Outcomes From Whole-Brain Reirradiation Using Pulsed Reduced Dose Rate Radiation Therapy

Abstract

Purpose Recurrent intracranial metastases after whole-brain irradiation pose a clinical challenge owing to the escalating morbidity associated with their treatment. Although stereotactic radiosurgery is increasingly being used, there are still situations in which whole-brain reirradiation (ReRT) continues to be appropriate. Here, we report our experience using whole-brain pulsed reduced dose rate radiation therapy (PRDR), a method that delivers radiation at a slower rate of 0.067 Gy/min to potentially increase sublethal damage repair and decrease toxicity. Methods and Materials Patients undergoing whole-brain ReRT with PRDR from January 1, 2001 to March 2019 were analyzed. The median PRDR ReRT dose was 26 Gy in 2 Gy fractions, resulting in a median total whole-brain dose of 59.5 Gy. Cox regression analysis was used for multivariate analysis. The Kaplan-Meier method was used for overall survival, progression free survival, and to evaluate the ReRT score. Binary logistic regression was employed to evaluate variables associated with rapid death. Results Seventy-five patients were treated with whole-brain PRDR radiation therapy. The median age was 54 (range, 26-72), the median Karnofsky performance status (KPS) was 80, and 86.7% had recursive partitioning analysis scores of 2. Thirty-two patients had over 10 metastases and 11 had leptomeningeal disease. The median overall survival was 4.1 months (range, 0.29-59.5 months) with a 1 year overall survival of 10.4%. Age, KPS, dexamethasone usage, and intracranial disease volume were significantly correlated with overall survival on multivariate analysis. A KPS ≤70 was associated with rapid death after radiation. The prognostic value of the ReRT score was validated. The most common acute toxicities were fatigue (23.1%) and headache (16.9%). Conclusions In this large cohort of patients with advanced intracranial metastases, PRDR achieves acceptable survival and may decrease toxicity associated with ReRT. PRDR is an easily implemented technique and is a viable treatment option for ReRT of brain metastases.

Pulsed-Reduced Dose Rate (PRDR) Radiotherapy for Recurrent Primary Central Nervous System Malignancies: Dosimetric and Clinical Results

“…This has also been used for re-irradiation to the whole brain for patients with recurrent brain metastases. For example, Burr et al reported the results of 75 patients treated with PRDR to the entire brain (26 Gy in 13 fractions) over an 18 years period, with the most common toxicities being fatigue (23%) and headaches (17%), but with a median survival of only 4.1 months limiting long-term toxicity evaluation [ 34 ]. Additionally, this technique has demonstrated promise in re-irradiation of other sites outside the CNS axis, such as recurrent breast cancer [ 35 ] and head and neck cancer [ 36 ].…”

“…The following supporting information can be downloaded at: , Figure S1: Forest plots demonstrating the (a) progression-free survival with PRDR and (b) overall survival with PRDR [ 34 , 35 ]; Table S1: Dose constraints for PRDR plan and initial plan.…”

Re-Whole Brain Radiotherapy May Be One of the Treatment Choices for Symptomatic Brain Metastases Patients

“…The characteristics of previous reports are shown in Table 1 [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. All reports were retrospective in nature, the median age of the patients was 48–60 years, the median time between administration of the first WBRT and re-WBRT was 5–29 months, and the majority of cases were of lung cancer (including non-small cell lung cancer [NSCLC] and small cell lung cancer [SCLC]), breast cancer, and melanoma.…”

“…Previous reports suggested various negative prognostic factors using multivariate analysis. The prognostic factors suggested in two or more reports were the primary sites of SCLC [ 33 , 37 ], presence of extracranial metastasis [ 30 , 37 , 39 ], low KPS (<60–80) [ 30 , 32 , 35 , 37 , 38 , 40 ], and a short time between the first WBRT and re-WBRT [ 32 , 37 ].…”

“…There were no patients with a score of 0 in this study, and most patients who received re-WBRT had negative prognostic factors in real clinical situations. Regarding this score, Burr et al reported that the score of 1–2 was significantly associated with improvement in overall survival compared to the score of 3–4 (MST was 4.6 months vs. 2.9 months, respectively) [ 40 ]. Although these reports were also retrospective in nature, the reirradiation score was a helpful criterion for clinicians.…”