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Purpose: Cancer diagnosis and treatment, including radiation therapy (RT), cause significant patient stress. Mindfulness and social support have been shown to help manage the psychological effects of cancer treatment. The objective of our study was to determine the sociodemographic and clinical factors associated with stress burden in patients receiving RT. Methods and Materials: Patients receiving RT for cancer at a single institution were given a 3-section survey to complete during the first on-treatment visit. The survey included the Perceived Stress Scale, Medical Outcomes Study Social Support Survey, and Mindfulness Attention Awareness Scale, which were used to measure stress, social support, and trait mindfulness, respectively. Linear regression analysis was performed to determine associations between perceived stress and age, patient sex, race and ethnicity, treatment intent, disease site, trait mindfulness, and social support. Factors significant in univariable analysis were analyzed with a multivariable analysis. Results: A total of 93 patients undergoing RT at a tertiary care academic institution were recruited from July to September 2019. Median scores for Perceived Stress Scale, Medical Outcomes Study Social Support Survey, and Mindfulness Attention Awareness Scale were 14.6 (range, 0-31; SD, 6.9), 4.2 (range, 1-5; SD, 1.0), and 5.1 (range, 3.1-6.0; SD, 0.8), respectively. On univariable analysis, mindfulness and social support were associated with decreased stress burden, and female sex and palliative intent were associated with increased stress burden. These factors all maintained significance in multivariable analysis. Conclusions: These results suggest measures to improve mindfulness and perceived social support, such as mindfulness meditation and psychoeducational approaches, may lessen the stress burden and improve quality of life for patients undergoing RT. Future studies should analyze the longitudinal impact of individual patient characteristics, including patient sex and treatment intent, to better understand their effects on psychological maladjustment during cancer care.

Purpose: Compared with photon-based techniques, proton beam radiation therapy (PBT) may improve the therapeutic ratio of radiation therapy (RT) for locally advanced pancreatic cancer (LAPC), but available data have been limited to single-institutional experiences. This study examined the toxicity, survival, and disease control rates among patients enrolled in a multi-institutional prospective registry study and treated with PBT for LAPC. Methods and Materials: Between March 2013 and November 2019, 19 patients with inoperable disease across 7 institutions underwent PBT with definitive intent for LAPC. Patients received a median radiation dose/fractionation of 54 Gy/30 fractions (range, 50.4-60.0 Gy/19-33 fractions). Most received prior (68.4%) or concurrent (78.9%) chemotherapy. Patients were assessed prospectively for toxicities using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Kaplan-Meier analysis was used to analyze overall survival, locoregional recurrence-free survival, time to locoregional recurrence, distant metastasis-free survival, and time to new progression or metastasis for the adenocarcinoma cohort (17 patients). Results: No patients experienced grade ≥3 acute or chronic treatment-related adverse events. Grade 1 and 2 adverse events occurred in 78.7% and 21.3% of patients, respectively. Median overall survival, locoregional recurrence-free survival, distant metastasis-free survival, and time to new progression or metastasis were 14.6, 11.0, 11.0, and 13.9 months, respectively. Freedom from locoregional recurrence at 2 years was 81.7%. All patients completed treatment with one requiring a RT break for stent placement. Conclusions: Proton beam RT for LAPC offered excellent tolerability while still maintaining disease control and survival rates comparable with dose-escalated photon-based RT. These findings are consistent with the known physical and dosimetric advantages offered by proton therapy, but the conclusions are limited owing to the patient sample size. Further clinical studies incorporating dose-escalated PBT are warranted to evaluate whether these dosimetric advantages translate into clinically meaningful benefits.

Purpose: Stereotactic body radiation therapy (SBRT) is commonly used to treat spinal metastases in combination with immunotherapy (IT). The optimal sequencing of these modalities is unclear. This study aimed to investigate whether sequencing of IT and SBRT was associated with differences in local control (LC), overall survival (OS), and toxicity when treating spine metastases. Methods and Materials: All patients at our institution who received spine SBRT from 2010 to 2019 with systemic therapy data available were reviewed retrospectively. The primary endpoint was LC. Secondary endpoints were toxicity (fracture and radiation myelitis) and OS. Kaplan-Meier analysis was used to determine whether IT sequencing (before versus after SBRT) and use of IT were associated with LC or OS. Results: A total of 191 lesions in 128 patients met inclusion criteria with 50 (26%) lesions in 33 (26%) patients who received IT. Fourteen (11%) patients with 24 (13%) lesions received the first IT dose before SBRT, whereas 19 (15%) patients with 26 (14%) lesions received the first dose after SBRT. LC did not differ between lesions treated with IT before SBRT versus after SBRT (1 year 73% versus 81%, log rank = 0.275, P = .600). Fracture risk was not associated with IT timing (χ2 = 0.137, P = .934) or receipt of IT (χ2 = 0.508, P = .476), and no radiation myelitis events occurred. Median OS was 31.8 versus 6.6 months for the IT after SBRT versus IT before SBRT cohorts, respectively (log rank = 13.193, P < .001). On Cox univariate analysis and multivariate analysis, receipt of IT before SBRT and Karnofsky performance status

Introduction Curative intent treatment of head and neck cancer (HNC) is frequently radiation therapy over 7 weeks with concurrent chemotherapy. This regimen is effective but carries a burden of toxicity leading to severe pain and treatment breaks portending inferior outcomes. Conventional palliation methods include opioids, anticonvulsants and local anaesthetics. Breakthrough toxicities are nevertheless ubiquitous and present an urgent unmet need. Ketamine is an inexpensive drug with mechanisms of analgesia outside the opioid pathway including N-methyl-D-aspartate (NMDA) receptor antagonism and a pharmacologically unique property of opioid desensitisation. Systemic ketamine is validated in randomised controlled trials for efficacy in reducing pain and/or opioid burden in the oncologic setting. Literature supports peripherally administered ketamine for pain control without systemic toxicity. These data support our rationale of using ketamine mouthwash to decrease acute toxicity of curative treatment of HNC, the efficacy of which is our aim to elucidate.Methods and analysis This is a phase II, Simon’s two-stage trial. Patients have pathologically confirmed HNC and an intended regimen of 70 Gy of radiation with concurrent cisplatin. The protocol is initiated on diagnosis of grade 3 mucositis and consists of 2 weeks of 4 times daily (QID) ketamine mouthwash use. The primary endpoint is pain response defined as a combination of pain score and opioid use. 23 subjects will be enrolled in stage 1. If statistical criteria are met, 33 subjects will be enrolled in stage 2. Secondary endpoints include daily pain, daily opioid use, dysphagia at baseline and completion, nightly sleep quality, feeding tube placement and any unscheduled treatment breaks.Ethics and dissemination All trial data will be stored in an Institutional Review Board (IRB) approved database. The protocol is registered under Northwell IRB registration number #22-0292 and U.S. Food and Drug Administration (FDA) Investigational New Drug (IND) approval has been granted under IND number 161609. Results are intended to be published in an open-source journal and further data, statistics and source documents are available on request.Trial registration number NCT05331131.

Background: Radiation-induced hypothyroidism is a common toxicity of head and neck radiation. Our re-planning study aimed to reduce thyroid dose while maintaining target coverage with IMRT. Methods: We retrospectively identified patients with oral-cavity (n = 5) and oropharyngeal cancer (n = 5). Treatment plans were re-optimized with 45 Gy thyroid mean dose constraint, then we cropped the thyroid out of PTVs and further reduced thyroid dose. Target coverage was delivering 100% dose to ≥ 93% of PTV and 95% of dose to > 99% of PTV. Results: Originally, average mean dose to thyroid was 5580 cGy. In model I, this dropped to 4325 cGy (p

Purpose: Mindfulness, defined as awareness of the moment while acknowledging and accepting one's feelings, thoughts, and sensations, is the aim of mindfulness meditation. Our objective was to investigate the relationship between burnout, mindfulness, fulfillment, and other personal characteristics in radiation oncology (RO) residents/attendings compared with other specialties. Methods and Materials: From December 2019 to February 2020, residents and attendings in multiple specialties at a single tertiary care academic institution were sent surveys, including the mindfulness attention awareness scale, Stanford professional fulfillment index, and a personal questionnaire. A Pearson correlation was conducted on the relationship between mindfulness, fulfillment, disengagement, and exhaustion. To determine risk factors for burnout (overall burnout ≥ 1.33), a univariate analysis was conducted to yield odds ratios (ORs) on debt, specialty, income, sleep, exercise, marital status, number of children, work hours, mindfulness (mindfulness attention awareness scale ≥ 4), fulfillment (professional fulfillment ≥ 3), and time with family/friends. Significant factors on univariate analysis were entered into multivariate analysis. Results: There were 180 surveys completed by 60 residents and attendings across 17 specialties. Eighteen (30%) respondents were in RO. Mindfulness positively correlated with fulfillment (P < .001, r = 0.534), negatively correlated with exhaustion (P < .001, r = -0.578), and negatively correlated with disengagement (P < .001, r = -0.483). Univariate analysis for factors associated with burnout was significant for mindfulness (OR = 0.065, P < .001), RO versus other specialty (OR = 0.024, P = .044), working >60 h/wk (OR = 5.091, P = .018), spending >10 h/wk with family or friends (OR = 0.120, P = .001), and fulfillment (OR = 0.103, P < .001). Multivariate analysis showed mindfulness and fulfillment to significantly decrease odds of burnout. Conclusions: RO physicians experienced less burnout than physicians in other specialties at our institution. Mindfulness, professional fulfillment, moderate work hours, and spending time with loved ones protected against burnout. Further study of interventions to promote mindfulness and fulfillment may help us understand how best to improve the mental and emotional health of RO physicians.

Abstract Bazex syndrome is a rare paraneoplastic dermatosis that precedes diagnosis of cancer. Awareness of this syndrome is important, as it allows early detection of underlying malignancy and may prevent misdiagnosis and delays in cancer treatment.

An enormous amount of efforts have been poured to find an effective therapeutic agent for the treatment of neurodegenerative diseases including Alzheimer's disease (AD). Among those, neurotrophic peptides that regenerate neuronal structures and increase neuron survival show a promise in slowing neurodegeneration. However, the short plasma half-life and poor blood-brain-barrier (BBB)-permeability of neurotrophic peptides limit their in vivo efficacy. Thus, an alternative neurotrophic agent that has longer plasma half-life and better BBB-permeability has been sought for. Based on the recent findings of neuroprotective polysaccharides, we searched for a BBB-permeable neuroprotective polysaccharide among natural polysaccharides that are approved for human use. Then, we discovered midi-GAGR, a BBB-permeable, long plasma half-life, strong neuroprotective and neurotrophic polysaccharide. Midi-GAGR is a 4.7kD cleavage product of low acyl gellan gum that is approved by FDA for human use. Midi-GAGR protected rodent cortical neurons not only from the pathological concentrations of co-/post-treated free reactive radicals and Aβ42 peptide but also from activated microglial cells. Moreover, midi-GAGR showed a good neurotrophic effect; it enhanced neurite outgrowth and increased phosphorylated cAMP-responsive element binding protein (pCREB) in the nuclei of primary cortical neurons. Furthermore, intra-nasally administered midi-GAGR penetrated the BBB and exerted its neurotrophic effect inside the brain for 24 h after one-time administration. Midi-GAGR appears to activate fibroblast growth factor receptor 1 (FGFR1) and its downstream neurotrophic signaling pathway for neuroprotection and CREB activation. Additionally, 14-day intranasal administration of midi-GAGR not only increased neuronal activity markers but also decreased hyperphosphorylated tau, a precursor of neurofibrillary tangle, in the brains of the AD mouse model, 3xTg-AD. Taken together, midi-GAGR with good BBB-permeability, long plasma half-life, and strong neuroprotective and neurotrophic effects has a great therapeutic potential for the treatment of neurodegenerative diseases, especially AD.