Curative Irradiation of Limited Endobronchial Carcinomas With High-Dose Rate Brachytherapy: Results of a Pilot Study

doi:10.1378/chest.111.5.1417

Chest

Volume 111, Issue 5, May 1997, Pages 1417-1423

https://doi.org/10.1378/chest.111.5.1417 Get rights and content

Objectives of the study

Pilot study to assess high-dose rate (HDR) brachytherapy as sole treatment for limited endobronchial non-small cell lung carcinomas.

Inclusion criteria

Proximal non-small cell lung cancer in a not previously irradiated area, with a maximal diameter of 1 cm, no visible tumor on CT scan, lack of other treatment options in patients with severe, chronic respiratory failure, surgery, or external radiotherapy for a previous lung cancer.

Treatment protocol

Treatment was based on an escalating dose protocol. Patients received three to five fractions of 7 Gy prescribed at 10 mm from the center of the applicator, once a week.

Results

Nineteen patients were included in this trial. The first two patients received three fractions of 7 Gy, the four next patients received four fractions, and the 13 remaining patients were treated with five fractions of 7 Gy. Two months after the end of the procedure, tumors in 15 of 18 evaluable patients (83%) were locally controlled with negative results of biopsies. At 1 year, local control was still obtained in 12 of 16 evaluable patients (75%). With a mean follow-up of 28 months, 1-year and 2-year actuarial survival rates were 78% and 58%, respectively, with a 28-month median survival. One patient with local control died from hemoptysis 12 months after treatment. Two patients suffered from severe necrosis of the bronchial wall; one of them died from hemoptysis.

Conclusion

HDR brachytherapy is an effective treatment for small endobronchial tumors. Late toxicity on the bronchial wall is still too high and was attributed mainly to contact between the catheter and the bronchial mucosa. Exclusive HDR brachytherapy should be restricted to carefully selected patients for whom there is no alternative curative treatment. New bronchial applicators and a lower dose per fraction may reduce the incidence and attenuate the severity of late complications.

Section snippets

Patient Selection Criteria

The patients included in the trial fulfilled the following criteria: (1) histologic evidence of non-small cell lung cancer in a nonirradiated tissue accessible to flexible fiberoptic bronchoscopy; (2) endoscopic measurement of the lesion ≤1 cm; (3) exclusive endobronchial development proved by the absence of visibility of the tumor on CT scan; (4) absence of hilar or mediastinal lymph node enlargement >1 cm on CT scan (NO); (5) contraindication of alternative therapy (ie, surgery or curative

Population

From July 1990 to May 1993, 19 patients were included in the trial. They were all men (mean age, 61.6±13.6 years). The details of the lesions treated are listed in Table 1. The contraindications for surgery or external radiotherapy included respiratory insufficiency with chronic obstructive lung disease (FEV₁ <0.8 L) in five patients, surgical treatment of a previous tumor for 10 patients (pneumonectomy in six) combined with mediastinal irradiation for five of these patients, treatment of a

DISCUSSION

The endoscopically evidenced tumoral regression after HDR endobronchial brachytherapy in patients treated palliatively for lung cancer prompted use of this technique as a curative treatment in early stages of non-small cell lung cancer. In view of the lack of long-term toxicity data on HDR endobronchial brachytherapy, we selected a population of patients whose tumoral lesions were limited to the bronchial wall and for whom respiratory insufficiency ruled out surgical treatment or external

ACKNOWLEDGMENTS

We would like to thank the physicians, chest physicians, and radiotherapists who participated in this trial: Drs. Brune, Canat, Caporal, Coquard, Delaroche, Fauchon, Fournel, Gadiolet, Guérin, Martel, Mornex, Saugier, and Vergnon.

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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.
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Squamous cell carcinoma of the lung arises from preinvasive progenitors in the central airways. The archetypal model appears to be a stepwise morphological progression until there is invasion of the basement membrane. However, not every lesion appears to follow this course and many individuals can have stable disease, or indeed regress to normal epithelium. From our increased understanding of the molecular pathology it is becoming apparent that the respiratory epithelium accumulates progressive genetic and epigenetic insults in response to carcinogens. Still, little is known about how to predict those ‘at risk’ of progression, and it is likely that in the future molecular signatures will underpin prediction models of developing invasive lung cancer. Currently, autofluorescence bronchoscopy gives us the ability to follow the natural history of these lesions, with the prospect that detecting and treating lesions early may improve survival. However, treatment remains controversial, and radical therapies are offered to individuals with carcinoma in situ who may never develop invasive cancer. This has paved the way for the use of minimally invasive bronchoscopic treatments, which, while apparently effective, have not been tested in randomised controlled trials. In this paper we describe the known biology and natural history of preinvasive lesions and review the current treatment strategies.
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En dehors de son rôle essentiel dans le diagnostic, l’endoscopie bronchique est devenue incontournable dans la prise en charge thérapeutique de ce cancer. En particulier, l’endoscopie bronchique joue un rôle important dans la thérapeutique du cancer avec obstruction bronchique qui ne relève pas de la chirurgie. Les techniques endoscopiques, en assurant une désobstruction bronchique rapide, permettent de diminuer les symptômes et les complications sévères, respiratoires ou infectieuses, liées à cette obstruction bronchique. L’amélioration de l’état respiratoire des patients qui en découle permettra une prise en charge thérapeutique curative (chimiothérapie et radiothérapie) plus complète et plus efficace. La prise en charge thérapeutique moderne du cancer bronchique doit intégrer les techniques endoscopiques d’action locale aux thérapeutiques générales à visée curative dans une approche thérapeutique multimodale. Par ailleurs, l’endoscopie moderne offre aussi des possibilités de traitement des lésions cancéreuses bronchiques radio-occultes. La photothérapie, et, dans une moindre mesure, la cryothérapie, l’électrocautérisation et la curie-thérapie, apparaissent comme des techniques endoscopiques alternatives pour le traitement des lésions cancéreuses précoces si le traitement chirurgical ne peut être envisagé.
Except its essential role in the diagnosis, bronchial endoscopy also takes an important part in the treatment of lung cancer. First, bronchial endoscopy has a key-role in the treatment of cancer with bronchial obstruction. Endoscopic techniques can lead to quick bronchial desobstruction and therefore they allow symptoms improvement and decrease of respiratory and infectious complications. This improvement of the patient health situation also will permit a more complete and efficient approach using curative therapies (radiotherapy and chemotherapy). Endoscopic local treatment must be integrated in a multimodal therapeutic approach in association with curative treatments. Modern endoscopy also contributes into the treatment of early roentgen occult lung cancer. Phototherapy, and as an alternative, techniques of electrocautery, cryotherapy and brachytherapy, can be used to treat these early lung cancer in patients who are not surgical candidates.
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The aim of this work was to evaluate outcomes after definitive high-dose-rate endobronchial brachytherapy (HDR-BT) for lung cancer.
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Most patients with central type lung cancer (CTLC) are not candidates for surgery; systemic chemotherapy and external beam radiotherapy are the main treatments but have not greatly affected patient outcome. Combined percutaneous and endobronchial cryotherapy has been used successfully to treat CTLC; this study aimed to determine its feasibility and safety. Forty-seven patients with unresectable CTLC (22 endotracheal, 26 tracheal wall and 21 extratracheal tumors) underwent 69 sessions of combined percutaneous cryosurgery, endobronchial cryosurgery and airway stenting. The long diameter of all tumors was <5 cm. Biopsy showed non-small cell lung cancer (NSCLC) in 40 patients (medium or well differentiated in 20 cases, poorly differentiated in 20) and small cell lung cancer (SCLC) in seven. Within 3 days after treatment, ventilatory capacity and performance status had obviously increased and cough, signs of dyspnea, hemoptysis and atelectasis improved significantly, but symptoms of pneumothorax and pleural effusion emerged. After 2 weeks, all complications had disappeared completely, as had cough. Progression-free survival (PFS) for endotracheal tumors (8 ± 4 months) was shorter than that for tracheal wall (13 ± 6 months, P < 0.05) and extratracheal (14 ± 8 months, P < 0.01) tumors. The PFS of NSCLC (11 ± 5 months) was significantly longer than that of SCLC (4 ± 2 months, P < 0.0001). The PFS of medium or well differentiated CTLC (15 ± 8 months) was significantly longer than that of poorly differentiated CTLC (7 ± 3 months, P < 0.0001). In conclusion, combined cryotherapy is a safe and effective treatment for CTLC, with PFS largely influenced by tumor location and pathologic type.
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Citation Excerpt :
Additionally, 9% and 4% of patients had grade 2 or 3 radiation bronchitis, respectively.99 In two smaller studies, CR rates with brachytherapy were reported in 83% to 85% of patients.82,100 Bronchoscopic electrocautery causes tissue destruction by the use of a high-frequency, heat-generating electrical current.
Bronchial intraepithelial lesions may be precursors of central airway lung carcinomas. Identification and early treatment of these preinvasive lesions might prevent progression to invasive carcinoma.
We systematically reviewed the literature to develop evidence-based recommendations regarding the diagnosis and treatment of intraepithelial lesions.
The risk and timeline for progression of bronchial intraepithelial lesions to carcinoma in situ (CIS) or invasive carcinoma are not well understood. Multiple studies show that autofluorescence bronchoscopy (AFB) is more sensitive that white light bronchoscopy (WLB) to identify these lesions. In patients with severe dysplasia or CIS in sputum cytology who have chest imaging studies showing no localizing abnormality, we suggest use of WLB; AFB may be used as an adjunct when available. Patients with known severe dysplasia or CIS of central airways should be followed with WLB or AFB, when available. WLB or AFB is also suggested for patients with early lung cancer who will undergo resection for delineation of tumor margins and assessment of synchronous lesions. However, AFB is not recommended prior to endobronchial therapy for CIS or early central lung cancer. Several endobronchial techniques are recommended for the treatment of patients with superficial limited mucosal lung cancer who are not candidates for resection.
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Chest

Preliminary ReportCurative Irradiation of Limited Endobronchial Carcinomas With High-Dose Rate Brachytherapy: Results of a Pilot Study

Objectives of the study

Inclusion criteria

Treatment protocol

Results

Conclusion

Section snippets

Patient Selection Criteria

Population

DISCUSSION

ACKNOWLEDGMENTS

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Chest

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Chest

Chest

Chest

Ann Oncol

Int J Radiat Oncol Biol Phys

Chest

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Preliminary Report
Curative Irradiation of Limited Endobronchial Carcinomas With High-Dose Rate Brachytherapy: Results of a Pilot Study