Upfront Versus Delayed Systemic Therapy in Patients With Oligometastatic Cancer Treated With SABR in the Phase 2 SABR-5 Trial.

PURPOSE: The optimal sequencing of local and systemic therapy for oligometastatic cancer has not been established. This study retrospectively compared progression-free survival (PFS), overall survival (OS), and SABR-related toxicity between upfront versus delay of systemic treatment until progression in patients in the SABR-5 trial. METHODS AND MATERIALS: The single-arm phase 2 SABR-5 trial accrued patients with up to 5 oligometastases across SABR-5 between November 2016 and July 2020. Patients received SABR to all lesions. Two cohorts were retrospectively identified: those receiving upfront systemic treatment along with SABR and those for whom systemic treatment was delayed until disease progression. Patients treated for oligoprogression were excluded. Propensity score analysis with overlap weighting balanced baseline characteristics of cohorts. Bootstrap sampling and Cox regression models estimated the association of delayed systemic treatment with PFS, OS, and grade ≥2 toxicity. RESULTS: A total of 319 patients with oligometastases underwent treatment on SABR-5, including 121 (38%) and 198 (62%) who received upfront and delayed systemic treatment, respectively. In the weighted sample, prostate cancer was the most common primary tumor histology (48%) followed by colorectal (18%), breast (13%), and lung (4%). Most patients (93%) were treated for 1 to 2 metastases. The median follow-up time was 34 months (IQR, 24-45). Delayed systemic treatment was associated with shorter PFS (hazard ratio [HR], 1.56; 95% CI, 1.15-2.13; P = .005) but similar OS (HR, 0.90; 95% CI, 0.51-1.59; P = .65) compared with upfront systemic treatment. Risk of grade 2 or higher SABR-related toxicity was reduced with delayed systemic treatment (odds ratio, 0.35; 95% CI, 0.15-0.70; P < .001). CONCLUSIONS: Delayed systemic treatment is associated with shorter PFS without reduction in OS and with reduced SABR-related toxicity and may be a favorable option for select patients seeking to avoid initial systemic treatment. Efforts should continue to accrue patients to histology-specific trials examining a delayed systemic treatment approach.

Recurrent Extraneural Metastatic Medulloblastoma in an Adult Presenting With a Superscan and Treated With Radium-223.

A 32-year-old man with medulloblastoma was initially treated with subtotal resection and craniospinal irradiation. He developed recurrent metastatic disease three years later with extensive bone-only metastases. Biopsy of the bone lesions confirmed metastatic medulloblastoma and restaging investigations demonstrated a superscan with no evidence of recurrence in the craniospinal axis. Extraneural metastatic medulloblastoma is rare, and the presentation with diffuse bone-only metastases with a superscan on imaging is unique. The patient had diffusely painful bone metastases requiring multiple hospitalizations for poor pain control. He declined chemotherapy and was treated with radium-223, an alpha particle emitting radionuclide therapy typically used in metastatic castrate-resistant prostate cancer. The patient received three out of a planned six cycles of radium-223 before it was discontinued due to myelosuppression requiring multiple blood transfusions, and restaging demonstrated local recurrence in the posterior fossa. This is the first report to our knowledge describing the use of radium-223 in a patient with extraneural bone-only metastatic medulloblastoma. Further research into the effect of radium-223 in patients with diffuse bone-only metastases from non-prostate cancer primary tumors is warranted.

Two Cases of Primary Spinal Glioblastoma in Adults Treated With Multimodality Therapy.

Primary spinal glioblastoma (GBM) is a rare disease entity with no established standard treatment. We present two cases of primary spinal GBM initially presenting with motor-sensory deficits and back pain. Management varied in that the first patient received subtotal resection followed by radiation therapy, while the second patient underwent gross total resection followed by radiation therapy and temozolomide. The first patient died from hypoxemia secondary to disease progression affecting diaphragmatic motion three months after diagnosis. The second patient progressed intracranially and died 7.4 months after diagnosis. There is no standard of care for primary spinal GBM, so treatment should follow a multidisciplinary discussion focused on patient-specific goals. These cases highlight the poor prognosis of primary spinal GBM despite different treatment approaches, necessitating accurate reporting of all similar cases to help improve knowledge and management of this rare malignancy.

Hypofractionated radiotherapy in postmastectomy locally advanced breast cancer: an interim report on acute toxicities and dosimetry.

Background: There is a growing interest in the use of hypofractionation in the setting of post-mastectomy radiation therapy (PMRT). Here, we present an interim report on the acute toxicities and the dosimetry of a 15-day hypofractionated regimen. Materials and methods: Patients aged 18-75 years who underwent mastectomy and had pathological stage IIB-IIIC or any clinical stage who had received neoadjuvant chemotherapy were treated with PMRT at a dose of 43.5 Gy in 15 fractions. Acute toxicities were scored using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results: Between September 2020 and September 2021, 92 patients were enrolled in the study. Majority experienced grade 1 dermatitis during the course of treatment. Skin toxicities peaked two weeks after PMRT in which 57 patients (62%) had grade 2 dermatitis and 6 patients (7%) had grade 3 dermatitis. Most resolved one month after treatment, with all resolving at three months. Grade 2 fatigue occurred in 4 patients (4%). There were no grade 3 fatigue or pneumonitis of any grade. The average V95% for the chest wall, axilla, and supraclavicular fossa were 91.5%, 99.3%, and 97.5%, respectively. Average ipsilateral lung V17 was 43.6%, while the mean heart dose averaged at 3.46 Gy. Conclusion: This interim report showed that hypofractionated PMRT is associated with a low incidence of clinically significant acute toxicities. With the use of the 3-dimensional conformal radiotherapy technique and volume-based planning, adequate target volume coverage and acceptable heart doses were achieved, although with a slightly higher ipsilateral lung dose.

Intraoperative radiotherapy for glioblastoma: A systematic review of techniques and outcomes.

BACKGROUND: Despite multimodality treatment, the prognosis of glioblastoma (GBM) has remained poor. Intraoperative radiation therapy (IORT) offers additional local control by directly applying a radiation source to the resection margin, where most recurrences occur. METHODS: We performed a systematic review on the oncologic outcomes and toxicities of IORT for GBM in the era of modern external beam radiation therapy (EBRT) and chemotherapy with temozolamide. RESULTS: Four studies representing 123 patients were included. Majority (81%) were newly diagnosed, and gross total resection was reported in 13-80% of cases. IORT modalities included electrons from a linear accelerator (LINAC) and photons from a 50-kV x-ray device. Median doses were from 12.5 to 20 Gy for electron-based studies and 10-25 Gy for photon-based studies. Adjuvant treatment consisted of 46-60 Gy post-operative EBRT in electron-based studies and the Stupp protocol in photon-based studies. Complications included radiation necrosis (2.8-33%), infection, hematoma, perilesional edema, and wound dehiscence. Median time to local recurrence was 9.9-16 months and the reported overall progression-free survival was 11.2-12.2 months. Median overall survival was 13-14.2 months for the electron-based studies and 13.8-18 months for the photon-based studies. CONCLUSION: IORT resulted in improved local control and comparable overall survival rates with the Stupp protocol. Although photon-based IORT had better results than electron IORT, this may be due to improvements in other forms of adjuvant treatment rather than the IORT modality itself. The overall effect of IORT on GBM treatment is still inconclusive due to the small number of patients and heterogeneous reporting of data.