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Induction Therapy for Locally Advanced Head and Neck Squamous Cell Carcinoma.

ABSTRACT: The optimal approach to locally advanced head and neck squamous cell carcinoma (LAHNSCC) treatment remains controversial. For non-resectable LAHNSCC, the clinical interest of induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) or radiotherapy has been questioned. With the approval of immunotherapy and targeted therapy for this disease, treatment options have become more complex. Although new trial data have appeared every year, the results are still inconclusive. In this review, we provide readers with information on new strategies for LAHNSCC induction therapy, which will facilitate evidence-based decision making in LAHNSCC treatment.

SUBMITTER: Zheng S

PROVIDER: S-EPMC10260727 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Induction Therapy for Locally Advanced Head and Neck Squamous Cell Carcinoma.

Zheng Shuwen S Feng Yumei Y Li Chan C Zhang Jie J Xie Ke K

Oncology and therapy 20230321 2

The optimal approach to locally advanced head and neck squamous cell carcinoma (LAHNSCC) treatment remains controversial. For non-resectable LAHNSCC, the clinical interest of induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) or radiotherapy has been questioned. With the approval of immunotherapy and targeted therapy for this disease, treatment options have become more complex. Although new trial data have appeared every year, the results are still inconclusive. In this revie ...[more]

PMID: 36943658

Similar Datasets

Response to induction chemotherapy as a prognostic indicator in locally advanced head and neck squamous cell carcinoma.

Project description:PurposeInduction chemotherapy (IC) for patients with locally advanced stage Head and Neck Squamous Cell Carcinomas (HNSCC) before radio-chemotherapy (RCT) or surgery remains a potential treatment option. This study analyzed how the response to IC correlates with survival outcomes.MethodsWe conducted a retrospective single-center study at a tertiary cancer center. Tumors were categorized by anatomical site and response to IC (non-responders vs. responders). Data were analyzed using Kaplan-Meier survival curves and Cox regression analysis.ResultsA total of 48 patients received IC. Of these, 33 patients were radiologically evaluable for response. The majority of evaluable patients received either TPF (Docetaxel, Cisplatin, 5-Fluorouracil) (58%) or TP (Docetaxel, Cisplatin) (24%) as their IC regimen. Tumor reduction of 30% or more was observed in 23 patients (69.7%), the tumor control rate was 97%. The 2-year event-free survival (EFS) in the IC evaluable population was 53.1%, overall survival (OS) was 63.6%, and recurrence-free survival (RFS) was 62.5%. Patients with laryngeal or hypopharyngeal tumors that did not respond to IC had a significantly poorer prognosis. This effect was not statistically significant in tumors of the oral cavity or oropharynx, where it was only observed as a trend.ConclusionIC is highly effective in treating locally advanced stage HNSCC. The response to IC is prognostic for survival, particularly in cancers of the larynx and hypopharynx.

| S-EPMC11615028 | biostudies-literature

Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck: role, controversy, and future directions.

Project description:BackgroundThe value of induction chemotherapy (ICT) remains under investigation despite decades of research. New advancements in the field, specifically regarding the induction regimen of choice, have reignited interest in this approach for patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Sufficient evidence has accumulated regarding the benefits and superiority of TPF (docetaxel, cisplatin, and fluorouracil) over the chemotherapy doublet cisplatin and fluorouracil. We therefore sought to collate and interpret the available data and further discuss the considerations for delivering ICT safely and optimally selecting suitable post-ICT regimens.DesignWe nonsystematically reviewed published phase III clinical trials on TPF ICT in a variety of LA SCCHN patient populations conducted between 1990 and 2017.ResultsTPF may confer survival and organ preservation benefits in a subgroup of patients with functionally inoperable or poor-prognosis LA SCCHN. Additionally, patients with operable disease or good prognosis (who are not candidates for organ preservation) may benefit from TPF induction in terms of reducing local and distant failure rates and facilitating treatment deintensification in selected populations. The safe administration of TPF requires treatment by a multidisciplinary team at an experienced institution. The management of adverse events associated with TPF and post-ICT radiotherapy-based treatment is crucial. Finally, post-ICT chemotherapy alternatives to cisplatin concurrent with radiotherapy (i.e. cetuximab or carboplatin plus radiotherapy) appear promising and must be investigated further.ConclusionsTPF is an evidence-based ICT regimen of choice in LA SCCHN and confers benefits in suitable patients when it is administered safely by an experienced multidisciplinary team and paired with the optimal post-ICT regimen, for which, however, no consensus currently exists.

| S-EPMC5961254 | biostudies-literature

Late toxicities in locally advanced head and neck squamous cell carcinoma treated with intensity modulated radiation therapy.

Project description:PurposeThe study aims to report late toxicities in locally advanced head-and-neck squamous cell carcinoma (LAHNSCC) treated with intensity-modulated radiation therapy (IMRT).Materials and methodsA retrospective study was conducted on 103 patients of LAHNSCC treated with IMRT. We analyzed the cumulative incidence of late xerostomia, dysphagia, and aspiration at an interval of 6-month, 1-year, 2-year, and 3-year from the start of IMRT.ResultsAt a median follow up of 4.2 years (interquartile range, 3.5 to 6 years), the cumulative incidence of grade ≥2 late xerostomia was 5.5%, dysphagia was 6.9%, and aspiration was 11.1%. Logistic regression showed that Dmean of ≥26 Gy to parotids had higher risk of xerostomia (hazard ratio [HR] = 5.19; 95% confidence interval [CI], 1.90-14.22; p = 0.001). Late dysphagia was associated with Dmean of ≥45 Gy to pharyngeal constrictors (PC) (HR = 7; 95% CI, 1.84-26.61; p =0.004), ≥55 Gy to larynx (HR = 3.25; 95% CI, 1.15-9.11; p = 0.025), and adjuvant RT (HR = 5.26; 95% CI, 1.85-14.87; p = 0.002). Aspiration was associated with Dmean of ≥45 Gy to larynx (HR = 6.5; 95% CI, 1.93-21.88; p = 0.003), Dmean of ≥55 Gy to PC (HR = 3.54; 95% CI, 1.25-9.98; p = 0.017), and patients having late dysphagia (HR = 4.37; 95% CI, 1.55-12.31; p = 0.005).ConclusionIMRT is a feasible radiation delivery technique in LAHNSCC with a decreased late toxicity profile.

| S-EPMC8497871 | biostudies-literature

Targeted Therapy in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (LA-R/M HNSCC).

Project description:Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemoradiotherapy is an alternative for patients with locally advanced disease. In recurrent/metastatic disease and after progression to platin-based regimens, no standard treatments other than best supportive care are currently available. Most SCCHN tumours overexpress the epidermal growth factor receptor (EGFR). This receptor is a tyrosine-kinase membrane receptor that has been implicated in angiogenesis, tumour progression and resistance to different cancer treatments. In this review, we analysed the different drugs and pathways under development to treat SCCHN, especially recurrent/metastatic disease. Until now, the EGFR signalling pathway has been considered the most important target with respect to new drugs; however, new drugs, such as immunotherapies, are currently under study. As new treatments for SCCHN are developed, the influence of therapies with respect to overall survival, progression free survival and quality of life in patients with this disease is changing.

| S-EPMC4810111 | biostudies-literature

Targeting the Tumor Microenvironment through mTOR Inhibition and Chemotherapy as Induction Therapy for Locally Advanced Head and Neck Squamous Cell Carcinoma: The CAPRA Study.

Project description:Mammalian target of rapamycin (mTOR) regulates cellular functions by integrating intracellular signals and signals from the tumor microenvironment (TME). The PI3K-AKT-mTOR pathway is activated in 70% of head and neck squamous cell carcinoma (HNSCC) and associated with poor prognosis. This phase I-II study investigated the effect of mTOR inhibition using weekly everolimus (30 mg for dose level 1, 50 mg for dose level 2) combined with weekly induction chemotherapy (AUC2 carboplatin and 60 mg/m2 paclitaxel) in treatment-naïve patients with locally advanced T3-4/N0-3 HNSCC. Patients received 9 weekly cycles before chemoradiotherapy. Objectives were safety and antitumor activity along with tissue and blood molecular biomarkers. A total of 50 patients were enrolled. Among 41 evaluable patients treated at the recommended dose of 50 mg everolimus weekly, tolerance was good and overall response rate was 75.6%, including 20 major responses (≥50% reduction in tumor size). A significant decrease in expression of p-S6K (p-value: 0.007) and Ki67 (p-value: 0.01) was observed in post-treatment tumor tissue. Pro-immunogenic cytokine release (Th1 cytokines IFN-γ, IL-2, and TNF-β) was observed in the peripheral blood. The combination of everolimus and chemotherapy in HNSCC was safe and achieved major tumor responses. This strategy favorably impacts the TME and might be combined with immunotherapeutic agents.

| S-EPMC9496893 | biostudies-literature

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

Gene expression signatures and molecular markers predict response to therapy in locally advanced head and neck squamous cell carcinoma.

Project description:Locally advanced head and neck squamous cell carcinomas (HNSCC) are commonly treated with chemoradiotherapy (CRT) or induction chemotherapy followed by radiotherapy/CRT or surgery. The purpose of our study was to identify expression signatures and molecular markers able to anticipate tumor response to therapy and clinical outcome. We performed a study with 63 pre-treatment tumor biopsies from locally advanced HNSCC treated with either of the two standard treatments. Cluster analysis identified three tumor subtypes associated with significant differences in local recurrence-free survival (LRFS) and overall survival (OS). Tumor subtype 1, associated with low LRFS and OS, showed features of epithelial-mesenchymal transition and undifferentiation. It also overexpressed genes related to cell adhesion, NF-κB and integrin signalling pathways. Tumor subtype 3, associated with a high LRFS and OS, showed a high degree of differentiation and overexpressed genes located in chromosome regions 19q13 and 1q21. Tumor subtype 2, with a LRFS that was similar to subtype 3 and an OS similar to subtype 1, overexpressed genes involved in branching morphogenesis. ROC analysis identified genes associated with local recurrence and survival. Using qRT-PCR we confirmed the association of RAB25, DUOX1 and THBS1 expression with LRFS and OS. Patients whose tumors displayed high RAB25 or DUOX1 mRNA levels had longer LRFS and OS than patients with low mRNA levels. In contrast, patients bearing tumors with high THBS1 levels had a shorter OS than patients with low THBS1 levels. RAB25, DUOX1 and THBS1 could be good molecular markers to identify patients who would benefit from genotoxic treatment. Sixty three pretreatment HNSCC biopsies and five normal mucosas were assayed using the Affymetrix HG-U133A2.0 array.

2011-05-31 | E-GEOD-23036 | biostudies-arrayexpress

Induction chemotherapy with concurrent chemoradiotherapy versus concurrent chemoradiotherapy for locally advanced squamous cell carcinoma of head and neck: a meta-analysis.

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.

| S-EPMC4455182 | biostudies-literature

A Phase II Study of Genexol-PM and Cisplatin as Induction Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma.

Project description:Lessons learnedInduction chemotherapy with Genexol-PM and cisplatin demonstrated modest tumor response in locally advanced head and neck squamous cell carcinoma.Considering favorable toxicity profiles and promising survival data, further studies on this regimen are warranted in patients with head and neck squamous cell carcinoma.BackgroundGenexol-PM is a polymeric micellar formulation of paclitaxel without Cremophor EL. We investigated the efficacy and safety of Genexol-PM plus cisplatin as induction chemotherapy (IC) in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC).MethodsPatients received Genexol-PM (230 mg/m2) and cisplatin (60 mg/m2) every 3 weeks as IC. After three cycles of IC, definitive treatment of either concurrent chemoradiotherapy (CCRT) with weekly cisplatin (30 mg/m2) or surgery was performed. The primary endpoint was overall response rate (ORR) after IC.ResultsOf 52 patients enrolled, 47 completed three cycles of IC, and the ORR was 55.8% (95% confidence interval, 42.3-69.3). Although there was one treatment-related death, toxicity profiles to Genexol-PM and cisplatin were generally favorable, and the most common grade 3 or 4 toxicities were neutropenia (15.4%), anorexia (7.7%), and general weakness (7.7%). Fifty-one patients received definitive treatment (CCRT [n = 44] or radical surgery [n = 7]). The rate of complete response following CCRT was 81.8% (36/44). After a median follow-up of 39 months, estimates of progression-free survival (PFS) and overall survival (OS) at 3 years were 54.3% and 71.3%, respectively.ConclusionIC with Genexol-PM and cisplatin demonstrated modest tumor response with well-tolerated toxicity profiles for patients with LA-HNSCC.

| S-EPMC6656523 | biostudies-literature

Nab-paclitaxel-based compared to docetaxel-based induction chemotherapy regimens for locally advanced squamous cell carcinoma of the head and neck.

Project description:We previously reported that nab-paclitaxel-based induction chemotherapy (IC) and concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent survival in head and neck squamous cell carcinoma (HNSCC). We compare the disease-specific survival (DSS) and overall survival (OS) between patients given nab-paclitaxel, cisplatin, and fluorouracil with cetuximab (APF-C) and historical controls given docetaxel, cisplatin, and fluorouracil with cetuximab (TPF-C). Patients with locally advanced HNSCC were treated with APF-C (n = 30) or TPF-C (n = 38). After 3 cycles of IC, patients were scheduled to receive cisplatin concurrent with definitive radiotherapy. T and N classification and smoking history were similar between the two groups and within p16-positive and p16-negative subsets. The median duration of follow-up for living patients in the APF-C group was 43.5 (range: 30-58) months versus 52 (range: 13-84) months for TPF-C. The 2-year DSS for patients treated with APF-C was 96.7% [95% Confidence Interval (CI): 85.2%, 99.8%] and with TPF-C was 77.6% (CI: 62.6%, 89.7%) (P = 0.0004). Disease progression that resulted in death was more frequent in the TPF-C group (39%) compared with the APF-C group (3%) when adjusted for competing risks of death from other causes (Gray's test, P = 0.0004). In p16 positive OPSCC, the 2-year DSS for APF-C was 100% and for TPF-C was 74.6% (CI: 47.4%, 94.6%) (P = 0.0019) and the 2-year OS for APF-C was 94.1% (CI: 65.0%, 99.2%) and for TPF-C was 74.6% (CI: 39.8%, 91.1%) (P = 0.013). In p16 negative HNSCC, the 2-year DSS for APF-C was 91.7% (CI: 67.6%, 99.6%) and for TPF-C was 82.6% (CI: 64.4%, 94.8%) (P = 0.092). A 2-year DSS and OS were significantly better with a nab-paclitaxel-based IC regimen (APF-C) compared to a docetaxel-based IC regimen (TPF-C) in p16-positive OPSCC.

| S-EPMC4402061 | biostudies-literature

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