Impact of environmental temperature on the survival outcomes of breast cancer: A SEER-based study.

BACKGROUND: Experimental evidence in tumor-bearing mouse models shows that exposure to cool, that is, sub-thermoneutral environmental temperature is associated with a higher tumor growth rate and an immunosuppressive tumor immune microenvironment than seen at thermoneutral temperatures. However, the translational significance of these findings in humans is unclear. We hypothesized that breast cancer patients living in warmer climates will have better survival outcomes than patients living in colder climates. METHODS: A retrospective population-based analysis was conducted on 270,496 stage I-III breast cancer patients, who were retrieved from the Surveillance, Epidemiology and End Results (SEER) over the period from 1996 to 2017. The average annual temperature (AAT) was calculated based on city level data from the National Centers for Environmental Information. RESULTS: A total of 270, 496 patients were analyzed. Temperature as assessed in quartiles. After adjusting for potential confounders, patients who lived in the 3rd and 4th quartile temperature regions with AAT 56.7-62.5°F (3rd quartile) and > 62.5°F (4th quartile) had a 7% increase in the OS compared to patients living at AAT < 48.5°F (1st quartile) (HR 0.93, 95% CI 0.90-0.95 and HR 0.93, 95% CI 0.91-0.96, respectively). For DSS, When comparing AAT quartiles, patients living with AAT in the range of 56.7-62.5°F and > 62.5°F demonstrated a 7% increase each in DSS after adjustment (HR 0.93, 95% CI 0.90-0.96 and HR 0.93, 95% CI 0.90-0.96). CONCLUSIONS: Higher environmental temperatures are associated with significantly better OS and DSS in breast cancer patients. Future research is warranted to confirm this observation using large datasets to elucidate the underlying mechanisms and investigate novel therapeutic strategies to minimize this geographic disparity in clinical outcomes.

Effects of Immunotherapy on Quality-of-Life Outcomes in Patients with Gastroesophageal Cancers: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer care, with increasing data demonstrating improved survival outcomes using ICIs among patients with advanced gastroesophageal cancer (GEC). ICIs are also associated with a lower incidence of grade ≥ 3 adverse events (AEs) compared to chemotherapy, suggesting that ICIs may have favorable effects on health-related quality of life (HRQoL). This meta-analysis sought to evaluate the effects of ICIs on the HRQoL of patients with advanced GEC. METHODS: We conducted an online bibliographic search on Medline via PubMed using MeSH-based terms to retrieve randomized controlled trials (RCTs) that evaluated the effects of ICIs on HRQoL in patients with advanced GEC (we searched for all studies between 2018 and 2021). We included RCTs that incorporated ICIs as part of the intervention arm either as monotherapy (first or second line) or as a combination therapy (first-line) with another ICI or chemotherapy. We combined the HRQoL measures into a meta-analysis using standard random effects models, from which estimates of the average mean difference (MD) were obtained with 95% confidence intervals. We assessed the heterogeneity of the study outcomes using the Q and I2 statistics. RESULTS: We identified 11 phase 3 RCTs that met the inclusion criteria, with a mean enrollment of 820 patients. Eight RCTs used an ICI plus chemotherapy combination in the intervention arm, three had ICIs as monotherapy, and one had doublet ICI therapy in the intervention arm. All RCTs used chemotherapy for the control arm. Collectively, the trials reported 37 HRQoL measures using five different HRQoL tools. The pooled analysis favored the intervention over the control arm in terms of the Functional Assessment of Cancer Therapy-Esophageal (FACT-E) scores [MD 2.7 (95% CI 0.1 to 5.3), p < 0.041]. In a subgroup analysis of eight RCTs comparing combination therapy with ICIs plus chemotherapy versus chemotherapy alone, the effect estimates favored the ICI arm regarding the FACT-E [MD 2.7 (95% CI 0.1 to 5.3), p < 0.041] and the EORTC QLQ-OES18 pain scale [MD -2.2 (95% CI -4.3 to -0.2), p < 0.030]. Likewise, the effect estimates favored the ICI monotherapy arm over the chemotherapy arm regarding the QLQ-STO22 hair loss subscale [MD -23.2 (95% CI -29.7 to -16.7), p < 0.001], QLQ-STO22 dysphagia subscale [MD 6.7 (95% CI 1.7 to 11.7), p = 0.009], EQ-5D pain scale [MD 6.9 (95% CI 2.9 to 10.9), p < 0.001], and QLQ-OES18 saliva subscale [MD 5.8 (95% CI 0.1 to 11.6), p = 0.046]. CONCLUSIONS: In this meta-analysis, we found that the inclusion of ICIs as a first-line treatment for advanced GEC yielded better HRQoL outcomes than chemotherapy alone. Further research on the impact of ICIs on HRQoL is needed, with increasing evidence that ICIs improve the survival outcomes in patients with advanced GEC.

Association between Environmental Temperature and Survival in Gastroesophageal Cancers: A Population Based Study.

BACKGROUND: Cold stress suppresses antitumor response in animal models, leading to tumor growth. Recent studies have also shown a negative correlation between the average annual temperature (AAT) and cancer incidence. We hypothesized that esophageal cancer (EC) and gastric cancer (GC) patients living in warmer climates have improved survival outcomes than those living in colder climates. METHODS: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database from 1996 to 2015. We retrieved the National Centers for Environmental Information data to calculate the county-level AAT. Cox multivariate regression models were performed to measure the association between temperature (measured continuously at diagnosis and in 5-degree increments) and OS/DSS, adjusting for variables. All associations were compared at a significance level of 0.05. The OS and DSS were summarized using Kaplan-Meier methods. All statistics were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). RESULTS: A total of 17,408 EC patients were analyzed. The average age of the cohort was 65 years, 79% of which were males and 21% were females. Of them, 61.6% had adenocarcinoma, and 37.6% were squamous. After adjusting for covariates, patients in regions with an AAT > 53.5 °F had an 11% improvement in OS [HR 0.89 (95% CI 0.86-0.92), p < 0.0001] and 13% in DSS [HR 0.87 (95% CI 0.84-0.90), p < 0.0001]. When the temperature was analyzed in 5 °F increments, with each increment, there was a 3% improvement in OS [HR 0.97 (95% CI 0.96-0.98), p < 0.0001] and 4% in DSS [HR 0.96 (95% CI 0.95-0.97), p < 0.0001]. Subgroup analysis of squamous and adenocarcinoma showed similar results. These findings were validated in 20,553 GC patients. After adjusting for covariates, patients in regions with an AAT > 53.5 had a 13% improvement in OS [HR 0.87 (95% CI 0.85-0.90), p < 0.0001] and 14% in DSS [HR 0.86 (95% CI 0.83-0.89), p < 0.0001]. When analyzed in 5 °F increments, with each increment, there was a 4% improvement in OS [HR 0.96 (95% CI 0.952-0.971), p < 0.0001] and 4% in DSS [HR 0.96 (95% CI 0.945-0.965), p < 0.0001]. CONCLUSION: We showed for the first time that higher environmental temperatures are associated with significant improvements in OS and DSS in patients with gastro-esophageal cancers, notwithstanding the limitations of a retrospective database analysis. Further confirmatory and mechanistic studies are required to implement specific interventional strategies.

2/1 dose schedule of sunitinib is superior than the 4/2 regimen for the first-line therapy of clear cell metastatic renal cell carcinoma - An Indian experience.

BACKGROUND: Sunitinib remains the first-line treatment for favorable risk metastatic clear cell renal cell cancer (mccRCC). It was conventionally given in the 4/2 schedule; however, toxicity necessitated trying the 2/1 regimen. Regional variations in treatment response and toxicity are known, and there is no data from the Indian subcontinent about the outcomes of the alternative dosing schedule. METHODS: Clinical records of all consecutive adult patients who received sunitinib as first-line therapy for histologically proven mccRCC following cytoreductive nephrectomy from 2010-2018 were reviewed. The primary objective was to determine the progression-free survival (PFS), and the secondary objectives were to evaluate the response rate (objective response rate and clinical benefit rate), toxicity, and overall survival. A list of variables having a biologically plausible association with outcome was drawn and multivariate inverse probability treatment weights (IPTW) analysis was done to determine the absolute effect size of dosing schedules on PFS in terms of "average treatment effect on the treated" and "potential outcome mean." RESULTS: We found 2/1 schedule to be independently associated with higher PFS on IPTW analysis such that if every patient in the subpopulation received sunitinib by the 2/1 schedule, the average time to progression was estimated to be higher by 6.1 months than the 4/2 schedule. We also found 2/1 group to have a lower incidence than the 4/2 group for nearly all ≥ grade 3 adverse effects. Other secondary outcomes were comparable between both treatment groups. CONCLUSION: Sunitinib should be given via the 2/1 schedule in Indian patients.