Results of combined photodynamic therapy (PDT) and high dose rate brachytherapy (HDR) in treatment of obstructive endobronchial non-small cell lung cancer (NSCLC)

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Summary

Introduction

We reviewed the outcome of combined photodynamic therapy (PDT) and high dose rate brachytherapy (HDR) for patients with symptomatic obstruction from endobronchial non-small cell lung cancer.

Methods

Nine patients who received combined PDT and HDR for endobronchial cancers were identified and their charts reviewed. The patients were eight males and one female aged 52–73 at diagnosis, initially presenting with various stages of disease: stage IA (N = 1), stage IIA (N = 1), stage III (N = 6), and stage IV (N = 1). Intervention was with HDR (500 cGy to 5 mm once weekly for 3 weeks) and PDT (2 mg/kg Photofrin®, followed by 200 J/cm2 illumination 48 h post-infusion). Treatment group 1 (TG-1, N = 7) received HDR first; Treatment group 2 (TG-2, N = 2) received PDT first. Patients were followed by regular bronchoscopies.

Results

Treatments were well tolerated, all patients completed therapy, and none were lost to follow-up. In TG-1, local tumor control was achieved in six of seven patients for: 3 months (until death), 15 months, 2+ years (until death), 2+ years (ongoing), and 5+ years (ongoing, N = 2). In TG-2, local control was achieved in only one patient, for 84 days. Morbidities included: soft-tissue contraction and/or other reversible benign local tissue reactions (N = 8) and photosensitivity reactions (N = 2).

Conclusions

Combined HDR/PDT treatment for endobronchial tumors is well tolerated and can achieve prolonged local control with acceptable morbidity when PDT follows HDR and when the spacing between treatments is 1 month or less. This treatment regimen should be studied in a larger patient population.

Introduction

Most patients with non-small cell lung cancer (NSCLC) are diagnosed in advanced stage [1], when standard of care treatment generally consisting of chemotherapy and external beam radiation therapy (EBRT) cannot readily control this aggressive disease [2]. Local recurrence after first-line treatment often presents as endobronchial tumor, which is highly symptomatic due to its occlusion of the airways, leading to significant morbidity and mortality if untreated. Often, this airway compromise is accompanied by potentially life-threatening hemoptysis [3]. Primary early-stage NSCLC can also present as an obstructive mass with occlusive symptoms and hemoptysis, and may be inoperable due to its location or other factors. Endobronchial tumor growth adds further burden to a patient population in which lung function has often already been compromised by primary tumor and pre-existing chronic lung disease.

Measures taken to improve pulmonary function and eliminate hemoptysis can improve quality of life. In primary endobronchial tumors, the goal is to cure, while in recurrent cases, further treatment is often considered palliative and may not significantly improve patient survival. Possible interventions for obstructive endobronchial lesions include: EBRT, where meaningful doses are difficult to deliver in recurrent cases because prior courses have reached dose limits; chemotherapy, which is unlikely to succeed in a tumor in which first- and second-line agents have already failed and which is unnecessary for small early-stage primary tumors; and specifically designed bronchoscopic interventions, which have been more successful in this clinical situation.

Available bronchoscopic procedures include both ablative and non-ablative technologies, any of which can be used to mitigate airway obstruction. Bronchoscopic options include stenting, cryotherapy, electrocautery, argon plasma coagulation, Nd:YAG laser therapy, high dose rate brachytherapy (HDR), and photodynamic therapy (PDT) [4]. As there have been no large-scale randomized trials comparing these different modalities; equipment availability, user expertise, and the emergent nature of the obstruction often dictate the choice of intervention. Of the available therapies, stenting, electrocautery, argon plasma coagulation, and laser therapy offer the most immediate results, while the tissue effects of cryotherapy, HDR and PDT have a delayed onset [5]. However, both HDR and PDT appear to offer more prolonged local control of disease than the other bronchoscopic techniques [6], [7]. In addition, the use of multiple bronchoscopic modalities has been shown to significantly increase survival compared to the use of only a single modality [8] and sequential PDT/HDR treatments have been used to effectively control the growth of limited endobronchial carcinoma [9]. We postulated that sequential use of HDR and PDT would maximize local tumor control and minimize the overall number of interventions required for treatment of endobronchial NSCLC; we now report the outcomes of this intentionally combined treatment in nine patients.

Section snippets

Patients

We identified nine patients in the Leo Jenkins Cancer Center's computerized record system (from 1/2001 to 8/2008) who had received both photodynamic therapy (PDT) and high dose rate brachytherapy (HDR) for treatment of endobronchial tumors. These patients’ clinic and hospital records were thoroughly reviewed to determine the presentation and course of their disease and treatments, the details of their PDT and HDR interventions, and any adverse events or morbidities attributable to the PDT/HDR

Results

A summary of the results of the HDR and PDT treatments are shown in Table 2. Patient narratives are presented in Table 3.

Discussion

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in the US [13] and worldwide [14], and remains at epidemic levels in large part to widespread tobacco abuse [15]. While most in situ and early-stage (T1N0) NSCLC can be resected or ablated with excellent long term outcome [16], some are deemed inoperable and the majority of NSCLC patients are diagnosed with locally advanced or metastatic disease [1]. For patients with recurrent disease, treatment with

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