Given the role of systematic inflammation in cancer progression, lymphocyte-monocyte ratio (LMR) from peripheral blood has been suggested as a biomarker to assess the extent of inflammation in ...several solid malignancies. However, the role of LMR as a prognostic factor in head and neck cancer was unclear in several meta-analyses, and there is a paucity of literature including patients in North America. We performed an observational cohort study to evaluate the association of LMR with survival outcomes in North American patients with head and neck cancer.
A single-institution, retrospective database was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation from June 2007 to April 2021 at the Roswell Park Comprehensive Cancer Center. Primary endpoints were overall survival (OS) and cancer-specific survival (CSS). The association of LMR with OS and CSS was examined using nonlinear Cox proportional hazard model using restricted cubic splines (RCS). Cox multivariable analysis (MVA) and Kaplan-Meier method were used to analyze OS and CSS. Pre-radiation LMR was then stratified into high and low based on its median value. Propensity scored matching was used to reduce the selection bias.
A total of 476 patients met our criteria. Median follow up was 45.3 months (interquartile range 22.8-74.0). The nonlinear Cox regression model showed that low LMR was associated with worse OS and CSS in a continuous fashion without plateau for both OS and CSS. On Cox MVA, higher LMR as a continuous variable was associated with improved OS (adjusted hazard ratio aHR 0,90, 95% confidence interval CI 0.82-0.99, p = 0.03) and CSS (aHR 0.83, 95% CI 0.72-0.95, p = 0.009). The median value of LMR was 3.8. After propensity score matching, a total of 186 pairs were matched. Lower LMR than 3.8 remained to be associated with worse OS (HR 1.59, 95% CI 1.12-2.26, p = 0.009) and CSS (HR 1.68, 95% CI 1.08-2.63, p = 0.02).
Low LMR, both as a continuous variable and dichotomized variable, was associated with worse OS and CSS. Further studies would be warranted to evaluate the role of such prognostic marker to tailor interventions.
Objectives/Hypothesis
The effect of smoking and human papillomavirus (HPV) on overall survival (OS) of oropharyngeal squamous cell carcinoma (OPSCC) patients undergoing concurrent chemotherapy (CCRT) ...remains unclear.
Study Design
Retrospective review.
Methods
Clinical characteristics of OPSCC patients treated between 2008 and 2015 with CCRT were ed from medical records. OS curves and multivariate cox proportional hazard ratios (HRs) were examined.
Results
Of 120 evaluable patients, 71% had HPV+ tumors. Median follow‐up duration for the entire cohort was 41.5 months (range = 6–88 months). HPV+ current smokers experienced significantly worse 5‐year OS (73% alive vs. 36% alive, P = .01) and there was a similar trend in HPV− current smokers (66% alive vs. 31% alive, P = .28) compared to former/never smokers undergoing CCRT. In a multivariate cox proportional hazard model adjusted for age, gender, and overall tumor stage, HPV+ current smokers experienced nearly a fourfold increase in overall mortality in comparison to HPV+ never/former smokers (HR = 3.68, 95% CI = 1.35‐10.0). Similarly, current smokers with HPV− tumors (HR = 6.80, 95% CI = 1.11‐41.67) had increased mortality compared to never/former smokers.
Conclusions
Current smoking is associated with poor prognosis, independent of HPV status, in CCRT‐treated OPSCC patients. Current smoking produced an approximately four‐ to sevenfold increase in risk of mortality for HPV+ and HPV− patients, respectively. Regardless of pack years and HPV status, efforts should be made to achieve smoking cessation before CCRT.
Level of Evidence
4. Laryngoscope, 126:2733–2738, 2016
Positron-emission tomography (PET) has improved identification of the primary tumor as well as occult nodal burden in cancer of the head and neck. Nevertheless, there are still patients where the ...primary tumor cannot be located. In these situations, the standard of care is comprehensive head and neck radiation therapy however it is unclear whether this is necessary. This study examines the effects of radiation treatment volume on outcomes among using data from two cancer centers in unknown primary carcinoma of the head and neck.
Patients received unilateral (n = 34), or bilateral radiation (n = 28). Patient factors such as age, gender, smoking history, and patterns of failure were compared using Mann Whitney U and Chi Square. Overall survival (OS) and disease free survival (DFS) trends were estimated using Kaplan-Meier survival curves. Effect of treatment volume on survival was examined using multivariate cox proportional hazard regression model.
No significant differences were observed in the frequency of local (p = 0.32), regional (p = 0.50), or distant (p = 0.76) failures between unilateral and bilateral radiation therapy. By Kaplan-Meier estimates, OS (3-year OS bilateral = 71.67%, unilateral = 77.90%, p = 0.50) and DFS (3-year DFS bilateral = 77.92%, unilateral = 69.43%, p = 0.63) were similar between the two treatment approaches. Lastly, multivariate analysis did not demonstrate any significant differences in outcome by treatment volumes (OS: HR = 0.74, 95% CI: 0.31, 1.81, p = 0.51; DFS: HR: 0.68, 95% CI: 0.24, 1.93, p = 0.47).
Unilateral radiation therapy compared with bilateral produced similar survival.
Oral potentially malignant disorders (OPMDs) are precursors to over 80% of oral cancers. Hematoxylin and eosin (H&E) staining, followed by pathologist interpretation of tissue and cellular ...morphology, is the current gold standard for diagnosis. However, this method is qualitative, can result in errors during the multi-step diagnostic process, and results may have significant inter-observer variability. Chemical imaging (CI) offers a promising alternative, wherein label-free imaging is used to record both the morphology and the composition of tissue and artificial intelligence (AI) is used to objectively assign histologic information. Here, we employ quantum cascade laser (QCL)-based discrete frequency infrared (DFIR) chemical imaging to record data from oral tissues. In this proof-of-concept study, we focused on achieving tissue segmentation into three classes (connective tissue, dysplastic epithelium, and normal epithelium) using a convolutional neural network (CNN) applied to three bands of label-free DFIR data with paired darkfield visible imaging. Using pathologist-annotated H&E images as the ground truth, we demonstrate results that are 94.5% accurate with the ground truth using combined information from IR and darkfield microscopy in a deep learning framework. This chemical-imaging-based workflow for OPMD classification has the potential to enhance the efficiency and accuracy of clinical oral precancer diagnosis.
Financial toxicity (FT) can be devastating to cancer patients, and solutions are urgently needed. We investigated the impact of financial counseling (FC) on FT in head and neck cancer (HNC) patients.
...Via a single-institution database, we reviewed the charts of HNC patients who underwent definitive or post-operative radiotherapy, from October 2013 to December 2020. Of these patients, 387 had provided baseline and post-treatment information regarding financial difficulty. In July 2018, a dedicated financial counselor was provided for radiation therapy patients and we subsequently examined the impact of FC on financial difficulty scores.
Following the hiring of a dedicated financial counselor, there was a significant increase in the proportion of patients receiving FC (5.3% vs. 62.7%,
< 0.0001). Compared with baseline scores, patients who did not undergo FC had a significant increase in reported financial difficulty at the end of treatment (
= 0.002). On the other hand, there was no difference in pre- and post-treatment scores in patients who had received FC (
= 0.588). After adjusting for gender and nodal status with a multiple linear regression model, FC was significantly associated with change in financial difficulty (β = -0.204 ± 0.096,
= 0.035). On average, patients who received FC had a 0.2 units lower change in financial difficulty score as compared with those with the same gender and nodal stage but without FC.
Providing a dedicated financial counselor significantly increased the proportion of HNC receiving FC, resulting in the stabilization of financial difficulty scores post-treatment. Based on a multiple linear regression model, FC was independently associated with reduced financial difficulty. The employment of a financial counselor may be a viable, hospital-based approach to begin to address FT in HNC.
•The optimal threshold of anemia for head and neck cancer patients is unclear.•Threshold of anemia was determined to be hemoglobin of 11.4.•Anemia was associated with worse overall and ...progression-free survival outcomes.•Anemia was prognostic for survival among patients with HPV-negative tumors.
We sought to define the optimal threshold for anemia in North American head and neck cancer patients and evaluate its role as a prognostic biomarker.
A single-institution database was queried for patients with head and neck cancer who underwent chemoradiation from January 2005 to April 2021. An optimal threshold of hemoglobin (Hgb) level was defined based on maximum log-rank test statistic. Cox multivariable analysis (MVA), Kaplan-Meier, and propensity score matching were performed to evaluate treatment outcomes.
A total of 496 patients were identified. Threshold for Hgb was determined to be 11.4 for both overall survival (OS) and progression-free survival (PFS). Low Hgb was associated with worse OS (adjusted hazards ratio aHR 2.41, 95 % confidence interval CI 1.53–3.80, p < 0.001) and PFS (aHR 2.01, 95 % CI 1.30–3.11, p = 0.002). Similar findings were observed among 39 matched pairs for OS (5-year OS 22.3 % vs 49.0 %; HR 2.22, 95 % CI 1.23–4.03, p = 0.008) and PFS (5-year PFS 24.3 % vs 39.1 %; HR 1.78, 95 % CI 1.02–3.12, p = 0.04). Among those with HPV-negative tumors, low Hgb was associated with worse OS (aHR 13.90, 95 % CI 4.66–41.44, p < 0.001) and PFS (aHR 5.24, 95 % CI 2.09–13.18, p < 0.001). However, among those with HPV-positive tumors, low Hgb was not associated with both OS (aHR 1.75, 95 % CI 0.60–5.09, p = 0.31) and PFS (aHR 1.13, 95 % CI 0.41–3.14, p = 0.82).
Low Hgb below 11.4 was an independent adverse prognostic factor for worse survival. It was also prognostic among patients with HPV-negative tumors, but not for HPV-positive tumors.
The immune cell niche associated with oral dysplastic lesion progression to carcinoma is poorly understood. We identified T regulatory cells (Treg), CD8+ effector T cells (Teff) and immune checkpoint ...molecules across oral dysplastic stages of oral potentially malignant disorders (OPMD). OPMD and oral squamous cell carcinoma (OSCC) tissue sections (N = 270) were analyzed by immunohistochemistry for Treg (CD4, CD25 and FoxP3), Teff (CD8) and immune checkpoint molecules (PD-1 and PD-L1). The Treg marker staining intensity correlated significantly (p < 0.01) with presence of higher dysplasia grade and invasive cancer. These data suggest that Treg infiltration is relatively early in dysplasia and may be associated with disease progression. The presence of CD8+ effector T cells and the immune checkpoint markers PD-1 and PD-L1 were also associated with oral cancer progression (p < 0.01). These observations indicate the induction of an adaptive immune response with similar Treg and Teff recruitment timing and, potentially, the early induction of exhaustion. FoxP3 and PD-L1 levels were closely correlated with CD8 levels (p < 0.01). These data indicate the presence of reinforcing mechanisms contributing to the immune suppressive niche in high-risk OPMD and in OSCC. The presence of an adaptive immune response and T-cell exhaustion suggest that an effective immune response may be reactivated with targeted interventions coupled with immune checkpoint inhibition.
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