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Purpose: The purpose of this study was to evaluate the feasibility and safety of dose-escalated proton beam therapy for treating chordomas and chondrosarcomas of the skull base and spine. Methods: A prospective cohort of 54 patients (42 with chordomas and 12 with chondrosarcomas) was enrolled between 2010 and 2018. The primary endpoints were feasibility and 5 days, none for toxicities related to treatment. There were no grade 4 acute toxicities and 1 grade 3 acute toxicity (sensory neuropathy). The only 2 grade 3 late toxicities recorded, osteoradionecrosis and intranasal carotid blowout (mild and not emergently treated), occurred in a single patient. We report overall survival as 83% at 5 years, with local failure-free survival and progression-free survival rates of 72% and 68%, respectively. Five patients developed distant disease, and among the 9/54 patients who died, 4 deaths were not attributed to treatment or recurrence. Conclusions: Our findings suggest that high-dose proton therapy alone or in combination with IMRT is a safe and effective treatment option for chordomas and chondrosarcomas of the skull base and spine.

Two-dimensional heterostructures (2D HSs) have emerged as a new class of materials where dissimilar 2D materials are combined to synergise their advantages and alleviate shortcomings. Such a combination of dissimilar components into 2D HSs offers fascinating properties and intriguing functionalities attributed to the newly formed heterointerface of constituent components. Understanding the nature of the surface and the complex heterointerface of HSs at the atomic level is crucial for realising the desired properties, designing innovative 2D HSs, and ultimately unlocking their full potential for practical applications. Therefore, this review provides the recent progress in the field of 2D HSs with a focus on the discussion of the fundamentals and the chemistry of heterointerfaces based on van der Waals (vdW) and covalent interactions. It also explains the challenges associated with the scalable synthesis and introduces possible methodologies to produce large quantities with good control over the heterointerface. Subsequently, it highlights the specialised characterisation techniques to reveal the heterointerface formation, chemistry and nature. Afterwards, we give an overview of the role of 2D HSs in various emerging applications, particularly in high-power batteries, bifunctional catalysts, electronics, and sensors. In the end, we present conclusions with the possible solutions to the associated challenges with the heterointerfaces and potential opportunities that can be adopted for innovative applications.

Purpose: Spatially fractionated radiation therapy (SFRT), which delivers highly nonuniform dose distributions instead of conventionally practiced homogeneous tumor dose, has shown high rates of clinical response with minimal toxicities in large-volume primary or metastatic malignancies. However, prospective multi-institutional clinical trials in SFRT are lacking, and SFRT techniques and dose parameters remain variable. Agreement on dose prescription, technical administration, and clinical and translational design parameters for SFRT trials is essential to enable broad participation and successful accrual to rigorously test the SFRT approach. We aimed to develop a consensus for the design of multi-institutional clinical trials in SFRT, tailored to specific primary tumor sites, to help facilitate development and enhance the feasibility of such trials. Methods and Materials: Primary tumor sites with sufficient pilot experience in SFRT were identified, and fundamental trial design questions were determined. For each tumor site, a comprehensive consensus effort was established through disease-specific expert panels. Clinical trial design criteria included eligibility, SFRT technology and technique, dose and fractionation, target- and normal-tissue dose parameters, systemic therapies, clinical trial endpoints, and translational science considerations. Iterative appropriateness rank voting, expert panel consensus reviews and discussions, and public comment posting were used for consensus development. Results: Clinical trial criteria were developed for head and neck cancer and soft-tissue sarcoma. Final consensus among the 22 trial design categories each (a total of 163 criteria) was high to moderate overall. Uniform patient cohorts of advanced bulky disease, standardization of SFRT technologies and dosimetry and physics parameters, and collection of translational correlates were considered essential to trial design. Final guideline recommendations and the degree of agreement are presented and discussed. Conclusions: This consensus provides design guidelines for the development of prospective multi-institutional clinical trials testing SFRT in advanced head and neck cancer and soft-tissue sarcoma through in-advance harmonization of the fundamental clinical trial design among SFRT experts, potential investigators, and the SFRT community.

Summary:. Based on the findings of two consecutive cases of upper extremity compartment syndrome encountered at our institution, we hypothesize that the presence of compartment syndrome in the unstable COVID-19 patient may be associated with high mortality and low limb salvage rates. A literature search was conducted with key search terms, including “compartment syndrome, fasciotomy, COVID, and coronavirus.” Articles describing patients with a confirmed COVID-19 diagnosis who developed extremity compartment syndrome were included in our study. The primary outcome investigated was patient survival. Secondary outcomes included limb survival and limb salvage. Limb salvage was calculated in patients who survived to time of discharge, whereas limb survival was counted for all patients. We then added our two cases to the findings reported in our literature to determine current overall limb salvage and patient survival rates. Our review of the literature yielded six case reports of ten extremities that developed compartment syndrome in the COVID-19 positive patient. Overall survival was four of six patients (67%). The overall limb survival rate at the time of hospital discharge was three of 10 (30%). With the addition of our two cases, overall survival was four of eight (50%) and overall limb survival rate was three of 12 (25%). Furthermore, with inclusion of our two cases, the patient survival rate of hemodynamically unstable patients was only three of seven (43%). The development of compartment syndrome in the unstable COVID-19 patient may be a harbinger of death, and the decision to proceed with operative intervention is challenging, complex, and in some cases must prioritize life over limb.

Purpose: Concurrent chemoradiation therapy is a curative treatment for squamous cell carcinoma of the anus, but patients can suffer from significant treatment-related toxicities. This study was undertaken to determine whether intensity modulated proton therapy (IMPT) is associated with less acute toxicity than intensity modulated radiation therapy (IMRT) using photons. Materials and Methods: We performed a multi-institutional retrospective study comparing toxicity and oncologic outcomes of IMRT versus IMPT. Patients with stage I-IV (for positive infrarenal para-aortic or common iliac nodes only) squamous cell carcinoma of the anus, as defined by the American Joint Committee on Cancer's AJCC Staging Manual, eighth edition, were included. Patients with nonsquamous histology or mixed IMPT and IMRT treatment courses were excluded. Acute nonhematologic toxicities, per the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 4, were recorded prospectively at all sites. Acute and late toxicities, dose metrics, and oncologic outcomes were compared between IMRT and IMPT using univariable and multivariable statistical methods. To improve the robustness of our analysis, we also analyzed the data using propensity score weighting methods. Results: A total of 208 patients were treated with either IMPT (58 patients) or IMRT (150 patients). Of the 208 total patients, 13% had stage I disease, 36% stage II, 50% stage III, and 1% stage IV. IMPT reduced the volume of normal tissue receiving low-dose radiation but not high-dose radiation to bladder and bowel. There was no significant difference between treatment groups in overall grade 3 or greater acute toxicity (IMRT, 68%; IMPT, 67%; P = .96) or 2-year overall grade 3 or greater late toxicity (IMRT, 3.5%; IMPT, 1.8%; P = .88). There was no significant difference in 2-year progression-free survival (hazard ratio, 0.8; 95% CI, 0.3-2.0). Conclusions: Despite reducing the volume of normal tissue receiving low-dose radiation, IMPT was not associated with decreased grade 3 or greater acute toxicity as measured by CTCAE. Additional follow-up is needed to assess whether important differences arise in late toxicities and if further prospective evaluation is warranted.