Mihailo Miljanic

Background: Adrenal metastases are often treated with stereotactic ablative radiation (SAbR). We aimed to assess the incidence, timing, and factors associated with the development of primary adrenal insufficiency (PAI) following SAbR. Methods: A retrospective cohort study comprised 66 consecutive patients (73% men, median age 61 years) who underwent SAbR for adrenal metastasis. Results: The series encompassed metastases from renal cell carcinoma (41%), lung tumors (38%), colorectal adenocarcinoma (9%), melanoma (5%), and others (7%). Median follow-up was 17 months from SAbR. Nine (14%) patients developed PAI at a median of 4.3 months (range, 0.7–20.2). The incidence of PAI was 44% in patients with prior adrenalectomy receiving unilateral SAbR, 44% with bilateral SAbR, 2% with unaffected contralateral gland, and 0% with bilateral metastases treated with unilateral SAbR. PAI was associated with prior adrenalectomy (odds ratio [OR] 32) and bilateral SAbR (OR 8.2), but not age, sex, metastasis size, or biological effective dose. Post-SAbR 6-month and 1-year local control rates were 82% and 75%, respectively. Conclusions: Patients undergoing SAbR for adrenal metastasis are at high risk of developing PAI. PAI is associated with bilateral SAbR and contralateral adrenalectomy. PAI is unlikely with a remaining unaffected adrenal gland or in the setting of bilateral adrenal metastases with unilateral SAbR.

Purpose This case series and literature review aims to investigate the efficacy and safety of definitive ablative radiation therapy as a treatment modality for non-operable patients with early stage breast cancer. We present two cases demonstrating the potential of this approach to achieve durable responses. Methods We assessed the long-term response of two non-operable patients diagnosed with Stage II (cT2N0M) and Stage IA (T1bN0M0) invasive ductal carcinoma (IDC), who were deemed unfit for surgery due to significant co-morbid conditions. Definitive ablative radiation therapy was administered using stereotactic partial breast irradiation with ablative doses delivered in either a single fraction or two fractions. Serial imaging was conducted to assess treatment response and monitor adverse events. Results Both patients exhibited notable treatment responses following definitive ablative radiation therapy. The first patient, an 84-year-old woman, experienced a 69% reduction in tumor size over a follow-up period exceeding 2 years. The second patient, an 87-year-old woman, achieved complete resolution of disease on imaging, with no signs of progression even 26 month post-treatment. Both patients tolerated the treatment well, without significant treatment-related adverse events. Conclusions Our case series suggests that definitive ablative radiation therapy may serve as a safe and effective treatment option for non-operable patients with early stage breast cancer. The observed durable treatment responses and minimal toxicity support the potential of this approach. Furthermore, a longer interval between ablative radiation therapy and surgery may enhance treatment response, potentially leading to increased complete pathologic response rates.

In this commentary, we describe the potential of highly ablative doses utilizing Stereotactic Body Radiation Therapy (SBRT) in single or few fractions to enhance immune-responsiveness, how timing of this approach in combination with immune-checkpoint inhibitors may augment treatment-effect, and whether Personalized Ultrafractionated Stereotactic Adaptive Radiation Therapy (PULSAR) is an avenue for future advancement in the continued endeavor to foster a systemic effect of therapy beyond the radiation treatment field. The ablative potential of SBRT may support an increase in tumor-antigen presentation, enhancement of immune-stimulatory components, and an improvement in tumor-microenvironment immune cell infiltration. Furthermore, the latest advancement of ablative radiation delivery is PULSAR-based therapy, whereby ablative doses are delivered in pulses of treatment that may be several weeks apart, combined with adaptive treatment to tumor changes across time. The benefits of this novel approach include the ability to optimize direct tumor control by assessment of tumor size and location via dedicated imaging acquired prior to each delivered pulse, and further potentiation of immune recognition through combination with concurrent immune-checkpoint blockade.