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  Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 56  |  Issue : 3  |  Page : 236-240
 

Use of interventional bronchoscopic treatment in small cell lung cancer


1 Yedikule Chest Disease and Thoracic Surgery Training and Research Hospital, Department of Pulmonary Medicine, Istanbul, Turkey
2 Süreyyapaşa Chest Disease and Thoracic Surgery Training and Research Hospital, Department of Pulmonary Medicine, Istanbul, Turkey
3 Istanbul Bilim University, School of Medicine, Department of Pulmonary Medicine, Istanbul, Turkey

Date of Web Publication19-Jul-2019

Correspondence Address:
Sinem N Sökücü
Yedikule Chest Disease and Thoracic Surgery Training and Research Hospital, Department of Pulmonary Medicine, Istanbul
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_45_18

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  Abstract 


AIMS: Small cell lung cancer (SCLC) constitutes 15%-25% of all lung cancers. Their treatment approach is different from nonsmall cell lung cancer. Central airway obstruction develops at the time of diagnosis or eventually at some time as the disease progress. Quick relief of symptoms with chemotherapy will cause to postpone interventional bronchoscopy which divest patient from benefits of this procedure. There is a few data about the use of interventional bronchoscopy in SCLC.
SUBJECTS AND METHODS: Between January 2005 and December 2012, rigid bronchoscopy under general anaesthesia was done in a total of 944 cases. Among them, 52 consecutive SCLC cases were evaluated retrospectively.
STATISTICAL ANALYSIS: Survival was calculated from the date of application of therapeutic bronchoscopy using statistical software.
RESULTS: From the 52 cases (41 males) mean age of the patients were 56,87 ± 10,16 (range 34-78). Most common obstruction areas were distal trachea and carina invasion involving both main bronchus (n: 12; 23%). Most common method used was mechanical desobstruction after coagulation with diode diode laser or APC. A total of 16 stents was applied to 15 of the cases from 52 cases (28.8%). Most common used stent was silicon Y stent (n: 11). Most common complication during the procedure was bleeding that was mild in 11 cases and massive in 1. One patient died during the procedure (1.9%).
CONCLUSIONS: Multimodal interventional bronchoscopic methods seem to be a last option but may be useful in the management of advanced airway obstruction in the setting of SCLC. The choice of modality may be chosen depending upon individual patient characteristics as appropriate.


Keywords: Endobronchial treatment, small cell lung cancer, stent, survival


How to cite this article:
Ozdemir C, Sökücü SN, Berk A, Dalar L. Use of interventional bronchoscopic treatment in small cell lung cancer. Indian J Cancer 2019;56:236-40

How to cite this URL:
Ozdemir C, Sökücü SN, Berk A, Dalar L. Use of interventional bronchoscopic treatment in small cell lung cancer. Indian J Cancer [serial online] 2019 [cited 2019 Aug 20];56:236-40. Available from: http://www.indianjcancer.com/text.asp?2019/56/3/236/263034





  Introduction Top


Despite all current efforts in prevention such as smoking cessation, early detection such as low-dose computed tomography screening in high risk populations, early treatment, and development of new chemotherapeutic agents, the overall prognosis of lung cancer is still poor with 5-year survival rate about 16.3%.[1] Small-cell lung cancer (SCLC) is one of the most common histopathologic types of lung cancer.[1] They are different from nonsmall cell lung cancer (NSCLC) due to early dissemination, short doubling time, tendency to widespread metastases at the time of diagnosis, and low chance for surgical resection at the time of diagnosis. They are also different in a way that endobronchial extension is rare.[2],[3] The presence of distant metastases in case of small-cell lung cancer (SCLC) is greater with 60%–70%. The median survival is 7–12 months, and the proportion alive at 5 years is 2%.[4]

Central airway obstruction (CAO) manifests with symptoms of respiratory distress, bleeding or post-obstructive pneumonia and decreases survival.[5] It can be seen at the time of diagnosis or at some time as the disease progresses. For this reason, interventional bronchoscopic methods are needed in the handling of these tumours in adjunct with chemo-radiotherapy (CT-RT) modalities at any time during the disease. But in most of the cases, although this is a false prejudıce, interventional bronchoscopic methods were the last treatment option. In the late stage cases, both the application of the interventional procedures are hard to apply and the benefit of the therapy is lower.

Most of the studies about interventional bronchoscopy include NSCLC patients and there is little data about the use of interventional bronchoscopy in SCLC. In fact, there is no series in English literature just evaluating the effect of interventional bronchoscopic methods in these patients. Data about the place of interventional bronchoscopic methods in these patients were mostly from case reports or from little number of SCLC patients involved in large series.[5],[6],[7] In this paper, we share our experience in managing these tumours with interventional bronchoscopic methods and survival of these patients.


  Subjects and Methods Top


Total of 944 cases underwent rigid bronchoscopy under general anaesthesia between January 2005 and December 2012 in our interventional pulmonology unit with the same team were evaluated. From these data, 52 consecutive SCLC cases were evaluated from the records retrospectively. All of the cases were referred to interventional pulmonology (IP) unit for symptoms of airway obstruction and underwent interventional bronchoscopy due to their physical examination, radiological imaging methods or fiberoptic bronchoscopy evaluation findings. Institutional review board was taken for this retrospective data analysis (1119-09/11/2017). Indications for the applied methods, complications and effect of the procedure to the survival of these patients were evaluated.

All of the interventional procedures were performed by a rigid bronchoscopy (Efer-Dumon; Efer Co. Paris, France) under general anesthesia in the operating room with the full assistance of an anaesthesiologist. The rigid bronchoscope preferred in all procedures for allowing better gas exchange and passage of multiple instruments. Endoscopic evaluation of the airway, localisation and borders of the obstruction area and aspiration of the secretions and coagulum were done by fiberoptic bronchoscope through rigid bronchoscope. Diode laser (5-25 watt pulse time, Biolitec Ceralas D50, Germany) and argon plasma coagulation (high-frequency electrosurgical generator applied with 1.5-mm diameter probe, 40 watt continuous, ERBE Corp.) were used for the ablation of airway tumour tissue. Coring of the tumour with the tip of the rigid bronchoscope was typically employed to debulk the tumour after laser and APC application. Cryotherapy (ERBE, Tubingen, Germany) was used for residue tissue ablation, endobronchial biopsy and tumour cryodebridement. Airway stenting was considered in patients with extrinsic compression and combined extrinsic compression and intrinsic lesions in whom it was impossible to restore more than 50% of the lumen after airway dilatation or who required frequently (<1 month) repeated airway dilatation.

Hemorrhage during the procedure was classified as mild moderate or severe during the procedure depending on the way it stopped. Mild haemorrhage was the one that stopped by itself, moderate hemorrhage was the one that stopped by medical treatment (cold lavage with adrenaline) and severe haemorrhage was the one that is stopped by using APC.

Statistical analyses were performed using statistical software (SPSS 13.0 for Windows; SPSS; Chicago, IL and MedCalc version 11.6.). Data are presented as mean ± standard deviation unless otherwise indicated and presented as median (interguartile range). Survival was calculated from the date of therapeutic bronchoscopy. Probabilities of survival were calculated using the Kaplan-Meier estimator.


  Results Top


From a total of 944 patients that underwent interventional bronchoscopic evaluation between January 2005 and December 2012, 52 (5.51%) of them had a diagnosis of SCLC. From the 52 cases, 41 (78.8%) were male. Mean age of the patients was 56,87 ± 10,16 years (range 34-78 years). Comorbidities of the cases were as follows: 7 of them had chronic obstructive pulmonary disease; 6 of them had diabetes mellitus; 9 of them had hypertension; 2 of them had congestive heart failure; and 3 of them coronary artery disease. Two of the patients were tracheotomised.

As a total of 67 rigid bronchoscopy procedure was done with a median 1 IQR: 0,0 (1-5) per patient. In 10 (19.2%) patient repeat procedures were needed. While 56 fiberoptic bronchoscopy was done in 36 patients with a median 1 IQR: 1 (0-7) per all patient and a median 1 IQR: 1 (1-7) per patient that was undergone fiberoptic bronchoscopy for cleaning or follow-up purposes.

Presenting symptoms of the patients were dyspnoea which was seen in 47 (90.3%) patients, cough in 21 patients (40.3%), sputum production and hemoptysis each in 13 patients (25%) and weight loss in 10 patients (19.2%).

Most common obstruction areas were distal trachea and carina invasion involving both main bronchus (n: 12; 23%) [Table 1]. Most common method used was mechanical debulking after coagulation with diode laser or APC. All the methods used and number of sessions were given in [Table 2]. Stent was applied if less than 50% of airway patency was maintained after airway dilatation and mechanical debulking with the rigid scope [Figure 1]. A total of 16 stents were applied to 15 of the cases (28.8%). Most common used stent was silicon Y stent (n: 11).
Table 1: Location of the tumour in the bronchial tree

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Table 2: Applied methods per patient and number of sessions

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Figure 1: A 57-year-old male patient. Trachea was 80% obstructed 4 cm from the vocal cords. Right main bronchus was open but left main bronchus was deviated laterally and significantly obstructed (a). 18 × 14 × 14 mm Dumon Y stent was placed after mechanical core out (b)

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Most common complication observed during the procedures was hemorrhage (n: 12, 23%). It was mild in six patients, moderate in three and severe in three of them. Other than hemorrhage hypertensive attack were seen in two patients during the procedure that was handled with cold saline application with or without epinephrin. In one patient, procedure was ended earlier then it was planned due to hypoxia developed. We lost one patient during the procedure due to cardiac arrhythmia and respiratory insufficiency (1.9%). Agitation was observed in postoperative stage in one patient.

From the 15 stents, stent migration was seen in two of the patients during follow up. In the first one stent located in the trachea migrated distally and in the second case stent in the right bronchus migrated proximally. Granulatıon was seen in 3 patient but only 2 of them required intervention. Mucostasis was seen in 3 patient, and in two of them it was a tracheal stent in the other one it was a left bronchial stent. Follow up time was median 37,00 ± 11,87 days (95% CI: 13,78-60,22) calculated from the time passed from the first rigid bronchoscopy until death or up to 01.01.2017 [Figure 2]. Two of the patients were still alive at 01.01.2017. But 18 (42.9%) of the patients died in the first month.
Figure 2: Survival analysis of the patients

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  Discussion Top


Although there is an increase of new treatment options and the development of new drugs, increasing number of patients were referred to interventional bronchoscopy units for the bronchoscopic evaluation and treatment. To increase quality of life, quick symptom palliation and airway patency interventional bronchoscopic methods were used frequently.

Central airway obstruction develops in 30% of lung cancer patients at the time of diagnosis or in the follow-up.[8],[9] Also nearly 40% of lung cancer deaths are related to advanced locoregional disease.[9] Optimum treatment of central airway obstruction is surgical resection and reconstruction. This is not be possible all the time because they are usually poor surgical candidates. Major indications for endobronchial treatment in lung cancer include central airway obstruction causing symptoms such as dyspnoea, atelectasis, post-obstructive pneumonia, and hemoptysis. In our series, dyspnoea was the most common complaint (90.3%).

In general, bronchoscopic findings of endobronchial lesions of primary lung carcinoma are difficult to distinguish from those of metastatic lung carcinoma and benign tumours.[10],[11] For this reason, we included only patients with bronchoscopic biopsy results of pathological diagnosis of SCLC. Although endobroncial extension is thought to be rare in these tumours, there are case reports in literature.[3],[12],[13] As we know in studies evaluating effect of interventional bronchoscopic methods most of the patient population constituted from NSCLC patients with malign airway obstructions. SCLC constitutes only a small part. In a series of 2008 cases of malignant airway obstruction that were treated endoscopically only 103 of them were SCLC.[5] In our series 5.5% of our cases that have undergone endobronchial treatment in our center have a definite diagnosis of SCLC.

Bronchoscopic debulking and use of endobronchial laser applications and APC in malign CAO can provide relief of dyspnoea, increase in performance and quick increase in quality of life.[14],[15] After resolving of endoluminal component of the tumour tissue by laser or APC, stents could be applied for the external components to maintain airway patency.[15],[16] Quick symptom palliation can be achieved by the use of combined methods. As its effects take time, cryotherapy was used other then emergency situations. Other then tumour ablation, cryotherapy can also be used to take out tumour tissue and secretions that was spilled into the lumen from the tumour after coagulation by laser or APC or desobstruction by core out method. In our series, cryotherapy was only used in three patients while core out, laser and APC were used frequently. In 19.2% of the patients, repeating procedures were needed.

Tracheobronchial stents are implanted to re-establish patency of extraluminal compressed airways as well as to stabilise airway patency after endoscopic removal of endoluminal obstruction resulting from malignant processes.[17] Tracheobronchial stents offer minimally invasive palliative therapy for patients with unresectable malignant central airway obstruction. The benefit of airway stents is particularly seen in the short-term period where they provide symptomatic improvement and have low complication risk.

In case of main carinal obstruction, Y-shaped stents consisting of the tracheal body and two bronchial limbs are necessary to treat airway obstructions involving the lower trachea, main carina and proximal mainstem bronchi are better to use due to the anatomy of the carina.[17],[18] In current series, stents were applied for 15 (36%) of the cases and from these 11 of them were silicon Y stents.

Endobronchial treatment of CAO also bring about complications that develop due to these procedures. Although airway stents have lots of benefits, there are also some possible stent-related problems. The major complications are excessive granulation tissue and tumour in growth, which occur primarily after 30 days.[19] Other stent-related complications were stent-associated respiratory infection. In a review involving 501 patients, pneumonia was the most common type of infection.[20] Also mucostasis is another stent-related complication which is frequently seen. The choice of different airway stents can be made based on the nature and site of the lesion. In a case series including three patients by Tahiri et al. carinal complications caused by SCLC found to be difficult problems to deal with and suggest using silicone Y-stenting in the management of this problem.[21]

Complications such as airway burns, bronchial wall perforation, bleeding and hypoxia can be caused by both laser and APC.[20] In a multi-central study done by evaluation of 554 therapeutic procedures has reported a complication rate of 19.8% and a 30-day mortality of 7.8% after the therapeutic bronchoscopy in malign airway obstructions, reflecting the severity of illness and poor underlying health status.[22] It is important to realise that majority of these patients with limited cardiorespiratory reserves. Therefore, an experienced team should handle these patients to avoid major procedure-related complications. Our complications in our SCLC series are not different from the published complications due to NSCLC series and although we observed bleeding and hypoxia during the procedures we did not observed any airway burns or bronchial wall perforation. We lost one patient during the procedure due to cardiac arrhythmia and respiratory insufficiency. Our 30-day mortality is 42.9% which is related to disease progression and late stage of the patients at the presentation to our interventional pulmonology unit.

Survival can be estimated based on the diagnosis, stage of the disease at the diagnosis, site of the lesion and treatment modality used.[23] In our time, it is still debatable whether therapeutic bronchoscopy improves the overall survival of patients with malignant central airway obstruction due to lack of prospective randomised trials. Performing a prospective, blinded, randomised study on such patient population is neither feasible nor ethical. So the discussion is done over the extrapolation of data from case series, retrospective studies.[7],[24],[25] Therapeutic bronchoscopy procedures such as laser and insertion of airway stents are used to relieve respiratory distress, improve quality of life, and potentially prolong survival.[26],[27] Interventional bronchoscopic techniques in the treatment of malign CAO developed due to SCLC are frequently needed pre or post CT/RT. The timing of the interventional bronchoscopic procedure should be evaluated carefully in these patients. These are not the treatment options to be applied as an alternative to traditional treatment options or in cases which are unresponsive to these treatments. When the CAO develops, either at the time of diagnosis or in the follow of the treatment, endobronchial treatment option must be kept in mind and by symptom palliation time can be saved for the other treatments. Endobronchial treatments methods should not be evaluated as a last option for these patients before death but as a component of the tumour treatment. But it is still the last option in life-threatening conditions.

One of the limitations of our study is that because our centre is a referral centre for interventional bronchoscopy, treatment methods for all the patients before and after the bronchoscopic interventions were not documented for all the patients. But what we know is that these patients were extensive stage SCLC patients with suspicion of malignant airway obstruction. We lack information about the chemotherapy history of the patients. Also we do not have results about symptom score, dyspnoea scale, or pulmonary function tests before and after the bronchoscopic intervention. Hence our conclusion depends on clinical symptom palliation and atelectasis resolving after bronchoscopic interventions.

Interventional bronchoscopic treatment seems to be a last option treatment in terminal stage SCLC patients. Other than emergency situations (suffocation and haemoptysis) chemoradiotherapy thought to be enough as a treatment option for airway management. Multimodal interventional bronchoscopic methods may be useful in the management of advanced airway obstruction in the setting of SCLC. The choice of modality may be chosen depending upon individual patient characteristics as appropriate.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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