Highlights • Inflammation was associated with fatigue in head and neck cancer (HNC) patients. • IL-6 and CRP correlated with fatigue both before and after IMRT in HNC patients. • Increase in IL-6 and ...CRP from pre- to post-IMRT correlated with increased fatigue. • Up-regulated gene transcripts associated with fatigue and IMRT were related to NFkB.
•Lower blood butyrate concentrations were associated with higher fatigue.•Lower blood iso/valerate concentrations were associated with higher fatigue.•High vs. low SCFAs were linked with inflammation ...and lipid metabolism gene pathways.
Fatigue among patients with head and neck cancer (HNC) has been associated with higher inflammation. Short-chain fatty acids (SCFAs) have been shown to have anti-inflammatory and immunoregulatory effects. Therefore, this study aimed to examine the association between SCFAs and fatigue among patients with HNC undergoing treatment with radiotherapy with or without concurrent chemotherapy. Plasma SCFAs and the Multidimensional Fatigue Inventory-20 were collected prior to and one month after the completion of treatment in 59 HNC patients. The genome-wide gene expression profile was obtained from blood leukocytes prior to treatment. Lower butyrate concentrations were significantly associated with higher fatigue (p = 0.013) independent of time of assessment, controlling for covariates. A similar relationship was observed for iso/valerate (p = 0.025). Comparison of gene expression in individuals with the top and bottom 33% of butyrate or iso/valerate concentrations prior to radiotherapy revealed 1,088 and 881 significantly differentially expressed genes, respectively (raw p < 0.05). The top 10 Gene Ontology terms from the enrichment analyses revealed the involvement of pathways related to cytokines and lipid and fatty acid biosynthesis. These findings suggest that SCFAs may regulate inflammatory and immunometabolic responses and, thereby, reduce inflammatory-related symptoms, such as fatigue.
Epigenetic age acceleration (EAA) is robustly linked with mortality and morbidity. This study examined risk factors of EAA and its association with overall survival (OS), progression-free survival ...(PFS), and quality of life (QOL) in patients with head and neck cancer (HNC) receiving radiation therapy.
Patients without distant metastasis were enrolled and followed before and at the end of radiation therapy and at 6 and 12 months after radiation therapy. EAA was calculated with DNAmPhenoAge at all 4 time points. Risk factors included demographic characteristics, lifestyle, clinical characteristics, treatment-related symptoms, and blood biomarkers. Survival data were collected until August 2020, and QOL was measured using Functional Assessment of Cancer Therapy-HNC.
Increased comorbidity, symptoms unrelated to human papilloma virus, and more severe treatment-related symptoms were associated with higher EAA (P = .03 to P < .001). A nonlinear association (quadratic) between body mass index (BMI) and EAA was observed: decreased BMI (<35 kg/m
; P = .04) and increased BMI (≥35 kg/m
; P = .01) were linked to higher EAA. Increased EAA (per year) was associated with worse OS (hazard ratio HR, 1.11 95% confidence interval {CI}, 1.03-1.18; P = .004; HR, 1.10 95% CI, 1.01-1.19; P = .02 for EAA at 6 and 12 months after treatment, respectively) and PFS (HR, 1.10 95% CI, 1.02-1.19; P = .02; HR, 1.14 95% CI, 1.06-1.23; P < .001; and HR, 1.08 95% CI, 1.02-1.14; P = .01) for EAA before, immediately after, and 6 months after radiation therapy, respectively) and QOL over time (β = -0.61; P = .001). An average of 3.25 to 3.33 years of age acceleration across time, which was responsible for 33% to 44% higher HRs of OS and PFS, was observed in those who died or developed recurrence compared with those who did not (all P < .001).
Compared with demographic and lifestyle factors, clinical characteristics were more likely to contribute to faster biological aging in patients with HNC. Acceleration in epigenetic age resulted in more aggressive adverse events, including OS and PFS. EAA could be considered as a marker for cancer outcomes, and decelerating aging could improve survival and QOL.
The PACIFIC trial established consolidative durvalumab after concurrent chemoradiation as standard-of-care in patients with stage III or unresectable non-small cell lung cancer (NSCLC). Black ...patients, however, comprised just 2% (n = 14) of randomized patients in this trial, warranting real-world evaluation of the PACIFIC regimen in these patients.
This single-institution, multi-site study included 105 patients with unresectable stage II/III NSCLC treated with concurrent chemoradiation followed by durvalumab between 2017 and 2021. Overall survival (OS), progression-free survival (PFS), and grade ≥3 pneumonitis-free survival (PNFS) were compared between Black and non-Black patients using Kaplan-Meier and Cox regression analyses.
A total of 105 patients with a median follow-up of 22.8 months (interquartile range, 11.3-37.3 months) were identified for analysis, including 57 Black (54.3%) and 48 (45.7%) non-Black patients. The mean radiation prescription dose was higher among Black patients (61.5 ± 2.9 Gy vs. 60.5 ± 1.9 Gy; p = .031), but other treatment characteristics were balanced between groups. The median OS (not-reached vs. 39.7 months; p = .379) and PFS (31.6 months vs. 19.3 months; p = .332) were not statistically different between groups. Eight (14.0%) Black patients discontinued durvalumab due to toxicity compared to 13 (27.1%) non-Black patients (p = .096). The grade ≥3 pneumonitis rate was similar between Black and non-Black patients (12.3% vs. 12.5%; p = .973), and there was no significant difference in time to grade ≥3 PNFS (p = .904). Three (5.3%) Black patients and one (2.1%) non-Black patient developed grade 5 pneumonitis.
The efficacy and tolerability of consolidative durvalumab after chemoradiation appears to be comparable between Black and non-Black patients.
As immunotherapy has improved distant metastasis-free survival (DMFS) in Non-Small Cell Lung Cancer (NSCLC), isolated locoregional recurrences have increased. However, management of locoregional ...recurrences can be challenging. We report our institutional experience with definitive intent re-irradiation using Intensity Modulated Proton Therapy (IMPT).
Retrospective cohort study of recurrent or second primary NSCLC or LS-SCLC treated with IMPT. Kaplan-Meier method and log-rank test were used for time-to-event analyses.
22 patients were treated from 2019 to 2021. After first course of radiation (median 60 Gy, range 45-70 Gy), 45% received adjuvant immunotherapy. IMPT re-irradiation began a median of 28.2 months (8.8-172.9 months) after initial radiotherapy. The median IMPT dose was 60 GyE (44-60 GyE). 36% received concurrent chemotherapy with IMPT and 18% received immunotherapy after IMPT. The median patient's IMPT lung mean dose was 5.3 GyE (0.9-13.9 GyE) and 5 patients had cumulative esophagus max dose >100 GyE with 1-year overall survival (OS) 68%, 1-year local control 80%, 1-year progression free survival 45%, and 1-year DMFS 60%. Higher IMPT (HR 1.4; 95% CI 1.1-1.7, p=0.01) and initial radiotherapy mean lung doses (HR 1.3; 95% CI 1.0-1.6, p=0.04) were associated with worse OS. Two patients developed Grade 3 pneumonitis or dermatitis, one patient developed Grade 2 pneumonitis, and seven patients developed Grade 1 toxicity. There were no Grade 4 or 5 toxicities.
Definitive IMPT re-irradiation for lung cancer can prolong disease control with limited toxicity, particularly in the immunotherapy era.
Introduction
Tobacco cessation is a critical but challenging intervention for cancer patients. Our National Cancer Institute‐designated Comprehensive Cancer Center instituted a tobacco cessation ...program in 2019. This manuscript reports on the first 2 years of our experience.
Methods
Patients were referred to the program by their care team, and a certified tobacco treatment specialist contacted patients remotely and provided behavioral therapy and coordinated pharmacotherapy. We retrospectively captured data from patients with a cancer diagnosis referred to the tobacco cessation program. Univariate and multivariable logistic regression analyses with the backward elimination approach were performed to determine factors associated with patient acceptance of referral to the tobacco cessation program. Tobacco cessation rates after referral to the program were also captured.
Results
Between July 2019 and August 2021, 194 patients were referred to the tobacco cessation program. Of the 194 patients referred, 93 agreed to enroll in the tobacco cessation program (47.9%), of which 84 requested pharmacotherapy (90.3%). Twenty‐four were able to cease tobacco use (25.8%). Only 7 patients out of the 101 patients (6.9%) who declined cessation services were successful (p < 0.001). On univariate logistic regression, race (p = 0.027) and marital status (p = 0.020) were associated with referral acceptance. On multivariable analysis, single patients (odds ratio OR = 0.33) and Caucasian patients (OR = 0.43) were less likely to accept a referral.
Conclusions
Access to tobacco cessation services is a critical component of comprehensive cancer care. Our experience highlights the need to understand patient‐specific factors associated with engagement with a tobacco cessation program during cancer treatment. The use of pharmacotherapy is also a critical component of successful tobacco cessation.
At a National Cancer Institute‐designated cancer center, a tobacco cessation program was implemented, and under half of cancer patients engaged in the program. Single patients and Caucasian patients were less likely to engage with the program. Further efforts are needed to increase engagement of patients with tobacco cessation programs as we found higher tobacco cessation rates with program participation.
Cardiac radiation dose was a predictor of inferior overall survival in the Radiation Therapy Oncology Group 0617 non-small cell lung cancer trial. We examined the association between radiation ...therapy (RT) and cardiac events (CE) for patients with small cell lung cancer (SCLC).
The US population-based Surveillance, Epidemiology, and End Results Program and Medicare claims databases were queried for rates of CE among patients with SCLC treated with chemotherapy (CTX) ± RT. Propensity score matching (PSM) and multivariate analysis were conducted. Patients were matched for actual/theoretical RT start date (to prevent immortal time bias) and then full PSM balanced clinical characteristics. Cumulative incidence function curves were generated.
From 2000 to 2011, 7060 patients were included: 2892 limited-stage SCLC (LS-SCLC) and 4168 extensive-stage SCLC. Grouping LS-SCLC and extensive-stage SCLC together, the incidence of CE for the CTX + RT and CTX-only groups was 44.1% versus 39% at 60 months (P = .008). After PSM (5286 patients), the incidence of CE for the CTX + RT and CTX-only groups was 43% versus 38.6% at 60 months (P = .033). Analysis of only LS-SCLC (2016 patients) demonstrated that the incidence of CE for CTX + RT versus CTX-only groups was 50.3% versus 42% at 60 months (P = .0231). Multivariate analysis again demonstrated an association between CE and RT (hazard ratio 1.20; 95% confidence interval 1.06-1.37; P = .005). After PSM (1614 patients), the incidence of CE for CTX + RT versus CTX-only groups was 51.7% versus 41.6% at 60 months (P = .0042).
Patients with SCLC are at significant risk of developing CE posttreatment; RT is associated with an absolute increase in the rate of CE at 5 years of approximately 5% for all patients with SCLC and up to 10% for patients with LS-SCLC. Cardiac risk management and cardiac-sparing RT techniques should be further evaluated for patients with SCLC.
Micro-Abstract Intensity-modulated radiation therapy (IMRT) has been previously shown to improve quality of life, dosimetry, and toxicity in comparison to 3-dimensional conformal radiation therapy in ...the treatment of locally advanced non–small-cell lung cancer. It remains unclear what patient and disease characteristics, if any, may selectively benefit from the use of IMRT. We sought to identify subgroups of patients that may preferentially derive benefit from IMRT using a large prospectively acquired national database. Usage of IMRT in T3/T4 was associated with improved survival.
Background
Significant controversy remains regarding the care of patients with clinical stage III (N2‐positive) NSCLC. Although multimodality therapy is effective, the roles of surgery, chemotherapy, ...and radiotherapy are not fully defined and the optimal treatment approach is not firmly established. We analyzed outcomes and predictors associated with trimodality therapy (TT) in the National Cancer Database.
Materials and Methods
The NCDB was queried from 2004 to 2014 for patients with NSCLC diagnosed with stage III (N2) disease and treated with chemotherapy and radiation (CRT). Three cohorts of patients were studied: CRT only/no surgery (NS), CRT plus lobectomy (LT), and CRT plus pneumonectomy (PT). The univariate and multivariable analyses (MVA) were conducted using Cox proportional hazards model and log‐rank tests.
Results
A total of 29,754 patients were included in this analysis: NS 90.1%, LT 8.4%, and PT 1.5%. Patient characteristics: median age 66 years; male 56% and white 85%. Patients treated at academic centers were more likely to receive TT compared with those treated at community centers (odds ratio: 1.85 1.53–2.23; p < .001). On MVA, patients that received TT were associated with better survival than those that received only CRT (hazard ratio: 0.59 0.55–0.62; p < .001). The LT group was associated with significantly better survival than the PT and NS groups (median survival: 62.8 months vs. 51.8 months vs. 34.2 months, respectively). In patients with more than two nodes involved, PT was associated with worse survival than LT and NS (median survival: 51.4 months in LT and 39 months in NS vs. 37 months in PT). The 30‐day and 90‐day mortality rates were found to be significantly higher in PT patients than in LT.
Conclusion
TT was used in less than 10% of patients with stage III N2 disease, suggesting high degree of patient selection. In this selected group, TT was associated with favorable outcomes relative to CRT alone.
Implications for Practice
This analysis demonstrates that trimodality therapy could benefit a selected subset of patients with stage III (N2) disease. This plan should be considered as a treatment option following patient evaluation in a multidisciplinary setting in experienced medical centers with the needed expertise.
This study researched new diagnoses of non‐small cell lung cancer in the U.S. to evaluate outcomes and predictors associated with trimodalilty therapy‐surgery, radiotherapy, and chemotherapy.
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