High-risk Head And Neck Squamous Cell Carcinoma Research Articles

Phase II feasibility trial of a 3-week cycle of cisplatin plus radiation for post-operative high-risk head and neck cancer in a Japanese population.

e16007 Background: The current standard of care for post-operative high-risk head and neck squamous cell carcinoma (HNSCC) is a three-week cycle of cisplatin plus radiation (RT). In two pivotal trials (RTOG 9501 and EORTC 22931), however, the complete delivery rate of three cycles of cisplatin and RT was only about 60%. Here, we evaluated the feasibility and safety of adjuvant cisplatin plus RT in a Japanese population. Methods: Post-operative high-risk HNSCC patients were enrolled. Definitive surgery for locoregional recurrence was allowed. High-risk factors were a microscopically incomplete resection (ICR), extracapsular extension (ECE), and two or more lymph node metastases. Subjects received three cycles of cisplatin (100mg/m2) concomitant with RT (66Gy/33 Fr). Protocol treatment completion was defined as three cycles of cisplatin with a total dose of more than 240 mg/m2 with RT. Results: From August 2006 to May 2009, 25 eligible subjects were accrued, including 13 males, with a median age of 59 years, ECOG PS 0/1 (18/7), stage III/IVa/IVb/recurrent (1/18/1/5), oral cavity/oropharynx/hypopharynx/larynx (17/4/3/1), and ICR and/or ECE in 20. Protocol completion rate was 80%. Lower limit of the one-sided 90% CI was 66%, which met the predefined statistical criteria. Median relative DI of cisplatin was 0.83. Grade 3/4 acute toxicity included mucositis (44%), dysphagia (28%), dermatitis (24%), nausea/vomiting (16%), neutropenia (32%), and anemia (36%). Grade 3/4 late toxicity included dysphagia (10%), xerostomia (5%), and osteonecrosis (5%). 1-year feeding tube rate was 20%. No treatment-related deaths were observed. With a median follow-up of 25 months, 13 have had progression and 10 have died. Estimated 2-year OS and RFS were 58% and 47%. Univariate analysis revealed that oral cavity cancer and locoregional recurrence might be poor prognostic factors.Conclusions: This is the first phase II feasibility trial of a three-week cycle of cisplatin plus RT for post-operative high-risk HNSCC in an Asian population. Adjuvant three-week cycle of cisplatin plus RT was feasible and safety profile was identical to those in pivotal phase III trials.

Molecular therapy in head and neck oncology

Therapeutic management of locally advanced, recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is often limited by a rather unfavorable efficacy and toxicity ratio. Since the 1990s, targeted molecular therapy has been extensively investigated both as a single modality and in combination with cytotoxic treatments, such as radiotherapy or chemotherapy. EGFR is commonly over expressed in HNSCC and is an attractive molecular target. The EGFR signaling pathway is involved in a variety of cellular responses including cell growth and proliferation, and monoclonal antibodies and small-molecule inhibitors have been developed to inhibit EGFR pathways. Agents that target angiogenesis have also been tested in combination with EGFR inhibitors. A number of phase I/II and phase III studies have demonstrated that patients with high-risk HNSCC or those receiving palliative treatment for recurrent or metastatic disease benefit from the addition of EGFR inhibitors to chemotherapy and radiotherapy. This Review discusses the rationale for using targeted therapies based on inhibition of EGFR and angiogenesis, and describes the most recent preclinical and clinical evidence of the important role for targeted therapies in the management of head and neck cancers.

Phase III randomized trial of postoperative radiotherapy (RT) with or without carboplatin (Cb) in patients (pts) with head and neck squamous cell carcinoma (HNSCC)

6078 Background: Postoperative RT plus cisplatin is a standard treatment in high-risk resected HNSCC. However, the role of Cb in the same setting has not been established. Methods: Eligible were pts with macroscopically resected stage III/IV HNSCC with high-risk pathologic features (=3 nodes, extracapsular extension, perineural or angiolymphatic invasion, or involved margins), ECOG performance status 0–2, and adequate laboratory parameters. Pts were randomized to receive RT 59.4 Gy (1.8 Gy/day) versus the same RT plus Cb 100 mg/m2 intravenously once weekly during RT. The primary endpoint was the 2-year disease-free survival (DFS); with a projected sample size 100 patients/arm, the power was 0.81 with alpha 0.1 to detect a 15% improvement (50% to 65%). Results: From 4/94 to 4/02, 76 pts were randomized, of whom 72 pts were eligible and analyzable (36/arm). The study was prematurely closed due to slow accrual. Median age 54 years (24–83); male/female: 60 pts/12 pts; primary sites: oral cavity (n=26), oropharynx (n=23), hypopharynx (n=8), larynx (n=15); stage III/IV: 6 pts/66 pts; ECOG performance status 0/1/2: 40 pts/30 pts/2 pts. Median follow-up was 5.3 years. The 2-, 3- and 5-year DFS with RT/Cb vs. RT was 70%, 60%, and 46% vs. 55% (p=0.21), 51% (p=0.48), and 43% (p=0.79) and the 2-, 3- and 5-year overall survival (OS) was 74%, 71%, and 47% vs. 51% (p=0.04), 51% (p=0.07) and 40% (p=0.59). There were no statistically significant differences in median DFS or OS. In the subset of pts with primary sites other than the oropharynx (n=49), RT/Cb resulted in better OS vs. RT (p=0.05, Wilcoxon; p=0.27, log-rank). RT/Cb was associated with infrequent grade III/IV toxicities, including leukopenia (RT/Cb 8% vs. RT 0%), stomatitis (11% vs. 3%), and dermatitis (6% vs. 3%). Gastrostomy tube was placed in 15 pts (RT/Cb 8 vs. RT 7). Conclusions: Our data do not show a statistically significant improvement in DFS with RT/Cb vs. RT but this may reflect insufficient sample size. The potential benefit of RT/Cb for a subset of pts merits further study. No significant financial relationships to disclose.

Molecular signatures associated with clinical outcome in patients with high-risk head-and-neck squamous cell carcinoma treated by surgery and radiation

The local-regional control rate for advanced head-and-neck squamous cell carcinoma (HNSCC) remains poor and is unpredictable for a given individual. This study examined whether gene expression patterns developed from tumors from surgicopathologic, criteria-defined, high-risk HNSCC patients could be correlated with clinical outcomes, namely, metastasis or nonrecurrent disease. Fifteen primary tumors from patients treated with a consistent protocol of surgery followed by radiotherapy were examined. Seven of these tumors were from high-risk patients who developed distant metastasis (DM), and eight tumors were from patients with no recurrence (NR) (median follow-up, 59 months). Unsupervised clustering of gene expression did not separate the two groups from one another, but when supervised methodologies were applied, 205 genes discriminated the two groups. Within the DM group, genes associated with cell growth and proliferation; DNA replication, recombination, and repair; antiapoptotic pathways; cell adhesion; and angiogenesis were identified. For NR samples, discriminatory genes were associated with the onset of apoptosis. Our data suggest that gene expression analysis of surgically excised HNSCC tumors from patients considered at high risk for recurrence has the potential to identify individuals susceptible to metastasis on the basis of distinct gene-expression patterns. These patients would be ideal candidates for testing systemic therapy.

1092 PUBLICATION Prognostic significance of clinical-pathological features in high-risk head and neck squamous cell carcinoma (HNSCC) patients (pts) treated with postoperative concurrent chemoradiation (CRT)

1092 PUBLICATION Prognostic significance of clinical-pathological features in high-risk head and neck squamous cell carcinoma (HNSCC) patients (pts) treated with postoperative concurrent chemoradiation (CRT)

Postoperative chemoradiotherapy for high-risk head-and-neck squamous cell carcinoma

Purpose To describe the use of postoperative concurrent chemoradiotherapy, with either weekly cisplatin or carboplatin, for high-risk head-and-neck squamous cell carcinoma (HNSCC) in a single institutional setting. Methods and materials Between July 1999 and January 2003, 47 patients were treated with postoperative chemoradiotherapy. Results Of the 47 patients, 41 (87%) had Stage III-IV disease. The predominant primary site was the oral cavity in 24 patients (51%), 27 had nodal disease with extracapsular extension, and 26 had positive or close mucosal margins (<5 mm). Ten patients had undergone resection of recurrent disease after previous surgery. Twenty-seven (57%) were treated with cisplatin, and the remaining patients received carboplatin because of contraindications to cisplatin. The median radiotherapy dose was 60 Gy (range, 50–66 Gy). Of the 47 patients, 45 (96%) completed at least four of the six planned doses of chemotherapy and 45 (96%) completed the planned course of radiotherapy. Nineteen patients (40%) had confluent mucositis, eight (17%) had Grade 3-4 hematologic toxicity, and four (9%) had febrile neutropenia. No treatment-related deaths occurred. The estimated 2-year locoregional control, progression-free survival, and overall survival rate was 73%, 56%, and 62%, respectively. Excluding the 10 patients with recurrence after previous surgery, the locoregional control, progression-free survival, and overall survival rate was 81%, 64%, and 71%, respectively. Five cases of Grade 3-4 late treatment-related sequelae developed. Conclusion Treatment with postoperative concurrent weekly cisplatin or carboplatin and radiotherapy was reasonably well tolerated. Acute and late toxicity was acceptable. The overall results achieved are comparable with the preliminary results of recent randomized trials. Patients treated after resection of recurrent disease (after previous surgery alone) fared worse than those treated at the initial resection.