Palliative Endobronchial Brachytherapy for Central Lung Tumors: A Prospective, Randomized Comparison of Two Fractionation Schedules

doi:10.1378/chest.107.2.463

Chest

Volume 107, Issue 2, February 1995, Pages 463-470

https://doi.org/10.1378/chest.107.2.463 Get rights and content

Aim of the study

Remote high dose rate brachytherapy is an effective local treatment modality for central lung tumors and has the potential to improve survival time. Optimal dose and fractionation schemes have not been identified yet. We conducted a prospective randomized study to compare two treatment schedules in terms of survival time, local tumor control, and possible complications.

Design

Group 1 received 4 brachytherapies with a dose of 3.8 Gy (at a 10-mm depth) on a weekly basis, and group 2 received 2 treatments with 7.2 Gy (at a 10-mm depth) at a 3-week interval. At a depth of 5 mm, the calculated doses would be 8 and 15 Gy. This study is still ongoing. Here we report interim results.

Patients

Ninety-three patients with advanced cancer were included in the study; 44 were in group 1 and 49, in group 2. Both groups were comparable regarding age, sex, tumor stage, Karnofsky performance status, and histologic findings.

Interventions

A mean total irradiation dose of 13.4±5.2 Gy for group 1 and 13.7±4.4 for group 2 were applied (calculated at 10 mm from the source axis, equivalent to 27.9 Gy in group 1 and 28.5 Gy in group 2 at a 5-mm depth).

Results

The 1-year survival rate was 11.4% in group 1 and 20.4% in group 2. No significant difference in survival time was found, but mean survival was longer in group 2 (49 weeks) than in group 1 (26 weeks). Local control after 3 months was comparable in both groups. Fatal hemoptysis occurred at a similar rate in group 1 (22.2%) and in group 2 (21.1%).

Conclusion

High-dose rate brachytherapy with 2×7.2 Gy with a 3-week interval is equivalent to a 4×3.8-Gy regimen on a weekly basis. The shorter treatment schedule is more convenient for patients, does not cause more side effects, and provides an equal local tumor control.

Section snippets

Study Site

After approval by the Ethics Committee of the School of Medicine, University of Munich, this study started in January 1989 and is ongoing.

Patients Selection and Randomization

Ninety-three patients were included in this study according to the following inclusion criteria: lung cancer, proven by histologic or cytologic studies; cancer localization in the trachea or in the mainstem or lobar bronchi; substantial occlusion evidenced by bronchoscopic examination; no alternative treatment options such as surgery, external radiotherapy,

Clinical Data

Ninety-three patients were included in this study; 44 subjects were in group 1 (4×3.8 Gy) and 49 were in group 2 (2×7.2 Gy). The minimum observation time was 3 months with a median observation time of 2.5 years. The main demographic and medical data are shown in Table 1. Group 1 consisted of 36 (81.8%) men and 8 (18.2%) women and group 2 consisted of 34 (69.4%) men and 15 (30.6%) women. The mean age was 66.2±10.4 in group 1 and 64.0± 10.3 in group 2. Most patients had a very advanced tumor

DISCUSSION

The results presented are based on a study population of 93 patients with far advanced lung cancer. Our investigation shows no disadvantage for the fractionation regimen employing 2 times 7.2 Gy with a 3-week interval when compared with a more fractionated schedule (4×3.8 Gy weekly). Survival time in the group receiving two applications is not significantly higher than with the more fractionated schedule, but the trend toward longer survival is obvious. Local disease control and side effects

CONCLUSION

In this prospective and randomized study, 93 patients were evaluated and distributed in two treatment groups, one receiving 15.4 Gy in 4 fractions of 3.8 Gy and, the other receiving 14.4 Gy in 2 fractions of 7.2 Gy. The overall survival is slightly better for group 2, but median survival time is the same. Local control is a little better in group 1, but this has no influence on survival time. Occurrence of fatal hemorrhages also is equal in both groups, depending on the types of histologic

ACKNOWLEDGMENT

We are indebted to Mrs. Diane Keaton and Mrs. S. M. Lang, MD, for editorial assistance.

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2023, Brachytherapy
To evaluate clinical outcomes of endobronchial malignancy treated using high-dose-rate endobronchial brachytherapy (HDREB).
A retrospective chart review was conducted for all patients treated with HDREB for malignant airway disease between 2010 and 2019 at a single institution. Most patients had a prescription of 14 Gy in two fractions given a week apart. The Wilcoxon signed rank test and paired samples t test were used to compare changes in mMRC dyspnea scale prior to and after brachytherapy at first followup appointment. Toxicity data were collected for dyspnea, hemoptysis, dysphagia, and cough.
A total of 58 patients were identified. Most (84.5%) had primary lung cancer with advanced cancers, stage III or IV (86%). Eight were treated while admitted in the ICU. Previous external beam radiotherapy (EBRT) was received by 52%. An improvement in dyspnea was seen in 72%, with an mMRC dyspnoea scale score improvement of 1.13 points (p < 0.001). Most (22, 88%) had an improvement in hemoptysis and 18 out of 37 (48.6%) had an improvement in cough. Grade four to five events occurred in 8 (13%) at the median time of 2.5 months from brachytherapy. Twenty-two patients (38%) had complete obstruction of the airway treated. Median progression free survival was 6.5 months and median survival was 10 months.
We report a significant symptomatic benefit among patients receiving brachytherapy with endobronchial malignancy, with rates of treatment related toxicities similar to prior studies. Our study identified new subgroups of patients, ICU patients & those with complete obstruction, who benefited from HDREB.
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The impact of the fractionation schedule on survival was not statistically significant in a multivariate analysis (p = 0.853) (25). Similarly, an RCT investigated two groups of patients with lung cancer treated with HDR endobronchial BT (2 × 7.2 Gy per week, n = 49 vs. 4 × 3.8 Gy per week, n = 44), and the local control, overall survival, and fatal hemoptysis was found to be of no significant difference between groups (26). In another RCT, twice 7.2 Gy (n = 82) application was found superior to four times 3.8 Gy (n = 60) application per week with a 3 weeks’ interval schedule in time of local tumor response (median 12 vs. 6 weeks; p ≤ 0.015); however, there was no significant difference in survival (median 18 vs. 19 weeks, p = n.s.) and fatal hemoptysis between groups (12.2% vs. 18.3%, respectively.
Brachytherapy (BT) is a minimally invasive anticancer radiotherapeutic modality where the tumor is directly irradiated via a radioactive source that is precisely implanted in or adjacent to the tumor. BT for lung cancer may be conducted in the form of endobronchial BT and radioactive seed implantation (RSI-BT), mainly for nonsmall cell lung cancer (NSCLC). For patients with early-stage lung cancer who are not suitable for surgery or external beam radiotherapy (EBRT), BT may be used as an alternative treatment, and curative results could be achieved in certain patients with cancer confined to the trachea lumen. For patients with locally advanced/metastatic lung cancer, BT could be selectively applied alone or as a boost to EBRT, which could improve the local tumor control and patient’s survival. In addition, BT is also useful as a salvage treatment in select patients with locally recurrent/residual lung cancer that failed other treatments (e.g., surgery, chemotherapy, and EBRT). However, clinical outcomes are mainly obtained from retrospective studies. Prospective studies are limited and needed. In recent years, the introduction of modern image guidance, novel radioactive seeds, BT treatment planning systems (BT-TPS), after-loading technique, and three-dimensional printing template (3D-PT) assistance, among others, have potentially improved the clinical outcomes of BT. However, a comprehensive review of BT with newly published literature was lacking. This review is to discuss BT for NSCLC based on recent literature published in PubMed.
Endoluminal brachytherapy: Bronchus and oesophagus
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Endobronchial brachytherapy could be proposed in case of endoluminal tumours either as a palliative or a curative treatment. As a curative treatment, endobronchial brachytherapy could obtain a high local control rate in case of limited disease. In palliative setting, endobronchial brachytherapy improved thoracic symptoms in more than 80% of cases, but it is less efficient than external beam radiation therapy for palliation. It could be also proposed to maintain the airway open after laser therapy. Oesophageal brachytherapy is a valuable option as a palliative treatment, underused at this time. It causes less side effects and a better quality of life compared to self-expanded metallic stents. For a curative aim, there is today no demonstration that a combination of external beam radiotherapy and oesophageal brachytherapy give better results than external beam radiotherapy alone in locally advanced tumours. For superficial diseases, the combination of external beam radiotherapy and oesophageal brachytherapy seems, on the contrary, promising.
La curiethérapie endobronchique peut être proposée pour les tumeurs endoluminales, soit dans une optique curative, soit à visée palliative. Pour les lésions limitées à la bronche, elle permet d’obtenir le contrôle local pour un nombre élevé de patients. À visée palliative, elle améliore les symptômes thoraciques dans plus de 80 % des cas, mais son effet palliatif est moindre que celui de la radiothérapie externe. Elle peut être aussi proposée après désobstruction par laser pour prolonger la perméabilité des voies aériennes. La curiethérapie endo-œsophagienne est une option intéressante à visée palliative actuellement sous-utilisée. Elle donne moins d’effets secondaires que la pose de prothèses métalliques auto-expansibles avec des résultats en qualité de vie meilleurs. À visée curative, il n’y a aujourd’hui pas de démonstration qu’elle apporte un bénéfice dans la prise en charge des tumeurs localement évoluées. Pour les tumeurs superficielles, l’association d’une radiothérapie externe et d’une curiethérapie apparaît prometteuse.
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Palliative radiation can be useful in numerous clinical scenarios with respect to primary or metastatic thoracic tumors. Extensive stage small cell lung cancer (SCLC) and locally advanced, unresectable nonsmall cell lung cancer (NSCLC) are the most common causes of symptoms that can be managed even in the setting of incurable underlying disease. Dyspnea, pain, hemoptysis, and superior vena cava syndrome are some manifestations of thoracic tumor invasion that compromise quality of life and survival. Multiple trials have been conducted to assess symptom relief and survival, with some conflicting evidence. Palliation of symptoms is reasonably achieved in most of these studies, and some show benefits in survival or tumor regression. Various fractionation schemas have been studied to determine the optimal symptom control. Metaanalyses have attempted to identify subsets of patients that benefit more, with performance status emerging as consistent predictor of benefit. Patient selection remains crucial to determining the risk–benefit ratio of any regimen.
A prospective analysis of high-dose-rate endobronchial brachytherapy in the palliation of obstructive symptoms in lung cancer patients: A single-institution experience
2015, Brachytherapy
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A wide array of dose and fractionation schedules is seen in published case series, complicating interpretation of the literature. Studies have attempted to determine the optimal dose and fractionation but have largely found no significant difference between regimens (9, 12, 13), yet suggestion of a dose response for toxicity and local control has been made (14, 15). Additionally, the role of HDREBBT as a boost has been explored but the results have been mixed (9, 12, 14,16–21).
Obstructive symptoms that affect quality of life (QOL) are commonly caused by endobronchial disease in many patients with locally advanced, inoperable lung cancer. High-dose-rate endobronchial brachytherapy (HDREBBT) has been used to palliate these symptoms, yet its role is not well defined in the literature.
Ninety-eight patients with locally advanced, inoperable lung cancer received HDREBBT. They were prospectively followed for survival, QOL, and toxicity endpoints. QOL measures were captured using the Quality of Life Questionnaire–Lung Cancer 30 and –Lung Cancer 13.
At 1-year follow-up, no significant toxicities were seen. Overall survival was 13.4% at 12 months (mean 192 days). Performance status, additional treatment after HDREBBT and treatment intent affected overall survival on univariate analysis (p < 0.05). Mean hemoptysis-free survival for all patients was 232.3 days, cough-free survival was 140.3 days, and dyspnea-free survival was 173.5 days. There was no impact of any treatment- or patient-related factors of these outcomes on multivariate analysis, including additional treatment modalities and HDREBBT dose.
HDREBBT is a safe and effective way to palliate endobronchial symptoms. Additional external-beam radiation therapy, chemotherapy, or chemoradiation after HDREBBT improves survival, but does not affect QOL measures.
Definitive high-dose-rate endobronchial brachytherapy of bronchial stump for lung cancer after surgery
2013, Brachytherapy
The aim of this work was to evaluate outcomes after definitive high-dose-rate endobronchial brachytherapy (HDR-BT) for lung cancer.
We treated 34 patients after surgery for lung cancer, without nodal or distant metastases, with HDR-BT. Two groups were analyzed, one with local recurrence in stump after prior surgery (n = 13) and a second with nonradical primary lobar resection found in histopathologically positive margins (n = 21). There were 27 men and 7 women with a median age of 57.4 years. Twenty-five patients received sole brachytherapy with 4 fractions of 7.5 Gy and 9 received combined treatment consisting of 2 fractions of 6 Gy (HDR-BT) and 50 Gy from external beam radiotherapy. Overall survival time (OS) and overall disease-free survival time (OFS) were compared with prognostic factors.
The complete local and radiologic response rate evaluated at the first month after HDR-BT was 73.5% (25/34). The partial response rate was 26.5%. OFS time in total group was 17.4 months; OS was 18.8 months. Differences were found in OS between both groups—primary tumor or recurrence (log-rank test, p = 0.048). Differences were not found according to gender (p = 0.36), clinical stage (p = 0.76), histopathology (p = 0.93), treatment dose (p = 0.45), sole or combined treatment (p = 0.16), or grade of remission in week 4 (p = 0.15).
HDR-BT of a stump recurrence or after nonradical resection leads to a long-term OS rate in patients with localized lung cancer and could be considered curative. We found no correlations between OS and chosen clinical data; adjuvant HDR-BT gave better results.

View all citing articles on Scopus

Supported by Wilhelm-Sander-Stiftung 87.015.1 and 87.015-2.

Presented in parts at the 17th World Congress on Diseases of the Chest, Amsterdam, Netherlands, 1993.

Reprint requests: Dr. Huber, Ludwig Maximilians Universität, Klinikum Innenstadt, Medizinische Klinik, Pneumologische Abteilung Zi. 162, Ziemssenstrasse 1, D 80336, München, Germany

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Clinical Investigations: Tumors and PseudotumorsPalliative Endobronchial Brachytherapy for Central Lung Tumors: A Prospective, Randomized Comparison of Two Fractionation Schedules

Aim of the study

Design

Patients

Interventions

Results

Conclusion

Section snippets

Study Site

Patients Selection and Randomization

Clinical Data

DISCUSSION

CONCLUSION

ACKNOWLEDGMENT

Clin Chest Med

Clin Chest Med

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Chest

Lung Cancer

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Chest

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Chest

Int J Radiat Oncol Biol Phys

Chest

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Cancer statistics, Ca-A

CA Clin

Clinical Investigations: Tumors and Pseudotumors
Palliative Endobronchial Brachytherapy for Central Lung Tumors: A Prospective, Randomized Comparison of Two Fractionation Schedules