Multiplex Immunofluorescence Captures Progressive Immune Exhaustion with Advancing Penile Squamous Cell Cancer Stage.

Penile squamous cell carcinoma (PSCC) is a rare and deadly malignancy. Therapeutic advances have been stifled by a poor understanding of disease biology. Specifically, the immune microenvironment is an underexplored component in PSCC and the activity of immune checkpoint inhibitors observed in a subset of patients suggests immune escape may play an important role in tumorigenesis. Herein, we explored for the first time the immune microenvironment of 57 men with PSCC and how it varies with the presence of human papillomavirus (HPV) infection and across tumor stages using multiplex immunofluorescence of key immune cell markers. We observed an increase in the density of immune effector cells in node-negative tumors and a progressive rise in inhibitory immune players such as type 2 macrophages and upregulation of the PD-L1 checkpoint in men with N1 and N2-3 disease. There were no differences in immune cell densities with HPV status.

Factors Associated With Node-Positive Disease in Estrogen Receptor-Positive Breast Cancer Patients.

INTRODUCTION: Larger tumor size and shorter tumor-to-nipple distance at diagnosis are associated with greater risk of lymph node involvement in breast cancer. However, the relationship between receptor subtype status and lymph node metastasis remains unclear. Our objective was to examine the association between primary tumor size, location, and nodal metastasis across estrogen receptor (ER)+/ progesterone receptor (PR)+/ human epidermal growth factor receptor 2 (HER2)-, ER+/PR-/HER2-, ER+/PR+/HER2+, and ER+/PR-/HER2+ tumors. METHODS: A single-institution retrospective chart review was conducted of breast cancer patients diagnosed between 1998 and 2019 who underwent nodal evaluation during primary surgery. Neoadjuvant chemotherapy, pure ductal carcinoma in situ, inflammatory, recurrent, metastatic, bilateral, multicentric, and multifocal disease were excluded. Descriptive statistics (proportions and frequencies for categorical variables and medians [Q1-Q3] for continuous variables) were used to summarize patient characteristics. Kruskal-Wallis test was applied to test the association of outcome variables and continuous variables. Chi-square test or Fisher exact test was applied to test the association of outcome variables and categorical variables. RESULTS: Six hundred eighteen ER + patients had a median tumor size of 1.7 cm (1.1-2.5 cm). Two hundred ninety six out of 618 (47.9%) were node-positive and 188/618 (30.4%) had axillary dissection. Eighty four point three percent of patients were ER+/PR+/HER2-, 6.31% were ER+/PR-/HER2-, 6.96% were ER+/PR+/HER2+, and 1.13% were ER+/PR-/HER2+. Median tumor size was significantly larger in node-positive cases compared to node-negative cases in ER+/PR+/HER2-, ER+/PR+/HER2+, and ER+/PR-/HER2- subgroups. In ER+/PR+/HER2-patients, median tumor-nipple distance was significantly shorter in node-positive patients compared to node-negative patients. Upper outer quadrant location was significantly associated with nodal positivity in ER+/PR-/HER2- patients. CONCLUSIONS: Across ER + patients, the significance between tumor size, location, and lymph node positivity varied significantly when differentiating by PR and HER2 status.

Factors Predictive of Positive Lymph Nodes for Breast Cancer.

BACKGROUND: Axillary node status is an important prognostic factor in breast cancer. The primary aim was to evaluate tumor size and other characteristics relative to axillary disease. MATERIALS AND METHODS: Single institution retrospective chart review of stage I-III breast cancer patients collected demographic and clinical/pathologic data from 1998-2019. Student's t-test, Chi-squared test (or Fisher exact test if applicable), and logistic regression models were used for testing the association of pN+ to predictive variables. RESULTS: Of 728 patients (mean age 59 yrs) with mean follow up of 50 months, 86% were estrogen receptor +, 10% Her2+, 78% ER+HER2-negative, and 10% triple-negative. In total, 351/728 (48.2%) were pN+ and mean tumor size was larger in pN+ cases compared to pN- cases (mean = 27.7 mm versus 15.5 mm) (p < 0.001). By univariate analysis, pN+ was associated with lymphovascular invasion (LVI), higher grade, Her2, and histology (p < 0.005). Tumor-to-nipple distance was shorter in pN+ compared to pN- (45 mm v. 62 mm; p< 0.001). Age < 60, LVI, recurrence, mastectomy, larger tumor size, and shorter tumor-nipple distance were associated with 3+ positive nodes (p < 0.05). CONCLUSIONS: Larger tumor size and shorter tumor-nipple distance were associated with higher lymph node positivity. Age less than 60, LVI, recurrence, mastectomy, larger tumor size, and shorter tumor-nipple distance were all associated with 3+ positive lymph nodes.

A Cohort Study of the Antitumor Efficacy and Toxicity Profile of Alpelisib for Metastatic or Locally Advanced HR+, HER2- Breast Cancer: A Single-Institution Experience.

INTRODUCTION: Alpelisib is approved in combination with endocrine therapy (ET) to treat patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) progressive metastatic breast cancer (MBC). The SOLAR-1 trial demonstrated the efficacy of this oral agent and showed that, while alpelisib improves outcomes compared to placebo, it is also associated with clinically relevant adverse events (AEs). There is a pressing need for improved knowledge on the effectiveness and tolerability of this agent in real-world patient populations. METHODS: We conducted a retrospective cohort study of patients with HR+, HER2- MBC treated with alpelisib and ET. We assessed the safety, tolerability, and effectiveness of alpelisib in a real-world population. Deidentified patient-, tumor-, and outcome-related data, including AEs, were collected and summarized. Kaplan-Meier methods were applied for survival analyses, and stratified analyses of interest were conducted. A p value <0.05 was considered statistically significant. RESULTS: A total of 76 women treated with alpelisib + ET were included in our cohort. Most had been previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and chemotherapy for MBC. The estimated median progression-free survival was 5.2 months (95% CI, 4.1-8.0). The median overall survival was longer among patients without prior everolimus therapy (hazard ratio, 4.28 [95% CI, 1.64-11.16]; p = 0.0012), and no significant outcome differences were observed between patients treated with different starting doses of alpelisib. Approximately 31.6% of patients permanently discontinued alpelisib due to AEs, and 32.9% had at least one dose reduction. The most common grade 3/4 AEs were hyperglycemia (21%), fatigue (13.2%), and diarrhea (10.5%). CONCLUSIONS: For progressive HR+, HER2- MBC, alpelisib + ET showed effectiveness in a real-world patient population that was comparable to published clinical trial data, regardless of starting dose. However, the effectiveness of alpelisib following previous everolimus exposure may be limited and, hence, should be a consideration to decide sequencing of therapy in these patients. Patients treated with alpelisib are at risk for clinically relevant AEs and require close monitoring.

SARS-CoV-2 antibody response duration and neutralization following natural infection.

Background: The role of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody response from natural infection and vaccination, and the potential determinants of this response are poorly understood. Characterizing this antibody response and the factors associated with neutralization can help inform future prevention efforts and improve clinical outcomes in those infected. Objectives: The goals of this study were to prospectively evaluate SARS-CoV-2 antibody levels and the neutralizing antibody responses among naturally infected adults and to determine demographic and behavioral factors independently associated with these responses. Methods: Serum was collected from seropositive individuals at baseline, four-weeks, and three-months following their first study visit to be evaluated for antibody levels. Detection of neutralizing antibodies was performed at baseline. Participant demographic and behavioral information was collected via web questionnaire prior to their first visit. Results: At baseline, higher antibody levels were associated with better neutralization capacity, with 83% of participants having detectable neutralizing antibodies. We found an age-dependent effect on antibody level and neutralization capacity with participants over 65 years having significantly higher levels. Ethnicity, heart disease, autoimmune disease, and COVID symptoms were associated with higher antibody levels, but not with increased neutralization capacity. Work environment during the pandemic correlated with increased neutralization capacity, while kidney or liver disease and traveling out of state after February 2020 correlated with decreased neutralization capacity, however neither correlated with antibody levels. Conclusions: Our data show that natural infection by SARS-CoV-2 can induce a humoral response reflected by high antibody levels and neutralization capacity.

Tumor Characteristics Associated with Axillary Nodal Positivity in Triple Negative Breast Cancer.

Larger-size primary tumors are correlated with axillary metastases and worse outcomes. We evaluated the relationships among tumor size, location, and distance to nipple relative to axillary node metastases in triple-negative breast cancer (TNBC) patients, as well as the predictive capacity of imaging. We conducted a single-institution, retrospective chart review of stage I-III TNBC patients diagnosed from 1998 to 2019 who underwent upfront surgery. Seventy-three patients had a mean tumor size of 20 mm (range 1-53 mm). All patients were clinically node negative. Thirty-two patients were sentinel lymph node positive, of whom 25 underwent axillary lymph node dissection. Larger tumor size was associated with positive nodes (p < 0.001): the mean tumor size was 14.30 mm in node negative patients and 27.31 mm in node positive patients. Tumor to nipple distance was shorter in node positive patients (51.0 mm) vs. node negative patients (73.3 mm) (p = 0.005). The presence of LVI was associated with nodal positivity (p < 0.001). Tumor quadrant was not associated with nodal metastasis. Ultrasound yielded the largest number of suspicious findings (21/49), with sensitivity of 0.25 and specificity of 0.40. On univariate analysis, age younger than 60 at diagnosis was also associated with nodal positivity (p < 0.002). Comparative analyses with other subtypes may identify biologic determinants.

Surgeon and Radiologist Evaluation of Electromagnetic Chip Localization for Benign and Malignant Breast Lesions.

BACKGROUND: SmartClipTM is a food and drug administration-approved, electromagnetic chip (EMC) localization system that provides three-dimensional navigation for the excision of soft tissue lesions. The purpose of this study was to analyze the accuracy and feasibility of EMC radiologic and surgical localization for benign and malignant breast lesions. PATIENTS AND METHODS: An institutional review board-approved, single institution, prospective study from October 2020 to September 2022 of 38 women undergoing breast conserving surgery with EMC localization of a single lesion > 5 mm on mammogram (MMG) or ultrasound (US) imaging. Surveys from performing breast radiologists and breast surgeons were collected after image-guided localization and surgical excision. RESULTS: Seventy-six survey responses from nine radiologists and four surgeons were received. The deployment needle and EMC were highly visible in 86.8% and 76.3% of procedures, respectively. There was no difficulty in deployment for 92.1% of procedures. The EMC was in the correct location on postdeployment MMG in 97.4% of cases. Three instances of EMC migration occurred, one 1 cm from target lesion. The targeted mass and EMC were within the surgical specimen in 97.4% of cases. On specimen radiograph, 39.5% of the EMCs were 0-1 mm from the center of the target lesion, 18.4% were within 2-4 mm, and 23.7% were within 5-10 mm. Mean operating room time for all cases was 65 min. One case required US to localize the target due to console malfunction. CONCLUSION: There was successful EMC deployment by radiologists with accurate visualization and successful surgical excision in most cases. The EnVisioTM SmartClipTM system is a reproducible and accurate localization method for benign and malignant breast lesions.

Retrospective Study of Treatment Patterns and Natural History of Patients with T1a/b N0 Triple-Negative Breast Cancers: A Single-Institution Experience.

INTRODUCTION: T1a/b, node-negative (node-), triple-negative breast cancers (TNBCs) are underrepresented in randomized drug-approving clinical trials. Given their low incidence, the clinicopathological features, natural history, and treatment patterns of these tumors remain insufficiently understood. METHODS: We conducted a single-institution retrospective cohort study of patients with T1a/b, N0, M0 TNBCs. Deidentified patient- and tumor-related data were collected and summarized. Kruskal-Wallis, χ2, or Fisher exact tests were used to evaluate associations of interest. Kaplan-Meier methods, log-rank tests, and Cox's proportional hazards models were applied for survival analyses. RESULTS: Of 108 cases of node- TNBCs measuring ≤2 cm, 34 node- T1a/b tumors were included in our analysis. All cases had an intermediate to high histological grade, and most had a Ki-67 score of ≥20%. All patients received adjuvant chemotherapy, and many underwent mastectomy (47%). Docetaxel combined with cyclophosphamide was the most common adjuvant chemotherapy regimen (75%). We did not observe significant associations between improved outcomes and treatment with anthracycline-containing regimens. Among patients with node- pT1a/b tumors, the estimated 3-year recurrence-free survival (RFS) and distant RFS rates were both 96.3% (95% CI: 76.5-99.5), and the overall survival rate was estimated to be 100% (95% CI: 100-100). There were no cases of local recurrences observed. CONCLUSIONS: In our cohort, all patients with T1a/b node- TNBCs were treated with adjuvant chemotherapy and had favorable outcomes even when treated with anthracycline-sparing regimens.

Impact of weight and creatinine adjustments on the accuracy of Cockcroft-gault equation in hematopoietic cell transplant patients.

BACKGROUND: Hematopoietic cell transplant (HCT) patients undergo pre- transplant renal function evaluation to confirm transplant eligibility and tailor pharmacotherapy. There is limited evidence regarding the most accurate method of estimating creatinine clearance (CrCl) within this patient population and no studies exist that evaluate the weight utilized within the Cockcroft-Gault (CG) equation in HCT patients. This study evaluates different weight and serum creatinine (SCr) adjustments utilized within the CG equation estimating for renal clearance in patients undergoing HCT. OBJECTIVE: This is a retrospective, single center analysis of adult HCT patients who underwent pre-transplant evaluation with a measured CrCl using a 24-h urine creatinine collection. The primary outcome was to evaluate the correlation of various weights used in estimation of CrCl compared to measured CrCl. Key secondary outcomes include evaluation of the impact of various weights on estimated CrCl in subpopulations, evaluation of adjusting SCr to pre-determined limits, and determination of an appropriate obesity threshold to utilize body weight adjustments. RESULTS: Seven-hundred and forty-two patients were included in the study. In the primary analysis, CG utilizing adjusted body weight (ADjBW0.4 ) had a greater correlation (r = .812) to measured CrCl when compared to total or ideal body weight (r = .801 and r = .790 respectively). The threshold of 120% of ideal body weight (IBW) produced less bias and greater accuracy in comparison to the threshold of 140% IBW. In patients 60 years or older, rounding low SCr values up .8 or 1 mg/dL resulted in decreased correlation and a greater mean difference in comparison to not rounding SCr. CONCLUSION: In HCT patients who are overweight or obese, ADjBW .4 is the most accurate weight for the CG equation. In HCT patients who have a total body weight < 120% IBW, total body weight is the most accurate weight to utilize. Rounding up low SCr to .8 or 1 mg/dL does not improve the accuracy or led to less bias of the CG equation.

Safety and immunogenicity of a third dose of mRNA-1273 vaccine among cancer patients.

BACKGROUND: Compared to the general population, cancer patients are at higher risk of morbidity and mortality following SARS-CoV-2 infection. The immune response to a two-dose regimen of mRNA vaccines in cancer patients is generally lower than in immunocompetent individuals. Booster doses may meaningfully augment immune response in this population. We conducted an observational study with the primary objective of determining the immunogenicity of vaccine dose three (100 µg) of mRNA-1273 among cancer patients and a secondary objective of evaluating safety at 14 and 28 days. METHODS: The mRNA-1273 vaccine was administered ∼7 to 9 months after administering two vaccine doses (i.e., the primary series). Immune responses (enzyme-linked immunosorbent assay [ELISA]) were assessed 28 days post-dose three. Adverse events were collected at days 14 (± 5) and 28 (+5) post-dose three. Fisher exact or X2 tests were used to compare SARS-CoV-2 antibody positivity rates, and paired t-tests were used to compare SARS-CoV-2 antibody geometric mean titers (GMTs) across different time intervals. RESULTS: Among 284 adults diagnosed with solid tumors or hematologic malignancies, dose three of mRNA-1273 increased the percentage of patients seropositive for SARS-CoV-2 antibody from 81.7% pre-dose three to 94.4% 28 days post-dose three. GMTs increased 19.0-fold (15.8-22.8). Patients with lymphoid cancers or solid tumors had the lowest and highest antibody titers post-dose three, respectively. Antibody responses after dose three were reduced among those who received anti-CD20 antibody treatment, had lower total lymphocyte counts and received anticancer therapy within 3 months. Among patients seronegative for SARS-CoV-2 antibody pre-dose three, 69.2% seroconverted after dose three. A majority (70.4%) experienced mostly mild, transient adverse reactions within 14 days of dose three, whereas severe treatment-emergent events within 28 days were very rare (<2%). CONCLUSION: Dose three of the mRNA-1273 vaccine was well-tolerated and augmented SARS-CoV-2 seropositivity in cancer patients, especially those who did not seroconvert post-dose two or whose GMTs significantly waned post-dose two. Lymphoid cancer patients experienced lower humoral responses to dose three of the mRNA-1273 vaccine, suggesting that timely access to boosters is important for this population.

Dichotomous Nitric Oxide-Dependent Post-Translational Modifications of STAT1 Are Associated with Ipilimumab Benefits in Melanoma.

Although Ipilimumab (anti-CTLA-4) is FDA-approved for stage III/IV melanoma adjuvant treatment, it is not used clinically in first-line therapy, given the superior relapse-free survival (RFS)/toxicity benefits of anti-PD-1 therapy. However, it is important to understand anti-CTLA-4's mechanistic contribution to combination anti-PD-1/CTLA-4 therapy and investigate anti-CTLA-4 therapy for BRAF-wild type melanoma cases reresected after previous adjuvant anti-PD-1 therapy. Our group published that nitric oxide (NO) increased within the immune effector cells among patients with longer RFS after adjuvant ipilimumab, whereas NO increased within the immune suppressor cells among patients with shorter RFS. Herein, we measured the post-translational modifications of STAT1 (nitration-nSTAT1 and phosphorylation-pSTAT1) that are important for regulating its activity via flow cytometry and mass spectrometry approaches. PBMCs were analyzed from 35 patients undergoing adjuvant ipilimumab treatment. Shorter RFS was associated with higher pSTAT1 levels before (p = 0.007) and after (p = 0.036) ipilimumab. Ipilimumab-treated patients with high nSTAT1 levels before and after therapy in PBMCs experienced decreased RFS, but the change in nSTAT1 levels before and after ipilimumab therapy was associated with longer RFS (p = 0.01). The measurement of post-translational modifications in STAT1 may distinguish patients with prolonged RFS from ipilimumab and provide mechanistic insight into responses to ipilimumab combination regimens.

Factors Influencing Lymph Node Positivity in HER2/neu+ Breast Cancer Patients.

Axillary lymph node metastases are a key prognostic factor in breast cancer treatment. Our aim was to evaluate how tumor size, tumor location, and imaging results correlate to axillary lymph node diseases for patients with stage I-III HER2/neu+ breast cancer. This is a single-institution retrospective chart review of female breast cancer patients diagnosed with primary invasive Her2/neu+ breast cancer who were treated with upfront surgical resection from 2000-2021. Of 75 cases, 44/75 (58.7%) had nodal metastasis, and there was a significant association of larger tumor size to nodal metastases (p ≤ 0.001). Patients with negative nodes had a smaller mean tumor size (n = 30; 15.10 mm) than patients with positive nodes (n = 45; 23.9 mm) (p = 0.002). Preoperative imaging detected suspicious nodes in 36 patients, and ultrasound detected the most positive nodes (14/18; p = 0.027). Our data confirms that tumor size at diagnosis is correlated with a higher likelihood of axillary involvement in patients with Her2/neu+ breast cancer; notably, a large proportion of Her2/neu+ breast cancers have metastatic involvement of axillary lymph nodes even with small primary lesions.

An miRNA Signature Predicts Grading of Pancreatic Neuroendocrine Neoplasms.

BACKGROUND/AIM: Grading pancreatic neuroendocrine neoplasms (PNENs) via mitotic rate and Ki-67 index score is complicated by interobserver variability. Differentially expressed miRNAs (DEMs) are useful for predicting tumour progression and may be useful for grading. PATIENTS AND METHODS: Twelve PNENs were selected. Four patients had grade (G) 1 pancreatic neuroendocrine tumours (PNETs); 4 had G2 PNETs; and 4 had G3 PNENs (2 PNETs and 2 pancreatic neuroendocrine carcinomas). Samples were profiled using the miRNA NanoString Assay. RESULTS: There were 6 statistically significant DEMs between different grades of PNENs. MiR1285-5p was the sole miRNA differentially expressed (p=0.03) between G1 and G2 PNETs. Six statistically significant DEMs (miR135a-5p, miR200a-3p, miR3151-5p, miR-345-5p, miR548d-5p and miR9-5p) (p<0.05) were identified between G1 PNETs and G3 PNENs. Finally, 5 DEMs (miR155-5p, miR15b-5p, miR222-3p, miR548d-5p and miR9-5p) (p<0.05) were identified between G2 PNETs and G3 PNENs. CONCLUSION: The identified miRNA candidates are concordant with their patterns of dysregulation in other tumour types. The reliability of these DEMs as discriminators of PNEN grades support further investigations using larger patient populations.

Factors related to human papillomavirus vaccine uptake and intentions among adults aged 18-26 and 27-45 years in the United States: A cross-sectional study.

BACKGROUND: The current study examined self-reported human papillomavirus (HPV) vaccination uptake and intentions, and associations with psychosocial constructs among United States adults aged 18 to 26 and 27 to 45 years. METHODS: Data were collected via an online survey from participants recruited from a research panel. Outcomes were HPV vaccination uptake and intentions. Multivariable binary and ordered logistic regression models were used to examine associations between HPV vaccination outcomes and psychosocial constructs, sociodemographics, and previous health behaviors. RESULTS: HPV vaccination uptake in both age cohorts (N =  2722) was associated with multiple variables, including but not limited to: provider recommendation (adjusted odds ratio [aOR], 11.63 [95% CI, 7.70-17.56] and aOR, 14.26 [95% CI, 9.52-21.38], for those aged 18 to 26 and 27 to 45 years, respectively) and positive HPV vaccine attitudes (aOR, 2.40 [95% CI, 1.70-3.40] and aOR, 1.46 [95% CI,1.06-2.02]). Among those who did not report or were unsure of prior HPV vaccination (N =1894), only 4.6% and 8.1% (aged 18-26 and 27-45 years, respectively) reported being very likely to receive the HPV vaccine in the next year. Increased intentions were associated with more positive vaccine attitudes (aOR, 2.45 [95% CI, 1.91-3.15] and aOR, 2.19 [95% CI, 1.72-2.78]) and provider recommendation (yes vs no; aOR, 1.97 [95% CI, 1.38-2.83] and aOR, 1.82 [95% CI, 1.31-2.52]; don't know/can't remember vs no; aOR, 1.38 [95% CI, 1.03-1.84] and aOR, 1.60 [95% CI, 1.17-2.18]). Sociodemographics and health behaviors associated with increased intentions differed for each age cohort. CONCLUSIONS: Individual and interpersonal factors were associated with HPV vaccination uptake and intentions. Findings reveal the need for targeted interventions to improve HPV vaccination rates among these age groups.

Factors associated with parental COVID-19 vaccine attitudes and intentions among a national sample of United States adults ages 18-45.

PURPOSE: This study explored factors associated with parents' attitudes and intentions to seek information about the COVID-19 vaccine for their children (ages 0-18) and intentions to vaccinate their age-eligible children. DESIGN AND METHODS: As part of an anonymous online cross-sectional survey, parents' vaccine attitudes, COVID-19 vaccine intentions for their children, health literacy, health numeracy, and sociodemographic variables were assessed. Multivariable ordered logistic regression models identified factors associated with parents' COVID-19 vaccine intentions for their children. RESULTS: Parents/guardians (n = 963) were mostly White (82.3%), insured (88.0%), and college graduates (57.3%). Men reported higher intentions than women to seek information about the COVID-19 vaccine for their children (p = 0.003) and higher intentions to vaccinate their children (p = 0.049). Parental characteristics associated with increased intentions to have their children vaccinated included higher educational attainment (p < 0.001), more positive general vaccine attitudes (p < 0.001), preference for health information in a language other than English (p = 0.006), higher income (p = 0.048), having health insurance (p = 0.05), health literacy (p = 0.024), and health numeracy (p = 0.049). CONCLUSIONS: Multiple sociodemographic characteristics including male gender, higher health literacy and numeracy, and language preference are noteworthy factors associated with parental COVID-19 vaccine intentions that could inform the planning and implementation of educational interventions. PRACTICE IMPLICATIONS: Nurses are important sources of trusted information and play an important role in parent/family health education and in understanding myriad factors that may improve attitudes and enhance readiness toward vaccine uptake. Our findings emphasize the potential value of examining tailored/targeted COVID-19 vaccine education according to key influencing factors.

Impact of the COVID-19 pandemic on human papillomavirus (HPV) vaccination among a national sample of United States adults ages 18-45: A cross-sectional study.

To assess how the COVID-19 pandemic affected catch-up HPV vaccination among age-eligible adults (ages 18-45). The current study leverages a national, cross-sectional sample of US adults ages 18-45 years to assess the prevalence and determinants of COVID-19 pandemic-related disruptions to catch-up HPV vaccination in 2021. The sample was restricted to adults intending to receive the HPV vaccine. Multinomial logistic regression analysis was conducted to assess the probability of 1) pandemic-related HPV vaccination disruption and 2) uncertainty about pandemic-related HPV vaccination disruption. Report of 'no pandemic-related HPV vaccination disruption' served as the reference category. Among adults intending to get the HPV vaccine (n = 1,683), 8.6 % reported pandemic-related HPV vaccination disruption, 14.7 % reported uncertainty about vaccination disruption, and 76.7 % reported no disruption. Factors associated with higher odds of pandemic-related vaccination disruption included non-English language preference (OR: 3.20; 95 % CI: 1.99-5.13), being a parent/guardian (OR: 1.77; 95 % CI: 1.18-2.66), having at least one healthcare visit in the past year (OR: 1.97; 95 % CI: 1.10-3.53), being up-to-date on the tetanus vaccine (OR: 1.81; 95 % CI: 1.19-2.75), and being a cancer survivor (OR: 2.57; 95 % CI: 1.52-4.34). Catch-up HPV vaccination for age-eligible adults is a critical public health strategy for reducing HPV-related cancers. While a small percentage of adults reported pandemic-related disruptions to HPV vaccination, certain adults (e.g., individuals with a non-English language preference and cancer survivors) were more likely to report a disruption. Interventions may be needed that increase accessibility of catch-up HPV vaccination among populations with reduced healthcare access during the pandemic.

Tolerance and Outcomes of Neoadjuvant Chemotherapy in Geriatric Breast Cancer Patients.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is an established treatment option for patients with human epidermal growth factor receptor 2-positive (Her2+) or triple-negative breast cancer (TNBC). However, the toxicities associated with NAC may lead to reduced tolerance in geriatric patients due to medical comorbidities. Our objective is to evaluate the tolerance and outcomes of NAC in geriatric patients with TNBC and Her2+ breast cancer. MATERIALS AND METHODS: An institutional review board approved, retrospective study of 43 geriatric (≥70 y) and 103 non-geriatric (<70 y) patients with TNBC and Her2+ breast cancer was conducted. Demographic, comorbidity, treatment, and toxicity variables were collected. Log-rank tests and Cox regression visualized survival outcomes evaluated associations with clinical and demographic variables. Descriptive statistics were performed. RESULTS: Following NAC, 30% geriatric patients had a pathologic complete response in the primary tumor, 54% had a partial response, and 16% had no response. Of the non-geriatric patients, 24% had a pathologic complete response, 64% had a partial response, and 12% showed no response. NAC-associated toxicities occurred in 81% of geriatric patients and 73% non-geriatric patients, with neutropenia occurring most frequently in both groups. Dose reduction and early discontinuation of NAC each occurred more frequently in the geriatric group (14%; 23%) than the non-geriatric group (7%; 6%). Higher post-treatment Eastern Cooperative Oncology Group scores were associated with worse overall survival and worse recurrence-free survival in both groups. CONCLUSIONS: NAC was associated with reduced tumor and nodal stage in most geriatric patients; however, NAC-associated toxicities were common and led some patients to reduce or stop their NAC regimen prematurely.

Neutralizing Antibody Response following a Third Dose of the mRNA-1273 Vaccine among Cancer Patients.

Cancer patients are at an increased risk of morbidity and mortality from SARS-CoV-2 infection and have a decreased immune response to vaccination. We conducted a study measuring both the neutralizing and total antibodies in cancer patients following a third dose of the mRNA-1273 COVID-19 vaccine. Immune responses were measured with an enzyme-linked immunosorbent assay (ELISA) and neutralization assays. Kruskal-Wallis tests were used to evaluate the association between patient characteristics and neutralization geometric mean titers (GMTs), and paired t-tests were used to compare the GMTs between different timepoints. Spearman correlation coefficients were calculated to determine the correlation between total antibody and neutralization GMTs. Among 238 adults diagnosed with cancer, a third dose of mRNA-1273 resulted in a 37-fold increase in neutralization GMT 28 days post-vaccination and maintained a 14.6-fold increase at 6 months. Patients with solid tumors or lymphoid cancer had the highest and lowest neutralization GMTs, respectively, at both 28 days and 6 months post-dose 3. While total antibody GMTs in lymphoid patients continued to increase, other cancer types showed decreases in titers between 28 days and 6 months post-dose 3. A strong correlation (p < 0.001) was found between total antibody and neutralization GMTs. The third dose of mRNA-1273 was able to elicit a robust neutralizing antibody response in cancer patients, which remained for 6 months after administration. Lymphoid cancer patients can benefit most from this third dose, as it was shown to continue to increase total antibody GMTs 6 months after vaccination.