Recurrent Head and Neck Cancer
As mentioned previously, surveillance after treatment of head and neck cancer is mandatory, because early detection of second primary cancers or locoregional recurrence affords the best chance for disease control. Nearly two-thirds of patients whose head and neck cancer recurs develop a tumor at (or near) the primary site or in the neck nodes. Eighty percent of head and neck cancer recurrences eventuate within 2 years.
Differentiating Recurrence From Late Complications of Irradiation
Differentiating between recurrent carcinoma and significant sequelae of radiotherapy is a difficult clinical problem at all sites within the head and neck. Any suspicious mucosal changes, enlarged nodes in the neck, or discrete subcutaneous nodules warrant prompt biopsy.
Candidates for Surgery
Different choices of first treatment (ie, surgery or radiation therapy) and the intensity of follow-up influence success in treating recurrence. Aggressive surgical intervention should be offered to two groups of patients with recurrent local or regional disease: those whose therapy is chosen with curative intent and those with the prospect of significant palliation.
The types of recurrence that may be approached surgically with the greatest likelihood of success include (1) metastases in the neck after initial treatment limited to the primary tumor alone and (2) reappearance or persistence of cancer at a site previously treated with radiotherapy alone. Salvage resection may also be considered in other situations, however, including, for example, the appearance of cancer in the neck after prior irradiation or neck dissection, at the margins after previous resection, and even at the base of the skull.
After surgery for head and neck cancer, patients remain at high risk for locoregional recurrence. In one study, 130 patients who had undergone surgery for recurrent disease were randomized to observation or to postoperative reirradiation combined with concomitant hydroxyurea and 5-FU. A higher incidence of treatment-related mortality and severe acute and chronic toxicity was found in the treatment group. The disease-free, but not overall, survival was improved in the treatment arm (P = .006 and .5, respectively).
Surgery is the standard of care for the treatment of recurrent disease, but there is a growing body of evidence suggesting that reirradiation with concurrent chemotherapy can cure select patients when resection is not possible. Several institutions have reported experiences re-treating patients, and these results led to the development of the first multi-institution reirradiation study.
A single-arm, phase II study (RTOG 96-10) evaluated toxicity and therapeutic results for patients with recurrent squamous cell carcinoma of the head and neck. Eighty-six patients received four weekly courses of 1.5-Gy fractions twice daily with concurrent 5-FU and hydroxyurea. Each cycle was separated by 1 week of rest. The median survival was 8.1 months, and the 1- and 2-year survival rates were 41.7% and 16.2%, respectively. Compared with patients who experienced early recurrences, patients whose disease recurred 3 years after the original irradiation fared better, with 1- and 2-year survival rates of 48.1% and 32.1%, respectively.
The first results for the entire cohort of patients for RTOG 99-11, the successor trial to RTOG 96-10, were presented in 2005. In this study, patients with locally recurrent or second primary head and neck tumors who previously received radiation therapy were treated with split-course hyperfractionated radiotherapy (60 Gy total; 1.5 Gy/fraction twice daily for 5 days every 2 weeks for four cycles) in combination with cisplatin(Drug information on cisplatin) (15 mg/m2 IV daily) for five courses and paclitaxel(Drug information on paclitaxel) (20 mg/m2 IV daily) for five courses every 2 weeks for four cycles. Granulocyte colony-stimulating factor (G-CSF) support was administered on days 6 through 13 of each 2-week cycle. Of the 105 patients enrolled, 99 were eligible for analysis, and 23% of the patients had second primary head and neck tumors. The median prior dose of radiotherapy was 65.4 Gy (range, 45 to 75 Gy), and the median time from prior radiotherapy was 40 months.
Of eight patients with grade 5 (fatal) toxicities, five occurred during the acute period (dehydration, pneumonitis, neutropenia [2 cases], and cerebrovascular accident) and three during the late period (two of three attributable to carotid hemorrhage). Other acute toxicities included leukopenia (30% grade 3/4), anemia (21% grade 3/4), and GI toxicity (48% grade 3/4). The median follow-up for patients was 23.6 months, and the median survival was 12.1 months.
The estimated 1- and 2-year overall survival rates were 50.2% and 25.9%, respectively. Median survival time and the 1-year progression-free survival rate were 7.8 months and 35%, respectively. Overall survival was significantly better (P = .044) than for the historic control in RTOG 96-10 (estimated 1- and 2-year overall survival rates, 41.7% and 16.7%, respectively).
Despite significant toxicity and high mortality, hyperfractionated split-course reirradiation with concurrent cisplatin and paclitaxel chemotherapy proved feasible in this select patient population. This approach was to be tested in RTOG 04-21, a phase III trial randomizing patients between reirradiation with concurrent cisplatin and paclitaxel chemotherapy vs chemotherapy alone; however, this trial was closed in early 2007 because of a lack of accrual.
Unless a patient cannot tolerate an operation, resection of discrete local or regional recurrent tumors should be entertained as the first course of treatment. Management of recurrences involves complex decision making and requires familiarity with multidisciplinary care.
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