audit of inoperable NSCLC patients, 3-month toxicity was significantly higher in patients treated with cCRT (21.9% vs. 17.7% for seqCRT) higher TNM stage IIIC, and poor performance (WHO≥2) patients.The 3-months mortality was not significantly different for tested parameters. Age was not a risk factor for acute toxicity, nor 3 months mortality.