Introduction of SGRT in clinical practice.

To describe the rationale and process how SGRT was implemented in our department from the original decision to daily clinical practice.

Establishing radiological percutaneous gastrostomy with balloon-retained tubes as an alternative to endoscopic and surgical gastrostomy in patients with tumours of the head and neck or oesophagus.

The purpose of this study was to report our experience introducing radiological percutaneous gastrostomy (RPG) catheters at a hospital where hitherto only endoscopic and surgical methods have been used. The feasibility, success, time requirements, and complications of RPG were prospectively evaluated during a 12-month period. 26 consecutive patients (median age 63 years, range 41-91 years) underwent gastropexy with T-fasteners followed by insertion of a 12-18 F balloon tube through a peel-away introducer and were followed-up clinically and radiologically. Success and complications occurring within 30 days were assessed. RPG was technically successful in all cases. Median procedure time was 34 min (range 20-90 min), median fluoroscopy time 6.9 min (range 2.3-30 min). 13 surgical gastrostomies were avoided. One minor complication (peristomal leakage) occurred in a patient with gastric reflux and atony. Another patient destroyed the balloon of his tube by injecting food into the balloon port, which led to tube dislocation and peritonitis. In conclusion, radiological gastrostomy can be quickly learned by radiologists and is readily accepted by clinicians. It is an alternative to surgical gastrostomy when percutaneous endoscopic gastrostomy is not feasible, but can also be used as the primary method instead of the endoscopic method.

Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma.

BACKGROUND: Epidemiologic evidence points to a connection between viral infection by the human papillomavirus (HPV) and a subgroup of squamous cell carcinoma of the oropharynx. To assess the impact of HPV infection on the response of these tumors toward radiotherapy, the authors retrospectively determined the presence of the virus and the integrity of the viral E2 gene in tumors of patients who have undergone curative irradiation. METHODS: Paraffin embedded biopsies from 99 patients were analyzed for HPV infection and E2 gene integrity by multiplex PCR. The experimental findings were correlated with clinical characteristics, known risk factors, and treatment outcome. RESULTS: Fourteen of 99 tumors were HPV positive (11 HPV16, 1 HPV33, 1 HPV35, and 1 HPV45). Human papillomavirus positivity was closely linked to female gender (odds ratio [OR], 5.75; P = 0.004), age older than 56 years (OR, 7.42; P = 0.012), nonsmokers (OR, 21.33; P = 0.00001), and alcohol abstainers (OR, 5.35; P = 0.012). There was an inverse association with p53 nuclear immunoreactivity (OR, 0.06; P = 0.008). The Kaplan-Meier survival estimates showed a better local control (P = 0.050, log-rank) and a better overall survival (P = 0.046, log-rank) for patients with HPV positive tumors. In the multivariate analysis, HPV positivity remained to be associated with a lower risk of local failure (risk ratio [RR], 0.31; P = 0.048). Four of 11 HPV16 positive tumors had a disrupted E2 gene. Only tumors with a disrupted E2 gene manifested local treatment failure. CONCLUSIONS: Human papillomavirus positivity designates a specific subgroup of oropharyngeal squamous cell carcinomas of the oropharynx that arise preferentially among individuals with no consumption of tobacco and alcohol and that have a favorable outcome attributable to an increased sensitivity toward radiotherapy.

Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer.

Hypoxia has long been recognized as detrimental to the successful treatment of malignant tumors with ionizing radiation. Because hypoxia-inducible factor (HIF)-1alpha plays an essential role in oxygen homeostasis in vitro, we explored the predictive potential of this factor in a cohort of 98 patients with squamous cell cancer of the oropharynx, who were treated by curative radiation therapy. Ninety-four % of the primary tumors showed overexpression of HIF-1alpha, relative to the surrounding tissue, as determined by immunohistochemistry. The degree of HIF-1alpha immunoreactivity correlated inversely with both the rate of complete remission of the primary tumor (odds ratio, 0.33; P = 0.03) and lymph node metastases (odds ratio, 0.34; P = 0.02) as well as with local failure-free survival (risk ratio, 2.15; P = 0.006), disease-free survival (risk ratio, 2.01; P = 0.008), and overall survival (risk ratio, 2.17; P = 0.002). The multivariate analysis revealed the predictive power of HIF-1alpha to be independent of other covariables. We conclude that HIF-1alpha is overexpressed in the vast majority of patients with squamous cell cancer of the oropharynx and that the degree of expression has predictive and prognostic significance in individuals undergoing curative radiation therapy.

Involvement of the hepatocyte growth factor/scatter factor receptor c-met and of Bcl-xL in the resistance of oropharyngeal cancer to ionizing radiation.

The activation of cytoplasmic signal transduction pathways by a number of growth factors and their tyrosine-kinase receptors, including hepatocyte growth factor/scatter factor (HGF/SF) and its receptor c-met, exerts an inhibitory influence on apoptosis induced by ionizing radiation in vitro. The clinical relevance of the aforementioned ligand-receptor pair, of Bcl-xL, which is targeted by HGF/SF/c-met signaling, and of Bcl-2, was assessed by evaluating their predictive and prognostic impact in a cohort of 97 patients with radically irradiated squamous cell cancers of the oropharynx. Immunohistochemical expression of c-met and Bcl-xL was correlated with decreased rates of complete remission of the primary tumor in both the univariate (c-met: P = 0.01; Bcl-xL: P = 0.001) and multivariate analyses. Expression of c-met was, moreover, a significant and independent predictor of impaired local failure-free survival (P = 0.003), disease-free survival (P = 0.003) and overall survival (p = 0.001). Bcl-2 expression was, on the other hand, associated with a favorable outcome, in terms of both local failure-free survival (P = 0.01) and overall survival (P = 0.001). In accordance with in vitro data, c-met and Bcl-xL appear to be involved in the resistance of oropharyngeal cancers to ionizing radiation, and may therefore represent attractive targets for radiosensitization.

Intratumoral microvessel density predicts local treatment failure of radically irradiated squamous cell cancer of the oropharynx.

PURPOSE: To determine the predictive value of intratumoral microvessel density (IMD), and of the expression of p53, vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) for the radiocurability of patients with squamous cell cancer of the oropharynx. MATERIALS AND METHODS: 139 patients with squamous cell cancer of the oropharynx were radically irradiated (median dose, 74 Gy) between 1991 and 1997. Biopsies from 100 patients were processed for immunohistochemistry. IMD was determined in hot spot areas of tissue stained with anti-CD31 at a magnification of x200. Staining for p53 was considered positive if more than 10% of the cell nuclei overexpressed the protein. Immunostaining of VEGF and TSP-1 was assessed semiquantitatively. RESULTS: Increasing IMD (range, 54-282) was strongly correlated with incomplete remission of both the primary tumors (p = 0.01) and lymph node metastases (p = 0.02). Moreover, multivariate Cox regression analysis revealed local failure-free survival to decline with increasing IMD (IMD continuous: risk ratio = 1.01 per increase of 1 microvessel, p = 0. 0001; IMD categorical: 130: risk ratio = 13.01). Neither the expression of p53, nor that of VEGF or TSP-1 was associated with the treatment outcome or IMD, but VEGF and TSP-1 expression were positively correlated (p = 0.02). CONCLUSION: IMD represents a powerful and independent predictive factor for local treatment failure in radically irradiated patients with squamous cell cancer of the oropharynx.

[Skin and mucous membrane reactions during and after radiotherapy]. / Haut- und Schleimhautreaktionen während und nach Radiotherapie.

The temporary acute reactions during radiotherapy are a burden for the patient. These reactions are due to a depletion of stem cells and depend on the single dose, the total dose and the irradiated volume. The WHO describes the acute changes in a graded scale from 0 to IV. A knowledge of the course of these events helps the otolaryngologist to inform patients competently, calm their fears and give support during treatment. Efficacious measures to alleviate symptoms are presented.

Carcinoma of the oropharynx: local failure as the decisive parameter for distant metastases and survival.

OBJECTIVE: How important and predictive are clinical parameters and locoregional failure after radical radiotherapy of oropharyngeal carcinomas for the probability of the occurrence of distant metastases? PATIENTS AND METHODS: From 1 August 1990 to 1 October 1998, 139 patients with carcinomas of the oropharynx were treated in a prospective study by radical radiotherapy and evaluated in regard to the clinical parameters reflex-otalgia, predominant structure of tumor growth, T-category, presence of involved lymph nodes, and smoking and drinking habits. Twenty-nine patients received a concomitant chemotherapy. Twenty-five out of 139 patients had a planned neck dissection after completion of radiotherapy. Ten patients received a salvage operation. RESULTS: The median follow up time was 24 months (range, 4 to 74). Two- and 5-year overall survival rates according to Kaplan Meier were 56.1 and 49.6%. The tumors were controlled in 77/139 patients (55%). The therapy failed in 62/139 patients (45%). Both groups, 62 patients with locoregional therapy failure and 77 patients with locoregionally control led tumors, were comparable in regard to performance status (Karnofsky index), age, gender, TNM-categories, histological differentiation, drinking habits, pretherapeutic diagnostics, total dose (Gy), and number of simultaneous chemotherapy cycles. Locoregional tumor control was significantly determined by the parameters reflex-otalgia (p < 0.0078), predominant growth pattern (p < 0.012), T-category (p < 0.03), and smoking (p < 0.0285). The median survival time of patients with locoregional failure is 17 months. At this moment 81% of locoregionally controlled patients are still alive. In 14/62 patients (23%) with locoregional failure, distant metastases were detectable against 4/77 (5%) of locally controlled patients, p < 0.0026. Probability of local control and distant metastases, predominantly pulmonary, reached a plateau after 24 months. CONCLUSIONS: Locoregional tumor control, determined by several clinical parameters, is an important parameter for the probability of the development of distant metastases. Failure of local therapy is caused by the biologic aggressiveness of the tumor.

[Campaign against radio-xerostomia]. / Kampf der Radio-Xerostomie.

The radiation induced xerostomia is a common and, up to now, irreversible side effect of the definitive or postoperative treatment of ENT cancers. A possible mechanism is the apoptosis of serous gland cells. The sequelae of xerostomia are increasing cavities, plaques and parodontosis, infections in the pharynx, taste alterations and weight loss. Therapeutic approaches include improved oral hygiene, dietetic adjustments, artificial saliva and most recently, medication. Pilocarpine, a parasympathomimeticum, results in a degranulation of the secretoric granula and consequently, lowers the radiosensitivity of the cells. Amifostine acts a scavenger of radicals and is concurrently tested in a phase III clinical trial to evaluate the selective protection of normal tissue during radiotherapy.

[Management of skin and mucous membrane reactions in patients treated with irradiation]. / Die Pflege von Haut- und Schleimhautreaktionen bei Patientlnnen, die bestrahlt werden.

Acute reactions during radiotherapy are due to a depletion of stem cells. Depending on single and total dose and the irradiated volume there is a different degree of changes of the skin and mucosa. To alleviate symptoms, several efficacious, prophylactic measures of care should be used.

No predictive value of the micronucleus assay for patients with severe acute reaction of normal tissue after radiotherapy.

In approximately 5% of cancer patients undergoing radiotherapy, this treatment has to be interrupted because of an acute reaction of normal tissues. To test the possibility of predicting this type of reaction, the micronucleus assay was used to determine radiosensitivities of peripheral blood lymphocytes of 15 patients with severe acute reaction of normal tissue, 15 patients without this reaction and 15 healthy donors. Whole-blood cultures were irradiated with X-rays (4 Gy, 1.08 Gy/min) and treated with cytochalasin B. The micronuclei scores observed in irradiated cells were corrected for the scores in unirradiated cells. Intra-individual and interindividual variations in micronuclei scores were analysed in samples from healthy donors, and highly significant interindividual differences were found (P < 0.001). Scores of cells not irradiated in vitro were higher for cancer patients before radiotherapy than for healthy donors (P < 0.001), and those for cancer patients after radiotherapy were higher than for patients before radiotherapy (P < 0.001). Average micronuclei scores induced by in vitro irradiation were significantly higher in samples from cancer patients compared with those from healthy donors (P < 0.01). Moreover, all subgroups of cancer patients included individuals with very high levels of micronuclei after in vitro irradiation. There was, however, no relationship between the micronuclei scores and the occurrence of severe acute reactions in normal tissues.

[Predictive significance of reflex otalgia in local radical radiotherapy of oropharyngeal carcinomas]. / Prädiktive Bedeutung der Reflexotalgie in der lokal radikalen Radiotherapie von Oropharynxkarzinomen.

BACKGROUND: Patients with carcinomas of the upper aero-digestive tract often suffer from ear pain as a tumor associated syndrome. This prospective study examines the predictive and prognostic value of this symptom. PATIENTS AND METHODS: Ninety-six consecutive patients who completed a locally radiotherapy of a carcinoma of the oropharynx were prospectively evaluated and followed. Forty-nine out of 96 patients stated the symptom, either spontaneously or after questioning. The 2 groups showed no difference regarding TNM-classification, histology and total dose. Overall survival, local control and disease specific survival were calculated according to Kaplan-Meier and compared by the log-rank test. RESULTS: A clinically complete remission was obtained in significantly fewer patients with reflex-otalgia as compared to patients without reflex-otalgia, 61.2% versus 89.3%, p < 0.002. Local control of patients with reflex-otalgia was significantly less with 49%, mean follow-up 564 days, in comparison to local control in patients without reflex-otalgia, mean follow-up 613 days, p = 0.01. Disease specific survival was significantly worse for patients with reflex-otalgia, p < 0.012. The probability of local control of T1/T2 tumors with reflex-otalgia was similar to T3/T4 tumors without reflex-otalgia. Local control for all tumor categories combined is 74% for patients without reflex-otalgia versus 49% for patients with reflex-otalgia. CONCLUSION: In our patients, reflex-otalgia is a new and statistically significant parameter for the probability of local control and disease specific survival.