Dosimetric characterization of a new surface-conforming electron MLC prototype.

The purpose is to reduce normal tissue radiation toxicity for electron therapy through the creation of a surface-conforming electron multileaf collimator (SCEM). The SCEM combines the benefits of skin collimation, electron conformal radiotherapy, and modulated electron radiotherapy. An early concept for the SCEM was constructed. It consists of leaves that protrude towards the patient, allowing the leaves to conform closely to irregular patient surfaces. The leaves are made of acrylic to decrease bremsstrahlung, thereby decreasing the out-of-field dose. Water tank scans were performed with the SCEM in place for various field sizes for all available electron energies (6, 9, 12, and 15 MeV) with a 0.5 cm air gap to the water surface at 100 cm source-to-surface distance (SSD). These measurements were compared with Cerrobend cutouts with the field size-matched at 100 and 110 cm SSD. Output factor measurements were taken in solid water for each energy at dmax for both the cerrobend cutouts and SCEM at 100 cm SSD. Percent depth dose (PDD) curves for the SCEM shifted shallower for all energies and field sizes. The SCEM also produced a higher surface dose relative to Cerrobend cutouts, with the maximum being a 9.8% increase for the 3 cm × 9 cm field at 9 MeV. When compared to the Cerrobend cutouts at 110 cm SSD, the SCEM showed a significant decrease in the penumbra, particularly for lower energies (i.e., 6 and 9 MeV). The SCEM also showed reduced out-of-field dose and lower bremsstrahlung production than the Cerrobend cutouts. The SCEM provides significant improvement in the penumbra and out-of-field dose by allowing collimation close to the skin surface compared to Cerrobend cutouts. However, the added scatter from the SCEM increases shallow PDD values. Future work will focus on reducing this scatter while maintaining the penumbra and out-of-field benefits the SCEM has over conventional collimation.

Non-invasive stereotactic ablative boost in patients with locally advanced cervical cancer.

INTRODUCTION: The current literature is insufficient to guide care for patients with cervical cancer ineligible for brachytherapy. Stereotactic ablative radiotherapy boost is a clinical necessity for these patients, but highly debated among radiation oncologists. OBJECTIVE: To report toxicity and survival outcomes in a large cohort of patients with locally advanced cervical cancer treated with a non-invasive stereotactic ablative radiotherapy boost instead of brachytherapy METHODS: Patients with locally advanced cervical cancer were entered, between January 2008 and December 2018, who were recommended definitive intent external boost after pelvic radiotherapy to 45-50.4 Gy concurrent with weekly cisplatin and simultaneous/sequential nodal boost up to 55-66 Gy. Simulation CT was facilitated using radio-opaque fiducials, empty rectum, dedicated bladder filling, and whole body vaculoplastic immobilization. Kaplan-Meier survival estimates were used to report local/regional recurrences, distant metastases, cancer-specific survival, and overall survival. RESULTS: A total of 25 patients were analyzed. Median follow-up was 25 months (range 6-54). Patients received stereotactic ablative radiotherapy due to refusal of brachytherapy (9/25, 36%), medical co-morbidities limiting implantation (9/25, 36%), or technical infeasibility (7/25, 28%). Typical fractionation was 24-30 Gy in 4-5 fractions (24/25, 96%). The most common long-term toxicity was grade 1-2 vaginal dryness, discomfort, stenosis, and/or dyspareunia (4/25, 16%). One patient had new post-treatment grade 4 fistula in an area of previous tumor erosion (1/25, 4%). Overall survival, cancer specific survival, loco-regional control, and distant control were 95.5%, 100%, 95.5%, and 89.1%, respectively, at 2 years. CONCLUSION: Further study of stereotactic ablative radiotherapy boost for cervical cancer is needed; a brachytherapy-similar approach portends clinical success with 95.5% overall survival and loco-regional control at 2 years.

Emotional disclosure and cognitive processing in couples coping with head and neck cancer.

Head and neck cancer (HNC) patients and their spouses experience communication problems and high rates of emotional distress. Couple-based interventions that encourage emotional disclosure hold promise for improving cognitive processing and distress in this population, but more research needs to examine when and for whom emotional disclosure is an effective coping strategy. In this observational study, 125 HNC patients (83% male) and their spouses were videotaped discussing a cancer-related concern in the laboratory. Discussions were coded with the specific affect coding system. Actor-partner interdependence models showed that patient expression of negative emotions (i.e., disdain, contentiousness, distress) was not related to his/her own or the spouse's cognitive processing (assessed as reaction times to cancer and noncancer words on a computerized cognitive task administered immediately following the discussion). When spouses expressed support (e.g., interest, validation), they had better cancer- (effect size r = - 0.21) and noncancer-related cognitive processing (r = - 0.17), but patients did not. However, when spouses expressed disdain (e.g., contempt) and contentiousness (e.g., criticism, domineering), patients had poorer cancer- (r = 0.20-0.22) and noncancer-related cognitive processing (r = 0.19-0.26). Findings suggest consideration of the valence of affective expression and which partner is disclosing/listening before unilaterally encouraging HNC couples to openly express emotions as a means of alleviating distress.

Nicotine Modulates Growth Factors and MicroRNA to Promote Inflammatory and Fibrotic Processes.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease that destroys the structure and function of the lungs. Risk factors include advanced age and genetic predisposition. However, tobacco use is the chief modifiable risk factor. The prevalence of tobacco use in IPF reaches up to 80%. Although tobacco smoke contains over 5000 chemicals, nicotine is a major component. Nicotine is a bioactive molecule that acts upon nicotinic acetylcholine receptors expressed on neuronal and non-neuronal cells including endothelial cells. Accordingly, it has a pleiotropic effect on cell proliferation and angiogenesis. The angiogenic effect is partly mediated by stimulation of growth factors including fibroblast, platelet-derived, and vascular endothelial growth factors. Nintedanib, a Food and Drug Administration-approved drug for IPF, works by inhibiting receptors for these growth factors, suggesting a pathobiologic role of the growth factors in IPF and a potential mechanism by which tobacco use may exacerbate the disease process; additionally, nicotine downregulates anti-inflammatory microRNAs (miRs) in lung cells. Here, we profiled the expression of miRs in lung tissues explanted from a lung injury model and examined the effect of nicotine on one of the identified miRs (miR-24) and its downstream targets. Our data show that miR-24 is downregulated during lung injury and is suppressed by nicotine. We also found that nicotine upregulates the expression of inflammatory cytokines targeted by miR-24. Finally, nicotine stimulated growth factors, fibroblast proliferation, collagen release, and expression of myofibroblast markers. Taken together, nicotine, alone or as a component of tobacco smoke, may accelerate the disease process in IPF through stimulation of growth factors and downregulation of anti-inflammatory miRs.

Inversely and adaptively planned interstitial brachytherapy: A single implant approach.

OBJECTIVE: To evaluate the efficacy, feasibility and safety of image-based, inversely and adaptively planned high-dose rate interstitial brachytherapy (HDR-ISBT) to treat advanced primary or recurrent gynecologic malignancy in a single implant, three-consecutive-day regimen. METHODS: Clinical demographics and outcome data were abstracted from all patients with primary and recurrent gynecologic malignancies who received HDR-ISBT boost from 2014 to 2017. Treatment consisted of a single implant (~7 Gy × 4 fractions) of interstitial needles using the Syed-Neblett template over a three-day hospital admission. CT-based (3D) simulation with inverse and adaptive planning was utilized for each fraction. MR prior to and MR immediately after external beam therapy were fused for HDR-ISBT target delineation. RESULTS: Forty women with an overall median follow-up of 18 months (range: 6-54 months) received an HDR-ISBT boost. Of the 30 primary cases (83% cervix, 10% vaginal, 7% uterine), 44% had organ invasion (bladder, rectal or both) on MRI. Median coverage and dose are reported (V100: 98%, HR-CTV EQD2: 85.1 Gy, D90: 92 Gy). A significant association existed between rectal doses exceeding GEC-ESTRO recommendations (D2cc < 75 Gy) and the development of grade 3 gastrointestinal toxicity with a relative risk of 1.4 [1.1-1.8] (p = .046). Actuarial two-year overall survival (OS), local control (LC) and progression-free survival (PFS) were 81%, 81% and 64%, respectively. CONCLUSIONS: A four fraction, inversely and adaptively planned, single-implant approach of image-based HDR-ISBT provides excellent coverage, minimal toxicity and effective local control in patients with advanced and recurrent disease.

Stereotactic Body Radiation Therapy, Intensity-Modulated Radiation Therapy, and Brachytherapy Boost Modalities in Invasive Cervical Cancer: A Study of the National Cancer Data Base.

BACKGROUND AND PURPOSE: Our objective was to determine whether stereotactic body radiotherapy (SBRT), intensity-modulated radiation therapy (IMRT), and brachytherapy boost techniques have comparable overall survival in treating cervical cancer when adjusted for known prognostic factors. MATERIALS AND METHODS: We used the National Cancer Database to study women with invasive cervical cancer who were treated with radiation between 2004 and 2013. A logistic regression model was built to identify factors associated with the receipt of SBRT and IMRT. Outcomes were compared using Kaplan-Meier and propensity score matching. RESULTS: Of all 15,905 patients, 14,394 (90.5%) received brachytherapy, 42 (0.8%) received SBRT, and 1468 (9.2%) received IMRT. After propensity score matching, there was no significant difference in overall survival (OS) for patients who received SBRT boost versus brachytherapy boost (hazard ratio = 1.477, 95% confidence interval = 0.746-2.926, P = 0.263) but a significant OS detriment in patients who received IMRT boost versus brachytherapy boost (hazard ratio = 1.455, 95% confidence interval = 1.300-1.628, P < 0.001). CONCLUSIONS: In a propensity-matched analysis, those who received SBRT boost had equal OS when compared with brachytherapy, but those who received IMRT boost had worse OS when compared with brachytherapy.

Factors Associated With Radiation Treatment Compliance for Women With Cervical Cancer in a Safety Net Health System.

OBJECTIVE: The aim of the study was to determine whether patient characteristics are associated with radiation treatment noncompliance. METHODS/MATERIALS: We retrospectively studied 244 patients with cervical cancer treated with chemoradiation between May 2006 and August 2015 at a safety net health center. Compliance with treatment was defined as missing less than 2 days of scheduled radiation. RESULTS: Treatment records revealed a compliance rate of 50.8% in this population. Factors associated with noncompliance were younger age (hazard ratio [HR], 1.037; P = 0.004), presence of psychiatric diagnosis (HR, 0.581; P = 0.044), and having insurance (HR, 0.484; P = 0.022). Noncompliance was associated with a decrease in disease-free survival (HR, 0.555; P = 0.042) but was not associated with overall survival. International Federation of Gynecology and Obstetrics stage was associated with detriment in overall survival on multivariate analysis (HR, 2.034; P = 0.001). CONCLUSIONS: Younger patients, those with psychiatric illness, and those with insurance define a group that is more likely to be noncompliant with treatment and hence may require up-front intervention to improve outcomes.

Treatment Compliance and Outcomes for Women With Locoregionally Advanced Cervical Cancer Treated in a Safety Net Health System.

OBJECTIVE: This study aims to assess treatment compliance among women undergoing definitive chemoradiation with weekly cisplatin for cervical cancer within a safety net health system and to quantify the impact of chemotherapy compliance on outcomes. MATERIALS AND METHODS: All women who were treated for International Federation of Gynecology and Obstetrics stage IB2 to stage IVA cervical cancer between April 2008 and May 2014 were identified. Treatment delays were attributed to toxicity, comorbid conditions, or system issues, or categorized as patient-initiated. Disease-free survival and overall survival of women who received fewer than 6 versus 6 or more doses of weekly cisplatin 40 mg/m were compared using Kaplan-Meier analyses. RESULTS: One hundred nineteen women (mean [SD] age, 48.5 [11.8] years) were identified. Most women (n = 112; 94.1%) completed definitive radiotherapy, requiring a mean (SD) of 56.5 (20.1) days. Sixty-four women (57.1%) completed definitive radiotherapy in 56 days or less. Only 44 women (36.4%) received 6 or more cycles of cisplatin. Of 122 delayed cycles, reasons for delay were as follows: grade 2 or higher toxicity (n = 70; 57.4%), medical comorbidity (n = 12; 9.8%), system issues (n = 9; 7.4%), and patient-initiated (n = 14; 11.5%). Multiple issues complicated treatment for 3 doses (2.5%). Reasons for delay were not documented in 14 doses (11.5%). Among patients who received 6 or more cycles, disease-free survival improved by 17.4 months (mean [SD], 61.1 [3.7] vs 43.7 [4.3] months, P = 0.002) and overall survival improved by 8.6 months (mean [SD], 68.7 [2.3] vs 60.1 [3.7] months, P = 0.011). CONCLUSIONS: Higher rates of toxicity and psychosocial barriers to chemotherapy compliance adversely impact survival among women who seek care in low-resource settings. In our population, administration of all 6 cycles of cisplatin was necessary for optimal survival benefit. Future efforts to improve cervical cancer outcomes should address preventable reasons for treatment delays among underinsured or uninsured individuals.

Quality Assurance for Stereotactic Body Radiation Therapy for Gynecologic Malignancies.

The use of stereotactic body radiation therapy (SBRT) is not well studied or reported in the treatment of gynecologic malignancies, despite its success in the definitive management of other cancer sites. This report describes a rigorous quality assurance process for patients to undergo dose escalation to the pelvis via stereotactic photon beam irradiation. Patients who receive SBRT must be ineligible for conventional brachytherapy boost and undergo comprehensive informed consent. Fiducial placement, bowel prep, Foley catheter placement with standardized bladder filling, computerized tomography (CT) simulation with whole-body immobilization, magnetic resonance imaging (MRI)-assisted target delineation, planning aims based on the established brachytherapy literature, and physics consultation for SBRT plan optimization are necessary. Prior to each fraction, the simulation position is reproduced and verified with on-table cone beam CT, and the position is maintained with whole-body immobilization. Following treatment, the treating physician is active in survivorship and toxicity management. Gynecologic SBRT is an ongoing area of study, and preliminary successes in delivering high-quality stereotactic dose escalation suggest prospective investigation is warranted. By adhering to strict quality control measures and following a pre-defined best standard of practice, patients with gynecologic malignancies who are ineligible for traditional brachytherapy procedures can be safely treated with SBRT.

Computational approaches for drug repurposing in oncology: untapped opportunity for high value innovation.

Historically, the effort by academia and industry to develop new chemical entities into lifesaving drugs has limited success in meeting the demands of today's healthcare. Repurposing drugs that are originally approved by the United States Food and Drug Administration or by regulatory authorities around the globe is an attractive strategy to rapidly develop much-needed therapeutics for oncologic indications that extend from treating cancer to managing treatment-related complications. This review discusses computational approaches to harness existing drugs for new therapeutic use in oncology.

Proton pump inhibitors and sensitization of cancer cells to radiation therapy.

This review article outlines six molecular pathways that confer resistance of cancer cells to ionizing radiation, and describes how proton pump inhibitors (PPIs) may be used to overcome radioresistance induced by alteration of one or more of these signaling pathways. The inflammatory, adaptive, hypoxia, DNA damage repair, cell adhesion, and developmental pathways have all been linked to the resistance of cancer cells to ionizing radiation. Here we describe the molecular link between alteration of these pathways in cancer cells and development of resistance to ionizing radiation, and discuss emerging data on the use of PPIs to favorably modify one or more components of these pathways to sensitize cancer cells to ionizing radiation. Understanding the relationship between altered signaling pathways, radioresistance, and biological activity of PPIs may serve as a basis to repurpose PPIs to restore key biological processes that are involved in cancer progression and to sensitize cancer cells to radiation therapy.

Feasibility and value of salivary cortisol sampling to reflect distress in head and neck cancer patients undergoing chemoradiation: A proof-of-concept study.

Background: Head and neck cancer (HNC) patients undergoing chemo/radiation commonly experience severe and persistent distress associated with treatment related fear and physical side effects such as xerostomia, dysphagia, and dryness of mouth. Cortisol, a stress sensitive hormone, can be easily measured in saliva to reflect biobehavioral responses to such stressors. Unfortunately, it has not been used in this population due to concerns associated with chemoradiation (C/RT) related xerostomia. Methods: In a proof-of-concept study, we explored the feasibility of collecting salivary cortisol as a marker of fear and distress in HNC patients. Ten HNC subjects undergoing C/RT provided saliva samples for 3 consecutive days across three timepoints (pre-treatment, 3-weeks and 1-month post-treatment) and completed concurrent depression, anxiety and swallowing related fear measures. Results: Salivary cortisol collection adherence was between 80-60%. It was not impacted by xerostomia. Diurnal cortisol pattern demonstrated dysregulation at pretreatment in 62%, and flattened aberrant slopes continued at 3-weeks and beyond in 50% of subjects. Conclusions: Our study supports the feasibility and utility of salivary cortisol measurement in HNC patients across the treatment trajectory. Diurnal cortisol measures may be a valuable tool to detect and monitor treatment distress during C/RT in this population.

Combination of esomeprazole and pirfenidone enhances antifibrotic efficacy in vitro and in a mouse model of TGFß-induced lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease of unknown etiology. Currently, pirfenidone and nintedanib are the only FDA-approved drugs for the treatment of IPF and are now the standard of care. This is a significant step in slowing down the progression of the disease. However, the drugs are unable to stop or reverse established fibrosis. Several retrospective clinical studies indicate that proton pump inhibitors (PPIs; FDA-approved to treat gastroesophageal reflux) are associated with favorable outcomes in patients with IPF, and emerging preclinical studies report that PPIs possess antifibrotic activity. In this study, we evaluated the antifibrotic efficacy of the PPI esomeprazole when combined with pirfenidone in vitro and in vivo. In cell culture studies of IPF lung fibroblasts, we assessed the effect of the combination on several fibrosis-related biological processes including TGFß-induced cell proliferation, cell migration, cell contraction, and collagen production. In an in vivo study, we used mouse model of TGFß-induced lung fibrosis to evaluate the antifibrotic efficacy of esomeprazole/pirfenidone combination. We also performed computational studies to understand the molecular mechanisms by which esomeprazole and/or pirfenidone regulate lung fibrosis. We found that esomeprazole significantly enhanced the anti-proliferative effect of pirfenidone and favorably modulated TGFß-induced cell migration and contraction of collagen gels. We also found that the combination significantly suppressed collagen production in response to TGFß in comparison to pirfenidone monotherapy. In addition, our animal study demonstrated that the combination therapy effectively inhibited the differentiation of lung fibroblasts into alpha smooth muscle actin (αSMA)-expressing myofibroblasts to attenuate the progression of lung fibrosis. Finally, our bioinformatics study of cells treated with esomeprazole or pirfenidone revealed that the drugs target several extracellular matrix (ECM) related pathways with esomeprazole preferentially targeting collagen family members while pirfenidone targets the keratins. In conclusion, our cell biological, computational, and in vivo studies show that the PPI esomeprazole enhances the antifibrotic efficacy of pirfenidone through complementary molecular mechanisms. This data supports the initiation of prospective clinical studies aimed at repurposing PPIs for the treatment of IPF and other fibrotic lung diseases where pirfenidone is prescribed.

Esomeprazole attenuates inflammatory and fibrotic response in lung cells through the MAPK/Nrf2/HO1 pathway.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is an orphan disease characterized by progressive loss of lung function resulting in shortness of breath and often death within 3-4 years of diagnosis. Repetitive lung injury in susceptible individuals is believed to promote chronic oxidative stress, inflammation, and uncontrolled collagen deposition. Several preclinical and retrospective clinical studies in IPF have reported beneficial outcomes associated with the use of proton pump inhibitors (PPIs) such as esomeprazole. Accordingly, we sought to investigate molecular mechanism(s) by which PPIs favorably regulate the disease process. METHODS: We stimulated oxidative stress, pro-inflammatory and profibrotic phenotypes in primary human lung epithelial cells and fibroblasts upon treatment with bleomycin or transforming growth factor ß (TGFß) and assessed the effect of a prototype PPI, esomeprazole, in regulating these processes. RESULTS: Our study shows that esomeprazole controls pro-inflammatory and profibrotic molecules through nuclear translocation of the transcription factor nuclear factor-like 2 (Nrf2) and induction of the cytoprotective molecule heme oxygenase 1 (HO1). Genetic deletion of Nrf2 or pharmacological inhibition of HO1 impaired esomeprazole-mediated regulation of proinflammatory and profibrotic molecules. Additional studies indicate that activation of Mitogen Activated Protein Kinase (MAPK) pathway is involved in the process. Our experimental data was corroborated by bioinformatics studies of an NIH chemical library which hosts gene expression profiles of IPF lung fibroblasts treated with over 20,000 compounds including esomeprazole. Intriguingly, we found 45 genes that are upregulated in IPF but downregulated by esomeprazole. Pathway analysis showed that these genes are enriched for profibrotic processes. Unbiased high throughput RNA-seq study supported antifibrotic effect of esomeprazole and revealed several novel targets. CONCLUSIONS: Taken together, PPIs may play antifibrotic role in IPF through direct regulation of the MAPK/Nrf2/HO1 pathway to favorably influence the disease process in IPF.

Esomeprazole enhances the effect of ionizing radiation to improve tumor control.

The resistance of cancer cells to radiation-based treatment is a major clinical challenge confounding standard of care in cancer. This problem is particularly notable in many solid tumors where cancer cells are only partially responsive to radiation therapy. Combination of radiation with radiosensitizers is able to enhance tumor cell killing. However, currently available radiosensitizers are associated with significant normal tissue toxicity. Accordingly, there is an unmet need to develop safer and more effective radiosensitizers to improve tumor control. Here, we evaluated the radiosensitizing effect of the FDA-approved drug esomeprazole in normal and radioresistant human head and neck squamous cell carcinoma (HNSCC) cells in vitro, and in a mouse model of HNSCC. For the in vitro studies, we used cancer cell colony formation (clonogenicity) assay to compare cancer cell growth in the absence or presence of esomeprazole. To determine mechanism(s) of action, we assessed cell proliferation and profiled cell cycle regulatory proteins. In addition, we performed reverse phase protein array (RPPA) study to understand the global effect of esomeprazole on over 200 cancer-related proteins. For the in vivo study, we engrafted HNSCC in a mouse model and compared tumor growth in animals treated with radiation, esomeprazole, and combination of radiation with esomeprazole. We found that esomeprazole inhibits tumor growth and dose-dependently enhances the cell killing effect of ionizing radiation in wildtype and p53-mutant radioresistant cancer cells. Mechanistic studies demonstrate that esomeprazole arrests cancer cells in the G1 phase of the cell cycle through upregulation of p21 protein and inhibition of cyclin-dependent kinases (Cdks) type 1 (Cdk1) and type 2 (Cdk2). In vivo data showed greater tumor control in animals treated with combination of radiation and esomeprazole compared to either treatment alone, and that this was associated with inhibition of cell proliferation in vivo. In addition, combination of esomeprazole with radiation significantly impaired repair following radiation-induced DNA damage. Our studies indicate that esomeprazole sensitizes cancer cells to ionizing radiation, and is associated with upregulation of p21 to arrest cells in the G1 phase of the cell cycle. Our findings have significant therapeutic implications for the repurposing of esomeprazole as a radiosensitizer in HNSCC and other solid tumors.

Risk of thyroid cancer after therapeutic irradiation in adult patients: An Age-Based surveillance, epidemiology, and end results analysis.

OBJECTIVES/HYPOTHESIS: One risk of radiation therapy exposure (XRTe) is second primary thyroid cancer (SPTC). Previous reports examined this in children, but no population-based studies have explored XRTe and SPTC across all ages or stratified by histological subtypes. STUDY DESIGN: Database study. METHODS: We report patient characteristics of a Surveillance, Epidemiology, and End Results (SEER) dataset of SPTC (n = 4,669) using χ2 and t tests. Odds ratio (OR) for SPTC was determined based on age, histology, and XRTe compared to expected values in the SEER database. Kaplan-Meier survival and Cox proportional hazard ratios were reported to determine factors influencing latent survival (LS; time from initial diagnosis to SPTC) and overall survival in univariate and multivariate models. RESULTS: Extrathyroid extension and node status based on XRTe were similar (P = .684 and P = .776, respectively). XRTe patients were more likely to have smaller tumors (17.6 vs. 19.3 mm, P = .007). XRTe patients were diagnosed with SPTC at younger ages (59.8 vs. 62.7 years, P < .001) without a difference in LS (7.45 vs. 7.50 years, P = .426). Patients aged 1 to 14 years and 15 to 29 years at diagnosis of first cancer are at higher risk of SPTC after XRTe (OR = 1.89, P = .005 and OR = 2.35, P = .001, respectively), unlike patients age 30 to 44 years and 45+ years (OR = 1.03, P = .823 and OR = 0.97, P = .624, respectively). This difference is not present for follicular and medullary SPTC. CONCLUSIONS: Patients aged 30+ years receiving radiation therapy (XRT) do not have an increased risk of SPTC. Deliberation is necessary in recommending, planning, and delivering XRT to minimize risk of subsequent malignancy in younger patients. LEVEL OF EVIDENCE: NA Laryngoscope, 130: 2081-2086, 2020.

Stereotactic Radiosurgery Versus Whole Brain Radiation Therapy: A Propensity Score Analysis and Predictors of Care for Patients With Brain Metastases From Breast Cancer.

BACKGROUND: Metastases to the brain occur in 10%-16% of patients with breast cancer, with incidence reportedly increasing. Historically, brain metastases (BM) have been treated with whole-brain radiation therapy (WBRT), but stereotactic radiosurgery (SRS) is an increasingly favored treatment option. In this study we used a population-level database to compare patterns of care and survival between WBRT and SRS for BM from breast cancer. MATERIALS AND METHODS: The National Cancer Database was used to select patients treated with radiation for BM from primary breast cancer. Groups were classified on the basis of the modality of radiation delivered to the brain and compared across several demographic factors. A Kaplan-Meier survival curve and Cox multivariate analysis were used to compare overall survival. A matched analysis using propensity scores was used to further reduce confounders and compare survival. RESULTS: The treatment groups were significantly different across several socioeconomic variables including income, insurance status, and treatment setting. The percentage of patients who received SRS increased dramatically in the second half of the analyzed time period (P < .001). Unadjusted median survival was significantly longer for patients who received SRS versus those who received WBRT (P < .001). This finding persisted after propensity score-matching. CONCLUSION: Receipt of SRS was associated with different socioeconomic variables and longer overall survival compared with WBRT, highlighting the need for less toxic treatment for patients who are now living longer. The results revealed important socioeconomic differences between patients selected for SRS versus WBRT and emphasizes disparities in access to modern radiation techniques across the United States.

Topical Esomeprazole Mitigates Radiation-Induced Dermal Inflammation and Fibrosis.

Radiation therapy is a mainstream strategy in the treatment of several cancer types that are surgically unresectable. Unfortunately, cancer patients often suffer from unintended consequences of radiotherapy, including the development of skin inflammation (dermatitis), which may progress to fibrosis. These morbid complications often require interruption of radiotherapy and threaten the relapse of underlying cancer. Current treatment options for radiation dermatitis are suboptimal and compel the need to develop safer, more effective therapies. In this study, we assessed the biophysical properties of topically-formulated esomeprazole (here referred to as dermaprazole) and performed proof-of-concept studies to evaluate its efficacy in vitro and in vivo. We found that dermaprazole induced nuclear translocation of erythroid 2-related factor 2 (Nrf2) and significantly upregulated heme oxygenase 1 (HO1) gene and protein expression in a 3D human skin model. Our animal study demonstrated that dermaprazole improved macroscopic appearance of the irradiated skin and accelerated healing of the wounds. Histopathology data corroborated the photographic evidence and confirmed that both prophylactically and therapeutically administered dermaprazole conferred potent anti-inflammatory and antifibrotic effects. Gene expression data showed that dermaprazole downregulated several pro-oxidant, pro-inflammatory and profibrotic genes. In conclusion, topical formulation of the FDA-approved drug esomeprazole is highly effective in attenuating dermal inflammation and fibrosis.

Silent Neoplastic Cardiac Invasion in Small Cell Lung Cancer: A Case Report and Review of the Literature.

BACKGROUND Secondary malignant tumor of the heart is one of the most life-threatening complications of lung cancer. Several published case reports have documented non-small cell lung cancer (NSCLC) patients with neoplastic cardiac invasion. However, the number of reported cases of small cell lung cancer (SCLC) with neoplastic cardiac invasion is limited. CASE REPORT We present a rare case of advanced SCLC in a patient with asymptomatic neoplastic cardiac invasion. We also discuss radiation therapy modalities that should be considered in SCLC patients with cardiac invasion. CONCLUSIONS Clinicians should be vigilant about cases of SCLC with asymptomatic intra-cardiac invasion and practice caution when diagnosing, as well as treating with radiation as a monotherapy.

Dyadic Coping in Patients Undergoing Radiotherapy for Head and Neck Cancer and Their Spouses.

Background: Head and neck cancer (HNC) adversely affects the psychological (i.e., depression, anxiety) and marital adjustment of patients and their spouses. Dyadic coping refers to how couples cope with stress. It includes positive actions like sharing practical or emotional concerns (i.e., problem- and emotion-focused stress communication; PFSC, EFSC), and engaging in problem- or emotion-focused actions to support each other (problem- and emotion-focused dyadic coping; PFDC, EFDC). It also includes negative actions like avoidance (negative dyadic coping; NEGDC). In this secondary analysis of a randomized pilot trial of a couple-based intervention called SHARE (Spouses coping with the Head And neck Radiation Experience), we first examined associations between patients' and spouses' dyadic coping (and satisfaction with dyadic coping; SATDC) and their own/each other's psychological and marital adjustment. Next, we examined the effects of SHARE relative to usual medical care (UMC) on patients' and spouses' dyadic coping. Finally, we examined whether changes in dyadic coping were associated with changes in patients' and spouses' psychological and marital adjustment. Methods and Measures: Thirty HNC patients (80% men) and their spouses (N = 60) completed baseline surveys prior to initiating radiotherapy (RT) and were randomized to SHARE or UMC. One month after RT, they completed follow-up surveys. Results: Baseline multilevel Actor-Partner Interdependence Models revealed significant actor effects of PFSC (effect size r = -0.32) and PFDC (r = -0.29) on depression. For marital adjustment, significant actor effects were found for PFSC, PFDC, EFDC, and SATDC (p < 0.05, r = 0.23 to 0.38). Actor (r = -0.35) and partner effects (r = -0.27) for NEGDC were also significant. Moderate to large effect sizes were found in favor of SHARE on PFSC (Cohen's d = 1.14), PFDC (d = 0.64), NEGDC (d = -0.68), and SATDC (d = 1.03). Improvements in PFDC were associated with reductions in depression and anxiety (p < 0.05); and, improvements in SATDC were associated with improvements in anxiety and marital adjustment (p < 0.05). Conclusion: The SHARE intervention improved positive and decreased negative dyadic coping for patients and spouses. Increases in positive dyadic coping were also associated with improvements in psychological and marital adjustment. Although findings are preliminary, more research on ways to integrate dyadic coping into oncology supportive care interventions appears warranted.