A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC.

Five-year survival for human papilloma virus-unrelated head and neck squamous cell carcinomas remain below 50%. We assessed the safety of administering combination hypofractionated stereotactic body radiation therapy with single-dose durvalumab (anti-PD-L1) neoadjuvantly (n = 21) ( NCT03635164 ). The primary endpoint of the study was safety, which was met. Secondary endpoints included radiographic, pathologic and objective response; locoregional control; progression-free survival; and overall survival. Among evaluable patients at an early median follow-up of 16 months (448 d or 64 weeks), overall survival was 80.1% with 95% confidence interval (95% CI) (62.0%, 100.0%), locoregional control and progression-free survival were 75.8% with 95% CI (57.5%, 99.8%), and major pathological response or complete response was 75% with 95% exact CI (51.6%, 100.0%). For patients treated with 24 Gy, 89% with 95% CI (57.1%, 100.0%) had MPR or CR. Using high-dimensional multi-omics and spatial data as well as biological correlatives, we show that responders had: (1) an increase in effector T cells; (2) a decrease in immunosuppressive cells; and (3) an increase in antigen presentation post-treatment.

Radiation dose uncertainty and correction for a mouse orthotopic and xenograft irradiation model.

PURPOSE: In animal irradiation models, reported dose can vary significantly from the actual doses delivered. We describe an effective method for in vivo dose verification. MATERIALS AND METHODS: Mice bearing commercially-available cell line or patient-derived tumor cell orthotopic or flank xenografts were irradiated using a 160 kVp, 25 mA X-ray source. Entrance dose was evaluated using optically-stimulated luminescence dosimeters (OSLD) and exit dose was assessed using radiochromic film dosimetry. RESULTS: Tumor position within the irradiation field was validated using external fiducial markers. The average entrance dose in orthotopic tumors from 10 OSLDs placed on two different animal irradiation days was 514 ± 37 cGy (range: 437-545). Exit dose measurements taken from seven radiochromic films on two separate days were 341 ± 21 cGy (a 34% attenuation). Flank tumor irradiation doses measured by OSLD were 368 ± 9 cGy compared to exit doses of 330 cGy measured by radiochromic film. CONCLUSION: Variations related to the irradiation model can lead to significant under or overdosing in vivo which can affect tumor control and/or biologic endpoints that are dose-dependent. We recommend that dose measurements be determined empirically based on the mouse model and irradiator used and dose compensation adjustments performed to ensure correct and appropriate doses.

The relationship between thyroid dose and diagnosis of primary hypothyroidism in pediatric brain tumor patients receiving craniospinal irradiation.

PURPOSE: The aim of this work is to determine if a relationship exists between thyroid dose and incidence of primary hypothyroidism (PH) in children undergoing craniospinal irradiation (CSI). METHODS: A total of 22 patients received CSI with evaluable thyroid dose information. All patients received concurrent chemotherapy and 21 patients (95%) received adjuvant chemotherapy. Median follow-up was 42.9 months. RESULTS: The incidence of PH in our cohort was 59% at a median time after radiotherapy of 3.5 years (range: 8 months to 7.5 years). Mean thyroid dose appeared to best predict for PH, with a median of 2080 cGy for patients with PH versus 1736 cGy for children without PH (p=0.057). There was no association between the rate of PH and sex, age, CSI dose, minimum thyroid dose and maximum thyroid dose. CONCLUSIONS: A relationship may exist between the mean thyroid dose and incidence of PH in patients undergoing CSI. Thus, new strategies to protect the thyroid gland may be warranted.

Supine craniospinal irradiation setup with two spine fields.

Craniospinal irradiation is an integral part of treatment for a number of cancers. Typically, patients are positioned prone, which allows visualization of field matches. However, a supine position allows better airway access for patients requiring anesthesia, and is more comfortable for patients. One potential difficulty with supine positioning occurs when the patient is tall and requires matching 2 spine fields. We describe a technique to match the spine fields using light fields on the bottom of the treatment table, and verified the approach on a phantom. The accuracy of the technique is demonstrated for the first 4 patients, with the majority of field gaps and overlaps below our clinical tolerance of 2 mm.