Objectives: We recently reported that deep learning (DL) using pelvic magnetic resonance imaging is useful for predicting the severity of urinary incontinence (UI) after robot-assisted radical prostatectomy (RARP). However, our results were limited because the prediction accuracy was approximately 70%. We aimed to develop a more accurate prediction system that can be used to inform patients on recovery from UI after RARP using a DL model based on intraoperative video images. Materials and Methods: This study included 101 patients with prostate cancer who underwent RARP. Three snapshots showing the pelvic cavity (before bladder neck incision, just after prostate removal, and after vesicourethral anastomosis) from intraoperative video records, as well as preoperative and intraoperative covariates, were assessed. We evaluated the DL models plus simple or ensemble machine learning, and their sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were analyzed. Results: Sixty-four and 37 patients demonstrated ‘early continence’ and ‘late continence’, respectively, at the 3-month follow-up. The combination of DL and simple machine learning using intraoperative video snapshots with clinicopathological parameters had a notably high performance (AUC, 0.683 to 0.749) for predicting early recovery from post-prostatectomy UI. Notably, the combination of DL and ensemble artificial neural network using intraoperative video snapshots had the highest performance (AUC, 0.882; sensitivity, 92.2%; specificity, 78.4%; overall accuracy, 85.3%) for predicting early recovery from post-prostatectomy UI. In contrast, DL and ensemble ML with clinicopathological parameters (Method 4) achieved no additive effects (AUC, 0.690 to 0.747) compared with DL and simple ML with clinicopathological parameters. Internal validation was performed on additional 30 cases with similar results. Conclusions: Our results suggest that DL algorithms using intraoperative video images can be used to reliably inform patients regarding their recovery from UI after RARP. (287 words)

Background: To understand the changing trends in reporting of race and sex as a demographic variable in phase III lung cancer clinical trials published over the last 35 years. Methods: A total of 426 articles reporting results of phase 3 lung cancer clinical trials published from 1984 to 2019 were identified in PubMed. Statistical analysis on trends over time on percentage of minority and female participation were performed. Results: Only 137 (32.2%) of the 426 studies analyzed reported race of participants. Among those studies, we found that the mean participation rate of white participants was significantly higher (82.65%) (p < 0.001). We found a decrease in African American participants and an increase in Asian participants over time. When looking at sex, we found that although the rate of male participation (69.02%) was significantly higher than that of female participation (30.98%), the female participation has improved with time at a rate of 0.65% per year. Conclusions: We found that the reporting and participation of minority races continues to lag that of other demographic factors like sex in phase III clinical trials in lung cancer. Especially in African Americans, where the participation in lung cancer phase III clinical trials has declined despite the rising incidence in lung cancer.

There is limited and conflicting data regarding loss of immunity in childhood cancer survivors who did not undergo hematopoietic stem cell transplantation. This retrospective study included 28 childhood cancer survivors whose treatment consisted of at least 3 months of chemotherapy. Decreased seropositivity for measles, mumps, rubella, varicella, tetanus, and hepatitis B was found in patients across all categories of malignancy compared to the general population. Results were more pronounced for those with hematological malignancies. This study indicates that pediatric cancer survivors, especially those with hematological malignancies, may have greater loss of protective antibodies from primary vaccinations.

Introduction: Obesity is a major risk factor in the development of endometrial cancer (EC) in young patients of reproductive age. Fertility sparing treatment is a viable option for a select group of patients with early EC, and involves systemic and intra-uterine hormonal therapy. Weight loss has been associated with improved outcomes in this group. Bariatric surgery (BS) has been shown to be the most efficient and durable method of weight loss in obese patients. However, there is a paucity of data studying the benefit of BS as part of fertility sparing treatment. Methods: We present a retrospective case series of five patients who are undergoing fertility sparing treatment for early EC, who also underwent BS for treatment of obesity and related comorbidities. We aim to show early regression of EC for all the patients and also report on the other health benefits of BS. Results: All five patients in the series achieved regression of EC within six months of undergoing BS. They also achieved significant weight loss consistent with previous studies, and three patients who had comorbidities related to obesity had remission of these conditions. One of the patients with EC regression also managed to conceive with IVF. Conclusion: Patients on fertility sparing treatment for early EC who underwent BS was associated with early regression within 6 months, significant weight loss and resolution of comorbidities. BS could be a promising component of fertility sparing treatment. Long term, prospective studies are required to confirm the benefits reported in this case series.

Background: As the ongoing public health crisis from Coronavirus Disease 2019 (COVID-19) pandemic puts strains on current models of cancer care, many health care centers had to adapt to minimize the risk of exposure and infection. The effects of the COVID-19 pandemic in a comprehensive cancer center were determined. Purpose: To measure the impact of the COVID-19 pandemic on care delivery at a comprehensive cancer center. Methods: The number of on-site and telehealth visits (TH) were obtained from scheduling software. Multiple factors including total visits, telehealth visits, screenings for cancer diagnosis, and cancer treatments were tracked from two years before the pandemic onset through 2022. The length of stay (LOS) and Case Mix Index (CMI) were calculated using hospital database. Results: In the third quarter of FY 2020, telehealth visits (TH) represented a fifth of total patient encounters. Cancer treatments, such as chemotherapy, radiation therapy, and surgery, decreased during the pandemic with number of surgeries being most affected (23% decrease in 2020 compared to the previous fiscal year). The average length of stay (LOS) was also longer with less discharges per given time during the pandemic. The increased LOS was related to increased severity of patient illnesses since CMI was higher. Screening mammograms decreased to a nadir of 58% in 2021 as compared to those screened in pre-pandemic fiscal years. Conclusions : The COVID-19 pandemic impacted many aspects of care, such as treatment and screenings. Many of these factors had to be postponed due to the fear of acquiring COVID-19 and access to care. The findings presented implicate that the delays and changes in cancer care during the pandemic resulted in less screening and treatment of more advanced disease.

Background Tumor deposits (TD) are considered as Extranodal Extension (ENE) in the AJCC 8th edition of Head and Neck Squamous Cell Carcinoma (HNSCC) TNM staging. Methods We analyzed TDs in patients with HNSCC who underwent surgery and adjuvant radiotherapy ± chemotherapy. Overall Survival (OS) and progression rate were compared to patients with ENE. Results ENE was detected in 50 patients, while TDs in 21. Based on the presence of ENE alone or TDs, the mean time to progression was significant (p<0.005). OS at three years was 55.7% for the whole study group, 60.4% in ENE and 38.4% in TDs. OS difference between the N2a-ENE, N3b-ENE, and the TDs ± ENE group was significant (p=0.05). The hazard ratio between ECs and TDs was Exp (B) 2.296 (p= 0.027). Conclusions The prognostic implication of TDs represents an independent risk factor, and a separate classification might be required.

Significant racial disparities in prostate cancer incidence and mortality have been reported between African American Men (AAM) who are at increased risk for prostate cancer, and European American Men (EAM). In most of the studies carried out on prostate cancer, this population is underrepresented. With the advancement of genome-wide association studies (GWAS), several genetic predictor models of prostate cancer risk have been elaborated, as well as numerous studies that identify both germline and somatic mutations with clinical utility. Despite significant advances, the AAM population continues to be underrepresented in genomic studies, which can limit their generalizability and potentially widen disparities. Here we outline racial disparities in currently available genomic applications that are used to estimate the risk of individuals developing prostate cancer and to identify personalized oncology treatment strategies. While the incidence and mortality of prostate cancer are different between AAM and EAM. the biological features and differences of prostate tumors in AAM and EAM are still being described. Samples from AAM remain to be unrepresented in different studies. This disparity impacts the available genomic data on prostate cancer. As a result, the disparity can limit the predictive utility of the genomic applications that have been developed and may lead to widening disparities. More studies with substantially higher recruitment and engagement of African American patients are necessary to overcome this disparity.

Background Malignant brain tumors are among the most threatening diseases of the central nervous system, and despite increasingly updated treatments, the prognosis has not been improved. Tumor treating fields (TTFields) are an emerging approach in cancer treatment using intermediate-frequency and low-intensity electric field, and can lead to development of novel therapeutic options. Recent findings A series of biological processes induced by TTFields to exert anti-cancer effects have been identified, and applications of TTFields in oncology have been increasingly reported. This review addresses the mechanisms of TTFields and recent advances in the application of TTFields therapy in malignant brain tumors, especially in glioblastoma (GBM). Conclusions As a novel therapeutic strategies, TTFields have shown promising results in many clinical trials, especially in GBM, and continue to evolve. A growing number of patients with malignant brain tumors are being enrolled in ongoing clinical studies demonstrating that TTFields-based combination therapies can improve treatment outcomes.

Background Several good results of clinical trial of nivolumab or involving nivolumab in advanced esophageal squamous cell carcinoma were reported. However, the response rate was still poor. A rare phenomenon called the “abscopal effect” refers to the regression of not only the irradiated tumor but also non-irradiated distant tumors after local radiotherapy. The mechanism is not completely clear, but it is thought that the activation of anti-tumor immunity induced by radiotherapy is the main factor. Case A 66-year-old man with recurred and nivolumab resistant esophageal squamous cell carcinoma in left-side cervical and abdominal para-aortal lymph node metastasis was treated with a total of 40 Gy (10 fractions) of radiotherapy to the left-side cervical lymph node metastasis which caused neck pain as a palliative treatment. Nivolumab was resumed the day after completion of radiotherapy. At 3 months after radiotherapy showed that the irradiated lesion in the left neck had regressed to a scar-like appearance. Notably, the abdominal para-aortal lymph nodes outside the irradiation area, which had previously tended to progress, had also shrunk (abscopal effect). The T cell receptor and B cell receptor (TCR/BCR) repertoire analysis before and after radiotherapy revealed that radiotherapy caused the changes in the TCR/BCR repertoire. Conclusion Changes in the TCR/BCR receptor repertoire repertoires were assumed to be a part of the mechanism of the abscopal effect. The findings in this patient suggest that combination of immune checkpoint inhibitors and radiotherapy can be a promising treatment approach, even for patients with immune checkpoint inhibitors resistant cancer.

Background: The six-transmembrane epithelial antigen of the prostate 3 (STEAP3) plays an essential role in iron uptake as an iron reductase. Previous studies found that STEAP3 may play crucial roles in tumorigenesis. However, a comprehensive pan‐cancer analysis of the prognosis and immunity of STEAP3 has not yet been reported. Methods: We performed a systematic analysis of the prognosis and immunity of STEAP3 in human pan-cancer. The data analysis and visualization were completed with R and Cytoscape. STEAP3 expression in cell lines and tissues was measured in multiple ways. Functional validation experiments were performed by shRNA knockdown inA498 and 786-O cell lines. Cell proliferation and invasive ability was detected by CCK-8 assay, transwell assay and wound healing assay. Results: In most tumor tissues, STEAP3 expression was remarkably upregulated and correlated with prognosis, particularly in clear cell renal cell carcinoma (ccRCC). Furthermore, STEAP3 expression was closely correlated with immune infiltrates and may induce recruitment and polarization of M2 macrophages in ccRCC. STEAP3 may be valuable for predicting responses to immune-checkpoint blockade (ICB) therapy. In addition, enrichment analysis results indicated that STEAP3 was positively related to immune-related pathways, P53 pathways and epithelial-mesenchymal transition (EMT). Finally, we demonstrated that STEAP3 was highly expressed in ccRCC tissues and might stimulate EMT via the downregulation of CDH1 in vitro in ccRCC. Conclusion: STEAP3 might function as a prognostic biomarker and immunotherapy response predictor in various cancers. Especially in ccRCC, STEAP3 is a new prognostic biomarker and exerts tumor-promoting function via stimulating the invasion and EMT and inducing recruitment and polarization of M2 macrophages.

Background: Sinonasal undifferentiated carcinoma (SNUC) is an exceedingly rare head and neck malignancy. No consensus exists on treatment for metastatic disease. Case: A 56-year-old female was diagnosed with SNUC after endorsing sinus congestion, diplopia, and right orbital pain. Initially treated with surgery and radiation, she later developed significant metastatic disease. She demonstrated progression of her hepatic metastases under pembrolizumab therapy. However, the addition of ipilimumab and a COX-2 inhibitor resulted in significant improvement in her lesions as well as an ongoing durable response. Her regimen was complicated by immune-related adverse events successfully treated with steroids.Conclusion: Dual checkpoint inhibition deserves consideration when treating metastatic SNUC, especially after single agent therapy has failed. The positive effect of this treatment may be augmented by IDO1 inhibition.

Background: Clinical trials evaluating immune checkpoint inhibition (ICI) in recurrent high-grade gliomas (rHGG) report 7-20% 6-month progression-free survival (PFS), while re-irradiation demonstrates 28%-39% 6-month PFS. Aims: We evaluate outcomes of patients treated with ICI and concurrent re-irradiation utilizing stereotactic body radiotherapy / fractionated stereotactic radiosurgery (SBRT) compared to ICI monotherapy. Methods and Results: Patients >18-years-old with rHGG (WHO grade III and IV) receiving ICI+SBRT or ICI monotherapy between 1/1/16-1/1/19 were included. Adverse events, 6-month PFS and overall survival (OS) were assessed. Log-rank tests were used to evaluate PFS and OS. Histogram analyses of apparent diffusion coefficient maps and dynamic contrast-enhanced magnetic resonance perfusion metrics were performed. Twenty-one patients with rHGG (ICI+SBRT: 16; ICI: 5) were included. The ICI+SBRT and ICI groups received a mean 7.25 and 6.2 ICI cycles, respectively. There were five grade 1, one grade 2 and no grade 3-5 AEs in the ICI+SBRT group, and four grade 1 and no grade 2-5 AEs in the ICI group. Median PFS was 2.85 and 1 month for the ICI+SBRT and ICI groups; median OS was 7 and 6 months among ICI+SBRT and ICI groups, respectively. There were significant differences in pre- and post-treatment tumor volume in the cohort (12.35 vs. 20.51; p=0.03), but not between treatment groups. Conclusions: In this heavily pretreated cohort, ICI with re-irradiation utilizing SBRT was well tolerated. Prospective studies are warranted to evaluate potential therapeutic benefits to re-irradiation with ICI+SBRT in rHGG.

Background: Human papillomavirus (HPV) is the causative agent of nearly all forms of cervical cancer, which can arise upon viral integration into the host genome and concurrent loss of viral regulatory gene E2. Gene-based delivery approaches show that E2 reintroduction reduces proliferative capacity and promotes apoptosis in vitro. This work explored if our calcium-dependent protein-based delivery system, TAT-CaM could deliver functional E2 protein directly into cervical cancer cells to limit proliferative capacity and induce cell death. Methods: TAT-CaM and the HPV16 E2 protein containing a CaM-binding sequence (CBS-E2) were expressed and purified from E. coli. Calcium-dependent binding kinetics were verified by Biolayer Interferometry. Equimolar TaT-CaM:CBS-E2 constructs were delivered into the HPV16+ SiHa cell line and uptake verified by confocal microscopy. Proliferative capacity was measured by MTS assay and cell death was measured by release of lactate dehydrogenase. As a control for specificity to HPV+ cells, human microvascular cells (HMECs) were used. Results: TAT-CaM bound CBS-E2 with high affinity in the presence of calcium and rapidly disassociated in its absence. After introduction by TAT-CaM, E2 was detected in cellular interiors by orthogonal projects taken at the depth of the nucleus. In dividing cells, E2 relocalized to regions associated with the mitotic spindle. Cells receiving a single daily dose of CBS-E2 for 4 days showed a significant reduction in metabolic activity at low doses and cell death at high doses compared to controls. This phenotype was retained for 7 days with no further treatments. When subcultured at day 12, treated cells regained their proliferative capacity. Conclusions: Using the TAT-CaM platform, bioactive E2 protein was delivered into living cervical cancer cells, inducing senescence and cell death in a time- and dose-dependent manner. These results suggest that this nucleic acid and virus-free delivery method could be harnessed to develop novel, effective protein therapeutics.

Background Multiple myeloma (MM) patients have variable responses to mRNA vaccination to COVID-19. Little is known regarding their vaccine-induced antibody levels over time. Methods We monitored spike IgG antibody levels over 24 weeks among a subset of 18 MM patients who showed a full response after two mRNA vaccinations. MM patients had a more rapid decline in antibody levels as compared to 8 healthy controls, with power law half-lives of 72 days (versus 107 days) and exponential half-lives of 37 days (versus 51 days). Results The patients with longer SARS-CoV-2 antibody half-lives were more likely to have undetectable monoclonal protein than those with shorter half-lives, suggesting better disease control may correlate with longer duration of vaccine-induced antibodies. Regardless, by 16 weeks post-second dose of mRNA vaccination, the majority of patients had antibody levels below 250 binding arbitrary units per milliliter, which would be unlikely to contribute significantly to preventing COVID-19. Conclusions Thus, even MM patients who respond adequately to vaccination are likely to require more frequent booster doses than the general population.

Objective: Immunochemotherapy has become a new treatment for advanced esophageal squamous cell carcinoma (ESCC). We aimed to study the clinical efficacy and toxicity of immunochemotherapy based on PD-1/PD-L1 compared with chemotherapy alone in the treatment of advanced ESCC, focusing on analyzing the influence of PD-L1 expression level. Methods: Randomized controlled trials comparing PD-1/PD-L1 based immunochemotherapy wirh chemotherapy alone for advanced ESCC were included. We extracted efficacy data [objective response rate (ORR), disease control rate (DCR), overall survival (OS) rate, progression-free survival (PFS) rate] and safety data (treatment-related adverse events, treatment-related mortality) and performed meta-analyses. Results: 5 articles were included. Compared with chemotherapy alone, the ORR and DCR of immunochemotherapy increased by 2.05 times and 1.54 times, respectively. Overall, patients receiving immunochemotherapy had a significant long-term survival advantage [OS: hazard ratio (HR)=0.68, 95% hazard ratio (CI) 0.61-0.75; PFS: HR=0.62, 95%CI 0.55, 0.70, respectively]. Even with PD-L1 tumor proportion score <1%, immunochemotherapy also showed a significant survival advantage [OS: HR=0.65, 95%CI 0.46-0.93; PFS: HR=0.56, 95%CI 0.46-0.69, respectively]. However, for PD-L1 combined positive score (CPS)<1, the survival advantage of immunochemotherapy was not significant [OS: HR=0.89, 95%CI 0.42-1.90; PFS: HR=0.71, 95%CI 0.47-1.08, respectively]. The toxicity of immunochemotherapy was higher than that of chemotherapy alone, but there was no statistical difference in treatment-related mortality (odds ratio=1.11, 95%CI 0.67-1.83). Conclusions: In this study, PD-1/PD-L1 based immunochemotherapy significantly could improve survival outcomes in patients with advanced ESCC. For patients with CPS<1, the survival advantage of immunochemotherapy was not significant. The toxicity of immunochemotherapy was acceptable.

Background. Endomertrial adenocarcinoma (EC) with early stage, high grade is rare seen metastasis. Here, we describe a unique case of axillary lymph node and breast metastasis from high grade endomertrial adenocarcinoma after a 4-year period. Cases. We presented a case of a 60-year-old woman with EC and received surgery in 2013. However, a metastatic tumor appeared at the axillary lymph node and the breast 4 years after surgery. Then she received an operation and 6 cycles adjuvant chemotherapy. 31 months following, she is alive without disease. Conclusions. A correct diagnosis should be made by combining the patient’s past clinical history, morphologic and immunohistochemical test results. Knowledge of this rare metastatic site will help the physician make the correct diagnosis.

Background: Psychological distress is associated with worsening symptoms during the active treatment period and lower quality of life in women with early-stage breast cancer. Many studies have indicated risk for heightened psychological distress across the breast cancer trajectory. Aim: The purpose of this review is to examine the literature for instruments used to measure psychological distress among women with breast cancer during chemotherapy. Methods: This study used the Arksey and O’Malley framework of scoping reviews. Two databases, PubMed & CINAHL, were searched for peer-reviewed original articles that were published within the last ten years, included participants with a diagnosis of breast cancer stages I to III, and receiving chemotherapy, English text articles, and studies that report psychological distress measures.  Results: The initial screening yielded 529 relevant studies. After applying the exclusion criteria, a total of 17 studies concerning the assessment of psychological distress during chemotherapy were retained for the analysis of variables and measures of psychological distress. The instruments used to measure for psychological distress varied with a total of 22 measures. The most frequently utilized measure was the Hospital Anxiety and Depression Scale ( n=5), followed by the Impact of Event Scale ( n=2), the Distress Thermometer ( n=2), and the Perceived Stress Scale ( n=2).  Conclusion: This review identified the gaps related to inconsistencies in the operationalization and instruments used to measure psychological distress among breast cancer survivors during chemotherapy. Standardization of measures assessing psychological distress, along with conceptual clarity, is essential for measuring distress in research and clinical practice.

Background: The role and mechanism of centromeric protein N (CENPN), which has been associated with the development of various cancer types, are yet unclear in Gastric adenocarcinoma (STAD). Methods: Data from The Cancer Genome Atlas and Genotype Tissue Expression were used to examine the expression of CENPN in STAD and neighboring tissues. Xiantao Academic was used to perform Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis on CENPN. By reviewing TCGA database, the relationship between CENPN expression and immune cell infiltration was assessed. The expression of CENPN in STAD and surrounding tissues was confirmed by immunohistochemical staining, and the correlation between CENPN expression and clinicopathological characteristics was examined. CENPN was depleted in AGS cells with siRNAs, and its impact on proliferation was measured by CCK-8 and EdU assays. Following siRNA transfection, flow cytometry was performed to identify cell cycle and apoptotic alterations in AGS cells. Results: CENPN was highly expressed in STAD tissues. The degree of invasion, TNM stage, and lymph node metastases were all substantially linked with CENPN expression. GO|KEGG Enrichment analysis revealed that CENPN was essential for the cell cycle, DNA replication, chromosomal segregation, and nuclear division, among other important signaling pathways. Further investigation revealed a positive correlation between CENPN expression and Th2 cells and NK CD56dim cells and a negative correlation between CENPN expression and mast cells , pDC cells,NK cells and B cells. When CENPN expression in AGS cells was knocked down, cell proliferation dramatically reduced, and the percentage of cells in the S and G2-M phases decreased significantly. In addition, compared to the control group, the proportion of apoptotic AGS cells significantly increased after downregulating the expression level of CENPN. Conclusion: According to our data, CENPN acts as an oncogene in STAD and may be a viable therapeutic target.