Horizons: Nuclear Astrophysics in the 2020s and Beyond

Nuclear Astrophysics is a field at the intersection of nuclear physics and astrophysics, which seeks to understand the nuclear engines of astronomical objects and the origin of the chemical elements. This white paper summarizes progress and status of the field, the new open questions that have emerged, and the tremendous scientific opportunities that have opened up with major advances in capabilities across an ever growing number of disciplines and subfields that need to be integrated. We take a holistic view of the field discussing the unique challenges and opportunities in nuclear astrophysics in regards to science, diversity, education, and the interdisciplinarity and breadth of the field. Clearly nuclear astrophysics is a dynamic field with a bright future that is entering a new era of discovery opportunities.Comment: 96 pages. Submitted to Journal of Physics

Horizons: nuclear astrophysics in the 2020s and beyond

Nuclear astrophysics is a field at the intersection of nuclear physics and astrophysics, which seeks to understand the nuclear engines of astronomical objects and the origin of the chemical elements. This white paper summarizes progress and status of the field, the new open questions that have emerged, and the tremendous scientific opportunities that have opened up with major advances in capabilities across an ever growing number of disciplines and subfields that need to be integrated. We take a holistic view of the field discussing the unique challenges and opportunities in nuclear astrophysics in regards to science, diversity, education, and the interdisciplinarity and breadth of the field. Clearly nuclear astrophysics is a dynamic field with a bright future that is entering a new era of discovery opportunities

Patritumab or placebo, with cetuximab plus platinum therapy in recurrent or metastatic squamous cell carcinoma of the head and neck: A randomised phase II study.

BACKGROUND:The fully human monoclonal antibody patritumab blocks HER3 activation, a resistance mechanism to cetuximab, induced by heregulin (HRG). A phase Ib study in recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) demonstrated tolerability and tumour response of patritumab + cetuximab + platinum. METHODS:This was a randomised, double-blind, phase II study of patritumab + cetuximab with platinum-based therapy for first-line treatment of R/M SCCHN (Clinicaltrials.gov identifier: NCT02633800). Patients aged ≥18 years received patritumab or placebo, both combined with cetuximab + cisplatin or carboplatin. Co-primary end-points were progression-free survival (PFS) in the intent-to-treat (ITT) and the high-expression HRG (HRG high) populations. RESULTS:Eighty-seven patients (n = 43 in the patritumab group; n = 44 in placebo group) enrolled. A median (range) of 6.5 (1-24) patritumab cycles were completed. Median PFS was similar between the patritumab group and placebo group in the ITT population (5.6 versus 5.5 months; hazard ratio [HR] 0.99 [95% confidence interval [CI], 0.6-1.7]; P = 0.96) and HRG-high subgroup (n = 51; 5.6 versus 5.6 months; HR 0.93 [95% CI, 0.5-1.8]; P = 0.82). Median overall survival in the ITT population was also similar (10.0 versus 12.7 months; HR 1.3 [95% CI, 0.69-2.29]; P = 0.46). All patients experienced ≥1 treatment-emergent adverse event (TEAE). Grade ≥III TEAEs were more frequent in the patritumab than the placebo group (84.1% versus 60.5%). The most common grade ≥III patritumab-related TEAE in the patritumab group (20.5% overall) was rash (6.8%). CONCLUSION:Patritumab + cetuximab + platinum was tolerable but not superior to cetuximab + platinum

Randomized Phase 2 Trial of a Novel Clonidine Mucoadhesive Buccal Tablet for the Amelioration of Oral Mucositis in Patients Treated With Concomitant Chemoradiation Therapy for Head and Neck Cancer.

Oral mucositis (OM) is a frequent and painful sequela of concomitant chemoradiation (CRT) used for the treatment of head and neck cancer (HNC) for which there is no effective intervention. This randomized, placebo-controlled study evaluated the efficacy of a novel, mucoadhesive topical tablet formulation of clonidine in mitigating CRT-induced OM in patients with HNC. Patients with HNC undergoing adjuvant radiation therapy (60-66 Gy; 5 × 1.8-2.2 Gy/wk) with concomitant platinum-based chemotherapy received daily local clonidine at 50 μg (n = 56), 100 μg (n = 65), or placebo (n = 62) via a topical mucobuccal tablet starting 1 to 3 days before and continuing during treatment. The primary endpoint was the incidence of severe OM (severe OM [SOM], World Health Organization grade 3/4). SOM developed in 45% versus 60% (P = .06) of patients treated with clonidine compared with placebo and occurred for the first time at 60 Gy as opposed to 48 Gy (median; hazard ratio, 0.75 [95% confidence interval, 0.484-1.175], P = .21); median time to onset was 45 versus 36 days. Opioid analgesic use, mean patient-reported mouth and throat soreness, and CRT compliance were not significantly different between treatment arms. Adverse events were reported in 90.8% versus 98.4%, nausea in 49.6% versus 71.0%, dysphagia in 32.8% versus 48.4%, and reversible hypotension in 6.7% versus 1.6% of patients on clonidine versus placebo, respectively. Although the primary endpoint was not met, the positive trends of OM-associated outcomes suggest that the novel mucoadhesive tablet delivery of clonidine might favorably affect the course and severity of CRT-induced SOM and support further evaluation