[en] Purpose: Endobronchial brachytherapy has become more widely used to increase the total local dose of irradiation ('boost') applied for the treatment of lung cancer. Apart from treatment for local stenosis, endobronchial brachytherapy in combination with external irradiation (EI) has the potential to improve local tumor control and perhaps prolong survival, but the real benefit has not been proven yet. To evaluate the possible effects of external irradiation with an additional boost of high dose rate (HDR) brachytherapy, we conducted a prospective randomized study. Methods and Materials: Design--two groups were compared: Group 1 was treated with external radiotherapy alone (planned dose 60 Gy); Group 2 received an additional boost of HDR brachytherapy of scheduled 4.8 Gy each (at 10 mm from the source axis) before and after external irradiation. Patients--98 patients with advanced inoperable lung cancer were included in the study, 42 in Group 1 and 56 in Group 2. Both groups were comparable with respect to age, sex, tumor stage, Karnofsky performance status (KPS), and histology. Results: A mean total external irradiation dose of 50.5 ± 14.1 Gy in Group 1 and 50 ± 12.5 Gy in Group 2 was applied. Group 2 received an additional dose of 7.44 ± 2.6 Gy (at 10 mm depth) through brachytherapy. The median survival time in both groups was comparable (28 weeks and 27 weeks, respectively). In patients with squamous cell carcinoma (68 patients) Group 2 showed an advantage in median survival with borderline significance (40 vs. 33 weeks, p = 0.09). Group 2 showed also a better local tumor control in all patients; patients with squamous cell carcinoma had a significantly longer period of local tumor control. Fatal hemoptysis was the cause of death in 6 (14.2%) patients in Group 1 and 11 (18.9%) in Group 2 (p = 0.53). Conclusions: High dose rate brachytherapy in patients with inoperable lung cancer increased local control in our randomized study when used in combination with external irradiation. Survival time was also longer, but with no clear statistical significance. This applied especially to patients with squamous cell carcinomas. There was no statistically significant difference in the incidence of fatal hemoptysis between the two groups

[en] Purpose: High-dose-rate (HDR) brachytherapy of human lung cancer is well established, however fractionation schemes and dosages are based mainly on experience. The aim of this investigation was to study the effects of different doses of HDR iridium-192 on normal human bronchial epithelium in three-dimensional miniorgans of the human bronchial wall. Methods and Materials: Forty-eight biopsies from normal bronchi were cultivated for 14 days and exposed at random to different doses of HDR iridium 192 (0 Gy, 30 Gy, 45 Gy, 60 Gy, or 75 Gy). Cell viability was assessed immediately after irradiation, after 4 or 18 days by fluorescent staining, and cell damage of the culture was analyzed by light microscopy. Lactate dehydrogenase (LDH) was measured in the supernatant for 4 days. Results: There was no histologically apparent tissue damage regardless of the irradiation dose. The number of nonvital cells increased in irradiated miniorgans depending on the dose used (p < 0.05 at 75 Gy). This effect occurred early and was less pronounced with time. LDH measurements showed an increase only in the first 24 hours. Conclusions: Our results confirm that normal bronchial epithelium has a high tolerance to early epithelial damage by irradiation. This model of human bronchial miniorgans is useful for further studies of the effects of irradiation on human bronchi

[en] To determine the efficacy of high dose rate endobronchial brachytherapy (HDR-BT) for the treatment of centrally located lung tumors, two different fractionation schedules were compared regarding local tumor response, side effects and survival. Mature retrospective results with longer follow-up and more patients were analyzed. Initial results were published by Huber et al. in 1995. 142 patients with advanced, centrally located malignant tumors with preferential endoluminal growth were randomized to receive 4 fractions of 3.8 Gy (time interval: 1 week, n = 60, group I) or 2 fractions of 7.2 Gy (time interval: 3 weeks, n = 82, group II) endobronchial HDR-BT. Age, gender, tumor stage, Karnofsky Performance Score and histology were equally distributed between both groups. Local tumor response with 2 fractions of 7.2 Gy was significantly higher as compared to 4 fractions of 3.8 Gy (median 12 vs. 6 weeks; p ≤ 0.015). Median survival was similar in both groups (19 weeks in the 4 fractions group vs. 18 weeks in the 2 fractions group). Fatal hemoptysis was less frequent following irradiation with 2 × 7.2 Gy than with 4 × 3.8 Gy, although the difference did not achieve statistical significance (12.2% vs. 18.3%, respectively. p = 0,345). Patients presenting with squamous cell carcinoma were at higher risk of bleeding compared to other histology (21.9% vs. 9%, p = 0,035). Multivariate analysis with regard to overall survival, revealed histology (p = 0.02), Karnofsky Performance Score (p < 0.0001) and response to therapy (p < 0.0001) as significant prognostic factors. For patients showing complete response the median survival was 57 weeks, while for patients with progressive disease median survival time was 8 weeks, p < 0.0001. The KPS at the start of the treatment was significantly correlated with survival. Patients presenting with a KPS ≤ 60 at the start had a significantly (p = 0,032) shorter survival time (10 weeks) than patients with a KPS > 60 (29 weeks). Moreover, the Karnofsky Performance Score of most patients improved during therapy (p = 0,001), suggesting successful palliation of cancer associated symptoms. Multivariate analysis with regard to local tumor control found no significant factors. Endobronchial HDR-BT is an effective local treatment for advanced centrally located malignant tumors with endoluminal tumor growth. Local tumor response was significantly higher after HDR-BT with 2 × 7.2 Gy

[en] Purpose: To evaluate the long-term mechanical behavior in vivo of expandable endobronchial wire stents, we imaged three different prostheses in the treatment of tracheobronchial disease. Methods: Six patients with bronchial stenoses (three benign, three malignant) underwent insertion of metallic stents. Two self-expandable Wallstents, two balloon-expandable tantalum Strecker stents and two self-expandable nitinol Accuflex stents were used. Measurements of deformation properties were performed during voluntary cough by means of fluoroscopy, at 1 month and 7-10 months after implantation. The procedures were videotaped, their images digitized and the narrowing of stent diameters calculated at intervals of 20 msec. Results: After stent implantation all patients improved with respect to ventilatory function. Radial stent narrowing during cough reached 53% (Wallstent), 59% (tantalum Strecker stent), and 52% (nitinol Accuflex stent) of the relaxed post-implantation diameter. Stent compression was more marked in benign compared with malignant stenoses. In the long term permanent deformation occurred with the tantalum Strecker stents; the other stents were unchanged. Conclusion: Endobronchial wire stents can be helpful in the treatment of major airway collapse and obstructing bronchial lesions. However, evidence of material fatigue as a possible effect of exposure to recurrent mechanical stress on the flexible mesh tube may limit their long-term use. This seems to be predominantly important in benign bronchial collapse

[en] Concurrent chemoradiotherapy (CRT) is considered standard for inoperable stage III non-small cell lung cancer (NSCLC). Consolidation chemotherapy (CC) following CRT is intended to further improve outcomes, yet studies have shown discordant results. This phase III study assessed CRT followed by best supportive care (BSC) or consolidation with oral vinorelbine and cisplatin. Patients received two cycles of oral vinorelbine (50 mg/m"2 days 1, 8 and 15) + cisplatin (20 mg/m"2 days 1-4) q4w + radiotherapy (RT; 66 Gy). Patients with at least stable disease (SD) were randomised to either two cycles oral vinorelbine (60-80 mg/m"2 days 1 and 8) + cisplatin (80 mg/m"2 day 1) q3w + BSC or BSC alone. Primary endpoint was progression-free survival (PFS). A total of 279 patients were enrolled for CRT and 201 patients were randomised to CC or BSC. Both CRT and CC were well tolerated, with limited radiation-mediated grade 3/4 toxicities (CRT/CC/BSC: oesophagitis-related events 12.9 %/3.1 %/0 %; grade 3 pneumonitis 0 %/0 %/2 %) and chemotherapy-mediated grade 3/4 toxicities (CRT/CC: neutropenia 11.2 %/22.1 %; leukopenia 18.3 %/26.7 %; grade 3 nausea 5.0 %/2.3 %, grade 3 vomiting 3.2 %/3.5 %). Median PFS from randomisation was 6.4 (5.0-8.7) and 5.5 (3.8-7.4) months in the CC and BSC arms (hazard ratio, HR = 0.93 [0.69-1.26]; p = 0.63), respectively; median overall survival (OS) 20.8 (13.5-25.3) and 18.5 (13.6-24.7) months, respectively. Consolidation chemotherapy after concurrent CRT did not prolong PFS or OS. Concurrent RT with oral vinorelbine and cisplatin demonstrated a favourable safety profile and represents a suitable treatment regimen for inoperable stage III NSCLC. (orig.)