Stereotactic body radiotherapy plus rucosopasem in locally advanced or borderline resectable pancreatic cancer: GRECO-2 phase II study design.

Ablative doses of stereotactic body radiotherapy (SBRT) may improve pancreatic cancer outcomes but may carry greater potential for gastrointestinal toxicity. Rucosopasem, an investigational selective dismutase mimetic that converts superoxide to hydrogen peroxide, can potentially increase tumor control of SBRT without compromising safety. GRECO-2 is a phase II, multicenter, randomized, double-blind, placebo-controlled trial of rucosopasem in combination with SBRT in locally advanced or borderline resectable pancreatic cancer. Patients will be randomized to rucosopasem 100 mg or placebo via intravenous infusion over 15 min, before each SBRT fraction (5 × 10 Gy). The primary end point is overall survival. Secondary end points include progression-free survival, locoregional control, time to metastasis, surgical resection rate, best overall response, in-field local response and acute and long-term toxicity.

The use of high doses of radiation delivered directly to tumors (stereotactic body radiation therapy [SBRT]) may improve survival compared with lower doses of radiation in patients with pancreatic cancer, but it may increase side effects. Rucosopasem, an investigational new drug being developed, can potentially improve the ability of SBRT to treat tumors without decreasing safety. In a previous study, median overall survival was improved when patients were treated with SBRT plus avasopasem, a drug that works the same way as rucosopasem. GRECO-2 is a clinical trial of rucosopasem used in combination with SBRT for treatment of localized pancreatic cancer. Patients will be randomly selected to receive either rucosopasem 100 mg or placebo via intravenous infusion over 15 min, before each SBRT treatment. The main result being studied is overall survival. Additional results include amount of time before tumors start to grow, how often patients get tumors surgically removed, best overall response and long-term safety. Clinical Trial Registration: NCT04698915 (ClinicalTrials.gov).

Automated health chats for symptom management of head and neck cancer patients undergoing radiation therapy.

OBJECTIVE: To report the early experience using an automated chatbot (Chats)for patient-reported outcomes (PRO) and symptom self-managementinhead and neck cancer (HNC) patients undergoing radiation treatment (RT). METHODS: Patients aged ≥ 18 yearsdiagnosed with HNC who were scheduled to begin RT were given the option to use Chats from June 2018 to June 2019. Enrolled patients received chat notifications two days before weekly on-treatment visitsand every 1-4 weeks after RT for an additional 4 months. After the first in-person follow-up visit, participants completed an electronic usability and satisfaction questionnaire. RESULTS: Of 95 patients who agreed to participate, 84 were eligible for analysis.Participantswere significantly younger than patients who declined participation (mean age 61.3 vs 68.3 years;p-value < 0.001). Patient engagement with Chats was highest at 67% during the first month and declined over time (p-value = 0.004). Concordance between PRO and clinician-reported outcomes (CRO) was fair, ranging from 0.10 to 0.43 (Cohen κ statistics). The most commonly under-reported symptoms were salivary duct inflammation (53%), xerostomia (41%), and mucositis (37%). 89% (39 of 44) of patients who completed surveys found Chats easy to use, and 61% reported that Chats helped with symptom self-management and reduced the need to call the care team. CONCLUSIONS: These early results suggest that an interactive chatbot is feasible and provides support for HNC patients during and after RT. Chats identified discordance between PRO and CRO. Further study is required to measure benefits of Chats in a larger population.

Subtotal Resection Followed by Adjuvant Radiosurgery for Large Vestibular Schwannomas: Outcomes with Regard to the Timing and Regimen of Irradiation.

OBJECTIVE: To evaluate the results of combined management of large vestibular schwannomas (VS) with initial subtotal resection (STR) followed by adjuvant stereotactic radiosurgery (SRS), with a particular emphasis on the timing and regimen of irradiation. METHODS: Seventeen patients underwent STR of a VS followed by SRS, whereas five others were observed after STR. Early SRS (<6 months after surgery) and late SRS (>6 months after surgery) were done in 8 and 9 patients, respectively. Single- and multisession SRS treatments were administered in 10 and 7 patients, respectively. The mean follow-up durations after surgery and SRS were 40 and 28 months, respectively. RESULTS: The rates of radiological and oncological tumor control after SRS were 82% and 100%, respectively. The tumor volume at the last follow-up and its relative changes after SRS did not differ significantly on the basis of the irradiation timing (early versus late) or on the basis of the irradiation regimen (single-session versus multisession). In no patient who was observed after STR of a VS was tumor regrowth noted during a mean follow-up period of 49 months. At 12 months after surgery, motor function of the ipsilateral facial nerve corresponded to House-Brackmann grades I, II, III, and IV in 16 patients (73%), 3 patients (14%), 1 patient (5%), and 2 patients (9%), respectively. Facial nerve function at the last follow-up did not differ significantly on the basis of the irradiation timing (early versus late) or on the basis of the irradiation regimen (single-session versus multisession). CONCLUSION: The combination of initial STR followed by adjuvant SRS is an effective treatment strategy for patients with a large VS. Although the optimal timing and regimen of postoperative irradiation of the residual lesion should be defined further, our preliminary data suggest that either early or late SRS after surgery may provide good tumor control and optimal functional results.

Combined kyphoplasty and intraoperative radiotherapy (Kypho-IORT) versus external beam radiotherapy (EBRT) for painful vertebral metastases - a randomized phase III study.

BACKGROUND: The spine is the most frequent location of bone metastases. Local treatment aims at palliation of pain and, given the increased likelihood of long-term cancer survival, at local control. Kyphoplasty and intraoperative radiotherapy (Kypho-IORT) provided instantaneous pain relief in 70% of patients at the first day after the intervention and resulted in local control rates of > 93% at 1 year in a recently conducted phase I/II trial. To assess its clinical value, we designed a phase III trial which tests Kypho-IORT against the most widespread standard-of-care, external beam radiotherapy (EBRT), in patients with painful vertebral metastases. METHODS: This phase III study includes patients ≥50 years of age with up to 4 vertebral metastases and a pain score of at least 3/10 points on the visual/numeric analogy scale (VAS). Patients randomized into the experimental arm (A) will undergo Kypho-IORT (Kyphoplasty plus IORT with 8 Gy prescribed to 13 mm depth). Patients randomized into the control arm (B) will receive EBRT with either 30 Gy in 10 fractions or 8 Gy as a single dose. The primary end point is pain reduction defined as at least - 3 points on the VAS compared to baseline at day 1. Assuming that 40% of patients in the Kypho-IORT arm and 5% of patients in the control arm will achieve this reduction and 20% will drop out, a total of 54 patients will have to be included to reach a power of 0.817 with a two-sided alpha of 0.05. Secondary endpoints are evaluation of the percentage of patients with a pain reduction of at least 3 points at 2 and 6 weeks, local tumor control, frequency of re-intervention, secondary fractures/sintering, complication rates, skin toxicity/wound healing, progression-free survival (PFS), overall survival (OS) and quality of life. DISCUSSION: This trial will generate level 1 evidence on the clinical value of a one-stop procedure which may provide instantaneous pain relief, long-term control and shortened intervals to further adjuvant (systemic) therapies in patients with spinal metastases. TRIAL REGISTRATION: Registered with ClinicalTrials.gov, number: NCT02773966 (Registration date: 05/16/2016).

Outcomes in the radiosurgical management of metastatic spine disease.

PURPOSE: Stereotactic body radiation therapy (SBRT) is a common treatment option for patients with metastatic tumors of the spine. The optimal treatment-, tumor-, and patient-specific characteristics necessary to achieve durable outcomes remain less well understood given the heterogeneous nature of the patient population this modality typically serves. The objective of this analysis was to better understand the determinants underlying SBRT spine treatment outcomes. METHODS AND MATERIALS: A total of 127 patients with 287 spine tumors were treated between March 2010 and May 2015. The median total doses for single-fraction and hypofractionated courses of treatment were 16 Gy (range, 16-20 Gy) and 24 Gy (range, 16-40 Gy), respectively. Radiologic local control and numeric pain score data were measured, and univariate and multivariate analyses were done to determine factors predictive of treatment response. RESULTS: Median follow-up was 5.9 months (range, 1-61 months). Radiologic local control was achieved in 84.7% of patients at 6 months and in 74.7% of patients at 1 year. Local control was found to be affected by the Spinal Instability Neoplastic Score, and was worse in patients with scores ≥7 (hazard ratio [HR]: 4.25; 95% confidence interval [CI], 1.57-11.51). Patients who required upfront surgical intervention to alleviate spinal cord compression, address mechanical spinal instability, or both had worse local control than those who did not require surgery (HR: 2.32; 95% CI, 1.04-5.17). Patients treated with a hypofractionated course compared with a single fraction had worse radiologic local control (HR: 2.63; 95% CI, 1.27-5.45). No patients developed radiation-induced myelitis after treatment, and the vertebral compression fracture rate was 9.1% after SBRT. CONCLUSIONS: Patients with potentially unstable spines or needing upfront spinal surgery before SBRT are less likely to achieve durable radiologic local control. Additionally, patients treated with single-fraction regimens have improved local control compared with those treated with hypofractionated radiation.