Squamous Cell Carcinoma Of Head And Neck Patients Research Articles

Impact of pretreatment body mass index on the survival of head and neck cancer patients.

Differences in pretreatment body mass index (BMI) have been associated with survival in squamous cell carcinoma of head and neck (SCCHN). We examined effects of BMI on survival in SCCHN patients after stratifying patients by tumor human papillomavirus (HPV) status and subsite. Totally 2204 SCCHN patients in a prospective study were included in this secondary analysis. Multivariable Cox models were used to evaluate associations between pretreatment BMI and overall survival, disease-specific survival, and disease-free survival. BMI was significantly higher among patients with HPV-positive tumors than HPV-negative tumors. BMI >25 kg/m2 was associated with improved survival, while BMI <18.5 kg/m2 was associated with reduced survival, particularly in patients with HPV-positive oropharyngeal cancer tumors. This exploratory analysis suggests that pretreatment BMI could be an independent prognostic factor of survival outcomes in SCCHN patients, particularly in patients with HPV-positive oropharyngeal cancer tumors. Further prospective investigations are warranted.

Induction Chemotherapy with Cisplatin, Paclitaxel, and Capecitabine (PTC) in Locally Advanced (LA) Squamous Cell Carcinoma of Head and Neck (SCCHN)

<h3>Purpose/Objective(s)</h3> In Guatemala's Roosevelt Hospital, most patients consult with locally advanced stages of SCCHN. Cisplatin, Docetaxel, and 5FU regimen has shown superiority over Cisplatin plus 5FU during the induction of LA cases, with afew reports supporting the substitution of 5FU with capecitabine for LA SCCHN. During the COVID-19 pandemic, we performed induction therapy with PTC in patients with LA SCCHN to reduce inpatient treatment. <h3>Materials/Methods</h3> We performed a retrospective analysis of patients with LA SCCHN with preserved swallowing function treated with Cisplatin 75mg/m², Paclitaxel 175mg/m², and Capecitabine 1000mg/m² twice a day for 14 days. RECIST and CTCAE were used to measure response and adverse events. <h3>Results</h3> A total of 16 LA SCCHN patients were treated with PTC induction. Treated patients were mostly men, smokers, and considered not candidates for surgical resection (Table 1). The mean of cycles administered was 3.5 (SD = 0.97). Regarding the response to the PTC regimen, 93.6% of patients achieved disease control. Only 6.2% of patients stopped capecitabine, whereas 37.5% required dose reduction. The main adverse events were nausea, vomiting, and diarrhea. <h3>Conclusion</h3> The PTC regimen worked as induction therapy for patients with LA SCCHN. The substitution of 5FU for Capecitabine requires prospective validation.

Integrated Analysis of RNA-Binding Proteins Associated With the Prognosis and Immunosuppression in Squamous Cell Carcinoma of Head and Neck.

RNA-binding proteins (RBPs) interacting with target RNAs play essential roles in RNA metabolism at the post-transcription level. Perturbations of RBPs can accelerate cancer development and cause dysregulation of the immune cell function and activity leading to evade immune destruction of cancer cells. However, few studies have systematically analyzed the potential prognostic value and functions of RBPs in squamous cell carcinoma of head and neck (SCCHN). Here, for the first time, we comprehensively identified 92 differentially expressed RBPs from The Cancer Genome Atlas (TCGA) database. In the training set, a prognosis risk model was constructed with six RBPs, including NCBP2, MKRN3, MRPL47, AZGP1, IGF2BP2, and EZH2, and validated by the TCGA test set, the TCGA all set, and the GEO data set. In addition, the risk score was related to the clinical stage, T classification, and N classification. Furthermore, the high-risk score was significantly correlated with immunosuppression, and low expression of EZH2 and AZGP1 and high expression of IGF2BP2 were the main factors. Thus, the risk model may serve as a prognostic signature and offer highlights for individualized immunotherapy in SCCHN patients.

Opposing Effects of Heparanase and Heparanase-2 in Head & Neck Cancer.

Squamous cell carcinoma of head and neck (SCCHN) is the most common cancer in the head and neck and is the sixth most common neoplasm worldwide. SCCHN has a high propensity to lymph node metastases, especially cancer of the pharynx. Prognosis of patients with SCCHN is severely influenced by the status of metastatic cervical lymph nodes and survival rates drop down to half when patients are presented with a metastatic node. The clinical relevance of heparanase as a prognostic marker in SCCHN was reported in several publications. Low levels of heparanase in SCCHN tumor cells was correlated with prolonged disease-free and overall survival. Furthermore, nuclear localization of heparanase predicts a favorable outcome compared to cytoplasmic localization. Heparanase staining was positively correlated with lymphatic vessel density and lymph node metastasis associated with the elevation of vascular endothelial growth factor C (VEGF-C). Heparanase ability to enhance phosphorylation of epidermal growth factor receptor (EGFR), and signal transducer and activator of transcription 3 (STAT3) were postulated to serve as critical molecular mechanisms by which heparanase facilitates tumor growth.Heparanase-2 (HPA2) is a close homolog of heparanase that lacks intrinsic HS-degrading activity but retains the capacity to bind HS with high affinity. HPA2 expression was markedly elevated in SCCHN patients, correlating with prolonged follow-up time to recurrence and inversely correlating with patients' N-stage. HPA2 appears to inhibit tumor dissemination, suggesting that HPA2 functions as a tumor suppressor. Thus, Heparanase and Heparanase-2 seem to exert opposing effects on SCCHN.

Nimotuzumab with intensity-modulated radiation therapy in unresectable and platinum-ineligible locally advanced head-and-neck cancer.

Background:Outcomes with conventional treatment are poor in patients with squamous cell carcinoma of head and neck (SCCHN). Treatment options are further limited for patients ineligible to receive platinum-based chemotherapy due to various factors such as geriatric age, comorbidity, and organ dysfunctions. The present study retrospectively evaluated the effectiveness of nimotuzumab when added to radiation therapy in unresectable, locally advanced SCCHN patients who were ineligible for platinum-based chemotherapy.Materials and Methods:The medical records of 21 patients with unresectable, locally advanced head-and-neck cancer and histologically confirmed squamous cell carcinoma who were ineligible for platinum-based chemotherapy treated with nimotuzumab and intensity-modulated radiation therapy (IMRT) from 2012 to 2017 were retrospectively analyzed. The tumor response rate and overall survival (OS) were analyzed. Patients were assessed for toxicity and adverse events (AEs) as per CTCAE version 4. Statistical analysis was performed using SPSS software.Results:The median number of doses of nimotuzumab received was 6, and median dose of radiotherapy was 60 Gy. The tumor response rate was calculated at 24 weeks after the completion of radiotherapy and was as follows: 76.2% (16) of patients showed complete response, 9.5% (2) of patients showed partial response, 4.8% (1) of patients showed stable disease, and 9.5% (2) of patients showed progression of disease. Median OS was 21 months, whereas 1-year survival rate was 63.7%. No Grade 3 or Grade 4 AEs were observed.Conclusion:Nimotuzumab with IMRT has achieved promising clinical outcomes in unresectable locally advanced SCCHN patients who are ineligible for platinum-based chemotherapy, without accumulation of toxicity.

Associations between expression levels of nucleotide excision repair proteins in lymphoblastoid cells and risk of squamous cell carcinoma of the head and neck

Squamous cell carcinoma of head and neck (SCCHN) is one of the most common malignancies worldwide, and nucleotide excision repair (NER) is involved in SCCHN susceptibility. In this analysis of 349 newly diagnosed SCCHN patients and 295 cancer-free controls, we investigated whether expression levels of eight core NER proteins were associated with risk of SCCHN. We quantified NER protein expression levels in cultured peripheral lymphocytes using a reverse-phase protein microarray. Compared with the controls, SCCHN patients had statistically significantly lower expression levels of ERCC3 and XPA (P = 0.001 and 0.001, respectively). After dividing the subjects by controls' median values of expression levels, we found a dose-dependent association between an increased risk of SCCHN and low expression levels of ERCC3 (adjusted OR, 1.75, and 95% CI: 1.26-2.42; Ptrend = 0.008) and XPA (adjusted OR, 1.88; 95% CI, 1.35-2.60; Ptrend = 0.001). We also identified a significant multiplicative interaction between smoking status and ERCC3 expression levels (P = 0.014). Finally, after integrating demographic and clinical variables, we found that the addition of ERCC3 and XPA expression levels to the model significantly improved the sensitivity of the expanded model on SCCHN risk. In conclusion, reduced protein expression levels of ERCC3 and XPA were associated with an increased risk of SCCHN. However, these results need to be confirmed in additional large studies.

Patient-reported symptoms and stepwise symptom management in patients on epidermal growth factor inhibitors: A retrospective, descriptive cohort study

Adverse events (AEs) of epidermal growth factor inhibitors (EGFRi) influence well-being with a risk to dose modifications (DMs). Hereby, clinical benefit of treatment might be affected. This retrospective cohort study was set up to gain insight into the suitability and added value of a patient-reported outcome measurement tool (PROM), together with a stepwise intervention management plan for EGFRi-related AEs in daily practice. The primary objective was to gain insight into total treatment duration and DMs, and the secondary objective to gain insight into patient-reported symptoms and well-being as well as healthcare professional-reported AEs. Sixty-eight patients on cetuximab and 19 on panitumumab treatment were included for analysis; 69% had squamous cell carcinoma of head and neck (SCCHN) and 26% metastatic colorectal carcinoma. DMs due to AEs occurred in 39% of the patients and dose discontinuations in 22%. Especially anorexia, dysphagia, oral pain and skin changes led to a decreased well-being. In patients on EGFRi, application of PROMs together with a stepwise symptom management plan enhances early recognition of symptom burden, pro-active symptom management and effect evaluation of interventions performed whereby well-being recovers. Since only SCCHN patients discontinued treatment due to AEs, patient-centred care focused on radiotherapy-related AEs, creates opportunities for amelioration.

MiR-1275 promotes cell migration, invasion and proliferation in squamous cell carcinoma of head and neck via up-regulating IGF-1R and CCR7

PurposemiRNAs can play vital role in migration, invasion and proliferation in Squamous cell carcinoma of head and neck (SCCHN). In our study, we attempted to validate the expression and function of miR-1275 in SCCHN, and we also identified the mechanism by which miR-1275 affects migration, invasion and proliferation of SCCHN. MethodsReal-time polymerase chain reaction (RT-PCR) was employed to evaluate the expression of miR-1275 in both SCCHN tissues and cell lines. The role of miR-1275 in SCCHN cells was verified by cell function experiments upon transfection with miR-1275 mimics and inhibitor. Western blot analysis was employed to test the target gene expression of miR-1275. Survival analysis was made with the information of SCCHN patients expressed miR-1275 from The Cancer Genome Atlas (TCGA) database. ResultsmiR-1275 expression was up-regulated in SCCHN tissues and advanced metastatic SCCHN cells. Increasing miR-1275 expression in SCCHN could promote cell migration, invasion and proliferation probably by upregulating Insulin-like growth factor 1 receptor (IGF-1R) and C-C chemokine receptor type 7(CCR7) protein levels, whereas inhibition of miR-1275 could lead the opposite effects, although others have already demonstrated that IGF-1R is a direct target of miR-1275. Survival analysis suggested that patients with lower miR-1275 expression may have a better outcome. ConclusionsHerein we report for the first time that miR-1275 could act as a tumor-promoter in SCCHN possibly by regulating its target gene via novel miRNA mechanisms. MiR-1275 plays an important role in promoting SCCHN progression. The miR-1275 may be a potential therapeutic target for SCCHN treatment in the future.

Similarity and difference in tumor-infiltrating lymphocytes in original tumor tissues and those of in vitro expanded populations in head and neck cancer.

Though adoptive tumor-infiltrating lymphocyte (TIL) therapy has been explored in clinical trials for many years, there is little information for the clonotype composition between TILs in original tumor tissues and TILs that were in vitro expanded and infused to cancer patients. To investigate the similarity/difference in TILs in original tumor tissues and those of in vitro expanded populations in squamous cell carcinoma of head and neck (SCCHN) as well as their correlation with somatic mutations in cancer cells, we performed whole exome analysis, expression profile analysis of immune-related genes, and T cell receptor (TCR) analysis of original TILs and in vitro expanded TILs in 8 surgically-resected HPV-negative fresh tumors with SCCHN. We found an unusually high number of non-synonymous somatic mutations (4290, 1779 and 901 mutations) in three SCCHN tumors, in which we identified mutations in mismatch repair genes, MSH2 or MSH4, or a DNA polymerase gene, POLE. Interestingly, dominant TCR clonotypes of expanded CD8+ TILs derived from these three tumors revealed high similarity to those in original tumors while for remaining tumors with the lower mutational load, we found that T cell clonotypes between TILs in original tumor tissues and those expanded in vitro were almost entirely different. Our findings might provide clinically useful information for identification of tumor-antigen-specific T cell clones that may lead to further improvement of adoptive TIL therapy for SCCHN patients.

Abstract 36: Changes in cellular and molecular immune markers in the peripheral blood of patients undergoing chemotherapy and radiation for squamous cell carcinoma of head and neck: A prospective pilot study

Abstract Objective: In order to help further development of novel immunotherapeutic targets related to signal-transducer and activator of transcription-3 (STAT3) in squamous cell carcinoma of head and neck (SCCHN), data are needed to help understand changes in immune-mediated signaling during treatment. The purpose of this study was to analyze changes in the mRNA or protein expression of inflammatory or immunosuppressive mediators in peripheral blood mononuclear cells (PBMC) or plasma, in SCCHN patients receiving concurrent chemotherapy and radiation therapy (CRT). Methods: This was a prospective biospecimen collection study of 15 patients with stage III-IV SCCHN who received CRT with curative intent. Blood specimens were obtained before, during weeks 1, 2, 4, 6, and 7 of CRT, and 6-12 weeks after treatment completion. Plasma and PBMC were separated from patients' blood using Vacutainer CPT tubes (BD Bioscience) within 2 hours after collection by centrifugation at 1800×g for 20 min at room temperature and stored in -80°C. Plasma samples were analyzed for 30 human cytokines and chemokines using Luminex FLEXMAP 3D system at the Clinical Immunobiology Correlative Studies (CICSL) core at City of Hope. mRNA was isolated from PBMCs acquired at the baseline and at the second week draw during RT from 6 patients and expression of 730 genes selected for immune profiling was evaluated using nCounter Immune Cell Profiling Assay, and data were analyzed using nSolver software (Nanostring). Results: Among the plasma level of 30 cytokines tested by Luminex Assay, IL-6 showed cumulative increase during RT (one-way ANOVA, p=0.046). At 6 week post RT, IL-6 level decreased comparable to baseline level. Plasma level of IFN-gamma was significantly increased at 2 week of RT and the level remained unchanged until 12 week post CRT (p=0.0004). In contrast, we observed pro-inflammatory cytokine IL-12 was significantly decreased during CRT (p=0.0004). Plasma level of a tumor promoting cytokine HGF was significantly increased during and 12 week post CRT (p=0.0035). Comparison of gene expression profiles in PBMC from 6 patients between baseline and the second week of CRT indicates that mRNA expression of 335 immune-regulators are differentially expressed (p&amp;lt;0.05) among 740 tested. Consistent with the plasma cytokine analysis, mRNA level of IL-6 in PBMC was 13.9 fold increased (p=0.003). Subsequently, increase in STAT3 expression was observed (1.7 fold, p=0.002) since IL-6 stimulates Janus kinase (JAK)-STAT pathway. In addition, mRNA expression of Th2 cytokines including IL-10, IL-5, and TGFb1 were significantly increased by greater than 2 folds (p&amp;lt;0.05). Conclusion: These results suggest CRT affects immune activation in SCCHN patients systemically, which may contribute to immune suppression and disease relapse after treatment. Our data provide an impetus for investigating STAT3-targeted therapies in SCCHN. Citation Format: Sagus Sampath, Hae Jung Won, Ellie Maghami, Erminia Massarelli, Nayana Vora, Lalit Vora, Marcin Kortylewski. Changes in cellular and molecular immune markers in the peripheral blood of patients undergoing chemotherapy and radiation for squamous cell carcinoma of head and neck: A prospective pilot study [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 36.

Prognostic implication of ERCC1 protein expression in resected oropharynx and oral cavity cancer

BackgroundExcision repair cross complement group 1 (ERCC1) expression is a predictive biomarker for platinum-containing treatment in squamous cell carcinoma of head and neck (SCCHN). However, the prognostic significance after surgical resection is not well understood. MethodsOropharynx (n=143) or oral cavity (n=61) SCCHN patients undergoing surgery were included. ERCC1 protein expression and HPV status were assessed by ERCC1 and p16 immunohistochemistry. ResultsThe ERCC1, over-expressed in 66.7% of patients, was associated with oral cavity cancer (P<0.001), well differentiation (P=0.036), and HPV negativity (P<0.001). In TCGA database, ERCC1 mRNA upregulation was enriched in HPV-negative and oral cavity cancers, and associated with HRAS mutation (P<0.001). The prognostic role of ERCC1 was not different according to HPV status. High ERCC1 expression showed a trend toward poor prognosis in patients with an advanced stage (P=0.079) with marginal significance. ConclusionsThe ERCC1 expression was not prognostic in surgically resected oropharynx/oral cavity SCCHN, irrespective of HPV status. However, it could provide additional prognostic information for advanced stage patients.

Reduced mRNA expression of nucleotide excision repair genes in lymphocytes and risk of squamous cell carcinoma of the head and neck.

Nucleotide excision repair (NER) plays a critical role in the development of smoking-related cancers. We hypothesize that mRNA expression levels of NER genes are associated with risk of the squamous cell carcinoma of head and neck (SCCHN). To test this hypothesis, we conducted a case-control study of 260 SCCHN patients and 246 cancer-free controls by measuring the mRNA expression levels of eight core NER genes in cultured peripheral lymphocytes. Compared with the controls, cases had statistically significantly lower expression levels of DDB1 and ERCC3 (P = 0.015 and 0.041, respectively). Because DDB1 and ERCC3 expression levels were highly correlated, we used DDB1 for further multivariate analyses and modeling. After dividing the subjects by controls' quartiles of expression levels, we found an association between an increased risk of SCCHN and low DDB1 expression levels [adjusted ORs and 95% CIs: 1.92 and 1.11-3.32, 1.48 and 0.85-2.59, 2.00 and 1.15-3.45 for the 2nd-4th quartiles, respectively, compared with the 1st quartile; Ptrend = 0.026]. We also identified a multiplicative interaction between sex and DDB1 expression levels (P = 0.007). Finally, the expanded model with gene expression levels, in addition to demographic and clinical variables, on SCCHN risk was significantly improved, especially among men. In conclusion, reduced DDB1 expression levels were associated with an increased risk of SCCHN. However, these results need to be validated in larger studies.

CIAP-2 Expression Increases in Elderly Patients with Squamous Cell Carcinoma of the Head and Neck

Summary Background Evidence indicates apoptosis deregulation is associated with aging. We correlated expression of cIAP-2, a member of the inhibitor of apoptosis protein family, with survival and age in patients with resected squamous cell carcinoma of head and neck (SCCHN). Methods Immunohistochemical (IHC) staining for cIAP-2 and other markers were performed using tissue microarrays from 103 resected SCCHN patients. Expression was grouped according to IHC scores (0–3) and statistical association with clinical–pathological factors was determined. Results High expression of cIAP-2 was found to be increased in patients aged 60 or greater. High expression of cIAP-2 and an age ≥60 were significantly associated with worse survival in univariate analysis, but only an age ≥60, and not cIAP-2 expression, was prognostic in multivariate analysis. Conclusion High expression of cIAP-2 was found more frequently in elderly SCCHN patients but was not independently associated with survival after adjusting other clinical–pathologic factors.

САР1 AS A SERUM MARKER FOR EARLY DETECTION OF LARYNGEAL AND HYPOPHARYNGEAL CANCERS

Squamous cell carcinoma of head and neck (SCCHN) is often asymptomatic until it reaches the advanced stage. Currently, there are no available markers that can accurately predict the risk of progression of epithelial dysplasia to squamous cell carcinoma. The purpose of the study was to evaluate the feasibility of using the level of adenylyl cyclase-associated protein 1 (CAP-1) in the blood serum to identify groups of increased risk of cancer in patients with chronic laryngeal and hypopharyngeal hyperplasia associated with epithelial dysplasia. Material and methods. The blood serums from 45 patients with SCCHN ( T 1–4 N 0–3 M 0 ), 12 patients with chronic inflammatory laryngeal and hypopharyngeal diseases and 15 heath subjects were examined. The blood analysis was performed using the CAP1 ELISA kit (Cusabio) on the Biochrom Anthos 2020 Microplate IEA Reader. Results . The serum level of САР 1 was higher by 75 % in patients with SCCHN ( Т 1 N 0 M 0 ) than in patients with chronic hyperplastic laryngitis. Moreover, differences in the serum level of САР 1 were observed between healthy subjects and patients with chronic laryngeal hyperplasia. In SCCHN patients with regional metastases, CAP1 concentration in the blood serum was 2 times higher compared to that observed in SCCHN patients without regional metastases (p≤0.01). Conclusion . The study results showed the feasibility of using the level of CAP1 for distinguishing patients with chronic hyperplastic laryngitis from those with laryngeal cancer, as well as for early detection of SCCHN and the development of new method for prediction of disease.

Human papillomavirus/p16 positive head and neck cancer in India: Prevalence, clinical impact, and influence of tobacco use.

Limited data are available on the prevalence and prognostic significance of human papillomavirus (HPV) in squamous cell carcinoma of head and neck (SCCHN) in the Indian population. The present study aimed to determine the prevalence of HPV and p16 in an Indian cohort of SCCHN and assess their correlation and influence of tobacco use on patient outcomes. The p16 and HPV status of 170 patients of SCCHN treated with curative chemoradiotherapy was determined using immunohistochemistry and polymerase chain reaction, respectively, and further correlated with their demographic characteristics. In addition, genotyping of HPV-positive samples was performed. Survival outcomes were analyzed and compared for both p16 positive (p16 +ve) and p16 negative (p16 -ve) population. The influence of tobacco use on outcomes was assessed. p16 expression was observed in 20% (34/170) cases whereas HPV positivity was detected in 39.4% (67/170) of SCCHN patients with HPV16 being the most common (91%) subtype. About 73.5% patients were p16 +ve among the tobacco users in this cohort (83.5%). Interestingly, p16 positivity was significantly associated with nonusers of tobacco (P = 0.02) and younger females (P = 0.06). The p16 +ve and p16 -ve groups did not exhibit a significant difference in the 5-year cause-specific survival (CSS) (79% vs. 72.2%), disease-free survival (DFS) (78.3% vs. 68.3%, P = 0.5), and locoregional control (LRC) (82.2% vs. 71.5%, P = 0.4). However, the outcome analyses in tobacco nonusers revealed a definite large improvement in CSS (P = 0.08) and a trend toward improvement in DFS (P = 0.15) and LRC (P = 0.11) in the p16 +ve versus the p16 -ve groups. The low prevalence of p16 positivity (20%) and dual HPV and p16 positivity (38.8%) in the studied Indian cohort indicates the low utility of p16 as a surrogate for HPV in the background of high tobacco burden. The outcomes are largely improved in a small subset of SCCHN cases comprising p16 +ve tobacco nonusers.

Initial experience of radiotherapy plus cetuximab for Japanese head and neck cancer patients

In Japan, cetuximab with concurrent bioradiotherapy (BRT) for squamous cell carcinoma of head and neck (SCCHN) was approved in December 2012. We herein report our initial experience of BRT, with special emphasis on acute toxicities of this combination therapy. Thirty-one non-metastatic SCCHN patients who underwent BRT using cetuximab between July 2013 and June 2014 were retrospectively evaluated. All patients received cetuximab with a loading dose of 400 mg/m2 one week before the start of radiotherapy, followed by 250 mg/m2 per week during radiotherapy. The median cycle of cetuximab was seven cycles and the median dose of radiotherapy was 70 Gy. Twenty-five patients (80.6%) accomplished planned radiotherapy and six cycles or more cetuximab administration. Six patients (19.4%) discontinued cetuximab. Grade 3 dermatitis, mucositis and infusion reaction occurred in 19.4%, 48.3% and 3.2%, respectively. One patient experienced Grade 3 gastrointestinal bleeding caused by diverticular hemorrhage during BRT. Grade 3 drug-induced pneumonitis occurred in two patients. The response rate was 74%, including 55% with a complete response. BRT using cetuximab for Japanese patients with SCCHN was feasible as an alternative for cisplatin-based concurrent chemoradiation, although longer follow-up is necessary to evaluate late toxicities.

Robot/Endoscope–Assisted Selective Neck Dissection by a Postauricular Facelift Approach for cN0 SCCHN

Objectives: We have developed a new novel neck dissection procedure by postauricular facelift incision using the da Vinci robot or endoscope to avoid a long visible neck scar. The aim of this study is to investigate the feasibility and efficacy of this novel procedure in squamous cell carcinoma of head and neck (SCCHN) comparing with conventional neck dissection. Methods: We analyzed 30 SCCHN patients with clinically node negative neck (cN0) who underwent robot/endoscope assisted selective neck dissection (SND) by postauricular facelift approach (11 patients, 12 necks) or conventional neck dissection (19 patients, 21 necks). Results: The distributions of gender and age did not differ between the two groups. The extent of SND was level I, II, and III in oral cancer, and level II, III, with/without IV, V in oropharynx, larynx, and hypopharynx cancer in both group. The robot/endoscope assisted SND was completed successfully in all patients. The mean operative time of SND was longer in the robot/endoscope group (219 ± 65 min) than the conventional group (144 ± 43 min) ( P &lt; 0.05). The mean number of lymph nodes removed was 24.6 ± 8.0 and 28.9 ± 8.2 in the robot/endoscope and conventional group, respectively ( P = 0.151), and the number of lymph nodes removed in each levels also did not differ between the two groups. There was no major postoperative complication in both groups. Conclusions: Robot or endoscope assisted SND by postauricular facelift approach is a cosmetically excellent procedure and comparable to conventional neck dissection in selected patients with cN0 SCCHN.

Randomized phase III trial of concurrent chemoradiotherapy vs accelerated hyperfractionation radiotherapy in locally advanced head and neck cancer

The aim of this study was to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) vs accelerated hyperfractionation with concomitant boost (CCB) as a primary treatment for patients with Stage III–IV squamous cell carcinoma of head and neck (SCCHN). A total of 85 non-metastatic advanced SCCHN patients were accrued from January 2003 to December 2007. Of these, 48 and 37 patients received CCRT and CCB, respectively. The patients were randomized to receive either three cycles of carboplatin and 5-fluorouracil plus conventional radiotherapy (CCRT, 66 Gy in 6.5 weeks) or hybrid accelerated radiotherapy (CCB, 70 Gy in 6 weeks). The primary endpoint was determined by locoregional control rate. The secondary endpoints were overall survival and toxicity. With a median follow-up of 43 months (range, 3–102), the 5-year locoregional control rate was 69.6% in the CCRT arm vs 55.0% in the CCB arm (P = 0.184). The 5-year overall survival rate was marginally significantly different (P = 0.05): 76.1% in the CCRT arm vs 63.5% in the CCB arm. Radiotherapy treatment interruptions of more than three days were 60.4% and 40.5% in the CCRT arm and CCB arm, respectively. The median total treatment time was 55.5 days in the CCRT arm and 49 days in the CCB arm. The rate of Grade 3–4 acute mucositis was significantly higher in the CCB arm (67.6% vs 41.7%, P = 0.01), but no high grade hematologic toxicities were found in the CCB arm (27.2% vs 0%). CCRT has shown a trend of improving outcome over CCB irradiation in locoregionally advanced head and neck cancer.

Determinants of oxidative stress and DNA damage (8-OhdG) in squamous cell carcinoma of head and neck

Squamous cell carcinoma of head and neck (SCCHN) is a major concern of health risk in developing countries, such as India. Apart from genetic configuration, environmental and lifestyle factors, as well as poor oral hygiene, provide free radical-generating environment, which may contribute to the development of cancer through DNA damage. Here we ascertained the various oxidative stress determinants in diagnosed SCCHN patients with health risk addictions. This study further evaluated the incremental effects inflicted by these lifestyle factors on redox status. The study included 100 consenting SCCHN patients and 90 matched healthy controls. Salivary total antioxidant capacity (TAC), glutathione (GSH), free radicals: such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) along with oxidative DNA adduct (8-OHdG) were monitored. Our findings indicated altered salivary oxidant-antioxidant status in SCCHN. A substantial rise in ROS (~2.0 folds) and RNS (~1.4 folds), together with significant lowering in TAC (~1.2 folds) and GSH (~1.7 folds) was observed. The 8-OHdG levels were also found to be considerably higher (P < 0.001) in salivary cell's DNA of these patients. Our results demonstrate significant redox imbalance in cancer patients suggesting their paramount importance in the development of SCCHN.

Associated risk of XRCC1 and XPD cross talk and life style factors in progression of head and neck cancer in north Indian population

Effective DNA repair machinery ensures maintenance of genomic integrity. Environmental insults, ageing and replication errors necessitate the need for proper DNA repair systems. Any alteration in DNA repair efficacy would play a dominant role in progression of squamous cell carcinoma of head and neck (SCCHN).Genotypes of XRCC1 gene–Arg194Trp, Arg280His, Arg399Gln and XPD Lys751Gln, by PCR-RFLP were studied in 278 SCCHN patients and an equal number of matched healthy controls residing in north India.In XRCC1 polymorphisms, Arg194Trp and Arg399Gln variants showed a reduced risk, whereas, XPD Lys751Gln variants exhibited ∼2-fold increase in SCCHN risk. With XRCC1-Arg280His variants, there was no association with SCCHN risk. Arg399Gln of XRCC1 appears to have a protective role in people those consume alcohol, while XPD Lys751Gln variants indicated ∼2-fold increased risk of SCCHN in all the co-variate groups.Comparison of gene–gene interaction among XRCC1 Arg280His and XPD Lys751Gln suggested enhanced risk of SCCHN by ∼2.3-fold in group one and ∼6.1-fold in group two. In dichotomized groups of this combination, the risk was ∼2.4 times. Haplotype analysis revealed the frequency of C–G–G–G and C–A–G–G to be significantly associated with an increased risk of SCCHN. On the contrary, T–G–A–A significantly diminished the risk. CART analysis results showed that the terminal node that contains homozygous mutants of XPD Lys751Gln and XRCC1 Arg194Trp, wild type of XRCC1 Arg399Gln and homozygous mutant of XRCC1 Arg280His, represent the highest risk group.Our results demonstrate high degree of gene–gene interaction involving DNA repair genes of NER and BER pathways, namely XRCC1 and XPD. This study amply demonstrates positive association of XPD Arg751Gln polymorphism with an increased risk of SCCHN. Further, XRCC1 Arg280His variant though dormant individually, may also contribute to the development of cancer in combination with XPD Arg751Gln.