Purpose: Palbociclib, a cyclin D kinase 4 (CDK4)/6 inhibitor, has shown radiosensitizing effects in preclinical studies. There is a strong rationale for adding palbociclib to cetuximab and radiotherapy in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), especially in p16-negative HNSCC. Patients and Methods: We conducted a phase I dose-escalation study (NCT03024489) using a classical 3+3 design to determine safety, tolerability, and MTD of palbociclib, cetuximab, and intensity-modulated radiotherapy (IMRT) combination. At the recommended phase II dose (RP2D), additional p16-negative patients were enrolled. Results: Twenty-seven patients with LA-HNSCC (13 in dose escalation, 14 in expansion) with oropharyngeal (41%) and hypopharyngeal (30%) cancers were enrolled. The MTD was not reached, and the RP2D of palbociclib was established at the full standard palbociclib dose of 125 mg/day for 21 days per cycle, administered for two cycles during IMRT. The most common grade 3–4 toxicities were mucositis (59%), radiation dermatitis (22%), and neutropenia (22%), with a febrile neutropenia rate of 7%. Common genomic alterations included mutations in TP53 (57%), GNAQ (35%), and PIK3CA (17%), and copy-number gains in CCND1 (22%), CCND2 (9%), and EGFR (9%). Overall, p16 expression was positive in 15% of patients. No correlation was observed between p16 status, genomic alterations, and preliminary efficacy. The objective response rate was 84%. The rates for 2-year locoregional control, event-free survival, and overall survival were 73%, 48%, and 71%, respectively. Conclusions: The palbociclib, cetuximab, and IMRT combination was well tolerated. The RP2D was established, while no MTD was determined. The regimen demonstrated promising preliminary efficacy, suggesting further investigation is warranted in patients with cisplatin-ineligible p16/human papilloma virus–unrelated LA-HNSCC.

Background: Osteoporosis is commonly evaluated using dual-energy X-ray absorptiometry (DXA) for bone mineral density (BMD). Non-contrast computed tomography (CT) scans provide an alternative for opportunistic osteoporosis assessment. This study aimed to evaluate screening thresholds for osteoporosis based on CT attenuation values in Hounsfield units (HU) of L1–L4 vertebrae from CT scans of the abdominal region, compared to DXA assessments of the lumbar spine and hips. Methods: Conducted retrospectively over approximately two years, the analysis included 109 patients who had both CT and DXA scans within 12 months, excluding those with metal artifacts affecting the vertebrae. CT attenuation values in the trabecular region of the vertebrae were measured and compared among three groups based on the lowest T-score from DXA. Results: In a predominantly female cohort (mean age 66.3 years), the lowest CT attenuation values for L1–L4 vertebrae showed a moderate correlation with the lowest T-score, with a Pearson correlation coefficient of 0.542 (95% CI: 0.388, 0.667). A HU threshold of ≤142 at the L1 vertebra showed 91.9% sensitivity and 48.4% specificity, while a threshold of ≤160 HU showed 97.3% sensitivity and 31.3% specificity for screening osteoporosis. Conclusions: This study supports the use of non-contrast CT with these HU thresholds as an opportunistic tool for osteoporosis assessment.

Bone Mineral Density and Trabecular Bone Score in Predicting Vertebral Fractures in Male Employees of the Electricity Generating Authority of Thailand: Purpose. Osteoporotic VF is frequently asymptomatic and affects not only women but also men. Identifying patients at risk is essential for early management and prevention. BMD and the TBS are measurements of bone strength and trabecular microarchitecture, respectively. Their role in VF prediction in men is less well-studied. We determined the BMD and TBS predictive ability for osteoporotic VF in men. Methods. A total of 115 male participants of the Electricity Generating Authority of Thailand (EGAT) cohorts without a history of VF who completed the baseline BMD and TBS measurements in 2012 and a thoracolumbar spine radiograph in 2017 were recruited. The VF was assessed using the Genant semiquantitative method. Logistic regression analysis was performed to identify factors associated with the fracture. The area under the receiving operator curve (AUC) was analyzed to define VF predictive ability. Results. Forty subjects (34.78) had VFs. The unadjusted relative risks (95 confidence interval) for VF for one standard deviation decrease in the TBS and low TBS were 1.319 (1.1571.506) and 2.347 (1.4963.682), respectively, and remained significant after BMD and age adjustment. For VF prediction, combined models had a greater AUC than models predicted from a single variable. The use of low TBS, femoral neck BMD, and age provided the best AUC (0.693). Conclusion. BMD and the TBS could predict osteoporotic VF in male EGAT employees. The use of both BMD and the TBS in the VF prediction process improved predictive ability.

Osteoporosis is commonly evaluated using dual-energy X-ray absorptiometry (DXA) for bone mineral density (BMD). Non-contrast computed tomography (CT) scans provide an alternative for opportunistic osteoporosis assessment. This study aimed to evaluate screening thresholds for osteoporosis based on CT attenuation values in Hounsfield units (HU) of L1-L4 vertebrae from abdominal CT scans, compared to DXA assessments of the lumbar spine and hips. Conducted retrospectively over about two years, the analysis included 109 patients who had both CT and DXA scans within 12 months, excluding those with metal artifacts affecting the vertebrae. CT attenuation values in the trabecular region of the vertebrae were measured and compared among three groups based on the lowest T-score from DXA. In a predominantly female cohort (mean age 66.3 years), significant correlations were found between the CT HU values of L1-L4 vertebrae and the lowest T-score. CT HU values differed significantly among normal (17.4%), low bone mass (46.8%), and osteoporosis (35.8%) groups (P < 0.001). A HU threshold of ≤142 at the L1 vertebra showed 91.9% sensitivity and 48.4% specificity, while a threshold of ≤160 HU showed 97.3% sensitivity and 31.3% specificity for screening osteoporosis. In conclusion, this study supports the utility of non-contrast CT with these HU thresholds as an opportunistic osteoporosis assessment.

Purpose:Palbociclib, a cyclin D kinase 4 (CDK4)/6 inhibitor, has shown radiosensitizing effects in preclinical studies. There is a strong rationale for adding palbociclib to cetuximab and radiotherapy in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), especially in p16-negative HNSCC.Patients and Methods:We conducted a phase I dose-escalation study (NCT03024489) using a classical 3+3 design to determine safety, tolerability, and MTD of palbociclib, cetuximab, and intensity-modulated radiotherapy (IMRT) combination. At the recommended phase II dose (RP2D), additional p16-negative patients were enrolled.Results:Twenty-seven patients with LA-HNSCC (13 in dose escalation, 14 in expansion) with oropharyngeal (41%) and hypopharyngeal (30%) cancers were enrolled. The MTD was not reached, and the RP2D of palbociclib was established at the full standard palbociclib dose of 125 mg/day for 21 days per cycle, administered for two cycles during IMRT. The most common grade 3–4 toxicities were mucositis (59%), radiation dermatitis (22%), and neutropenia (22%), with a febrile neutropenia rate of 7%. Common genomic alterations included mutations in TP53 (57%), GNAQ (35%), and PIK3CA (17%), and copy-number gains in CCND1 (22%), CCND2 (9%), and EGFR (9%). Overall, p16 expression was positive in 15% of patients. No correlation was observed between p16 status, genomic alterations, and preliminary efficacy. The objective response rate was 84%. The rates for 2-year locoregional control, event-free survival, and overall survival were 73%, 48%, and 71%, respectively.Conclusions:The palbociclib, cetuximab, and IMRT combination was well tolerated. The RP2D was established, while no MTD was determined. The regimen demonstrated promising preliminary efficacy, suggesting further investigation is warranted in patients with cisplatin-ineligible p16/human papilloma virus–unrelated LA-HNSCC.