Endobronchial Brachytherapy as Definitive Treatment for Endobronchial Metastasis After Surgery of Non-Small-Cell Lung Cancer

doi:10.21203/rs.3.rs-571170/v1

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Case Report

Endobronchial Brachytherapy as Definitive Treatment for Endobronchial Metastasis After Surgery of Non-Small-Cell Lung Cancer

https://doi.org/10.21203/rs.3.rs-571170/v1

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Background

Endobronchial metastasis is a very rare type of recurrence after lung cancer surgery. Surgical intervention may be difficult to perform due to the postoperative reduction in the activities of daily living (ADL) and the invasiveness associated with redo surgery. In such cases, endobronchial brachytherapy (EBBT) plays an important role not only as palliative treatment, but also as definitive treatment with curative intent.

Case presentation:

Three men (64, 69, and 74 years old) underwent combination therapy of external beam radiation therapy (EBRT) and EBBT for endobronchial metastasis after lobectomy of Stage Ⅰ-Ⅱ non-small-cell lung cancer (NSCLC): 2 cases of squamous cell carcinoma and 1 of adenocarcinoma. We used a special source-centralizing applicator for EBBT to avoid eccentric distribution of the radiation dose. Follow-up was considered to start from the end of brachytherapy. None of our patients experienced severe adverse events, and none needed extensive outpatient treatment. Local control was achieved in all cases by a bronchoscopic evaluation. All patients were alive after 31, 38, and 92 months of follow up, respectively. In the adenocarcinoma patient, two metastases to the lung were discovered three years after EBBT, and the patient underwent partial wedge resection.

Conclusions

EBBT may be a promising treatment with curative intent for endobronchial metastasis after surgery of NSCLC.

Cancer Biology

Oncology

Cardiothoracic Surgery

Endobronchial metastasis

Endobronchial brachytherapy

definitive treatment

Despite advances in radiation therapy, chemotherapy, and newly developed molecular-targeted-therapies, lung cancer remains a major health problem and a leading cause of cancer mortality worldwide. The majority of mortalities in case of postoperative non-small-cell lung cancer (NSCLC) are due to the development of recurrence. Endobronchial metastasis is a very rare type of recurrence defined in detail by Schoenbaum and Viamonte [1]. Patients with endobronchial metastasis often suffer from symptoms of airway obstruction, including coughing, hemoptysis, dyspnea, and wheezing. Therefore, removal of the bronchial obstruction can help to improve the patient’s clinical status. However, surgical intervention may be difficult due to the postoperative reduction in activities of daily living (ADL) and the invasiveness associated with redo surgery. In such cases, endobronchial brachytherapy (EBBT) plays an important role not only as palliative treatment, but also as definitive treatment with curative intent.

EBBT is the radiation therapy in which the radioactive material is targeted at the bronchial lumen carrying the target lesion. Historically, EBBT has often been used for palliative treatment and has been shown to be effective in improving bronchial stenosis and obstruction caused by tumors [2]. Recently, several studies have demonstrated that EBBT plays a limited but specific role in definitive treatment with curative intent in select cases of early endobronchial disease, in select advanced inoperable tumors combined with external beam radiotherapy (EBRT), or in the postoperative treatment of small, residual peribronchial disease [2–5].

We herein report our experience with EBBT as definitive treatment for endobronchial metastasis after surgery of NSCLC to assess the feasibility and efficacy of this approach.

Between 2013 and 2018, 3 men (64, 69 and 74 years old) underwent a combination therapy of EBRT and EBBT for endobronchial metastasis after lobectomy of Stage Ⅰ-Ⅱ NSCLC: 2 cases of squamous cell carcinoma and 1 of adenocarcinoma. At the timing of the initial surgery, R0 resection was achieved in all cases. The diagnosis of cancer recurrence was made by a bronchoscopic biopsy. In all patients, surgical intervention was considered difficult due to postoperative reductions in the ADL and the invasiveness associated with redo surgery.

In accordance with present Japanese guidelines, radiation therapy consisted of a combination of EBRT in 20 fractions of 2 Gy and EBBT in 3 fractions of 6 Gy. Chemotherapy was not performed, and EBRT was performed prior to EBBT. The aim of EBRT prior to EBBT is to reduce the tumor size and obtain a uniform dose distribution to the bronchial wall. We used a special source-centralizing applicator (Create Medic Co. Ltd., Yokohama, Japan) developed by Nomoto et al. for EBBT to avoid eccentric distribution of the radiation dose [6]. This applicator can hold the source-delivering catheter because the two self-expandable wings open according to the bronchial diameter [4]. The applicator is adjusted to the optimal position such that the tumor is located between the two wings [4]. The distance from the source axis to the bronchial wall was measured on the planning computed tomography (CT) image [4].

Follow-up was considered to start from the end of EBBT. The local response was evaluated by bronchoscopy performed one to two months after the end of EBBT. In addition, CT was performed every six months for the first two years and then yearly for at least five years of follow-up.

Case 1

A 64-year-old man underwent the right upper lobectomy for lung cancer of adenocarcinoma (2.0 cm, pT1bN0M0, pStageⅠA2). The patient had no postoperative complications and was discharged on postoperative day 9. Nine years after the initial surgery, postoperative follow-up CT showed a left endobronchial nodule near the peripheral tracheal bifurcation (Fig. 1a). Bronchoscopy confirmed a protruding lesion emanating from the posterior wall of the left main bronchus (Fig. 1b). After a diagnosis of adenocarcinoma by tumor resection using a bronchoscopic snare was made, we performed a combination of EBRT and EBBT for the small residual disease as definitive treatment. The patient had achieved a complete local response without adverse events at the time of the bronchoscopic evaluation (Fig. 1c). Three years after irradiation, CT revealed a new partly solid nodule at the left lower lobe. The patient then underwent partial wedge resection and is still alive at 90 months since the irradiation.

Case 2

A 69-year-old man underwent the right lower lobectomy for lung cancer of squamous cell carcinoma (4.0 cm, pT2aN0M0, pStageⅠB). Two weeks after the surgery, we performed right-sided open-window thoracostomy due to postoperative bronchopleural fistula. Three months after open-window thoracostomy, he was discharged after undergoing thoracoplasty with omental plombage. One year and six months after discharge, postoperative follow-up CT showed a right endobronchial nodule at the truncus intermedius (Fig. 2a). Fluorodeoxyglucose-positron emission tomography (FDG-PET) reveled an uptake at the lesion (maximum standardized uptake value [SUV_max]: 3.8) (Fig. 2b). After a diagnosis of squamous cell carcinoma was made by a bronchoscopic biopsy (Fig. 2c), we performed a combination of EBRT and EBBT for the endobronchial metastasis as definitive treatment. The patient had achieved a complete local response without adverse events at the time of the bronchoscopic evaluation (Fig. 2d). The patient has remained disease-free for 36 months since the irradiation.

Case 3

A 74-year-old man underwent the left lower lobectomy for lung cancer of squamous cell carcinoma (5.7 cm, pT2bN0M0, pStageⅡA). The patient had no postoperative complications and was discharged at postoperative day 6. Two years after discharge, postoperative follow-up CT showed a left endobronchial nodule near the peripheral tracheal bifurcation (Fig. 3a). FDG-PET reveled an uptake at the lesion (SUV_max: 7.4) (Fig. 3b). After a diagnosis of squamous cell carcinoma was made by a bronchoscopic biopsy(Fig. 3c), we performed a combination of EBRT and EBB for the endobronchial metastasis as definitive treatment. The patient had achieved a complete local response without adverse events at the time of the bronchoscopic evaluation (Fig. 3d). The patient has remained disease-free for 29 months since the irradiation.

The frequency of endobronchial metastasis from non-pulmonary malignancies is known to range from about 2–50%, varying by the definition of metastasis used and the types of cancer included [7–9]. The overall incidence of tracheal metastasis was 0.44% in surgically resected NSCLC, and the incidence of tracheal metastasis was lower in primary lung cancers than in non-pulmonary malignancies [9]. Hemoptysis with coughing is the most common symptom of endobronchial metastasis, with an incidence of 41%-62% reported [9]. In our cases, all patients with endobronchial metastasis were free from symptoms despite the endobronchial nodule shown on postoperative follow-up CT. To determine whether or not these lesions are sputum, it is useful to examine the lesion uptake of FDG by PET-CT. In our cases, the uptake of FDG was revealed in endobronchial lesions, but there were no metastatic lesions noted outside the thorax, including in the brain.

Schoenbaum and Viamonte reported that metastatic spread of malignant tumors to bronchi occurs by direct extension from mediastinal lesion, invasion of bronchus by parenchymal mass, or direct metastasis to the wall of the bronchi [1]. In our cases, endobronchial metastasis occurred despite the absence of lymph node metastasis, and the metastatic pathway was suspected of being the bronchial arteries in the bronchial wall.

Surgery was not indicated in the present cases because extensive adhesions were expected on the postoperative side and recurrence near the tracheal bifurcation might require extremely invasive and difficult surgery, such as carinal reconstruction or pneumonectomy. Therefore, we performed a combination of EBRT and EBBT as definitive treatment, and none of our patients experienced local recurrence. The most serious adverse events of EBBT are fatal hemoptysis and severe bronchitis due to over-irradiation. These adverse events are caused by the radioactive source being placed at eccentric locations in the bronchial lumen, thereby leading to localized hot spots on the bronchial mucous membrane [2]. We therefore used a special source-centralizing applicator to avoid eccentric distribution of the radiation dose. None of our patients experienced such severe adverse events, and none needed extensive outpatient treatment. This applicator was also used to protect the bronchial mucosa from high-dose irradiation in the reports of Kawamura et al. [10], Hosni et al. [5], and Nomoto et al. [4].

There have been several reports regarding the combination of EBRT and EBBT therapy in either a curative or palliative setting. Nomoto et al. reported that the 3-year overall and progression-free survival rates were 79% and 77%, respectively, in 15 patients [4]. In addition, Hosni et al. reported that the 2-year overall survival and local control rates were 67% and 89%, respectively, in 23 patients [5]. While these reports described relatively few patients, these outcomes suggested that EBBT may be expected to achieve excellent tumor control.

In conclusion, EBBT is possibly a promising treatment with curative intent for endobronchial metastasis after surgery of NSCLC.

NSCLC: non-small-cell lung cancer

ADL: activities of daily living

EBBT: endobronchial brachytherapy

EBRT: external beam radiotherapy

CT: computed tomography

FDG-PET: fluorodeoxyglucose-positron emission tomography

SUV_max: maximum standardized uptake value

Ethics approval and consent to participate: This study was approved by the Clinical Research Ethics Review Committee of Mie University Hospital (Ethics approval number: H2020-032).

Consent for publication: Written, informed consent was obtained from the patient for publication of this manuscript and any accompanying images.

Availability of data and materials: not applicable.

Competing interest: The authors state that there are no conflicts of interest, grants or any assistance to be disclosed.

Funding: none

Authors’ contribution: AI and MT designed the report, analyzed the data, and wrote the manuscript, and other coauthors contributed to the acquisition and interpretation of the data for the work and revised the manuscript. The authors read and approved the final manuscript.

Acknowledgements: Not applicable.

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You are reading this latest preprint version

Endobronchial Brachytherapy as Definitive Treatment for Endobronchial Metastasis After Surgery of Non-Small-Cell Lung Cancer

Status:

Version 1

Abstract

Background

Case presentation:

Conclusions

Figures

Background

Case Presentation

Case 1

Case 2

Case 3

Discussion And Conclusions

List Of Abbreviations

Declarations

References

Status:

Version 1