No abstract

Background The prognosis of patients with NSCLC harboring oncogenic driver gene alterations, such as EGFR gene mutations or ALK fusion, has improved dramatically with the advent of corresponding molecularly targeted drugs. As patients were followed up for about five years in most clinical trials, the long-term outcomes beyond 5 years are unclear. The objectives of this study are to explore the clinical course beyond five years of chemotherapy initiation and to investigate factors that lead to long-term survival. Methods One hundred and seventy-seven patients with advanced, EGFR-mutated or ALK-rearranged NSCLC who received their first chemotherapy between December 2008 and September 2015 were included. Kaplan Meier curves were drawn for the total cohort and according to subgroups of patients’ characteristics. Results Median OS in the total cohort was 40.6 months, the one-year survival rate was 89%, the three-year survival rate was 54%, and the five-year survival rate was 28%. Median OS was 36.9 months in EGFR-mutated patients and 55.4 months in ALK-rearranged patients. The OS curve seemed to plateau after 72 months, and most of the patients who were still alive after more than five years are on treatment. Female sex, age under 75 years, an ECOG PS of 0 to 1, ALK rearrangement, postoperative recurrence, and presence of brain metastasis were significantly associated with longer OS. Conclusions A tail plateau was found in the survival curves of patients with advanced, EGFR-mutated and ALK-rearranged NSCLC, but most were on treatment, especially with EGFR-mutated NSCLC.

IntroductionCancer-related insomnia (CRI), as a common complication in cancer survivors, may further lead to depression, anxiety and other symptoms. Acupuncture therapy is a promising therapeutic strategy for CRI. The effectiveness of acupuncture therapy on CRI has been validated by several relevant meta-analyses. Questions remain, however, including which acupuncture regimen is optimal. We aim to conduct the first network meta-analysis to compare different acupuncture therapies, rank their effectiveness and assess which approach could be optimal for treatment of CRI.Methods and analysisA comprehensive search of PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Database, VIP Database (China Science and Technology Journal Database), and China Biology Medicine (from inception until 1 March 2022) will be carried out to identify randomised controlled trials (RCTs) of acupuncture therapy for insomnia in cancer survivors, reported in English or Chinese. Reviews, animal studies, non-RCT studies, editorials and other secondary insomnia studies will be excluded. The primary outcome measure will be the Pittsburgh Sleep Quality Index. Pairwise meta-analysis will be performed in Stata and network meta-analysis by OpenBUGS, R and Stata. Network plots and funnel plots will be used to show the scale of studies and participants for each intervention and the potential publication bias, respectively. Both heterogeneity and consistency will be evaluated by R. ORs with 95% CIs and mean differences with 95% CI will be calculated in OpenBUGS and transformed into league figure and surface under the cumulative ranking by Stata to visualise the results.Ethics and disseminationEthical committee approval for this review is unnecessary since the data used will be extracted from pre-existing literature. The results will be submitted for publication in a peer-reviewed journal and presented at international academic conferences.

Cancer cachexia is associated with poor immunotherapeutic outcomes. This prospective observational study longitudinally evaluated the role of cachexia-related circulating cytokines in predicting the risk and benefit of PD-1/PD-L1 blockade in advanced lung cancer. Forty-one circulating cytokines at baseline and after one cycle of PD-1/PD-L1 blockade treatment were measured in patients with advanced lung cancer between 2019 and 2020. The cachexia-related cytokines were identified by comparing the levels of circulating cytokines between cachectic and non-cachectic patients. Among 55 patients, 49.1% were diagnosed with cachexia at the beginning of PD-1/PD-L1 blockade therapy. Baseline levels of the circulating cytokines IL-6, IL-8, IL-10, IL-15, and IP-10 were significantly higher in cachectic patients. In contrast, the level of eotaxin-1 was lower in cachectic patients than in those without cachexia. Higher IL-6 at baseline and during treatment was associated with a greater risk of immune-related adverse events, while higher IL-10 at baseline was linked to worse overall survival. More importantly, increased eotaxin-1 after one cycle of PD-1/PD-L1 blockade treatment was associated with higher objective response and better overall survival. A blood-based, cachexia-related cytokine assay may yield potential biomarkers for the early prediction of clinical response to PD-1/PD-L1 blockade and provide clues for improving the outcomes of cachectic patients.