Project description:ObjectiveTo study the prognostic value of leukocyte increase in a retrospective cohort of locally advanced head and neck squamous cell carcinoma (HNSCC) patients receiving definitive concurrent cisplatin and radiation.Materials and methodsClinical records of consecutive previously untreated locally advanced HNSCC patients treated in our Institution between March 2006 and October 2012 by concurrent cisplatin (100?mg/m2, every 3?weeks) and radiation (70?Gy in 7?weeks) were collected. The prognostic value of pretreatment leukocyte increase was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as a leukocyte count or a neutrophils count exceeding 10 and 7.5?G/L, respectively.ResultsWe identified 193 patients, all treated with concurrent cisplatin-based chemoradiotherapy. Respectively 24% and 20% patients displayed baseline leukocytosis or neutrophilia. Mean leukocyte count were significantly more elevated in current smokers, patients with performance status (PS) >0, T4 and less in HPV?+?tumor. The 5-year actuarial overall survival (OS) and progression-free survival (PFS) were 56% and 51% respectively. In univariate analysis, both leukocytosis and neutrophilia were strongly associated with worse OS and PFS (p?<?0.001). In multivariate analysis, N classification, HPV/p16, smoking status and leukocytosis were associated with worse OS and PFS. Patients with <3 cycles of cisplatin had worse survival.ConclusionIn locally advanced HNSCC treated with concurrent cisplatin and radiation, baseline leukocytosis predicts OS and PFS. In addition with HPV status, this independent biomarker could help identifying patients with high risk of tumor relapse.
Project description:Study on the impact of pretreatment malnutrition on treatment outcomes in locally advanced head and neck cancer (LAHNC) patients is still lacking. We prospectively collected various malnutrition assessment methods including nutrition indexes, inflammatory biomarkers, and lean body mass index (LBMI) data before treatments. The one year mortality rate was assessed, and the factors associated with this outcome were investigated. Furthermore, the association between malnutrition assessment methods was examined. A total of 113 patients were enrolled. By prognostic stratification based on the prognostic nutritional index (PNI) and platelet-to-lymphocyte ratio (PLR) combination, the low PNI/high PLR group had highest and the high PNI/low PLR group had the lowest mortality rate. Furthermore, the PNI was positively correlated with the LBMI, and the PLR was inversely correlated with the LBMI. PNI and PLR were found to be independent prognostic factors of one year mortality and also associated with the loss of muscle.
Project description:Concurrent chemoradiotherapy (CCRT) has been considered to be the standard of care for locally advanced squamous cell carcinoma of head and neck (LA-SCCHN). Whether induction chemotherapy (IC) with CCRT will further improve the clinical outcomes or not is still unclear. We conducted a meta-analysis to compare the two regimens for LA-SCCHN. Literature searches were carried out in PubMed, Embase, Cochrane Library and Chinese Biology Medicine from inception to November 2014. Five prospective randomized controlled trials (RCTs) with 922 patients were included in meta-analysis. Results were expressed as hazard ratios (HRs) or relative risks (RRs) with 95% confidence intervals (CIs). Compared with CCRT, IC with CCRT showed no statistically significant differences in overall survival (OS), progression-free survival (PFS), overall response rate (ORR) or locoregional recurrence rate (LRR), but could increase risks of grade 3-4 febrile neutropenia (P = 0.0009) and leukopenia (P = 0.04). In contrast, distant metastasis rate (DMR) decreased (P = 0.006) and complete response rate (CR) improved (P = 0.010) for IC with CCRT. In conclusion, the current studies do not support the use of IC with CCRT over CCRT, and the further positioning of IC with CCRT as standard treatment for LA-SCCHN will come from more RCTs directly comparing IC followed by CCRT with CCRT.
Project description:The aim of this national population-based retrospective study was to analyze the relationship between MetS and the incidence of HNC. In this Korean population-based cohort study, 9,598,085 subjects above the age of 20 were monitored from 1 January 2009 to 31 December 2018. In the study population, a total of 10,732 individuals were newly diagnosed with HNC during the 10-year follow-up. The hazard ratio (HR), after adjusting for age, gender, smoking status, alcohol intake, and exercise, indicated that participants with MetS were at a 1.06-fold (95% CI: 1.01-1.10) higher risk of having HNC than those without MetS. Participants with MetS showed an increased risk of developing oral cavity cancer (HR, 1.12; 95% CI, 1.03-1.23) and laryngeal cancer (HR, 1.18; 95% CI, 1.09-1.27). Among the components of MetS, elevated fasting glucose (HR = 1.04, 95% CI: 1.00-1.08) and elevated blood pressure (HR = 1.08, 95% CI: 1.04-1.13) were significantly associated with an increased HR for HNC in an adjusted multivariable model. The association between HNC and MetS remained significant even among individuals who had never smoked or were ex-smokers (HR: 1.09; 95% CI: 1.04-1.15), as well as those who did not drink or were mild drinkers (HR: 1.07; 95% CI: 1.02-1.12). The findings of this cohort study suggest MetS was associated with an increased risk for some types of HNCs. The results of this study could assist with etiological investigations and prevention strategies.
Project description:The management of locally advanced unresectable head and neck squamous cell cancer (HNSCC) continues to improve. One of the major advances in the treatment of HNSCC was the addition of chemotherapy to radiation in the treatment of non-surgical patients. The majority of the data regarding chemotherapy in HNSCC involve cisplatin chemotherapy with concurrent radiation. However, several new approaches have included targeted therapy against epidermal growth factor receptor and several recent studies have explored the role of induction chemotherapy in the treatment of HNSCC. The purpose of this article is to provide an overview of the role of chemotherapy in the treatment of locally advanced HNSCC.
Project description:The present study investigated clinical outcomes and prognostic factors of patients with locally advanced synchronous esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) receiving curative concurrent chemoradiotherapy (CCRT), and determined whether synchronous ESCC/HNSCC patients had worse prognosis compared to isolated ESCC patients. Using propensity score matching method, we compared 60 locally advanced synchronous ESCC/HNSCC patients with 60 matched isolated ESCC patients. Compared to 60 matched isolated ESCC patients, synchronous ESCC/HNSCC patients had significantly worse prognosis (13.5 months versus 17.2 months, P?=?0.01), more grade 3-4 CCRT toxicity, and higher percentage of CCRT interruption. For synchronous ESCC/HNSCC group, the 1-year and 2-year survival rates were 52% and 13%, respectively. Univariate analysis showed that early ESCC stage, non-T4b disease, and salvage operations were significantly associated with superior survival. In multivariate analysis, ESCC stage represented an independent prognosticator. For chemotherapy regimen during CCRT, cisplatin/5-fluorouracil had significantly more grade 3-4 mucositis/esophagitis and neutropenia than weekly cisplatin. In conclusion, synchronous ESCC/HNSCC patients receiving curative CCRT have worse prognosis and poorer compliance of CCRT compared to isolated ESCC patients. For these patients, ESCC stage and T4b disease were significantly associated with clinical outcomes, and salvage operation may improve overall survival.
Project description:Chemoradiotherapy (CRT) has led to improved efficacy in treating locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) but has led to almost universal in-field mucositis. Patients treated with the same regimen often have differences in mucositis occurrence and severity. Mucositis induced via radiation is known to represent an intense inflammatory response histologically. We hypothesized that patients destined to display severe mucocutaneous toxicity would demonstrate greater alterations in thermal intensity early in therapy than identically treated counterparts. This will allow identification of patients that will require more intensive supportive care using thermal imaging technology.Subjects with LA-SCCHN (oral cavity or oropharynx) being treated with the identical chemoradiotherapy regimen underwent baseline and weekly thermal imaging. Changes in skin temperature caused by mucositis and dermatitis compared with a reference area (?T were calculated and correlated to grade of mucositis based on NCI-CTCAE 3.0.Thirty-four subjects were enrolled. Grade 3 mucositis and dermatitis was observed in 53% and 21%, respectively. We observed a statistically significant positive association between an early rise in ?T and mucositis grade (p value=0.03).Thermal imaging is able to detect small and early changes in skin surface temperature that may be associated with development of mucositis in patients being treated with chemoradiotherapy.
Project description:PurposePembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC.Patients and methodsEligible patients included those with oral cavity (excluding lip), oropharyngeal, hypopharyngeal, or laryngeal stage III to IVB HNSCC (according to American Joint Committee on Cancer, 7th edition, staging system) eligible for cisplatin-based, standard-dose (70 Gy) chemoradiotherapy. Pembrolizumab was administered concurrently with and after chemoradiotherapy with weekly cisplatin. Safety was the primary end point and was determined by incidence of chemoradiotherapy adverse events (AEs) and immune-related AEs (irAEs). Efficacy was defined as complete response (CR) rate on end-of-treatment (EOT) imaging or with pathologic confirmation at 100 days postradiotherapy completion. Key secondary end points included overall (OS) and progression-free survival (PFS).ResultsThe study accrued 59 patients (human papillomavirus [HPV] positive, n = 34; HPV negative, n = 25) from November 2015 to October 2018. Five patients (8.8%) required discontinuation of pembrolizumab because of irAEs, all of which occurred during concurrent chemoradiotherapy; 98.3% of patients completed the full planned treatment dose (70 Gy) of radiotherapy without any delays ≥ 5 days; 88.1% of patients completed the goal cisplatin dose of ≥ 200 mg/m2. EOT CR rates were 85.3% and 78.3% for those with HPV-positive and -negative HNSCC, respectively.ConclusionPembrolizumab in combination with weekly cisplatin-based chemoradiotherapy is safe and does not impair delivery of curative radiotherapy or chemotherapy in HNSCC. Early efficacy data support further investigation of this approach.
Project description:Background: Chemoradiotherapy (CRT) including three cycles of cisplatin is considered the standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, around one-third of the patients cannot complete cisplatin because of toxicity. Carboplatin plus 5-fluorouracil (carbo-5FU) is another accepted treatment option with a different toxicity profile. We compared tolerability and efficacy of concomitant carbo-5FU and cisplatin. Patients and Methods: We conducted a retrospective analysis of LA-HNSCC patients treated with CRT in two Dutch cancer centers between 2007 and 2016. All patients received intensity-modulated radiotherapy. One center routinely administered carboplatin 300-350 mg/m2 at day 1, 22, and 43 followed by 5FU 600 mg/m2/day for 96 h. The other center used cisplatin 100 mg/m2 at day 1, 22, and 43. The primary endpoint of this study was chemotherapy completion rate. Secondary endpoints included overall survival (OS), disease-free survival (DFS), locoregional control (LRC) and distant metastasis-free interval (DMFS), toxicity, and unplanned admissions. Results: In the carbo-5FU cohort (n = 211), 60.2% of the patients completed chemotherapy vs. 76.7% (p < 0.001) of the patients in the cisplatin cohort (n = 223). Univariate analysis showed a higher risk of death in the carbo-5FU cohort [hazard ratio (HR) 1.53, 95% CI, 1.09-2.14, p = 0.01] with a 3-year OS of 65.4 vs. 76.5% for cisplatin. OS was independently associated with T and N stage and p16 status, but not with chemotherapy regimen (HR 1.08, 95% CI, 0.76-1.55, p = 0.65). Three-year DFS was 70.0% for carbo-5FU vs. 78.6% for cisplatin (HR 1.37, 95% CI, 0.93-2.01, p = 0.05). A similar outcome was observed for both LRC (HR 1.27, 95% CI, 0.74-2.09, p = 0.4) and DMFS (HR 1.08, 95% CI 0.62-1.90, p = 0.77). The risk of discontinuation for chemotherapy-associated toxicity was higher in the carbo-5FU cohort than in the cisplatin cohort (relative risk = 1.69). Conclusion: LA-HNSCC patients treated with concomitant carbo-5FU completed chemotherapy less frequently than patients treated with cisplatin. Treatment regimen was not an independent prognostic factor for OS.
Project description:In India, a considerable proportion of patients with head and neck cancer present with locoregionally advanced disease. Symptom palliation becomes a major objective in these cases when they could not be considered for a curative approach.The aim of this study is to assess the role of palliative radiotherapy for symptom control in patients with locally advanced head and neck cancer.This was a retrospective study.Between July 2015 and June 2016, 98 patients with stage IV head and neck cancer were treated with palliative radiotherapy 25 Gray (Gy)/4 fractions (fr)/1 fraction (6.25 Gy)/week. Presenting symptoms were noted. The primary end point was relief of symptoms in the 4th week after radiotherapy. Percentage symptom relief was quantified by the patient using a rupee scale. Treatment response was noted using the WHO criteria. Acute toxicity was graded as per the Radiation Therapy Oncology Group (RTOG) criteria.The most common presenting symptom was pain. At 4 weeks after radiotherapy completion, all patients had >50% pain relief. Dysphagia was improved in 82% of patients. Respiratory distress was improved in all the symptomatic patients. Tumor complete response (CR) was seen in 2 patients, partial response in 89, stable disease in 3, and progressive disease in 4. RTOG Grade 2 and 3 acute skin and mucosal toxicities were seen in 29% and 27% cases, respectively. No patient had Grade 4 adverse effect.Hypofractionated radiation could provide effective symptom palliation in advanced head and neck cancers. The weekly schedule was well tolerated and found convenient by the patients.