A gene expression-based immune content predictor for survival and postoperative radiotherapy response in head and neck cancer.
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ABSTRACT:
SUBMITTER: Li Y
PROVIDER: S-EPMC8430044 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Postoperative radiotherapy or concurrent chemoradiotherapy are routine clinical options for the treatment of head and neck squamous cell carcinoma (HNSCC). However, the benefit of adding chemotherapy to radiotherapy is contested. The present study aimed to develop a gene signature to predict the clinical benefit of postoperative chemoradiotherapy using public data from The Cancer Genome Atlas. A 22-gene signature was established, which demonstrated the best predictive value. Patients were separated into low-score and high-score subgroups based on the expression score of the 22-gene signature. In the high-score subgroup, patients who received chemoradiotherapy demonstrated improved overall survival, relapse-free survival and local regional control compared with those who received radiotherapy alone. However, in the low-score subgroup adding chemotherapy to radiotherapy was associated with worse patient outcomes. The predictive value of the 22-gene signature was independent of the conventional clinical variables. Gene set enrichment analysis revealed that the expression signatures of hypoxia phenotype and stem-like traits were significantly enriched in the low-score subgroup. In addition, the low-score subgroup was associated with the gene sets involved in resistance to anticancer drugs. In conclusion, hypoxia- or stem-like gene expression properties are associated with chemotherapy-resistance in HNSCC. The 22-gene signature may be useful as a predictive marker to help distinguish patients who will benefit from postoperative concurrent chemoradiotherapy.
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Project description:The application of radiotherapy to the treatment of cancer has existed for over 100 years. Although its use has cured many, much work remains to be done to minimize side effects, and in-field tumor recurrences. Resistance of the tumor to a radiation-mediated death remains a complex issue that results in local recurrence and significantly decreases patient survival. Here, we review mechanisms of radioresistance and selective treatment combinations that improve the efficacy of the radiation that is delivered. Further investigation into the underlying mechanisms of radiation resistance is warranted to develop not just novel treatments, but treatments with improved safety profiles relative to current radiosensitizers. This review is written in memory and honor of Dr. Peter Stambrook, an avid scientist and thought leader in the field of DNA damage and carcinogenesis, and a mentor and advocate for countless students and faculty.
| S-EPMC10228519 | biostudies-literature
Project description:Head and neck squamous cell carcinoma (HNSCC), the most frequent subtype of head and neck cancer, continues to have a poor prognosis with no improvement. The TNM stage is not satisfactory for individualized prognostic assessment and it does not predict response to therapy. In the present study, we downloaded the gene expression profiles from TCGA database to establish a training set and GEO database for a validation set. In the training set, we developed an 10 immune-related genes signature which had superior predictive value compared with TNM stage. A nomogram including clinical characteristics was also constructed for accurate prediction. Furthermore, it was determined that our prognostic signature might act as an independent factor for predicting the survival of HNSCC patients. As for the immune microenvironment, our results showed higher immune checkpoint expression (CLTA-4 and PD-1) in low-risk group which might reflect a positive immunotherapy response. Thus, our signature not only provided a promising biomarker for survival prediction, but might be evaluated as an indicator for personalized immunotherapy in patients with HNSCC.
| S-EPMC8109104 | biostudies-literature
Project description:Highlights • Paired holidays in the publicly funded Canadian healthcare system are significant predictors in local recurrence.• Treatment interruption or prolongation due to civic holidays results in poor oncologic outcomes in local recurrence.• Patients with early post-operative recurrences had poor oncologic outcomes, regardless of overall treatment time. Background Delays in starting postoperative radiotherapy (PORT) have been established as negative predictors for clinical outcomes in head and neck squamous cell carcinomas (HNSCC). Our study aimed to examine the effect of delays during PORT, and the impact of national holidays in Canada, a publicly funded system, on oncologic outcomes such as Overall Survival (OS) and Local Recurrence (LR). Methods The provincial cancer registry was queried to obtain demographic, pathologic, and outcomes data from cancer patients treated for all squamous cell carcinomas of the head and neck region treated between January 1, 2007 and November 30, 2019. All extracted information was cross-referenced and supplemented by chart review of patient electronic medical records. Extracted data were analyzed for OS and LR, in the context of Canadian national holidays causing delays during PORT. Results 1433 patients treated for HNSCCs were identified, of whom 338 were treated curatively with surgery followed by PORT. 68.6% of patients experienced at least one day of interruption during treatments due to holidays. LR was 15.4% and OS was 59.6% at 5 years. Treatment interruptions by holidays were predictive of local recurrence (HR, 2.38; 95% CI 1.17–4.83; p = 0.017). Patients that developed early recurrence prior to PORT had very poor oncologic outcomes. Conclusion Our findings were consistent with previously published studies in limiting the interval between surgery and PORT. We identified the novel finding of paired holidays as a significant predictor in determining LR, suggesting the importance of modifying RT delivery schedules and timing.
| S-EPMC10440354 | biostudies-literature
Project description:We aimed to identify a novel prognostic biomarker for head and neck squamous cell carcinoma (HNSCC) based on tumor immunology-related alternative splicing (AS). Data for 502 HNSCC and 44 normal samples were obtained from the TCGA database and used to establish an AS-related risk model through univariate, least absolute shrinkage, and selection operator Cox regression analyses. Fresh HNSCC and normal oral tissues were surgically obtained from 44 HNSCC patients. Western blotting and quantitative reverse transcription-PCR were used to assess gene expression levels. Kaplan-Meier was performed to evaluate patients' overall survival (OS) rate. The CIBERSORT algorithm, single-sample gene set enrichment analysis, and immune checkpoint analyses were performed to compare immune activities between subgroups. The risk model was established using 10 pivotal AS events first. Collagen Type III Alpha 1 Chain (COL3A1) were screened based on |log2FC| ≥ 1 and FDR < 0.05 criteria. COL3A1 expression levels in HNSCC tissues were elevated relative to normal tissues (p < 0.001). Moreover, COL3A1 was a reliable biomarker for HNSCC patients' prognostic prediction in both cohorts (p < 0.001, p = 0.0085, respectively). COL3A1 protein (p = 0.0054) and mRNA (p < 0.0001) levels were correlated with HNSCC differentiation. Furthermore, the T stage was correlated with COL3A1 expression (p = 0.043), and COL3A1 expression was an independent prognostic predictor for HNSCC patients (p = 0.006). Compared with the risk model, COL3A1 was better at evaluating immune cell infiltrations, immune activities, and immune checkpoint gene expressions of HNSCC lesions.
| S-EPMC9972170 | biostudies-literature
Project description:To compare the efficacy and toxicity of adjuvant proton beam vs. carbon-ion beam radiotherapy for head and neck cancers after radical resection and to explore the value of particle beam radiotherapy (PBRT) in postoperative radiotherapy for head and neck cancers. Data from 38 head and neck cancer patients who received adjuvant PBRT after complete surgical resection at the Shanghai Proton and Heavy Ion Center (SPHIC) between October 2015 and March 2019 were retrospectively analyzed. In total, 18 patients received adjuvant proton beam therapy (54-60 GyE/27-30 fractions) and 20 received adjuvant carbon-ion radiotherapy (CIRT) (54-60 GyE/18-20 fractions). Survival rates were calculated using Kaplan-Meier analysis. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Effects (version 4.03). With a median follow-up time of 21 (range, 3-45) months, the 2-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) rates were 93.3%, 87.4%, 94.1%, and 90.7%, respectively, for the entire cohort. The rates after proton beam therapy vs. CIRT were 94.1% vs. 91.7% (P=0.96), 88.1% vs. 86.2% (P=0.96), 94.4% vs. 93.3% (P=0.97), and 88.1% vs. 92.9% (P=0.57), respectively. Furthermore, 16 of the 18 (88.9%) patients developed acute grade I/II dermatitis (13 grade I; 3 grade II) after proton beam therapy, and only 7 of the 20 (35%) patients developed acute grade I dermatitis after CIRT (P=0.001). The incidence of acute grade I/II mucositis and xerostomia in proton and carbon ion cases were 45% vs. 55% (P=0.75) and 56% vs. 50% (P=0.87) respectively. Adjuvant proton beam therapy and CIRT after radical surgical resection for head and neck cancers provided satisfactory therapeutic effectiveness, but no significant difference was observed between the two radiotherapy technologies. However, adjuvant CIRT was associated with a more favorable acute toxicity profile as compared to proton beam therapy with significantly lower frequency and severity of acute dermatitis observed.
| S-EPMC9761156 | biostudies-literature
Project description:ImportanceThe standard of care for initiation of postoperative radiotherapy (PORT) in head and neck squamous cell carcinoma (HNSCC) is within 6 weeks of surgical treatment. Delays in guideline-adherent PORT initiation are common, associated with mortality, and a measure of quality care, but patient-specific tools to estimate the risk of these delays are lacking.ObjectiveTo develop and validate 2 nomograms (that use presurgical and postsurgical data) for predicting delayed PORT initiation.Design, setting, and participantsThis cohort study obtained patient data from January 1, 2004, to December 31, 2015, from the National Cancer Database. Adults aged 18 years or older with a newly diagnosed HNSCC who underwent surgical treatment and PORT at a Commission on Cancer-accredited facility were included. Data analysis was conducted from June 2, 2019, to January 29, 2020.ExposuresSurgical treatment and PORT.Main outcomes and measuresThe primary outcome measure was PORT initiation more than 6 weeks after the surgical intervention. Multivariable logistic regression models were created in a random selection of 80% of the sample (derivation cohort) and were internally validated with bootstrapping, assessed for discrimination by calibration plots and the concordance (C) index, and externally validated in the remaining 20% of the sample (validation cohort).ResultsThe study included 60 766 adults with HNSCC who were grouped into derivation and validation cohorts. The derivation cohort comprised 48 625 patients (mean [SD] age, 59.59 [11.3] years; 36 825 men [75.7%]) selected randomly from the full sample, whereas 12 151 patients (mean [SD] age, 59.63 [11.2] years; 9266 men [76.3%]) composed the validation cohort. The rate of PORT delay was 55.8% (n=27140) in the derivation cohort and 56.7% (n=6900) in the validation cohort. Both nomograms created to predict the risk of PORT initiation delay used variables, including race/ethnicity, insurance type, tumor site, and facility type. The nomogram based on presurgical variables included clinical stage and severity of comorbidity, whereas the nomogram with postsurgical variables included US region, length of stay, and care fragmentation between surgical and radiotherapy facilities. For the presurgical nomogram, the concordance indices were 0.670 (95% CI, 0.664-0.676) in the derivation cohort and 0.674 (95% CI, 0.662-0.685) in the validation cohort. For the nomogram with postsurgical variables, the concordance indices were 0.691 (95% CI, 0.686-0.696) in the derivation cohort and 0.694 (95% CI, 0.685-0.704) in the validation cohort.Conclusions and relevanceThis study found that a nomogram developed with presurgical data to generate personalized estimates of PORT initiation delay may improve pretreatment counseling and the delivery of interventions to patients at high risk for such a delay. A nomogram including postsurgical data can drive institutional quality improvement initiatives and enhance risk-adjusted comparisons of delay rates across facilities.
| S-EPMC7118672 | biostudies-literature
Project description:Background and purposeHead and neck squamous carcinoma (HNSCC), characterized by immunosuppression, is a group of highly heterogeneous cancers. Although immunotherapy exerts a promising influence on HNSCC, the response rate remains low and varies in assorted primary sites. Immunological mechanisms underlying HNSCC pathogenesis and treatment response are not fully understood. This study aimed to develop a differentially expressed genes (DEGs)-based risk model to predict immunotherapy efficacy and stratify prognosis of HNSCC patients.Materials and methodsThe expression profiles of HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The tumor microenvironment and immune response were estimated by cell type identification via estimating relative subset of known RNA transcripts (CIBERSORT) and immunophenoscore (IPS). The differential expression pattern based on human papillomavirus status was identified. A DEGs-based prognostic risk model was developed and validated. All statistical analyses were performed with R software (version 3.6.3).ResultsBy using the TCGA database, we identified DKK1, HBEGF, RNASE7, TNFRSF12A, INHBA, and IPIK3R3 as DEGs that were associated with patients' overall survival (OS). Patients were stratified into the high- and low-risk subgroups according to a DEGs-based prognostic risk model. Significant difference in OS was found between the high- and low-risk patients (1.64 vs. 2.18 years, P = 0.0017). In multivariate Cox analysis, the risk model was an independent prognostic factor for OS (hazard radio = 1.06, 95% confidence interval [1.02-1.10], P = 0.004). More CD8+ T cells and regulatory T cells were observed in the low-risk group and associated with a favorable prognosis. The IPS analysis suggested that the low-risk patients possessed a higher IPS score and a higher immunoreactivity phenotype, which were correlated with better immunotherapy response.ConclusionCollectively, we established a reliable DEGs-based risk model with potential prognostic value and capacity to predict the immunophenotype of HNSCC patients.
| S-EPMC7596453 | biostudies-literature
Project description:Saliva, a biological fluid, is a promising candidate for novel approaches to prognosis, clinical diagnosis, monitoring and management of patients with both oral and systemic diseases. However, to date, saliva has not been widely investigated as a biomarker for radiation exposure. Since white blood cells are also present in saliva, it should theoretically be possible to investigate the transcriptional biomarkers of radiation exposure classically studied in whole blood. Therefore, we collected whole blood and saliva samples from eight head and neck cancer patients before the start of radiation treatment, at mid-treatment and after treatment. We then used a panel of five genes: BAX, BBC3, CDKN1A, DDB2 and MDM2, designated for assessing radiation dose in whole blood to evaluate gene expression changes that can occur during radiotherapy. The results revealed that the expression of the five genes did not change in whole blood. However, in saliva, CDKN1A and DDB2 were significantly overexpressed at the end, compared to the start, of radiotherapy, and MDM2 was significantly underexpressed between mid-treatment and at the end of treatment. Interestingly, CDKN1A and DDB2 expressions also showed an increasing monotonic relationship with total radiation dose received during radiotherapy. To our knowledge, these results show for the first time the ability to detect gene expression changes in saliva after head and neck cancer radiotherapy, and pave the way for further promising studies validating saliva as a minimally invasive means of biofluid collection to directly measure radiation dose escalation during treatment.
| S-EPMC5552048 | biostudies-literature
Project description:PurposeCancer stem cells (CSCs) constitute a distinctive subpopulation of cancer cells that are competent in tumor initiation, invasion, recurrence, and resistance to chemoradiotherapy. CD44, a hyaluronic acid (HA) receptor has been considered as a potential CSC marker in head and neck cancer. The purpose of this study is to evaluate the correlation between CD44 and clinicopathological parameters, treatment response, survival, and recurrence.MethodsThe CD44 expression was examined by immunohistochemistry (IHC) in 90 samples of head and neck squamous cell carcinoma (HNSCC) confirmed patients. The expression of CD44 and its association with clinicopathological parameters, treatment response, and survival was determined.ResultsIn all HNSCC patient samples, CD44 was expressed consistently at different intensities. Tumor size (p < 0.001), stage (p < 0.001), and treatment response (p < 0.001) showed statistically significant association with CD44 expression. Alcohol and CD44 were observed as independent predictors of response to radiotherapy using multivariate ordinal logistic regression analysis. Analysis of 2-year overall survival (OS) showed that CD44 expression (p = 0.02), tumor size (p = 0.001), lymph node status (p < 0.001), stage (p < 0.001), and grade (p = 0.007) were significantly associated with OS. Using Cox regression analysis, lymph node status (p = 0.001), grade (p < 0.001), recurrence (p < 0.001), and CD44 expression (p = 0.003) were found to be potential independent predictors of OS.ConclusionOur findings suggest that CD44 contributes to resistance to radiotherapy and poor OS. The results also suggest that except for CD44 there could be other factors such as lymph node metastasis, grade, and alcohol which should be investigated as potential targets for therapy.
| S-EPMC9089225 | biostudies-literature