Brandi R. Page

Background: To examine the feasibility of adding ramipril for prevention of cognitive decline to chemoradiation treatment of glioblastoma (GBM). Methods: This prospective single-arm study (WF-1801) coordinated by the Wake Forest NCI Community Oncology Research Program Research Base (UG1CA189824) assessed feasibility, tolerability, and potential efficacy of ramipril to prevent treatment-induced cognitive decline in patients with GBM. Inclusion criteria and chemoradiotherapeutic paradigms were mirrored to the standard arm of NRG/RTOG 0825, such that cognitive outcomes could be compared. All patients were treated with ramipril during chemoradiation and for 4 weeks after completion of radiotherapy (RT). Major outcomes were retention and the Clinical Trial Battery Composite (CTB COMP) score of the cognitive tests. Results were compared to the corresponding outcomes from NRG/RTOG 0825. Results: A total of 75 participants were accrued between March 25, 2019 and November 14, 2023: median age was 63 years. The NRG/RTOG 0825 cohort was younger (median 57 years, P < .0001). Overall retention rate at 1-month post-RT (defined as compliant with 75% of doses and completion of cognitive testing) was 48% (1-sided 95% CI: 38%-100%); 61% of patients completed more than 75% of doses and 57% had a CTB COMP score through week 10. The median (range) change in the CTB COMP score at 1 month after RT completion was 0.01 (−82.6, 13.0) versus NRG/RTOG 0825 median of 0.10 (−48.2, 8.6); P = .49. Conclusions: The ramipril intervention did not meet the prespecified feasibility endpoint, neither did the cognitive scores differ significantly from the NRG/RTOG 0925 control group. We expect other agents will be the focus of future cytoprotective trials.

Background: Radiotherapy is essential for skull base tumor management but carries the risk of radiation-induced brain injury (RIBI). This spectrum ranges from transient radiation-induced contrast enhancement (RICE) to irreversible necrosis. Distinguishing these entities from tumor progression is critical, particularly with the increasing adoption of proton therapy. Methods: A comprehensive narrative review of the peer-reviewed literature was conducted up to October 1, 2025. The search strategy focused on adult patients treated for skull base malignancies, synthesizing data on dose–volume metrics, incidence rates, and modality-specific toxicity profiles. Results: RIBI represents a pathophysiological continuum. (a) Descriptive imaging patterns: In prospective proton therapy series, focal RICE occured in 15% of patients, typically at a median of 12 months, and often resolved spontaneously. (b) Modality comparison: Although proton therapy reduces integral brain dose versus photon therapy, elevated linear energy transfer (LET) at the distal Bragg peak may contribute to focal radiation-associated image changes (RAIC), particularly in the temporal lobes. (c) Risk stratification and diagnosis: Risk increased when >1% of the healthy brain received >57.6 Gy (Relative Biological Energy (RBE)) or when V67Gy exceeded 0.17 cc. Advanced MRI and amino acid positron emission tomography (PET) improved differentiation between radiation effects and tumor recurrence. Conclusions: Post-radiation imaging changes are common and often benign. Distinguishing RICE from progression requires multimodal imaging and adherence to specific dose constraints. Management should prioritize surveillance for asymptomatic lesions.

Background: Radiotherapy is an essential component for the treatment of skull skull‑base tumours. However, radiation‑induced brain injury (RIBI) appearing on magnetic resonance imaging (MRI) as pseudoprogression, radiation‑induced contrast enhancement (RICE), radiation necrosis, and other contrast‑enhancing brain lesions—remains an important late toxicity which is not very well characterized. Clarifying adult‑specific patterns, the role of positron emission tomography (PET), and differences between proton and photon therapy is clinically relevant. Methods: Narrative review of peer‑reviewed literature to 1 October 2025 focused on adult chordoma, chondrosarcoma, meningioma, adenoid cystic carcinoma, pituitary adenoma, craniopharyngioma, undifferentiated carcinoma of nasopharyngeal type (UCNT), and germinoma. Results: Radiation-induced brain injury (RIBI) may range from early transient brain oedema/enhancement to late necrosis. Lesions cluster in temporal and frontal lobes after skull‑base irradiation. Proton therapy generally reduces high‑dose exposure versus photons and is associated with fewer severe necrotic events, though asymptomatic RICE is common. Advanced MRI (diffusion, perfusion, spectroscopy, ASL, amide proton transfer) and positron emission tomography (PET) with Fluorodeoxyglucose (FDG) and amino‑acid tracers aid distinction between treatment effect and progression. Risk reflects dose–volume metrics, prior irradiation, and patient comorbidities. Conclusions: MRI/PET alterations after skull‑base radiotherapy vary by modality, dose, and tumor context. Integrating multimodal imaging with clinical factors should guide surveillance and management; prospective validation is needed.

The standard of care for locally advanced non-small-cell lung cancer (NSCLC) is either surgery combined with chemotherapy pre- or postoperatively or concurrent chemotherapy and radiotherapy. However, older and frail patients may not be candidates for surgery and chemotherapy due to the high mortality risk and are frequently referred to radiotherapy alone, which is better tolerated but carries a high risk of disease recurrence. Recently, immunotherapy with immune checkpoint inhibitors (ICIs) may induce a high response rate among cancer patients with positive programmed death ligand 1 (PD-L1) expression. Immunotherapy is also well tolerated among older patients. Laboratory and clinical studies have reported synergy between radiotherapy and ICI. The combination of ICI and radiotherapy may improve local control and survival for NSCLC patients who are not candidates for surgery and chemotherapy or decline these two modalities. The International Geriatric Radiotherapy Group proposes a protocol combining radiotherapy and immunotherapy based on the presence or absence of PD-L1 to optimize the survival of those patients.

Cutaneous skin carcinoma is a disease of older patients. The prevalence of cutaneous squamous-cell carcinoma (cSCC) increases with age. The head and neck region is a frequent place of occurrence due to exposure to ultraviolet light. Surgical resection with adjuvant radiotherapy is frequently advocated for locally advanced disease to decrease the risk of loco-regional recurrence. However, older cancer patients may not be candidates for surgery due to frailty and/or increased risk of complications. Radiotherapy is usually advocated for unresectable patients. Compared to basal-cell carcinoma, locally advanced cSCC tends to recur locally and/or can metastasize, especially in patients with high-risk features such as poorly differentiated histology and perineural invasion. Thus, a new algorithm needs to be developed for older patients with locally advanced head and neck cutaneous squamous-cell carcinoma to improve their survival and conserve their quality of life. Recently, immunotherapy with checkpoint inhibitors (CPIs) has attracted much attention due to the high prevalence of program death ligand 1 (PD-L1) in cSCC. A high response rate was observed following CPI administration with acceptable toxicity. Those with residual disease may be treated with hypofractionated radiotherapy to minimize the risk of recurrence, as radiotherapy may enhance the effect of immunotherapy. We propose a protocol combining CPIs and hypofractionated radiotherapy for older patients with locally advanced cutaneous head and neck cancer who are not candidates for surgery. Prospective studies should be performed to verify this hypothesis.

Xerostomia is a common consequence of radiotherapy in head and neck cancer. The objective was to compare the regional radiation dose distribution in patients that developed xerostomia within 6 months of radiotherapy and those recovered from xerostomia within 18 months post-radiotherapy. We developed a feature generation pipeline to extract dose volume histogram features from geometrically defined ipsilateral/contralateral parotid glands, submandibular glands, and oral cavity surrogates for each patient. Permutation tests with multiple comparisons were performed to assess the dose difference between injury vs. non-injury and recovery vs. non-recovery. Ridge logistic regression models were applied to predict injury and recovery using clinical features along with dose features (D10-D90) of the subvolumes extracted from oral cavity and salivary gland contours + 3 mm peripheral shell. Model performances were assessed by the area under the receiver operating characteristic curve (AUC) using nested cross-validation. We found that different regional dose/volume metrics patterns exist for injury vs. recovery. Compared to injury, recovery has increased importance to the subvolumes receiving lower dose. Within the subvolumes, injury tends to have increased importance towards D10 from D90. This suggests that different threshold for xerostomia injury and recovery. Injury is induced by the subvolumes receiving higher dose, and the ability to recover can be preserved by further reducing the dose to subvolumes receiving lower dose.

Although antidiscrimination laws and policies have improved the position of women over time, gender-based compensation disparities for women in science have persisted.^1-4 From the available reports, compensation for men exceeds that for women by approximately 7% to 8% among US physician researchers,^2,3 nearly 20% among Japanese surgeons,⁵ and 25% to 40% between scientists in public sectors in Europe^6,7 even after controlling for other factors such as years of experience and rank.

Introduction Radiation-induced cognitive decline (RICD) is a late effect of radiotherapy (RT) occurring in 30–50% of irradiated brain tumor survivors. In preclinical models, pioglitazone prevents RICD but there are little safety data on its use in non-diabetic patients. We conducted a dose-escalation trial to determine the safety of pioglitazone taken during and after brain irradiation. Methods We enrolled patients > 18 years old with primary or metastatic brain tumors slated to receive at least 10 treatments of RT (≤ 3 Gy per fraction). We evaluated the safety of pioglitazone at 22.5 mg and 45 mg with a dose-escalation phase and dose-expansion phase. Pioglitazone was taken daily during RT and for 6 months after. Results 18 patients with a mean age of 54 were enrolled between 2010 and 2014. 14 patients had metastatic brain tumors and were treated with whole brain RT. Four patients had primary brain tumors and received partial brain RT and concurrent chemotherapy. No DLTs were identified. In the dose-escalation phase, there were only three instances of grade ≥ 3 toxicity: one instance of neuropathy in a patient receiving 22.5 mg, one instance of fatigue in a patient receiving 22.5 mg and one instance of dizziness in a patient receiving 45 mg. The attribution in each of these cases was considered “possible.” In the dose-expansion phase, nine patients received 45 mg and there was only one grade 3 toxicity (fatigue) possibly attributable to pioglitazone. Conclusion Pioglitazone was well tolerated by brain tumor patients undergoing RT. 45 mg is a safe dose to use in future efficacy trials.