Definitive radiotherapy with interstitial implant boost for squamous cell carcinoma of the tongue base

BACKGROUND: The purpose of this study was to examine the long-term outcome of a cohort of patients with unresected base of tongue carcinoma who received interstitial brachytherapy after comprehensive external beam radiation therapy. METHODS: Between 1983 and 2000, 122 patients with primary or recurrent squamous cell carcinoma of the oropharynx or oral cavity received interstitial brachytherapy as part of their overall management. Forty patients had primary, unresected carcinoma of the base of tongue and are the subjects of this analysis. The median age was 54 years. Fifty-four percent had T3 or T4 disease, and 70% had clinical or radiographic lymphadenopathy. Twenty-four (60%) received two to three cycles of neoadjuvant chemotherapy. The oropharynx, bilateral neck, and supraclavicular fossae were comprehensively irradiated, and the tongue base received a median external beam dose of 61.2 Gy (50-72 Gy). The primary site was then boosted with an interstitial 192Iridium implant by use of a gold-button single-strand technique and three-dimensional treatment planning. The dose rate was prescribed at 0.4 to 0.5 Gy/hr. The median implant dose was 17.4 Gy (9.6-24 Gy) and adjusted to reach a total dose to the primary tumor of 80 Gy. N2 to 3 disease was managed by a planned neck dissection performed at the time of the implant. RESULTS: The median follow-up for all patients was 56 months, and the overall survival rates were 62% at 5 years and 27% at 10 years. The actuarial primary site control was 78% at 5 years and 70% at 10 years. The overall survival and primary site control were independent of T classification, N status, or overall stage. Systemic therapy was associated with an improvement in overall survival (p = .04) and a trend toward increased primary site control with greater clinical response. There were seven documented late effects, the most frequent being grade 3 osteonecrosis (n = 2), grade 2 swallowing dysfunction (n = 2), trismus (n = 2), and chronic throat pain (n = 1). CONCLUSIONS: In an era of greatly improved dose distributions made possible by three-dimensional treatment planning and intensity-modulated radiation therapy, brachytherapy allows a highly conformal dose to be delivered in sites such as the oropharynx. If done properly, the procedure is safe and delivers a dose that is higher than what can be achieved by external beam radiation alone with the expected biologic advantages. The long-term data presented here support an approach of treating advanced tongue base lesions that includes interstitial brachytherapy as part of the overall management plan. This approach has led to a 78% rate of organ preservation at 5 years, with a 5% incidence of significant late morbidity (osteonecrosis) that has required medical management.     

mTHPC-mediated photodynamic therapy in patients with advanced, incurable head and neck cancer: a multicenter study of 128 patients

BACKGROUND: The aim of this multicenter study was to assess tumor response, clinical quality-of-life benefit, survival, and safety after treatment with mTHPC in patients with recurrent/refractory squamous cell carcinoma of the head and neck unsuccessfully treated or unsuitable for treatment with conventional modalities. METHODS: One hundred twenty-eight patients were treated with mTHPC followed, 96 hours later, by illumination of the tumor surface with 652-nm laser light. Tumor response was assessed with WHO criteria and tumor mass reduction from baseline. Clinical quality-of-life benefit was based on the University of Washington Quality-of-Life questionnaire. RESULTS: By use of WHO criteria, 38% of evaluable patients achieved an overall tumor response, and 16% achieved a complete tumor response. Forty-three percent of assessable lesions achieved 100% tumor mass reduction, and 58% achieved 50% or greater tumor mass reduction. Fifty-three percent of evaluable patients experienced significant clinical quality-of-life benefit. Subset analyses revealed two subgroups in which significantly better responses were seen in patients with tumors 10 mm or less in depth and patients with fully illuminated lesions. In patients fulfilling both categories, overall tumor response was 54%, complete tumor response was 30%, and 61% demonstrated significant clinical quality-of-life benefit. Median survival was significantly better in responders. No major toxicities were detected. CONCLUSIONS: Patients with advanced cancer of the head and neck, who have exhausted other treatment options, can achieve significant clinical benefit and improvement in quality of life with mTHPC.     

Incidence and survival trends of lip,intra-oral cavity and tongue base cancers in south-east England

Background

Oral cavity cancers are on the increase in the UK. Understanding site-specific epidemiological trends is important for cancer control measures.This study demonstrates the changing epidemiological trends in lip, intra-oral cavity and tongue base cancers in south-east England from 1987 to 2006.

Aim: Methods

This was a retrospective study using anonymised data obtained from the Thames Cancer Registry (TCR) London. Data were analysed using SPSS v.17 and survival analyses with Kaplan-Meier and Cox regression. Age standardisation of the incidence rates was performed. It was conducted in south-east England, which has an average population of 12 million. The study analysed 9,318 cases (ICD-10 code C00–C06, C14). Kent Research Ethics Committee UK granted ethical approval.

Results

Oral cancers were more common in men, with male: female ratio of 1.6:1. Tongue cancers had the highest frequency at 3,088 (33.1%).Incidence varied with each cancer type. Mean incidence (per 1,000,000) ranged from 2.3 (lip cancer) to 13.8 (tongue cancer). There has been a statistically significant increase in incidence for cancers of the tongue base, other parts of tongue, gum and palate (p<0.001).Median survival time varied by sub-site, with lip cancer having the best median survival time (11.09 years) compared with tongue base cancer (2.42 years). Survival analyses showed worse prognosis for men, older age at diagnosis, and presence of synchronous tumours (p<0.001).

Conclusion

There is a rising incidence of tongue and tongue base, gum and palate cancers in south-east England with wide variability in survival. Oral cancer awareness and screening programmes should be encouraged.     

Vascular-targeted photodynamic therapy (padoporfin, WST09) for recurrent prostate cancer after failure of external beam radiotherapy: a study of escalating light doses

OBJECTIVE

To report on the efficacy of TOOKAD® (WST 09; NegmaLerads, Magny‐Les‐Hameaux, France) vascular‐targeted photodynamic therapy (VTP) as a method of whole‐prostate ablation in patients with recurrent localized prostate cancer after the failure of external beam radiotherapy (EBRT).

PATIENTS AND METHODS

Patients received a fixed photosensitizer dose of 2 mg/kg and patient‐specific light doses as determined by computer‐aided treatment planning. Up to six cylindrical light‐diffusing delivery fibres were placed transperineally in the prostate under ultrasonographic guidance. The treatment response was assessed by measuring serum prostate‐specific antigen (PSA) levels, lesion formation (avascular areas of tissue) measured on 7‐day gadolinium‐enhanced T1‐weighted magnetic resonance imaging (MRI) and a 6‐month biopsy.

RESULTS

Treatment of the whole prostate was possible with minimal effects on surrounding organs. An increased light dose improved the tissue response, with MRI‐detectable avascular lesions, encompassing up to 80% of the prostate in some patients. A complete response, as determined by the 6‐month biopsy, required that patients received light doses of at least 23 J/cm² in 90% of the prostate volume (D₉₀ > 23 J/cm²). Of the 13 patients who received at least this light dose, eight were biopsy‐negative at 6 months. In this group of eight patients, PSA levels decreased and did so to negligible levels for those patients with a baseline PSA level of <5 ng/mL. Side‐effects were modest and self‐limited in most patients; there were recto‐urethral fistulae in two patients, one of which closed spontaneously.

CONCLUSIONS

TOOKAD‐VTP can produce large avascular regions in the irradiated prostate, and result in a complete negative‐biopsy response at high light doses. A response rate of more than half for those patients receiving the highest light doses shows the clinical potential of TOOKAD‐VTP to manage recurrence of prostatic carcinoma after EBRT.     

Interstitial low-dose-rate brachytherapy in the treatment of recurrent head and neck malignancies

BACKGROUND: Recurrent head and neck malignancies are therapeutically challenging. Brachytherapy is a retreatment alternative to external-beam radiation therapy (EBRT). METHODS: Patients receiving brachytherapy during 1987-2004 for recurrent head and neck cancer were identified. Tumor and treatment characteristics and toxicities were recorded. Progression-free survival (PFS) and overall survival (OS) estimates were generated. The influence of prognostic factors was determined. RESULTS: Eighty-two patients were analyzable. Analysis was limited to patients who had brachytherapy for a first recurrence (n = 45). Brachytherapy (> or = 55 Gy) was a monotherapy in 22 of 45 patients. As part of their salvage brachytherapy treatments, 14 patients also underwent surgery; 3 patients also underwent EBRT; and 6 patients underwent surgery, EBRT, and brachytherapy. Retreatment morbidity included acute toxicity (n = 7) and late toxicity (n = 18). Median PFS was 15 months, and locoregional control rates at 1 and 2 years were 50% and 37%, respectively. Time to progression differed by site of the primary tumor (p = .10). Median OS was 16 months, and OS at 2 and 5 years was 33% and 11%, respectively. CONCLUSIONS: Brachytherapy for recurrent head and neck cancer has an acceptable toxicity profile and is viable alternative to EBRT. Further optimization of the best sites and doses for neck brachytherapy is required.     

Pain as sign of recurrent disease in head and neck squamous cell carcinoma

BACKGROUND: The role of pain in head and neck cancer is seldom addressed. This retrospective study examined in a group of 190 curatively treated patients to what extent pain complaints should be considered to be the first sign of recurrent disease. METHODS: The research population exists of 95 patients with a recurrent head and neck carcinoma and control group matched for age, gender, primary tumor, and duration of follow-up. RESULTS: Of the patients with proven recurrent disease, 70% reported pain complaints as the first symptom. In 35% of these cases, the complaints concerned referred pain, whereas in 65% localized pain complaints in the head and neck were registered. The median interval between reporting localized pain complaints and histologic confirmation of recurrence was 4 months. In the case of referred pain, this delay was 2.5 months. No statistically significant correlation between pain complaints and site of recurrence could be demonstrated. Only 2% of the control group reported pain complaints. CONCLUSIONS: This study confirms that each pain complaint after intentional curative treatment should be regarded as a warning sign. Recurrence of disease without preceding pain complaints (30%) emphasizes the importance of a thorough follow-up.