Cases Of Primary Cancer Research Articles

Validating Risk Prediction Models for Multiple Primaries and Competing Cancer Outcomes in Families With Li-Fraumeni Syndrome Using Clinically Ascertained Data.

There exists a barrier between developing and disseminating risk prediction models in clinical settings. We hypothesize that this barrier may be lifted by demonstrating the utility of these models using incomplete data that are collected in real clinical sessions, as compared with the commonly used research cohorts that are meticulously collected. Genetic counselors (GCs) collect family history when patients (ie, probands) come to MD Anderson Cancer Center for risk assessment of Li-Fraumeni syndrome, a genetic disorder characterized by deleterious germline mutations in the TP53 gene. Our clinical counseling-based (CCB) cohort consists of 3,297 individuals across 124 families (522 cases of single primary cancer and 125 cases of multiple primary cancers). We applied our software suite LFSPRO to make risk predictions and assessed performance in discrimination using AUC and in calibration using observed/expected (O/E) ratio. For prediction of deleterious TP53 mutations, we achieved an AUC of 0.78 (95% CI, 0.71 to 0.85) and an O/E ratio of 1.66 (95% CI, 1.53 to 1.80). Using the LFSPRO.MPC model to predict the onset of the second cancer, we obtained an AUC of 0.70 (95% CI, 0.58 to 0.82). Using the LFSPRO.CS model to predict the onset of different cancer types as the first primary, we achieved AUCs between 0.70 and 0.83 for sarcoma, breast cancer, or other cancers combined. We describe a study that fills in the critical gap in knowledge for the utility of risk prediction models. Using a CCB cohort, our previously validated models have demonstrated good performance and outperformed the standard clinical criteria. Our study suggests that better risk counseling may be achieved by GCs using these already-developed mathematical models.

Abstract 2195: Intrauterine device use and risk of invasive epithelial ovarian cancer: A population-based case-control study

Abstract Introduction: Ovarian, fallopian tube, and primary peritoneal cancers (hereafter referred to as ovarian cancer) are the most fatal gynecologic cancers. Thus, it is imperative to identify strategies that can reduce the risk of the disease. Several contraceptive methods have been shown to be associated with a reduced risk of ovarian cancer, including combined oral contraceptives, injectable progestins, and tubal ligation. However, the use of these contraceptive methods has been decreasing in the U.S., with a growing preference for intrauterine devices (IUDs) for pregnancy prevention. Previous case-control studies on the association between IUD use and ovarian cancer risk have found inconsistent results. Notably, previous studies had small sample sizes and did not restrict to invasive epithelial tumors. The current analysis assessed the association between IUD use and risk of invasive epithelial ovarian cancer in a large population-based case-control study. Methods: This analysis used data from 1,713 people diagnosed with primary invasive epithelial ovarian cancer (cases) and 2,348 cancer-free people (controls) participating in a case-control study conducted in Los Angeles, CA from 1992-2010. The study consisted of four waves of recruitment with similar enrollment and data collection methods. Logistic regression models were fit to assess the association between IUD use and risk of invasive epithelial ovarian cancer. All models were adjusted for age, race/ethnicity, education, first-degree family history of ovarian cancer, endometriosis, body mass index, duration of combined oral contraceptive use, parity, duration of breastfeeding, tubal ligation, and study wave. Heterogeneity across the study waves and the ovarian cancer histotypes was evaluated using standard meta-analysis techniques. Results: There was no statistically significant association between IUD use and risk of invasive epithelial ovarian cancer (odds ratio=1.09, 95% confidence interval 0.93-1.28). This result was consistent across the study waves and the ovarian cancer histotypes (p-values for heterogeneity>0.05). Conclusion: IUD use was not associated with the risk of invasive epithelial ovarian cancer. Analysis by IUD type (i.e., hormone-releasing vs copper IUDs) was not possible in this study as these data were not collected. Future research should examine whether the type of IUD (i.e. copper versus hormone-releasing) may have different effects on risk of ovarian cancer. Citation Format: Minh Tung Phung, Yuting Wang, Alice W. Lee, Malcolm C. Pike, Anna H. Wu, Celeste Leigh Pearce. Intrauterine device use and risk of invasive epithelial ovarian cancer: A population-based case-control study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2195.

Oral prednisolone and warfarin and risk of oesophageal cancer: A case-control study.

A recent epidemiological study systematically screened 250 prescription medications for associations with oesophageal cancer risk, using Scottish data, and identified an increased risk with use of prednisolone and warfarin. We investigated whether oral prednisolone or warfarin use was associated with increased oesophageal cancer risk. A case-control study was conducted within the Clinical Practice Research Datalink. In the primary analysis oesophageal cancer cases were identified from linked cancer registry records. Up to 5 cancer-free controls were matched to each case (based upon sex, birth year, GP practice and year of GP registration). Prednisolone and warfarin medications were identified from prescribing records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression after adjusting for covariates including demographics, comorbidities and medication use. There were 4552 oesophageal cancer cases and 22,601 matched control participants. Overall, there was no evidence of an increased risk of oesophageal cancer with oral prednisolone use (unadjusted OR=1.16 95% CI 1.06, 1.27 and adjusted OR=0.99 95% CI 0.89, 1.11) or warfarin use (unadjusted OR=1.12 95% CI 0.99, 1.28 and adjusted OR=1.08 95% CI 0.92, 1.27). In this large population-based study, oral prednisolone and warfarin were not associated with oesophageal cancer risk.

Residential greenness and lower breast and prostate cancer incidence: Evidence from a retrospective cohort study of 977,644 participants from Israel

BackgroundThere is limited evidence on the associations between residential greenness and cancer incidence in longitudinal studies. ObjectivesThe aim of the study was to evaluate the associations between weighted mean residential greenness exposure and cancer incidence. MethodsThis is a registry based retrospective cohort study of 977,644 participants. The residential greenness exposure was estimated for every participant, as the weighted mean residential greenness exposure. This was based on the mean Normalized Difference Vegetation Index (NDVI) in the residential small geographic area and the duration of the residence in this area. Cancer incidence cases included consecutive newly diagnosed cases of primary cancer. Analyses were conducted for all cancer sites, lung cancer, bladder cancer, breast cancer, prostate cancer and melanoma-skin cancer. Cox regression models were used to evaluate the crude and adjusted associations (hazards ratios (HR) and its 95 % confidence intervals (CIs)) between tertiles of residential greenness and cancer incidence. Further adjusted models to nitrogen oxides (NOx) were estimated. ResultsAfter adjustment to covariates, exposure to the highest tertile of residential greenness, compared to the lowest, were associated with lower risk for all cancer sites (HR = 0.88, 95 % CI: 0.86–0.90), breast cancer (HR = 0.85, 95 % CI: 0.80–0.89) and prostate cancer (HR = 0.85, 95 % CI: 0.79–0.91). In addition, lower risk were observed for the middle tertile of exposure and all cancer sites (HR = 0.88, 95 % CI: 0.86–0.90), breast cancer (HR = 0.88, 95 % CI: 0.84–0.92) and prostate cancer (HR = 0.83, 95 % CI: 0.79–0.89). There was no evidence for mediation by air pollution (NOx). DiscussionResidential greenness demonstrated beneficial associations with lower risk for all cancers, breast and prostate cancers. If our observations will be replicated, it may present a useful avenue for public-health intervention to reduce cancer burden through the provision of greenness exposure.

Solitary Pancreatic Metastasis from an Ovarian Carcinoma: A Diagnostic Perplexity

Ovarian cancer presenting as an isolated pancreatic metastasis after years of treatment is extremely rare. Most such patients are easily misdiagnosed as a case of primary pancreatic cancer. We herein describe a unique case of posttreatment high-grade serous papillary ovarian carcinoma metastasizing to the pancreas that mimicked primary pancreatic cancer and caused a diagnostic dilemma. The approach to such a case, pathogenesis, differential diagnosis, management, and a brief literature review is also presented.

Primary squamous cell carcinoma of the parotid salivary gland: a clinical observation

Introduction. Malignant tumors of the salivary glands account for 3–5 % of all cases of head and neck cancer. Squamous cell carcinoma is the rarest histological variant of this pathology. It accounts for an average of 1.6 %. Among large salivary gland tumors, squamous cell carcinoma most often occurs in the parotid salivary gland.Aim. To present a clinical case of primary disseminated cancer of the parotid salivary gland with squamous cell structure.Clinical observation. A 70-year-old patient was under observation who was diagnosed with a primary squamous cell tumor of the parotid salivary gland with multiple metastases during a complex examination. He was sick for about 6 months when asymmetry of left half of the face appeared due to a painful neoplasm in the parotid salivary gland. Recently, the patient has noted increased tumor growth. Objective examination revealed peripheral paralysis of the facial nerve on the left. In the parotid-masticatory region on the left, with a transition to the zygomatic region, there is a dense painful immobile exophytic tumor with infiltration into soft tissues of the face and skin 6.5 × 5.0 cm in size with an ulcer in the center. Laterally, it reaches the tragus, and at the bottom-the angle of the lower jaw. In the submandibular region on the left, metastatic lymph nodes 2.5 × 2.0 cm in size are palpated. A biopsy was collected. Histological conclusion: non-keratinizing squamous cell carcinoma. Expression of the programmed death receptor ligand (PD-L1) in the tumor is negative. Mutations of genes Her2-neu and BRAF were not detected. According to medical imaging methods, multiple metastases were found in the lungs, liver, zygomatic bone and tumor growth in the maxillary sinus on the left. The diagnosis was established: cancer of the parotid salivary gland, stage IVC, cT4N1M1, with metastases to the liver, lungs and bones. Polychemotherapy was prescribed according to the scheme: 5-fluorouracil + cisplatin + cetuximab + bisphosphonates. After 3 cycles, a partial regression is obtained.Conclusion. The primary squamous cell carcinoma is prone to an aggressive course and has an unfavorable prognosis, especially in patients over 60 years of age with skin and facial nerve damage, as well as the presence of regional and distant metastases. Differential diagnosis is necessary to exclude the secondary nature of the tumor. The presented case is a rare example of primary squamous cell carcinoma of the parotid salivary gland with extensive metastatic lesion and regression of the pathological process after polychemotherapy in combination with targeted therapy.

Lingual Artery as the Recipient Vessel of Choice in Patients Requiring a Second or Third Free Flap in Recurrent Oral Cancers and Vessel-Depleted Neck: A 5-Year Experience in a Single Institute.

Introduction  Reconstruction with free flaps becomes a challenge in recurrent cases having previously treated necks, in patients who have received prior radiation therapy or chemotherapy or both, and where the patient has already undergone free flap reconstruction in a prior surgery. Depleted cervical recipient vessels can increase the complexity of reconstruction in achieving successful free flap prefusion and thereby increasing flap thrombosis and eventually failure. Materials and Methods  Over a period of 5 years from January 2018 to February 2023, we encountered a total of 22 cases of recurrent or second primary oral cancer with bilateral necks operated, postadjuvant chemo-radiotherapy, and requiring a second or third free flap reconstruction. In most of the cases we resorted to the lingual artery as the recipient artery of choice. Results  No flap loss was reported. No cases were reexplored either for hematoma or for congestion. All patients recovered uneventfully. Conclusion  To the best of our knowledge, there has been no paper yet that focuses on the lingual artery to be the recipient vessel of choice in recurrent oral cancers. We find the lingual artery to be a reliable and safe option and advocate its usage as recipient vessel of choice in recurrent oral cancers requiring more than one free flap reconstruction.

Longitudinal analysis of long-term outcomes of colorectal cancer after laparotomy and laparoscopic surgery: The Shizuoka study.

Long-term cancer prognosis after initial surgical procedures is an unlikely endpoint for clinical trials. Medical claim databases may aid in addressing this issue regardless of limited information on disease and patient background. However, the long-term prognosis (especially regarding long-term care needs) following surgical procedures remains unclear. This study aimed to assess whether long-term outcomes, such as the exacerbation of long-term care needs and mortality, differ with surgical methods. Using a longitudinal study with linkage between medical claim and long-term care database, patients with primary colorectal cancer who underwent initial colonoscopies were identified through anonymized data in Japan (Shizuoka Kokuho Database, 2012-2018). Odds ratios (ORs) for long-term outcomes (long-term care needs and all-cause mortality during a 6.5-year follow-up period) were analyzed using logistic regression to compare laparoscopy and endoscopic surgery to laparotomy. Overall, 3,744 primary colorectal cancer cases (822 laparotomies, 705 laparoscopies, and 2,217 endoscopic surgeries) were included. Compared to the laparotomy group, the crude OR for exacerbation of long-term care needs in the laparoscopic surgery group was 0.376 (95% confidence interval, 0.227, 0.624), while the OR for all-cause mortality was 0.22 (0.329, 0.532). This is the first study to analyze long-term prognosis after surgery for patients with colorectal cancer to combine medical and long-term needs data. As the national health insurance claim database rarely includes information on cancer stage and comorbidities, better prognosis on endoscopic surgery may need careful interpretation. Therefore, laparoscopy has superior outcomes in terms of long-term care needs and mortality compared to those of laparotomy.

A Case of Double Primary Carcinoma was Accidentally Found During Operation: Hepatocellular Carcinoma and Appendiceal Mucinous Adenocarcinomas

Background: Synchronous double primary cancer of hepatocellular carcinoma (HCC) and appendiceal mucinous adenocarcinomas has not been reported. Liver metastasis of digestive tract tumors is so common that it is easy to ignore the existence of double primary cancer in the digestive system. The appendiceal malignant tumor itself is easy to be misdiagnosed or missed. For a better understanding of HCC and appendiceal mucinous adenocarcinomas, the information on our recent case has been summarized. Case Presentation: A 58-year-old man was admitted with repeated upper abdominal pain for one week. Imaging examination and liver biopsy pathology were diagnosed as hepatocellular carcinoma. Colonoscopy showed no obvious organic lesions in the terminal ileum and the whole large intestine. We had anatomical resection of the S5 and S6 segments of the liver. At the same time, two suspicious lesions in the right liver were ablated by microwave. But at the end of the operation, we accidentally found a hard mass about 3 cm × 3 cm in size at the end of the appendix. And the rapid pathological results showed appendiceal adenocarcinoma, so we had a right hemicolectomy. So far, the diagnosis of the patient was changed to synchronous double primary cancer consisting of HCC and appendiceal mucinous adenocarcinomas. Conclusion: It is the first time we have reported a case of synchronous double primary hepatic cancer consisting of HCC and appendiceal mucinous adenocarcinomas in the world. Due to the rarity and unspecific clinical features, it is extremely challenging to be diagnosed preoperatively. It requires a more comprehensive understanding of the patient's medical history, careful physical examination, and comprehensive exploration of the abdominal cavity during the operation to avoid missed diagnosis. Patients with HCC and appendiceal mucinous adenocarcinomas are generally associated with poor prognosis. It needs we put forward new countermeasures for the new question.

Ultravision joins the fight against peritoneal cancer

Ultravision join the fight against peritoneal cancer Peritoneal metastases (PM) refers to cancer that has spread from primary cancer in other organs in the abdomen to the peritoneum, the membrane that lines the abdominal cavity. According to the WHO, there are over seven million new primary abdominal cancer cases each year (1), and depending upon the primary cancer, up to 60% of these will present evidence of PM. (2) As a result, it is estimated that every 30 seconds, a patient is diagnosed with peritoneal metastases. In most cases, at diagnosis, it is typically an advanced, incurable disease. Current therapy guidelines recommend palliative systemic chemotherapy. However, with poor blood supply to the peritoneum, efficacy is poor, and side effects are debilitating. As a result, this terrible disease has a poor prognosis, with patient survival worse than lung and liver metastases. (3) It remains a high, unmet medical need.

Crystal structures and molecular dynamics simulations of a humanised antibody fragment at acidic to basic pH

Antibody-fragment (Fab) therapy development has the potential to be accelerated by computational modelling and simulations that predict their target binding, stability, formulation, manufacturability, and the impact of further protein engineering. Such approaches are currently predicated on starting with good crystal structures that closely represent those found under the solution conditions to be simulated. A33 Fab, is an undeveloped immunotherapeutic antibody candidate that was targeted to the human A33 antigen homogeneously expressed in 95% cases of primary and metastatic colorectal cancers. It is now used as a very well characterised testing ground for developing analytics, formulation and protein engineering strategies, and to gain a deeper understanding of mechanisms of destabilisation, representative of the wider therapeutic Fab platform. In this article, we report the structure of A33 Fab in two different crystal forms obtained at acidic and basic pH. The structures overlapped with RMSD of 1.33 Å overall, yet only 0.5 Å and 0.76 Å for the variable- and constant regions alone. While most of the differences were within experimental error, the switch linker between the variable and the constant regions showed some small differences between the two pHs. The two structures then enabled a direct evaluation of the impact of initial crystal structure selection on the outcomes of molecular dynamics simulations under different conditions, and their subsequent use for determining best fit solution structures using previously obtained small-angle x-ray scattering (SAXS) data. The differences in the two structures did not have a major impact on MD simulations regardless of the pH, other than a slight persistence of structure affecting the solvent accessibility of one of the predicted APR regions of A33 Fab. Interestingly, despite being obtained at pH 4 and pH 9, the two crystal structures were more similar to the SAXS solution structures obtained at pH 7, than to those at pH 4 or pH 9. Furthermore, the P65 crystal structure from pH 4 was also a better representation of the solution structures at any other pH, than was the P1 structure obtained at pH 9. Thus, while obtained at different pH, the two crystal structures may represent highly (P65) and lesser (P1) populated species that both exist at pH 7 in solution. These results now lay the foundation for confident MD simulations of A33 Fab that rationalise or predict behaviours in a range of conditions.

Analysis of clinicopathological features and prognosis of double primary cervical cancer and ovarian cancer based on SEER database.

Double primary cervical cancer and ovarian cancer refer to the simultaneous or successive appearance of cervical cancer and ovarian cancer in the same patient. Due to the low incidence, there are few relevant reports. Therefore, this study is the first population-based analysis of the clinicopathological features as well as the prognostic status of double primary cervical cancer and ovarian cancer. We look forward to providing a reference for future clinical diagnosis and treatment. In this study, 473 cases of double primary cervical cancer and ovarian cancer were collected from 1975 to 2019 through the SEER database. Double primary cancers were considered non-synchronous when they were diagnosed more than 6months apart and were classified as Group A. Double primary cancers were considered synchronous when the interval between diagnosis of the two tumors was less than or equal to 6months and was classified as group B. In this study, the incidence of double primary cervical cancer and ovarian cancer accounted for 0.39% of primary cervical cancer and 0.24% of primary ovarian cancer in the same period. 80% of patients developed second cancer within 107months of their first cancer being diagnosed. Compared with non-synchronous cancer, synchronous cancer is mainly characterized by simultaneous bilateral ovarian involvement and early clinical stage, but highly malignant, high lymph node metastasis rate, and poor prognosis. Most patients developed second cancer within 107months of their first cancer being diagnosed. Age at diagnosis, bilateral ovarian invasion, the interval between diagnoses, pathological type and stage of ovarian cancer, and grade of cervical cancer are important factors affecting survival, which still needs to be confirmed by more extensive studies in future.

Comparison of primary payer in cancer registry and discharge data.

To determine agreement between variables capturing the primary payer at cancer diagnosis across the Pennsylvania Cancer Registry (PCR) and statewide facility discharge records (Pennsylvania Health Care Cost Containment Council [PHC4]) for adults younger than 65 years, and to specifically examine factors associated with misclassification of Medicaid status in the registry given the role of managed care. Cross-sectional analysis of the primary cancer cases among adults aged 21 to 64 years in the PCR from 2010 to 2016 linked to the PHC4 facility visit records. We assessed agreement of payer at diagnosis (Medicare, Medicaid, private, other, uninsured, unknown) across data sources, including positive predictive value (PPV) and sensitivity, using the PHC4 records as the gold standard. The probability of misclassifying Medicaid in registry was estimated using multivariate logit models. Agreement of payers was high for private insurance (PPV, 89.7%; sensitivity, 83.6%), but there was misclassification and/or underreporting of Medicaid in the registry (PPV, 80%; sensitivity, 58%). Among cases with "other" and "unknown" insurance, 73.8% and 62.1%, respectively, had private insurance according to the PHC4 records. Medicaid managed care was associated with a statistically significant increase of 12.6 percentage points (95% CI, 9.4-15.8) in the probability of misclassifying Medicaid enrollment as private insurance in the registry. Findings suggest caution in conducting and interpreting research using insurance variables in cancer registries.

Cardiovascular Mortality in Ovarian Cancer Patients: An Analysis of Patient Characteristics Using the SEER Database.

Background and Objectives: Cardiovascular disease (CVD) is a major contributor to the high mortality rate among individuals with ovarian cancer. Nevertheless, there is limited understanding regarding the specific patient attributes that might impact the risk of CVD in this group. Materials and Methods: A retrospective cohort study was performed using the SEER database to analyze primary ovarian cancer cases from 2000 to 2019. Multivariable logistic regression analysis was employed to identify patient characteristics linked to cardiovascular mortality. Results: The cohort included 41,930 cases of patients who were alive, 54,829 cases of cancer-related deaths, 3003 cases of cardiovascular-related deaths, and 10,238 cases with other causes of death. Poorly differentiated cancer cells and distant metastasis were associated with a higher risk of cardiovascular mortality. Logistic regression analysis identified age, year of diagnosis, race, laterality, and staging as significant risk factors for cardiovascular cause of death. The risk of cardiovascular cause of death was lower in patients aged 31-60 and higher in those aged over 60 years old, and the risk also increased with a later year of diagnosis. Patients who were not white were at a higher risk of cardiovascular cause of death. Additionally, bilateral ovarian cancer and distant staging disease were linked to elevated risks of cardiovascular cause of death. Conclusion: Cardiovascular mortality is a significant concern in ovarian cancer patients, and several patient characteristics are associated with an increased risk. Our study suggests that targeted interventions to improve cardiovascular health in high-risk patients, such as those with comorbidities or an advanced stage at diagnosis, may improve survival in this population.

A case of primary multiple synchronous radiogenic cancer in clinical practice

There is an increase in the number of patients with secondary malignant neoplasms. In addition, in some subgroups after radical cancer treatment, the lifetime risk of developing secondary malignant neoplasms can be as high as 33 %. Secondary malignancies remain an important cause of death in patients who have received radical cancer treatment. The presented clinical case demonstrates the risk of developing primary multiple malignant neoplasms after radiation therapy and chemotherapy. A 39‑year-old patient with diffuse large B-cell non-Hodgkin lymphoma underwent definitive treatment including chemo-and radiotherapy. Ten years later, the patient developed the induced multiple malignant tumors: a malignant neoplasm of the heart — myofibrosarcoma of the right ventricle with invasion of the anterior wall of the right ventricle Stage IIIB G2T3N0M0, left breast cancer Stage IIIA T3N2M0. The choice of treatment tactics for this category of patients remains particularly difficult.

Recent Advances in Locoregional Therapy of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is responsible for 90% of primary hepatic cancer cases, and its incidence with associated morbidity and mortality is growing worldwide. In recent decades, there has been a revolution in HCC treatment. There are three main types of locoregional therapy: radiofrequency ablation, transarterial chemoembolisation, and transarterial radioembolisation. This article summarises recent advances in locoregional methods.

Immune profile of primary and recurrent epithelial ovarian cancer cases indicates immune suppression, a major cause of progression and relapse of ovarian cancer

BackgroundOvarian cancer is the third most prevalent cancer in Indian women. Relative frequency of High grade serous epithelial ovarian cancer (HGSOC) and its associated deaths are highest in India which suggests the importance of understanding their immune profiles for better treatment modality. Hence, the present study investigated the NK cell receptor expression, their cognate ligands, serum cytokines, and soluble ligands in primary and recurrent HGSOC patients. We have used multicolor flow cytometry for immunophenotyping of tumor infiltrated and circulatory lymphocytes. Procartaplex, and ELISA were used to measure soluble ligands and cytokines of HGSOC patients.ResultsAmong the enrolled 51 EOC patients, 33 were primary high grade serous epithelial ovarian cancer (pEOC) and 18 were recurrent epithelial ovarian cancer (rEOC) patients. Blood samples from 46 age matched healthy controls (HC) were used for comparative analysis. Results revealed, frequency of circulatory CD56Bright NK, CD56Dim NK, NKT-like, and T cells was reduced with activating receptors while alterations in immune subsets with inhibitory receptors were observed in both groups. Study also highlights differential immune profile of primary and recurrent ovarian cancer patients. We have found increased soluble MICA which might have acted as “decoy” molecule and could be a reason of decrease in NKG2D positive subsets in both groups of patients. Furthermore, elevated level of serum cytokines IL-2, IL-5, IL-6, IL-10, and TNF-α in ovarian cancer patients, might be associated with ovarian cancer progression. Profiling of tumor infiltrated immune cells revealed the reduced level of DNAM-1 positive NK and T cells in both groups than their circulatory counterpart, which might have led to decrease in NK cell’s ability of synapse formation.ConclusionsThe study brings out differential receptor expression profile on CD56BrightNK, CD56DimNK, NKT-like, and T cells, cytokines levels and soluble ligands which may be exploited to develop alternate therapeutic approaches for HGSOC patients. Further, few differences in the circulatory immune profiles between pEOC and rEOC cases, indicates the immune signature of pEOC undergoes some changes in circulation that might facilitated the disease relapse. They also maintains some common immune signatures such as reduced expression of NKG2D, high level of MICA as well as IL-6, IL10 and TNF-α, which indicates irreversible immune suppression of ovarian cancer patients. It is also emphasized that a restoration of cytokines level, NKG2D and DNAM-1on tumor infiltrated immune cells may be targeted to develop specific therapeutic approaches for high-grade serous epithelial ovarian cancer.

MLH1 Loss in Primary Prostate Cancer.

Among mismatch repair-deficient (MMRd) prostate cancers, loss of MLH1 is relatively uncommon and few cases have been reported in detail. Here, we describe the molecular features of two cases of primary prostate cancer with MLH1 loss detected by immunohistochemistry, and in one case, confirmed via transcriptomic profiling. Both cases were microsatellite stable on standard polymerase chain reaction (PCR)-based microsatellite instability (MSI) testing, but showed evidence of MSI on a newer PCR-based long mononucleotide repeat (LMR) assay and by next-generation sequencing. Germline testing was negative for Lynch syndrome-associated mutations in both cases. Targeted or whole-exome tumor sequencing using multiple commercial/academic platforms (Foundation, Tempus, JHU, and UW-OncoPlex) showed modestly elevated, though variable, tumor mutation burden estimates (2.3-10 mutations/Mb) consistent with MMRd, but without identifiable pathogenic single-nucleotide or indel mutations in MLH1. Copy-number analysis confirmed biallelic MLH1 loss in one case and monoallelic MLH1 loss in the second case, without evidence of MLH1 promoter hypermethylation in either. The second patient was treated with single-agent pembrolizumab and demonstrated a short-lived prostate-specific antigen response. These cases highlight the challenges in identifying MLH1-deficient prostate cancers using standard MSI testing and commercial sequencing panels, and support the utility of immunohistochemical assays and LMR- or sequencing-based MSI testing for detection of MMRd prostate cancers.

Resectability and prognosis of gallbladder cancer: a cross-sectional study of 100 cases from a tertiary care centre of Eastern Nepal.

It is a prospective observational study including all cases of primary cancers of the gallbladder in the Department of Surgical Gastroenterology at a tertiary care center over the period from January 2014 to December 2019. The primary endpoint was resectability and overall survival. During the study period, 100 patients with GBC were reported. The mean age at the time of diagnosis was 52.5 years, with a female predominance (67%). The curative intent resection (radical cholecystectomy) was possible in 30 (30%) patients; while 18 (18%) required palliative surgical treatment. The overall survival of the entire group was 9 months; while those patients who underwent surgery with curative intent had a median overall survival of 28 months after a median follow-up of 42 months. This study found that only one-third of patients achieve radical surgery with curative intent. Overall, the prognosis of patients is poor with a median survival of less than a year due to the advanced stage disease. Multimodality treatment, screening ultrasound, and neo-/adjuvant therapy may improve survival.

Abstract 6474: Stress-related sick leave and subsequent cancer risk: A Swedish national register study of 516 678 cancer cases

Abstract Background: Despite previous studies investigating psychological stress in relation to cancer risk, no consensus has been reached as to whether stress is a modifiable risk factor for cancer. This study aims to investigate whether sick leave due to psychological stress can affect the risk of developing cancer. Method: This is a matched case-control study using Swedish nation-wide register data (study period 2005-2018). The main exposure is stress-related sick leave defined as registered sick leave due to psychological stress with the diagnosis codes of F43 (International Classification of Diseases codes: ICD) and its subclassifications and hereafter referred to as stress leave. For each primary cancer case (except non-melanoma skin cancer), up to five cancer-free controls were matched based on sex, age and county. Conditional logistic regression, conditioned on matching factors and adjusting for socioeconomic factors, was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). For subgroup analyses by specific tumor sites, Bonferroni-corrected significance level of 0.002 (alpha value divided by the number of tumor sites = 0.05/24) was also applied. Results: The study comprised 516 678 cancer cases and 2 357 433 matched controls. Stress leave of any duration, was associated with a modestly increased risk of cancer, with the highest risk observed for 1-30 days of leave, vs no leave during follow-up (adjusted OR 1.05, 95% CI 1.02-1.09). In subgroup analyses by tumor sites, stress leave was associated with an increased risk of prostate cancer (adjusted OR for >90 days vs no stress leave 1.10, 95% CI 1.01-1.20) and cervix cancer (adjusted OR>90 days vs no leave 1.11, 95% CI 1.05-1.17). For lung cancer, an inverse risk relationship was found (adjusted OR>90 days vs no leave 0.88, 95% CI 0.77-0.99). For other tumor sites, associations were generally null or had wide confidence intervals. After applying a Bonferroni-corrected significance level, the association was still significant for cervical cancer. Further examination by sex, specific types of psychological stress and cancer groups based on established etiology (tobacco use, obesity, alcohol consumption and gastric hyperacidity) showed a clear exposure-response trend in men and pronounced associations for exhaustion disorder (ICD code: F43.8A) and tobacco-related cancers. In a post-hoc analysis, the association for other HPV-related cancers was similar to that for cervical cancer but not statistically significant. Conclusion: In this register study covering the entire Swedish population, we found that stress-related sick leave was associated with modestly higher risk of cancer, particularly the risk of cervical cancer. Potential higher risk of prostate cancer and lower risk of lung cancer were observed, though these associations were not statistically significant after controlling for multiple testing. Citation Format: Sai San Moon Lu, Jenny Hadrévi, Lisbeth Slunga Järvholm, Florentin Späth, Richard Palmqvist, Tommy Olsson, Sophia Harlid, Bethany van Guelpen. Stress-related sick leave and subsequent cancer risk: A Swedish national register study of 516 678 cancer cases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6474.