Brett G. Klamer

Background/Objectives: Locoregionally recurrent or persistent head and neck cancer (rpHNC) after prior radiotherapy carries a poor prognosis, and optimal salvage strategies remain uncertain. We evaluated survival, patterns of failure, and 90-day postoperative complications after salvage surgery combined with intraoperative electron radiation therapy (IOERT). Methods: We retrospectively identified 127 previously irradiated patients treated with salvage surgery and IOERT between 1999 and 2023. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan–Meier method, and locoregional failure (LRF) and distant failure were estimated using Aalen–Johansen cumulative incidence with death as a competing event. Associations were evaluated one predictor at a time in age- and sex-adjusted Cox (OS, DFS) and Fine-Gray (LRF) models without multiplicity adjustment, and they are exploratory. Results: With a median follow-up of 70 months, median overall survival (OS) was 20.5 months (95% CI, 14.6–40.2), with 1-, 2-, and 3-year OS rates of 63%, 48%, and 43%, respectively. Median disease-free survival (DFS) was 8.8 months. Positive surgical margins and extranodal extension (ENE) were associated with worse OS in separate age- and sex-adjusted models. The 1-, 2-, and 3-year cumulative incidences of LRF were 34.3%, 44.7%, and 49.8%, respectively. The corresponding cumulative incidences of distant failure were 21.6%, 24.0%, and 26.7%, respectively. Thirty-seven patients had a documented distant failure, of whom 27 (73%) experienced distant failure within one year. Available records documented three deaths within 90 days (3/127, 2.4%). Conclusions: Among rpHNC patients treated with this IOERT-containing multimodality salvage strategy, median OS was 20.5 months. Because the study lacked a salvage-surgery-only comparator, postoperative treatments were selectively administered, and complication reporting was incomplete, neither the efficacy nor the comparative safety of IOERT can be determined from these data.

Objective: The objective of this study was to examine referral practices after positive autism spectrum disorder screening with the modified checklist for autism in toddlers, revised with follow-up (M-CHAT-R/F) for potential variability based on demographic factors focusing on language and patient-reported need for interpretation. Methods: This was a retrospective cohort study. The study population consisted of 776 patients (mean age 25 months) with a positive M-CHAT-R/F (367 high risk, 409 moderate risk). Data collected included self-reported race, ethnicity, preferred language, interpreter need, screening results, and referrals placed at the time of screening. Patients with a prior autism spectrum disorder diagnosis were excluded. Data were analyzed using Pearson's χ ² test of independence and logistic regression to determine if demographic factors, focusing on preferred language and need for an interpreter, were associated with placement of recommended referrals. Results: Among children with a positive M-CHAT-R/F screen, 69% were referred to developmental behavioral pediatrics, 76% to behavioral health, 83% for early intervention, 93% for speech therapy, and 91% for audiology. In unadjusted stratified analysis, no significant differences were found in rates of referral to recommended services in relation to race, language spoken, or interpreter need. After a logistic regression analysis, no factors were predictive of higher or lower rates of referral to any service studied. Conclusion: We found no disparities in referrals after a positive M-CHAT-R/F in relation to preferred language or interpreter need. Further research could examine what factors can help prevent disparities in referral placement to recommended services.

Injuries of the metacarpophalangeal joint are a major cause of morbidity and catastrophic fracture in racing horses, yet early osseous pathology is often difficult to detect using conventional imaging. This pilot study aimed to correlate sodium fluoride Positron Emission Tomography (¹⁸F-NaF PET) radiopharmaceutical uptake with gross and histopathologic changes in the distal third metacarpal bone (MC3) and proximal first phalanx (P1). Five horses (three racing Thoroughbreds with fetlock injury and two non-racing controls) underwent ante-mortem ¹⁸F-NaF PET and cone-beam CT imaging (CBCT), followed by post-mortem gross and histologic examination of predefined anatomic sites. Quantitative PET measures, including maximum standardized uptake value (SUV_max), SUV_ratio, and PET grade, were compared with gross pathology and histopathologic scores for cartilage and subchondral bone. While there were significant regional correlations between PET metrics and gross or histologic scores at select sites, our results need to be considered in light of the small number of horses evaluated. Correlations between PET metrics and gross pathology score were identified on the distal metacarpus on the lateral dorsal condyle and on proximal P1 for lateral dorsal and mid-P1. Correlation of PET metrics and hyaline cartilage histopathology scores were found for dorsal medial and lateral P1, parasagittal dorsolateral P1 and the medial parasagittal groove of MC3. Correlation of PET metrics and histologic subchondral bone scores were significant for medial palmar condyle, medial parasagittal groove, and parasagittal palmar lateral of MC3. For P1, PET metrics and histologic subchondral bone scores were significantly correlated for parasagittal mid-lateral and medial dorsal regions. Overall, these findings demonstrate that ¹⁸F-NaF PET identifies localized bone remodeling that corresponds to histologic and gross pathology at specific fetlock regions, supporting its utility for detecting osseous injury, although relationships varied by anatomic location. Further work with larger numbers of horses is needed.

Cisplatin, one of the most ototoxic anti-neoplastic agents, causes permanent hearing loss in up to 90% of patients. We assessed ototoxicity rates and prospectively collected audiologic outcomes of patients receiving low-dose or high-dose cisplatin with concurrent cochlear-sparing intensity-modulated radiation therapy (IMRT). Patients with head and neck squamous cell carcinoma (HNSCC) receiving definitive or adjuvant cisplatin-based chemoradiotherapy (CRT) were analyzed. Cisplatin was administered either in low doses weekly (40 mg/m²) for up to seven doses or in high doses triweekly (100 mg/m²) for up to three doses. Cochlear-sparing IMRT was delivered in all cases. Audiologic data were prospectively collected before, during, and after treatment completion. The primary endpoint was a hearing change grade of ≥3 after CRT completion. Of the 96 HNSCC patients evaluated, 69 received weekly cisplatin and 58 received definitive CRT. Of patients receiving weekly cisplatin, 13% developed ≥G3 ototoxicity vs. 56% of patients who received triweekly cisplatin (p < 0.001). In multivariable modeling, the cisplatin dose schedule remained significant (OR: 8.4, 95%CI: 2.8–27.8, p < 0.001) for risk of severe irreversible ototoxicity. Triweekly cisplatin CRT significantly increased the ≥G3 severe irreversible ototoxicity risk compared to low-dose weekly cisplatin, irrespective of the cumulative cisplatin dose, even with the use of cochlear-sparing IMRT. No significant difference in oncologic outcomes was observed between the two schedules.

Background: Pediatric patients with metastatic and/or recurrent solid tumors have poor survival outcomes despite standard-of-care systemic therapy. Stereotactic ablative radiation therapy (SABR) may improve tumor control. We report the outcomes with the use of SABR in our pediatric solid tumor population. Methods: This was a single-institutional study in patients < 30 years treated with SABR. The primary endpoint was local control (LC), while the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. The survival analysis was performed using Kaplan–Meier estimates in R v4.2.3. Results: In total, 48 patients receiving 135 SABR courses were included. The median age was 15.6 years (interquartile range, IQR 14–23 y) and the median follow-up was 18.1 months (IQR: 7.7–29.1). The median SABR dose was 30 Gy (IQR 25–35 Gy). The most common primary histologies were Ewing sarcoma (25%), rhabdomyosarcoma (17%), osteosarcoma (13%), and central nervous system (CNS) gliomas (13%). Furthermore, 57% of patients had oligometastatic disease (≤5 lesions) at the time of SABR. The one-year LC, PFS, and OS rates were 94%, 22%, and 70%, respectively. No grade 4 or higher toxicities were observed, while the rates of any grade 1, 2, and 3 toxicities were 11.8%, 3.7%, and 4.4%, respectively. Patients with oligometastatic disease, lung, or brain metastases and those who underwent surgery for a metastatic site had a significantly longer PFS. LC at 1-year was significantly higher for patients with a sarcoma histology (95.7% vs. 86.5%, p = 0.01) and for those who received a biological equivalent dose (BED10) > 48 Gy (100% vs. 91.2%, p = 0.001). Conclusions: SABR is well tolerated in pediatric patients with 1-year local failure and OS rates of <10% and 70%, respectively. Future studies evaluating SABR in combination with systemic therapy are needed to address progression outside of the irradiated field.

Background: Breast cancer is the second most common cause of brain metastases (BM). Despite increasing incidence of BM in older women, there are limited data on the optimal management of BM in this age group. In this study, we assessed the survival outcomes and treatment patterns of older breast cancer patients ≥65 years old with BM compared to younger patients at our institution. Methods: An IRB-approved single-institutional retrospective review of biopsy-proven breast cancer patients with BM treated with 1- to 5-fraction stereotactic radiation therapy (SRS) from 2015 to 2020 was performed. Primary endpoint was intracranial progression-free survival (PFS) defined as the time interval between the end of SRS to the date of the first CNS progression. Secondary endpoints were overall survival (OS) from the end of SRS and radiation treatment patterns. Kaplan–Meier estimates and Cox proportional hazard regression method were used for survival analyses. Results: A total of 112 metastatic breast cancer patients with BMs were included of which 24 were ≥65 years old and 88 were p = 0.036), while younger patients were more frequently triple negative (32% vs. 12%, p = 0.074) and HER2 positive (42% vs. 29%, p = 0.3). Treatment-related adverse events were similar in both groups. Overall, 14.3% patients had any grade radiation necrosis (RN) (older vs. young: 8.3% vs. 16%, p = 0.5) while 5.4% had grade 3 or higher RN (0% vs. 6.8%, p = 0.7). Median OS after RT was poorer in older patients compared to younger patients (9.5 months vs. 14.5 months, p = 0.037), while intracranial PFS from RT was similar between the two groups (9.7 months vs. 7.1 months, p = 0.580). On univariate analysis, significant predictors of OS were age ≥65 years old (hazard risk, HR = 1.70, p = 0.048), KPS ≤ 80 (HR = 2.24, p < 0.001), HER2 positive disease (HR = 0.46, p < 0.001), isolated CNS metastatic disease (HR = 0.29, p < 0.001), number of brain metastases treated with RT (HR = 1.06, p = 0.028), and fractionated SRS (HR = 0.53, p = 0.013). On multivariable analysis, KPS ≤ 80, HER2 negativity and higher number of brain metastases predicted for poorer survival, while age was not a significant factor for OS after adjusting for other variables. Patients who received systemic therapy after SRS had a significantly improved OS on univariate and multivariable analysis (HR = 0.32, p < 0.001). Number of brain metastases treated was the only factor predictive of worse PFS (HR = 1.06, p = 0.041), which implies a 6% additive risk of progression for every additional metastasis treated. Conclusions: Although older women had poorer OS than younger women, OS was similar after adjusting for KPS, extracranial progression, and systemic therapy; and there was no difference in rates of intracranial PFS, neurological deaths, and LMD in the different age groups. This study suggests that age alone may not play an independent role in treatment-selection and that outcomes for breast cancer patients with BMs and personalized decision-making including other clinical factors should be considered. Future studies are warranted to assess neurocognitive outcomes and other radiation treatment toxicities in older patients.

Bicycling is a common childhood activity that is associated with significant injury risk. This study’s aim was to assess pediatric bicycle injury epidemiology and impacts of the COVID-19 pandemic. We conducted a cross-sectional evaluation of patients age < 18 years presenting with bicycle injury to a pediatric trauma center. A pre-pandemic period (1 March 2015–29 February 2020) was compared to the pandemic period (1 March 2020–28 February 2021). A total of 611 injury events for children < 18 years were included (471 pre-pandemic events and 140 pandemic events). The relative frequency of pandemic injuries was greater than pre-pandemic injuries (p < 0.001), resulting in a 48% increase in pandemic period injuries versus the pre-pandemic average (141 pandemic vs. 94.4/year pre-pandemic). Individuals of female sex represented a larger proportion of injuries in the pandemic period compared to the pre-pandemic period (37% pandemic vs. 28% pre-pandemic, p = 0.035). Injuries were more common on weekends versus weekdays (p = 0.01). Time series analysis showed a summer seasonality trend. Localizing injury events to ZIP codes showed regional injury density patterns. During COVID-19, there was an increase in bicycle injury frequency and proportional shift toward more injuries involving individuals of female sex. Otherwise, injury patterns were largely unchanged. These results demonstrate the necessity of safety interventions tailored to community needs.

Background: Immune checkpoint inhibitors (ICI) treatment in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) offers new therapeutic venues. We have previously developed a predictive survival model in this patient population based on clinical parameters, and the purpose of this study was to expand the study cohort and internally validate the model.Methods: A single institutional retrospective analysis of R/M HNSCC patients treated with ICI. Clinical parameters collected included p-16 status, hemoglobin (Hb), albumin (Alb), lactate dehydrogenase (LDH), neutrophil, lymphocyte and platelet counts. Cox proportional hazard regression was used to assess the impact of patient characteristics and clinical variables on survival. A nomogram was created using thermspackage to generate individualized survival prediction.Results: 201 patients were included, 47 females (23%), 154 males (77%). Median age was 61 years (IQR: 55-68). P-16 negative (66%). Median OS was 12 months (95% CI: 9.4, 14.9). Updated OS model included age, sex, absolute neutrophil count, absolute lymphocyte count, albumin, hemoglobin, LDH, and p-16 status. We stratified patients into three risk groups based on this model at the 0.33 and 0.66 quantiles. Median OS in the optimal risk group reached 23.7 months (CI: 18.5, NR), 13.8 months (CI: 11.1, 20.3) in the average risk group, and 2.3 months (CI: 1.7, 4.4) in the high-risk group. Following internal validation, the discriminatory power of the model reached a c-index of 0.72 and calibration slope of 0.79.Conclusions: Our updated nomogram could assist in the precise selection of patients for which ICI could be beneficial and cost-effective.