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State-of-the-art management of locally advanced head and neck cancer.

ABSTRACT: During the past 20 years, treatments for head and neck squamous cell carcinoma (HNSCC) have changed dramatically owing largely to the advent of novel approaches such as combined modality therapy as well as improvements in surgical and radiotherapeutic techniques. Locally advanced disease in particular, which engendered very high recurrence and mortality rates, is now associated with long-term disease-free survival in the majority of cases. This article will focus on locally advanced HNSCC, which frequently remains a clinical challenge, review state-of-the-art therapy, and introduce promising novel therapies. The field continues to evolve rapidly with new evidence during the past year clearly establishing the benefit of adjuvant chemoradiotherapy (CRT), as well as early evidence showing improved survival with the use of an epidermal growth factor receptor inhibitor in combination with radiotherapy. There are varied regimens in use for patients with locally advanced disease, but at the same time the multitude of options can plague the clinician when trying to select the most appropriate one. This article will attempt to put the various approaches into perspective and propose an evidence-based treatment algorithm.

SUBMITTER: Seiwert TY

PROVIDER: S-EPMC2361996 | biostudies-other | 2005 Apr

REPOSITORIES: biostudies-other

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Chemotherapy advances in locally advanced head and neck cancer.

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.

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Hypofractionated Radiotherapy for Palliation in Locally Advanced Head and Neck Cancer.

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.

| S-EPMC5545959 | biostudies-other

Radiotherapy for the management of locally advanced squamous cell carcinoma of the head and neck.

Project description:Squamous cell carcinomas of the head and neck (SCCHN) affect approximately 35 000 people in the United States yearly. Although survival has improved with advances in therapy, patients with advanced stages of SCCHN continue to have a poor prognosis. An understanding of rationale for treatment selection, newer developments in therapy, and treatment toxicity is critical.Standard methods of treating locally advanced SCCHN are reviewed. Advances in medical and radiotherapeutic management are discussed and the toxicities of therapy are described.Postoperative chemoradiation is used in patients with high-risk characteristics. Induction chemotherapy and altered fractionation radiation treatment have been evaluated as alternatives to definitive chemo-radiotherapy. Targeted agents such as cetuximab may prove to increase survival with minimal increase in toxicity profile. Technological improvements such as the use of intensity-modulated radiation treatment have proven to decrease some debilitating side effects from radiation treatment.Locally advanced SCCHN continues to present a therapeutic challenge. Survival, local control, and quality of life are all goals of treatment. The optimal method of treating locally advanced SCCHN is the subject of ongoing research. Long-term side effects can be minimized with the use of newer technologies and with careful treatment planning.

| S-EPMC2640438 | biostudies-other

Leukocytosis, prognosis biomarker in locally advanced head and neck cancer patients after chemoradiotherapy.

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.

| S-EPMC6068078 | biostudies-literature

Chemoradiotherapy for locally advanced head and neck cancer: 10-year follow-up of the UK Head and Neck (UKHAN1) trial.

Project description: Not available

| S-EPMC2806549 | biostudies-literature

Phase I Trial of Cetuximab, Radiotherapy, and Ipilimumab in Locally Advanced Head and Neck Cancer.

Project description:PurposeConcurrent radiotherapy with cetuximab, an anti-EGFR mAb, is a standard treatment for locally advanced head and neck squamous carcinoma (HNSCC). Cytotoxic T lymphocyte antigen-4-positive (CTLA-4+) regulatory T cells (Treg) dampen cellular immunity and correlate negatively with clinical outcomes. This phase I study added ipilimumab, an anti-CTLA-4 mAb, to cetuximab-radiotherapy.Patients and methodsA (3 + 3) design was used to establish the recommended phase II dose (RP2D) of ipilimumab, added at week 5 for four, every-3-week doses to fixed, standard cetuximab-radiotherapy. Eligible subjects had stage III to IVb, high-risk [human papillomavirus-negative (HPV-)] or intermediate-risk HPV-positive (HPV+)] HNSCC. Dose-limiting toxicity (DLT) was defined as any grade 4 adverse event (AE) except in-field radiation dermatitis or immune-related (ir) AE requiring ≥2 weeks of systemic steroids. Baseline tumor and serial blood specimens were collected for immune correlatives.ResultsFrom July 2013 to May 2016, 18 patients enrolled. Two of 6 in cohort 1 (ipilimumab 3 mg/kg) experienced grade 3 dermatologic DLTs, triggering deescalation of ipilimumab to 1 mg/kg. Dose level -1 was expanded to N = 12 without DLT. irAE included: grade 1, 2, and 3 dermatitis (2, 1, and 3 cases), grade 4 colitis (1), and grade 1 hyperthyroidism (1). Three-year disease-free survival (DFS) and overall survival were 72% [90% confidence interval (CI), 57-92] and 72% (90% CI, 56-92). High expression of coinhibitory receptors PD1/LAG3/CD39 on baseline tumor-infiltrating Treg was associated with worse DFS (HR = 5.6; 95% CI, 0.83-37.8; P = 0.08).ConclusionsThe RP2D for ipilimumab plus standard cetuximab-radiotherapy is 1 mg/kg in weeks 5, 8, 11, and 14. The regimen is tolerable and yields acceptable survival without cytotoxic chemotherapy.

| S-EPMC9164766 | biostudies-literature

Dose-dense TPF induction chemotherapy for locally advanced head and neck cancer: a phase II study.

Project description:BACKGROUND:Phase 3 studies suggest that induction chemotherapy (ICT) of cisplatin and 5-fluorouracil plus docetaxel (TPF) is effective but toxic for patients with squamous-cell carcinoma of the head and neck (SCCHN). Dose-dense chemotherapy may yield favorable outcomes compared with standard-dose chemotherapy, yet the optimal induction regimen remains undefined. We assessed the efficacy and tolerability of biweekly dose-dense TPF ICT in patients with SCCHN. METHODS:In this prospective phase II study, We enrolled patients with stage III/IV (AJCC 7th edition) unresectable squamous cell carcinoma of head and neck cancer. Patients received dose-dense TPF (ddTPF) with cisplatin and docetaxel 50?mg/m2 on day 1, leucovorin 250?mg/m2 on day1, followed by 48-h continuous infusion of 2500?mg/m2 of 5-fluorouracil on day 1 and 2, every 2?weeks for 6?cycles followed by radiotherapy. The primary endpoint was the response rate (RR) after ICT. RESULTS:Fifty-eight patients were enrolled from June 2014 to September 2015. Overall RR after ICT was 89.6% [complete response (CR), 31%; partial response (PR), 58.6%]. Grade 3/4 neutropenia, mucositis, and diarrhea incidences were 25.9, 1.7, and 1.7%, respectively. 94.8% of patients completed all treatment courses of ICT without dose reduction. The 3-year overall survival (OS) was 54.3% (95%CI: 39.7 to 66.8%) and progression-free survival (PFS) was 34.3% (95%CI: 22.0 to 46.9%). Multivariate analysis showed that CR after ICT is an independent prognostic factor for OS and PFS. CONCLUSIONS:Six cycles of ddTPF is an active, well-tolerated induction regimen for patients with SCCHN. The presence of CR after ICT predicted long-term survival. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT04397341 , May 21, 2020, retrospectively registered.

| S-EPMC7465725 | biostudies-literature

Cisplatin, cetuximab, and radiation in locally advanced head and neck squamous cell cancer: a retrospective review.

Project description:Efficacy of cisplatin versus cetuximab with radiation in locally advanced head and neck cancer (LAHNC) was evaluated. A total of 96 patients with newly diagnosed LAHNC treated at our institution between 2006 and 2011 with concurrent radiation and cisplatin (group A, n = 45), cetuximab (group B, n = 24), or started with cisplatin but switched to cetuximab because of toxicity (group C, n = 27) were reviewed. Chi-square test, analysis of variance, and log-rank test were used for analysis. The three groups had similar baseline characteristics, except for median age, T stage, albumin levels, hemoglobin levels, performance status, and comorbidities. A complete response (CR) was seen in 77%, 17%, and 67% of patients (P < 0.001), respectively. There was no significant difference in median overall survival (OS) between groups A and C. The median OS for groups A and C was not reached (>65 months), even though it was significantly longer than median OS for group B (11.6 months; P ? 0.001). The 2-year OS in groups A and C is significantly higher than that in group B (70% for groups A and C, 22% for group B). There is no significant difference in progression-free survival (PFS) between groups A and C. The median PFS for these groups was not reached (>62 months), and is significantly longer than that for group B (4.3 months; P ? 0.001). The 2-year PFS of group A (67%) and group C (76%) was significantly longer than that of group B (20%). Cisplatin with radiation appears to be more efficacious even in suboptimal dosing than cetuximab with radiation in LAHNC but the two groups were not well matched.

| S-EPMC4283547 | biostudies-literature

Characteristics and treatment patterns in older patients with locally advanced head and neck cancer (KCSG HN13-01).

Project description:Background/aimsTreatment decisions for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are complicated, and multi-modal treatments are usually indicated. However, it is challenging for older patients to complete treatments. Thus, we investigated disease characteristics, real-world treatment, and outcomes in older LA-HNSCC patients.MethodsOlder patients (aged ≥ 70 years) were selected from a large nationwide cohort that included 445 patients with stage III-IVB LA-HNSCC from January 2005 to December 2015. Their data were retrospectively analyzed and compared with those of younger patients.ResultsOlder patients accounted for 18.7% (83/445) of all patients with median age was 73 years (range, 70 to 89). Proportions of primary tumors in the hypopharynx and larynx were higher in older patients and older patients had a more advanced T stage and worse performance status. Regarding treatment strategies of older patients, 44.5% of patients received concurrent chemoradiotherapy (CCRT), 41.0% underwent surgery, and 14.5% did not complete the planned treatment. Induction chemotherapy (IC) was administered to 27.7% (23/83) of older patients; the preferred regimen for IC was fluorouracil and cisplatin (47.9%). For CCRT, weekly cisplatin was prescribed 3.3 times more often than 3-weekly cisplatin (62.2% vs. 18.9%). Older patients had a 60% higher risk of death than younger patients (hazard ratio, 1.6; p = 0.035). Oral cavity cancer patients had the worst survival probability.ConclusionOlder LA-HNSCC patients had aggressive tumor characteristics and received less intensive treatment, resulting in poor survival. Further research focusing on the older population is necessary.

| S-EPMC8747907 | biostudies-literature

microRNA profiling for prediction of chemoradiation efficacy in locally advanced head and neck squamous cell carcinoma

Project description:The predictive value of microRNAs for the efficacy of chemoradiation (CRTX) in locally advanced head and neck squamous cell carcinoma (HNSCC) was evaluated. Formalin-fixed, paraffin-embedded tumor material was collected from patients with locally advanced HNSCC treated within the ARO-0401 phase III trial with radiotherapy in combination with either 5-fluorouracil/cisplatin (CDDP-CRTX) or 5-fluorouracil/mitomycin C (MMC-CRTX).

2017-03-30 | E-MTAB-5198 | biostudies-arrayexpress

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