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Nils Hovdenak

Publications and source records attributed to Nils Hovdenak.

3 recordsLinked to original sources

Profiles and time course of acute radiation toxicity symptoms during conformal radiotherapy for cancer of the prostate.

Symptoms of gastrointestinal toxicity are dose-limiting for pelvic radiotherapy (RT). Existing toxicity registrations (RTOG/EORTC) are helpful in defining maximal tolerated doses, but tend to underestimate the total toxicity burden by excluding several minor complaints. We have applied a more detailed and quantitative recording of symptoms and related these scores to RT-induced endoscopic and histopathologic changes. Prevalence and severity of specific toxicity symptoms were recorded before, during (weeks 2 and 6) and 2 and 8 weeks after RT in 96 patients undergoing external beam RT for localized prostate cancer. RTOG/EORTC acute toxicity and ad hoc total toxicity scores (TTS) were recorded. TTS scores were calculated by adding scores based on visual analog scale (VAS) grading of individual symptoms Fifty of the patients also underwent sequential proctoscopy with mucosal biopsy. Individual symptoms increased, but differed in prevalence and intensity during and after RT TTS increased during the entire treatment course in spite of normalizing histopathologic and endoscopic changes from week 2 onwards. Twenty-seven patients had no RTOG/EORTC toxicity, four had grade 3 and none had grade 4 toxicity. All patients with grade 0 had increased TTS. Thus, TTS appeared more sensitive than RTOG/EORTC scoring. The study demonstrates that multiple toxicity symptoms contribute to total toxicity in response to pelvic RT. TTS is a feasible and sensitive method for detecting and quantifying acute toxicity and unveils morbidity which remains hidden with the RTOG/EORTC score system. The development and timing of symptoms may give clues to pathogenesis, treatment, and prophylaxis.

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Clinical significance of increased gelatinolytic activity in the rectal mucosa during external beam radiation therapy of prostate cancer.

PURPOSE: Rectal toxicity (proctitis) is a dose-limiting factor in pelvic radiation therapy. Mucosal atrophy, i.e., net extracellular matrix degradation, is a prominent feature of radiation proctitis, but the underlying mechanisms are not known. We prospectively examined changes in matrix metalloproteinase (MMP)-2 and MMP-9 (gelatinase A and B) in the rectal mucosa during radiation therapy of prostate cancer, as well as the relationships of these changes with symptomatic, structural, and cellular evidence of radiation proctitis. METHODS AND MATERIALS: Seventeen patients scheduled for external beam radiation therapy for prostate cancer were prospectively enrolled. Symptoms of gastrointestinal toxicity were recorded, and endoscopy with biopsy of the rectal mucosa was performed before radiation therapy, as well as 2 and 6 weeks into the treatment course. Radiation proctitis was assessed by endoscopic scoring, quantitative histology, and quantitative immunohistochemistry. MMP-2 and MMP-9 were localized immunohistochemically, and activities were determined by gelatin zymography. RESULTS: Symptoms, endoscopic scores, histologic injury, and mucosal macrophages and neutrophils increased from baseline to 2 weeks. Symptoms increased further from 2 weeks to 6 weeks, whereas endoscopic and cellular evidence of proctitis did not. Compared to pretreatment values, there was increased total gelatinolytic activity of MMP-2 and MMP-9 at 2 weeks (p = 0.02 and p = 0.004, respectively) and 6 weeks (p = 0.006 and p = 0.001, respectively). Active MMP-2 was increased at both time points (p = 0.0001 and p = 0.002). Increased MMP-9 and MMP-2 at 6 weeks was associated with radiation-induced diarrhea (p = 0.007 and p = 0.02, respectively) and with mucosal neutrophil infiltration (rho = 0.62). CONCLUSIONS: Pelvic radiation therapy causes increased MMP-2 and MMP-9 activity in the rectal mucosa. These changes correlate with radiation-induced diarrhea and granulocyte infiltration and may contribute to abnormal connective tissue remodeling in radiation proctitis.

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