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Gynecological cancers are among the most prevalent cancers in women worldwide. Brachytherapy, often used as a boost to external beam radiotherapy, is integral to treatment. Advances in computation, algorithms, and data availability have popularized the use of machine learning to predict patient outcomes. Recent studies have applied models such as logistic regression, support vector machines, and deep learning networks to predict specific toxicities in patients who have undergone brachytherapy. To develop and compare machine learning models for predicting grade 3 or higher toxicities in gynecological cancer patients treated with high dose rate (HDR) brachytherapy, aiming to contribute to personalized radiation treatments. A retrospective analysis was performed on gynecological cancer patients who underwent HDR brachytherapy with Syed-Neblett or Tandem and Ovoid applicators from 2009 to 2023. After applying exclusion criteria, 233 patients were included in the analysis. Dosimetric variables for the high-risk clinical target volume (HR-CTV) and organs at risk, along with tumor, patient, and toxicity data, were collected and compared between groups with and without grade 3 or higher toxicities using statistical tests. Seven supervised classification machine learning models (Logistic Regression, Random Forest, K-Nearest Neighbors, Support Vector Machines, Gaussian Naive Bayes, Multi-Layer Perceptron Neural Networks, and XGBoost) were constructed and evaluated. The training process involved sequential feature selection (SFS) when appropriate, followed by hyperparameter tuning. Final model performance was characterized using a 25% withheld test dataset. The top three ranking models were Support Vector Machines, Random Forest, and Logistic Regression, with F1 testing scores of 0.63, 0.57, and 0.52; normMCC testing scores of 0.75, 0.77, and 0.71; and accuracy testing scores of 0.80, 0.85, and 0.81, respectively. The SFS algorithm selected 10 features for the highest-ranking model. In traditional statistical analysis, HR-CTV volume, Charlson Comorbidity Index, Length of Follow-Up, and D2cc - Rectum differed significantly between groups with and without grade 3 or higher toxicities. Machine learning models were developed to predict grade 3 or higher toxicities, achieving satisfactory performance. Machine learning presents a novel solution to creating multivariable models for personalized radiation therapy.

BackgroundThe optimal access for thermal ablation of the liver has not been evaluated in the literature for the laparoscopic versus percutaneous techniques. The aim of this manuscript was to determine the optimal ablation technique and patient selection for hepatic malignancies by comparing the efficacy and recurrence-free survival of laparoscopic and percutaneous thermal ablation.MethodsA detailed literature search was made in PubMed, Web of Science, Google scholar, and EMBASE for related research publications. The data were extracted and assessed by two reviewers independently. Analysis of pooled data was performed, and Odds Ratio (OR) or Hazard Ratio (HR) with corresponding confidence intervals (CIs) was calculated and summarized respectively.ResultsA total of 10 articles were included with 1916 ablation patients. Laparoscopic ablation success (Median 100%) was found to be higher than percutaneous ablation success (median 89.4%) (p = ns). There was a higher percentage of both local and non-local hepatic recurrence in the patients treated with percutaneous ablation versus laparoscopic ablation. Meta-analysis indicated no difference in the adjusted hazard rate of recurrence by procedure type (p = 0.94). Laparoscopic ablation had a higher percentage of complications compared to percutaneous ablation (median lap 14.5% vs. perc 3.3%).ConclusionsWhile laparoscopic and percutaneous ablation are both effective interventions for hepatic malignancies, laparoscopic ablation was found to have improved ablation success and less local and non-local hepatic recurrence compared to percutaneous ablation.

Obesity is a strong risk factor for early-onset colon cancer (EOCC) and is associated with chronic inflammation largely mediated by macrophages. The macrophage-specific metabolite itaconate promotes growth in several types of cancer; however, its role in colon cancer (CC) is unknown. Here, we investigate a tumor promoting link between obesity-related hormones and itaconate within the NOTCH4-GATA4-IRG1 pathway in EOCC. Patient tissue (n=20) was obtained and qRT-PCR, ELISA, and mass spectrometry were performed to evaluate expression (Human Immune-Responsive Gene 1, encoding ACOD1), ACOD1 expression (Cis-aconitate decarboxylase 1, enzyme producing itaconate), and itaconate concentration in human CC versus EOCC. RNA sequencing data from 5 sources in the USA and Europe were obtained to perform -related differential expression analysis (n=178), -related survival analysis (n=185), and differential expression analysis and survival analysis related to genes of the NOTCH4-GATA4-IRG1 pathway (n=371). Furthermore, tumor versus normal colon was compared and the interaction of tissue with sex, age, and body mass index (BMI) was investigated. A coculture model using two CC cell lines (HT-29 and SW480) and THP-1 cell line-derived M0 and M2-like macrophages was used to evaluate NOTCH4-GATA4-IRG1 pathway-related gene expression following treatment with obesity-related hormones (leptin, adiponectin) and itaconate derivatives. Both ACOD1 and expression were elevated in human CC tissue compared to adjacent normal colon tissue. Normal colon itaconate levels were higher in EOCC patients compared to that in older patients. Plasma itaconate levels in CC patients correlated with their BMI. Survival was decreased in -positive stage IV CC. -associated gene expression within the NOTCH4-GATA4-IRG1 pathway differed in CC versus normal colon tissue: , , , and upregulation was associated with EOCC, while and were downregulated in CCs and associated with higher BMI. Adiponectin and leptin treatment of macrophages cocultured with CC cells increased expression. Obesity-related hormones can increase itaconate production in M2-like macrophages. expression and the NOTCH4-GATA4-IRG1 pathway are associated with EOCC, BMI, and patient survival. As a macrophage metabolite affecting inflammation, itaconate may have a particular immunotherapeutic role in patients with EOCC.

Background Anal squamous cell cancer (ASCC) incidence in Kentucky is increasing at an alarming rate. In 2009, the incidence surpassed the US national average (2.66 vs. 1.77/100,000 people), and currently, Kentucky ranks second by state per capita. The reasons for this rise are unclear. We hypothesize individuals with ASCC in Kentucky have some unique risk factors associated with worse outcomes. Methods Individuals with ASCC in a population‐level state database (1995–2016), as well as those treated at two urban university‐affiliated tertiary care centers (2011–2018), were included and analyzed separately. We evaluated patient‐level factors including demographics, tobacco use, stage of disease, HIV‐status, and HPV‐type. We evaluated factors associated with treatment and survival using univariable and multivariable survival analyses. Results There were 1698 individuals in state data and 101 in urban center data. In the urban cohort, 77% of patients were ever‐smokers. Eighty‐four percent of patients had positive HPV testing, and 58% were positive for HPV 16. Seventy‐two percent of patients were positive for p16. Neither smoking, HPV, nor p16 status were associated with disease persistence, recurrence‐free survival, or overall survival (all p > 0.05). Poorly controlled HIV (CD4 count <500) at time of ASCC diagnosis was associated disease persistence (p = 0.032). Stage III disease (adjusted HR = 5.25, p = 0.025) and local excision (relative to chemoradiation; aHR = 0.19, p = 0.017) were significantly associated with reduced recurrence‐free survival. Conclusions The rate of ASCC in Kentucky has doubled over the last 10 years, which is outpacing anal SCC rates in the US with the most dramatic rates seen in Kentucky women. The underlying reasons for this are unclear and require further study. There may be other risk factors unique to Kentucky. The incidence of Anal Squamous Cell carcinoma is markedly increasing in Kentucky and in the United States overall. This difference is more pronounced in women and may be due to the interplay of factors including smoking and human papilloma virus infection.

Introduction and hypothesis A variety of factors affect the amount of bother experienced by different women with equivalent pelvic organ prolapse (POP). The goal of this study was to describe the relationship between age and bother experienced from objectively equivalent stages of POP. Methods Records of all patients presenting to a pelvic floor subspecialty clinic between January 2014 and March 2015 were reviewed. Women with POP stage ≥ 2 were included. The level of bother experienced from prolapse symptoms was defined as the score on the validated Pelvic Organ Prolapse Distress Inventory (POPDI). Multiple linear regression was performed to examine the relationship between age and the POPDI score. A sample size of 150 patients was determined to have 80 % power to detect an effect of age equivalent to an increase in R2 of 0.05. Results A total of 229 charts were reviewed and 165 patients were included in the final analysis. The effect of age on prolapse bother in the entire population was quadratic ( p  = 0.0497). Women at both ends of the spectrum were less bothered by prolapse, whereas women in the 6th and 7th decades of life demonstrated the highest level of bother, irrespective of stage. This same quadratic relationship remained in women with stage 2 prolapse ( p  = 0.019). Conclusions Women in the 6th and 7th decades of life experience higher levels of bother from POP than older or younger women with the same stage of prolapse. This suggests that women in these decades of life might be at a higher risk for impairment of quality of life from POP.

Background Verrucous vulvar carcinoma (VC) is an uncommon and distinct histologic subtype of squamous cell carcinoma (SCC). The available literature on VC is currently limited to case reports and small single institution studies. Aims The goals of this study were to analyze data from the National Cancer Database (NCDB) to quantitate the incidence of VC and to investigate the effects of patient demographics, tumor characteristics, and treatment regimens on overall survival (OS) in women with verrucous vulvar carcinoma. Methods and results Patients diagnosed with vulvar SCC or VC between the years of 2004 and 2016 were identified in the NCDB. OS was assessed with Kaplan–Meier curves and the log‐rank test. Construction of a Cox model compared survival after controlling for confounding variables. The reported incidence of SCC of the vulva has significantly increased since 2004 (p < .0001). In contrast, the incidence of VC has remained stable (p = .344) since 2004. Compared to SCC, VC was significantly more likely to be diagnosed in older women (p < .0001) and treated with surgery alone (p < .0001). However, on propensity score weighted analysis there was a trend toward improved 5‐year OS in women with VC compared to those with SCC (63.4% vs. 57.7%, p = .0794). Multivariable Cox survival analysis showed an improvement in OS in VC patients treated with both primary site and regional lymph node surgery compared to primary site surgery alone (adjusted hazard ratio [aHR] 0.67, 95% confidence interval [CI] 0.46–0.97, p = .0357). Conclusion Verrucous carcinoma is more likely to present in older women. Regional lymph node surgery in addition to primary site surgery significantly improves OS in VC patients.

Aims Macrophages play an essential role in cancer development. Tumor‐associated macrophages (TAMs) have predominantly M2‐like attributes that are associated with tumor progression and poor patient survival. Numerous methods have been reported for differentiating and polarizing macrophages in vitro, but there is no standardized and validated model for creating TAMs. Primary cells show varying cytokine responses depending on their origin and functional studies utilizing these cells may lack generalization and validity. A distinct cell line‐derived TAM‐like M2 subtype is required to investigate the mechanisms mediated by anti‐inflammatory TAMs in vitro. Our previous work demonstrated a standardized protocol for creating an M2 subtype derived from a human THP‐1 cell line. The cell expression profile, however, has not been validated. The aim of this study was to characterize and validate the TAM‐like M2 subtype macrophage created based on our protocol to introduce them as a standardized model for cancer research. Methods and results Using qRT‐PCR and ELISA, we demonstrated that proinflammatory, anti‐inflammatory, and tumor‐associated marker expression changed during THP‐1‐derived marcrophage development in vitro, mimicking a TAM‐related profile (e.g., TNFα, IL‐1β). The anti‐inflammatory marker IL‐8/CXCL8, however, is most highly expressed in young M0 macrophages. Flow cytometry showed increased expression of CD206 in the final TAM‐like M2 macrophage. Single‐cell RNA‐sequencing analysis of primary human monocytes and colon cancer tissue macrophages demonstrated that cell line‐derived M2 macrophages resembled a TAM‐related gene profile. Conclusions The THP‐1‐derived M2 macrophage based on a standardized cell line model represents a distinct anti‐inflammatory TAM‐like phenotype with an M2a subtype profile. This model may provide a basis for in vitro investigation of functional mechanisms in a variety of anti‐inflammatory settings, particularly colon cancer development.

Endometrial dysfunction affects approximately 1% of infertile women, and there is currently no standard therapy for improving fertility treatment outcomes in these patients. In our study, we utilized a rodent model of thin endometrium to test whether intrauterine application of adipose-derived stromal vascular fraction cells (SVF) could improve morphological and physiological markers of endometrial receptivity. Using anhydrous ethanol, endometrial area and gland density were significantly reduced in our model of thin endometrium. Application of SVF was associated with a 29% reduction in endometrial vascular endothelial growth factor (VEGF) expression and significant increases in uterine artery systolic/diastolic velocity ratios and resistance index values, suggesting reduced diastolic microvascular tone. However, no significant improvements in endometrial area or gland density were observed following SVF treatment. 3D confocal imaging demonstrated poor engraftment of SVF cells into recipient tissue, which likely contributed to the negative results of this study. We suspect modified treatment protocols utilizing adjuvant estrogen and/or tail vein cell delivery may improve SVF retention and therapeutic response in subsequent studies. SVF is an easily-obtainable cell product with regenerative capability that may have a future role in the treatment of infertile women with endometrial dysfunction.

Introduction There are insufficient data on surface mold brachytherapy (SMB) in treating oral cancers. We reviewed our institutional experience to investigate the efficacy and toxicity of this treatment modality. Material and methods We retrospectively reviewed all the patients treated between 1989 and 2018 with high-dose-rate iridium-192 SMB for oral and oropharyngeal squamous cell carcinomas at our institution. Surface mold brachytherapy was delivered via an acrylic surface mold with 1–5 inserted catheters spaced 1 cm apart fabricated by our dental oncologist. The Kaplan-Meier product estimator was used to assess local control (LC), locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS). Cox proportional hazards regression analysis was used to assess the relationship of various variables and patient outcomes. Results Eighteen patients met the inclusion criteria and were evaluated. Indications for treatment were primary tumor (n = 13), local recurrence (2), locoregional recurrence (1), and oligometastatic disease (1). Ten patients received SMB alone and 8 received external beam radiotherapy with an SMB boost. The acute toxicity outcomes were as follows: no toxicity (n = 1), grade 1 (7), grade 2 (9), and grade 3 (1). Late effects were rare, only occurring in 3 patients. The one- and two-year LC were 81% and 68%, LRC 77% and 64%, DMFS 81% and 81%, and OS 77% and 46%. Conclusions Surface mold brachytherapy is a viable modality as either primary or boost treatment for superficial oral cancers. In our patients, this treatment method has a low toxicity profile and resulted in reasonable LC.

BackgroundGastroparesis is characterized by delayed gastric emptying without a significant obstructive pathology and is estimated to effect more than 5 million adults in the United States. Therapies for this condition are divided into two categories: gastric electrical stimulation or pyloric therapies to facilitate gastric emptying. Pyloric procedures include pyloroplasty, a well-documented procedure, and per-oral endoscopic myotomy (POP), a relatively novel endoscopic procedure that disrupts the pyloric muscles endoscopically. There is a paucity of literature comparing the two procedures. The aim of this study is to compare the outcomes of these two techniques. MethodsUnder an IRB protocol, data were collected prospectively from September 2018 through April 2021 at our institution for patients undergoing POP (n = 63 patients) or robotic pyloroplasty (RP) (n = 48). Preoperative and postoperative data including sex, race, age, BMI, and Gastroparesis Cardinal Symptom Index (GCSI) score were analyzed using univariate and multivariate analysis. ResultsThere was no significant difference in sex, age, and BMI for both cohorts, but patients with RP were more likely to have private insurance, pre-op reflux, and PPI (p < .05 for all). Patients who underwent POP had significantly shorter operative time compared to RP (median 27 min vs 90, p < 0.001). The average change between preoperative and postoperative GCSI scores was significantly decreased for both interventions (POP mean = 8.2, RP 16.8, p < 0.001 both). However, comparing both data, RP has significantly better improvement in postoperative GCSI score than POP in both univariate (p < 0.001) and multivariate analysis (p = 0.030). This was reflected in the individual symptoms with nausea (p < 0.001), ability to finish meal (p = 0.037), abdomen visibly larger (p = 0.037) and bloating (p = 0.022) all showing improvement in both groups, but with RP having a more significant decrease in the scoring of these symptoms than POP. There was no significant difference in the number of postoperative complications (POP 19% vs RP 13%, p = 0.440).ConclusionEven though both interventions are significantly associated with improvement of symptoms in patients with gastroparesis, our data demonstrates that robotic pyloroplasty has a superior response in comparison to per-oral endoscopic myotomy for the management of these symptoms. Per-oral pyloromyotomy has a similar complication rate to robotic pyloroplasty with a shorter operative time.