Optimization of dose and fractionation of endobronchial brachytherapy with or without external radiation in the palliative management of non-small cell lung cancer: a prospective randomized study. Combination of interventional pulmonology techniques (Nd:YAG laser resection and brachytherapy) with external beam radiotherapy in the treatment of lung cancer patients with Karnofsky Index < or =50. External irradiation versus external irradiation plus endobronchial brachytherapy in inoperable non-small cell lung cancer: a prospective randomized study. Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer. Combined Nd-YAG laser/HDR brachytherapy versus Nd-YAG laser only in malignant central airway involvement: a prospective randomized study. Efficacy and safety of photodynamic therapy versus Nd-YAG laser resection in NSCLC with airway obstruction. Remote afterloading brachytherapy for the local control of endobronchial carcinoma. Prolonged survival after high-dose rate endobronchial radiation for malignant airway obstruction. Radiochemotherapy with amifostine cytoprotection for head and neck cancer.
Endobronchial brachytherapy (EBBT) is an established modality for the palliation in advanced non-small cell lung cancer. We compared three different schedules using EBBT with or without external radiation (XRT) in this setting.
                Forty-five patients were randomized to three treatment arms. Arm A received XRT to a dose of 30 Gy/10 fr/2 weeks and two sessions of EBBT 8 Gy each. Arm B received the same XRT and a single session of EBBT 10 Gy at 1 cm. Arm C received only a single fraction of brachytherapy to a dose of 15 Gy at 1 cm without XRT. Symptomatic response rates, duration of symptom palliation, obstruction scores, quality of life outcomes and complications were assessed and compared.
                The overall symptomatic response rates were 91% for dyspnea, 84% for cough, 94% for hemoptysis and 83% for obstructive pneumonia. There was no significant difference between the arms. The median time to symptom relapse was 4-8 months for all symptoms and the median time to symptom progression was 6-11 months. The results were comparable between groups except for hemoptysis, where a shorter palliation was seen in Arm C that achieved statistical significance (P < 0.01). Quality of life showed significant improvement, with maximum benefit in Arm A. Complication rates were low. Only one patient died of fatal hemoptysis.
                EBBT is thus a safe and effective palliative tool in advanced non-small cell lung cancer, either alone or in conjunction with XRT. The difference between the treatment arms were not statistically significant in most categories, but patients treated with XRT and two endobronchial sessions of 8 Gy had the most consistent benefit in terms of all the parameters studied. To compare Nd: YAG laser resection with Nd: YAG laser plus brachytherapy and external beam radiotherapy (EBRT) in the palliation of malignant central airway obstruction symptoms due to lung cancer.
                In this prospective non-randomized study we evaluated the effects of Nd:YAG laser photoresection alone vs. Nd:YAG laser resection in combination with brachytherapy and EBRT on cough, dyspnoea, thoracic pain, haemoptysis, body weight loss, atelectasis, postobstructive pneumonia, endoscopic findings, disease-free period and survival rate in lung cancer patients. Only patients with Karnofsky index (KI) < or =50 were included. Sixty-four patients were divided into 2 groups: group I patients ( = 20) were treated only with Nd: YAG laser, and group II patients (n = 44) were treated with Nd: YAG laser followed by brachytherapy and EBRT.
                Group I patients showed statistically significant improvement in all investigated parameters but cough. Group II patients achieved significant improvement in all investigated parameters. Comparative statistical analysis between the 2 groups revealed statistically significant improvement in group II with regard to dyspnoea, haemoptysis, KI and atelectasis. No significant improvement in group II was seen when other investigated parameters were considered. Disease-free period and survival rate were significantly longer in group II (p< or =0.0005).
                The combination of interventional pulmonology procedures with standard modalities is the best option for the treatment of selected lung cancer patients. No randomized studies are available on the additional value of endobronchial brachytherapy (EBB) to external irradiation (XRT) regarding palliation of respiratory symptoms (RS). A prospective randomized study was initiated to test the hypothesis that the addition of EBB to XRT provides higher levels of palliation of dyspnea and other RS and improvement of quality of life (QoL) in patients with non-small cell lung cancer (NSCLC) with endobronchial tumour.
                Patients with previously untreated NSCLC, stages I-IIIb, WHO-performance status of 0-3 and with biopsy proven endobronchial tumour in the proximal airways were eligible. EBB consisted of two fractions of 7.5 Gy at 1 cm on day 1 and 8. XRT started at day 2. The XRT dose was 30 Gy (2 weeks) or 60 Gy (6 weeks). The EORTC QLQ-C30 and QLQ-LC13 were assessed before treatment and 2 weeks, 6 weeks, 3, 6 and 12 months after treatment. Re-expansion of collapsed lung was tested by the inspiratory vital capacity (IVC) and CT scan of the chest.
                Ninety-five patients were randomized between arm 1 (XRT alone) (n=48) or arm 2 (XRT+EBB) (n=47). The arms were well balanced regarding pre-treatment characteristics and QoL scores. The compliance for QoL-assessment was >90% at all times. No significant difference between the trial arms was observed with respect to response of dyspnea. However, a beneficial effect of EBB was noted concerning the mean scores of dyspnea over time (P=0.02), which lasted for 3 months. This benefit was only observed among patients with an obstructing tumour of the main bronchus. A higher rate of re-expansion of collapsed lung was observed in arm 2 (57%) compared to arm 1 (35%) (P=0.01). The inspiratory vital capacity (IVC) assessed 2 weeks after radiotherapy improved with 493 cm(3) in arm 2 and decreased 50 cm(3) in arm 1 (P=0.03). No difference was noted regarding the incidence of massive haemoptysis (13 vs. 15%).
                The addition of EBB to XRT in NSCLC is safe and provides higher rates of re-expansion of collapsed lung resulting in a transient lower levels of dyspnea. This beneficial effect was only observed among patients with obstructing tumours in the main bronchus. To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC).
                Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m(2)/day)/carboplatinum (70 mg/m(2)) on days 1--5 and 29--33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 microg, days 15--19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1--3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors).
                This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p = 0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p = 0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p = 0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p = 0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p = 0.84). For both tumor locations, prophylactically given G-CSF was a poor prognostic factor (Cox regression), and resulted in reduced LRC (log-rank test: +/- G-CSF, p = 0.0072).
                With accelerated radiotherapy, the efficiency of simultaneously given chemotherapy may be not as high as expected when compared to standard fractionated RT. Oropharyngeal carcinomas showed better LRC after HF-ACC-RCT vs. HF-ACC-RT; hypopharyngeal carcinomas did not. Prophylactic G-CSF resulted in an unexpected reduced local control and should be given in radiotherapy regimen only with strong hematologic indication. Laser debulking and prosthetic stents are useful modalities in the palliative treatment of initial inoperable or recurrent lung cancer. Recently, endobrochial brachytherapy was introduced to extend the duration of palliation and reduce the number of endoscopic treatments. This trial compares Nd-YAG laser alone and associated to high dose rated (HDR)-brachytherapy.
                From 1995 to 1998, 29 consecutive patients, with non-small cell lung cancer (NSCLC) and central airway involvement, were randomized in two groups: group 1 (15 patients) received Nd-YAG laser only; group 2 (14 patients) underwent a combined Nd-YAG laser/ HDR brachytherapy treatment.
                There was no mortality or morbidity related to the treatment. The period free from symptoms was 2.8 months for group 1 and increased to 8.5 months in group 2 (P<0.05). The disease's progression free period grew from 2.2 months of group 1 to 7.5 months of group 2 (P<0.05) and the number of further endoscopic treatment reduced from 15 to 3 (P<0.05).
                The results confirm the potential of brachytherapy to prolong relief from symptoms, lessen disease progression and reduce costs of treatment. A detailed analysis is presented of both groups. A prospective controlled randomized trial was performed in order to assess the effectiveness and safety of photodynamic therapy versus laser resection in 31 patients with partial or complete tracheobronchial obstruction due to inoperable non-small cell lung cancer. Fourteen patients received dihaematoporphyrin ether and argon dye laser photoradiation, and 17 patients received Nd-YAG laser resection. Endoluminal obstruction of >75% was found in 77.4% of the patients. Among the symptoms, cough was more severe in the Nd-YAG group (p=0.02). Patients in both groups experienced symptomatic relief after treatment (p=0.003). Patients in the photodynamic therapy (PDT) group showed a significantly longer time until treatment failure (p=0.03) and longer median survival (p=0.007). Bronchitis and photosensitization (both in the PDT group) were the most common adverse effects. There was one death, probably related to treatment, in the PDT group. Photodynamic therapy and neodymium-yttrium aluminium garnet laser resection showed similar effectiveness and safety in the palliation of symptoms. The more prolonged survival in the photodynamic therapy group may have been due to differences in tumour stage between the groups. The degree of obstruction improved after treatment in both groups. In conclusion, photodynamic therapy is a valid method of palliation in partially or totally obstructing non-small cell lung carcinoma. The study was designed to, (a) standardize endobronchial brachytherapy and, (b) to evaluate the relief of obstructive signs and symptoms.
                Patients with endobronchial carcinoma were treated on a protocol (n = 342) with remote afterloading brachytherapy. Group 1 patients were treated with medium dose rate and received 1000 cGy at 5 mm depth for three fractions (n = 47). Group 2 were treated with high dose rate, 1000 cGy to a 10 mm depth for three fractions (n = 144) and Group 3 received 750 cGy delivered to a 10 mm depth for three fractions (n = 151). Each group was divided into curative, palliative, and recurrent categories. Neodymium yttrium aluminum garnet photoresection was used in 24% of patients prior to brachytherapy.
                Evaluation consisted of symptom index scoring with weighted responses of hemoptysis 99%, obstructive pneumonia 99%, cough 85%, and dyspnea 86%. Obstruction improvement was 80% overall, curative 87%, palliative 84%, and recurrent 70% of mean pretreatment scores. Survival 10% alive, 88% expired, and 2% lost to follow-up. Cause of death was intrathoracic carcinoma 41%, metastatic carcinoma 38%, intercurrent disease 9%, and unknown cause 13%. Survival from diagnosis and first treatment was, respectively, for curative 10.8 and 9.5 months, palliative 14 and 5.6 months, and recurrent 25.6 and 6.2 months. Significant complications were fatal hemoptysis 7%, and radiation bronchitis and stenosis 11%.
                Endoluminal brachytherapy provides excellent palliation of the endobronchial portion of neoplastic disease. To show that prolonged survival can be observed after high-dose rate (HDR) endobronchial brachytherapy as the sole treatment for some selected patients presenting with an endobronchial malignant obstruction.
                Twenty-nine patients (group 1) who presented with an endoluminal localized tumor without metastatic extension were treated by HDR endobronchial brachytherapy and are compared with 22 subjects who presented with extraluminal dissemination and were palliatively treated (group 2). TREATMENT PROTOCOL: Treatment consisted of sessions of two exposures, delivering 7 Grays at a 10-mm radius from the center of the applicator each, and repeated every 15 days, to a maximum of six exposures. Endoscopic response and survival are the main criteria of assessment.
                Follow-up bronchoscopies, performed 2 months after the end of the procedure, showed tumor regressions: macroscopic complete responses (CR) were observed in 21 of 25 patients evaluable in group 1, and 6 of 22 in group 2, with histologic CR in 18 and 2 patients, respectively. Median overall survival was not reached in group 1 after 23 months of follow-up; it was 5 months for group 2.
                These results confirm that HDR brachytherapy can be used as a monotherapy for carefully selected patients who have small tumors to all appearances limited to the bronchial lumen and bronchial wall without adjacent parenchymal extension or metastatic disease. A randomized study was conducted to evaluate the protective activity of amifostine (A) against the dose-limiting toxicities of radiochemotherapy (RCT). Patients with head and neck cancer received radiotherapy (2 Gy/day 5 days a week up to 60 Gy) with carboplatin 70 mg/m2 on days 1-5 and 21-25 inclusive. Patients either received RCT alone (n = 14) or RCT + A at a dose of 500 mg prior to treatment with carboplatin (n = 25). There was a significant reduction in the incidence of grade 3/4 mucositis (P < 0.0001), acute grade 2 xerostomia (P < 0.0001) and grade 3/4 thrombocytopenia (P = 0.012) in these patients who received A. The incidence of grade 2 late xerostomia at 12 months is 16.7% and the incidence of loss of taste is 0% in patients treated with A, as opposed to 54.5% and 63.6% in patients who received RCT alone. There were 18 (72%) complete responses (CR) and 6 (24%) partial responses (PR) in patients who received A, compared with 6 (43%) CR and 6 PR (43%) in patients treated with RCT alone. The disease-free survival at 12 months is 85.7% in the RCT + A arm and 78.6% in the RCT alone arm. The use of amifostine reduces the incidence and severity of acute and late toxicities associated with RCT whilst preserving antitumour activity.
The evidence did not provide conclusive results that EBB plus EBRT improved symptom relief over EBRT alone. We were not able to provide conclusive evidence to recommend EBB with EBRT, EBB in preference to EBRT, chemotherapy or Nd-YAG laser. From heterogeneous information obtained from several small RCTs, we conclude that EBRT alone is more effective for palliation than EBB alone. For patients previously treated by EBRT who are symptomatic from recurrent endobronchial central obstruction, EBB may be considered in selected cases.