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Hybrid immunity against SARS-CoV-2 has not been well studied in pregnancy. We conducted a comprehensive analysis of neutralizing antibodies (nAb) and binding antibodies in pregnant individuals who received mRNA vaccination, natural infection, or both. A third vaccine dose augmented nAb levels compared to the two-dose regimen or natural infection alone; this effect was more pronounced in hybrid immunity. There was reduced anti-Omicron nAb, but the maternal-fetal transfer efficiency remained comparable to that of other variants. Vaccine-induced nAbs were transferred more efficiently than infection-induced nAbs. Anti-spike receptor binding domain (RBD) IgG was associated with nAb against wild-type (Wuhan-Hu-1) following breakthrough infection. Both vaccination and infection-induced anti-RBD IgA, which was more durable than anti-nucleocapsid IgA. IgA response was attenuated in pregnancy compared to non-pregnant controls. These data provide additional evidence of augmentation of humoral immune responses in hybrid immunity in pregnancy., (© 2024. The Author(s).)

Despite universal recommendations for COVID-19 mRNA vaccination in pregnancy, uptake has been lower than desired. There have been limited studies of the direct impact of COVID-19 mRNA vaccine exposure in human placental tissue. Using a primary human placental explants model, we investigated the uptake of two common mRNA vaccines (BNT162b2 Pfizer-BioNTech or mRNA-1273 Moderna), and whether exposure altered villous cytokine responses. Explants derived from second or third trimester chorionic villi were incubated with vaccines at supraphysiologic concentrations and analyzed at two time points. We observed minimal uptake of mRNA vaccines in placental explants by in situ hybridization and quantitative RT-PCR. No specific or global cytokine response was elicited by either of the mRNA vaccines in multiplexed immunoassays. Our results suggest that the human placenta does not readily absorb the COVID-19 mRNA vaccines nor generate a significant inflammatory response after exposure., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Objective: To evaluate the association between race/ethnicity, poverty, and mental health in youth with chronic conditions., Study Design: A cross-sectional comparative study was performed using the records of a tertiary care center from 2011 to 2015., Inclusion Criteria: children aged 4-17 years with ≥1 hospitalization or emergency department visit. Exclusion criteria were those with arrhythmias or treatment with clonidine/benzodiazepines. The primary outcome variable was diagnosis or medication for anxiety, depression, or attention deficit hyperactivity disorder. The primary predictor variable was diagnosis of cystic fibrosis (CF), sickle cell disease (SCD), or congenital heart disease (CHD)., Results: We identified 112 313 patients, 0.2% with CF, 0.4% with SCD, and 1.0% with CHD. Patients with CF had the highest prevalence (23%) and odds (OR, 4.21; 95% CI, 3.07-5.77) of anxiety or depression, whereas patients with SCD had the lowest prevalence (7%) and odds (OR, 1.54; 95% CI, 1.11-2.14). Those with CHD had a prevalence of up to 17%, with 3-4 times higher odds of anxiety or depression (OR, 3.70; 95% CI, 2.98-4.61). All non-White participants were less likely to be diagnosed or treated for anxiety or depression and attention deficit hyperactivity disorder. Although poverty increased the probability of anxiety or depression in patients with CHD, this finding was not seen in patients with CF or SCD., Conclusions: Children with CF, SCD, and CHD are at increased risk of anxiety or depression; however non-White patients are likely being underdiagnosed and undertreated. Increased screening and recognition in minority children are needed to decrease disparities in mental health outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Longitudinal data on COVID-19 messenger RNA (mRNA) vaccine reactogenicity and immunogenicity in pregnancy and for the mother-infant dyad are needed., Objective: To examine COVID-19 mRNA vaccine reactogenicity and immunogenicity in pregnancy and observe longitudinal maternal and infant outcomes., Design, Setting, and Participants: This prospective cohort study of pregnant individuals enrolled in the COVID-19 Vaccination in Pregnancy and Lactation study from December 1, 2020, through December 31, 2021, with follow-up through March 31, 2022, was conducted at a large academic medical center in an urban metropolitan area in California. Pregnant individuals receiving COVID-19 mRNA vaccines (mRNA-1273 [Moderna] and BNT162b2 [Pfizer-BioNTech]) were eligible. Of 81 participants enrolled, 5 were excluded after enrollment: 1 terminated pregnancy, 1 received the third vaccine dose prior to delivery, and 3 delivered prior to completing the initial vaccine series., Exposure: COVID-19 mRNA vaccination at any time during pregnancy., Main Outcomes and Measures: The primary outcomes were vaccine response as measured by blood Immunoglobulin G (IgG) titers after each vaccine dose and self-reported postvaccination symptoms. Patients' IgG titers were measured in cord blood and in infant blood at intervals up to 1 year of life; IgG and IgA titers were measured in maternal milk. Clinical outcomes were collected from medical records., Results: Of 76 pregnant individuals included in final analyses (median [IQR] maternal age, 35 [29-41] years; 51 [67.1%] White; 28 [36.8%] primigravid; 37 [48.7%] nulliparous), 42 (55.3%) received BNT162b2 and 34 (44.7%) received mRNA-1237. There were no significant differences in maternal characteristics between the 2 vaccine groups. Systemic symptoms were more common after receipt of the second vaccine dose than after the first dose (42 of 59 [71.2%] vs 26 of 59 [44.1%]; P = .007) and after mRNA-1237 than after BNT162b2 (25 of 27 [92.6%] vs 17 of 32 53.1%; P = .001). Systemic symptoms were associated with 65.6% higher median IgG titers than no symptoms after the second vaccine dose (median [IQR], 2596 [1840-4455] vs 1568 [1114-4518] RFU; P = .007); mean cord titers in individuals with local or systemic symptoms were 6.3-fold higher than in individuals without symptoms. Vaccination in all trimesters elicited a robust maternal IgG response. The IgG transfer ratio was highest among individuals vaccinated in the second trimester. Anti-SARS-CoV-2 IgG was detectable in cord blood regardless of vaccination trimester. In milk, IgG and IgA titers remained above the positive cutoff for at least 5-6 months after birth, and infants of mothers vaccinated in the second and third trimesters had positive IgG titers for at least 5 to 6 months of life. There were no vaccine-attributable adverse perinatal outcomes., Conclusions and Relevance: The findings of this cohort study suggest that mRNA COVID-19 vaccination in pregnancy provokes a robust IgG response for the mother-infant dyad for approximately 6 months after birth. Postvaccination symptoms may indicate a more robust immune response, without adverse maternal, fetal, or neonatal outcomes.

Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. Here, we evaluate the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during late pregnancy. We find no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we find time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persists during early infancy. Additionally, using phage immunoprecipitation sequencing, we find a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. Timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy., (© 2022. The Author(s).)

Pregnancy confers unique immune responses to infection and vaccination across gestation. To date, there are limited data comparing vaccine- and infection-induced neutralizing Abs (nAbs) against COVID-19 variants in mothers during pregnancy. We analyzed paired maternal and cord plasma samples from 60 pregnant individuals. Thirty women vaccinated with mRNA vaccines (from December 2020 through August 2021) were matched with 30 naturally infected women (from March 2020 through January 2021) by gestational age of exposure. Neutralization activity against the 5 SARS-CoV-2 spike sequences was measured by a SARS-CoV-2-pseudotyped spike virion assay. Effective nAbs against SARS-CoV-2 were present in maternal and cord plasma after both infection and vaccination. Compared with WT spike protein, these nAbs were less effective against the Delta and Mu spike variants. Vaccination during the third trimester induced higher cord-nAb levels at delivery than did infection during the third trimester. In contrast, vaccine-induced nAb levels were lower at the time of delivery compared with infection during the first trimester. The transfer ratio (cord nAb level divided by maternal nAb level) was greatest in mothers vaccinated in the second trimester. SARS-CoV-2 vaccination or infection in pregnancy elicits effective nAbs with differing neutralization kinetics that are influenced by gestational time of exposure.

Background: Data regarding symptoms in the lactating mother-infant dyad and their immune response to COVID-19 mRNA vaccination during lactation are needed to inform vaccination guidelines., Methods: From a prospective cohort of 50 lactating individuals who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. Symptoms in mother and infant were assessed by detailed questionnaires. Anti-SARS-CoV-2 antibody levels in blood and milk were measured by Pylon 3D automated immunoassay and ELISA. In addition, vaccine-related PEGylated proteins in milk were measured by ELISA. Blood samples were collected from a subset of infants whose mothers received the vaccine during lactation (4-15 weeks after mothers' 2nd dose)., Results: No severe maternal or infant adverse events were reported in this cohort. Two mothers and two infants were diagnosed with COVID-19 during the study period before achieving full immune response. PEGylated proteins were not found at significant levels in milk after vaccination. After vaccination, levels of anti-SARS-CoV-2 IgG and IgM significantly increased in maternal plasma and there was significant transfer of anti-SARS-CoV-2-Receptor Binding Domain (anti-RBD) IgA and IgG antibodies to milk. Milk IgA levels after the 2nd dose were negatively associated with infant age. Anti-SARS-CoV-2 IgG antibodies were not detected in the plasma of infants whose mothers were vaccinated during lactation., Conclusions: COVID-19 mRNA vaccines generate robust immune responses in plasma and milk of lactating individuals without severe adverse events reported., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Golan, Prahl, Cassidy, Gay, Wu, Jigmeddagva, Lin, Gonzalez, Basilio, Chidboy, Warrier, Buarpung, Li, Murtha, Asiodu, Ahituv, Flaherman and Gaw.)

Background: With advances in treatment, outcomes for early-stage breast cancer are improving. We investigated the combination of prone position and deep inspiration breath hold to decrease cardiac doses for left-sided breast radiotherapy., Material and Methods: Fifteen patients with left-sided breast cancer were enrolled on a single-institution prospective study. Each patient underwent 2 prone positioned computed tomography simulation scans utilizing free breathing and breath-hold. Separate treatment plans for each computed tomography simulation scan were created using tangential fields, and heart and left lung doses were compared between free breathing and breath-hold plans. The technique with the lower mean dose for the heart was used for treatment. All patients were treated with a hypofractionated regimen of 40 to 42 Gy in 15 to 16 fractions, followed by a lumpectomy cavity boost of 10 Gy in 5 fractions when indicated. Wilcoxon paired signed rank tests and paired t tests were performed for statistical analysis of dosimetric endpoints., Results: The median age of our patients was 58 years (range, 40-72 years). One patient was not able to tolerate prone positioning at simulation, leaving 14 patients with evaluable paired scans. The average mean heart dose with free breathing and with breath-hold was 0.93 Gy and 0.72 Gy, respectively (P = .0063). The average max heart dose with free breathing and with breath-hold was 15.70 Gy and 7.19 Gy, respectively (P = .001). The average mean left lung dose with free breathing and with breath-hold was 0.65 Gy and 0.88 Gy, respectively (P = .011)., Conclusions: Our results indicate that breath-hold using the real-time position management system may provide additional cardiac dose reduction in patients receiving prone left-breast radiotherapy treated with tangential fields., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To investigate maternal immunoglobulins' (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterise neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively and passively acquired antibodies in infants., Design: A prospective observational study., Setting: Public healthcare system in Santa Clara County (California, USA)., Participants: Women with symptomatic or asymptomatic SARS-CoV-2 infection during pregnancy and their infants were enrolled between 15 April 2020 and 31 March 2021., Outcomes: SARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life., Results: Of 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and 8 with severe-critical symptoms. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56% to 0.73%) and the cord blood was 58% (95% CI 0.49% to 0.66%). IgG levels significantly correlated between the maternal and cord blood (Rs=0.93, p<0.0001). IgG transplacental transfer ratio was significantly higher when the first maternal positive PCR was 60-180 days before delivery compared with <60 days (1.2 vs 0.6, p<0.0001). Infant IgG seroreversion rates over follow-up periods of 1-4, 5-12, and 13-28 weeks were 8% (4 of 48), 12% (3 of 25), and 38% (5 of 13), respectively. The IgG seropositivity in the infants was positively related to IgG levels in the cord blood and persisted up to 6 months of age. Two newborns showed seroconversion at 2 weeks of age with high levels of IgM and IgG, including one premature infant with confirmed intrapartum infection., Conclusions: Maternal SARS-CoV-2 IgG is efficiently transferred across the placenta when infections occur more than 2 months before delivery. Maternally derived passive immunity may persist in infants up to 6 months of life. Neonates are capable of mounting a strong antibody response to perinatal SARS-CoV-2 infection., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: AUTHOR DISCLOSUREThe authors have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.

Background: Data on anxiety, depression, and attention-deficit/hyperactivity disorder (ADHD) are lacking for youth with congenital heart disease (CHD), particularly those with simple CHD. This study aims to characterize these disorders in youth with CHD compared to those without CHD., Methods: A comparative cross-sectional study was conducted by using the electronic medical records of a large tertiary care hospital between 2011 and 2016. Inclusion criteria were youth aged 4 to 17 years with >1 hospitalization or emergency department visits. Exclusion criteria were patients with arrhythmias or treatment with clonidine and/or benzodiazepines. The primary predictor variable was CHD type: simple, complex nonsingle ventricle, and complex single ventricle. The primary outcome variable was a diagnosis and/or medication for anxiety and/or depression or ADHD. Data were analyzed by using logistic regression (Stata v15; Stata Corp, College Station, TX)., Results: We identified 118 785 patients, 1164 with CHD. Overall, 18.2% ( n = 212) of patients with CHD had a diagnosis or medication for anxiety or depression, compared with 5.2% ( n = 6088) of those without CHD. All youth with CHD had significantly higher odds of anxiety and/or depression or ADHD. Children aged 4 to 9 years with simple CHD had ∼5 times higher odds (odds ratio: 5.23; 95% confidence interval: 3.87-7.07) and those with complex single ventricle CHD had ∼7 times higher odds (odds ratio: 7.46; 95% confidence interval: 3.70-15.07) of diagnosis or treatment for anxiety and/or depression. Minority and uninsured youth were significantly less likely to be diagnosed or treated for anxiety and/or depression or ADHD, regardless of disease severity., Conclusions: Youth with CHD of all severities have significantly higher odds of anxiety and/or depression and ADHD compared to those without CHD. Screening for these conditions should be considered in all patients with CHD., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Pleomorphic invasive lobular carcinoma (PILC) is a distinct morphological and biologically aggressive variant of invasive lobular carcinoma (ILC). We hypothesized that was due to de novo activation of PI3K/Akt/mTOR pathway in PILC resulting in higher proliferation rate and markers of cell cycle activation. We identified PILC and ILC tumors and tested for PI3K/Akt/mTOR pathway activation by immunohistochemistry (PTEN and pS6K1) and gene expression analysis (by Nanostring nCounter system). Proliferation index (Ki67) was elevated in 85% of PILCs compared to 20% of ILCs ( p < 0.007). PTEN expression was high in all while pS6K1 was high in 8/9 PILCs compared to 3/9 ILCs ( p < 0.007). Gene expression analysis shows that PILCs have overexpression of genes involved in cell cycle proliferation, cellular proliferation, DNA damage, and repair genes but no difference in PI3K/Akt/mTOR pathway genes. PILCs are a biologically distinct group of ILC, and clinicopathological characteristics suggest they would have a more clinically aggressive behavior. In addition, our results indicate that PI3k/Akt/mTOR pathway and cell cycle proliferation are activated in majority of these tumors. Further studies are needed to investigate these mechanisms as there are approved therapies available that may benefit PILCs., Competing Interests: Jennifer Segar and Ritu Pandey declare no conflict of interest. Pavani Chalasani reports research funding from Pfizer, advisory boards participation for Novartis, Heron Therapeutics, Nanostring Technologies, Amgen, Bayer, Astrazeneca, Daiichi Sanko, Asthenex, and Zentalis., (Copyright © 2020 Jennifer M. Segar et al.)

Objective: To examine the relationship of the symptoms of diarrhea and fatigue by testing a model that included multiple dimensions of the cancer related-symptom experience., Methods: A secondary data analysis was conducted on data from the self-reports of 102 cancer patients co experiencing diarrhea and fatigue during treatment at a comprehensive cancer center in the Southeastern United States. Structural equational modeling was employed to examine the relationship between the 2variables. Fatigue and diarrhea were assessed using items from the Cancer Symptom Scale., Results: The structural model results showed that (a) the model fit was adequate (b) diarrhea explained 7% of the variance in fatigue, and (c) the structural or path coefficient between diarrhea and fatigue was significant (0.267; p<0.05). Diarrhea had the strongest effect on fatigue interference (0.251)., Conclusion: Diarrhea is a potential contributing factor to the symptom of fatigue and a potential target for interventions to prevent and ameliorate fatigue.

Introduction: The purpose of this study was to assess effects of three different educational intervention arms on knowledge of and intention to receive Pap testing and HPV co-testing., Methods: Three active educational intervention arms were developed: a fotonovela, a radionovela, and a digital story. A pilot randomized controlled trial of 160 Latinas was conducted to assess the effectiveness of the intervention arms in increasing knowledge of cervical cancer and HPV and intention to be screened for cervical cancer compared to an attention control group (flu vaccination)., Results: Women in all three treatment arms significantly increased knowledge about cervical cancer compared to control arm (p = 0.02). Knowledge about cervical cancer screening also increased in the active arms compared to control (p = 0.0003). Knowledge of HPV risk also increased relative to the control (p = 0.0001). There were no significant differences between the intervention arms in increased knowledge of cervical cancer or cervical cancer screening (p = 0.57 and 0.16, respectively)., Discussion: This study supported the use of small media interventions in narrative education form as effective in increasing knowledge and intention to be screened for cervical cancer. The three culturally relevant interventions, built on qualitative data, were all successful in increasing knowledge.

Aims and Objectives: To describe differences in fatigue severity in a sample of adult Puerto Rican patients during and postcancer treatments., Background: Hispanics, including Puerto Ricans, are an understudied population who are under-represented in clinical trials, especially in symptom research. Although symptom management is a clinical priority in oncology care, treatment-related differences in Puerto Rican cancer patients' report of fatigue severity have not been well described., Design/methods: A cross-sectional survey was conducted from data of self-report of 138 Puerto Rican patients during and postcancer treatments at two ambulatory facilities located in San Juan, Puerto Rico. Fatigue severity was assessed using the Fatigue subscale from the Functional Assessment of Cancer Therapy-Fatigue quality of life questionnaire Spanish version. Differences in fatigue severity across type of treatment (radiation therapy, chemotherapy, combined radiation chemotherapy and post-treatment) were evaluated using nonparametric (Kruskal-Wallis and Mann-Whitney test) statistical tests., Results: The majority of the participants had prostate (33%) and breast (32%) cancers and were receiving radiation therapy (43%) or chemotherapy (28%). The Kruskal-Wallis test showed that there was a statistically significant difference in fatigue scores between the different four treatment conditions, χ 2 (3) = 39.1, p = .001 with patients on combined radiation chemotherapy or chemotherapy alone experiencing more severe fatigue., Conclusions: Findings from the current study suggest that type of treatment is a key component of the symptom burden of fatigue among the Puerto Rican oncology population. Specially, patients receiving combined therapy or chemotherapy alone were at increased risk for experiencing severe fatigue, compared to radiation therapy and post-treatment patients., Relevance to Clinical Practice: With the worldwide increase in migration of Puerto Rican families, nurses need to recognise that type of treatment is a key component of the symptom burden of fatigue among the Puerto Rican population. The results of this study will improve understanding of treatment-related fatigue to identify therapeutic targets and improve quality of life of patients., (© 2017 John Wiley & Sons Ltd.)

Objective: To examine the health related quality of life (HRQOL) experienced by 79 Puerto Rican adults during cancer treatments., Methods: This study used a descriptive, cross-sectional design. Participants completed a demographics form and the Functional Assessment of Cancer Therapy-General QOL questionnaire (FACT-G). Descriptive statistics were generated., Results: Participants were ages 28-78; most of the participants had breast (38.0%), prostate (14.0%) and cervical and ovarian cancers (10.1%) treated with chemotherapy (45.6%). The participants had a mean total score on the FACT-G of 75.2 (SD = 18.9). As a group, the functional well-being was the most affected (mean 17.2, SD 6.8), and the Social/Familial was the least affected (mean 20.7, SD 6.0)., Conclusion: Cancer is the leading cause of death in the island of Puerto Rico. Female Puerto Rican cancer patients in this study sample had increased risk for experiencing worse: overall HRQOL, physical well-being and emotional well-being compared to males. Given that the Hispanic oncology population does not always report symptoms, risking under-assessment and under management, this suggests there may be a greater need for HRQOL surveillance for this population.

Genetic factors that influence inflammation and energy production/expenditure in cells may affect patient outcomes following treatment with external beam radiation therapy (EBRT). Sestrins, stress-inducible genes with antioxidant properties, have recently been implicated in several behaviors including fatigue. This proof-of-concept study explored whether the sestrin family of genes ( SESN1, SESN2, and SESN3) were differentially expressed from baseline to the midpoint of EBRT in a sample of 26 Puerto Rican men with nonmetastatic prostate cancer. We also examined whether changes in expression of these genes were associated with changes in fatigue scores during EBRT., Method: Participants completed the 13-item Functional Assessment of Cancer Therapy-Fatigue subscale, Spanish version. Whole blood samples were collected at baseline and at the midpoint of EBRT. Gene expression data were analyzed using the limma package in the R (version R 2.14.0.) statistical software. Linear models and empirical Bayes moderation, adjusted for radiation fraction (total number of days of prescribed radiation treatment), were used to examine potential associations between changes in gene expression and change in fatigue scores., Results: Expression of SESN3 (adjusted p < .01, log fold change -0.649) was significantly downregulated during EBRT, whereas the expressions of SESN1 and SESN2 remained unchanged. After adjustment for radiation fraction, change in SESN3 expression was associated with change in fatigue during EBRT (false discovery rate <.01)., Conclusions: Downregulation of SESN3, a novel pharmacoactive stress response gene, was associated with fatigue intensification during EBRT. SESN3 may serve as an interventional target and a biomarker for the cellular and molecular events associated with EBRT-related fatigue.

Objective: To examine the trajectory of fatigue experienced by 26 Puerto Rican (PR) men over the course of External Beam Radiation Therapy (EBRT) and to assess gene expression changes from baseline to midpoint of EBRT using microarray technology. Design/Research Approach- Prospective exploratory and comparative design study. Setting- RT facility located in San Juan, PR. Sample/Participants-26 PR men with non-metastatic prostate cancer., Methods: Participants completed 2 paper forms: demographics and the Spanish version of the 13-item FACT-fatigue at baseline, midpoint, and end of EBRT. Wholeblood samples were collected at baseline and at midpoint of EBRT. Descriptive data was analyzed using t-test, Wilcoxon, and Friedman test for repeated measures. Gene expression data was analyzed using the LIMMA package in R; the functional network analysis was conducted using Ingenuity Pathway analysis. Main Research Variable-Fatigue scores, gene expression., Results: Subjects were of ages 52-81 with fatigue scores that remained unchanged during EBRT (baseline=42.38, SD=9.34; midpoint=42.11, SD=8.93, endpoint=43.04, SD=8.62). Three hundred seventy-three genes (130-up regulated and 243-down regulated) were differentially expressed from baseline to mid-point of EBRT (FDR<0.01). The top distinct canonical pathways of the differentially expressed probesets (p<0.0001) were: "Phospholipase C Signaling," "Role of NFAT in Regulation of the Immune Response," and "Gαq Signaling.", Conclusion: While fatigue did not worsen over the course of EBRT for this sample as a group, there was variability in fatigue across the sample. It is possible that the over expression of the SESN3 gene, known to suppress oxidative damage, may have contributed to the attenuation of fatigue in this clinical population.

Purpose: Breast fibrosis is a common late effect after therapeutic irradiation that can result in pain, poor cosmesis, and functional impairment. Randomized trials have demonstrated that radiation fibrosis may be preventable with a medication regimen of pentoxifylline and vitamin E. This study investigates patient compliance with pentoxifylline therapy while examining possible correlations to compliance., Methods and Materials: We identified 90 patients who were prescribed pentoxifylline (400 mg 3 times daily) and vitamin E (400 IU once daily) after adjuvant breast radiation. A retrospective cohort study was conducted using medical record analysis. Data were collected, including patient age, comorbid conditions, concurrent medications, duration of pentoxifylline and vitamin E therapy, dose adjustments, patient-reported side effects, and cause for discontinuation. A multivariate analysis of the correlation between medication compliance and these categorical variables was assessed with a χ 2 analysis of independence., Results: Patient compliance with pentoxifylline and vitamin E therapy was found to be poor in 33 of 87 patients (38%) in the cohort, necessitating either dose reductions or discontinuation of therapy. There was a statistically significant correlation between concurrent antiemetic therapy and successful completion of pentoxifylline regimen. Of those on antiemetic therapy, 89% completed pentoxifylline as prescribed versus 48% of those without antiemetics ( P  < .001). There was a statistically significant correlation between concurrent proton pump inhibitor (PPI) therapy and discontinuation of pentoxifylline. Of those on PPI therapy, 33% completed pentoxifylline versus 81% of those not on PPIs ( P  < .001). All other variables examined were not significantly correlated with compliance., Conclusions: Patient compliance with pentoxifylline appears to be worse in clinical practice compared with previously published studies. Nausea was the most frequently reported indication for treatment modification or discontinuation. Concurrent antiemetic therapy was correlated with strong regimen compliance, but concurrent PPI therapy was correlated with poor compliance, independent of comorbid conditions.

Objective: Although opportunities to vaccinate against human papillomavirus (HPV) are available, vaccination rates in Puerto Rico remain low. Communication between parents and adolescents about sexual topics may influence decisions about HPV vaccination uptake, particularly among young women; yet, few studies have addressed this issue. This qualitative study explored Puerto Rican mothers' and daughters' communication on sex-related topics, and HPV, including the HPV vaccine., Design: Thirty participants, including 9 mothers and 21 daughters, participated in seven focus groups. Participants were divided into groups of mothers and daughters, and further stratified by vaccination status. Transcripts were analyzed using a modified grounded theory approach to identify emergent themes., Results: Focus group data revealed four main themes: (1) limited parent-daughter communication about sex-related topics; (2) daughters' discomfort discussing sex-related topics with their parents; (3) parental focus on abstinence; and, (4) limited parent-daughter communication about HPV and the HPV vaccine., Conclusion: Although daughters in this study struggled with feelings of embarrassment, invasion of privacy, encouragement of abstinence, and the fear of parents' reaction to them being sexually active prior to marriage, they also recognized the need to increase the parent-daughter communication about sex-related topics including HPV and the HPV vaccine. Educational efforts should target both daughters and parents to increase communication skills and self-efficacy and to enable them to discuss sexual health in open and nonjudgmental conversations.

Radiation therapy has historically been the pillar of curative treatment for Hodgkin lymphoma (HL). With improved efficacy of systemic therapy and the ever-increasing recognition of treatment-related morbidity in long-term survivors, the role of radiotherapy has evolved significantly. Modern combined modality therapy (CMT) with multi-agent chemotherapy followed by involved site radiation therapy (ISRT) to initially involved sites of disease remains the gold standard for the majority of patients with HL. Reduction of long-term treatment-related toxicity has become the major driver in clinical trial design for early-stage HL while improved disease-specific survival remains the goal in patients with more advanced and unfavorable disease. This review will address the data supporting the use of radiotherapy in HL as well as specific methods for reducing late toxicity from radiotherapy.

Purpose: To investigate Axxent (iCAD, Inc., San Jose, CA) electronic brachytherapy balloon deformation and its dosimetric impact because of an external flexible shield (FlexiShield [FS]; iCAD, Inc.)., Methods and Materials: Prostheses breast tissue phantom overlaid three spherical balloon applicators to simulate three clinical scenarios depending on minimum skin-to-balloon surface spacing (SS): balloon with SS of 2 cm, 1 cm, and balloon with 1 cm SS and touching the chest wall. Two sets of megavoltage CT (MVCT) scans were obtained with or without FS for 15 different sizes of balloons. For 45 pairs of MVCT scans, balloon deformation was measured in superior-inferior (d SI ) dimension on coronal and sagittal planes and anterior-posterior (d AP ) and lateral (d LAT ) dimensions on the equatorial plane of balloon. SS was also compared. A treatment plan was made on each MVCT scan. Doses at four balloon surface points and skin were compared. Conformity index value was also compared to evaluate three-dimensional dose distribution. Clinically, 20 Gy was prescribed to the surface of balloon., Results: Balloon deformation was observed with compression in SI and AP dimensions and expansion in lateral dimension. Average SI compression was 0.5 mm. Average d Lat - d AP was 2.4 mm, which resulted in elevated point doses at AP dimension by 10.8% of prescribed dose and reduced point doses at lateral dimension by 4.6%. FS decreased SS by 1.8 mm, increasing skin dose by 1.2 Gy, on average. Conformity index value was decreased from 0.922 to 0.908, on average., Conclusions: This phantom study demonstrates that use of skin shielding during breast intraoperative radiation therapy can cause balloon deformation and SS reduction, resulting in dosimetric changes that are disregarded in current practice., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Latinas have the highest rates of cervical cancer in the United States and the second highest rate of cervical cancer mortality. One factor in the disparity is the relatively low rate of screening for cervical cancer in this population., Methods: Eligible women who were out of adherence with cervical cancer screening (>3 years since their last Papanicolaou [Pap] test) were identified via medical record review by a federally qualified local health center. The effects of a low-intensity intervention (video delivered to participants' homes; n = 150) and a high-intensity intervention (video plus a home-based educational session; n = 146) on cervical cancer screening uptake in comparison with a control arm (usual care; n = 147) were investigated. A cost-effectiveness analysis of the interventions was conducted: all intervention costs were calculated, and the incremental cost-effectiveness ratio was computed. Finally, women with positive Pap tests were provided navigation by a community health educator to ensure that they received follow-up care., Results: A total of 443 Latinas participated. Seven months after randomization, significantly more women in the high-intensity arm received a Pap test (53.4%) in comparison with the low-intensity arm (38.7%; P < .001) and the usual-care arm (34.0%; P < .01). The incremental cost-effectiveness ratio for high-intensity women versus the control group amounted to $4.24. Twelve women had positive Pap tests, which encompassed diagnoses ranging from atypical squamous cells of unknown significance to invasive cancer; these women received navigation for follow-up care., Conclusions: A culturally appropriate, in-home, promotora-led educational intervention was successful in increasing cervical cancer screening among Latinas. Cancer 2017;123:666-674. © 2016 American Cancer Society., Competing Interests: The authors have no conflicts of interest to report, (© 2016 American Cancer Society.)

Background: Prostate cancer is the most frequently diagnosed cancer in men in Puerto Rico, and external beam radiation therapy (EBRT) is a popular treatment. Although symptom management is a clinical priority of comprehensive oncology care, symptom assessment at the time of primary or adjuvant EBRT has received limited attention., Objectives: This article examines the prevalence and severity of symptoms experienced by 54 Puerto Rican men prior to EBRT., Methods: Participants completed a demographic form and the MD Anderson Symptom Inventory. Descriptive statistics were generated., Findings: Most participants had received hormonal treatment, and about a third had received no treatment prior to EBRT. About a third of those who received hormonal treatment reported experiencing side effects before EBRT, and disturbed sleep, numbness and tingling, fatigue, and dry mouth were the most severe. Puerto Rican men with prostate cancer who receive hormonal treatment are at increased risk for experiencing symptom burden prior to EBRT. Greater need for symptom surveillance, treatment, and control may be needed among this population.

Purpose: To report the results of a prospective study that compares small bowel doses during prone and supine pelvic intensity modulated radiation therapy., Methods and Materials: Ten patients receiving pelvic radiation therapy each had 2 intensity modulated radiation therapy plans generated: supine and prone on a belly board (PBB). Computed tomography on rails was performed weekly throughout treatment in both positions (10 scans per patient). After image fusion, doses to small bowel (SB) loops and clinical target volume were calculated for each scan. Changes between the planned and received doses were analyzed and compared between positions. The impact of bladder filling on SB dose was also assessed., Results: Prone treatment was associated with significantly lower volumes of SB receiving ≥20 Gy. On average, prone on a belly board positioning reduced the volume of SB receiving a given dose of radiation by 28% compared with supine positioning. Target coverage throughout the treatment course was similar in both positions with an average minimum clinical target volume dose of 88% of the prescribed prone dose and 89% of the supine ( P = .54). For supine treatment, SB dose was inversely correlated with bladder filling ( P = .001-.013; P > .15 for prone). For 96% of treatments, the volume of SB that received a given dose deviated >10% from the plan. The deviation between the planned and delivered doses to SB did not differ significantly between the positions., Conclusions: Prone positioning on a belly board during pelvic IMRT consistently reduces the volume of SB that receives a broad range of radiation doses. Prone IMRT is associated with interfraction dose variation to SB that is similar to that of supine positioning. These findings suggest that prone positioning with daily image guided radiation therapy is an effective method for maximizing SB sparing during pelvic IMRT.

Purpose: Clinical evaluation of a "virtual" methodology for providing 6 degrees of freedom (6DOF) patient set-up corrections and comparison to corrections facilitated by a 6DOF robotic couch., Methods: A total of 55 weekly in-room image-guidance computed tomographic (CT) scans were acquired using a CT-on-rails for 11 pelvic and head and neck cancer patients treated at our facility. Fusion of the CT-of-the-day to the simulation CT allowed prototype virtual 6DOF correction software to calculate the translations, single couch yaw, and beam-specific gantry and collimator rotations necessary to effectively reproduce the same corrections as a 6DOF robotic couch. These corrections were then used to modify the original treatment plan beam geometry and this modified plan geometry was applied to the CT-of-the-day to evaluate the dosimetric effects of the virtual correction method. This virtual correction dosimetry was compared with calculated geometric and dosimetric results for an explicit 6DOF robotic couch correction methodology., Results: A (2%, 2mm) gamma analysis comparing dose distributions created using the virtual corrections to those from explicit corrections showed that an average of 95.1% of all points had a gamma of 1 or less, with a standard deviation of 3.4%. For a total of 470 dosimetric metrics (ie, maximum and mean dose statistics for all relevant structures) compared for all 55 image-guidance sessions, the average dose difference for these metrics between the plans employing the virtual corrections and the explicit corrections was -0.12% with a standard deviation of 0.82%; 97.9% of all metrics were within 2%., Conclusions: Results showed that the virtual corrections yielded dosimetric distributions that were essentially equivalent to those obtained when 6DOF robotic corrections were used, and that always outperformed the most commonly employed clinical approach of 3 translations only. This suggests that for the patient datasets studied here, highly effective image-guidance corrections can be made without the use of a robotic couch., (Copyright © 2012 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

High energy X-rays have been used for cancer therapy since their discovery in 1895. Major radiobiological discoveries and technological advances in radiation physics have greatly increased the accuracy of radiation. The recent integration of radiation therapy and imaging systems provides radiation oncologists with sophisticated dose delivery capability allowing continued improvements in the control of loco-regional and metastatic disease while decreasing toxicity. Key technical aspects of current radiation therapy are described with examples extending to several clinical areas., (Copyright © 2011 Wiley-Liss, Inc.)

Introduction: No prospective randomized trials exist to delineate the role of combined chemoradiotherapy (CRT) in the treatment of vaginal cancer (VC). We sought to describe the utilization rate of CRT and evaluate the potential survival benefit of CRT over radiotherapy alone in VC., Methods: A retrospective analysis of the SEER-Medicare-linked database was performed analyzing women with VC treated with external beam radiation and/or brachytherapy and diagnosed between 1991 and 2005., Results: Of the 1709 primary VC patients in the SEER-Medicare database, 326 met inclusion criteria. Most were white (80.1%) and in the 70- to 74-year age group (42.1%). Squamous cell carcinoma was the most predominant histologic diagnosis (80.4%). Brachytherapy was used in 34% of patients, whereas cisplatin was the chemotherapy of choice in 59% of CRT patients. Median follow-up was 21.5 months. Kaplan-Meier estimated that 5-year cause-specific survival (CSS) and overall survival (OS) was 67.6% and 27.1%, respectively. Before 1999, CRT was used in 7.5% of patients compared with 36.1% of patients thereafter (P < 0.001). Chemoradiotherapy was less likely to be used in patients older than 80 years (P < 0.001) but was otherwise balanced in race, stage, grade, histologic diagnosis, comorbidities, and brachytherapy use. Chemoradiotherapy did not correlate with CSS (hazard ratio [HR], 0.91; P = 0.84) or OS (HR, 1.34; P = 0.21) by multivariate analysis. Factors associated with worse CSS include stage IVA disease (HR, 4.2; P = 0.003) and 2 or more comorbidities (HR, 2.89; P = 0.03). Factors associated with worse OS include age older than 80 years (HR, 1.78; P = 0.04), stage IVA disease (HR, 3.35; P < 0.0001), and 2 or more comorbidities (HR, 2.58; P = 0.001)., Conclusions: Chemoradiotherapy utilization for VC has increased since 1999. We failed to delineate a CSS or OS benefit for CRT in this cohort.

Purpose: To evaluate two different techniques for whole-breast treatments delivered using the Hi-ART II tomotherapy device., Methods and Materials: Tomotherapy uses the standard rotational helical delivery. Topotherapy uses a stationary gantry while delivering intensity-modulated treatments. CT scans from 5 breast cancer patients were used. The prescription dose was 50.4 Gy., Results: On average, 99% of the target volume received 95% of prescribed dose with either technique. If treatment times are restricted to less than 9 min, the average percentage ipsilateral lung receiving > or =20 Gy was 22% for tomotherapy vs. 10% for topotherapy. The ipsilateral lung receiving > or =50.4 Gy was 4 cc for tomotherapy vs. 27 cc for topotherapy. The percentage of left ventricle receiving > or =30 Gy was 14% with tomotherapy vs. 4% for topotherapy. The average doses to the contralateral breast and lung were 0.6 and 0.8 Gy, respectively, for tomotherapy vs. 0.4 and 0.3 Gy for topotherapy., Conclusions: Tomotherapy provides improved target dose homogeneity and conformality over topotherapy. If delivery times are restricted, topotherapy reduces the amount of heart and ipsilateral lung volumes receiving low doses. For whole-breast treatments, topotherapy is an efficient technique that achieves adequate target uniformity while maintaining low doses to sensitive structures.