Acceleration of hyperfractionated chemoradiation regimen for advanced head and neck cancer

BACKGROUND: Our aim was to evaluate the acceleration of a hyperfractionated, concurrent chemoradiation regimen (HxCRT) for advanced head and neck squamous cell carcinoma (HNSCC). METHODS: Patients with unresectable HNSCC were treated based on a previously published HxCRT regimen: 1.25 Gy twice daily to 70 Gy concurrent with cisplatin 12 mg/m(2)/day and 5-fluorouracil 600 mg/m(2)/day for 5 days, weeks 1, 5. This regimen was accelerated in this series by shortening the treatment from 7 to 6 weeks by omitting the planned mid-treatment 1-week break. RESULTS: Forty-six patients with T3-4/N3 disease were treated. The main acute toxicity was pharyngeal. Median weight change during therapy in patients with and without enteral feeding tubes was -3.8% and -7.9%, respectively (p = .08). Fifteen percent had late grade III pharyngeal toxicity. Local/regional and distant failure rates were 28% and 17%, respectively; 52% are alive without evidence of disease. CONCLUSIONS: In nonresectable HNSCC, acceleration of the HxCRT regimen is feasible, requiring enteral feeding tubes during therapy in most patients.     

Isolated neck recurrence after definitive radiotherapy for node-positive head and neck cancer: salvage in the dissected or undissected neck

BACKGROUND: The role of salvage neck dissection for isolated regional recurrences after definitive radiotherapy (RT) is ill-defined. METHODS: Five-hundred fifty patients were treated with RT for lymph node-positive head and neck cancer. RT consisted of a median dose of 74.4 Gy. Chemotherapy was administered in 133 patients (24%). Patients were followed for neck failure after planned neck dissection (n = 341) or observation (n = 209). Salvage therapy was offered to those with isolated neck recurrences. RESULTS: There were 54 (10%) failures in the neck at a median 3.7 months after RT (range, 0 to 17 months). Thirteen patients had isolated recurrences after receiving definitive RT with (n = 11) or without (n = 2) neck dissection. Nine patients underwent attempted surgical salvage with or without re-irradiation and 4 were successfully salvaged without major complications. CONCLUSIONS: Patients with neck failure after definitive therapy usually have poor outcomes, but salvage attempts may be successful in selected patients with an isolated neck recurrence.     

Early experience with a hybrid accelerated radiotherapy schedule for locally advanced head and neck cancer

BACKGROUND: Our aim was to determine feasibility and efficacy of a hybrid radiotherapy schedule in locally advanced head and neck cancer. METHODS: Seventy-three patients with locally advanced head and neck cancer were irradiated according to a hybrid accelerated schedule consisting of 20 fractions of 2 Gy (once daily), followed by 20 fractions of 1.6 Gy (twice daily), to a total dose of 72 Gy. RESULTS: Locoregional control was 55% after 2 years. Overall survival was 59%, disease-specific survival was 63%, and disease-free survival was 46%. Acute toxicity was prospectively scored in all 73 patients: the most frequent toxicities were mucositis (50.7%, grade 3), dysphagia (47.9%, grade 3), and dermatitis (34.5%, grade 3). All patients were treated to full dose, without treatment interruption. CONCLUSION: With this regimen, acceptable locoregional control and survival rates are achieved. Toxicity was well manageable, suggesting that a combination of this schedule with concomitant chemotherapy is possible and could lead to further improvement in the treatment of locally advanced head and neck cancer.     

Radical external beam re‐irradiation in the treatment of recurrent head and neck cancer: Critical review

Management of patients with recurrent head and neck cancer remains a challenge for the surgeon as well as the treating radiation oncologist. Even in the era of modern radiotherapy, the rate of severe toxicity remains high with unsatisfactory treatment results. Intensity‐modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and heavy‐ion irradiation have all emerged as highly conformal and precise techniques that offer many radiobiological advantages in various clinical situations. Although re‐irradiation is now widespread in clinical practice, little is known about the differences in treatment response and toxicity using diverse re‐irradiation techniques. In this review, we provide a comprehensive overview of the role of radiation therapy in recurrent or second primary head and neck cancer including patient selection, therapeutic outcome, and risk using different re‐irradiation techniques. Critical review of published evidence on IMRT, SBRT, and heavy‐ion full‐dose re‐irradiation is presented including data on locoregional control, overall survival, and toxicity.     

Neck dissection in the combined-modality therapy of patients with locoregionally advanced head and neck cancer

PURPOSE: The purpose of this study was to evaluate the role of neck lymph node (ND) in the combined dissection modality therapy for locoregionally advanced head and neck. METHODS: We identified patients with N2-N3 head and neck cancers who were enrolled in three consecutive multicenter phase II studies of concurrent chemoradiotherapy utilizing 5-fluorouracil and hydroxyurea on an alternate-week schedule with radiotherapy twice daily plus either cisplatin (C-FHX) or paclitaxel (T-FHX). Patients with unknown primary tumors, nasopharyngeal or paranasal sinus primaries, nonsquamous histology, progression or death during therapy, or incomplete therapy were excluded. RESULTS: A total of 131 patients were analyzed. Seventy-nine percent had N2 stage. ND was performed in 92 patients (70%), either prior to enrollment (n = 31) or after chemoradiotherapy (n = 61). With a median follow-up of 4.6 years, the 5-year locoregional and neck progression-free survival (PFS) rates were higher in patients with ND versus patients without ND: 88% versus 74% (p =.02) and 99% versus 82% (p =.0007). respectively; there was also a trend toward improved overall survival (OS) with ND, but PFS and distant PFS were comparable. In the subset of patients with N3 disease, ND was associated not only with better locoregional control but also with improved distant PFS. However, in patients with clinical complete response (n = 92), no significant differences in PFS (68% vs 75% at 5 years, p =.53) or any other survival parameters with or without ND were observed. CONCLUSIONS: ND improves neck control and is required for patients with clinically residual disease or N3 neck cancer but has no significant impact on the outcome of patients with N2 stage disease who are rendered clinically disease-free with intensive concurrent chemoradiotherapy.     

Importance of the treatment package time in surgery and postoperative radiation therapy for squamous carcinoma of the head and neck

BACKGROUND: To determine the effect of treatment time-related factors on outcome in patients treated with surgery and postoperative radiation therapy (RT) for locally advanced squamous cell carcinoma of head and neck (SCCHN) METHODS: A retrospective review was performed on 208 consecutive patients treated from 1992 to 1997 with surgery and postoperative RT (> or =55 Gy) for SCCHN. The treatment time factors considered were (1) interval from surgery to the start of RT; (2) RT duration; and (3) the total time from surgery to completion of RT (treatment package time). Treatment package time was dichotomized into short (< or =100 days) vs long (>100 days) categories. Other variables considered were clinical and pathologic staging, margin status, RT dose, and tumor site. Patients were also divided into intermediate- and high-risk groups on the basis of eligibility for RTOG 95-01. Univariate (logrank) and multivariate analyses were performed. RESULTS: Median follow-up for surviving patients was 24 months. Actuarial 2-year locoregional control (LRC) and survival rates were 82% and 71%, respectively. In univariate analysis, factors associated with higher locoregional failure were high-risk group (p =.011), margin status (p =.038), pathologic stage (p =.035), clinical N stage (p =.006), package time (p =.013), and RT treatment time (p =.03). Package time was also a significant predictor of survival in univariate analysis (p =.021). The other two individual time factors, tumor factors, and RT dose were not significant. Both risk status and treatment package time were significant factors in a multivariate model of LRC. CONCLUSIONS: A total treatment package time of <100 days is associated with improved tumor control and survival. Every effort should be made to keep the time from surgery to the completion of postoperative RT to <100 days.     

Toxicity and outcome analysis of patients with recurrent head and neck cancer treated with hyperfractionated split-course reirradiation and concurrent cisplatin and paclitaxel chemotherapy from two prospective phase I and II studies

BACKGROUND: Patients with local recurrences or new head and neck primary tumors in previously irradiated tissues have few options for salvage treatment. One option for select patients is to undergo reirradiation with concurrent chemotherapy. The purpose of this study is to report the initial clinical results of the Fox Chase phase I and II prospective reirradiation and chemotherapy studies. METHODS: Between July 1996 and January 2002, 38 patients with locally recurrent unresectable squamous cell carcinoma of the head and neck were treated with concurrent chemotherapy and reirradiation on two prospective trials. All patients had received prior radiation therapy to the head and neck region (median dose, 64.2 Gy). Patients received cisplatin and paclitaxel along with hyperfractionated external beam radiation therapy to the site of recurrence. RESULTS: The median follow-up was 10 months. The median survival was 12.4 months, with actuarial rates of overall survival of 50% and 35% at 1 and 2 years, respectively. During follow-up, 63% of patients experienced local progression of disease, all in the irradiated field. Actuarial progression-free survival at 1 year was 33%, with a median time to progression of 7.3 months. Acute grade 3 to 4 toxicity included neutropenia, nausea, emesis, and mucositis. CONCLUSIONS: Hyperfractionated split-course reirradiation and concurrent cisplatin and paclitaxel chemotherapy demonstrates durable locoregional control in select patients, although late toxicity may occasionally be significant. Only sites of disease recurrence need to be covered in the reirradiation fields.