Is Sustained Virological Response a Marker of Treatment Efficacy in Patients with Chronic Hepatitis C Viral Infection with No Response or Relapse to Previous Antiviral Intervention?

Background: Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs.  Methods: We created a decision tree model based on a Cochrane systematic review on interferon retreatment for patients who did not respond to initial therapy or who relapsed following SVR. Extrapolating data to 20 years, we modelled the outcome from three scenarios: (1) observed medium-term (5 year) annual mortality rates continue to the long term (20 years); (2) long-term annual mortality in retreatment responders falls to that of the general population while retreatment non-responders continue at the medium-term mortality; (3) long-term annual mortality in retreatment non-responders is the same as control group non-responders (i.e., the increased treatment-related medium mortality “wears off”).  Results: The mean differences in life expectancy over 20 years with interferon versus control in the first, second, and third scenarios were -0.34 years (95% confidence interval (CI) -0.71 to 0.03), -0.23 years (95% CI -0.69 to 0.24), and -0.01 (95% CI -0.3 to 0.27), respectively. The life expectancy was always lower in the interferon group than in the control group in scenario 1. In scenario 3, the interferon group had a longer life expectancy than the control group only when more than 7% in the interferon group achieved SVR.  Conclusions: SVR may be a good prognostic marker but does not seem to be a valid surrogate marker for assessing HCV treatment efficacy of interferon retreatment. The SVR threshold at which retreatment increases life expectancy may be different for different drugs depending upon the adverse event profile and treatment efficacy. This has to be determined for each drug by RCTs and appropriate modelling before SVR can be accepted as a surrogate marker

T stage as prognostic factor in irradiated localized squamous cell carcinoma of the nasal vestibule

BACKGROUND: To investigate the impact of T stage according to Wang on the prognosis of irradiated nasal vestibule carcinoma. PATIENTS AND METHODS: Treatment results of 47 patients were retrospectively analyzed. Treatment consisted of external beam radiotherapy (n = 26) or interstitial radiotherapy (n = 19) or a combination of both (n = 2) for a primary, localized, squamous cell carcinoma of the nasal vestibule. Mean follow-up was 5 years and 7 months. RESULTS: T1/T2 tumors: Local control was achieved in 40 of 44 patients; surgical salvage was possible in 2 of 4 local failures. Five patients had recurrences in the neck, and four of them could be salvaged surgically. One patient had distant metastases develop. T3 tumors (n = 3): no T3 tumor could locally be cured by radiotherapy. One patient was salvaged surgically but died of regional and distant metastases. Disease-specific survival is significantly correlated with T stage according to Wang (p =.0001). Most (85%) patients were smokers, and eight of them (20%) had a second primary tumor develop in the lungs. CONCLUSIONS: The effect of radiotherapy is significantly correlated with T stage (p =.0001) and hence less successful in T3 lesions as primary treatment option. The high incidence of second primary tumors in the lung is indicative for a similar carcinogenic influence of smoking on the nasal vestibul

Quality-of-life assessment after supradose selective intra-arterial cisplatin and concomitant radiation (RADPLAT) for inoperable stage IV head and neck squamous cell carcinoma

OBJECTIVE: To evaluate quality-of-life (QOL) aspects of an organ preservation intra-arterial chemotherapy and concomitant radiation protocol, RADPLAT. DESIGN: Nonrandomized phase 2B feasibility trial. PATIENTS: Fifty consecutive patients with inoperable stage IV head and neck cancer. INTERVENTION: Supradose selective intra-arterial cisplatin and concomitant standard radiation (RADPLAT). MEASURES: Assessment with structured questionnaires before treatment and at 3, 6, and 12 months. RESULTS: Twenty-six patients were available for QOL assessment at 1 year (the "1-year QOL" group), as 16 patients died, 5 needed salvage surgery, and 3 were not available for interview (the "failure" group). Twelve-month results were mainly based on the first group. The functional well-being and head and neck scales showed a statistically significant improvement over time (P <.001). After 12 months, 21 patients (81%) returned to an oral diet, while 5 patients still needed tube feeding. For 23 patients (88%), the quality and strength of the voice was more or less normal. Of the 18 patients who were employed before their treatment, 10 were able to return to their job within 12 months. Xerostomia was reported by 17 patients (65%). Further detailed analysis showed statistically significant differences in pretreatment scores between the 1-year QOL group and the failure group, ie, physical well-being, functional well-being, and the head and neck scales (P <.05). Differences in these groups with respect to sex, age, tumor site, or stage could not be found. CONCLUSION: Given that only patients with locally (anatomic or functional) inoperable stage IV disease were treated, the results are promising, underlining the feasibility of the RADPLAT protoco

Increased risk of ischemic stroke after radiotherapy on the neck in patients younger than 60 years

PURPOSE: To estimate the risk of ischemic stroke in patients irradiated for head and neck tumors. PATIENTS AND METHODS: The incidence of ischemic stroke was determined in 367 patients with head and neck tumors (162 larynx carcinomas, 114 pleomorphic adenomas, and 91 parotid carcinomas) who had been treated with local radiotherapy (RT) at an age younger than 60 years. Relative risk (RR) of ischemic stroke was determined by comparison with population rates from a stroke-incidence register, adjusted for sex and age. Other risk factors for stroke (hypertension, smoking, hypercholesterolemia, diabetes mellitus [DM]) were registered. The median follow-up time after RT was 7.7 years (3,011 person-years of follow-up). RESULTS: Fourteen cases of stroke occurred (expected, 2.5; RR, 5.6; 95% confidence interval [CI], 3.1 to 9.4): eight in patients with laryngeal carcinoma (expected,1.56; RR, 5.1; 95% CI, 2.2 to 10.1), four in pleomorphic adenoma patients (expected, 0.71; RR, 5.7; 95% CI, 1.5 to 14.5), and two in parotid carcinoma patients (expected, 0.24; RR, 8.5, 95% CI, 1.0 to 30.6). Five of six strokes in patients irradiated for a parotid tumor occurred at the ipsilateral side. Analysis of other risk factors for cerebrovascular disease showed hypertension and DM to cause an increase of the RR after RT. After more than 10 years' follow-up, the RR was 10.1 (95% CI, 4.4 to 20.0). The 15-year cumulative risk of stroke after RT on the neck was 12.0% (95% CI, 6.5% to 21.4%). CONCLUSION: This is the first study to demonstrate an increased risk of stroke after RT on the neck. During medical follow-up, preventive measures should be taken to reduce the impact of the risk factors for cerebrovascular disease, to decrease stroke in these patient