Quality of interstitial PDR-brachytherapy-implants of head-and-neck-cancers: predictive factors for local control and late toxicity?

BACKGROUND AND PURPOSE: Parameters and indices related to the implant geometry in use for describing the quality of volume implants in interstitial brachytherapy were developed on the basis of LDR-brachytherapy. The aim of our study was to evaluate their usefulness for predicting late toxicity and local control in the PDR-brachytherapy of head-and-neck-tumors. PATIENTS AND METHODS: Between January 2000 and October 2004, 210 patients were treated with PDR-brachytherapy which was administered either postoperatively or as definitive treatment. Brachytherapy was used as sole treatment in some cases while in others a combination with EBRT was used. For assessment of quality of implants we analyzed the following indices and parameters using the univariate chi2 test and multivariate logistic regression analysis: V85, V120 and V150 (volume enclosed by the surface of the 85%-, 120%- and 150%-isodose), UI (uniformity index), QI (quality index), HI (homogeneity index), VGR (volume gradient ratio), DNR (dose non-uniformity ratio), LD (low dose), HD (high dose), PD (peak dose) and the intersource spacing. RESULTS: After a median follow-up of 24 months (4-50) the rate of - usually transient - soft tissue necrosis (STN) was 11%, osteoradionecrosis (ORN) was seen in 7.6% of cases and local relapse occurred in 7% of cases. Univariate analysis shows a significant influence on the development of soft tissue necrosis for V85, and on osteoradionecrosis for HD and PD. In the multivariate analysis a correlation between soft tissue necrosis and QI was found. For local control a correlation with QI, VGR and minimal tube distance was found using univariate analysis. CONCLUSIONS: Using interstitial PDR-brachytherapy in head-and-neck-tumors the probability of local control and of the development of soft tissue necrosis or osteoradionecrosis is dependent on dose and volume parameter like the volume of the reference isodose, the high and peak dose values, on the homogeneity of the dose distribution, quantified by the quality index or the volume gradient ratio as well on the minimal tube distance.

Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial.

PURPOSE: To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a randomized controlled trial of patients with head-and-neck cancer; at 12 months after radiotherapy (RT), amifostine had been shown to reduce xerostomia without changing tumor control. METHODS AND MATERIALS: Adults with head-and-neck cancer who underwent once-daily RT for 5-7 weeks (total dose, 50-70 Gy) received either open-label amifostine (200 mg/m2 i.v.) 15-30 min before each fraction of radiation (n = 150) or RT alone (control; n = 153). RESULTS: Amifostine administration was associated with a reduced incidence of Grade > or =2 xerostomia over 2 years of follow-up (p = 0.002), an increase in the proportion of patients with meaningful (>0.1 g) unstimulated saliva production at 24 months (p = 0.011), and reduced mouth dryness scores on a patient benefit questionnaire at 24 months (p < 0.001). Locoregional control rate, progression-free survival, and overall survival were not significantly different between the amifostine group and the control group. CONCLUSIONS: Amifostine administration during head-and-neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates, progression-free survival, or overall survival.

Expression of HIF-1 alpha in irradiated tissue is altered by topical negative-pressure therapy.

BACKGROUND AND PURPOSE: Despite the enormous therapeutic potential of modern radiotherapy, common side effects such as radiation-induced wound healing disorders remain a well-known clinical phenomenon. Topical negative pressure therapy (TNP) is a novel tool to alleviate intraoperative, percutaneous irradiation or brachytherapy. Since TNP has been shown to positively influence the perfusion of chronic, poorly vascularized wounds, the authors applied this therapeutic method to irradiated wounds and investigated the effect on tissue oxygenation in irradiated tissue in five patients. MATERIAL AND METHODS: With informed patients' consent, samples prior to and 4 and 8 days after continuous TNP with -125 mmHg were obtained during routine wound debridements. Granulation tissue was stained with hematoxylin-eosin, and additionally with CD31, HIF-1 alpha (hypoxia-inducible factor-1 alpha), and D2-40 to detect blood vessels, measure indirect signs of hypoxia, and lymph vessel distribution within the pre- and post-TNP samples. RESULTS: In this first series of experiments, a positive influence of TNP onto tissue oxygenation in radiation-induced wounds could be demonstrated. TNP led to a significant decrease of 53% HIF-1 alpha-positive cell nuclei. At the same time, a slight reduction of CD31-stained capillaries was seen in comparison to samples before TNP. Immunostaining with D2-40 revealed an increased number of lymphatic vessels with distended lumina and an alteration of the parallel orientation within the post-TNP samples. CONCLUSION: This study is, to the authors' knowledge, the first report on a novel previously not described histological marker to demonstrate the effects of TNP on HIF-1 alpha expression as an indirect marker of tissue oxygenation in irradiated wounds, as demonstrated by a reduction of HIF-1 alpha concentration after TNP. Since this observation may be of significant value to develop possible new strategies to treat radiation-induced tissue injury, further investigations of HIF-1 alpha regulation under TNP are warranted.