Acute Palliation of Intrathoracic Symptoms: No Improvement with Dose-Escalated Hypofractionated External Beam Radiotherapy

Abstract

Primary or metastatic malignant disease is a known cause of intrathoracic symptoms in oncologic patients and, frequently, obstruction of the bronchial tree may lead to dyspnea and/or hemoptysis. Local external beam radiotherapy (EBRT) can be an option to palliate such symptoms, even in spite of its low efficiency rate. We hypothesized that dose escalation could be safely delivered and further improve symptoms relief rates in patients who did not respond to an initial course of hypofractionated EBRT. A prospective, single arm, uni-institutional study was conducted, and eligible patients were offered a course of local hypofractionated EBRT, with 2 weekly fractions of 8 Gy, and an additional fraction of 8 Gy, if there were no symptoms improvement, one week apart. Study primary endpoint was to assess the rate of acute palliation of intrathoracic symptoms (hemoptysis resolution and/or dyspnea improvement, measured by the Modified Medical Research Council [mMRC] Dyspnea Scale). Secondary endpoints included the assessment of any possible treatment side-effects and late symptom improvement. Patients were clinically evaluated before every EBRT session, and if there was no clinical improvement after the second and immediately before the third session, the patient was recommend to continue the proposed treatment, to a total dose of 24 Gy. After that, follow-up was performed on a regular basis, to evaluate any possible treatment sub-acute or late side-effects or symptom improvement. After ERB approval, on September 2017, 8 eligible patients (5 males and 3 females) were initially enrolled, until interim analyses, on August 2018, when investigators decided to close accrual due to poor response to the treatment protocol. Median age of the patients was 51,5 years (39 - 72), all of them with metastatic disease and 5 of them (62,5 %) with a non-pulmonary primary malignancy. All of the patients presented with dyspnea, and 2 (25 %) of them also with hemoptysis, and, according to mMRC Dyspnea Scale, 6 patients (75 %) had a grade 3 or higher dyspnea symptom. Overall, 5 of the patients demanded a third session, but one patient died from disease progression before the second and one before the third session. After the completion of the treatment protocol, 4 patients had any acute dyspnea improvement and both the patients who presented with hemoptysis had symptom resolution (one after the second session, and therefore was not submitted to the third one). However, none evolved with significant dyspnea palliation after the third session. Except for one patient, that was still alive 12 months after the EBRT, all the other patients died within 4 months after the completion of the treatment. Two out of 3 patients who completed the 3 sessions also developed symptomatic actinic esophagitis. Dose-escalated hypofractionated EBRT didn’t provide acute palliation of intrathoracic symptoms in this small cohort of patients, despite any dyspnea improvement in 5 out of 8 patients.