Dose-response relationship of nasopharyngeal carcinoma above conventional tumoricidal level: a study by the Hong Kong nasopharyngeal carcinoma study group (HKNPCSG).

BACKGROUND AND PURPOSE: To define the dose-response relationship of nasopharyngeal carcinoma (NPC) above the conventional tumoricidal dose level of 66 Gy when the basic radiotherapy (RT) course was given by the 2D Ho's technique. PATIENTS AND METHODS: Data from all five regional cancer centers in Hong Kong were pooled for this retrospective study. All patients (n = 2426) were treated with curative-intent RT with or without chemotherapy between 1996 and 2000 with the basic RT course using the Ho's technique. The primary endpoint was local control. The prognostic significance of dose-escalation ('boost') after 66 Gy, T-stage, N-stage, use of chemotherapy, sex and age (< or =40 years vs >40 years) was studied. Both univariate and multivariate analyses were performed. RESULTS: On multivariate analysis, T-stage (P < 0.01; hazard ratio [HR], 1.58) and optimal boost (P = 0.01; HR, 0.34) were the only significant factors affecting local failure for the whole study population, and for the population of patients treated by radiotherapy alone, but not for patients who also received chemotherapy. The following were independent determinants of local failure for patient groups with different T-stages treated by radiotherapy alone: use of a boost in T1/T2a disease (P = 0.01; HR, 0.33); use of a boost (P < 0.01; HR, 0.60) and age (P = 0.01; HR, 1.02) in T3/T4 tumors. Among patients with T2b tumors treated by radiotherapy alone and given a boost, the use of a 20 Gy-boost gave a lower local failure rate than a 10 Gy-boost. There was no apparent excess mortality attributed to RT complications. CONCLUSIONS: Within the context of a multi-center retrospective study, dose-escalation above 66 Gy significantly improved local control for T1/T2a and T3/4 tumors when the primary RT course was based on the 2D Ho's technique without additional chemotherapy. 'Boosting' in NPC warrants further investigation. Caution should be taken when boosting is considered because of possible increase in radiation toxicity.

Nasopharyngeal intracavitary brachytherapy: the controversy of T2b disease.

BACKGROUND: Locally persistent nasopharyngeal carcinoma (NPC) carries an increased risk of local failure if additional treatment is not given. It has been shown that intracavitary brachytherapy is effective in the treatment of patients with T1 and T2a NPC, although its role in the treatment of T2b disease had remained uncertain. The objectives of the current study were to evaluate the outcomes of patients with T2b, locally persistent NPC who were treated with high-dose-rate (HDR) intracavitary brachytherapy and to explore whether routine brachytherapy boost could improve the local control of patients who had T2b NPC at initial diagnosis. METHODS: Thirty-four patients with locally persistent NPC who were treated during 1992-2000 with HDR intracavitary brachytherapy were analyzed retrospectively. All patients had T2b disease at initial diagnosis. They were treated with HDR intracavitary brachytherapy at doses of 22.5-24.0 grays (Gy) in 3 weekly sessions. To compare the efficacy of brachytherapy, another 403 consecutive patients with nonmetastatic T2b NPC who were treated with curative intent by external radiotherapy (ERT) during the same period were evaluated. RESULTS: An improvement in the 5-year actuarial local failure-free survival rate (brachytherapy group vs. ERT group: 96.9% vs. 81.5%; P = 0.024), the disease-specific survival rate (84.5% vs. 68.1%; P = 0.021), and the overall survival rate (78.3% vs. 63.1%; P = 0.034) was demonstrated in the group that had locally persistent NPC who were salvaged with brachytherapy. In assessing local control, the addition of brachytherapy was just short of statistical significance on multivariate analysis (P = 0.054). The complication rates were comparable between the brachytherapy group and the ERT group. CONCLUSIONS: The results suggested that patients with T2b NPC who have locally persistent disease can be salvaged effectively with brachytherapy. Their local control was even better than that achieved by patients who had clinical remission of local disease at the completion of ERT. Furthermore, it is possible that routine brachytherapy boost, after the completion of ERT, may improve local control in patients who have T2b disease at initial diagnosis. However, its exact benefit can be elucidated only by prospective, randomized studies.

Treatment results of 1070 patients with nasopharyngeal carcinoma: an analysis of survival and failure patterns.

BACKGROUND: The aim of this analysis was to evaluate the outcomes of patients with nasopharyngeal carcinoma (NPC) treated primarily by external beam irradiation (ERT) and to explore for possible ways to improve the treatment results. METHODS: One thousand seventy patients with nonmetastatic NPC treated from 1990 to 1998 were retrospectively analyzed. The distribution according to the Union Internationale Contre le Cancer (UICC) (1997 edition) staging system at initial diagnosis was as follows: stage I, n = 113; stage IIA, n = 38; stage IIB, n = 360; stage III, n = 306; stage IVA, n = 136; stage IVB, n = 117; T1, n = 284; T2a, n = 88; T2b, n = 398; T3, n = 149; T4, n = 151; N0, n = 321; N1, n = 393; N2, n = 238; N3a, n = 29; N3b, n = 89. Two hundred eight patients were given neoadjuvant chemotherapy. Ninety-seven patients were diagnosed with locally persistent disease and were salvaged with high dose rate intracavitary brachytherapy. Multivariate analysis was performed with the Cox regression proportional hazards model. RESULTS: The 5-year actuarial local failure-free survival, regional failure-free survival, distant metastasis-free survival, progression-free survival, cancer-specific survival, and overall survival rates were 80.9%, 93.3%, 77.2%, 62.7%, 71.4%, and 66.5%, respectively. Isolated distant metastasis occurred in 191 patients (18%). The distributions were as follow: stage I, 2.1% (two of 95); stage IIA, 5.7% (two of 35); stage IIB, 14.9% (45 of 302); stage III, 26.4% (62 of 235); stage IVA, 40% (40 of 100); stage IVB, 47.1% (40 of 85). Results of the multivariate analysis of various clinical endpoints were discussed. By studying these failure patterns, it is hoped that we could refine future treatments according to the failure patterns of patients with different risks of locoregional and distant failure. CONCLUSIONS: The 18% incidence of isolated distant metastasis is too high to be ignored. Maximizing the local control and minimizing the risk of distant metastasis and late complications should be the key objectives in designing future clinical trials.

Treatment results of high-dose-rate remote afterloading brachytherapy for cervical cancer and retrospective comparison of two regimens.

PURPOSE: To review the treatment results and complications of high-dose-rate (HDR) intracavitary brachytherapy for patients with carcinoma of the cervix in a single institute and to compare them with those of low-dose-rate (LDR) brachytherapy reported in the literature. METHODS AND MATERIALS: Two hundred twenty patients with carcinoma of the cervix were treated by primary radiotherapy between 1991 and 1998. The median age was 63 (range 24-84). The distribution according to Federation of Gynecology and Obstetrics (FIGO) staging system was as follows: Stage IB, 11.4%; IIA, 9.1%; IIB, 50.9%; IIIA, 3.6%; IIIB, 23.2%; and IVA, 1.8%. They were treated with whole pelvic irradiation giving 40 Gy to the midplane in 20 fractions over 4 weeks. This was followed by parametrial irradiation, giving 16-20 Gy in 8-10 fractions. HDR intracavitary brachytherapy was given weekly, with a dose of 7 Gy to point A for three fractions and, starting from 1996, 6 Gy weekly for four fractions. The median overall treatment time was 50 days (range 42-73 days). The median follow-up time was 4.7 years (range 3 months to 11.1 years). Multivariate analysis was performed using the Cox regression proportional hazards model. RESULTS: The complete remission rate after radiotherapy was 93.4% (211/226). The 5-year actuarial failure-free survival (FFS) and cancer-specific survival (CSS) rates for stage IB, IIA, IIB, IIIA, IIIB, and IVA were 87.7% and 86.6%, 85% and 85%, 67.8% and 74%, 46.9% and 54.7%, 44.8% and 50.4%, 0% and 25%, respectively. On multivariate analysis, young age (< 50) (p = 0.0054), adenocarcinoma (p = 0.0384), and stage (p = 0.0005) were found to be independent poor prognostic factors. The 5-year actuarial major complication rates (Grade 3 or above) were as follows: proctitis, 1.0%; cystitis, 0.5%; enteritis, 1.3%; and overall, 2.8%. On multivariate analysis, history of pelvic surgery was a significant prognosticator. The two HDR fractionation schedules were not a significant prognosticator in predicting disease control and complications. CONCLUSION: Our experience in treating cervical cancer with HDR intracavitary brachytherapy is encouraging. Our treatment results and complication rates were compatible with those of the LDR series. Further studies are eagerly awaited to better define the optimal fractionation schedule for HDR brachytherapy and the schedule on how chemotherapy may be combined with it.

High dose rate brachytherapy for early stage oral tongue cancer.

BACKGROUND: High dose rate (HDR) interstitial brachytherapy of the oral tongue is a new treatment modality. Our study evaluates the outcomes of patients with early stage oral tongue cancer as treated by HDR interstitial implant. METHODS: We reviewed the records of 19 patients who were seen between 1994 and 2000 with carcinoma of the oral tongue and whose primary tumors were treated solely with interstitial implant using HDR remote afterloading technique. Ten patients had T1 N0 disease, and the remaining 9 had T2 N0 disease. Elective neck treatment was withheld for 12 patients. The remaining seven patients had ipsilateral elective neck dissection. The male-female ratio was 1:0.9, and the median age was 60 years (range, 32-81 years). The median follow-up time was 43 months (range, 6-78 months). The afterloading catheters were positioned by the submandibular approach with the assistance of a template set. Fifteen patients had single planar implants, and the remaining four had double planar implants. The median number of catheters inserted was 5 (range, 4-9). The median dose given was 55 Gy in 10 fractions over 6 days. The minimal interfraction interval was 7 hours for the first 7 patients and was extended to 8 hours for the other 12. Mandibular shields were inserted before treatment. RESULTS: The mucositis lasted for 6 to 20 weeks (median, 9 weeks). One patient had local failure, and the 4-year local failure-free survival rate was 94.7%. Three of the 12 patients without elective neck treatment had ipsilateral regional failure develop. They were salvaged by neck node dissection and regionally remained in control. One patient with multiple nodal metastases and extracapsular spread had biopsy-proven liver metastases and died 6 months after implant. One of the seven patients who were treated with elective neck dissection had multiple nodal metastases and extracapsular spread. She was treated with postoperative radiotherapy to the neck. She died 30 months after implant with evidence of regional and distant failure. One patient treated with double planar implant had grade II necrosis of the soft tissue and bone develop. The necrosis resolved with conservative treatment. Another four patients had small area of soft tissue deficit of the tongue attributed to aggressive debulking or biopsy before brachytherapy. CONCLUSIONS: Our experience in treating early stage tongue cancer with HDR remote afterloading technique is encouraging, because it gives a local control rate of 94.7% at 4 years with acceptable morbidity. Further studies are eagerly awaited to delineate the optimum schedule for this new treatment modality.