History Of Other Cancers Research Articles

Consideration of Risk Factors of Family History of Lung Cancer or Personal History of Other Cancers for Lung Cancer Screening in Those Who Have Never Smoked

Consideration of Risk Factors of Family History of Lung Cancer or Personal History of Other Cancers for Lung Cancer Screening in Those Who Have Never Smoked

Survival Analysis of Early-Stage NSCLC Patients Following Lobectomy: Impact of Surgical Techniques and Other Variables on Long-Term Outcomes.

Survival Analysis of Early-Stage NSCLC Patients Following Lobectomy: Impact of Surgical Techniques and Other Variables on Long-Term Outcomes.

Pathogenic germline variant prevalence and genetic testing outcomes in patients with urothelial carcinoma.

741 Background: Urothelial carcinoma (UC) is rarely attributed to hereditary causes, but recent studies suggest inherited factors may play a larger role. Current guidelines recommend considering genetic evaluation in patients with bladder cancer diagnosed at <50 years old or a personal or family history of Lynch Syndrome-associated cancers. However, the full pathogenic germline variant landscape and optimal genetic evaluation criteria in UC remain poorly understood. In this study, we report the genetic testing outcomes and clinicopathologic characteristics of patients with UC who underwent genetic evaluation. Methods: A retrospective analysis of all patients with UC who underwent genetic evaluation and testing at the University of Michigan Cancer Genetics Clinic between 2002 and 2024 was performed. Patients who did not have a UC diagnosis code or did not undergo germline testing were excluded. Genetic testing outcomes, variant prevalence and characterization, and associated clinicopathologic features were recorded. Fisher’s Exact test was used to compare clinicopathologic factors between individuals found to have a pathogenic or likely pathogenic variant (PV/LPV) vs. those with negative or uninformative testing. Results: Among 151 patients referred to cancer genetics, 129 underwent genetic testing. Median age at diagnosis was 59 (IQR: 48-68). Most patients (58%) had non-muscle invasive disease at initial diagnosis; 26% had muscle invasive disease, 9% had metastatic disease, and 7% were unknown. Pure urothelial histology was most frequent (71%). A majority (83%) had primary tumor location in the bladder. The most common reasons for referral to genetic counseling were personal history of multiple cancers (58%), diagnosis at perceived younger age (19%), and suspicion for a hereditary syndrome based on syndromic features (9%). Among all tested patients, 35 (27%) had a confirmed PV/LPV; 18 (14%) had a variant of unknown significance (VUS) only. Most frequent PV/LPV genes were MSH2 (n=8, 6%), BRCA2 (n=5, 4%), CHEK2 (n=4, 3%), APC (n=4, 3%), and MUTYH (n=4, 3%). There were no statistically significant differences in testing outcomes based on age of diagnosis (<65 vs >65, p=0.83; <55 vs >55, p=0.16; <45 vs >45, p=0.61), primary tumor location, stage at initial diagnosis, personal history of other cancers, or first-degree family history of urothelial cancer. Oncoprint visualization will be presented. Conclusions: Among patients with UC referred to cancer genetics who had genetic testing, 27% had a confirmed PV/LPV, although this cohort was a selected population. Age threshold and traditional clinicopathologic features were not associated with genetic testing results. These findings may suggest a broader use of genetic evaluation in UC. Future studies should determine the optimal genetic evaluation criteria in UC given the impact on cascade testing and potential therapeutic implications.

Outcomes of surveillance in patients with intraductal papillary mucinous neoplasms (IPMNs) who tested negative for high-risk mutations (HRMs) in next-generation sequencing (NGS).

704 Background: HRMs in NGS have demonstrated high sensitivity and specificity for predicting advanced neoplasia in patients with IPMNs. However, the outcomes of surveillance in patients who tested negative for these HRMs have not been investigated in prior studies. This study aimed to identify the predictors of progression in patients with negative NGS results for HRMs. Methods: We conducted a retrospective review of prospectively collected data from patients who underwent NGS testing between 2016 and 2023 in our pancreatic cancer prevention program. Patients without IPMNs (i.e., negative for KRAS/GNAS), with HRMs, and those without at least one follow-up imaging post-NGS were excluded from the study. Progression was defined as the development of new or additional worrisome features or high-risk stigmata (per Kyoto guidelines), or advanced neoplasia (HGD/PDAC) following NGS testing. A Cox proportional hazards regression model was used to identify predictors of progression. Results: A total of 543 patients underwent NGS testing during the study period, of which 210 patients met the inclusion criteria. The median follow-up duration was 22 months (IQR = 12-36). Of these, 72 patients developed progression following NGS testing. A total of 11 patients underwent surgical resection, and 5 of them had HGD. Factors predictive of progression included a history of smoking (HR = 1.74; 95% CI = 1.06 - 2.86), larger cyst size (HR = 1.09; 95% CI = 1.03 - 1.16), and the presence of a dilated main pancreatic duct (MPD) (HR = 2.56; 95% CI = 1.5 - 4.4) prior to NGS testing. The median time to progression for patients with worrisome features was 33 months, compared to 59 months for those without worrisome features at baseline. Similarly, the median time to progression for patients with cysts ≥ 2 cm was 38 months, compared to 57 months for those with cysts < 2 cm. Conclusions: Patients who test negative for high-risk mutations in NGS are not exempt from the risk of progression. Any smoking history and presence of any worrisome features before NGS testing showed to be independent predictors of disease progression. For patients with smoking history, worrisome features or cysts ≥ 2 cm, frequent surveillance should be recommended following NGS testing. Results of Cox proportional hazards regression model for identifying the predictors of progression. Variables Hazards ratio (HR) 95% Confidence Interval P-value Age 0.99 0.96 – 1.01 0.257 Male sex 1.02 0.62 – 1.7 0.93 White race 1.07 0.63 – 0.83 0.8 Family history of pancreatic cancer 0.6 0.26 – 1.36 0.22 Personal history of other cancers 0.95 0.56 – 1.62 0.86 Diabetes 1.22 0.72 – 2.05 0.46 Any history of smoking 1.74 1.06 – 2.86 0.03* Pre-NGS cyst size (cm) 1.09 1.03 – 1.16 0.006* Pre-NGS dilated main pancreatic duct (≥5mm) 2.56 1.5 – 4.4 0.001* Pre-NGS presence of mural nodules 0.32 0.04 – 2.37 0.26 *Significant p-value.

Diagnostic accuracy and prognostic factors of uterine serous carcinoma in Japanese women: a multi-center study.

This multi-center retrospective study aimed to clarify the characteristics, diagnostic accuracy, treatment outcomes, and prognostic factors of uterine serous carcinoma (USC) in Japanese women. The medical records of 193 patients who were treated between 2006 and 2008 at 24 participating institutions in the Japanese Clinical Oncology Group were examined, and pathological slides of 188 patients were re-checked through central pathology review (CPR), hematoxylin-eosin staining, and immunohistochemistry. USC was confirmed in 144 of the 188 (76.6%) patients using CPR, and only 50% were correctly diagnosed preoperatively. Forty-three patients were diagnosed with non-serous carcinoma, whereas one patient had metastasis from another organ. The average age was 65.7 years, and 19% of patients had a history of other cancers. The incidence of stage III-IV disease was 52.8%, and lymph node metastasis was found in 28.5% of patients. Extrauterine spread and distant metastasis occurred in 39% and 14% of patients, respectively. The 2-year overall survival and progression-free survival (PFS) rates were 56% and 42%, respectively. The PFS of patients with stage I and II who underwent complete staging surgery was 92.3%, and that of those without lymph node dissection or omentectomy was 33.3%. Patients with USC had a significantly worse prognosis than 43 patients with non-serous carcinoma. USC in Japanese women has characteristics different from those of endometrioid carcinoma, worse prognosis, and is difficult to diagnose preoperatively. Complete surgical staging is necessary even for early-stage disease. Additionally, new adjuvant treatment strategies, including molecular targeted therapy, should be explored.

Outcomes of Surgical Resection of Primary Lung Cancer After Pancreatic Cancer.

This study aimed to elucidate the therapeutic significance of lung resection for primary lung cancer after pancreatic cancer surgery in contemporary cases. This retrospective cohort study included patients who had lung nodules and performed pulmonary resection after pancreatic cancer surgery at seven hospitals affiliated with the Thoracic Surgery Study Group of Osaka University between January 2009 and December 2021. Patients in which surgery was performed for biopsy purposes, those with a history of other cancers with potential for lung metastasis, patients who did not give their consent for enrollment, and patients determined to be ineligible by the attending physician were excluded from the study. A demographic analysis revealed that 17 patients were eligible for inclusion. Pathological diagnoses were established by institutional pathologists and occasionally aided by immunostaining and genetic testing. A survival analysis revealed a 3-year survival rate of 61.9% and a 5-year survival rate of 54.2% after lung resection. Subgroup analyses highlighted the impact of the interval between pancreatic cancer surgery and lung nodule detection, tumor diameter, and procedure on survival outcomes. This study underscores the therapeutic implications of lung resection for primary lung cancer following surgery for pancreatic cancer. Despite the challenges in preoperative diagnosis and treatment decisions, surgical intervention demonstrates promise, especially in select cases. Further research is needed to determine the best therapeutic strategies for this group.

Risk of Death From Other Diseases in Lung Cancer Patients After Sublobar Resection Versus Lobectomy.

A recent Japanese phase three clinical trial for lung cancer suggested a possible advantage of segmentectomy over lobectomy in terms of death from other diseases. This study aimed to compare the risk of death from other diseases based on surgical procedures in lung cancer patients without recurrence. We retrospectively reviewed 2121 patients without disease recurrence after curative resection for lung cancer at our institution. Patient characteristics and overall survival were compared between sublobar resection and lobectomy. The sublobar group (n = 595) had a significantly higher proportion of women, non-smokers, patients without comorbidities, patients with a history of other cancers, and patients with earlier-staged disease when compared with the lobectomy group (n = 1526). The overall survival was significantly longer in the sublobar group than in the lobectomy group (p = 0.0034). After adjusting for background characteristics in an analysis of 488 patients, the overall survival had a trend to be longer in the sublobar group than in the lobectomy group (p = 0.071). Our results suggested that the risk of death from other diseases was potentially higher after lobectomy than after sublobar resection. Although several clinical factors could influence the results, these results may support the benefit of sublobar resection, assuming that the curability of both procedures is similar.

The effect of epidermal growth factor receptor mutation on adjuvant chemotherapy with tegafur/uracil for patients with completely resected, non-lymph node metastatic non-small cell lung cancer (> 2cm): a multicenter, retrospective, observational study as exploratory analysis of the CSPOR-LC03 study.

The use of adjuvant osimertinib for epidermal growth factor receptor (EGFR) mutants is expected to expand to earlier stage I in the future, potentially competing with the current standard of care, oral tegafur/uracil (UFT), in Japan. However, the effect of EGFR mutation status on the therapeutic effect of UFT remains unclear. This study was conducted as an exploratory analysis of a retrospective observational study that investigated the real-world data of postoperative adjuvant chemotherapy in Japan (CSPOR-LC03). Between 2008 and 2013, 1812 patients with completely resected adenocarcinoma diagnosed as pathologic stage I (T1>2cm, TNM classification, sixth edition) who have maintained organ function, and no history of other cancers were included. The primary endpoint was the 5-year disease-free survival (DFS) rate, and we compared this rate between four groups classified based on the administration of adjuvant UFT and EGFR mutation status. Of the 933 (51%) patients with EGFR mutations, 394 underwent adjuvant UFT therapy. Of the 879 (49%) patients without EGFR mutations, 393 underwent adjuvant UFT therapy. The 5-year DFS of UFT+/EGFR+ and UFT-/EGFR+ patients were 82.0 and 87.1%, respectively, and those of UFT+/EGFR- and UFT-/EGFR- patients were 80.0 and 86.9%, respectively. DFS was significantly worse in the UFT+ group than in the UFT- group (P=0.015). Adjuvant UFT therapy was not an independent prognostic factor for DFS, regardless of the EGFR mutation status. In pathologic stage I (>2cm) lung adenocarcinomas with EGFR mutation, the survival benefit of adjuvant UFT was not observed.

Clinical significance of germline breast cancer susceptibility gene (gBRCA) testing and olaparib as maintenance therapy for patients with pancreatic cancer

BackgroundGermline breast cancer susceptibility gene (gBRCA) mutation in patients with pancreatic cancer (PC) is not common in clinical practice. Therefore, factors that efficiently show gBRCA mutations and the real-world outcomes of olaparib maintenance therapy have not been fully established. In the present study, we clarified the indicators for the effective detection of gBRCA mutation and the efficacy and safety of olaparib as maintenance therapy.MethodsWe retrospectively analyzed 84 patients with PC who underwent gBRCA testing (BRACAnalysis, Myriad Genetics, Salt Lake City, UT, USA) at our institute between January 2021 and March 2022. For each patient, clinical data were extracted from medical records.ResultsThe median patient age was 64 y (29–85 y), and 41 patients (48.8%) were male. The gBRCA mutations were identified in 10 (11.9%) patients; two patients had BRCA1 mutation and eight had BRCA2 mutation. All patients with gBRCA mutation had a family history of any cancer, and eight of them had a family history of Hereditary Breast and Ovarian Cancer syndrome (HBOC)-related cancer. The gBRCA mutation rate was higher for patients with PC with a family history of HBOC-related cancer compared to that in patients with PC having a family history of other cancers and no family history of cancer (22.9% vs. 4.1%; P = 0.014). In our study, eight out of 10 patients with gBRCA-positive PC received olaparib after platinum-based chemotherapy. The best responses to platinum-based chemotherapy included a complete response in one patient (12.5%) and a partial response in seven patients (87.5%). The median duration of treatment with platinum-based chemotherapy plus olaparib was 17.5 months (8–87 months), and the duration of treatment with olaparib maintenance therapy was 11 months (1–30 months). During olaparib maintenance therapy, three patients showed no disease progression. One of these three patients underwent conversion surgery after receiving olaparib for 12 months.ConclusionsThe gBRCA testing should be considered proactively, especially in patients with PC with a family history of HBOC-related cancer.

Prevalence of pathogenic or likely pathogenic germline mutations in patients with metastatic renal cell cancer.

110 Background: Data from the West suggests that 5-10% of patients with metastatic renal cell cancer (RCC) are known to harbor a pathogenic/likely pathogenic mutation in the RCC-associated genes. However, there are no data from the Indian subcontinent in this regard. Methods: This study was a prospective single-center cohort study conducted at a large tertiary care cancer center in northern India. Patients newly diagnosed with metastatic RCC were eligible to participate and, if willing, were offered pretest counseling and germline genetic testing. We performed whole exome sequencing on blood samples using next-generation sequencing on the Illumina platform. The frequency and spectrum of pathogenic/likely pathogenic (P/LP) variants were determined and classified using the ACMG guidelines, and clinical characteristics associated with mutation status were analyzed using a Fisher's exact test. Results: A total of 156 patients with metastatic RCC were enrolled in this study from October 2023 to February 2024. The median age at diagnosis was 44 years, and 67% were men. Histologically, 64% had clear cells, 12% had papillary, and 8% had unknown histology. In RCC-associated genes, 6 patients (3.8%) had P/Lp mutations, of which 4 had mutations in FH and 2 in VHL. Further P/LP variants in the non-RCC genes were detected in 12 additional patients (7.7%), of which 4 were in ATM, 2 in BRIP1, and one each in BRCA1, BARD1, PALB2, MUTYH, MSH6, and PMS2, respectively. The presence of germline P/LP mutation was associated with non-clear histology but not with age and sex. Patients with a P/LP mutation were more likely to have a family history of other cancers (most common, breast cancer) in first and second-degree relatives. Conclusions: 11.5% of patients with metastatic RCC were detected with germline P/LP variants, of which one-third had one of the RCC genes, and the rest had non-RCC gene mutations. Patients with mRCC should have access to germline genetic testing, and the gene panel for patients needs to be expanded to include genes previously classified as non-RCC genes.

Germline variants in patients diagnosed with pediatric soft tissue sarcoma.

While soft tissue sarcomas affect younger patients, few studies have assessed the distribution of underlying pathogenic germline variants. We retrospectively identified all pediatric and young adult patients (0-22 years) at Haukeland University Hospital, Norway (1981-2019), through clinical and pathological records. We identified n = 46 eligible patients. From these 46 patients, adequate material representing normal tissue was available for n = 41 cases (n = 24 diagnosed with rhabdomyosarcoma, 9 with synovial sarcomas, 2 with Ewing sarcomas, and 6 without further classification), with matching tumor tissue for n = 40. Normal tissue samples were analyzed for germline pathogenic variants (PVs) by targeted sequencing of 360 cancer genes. Out of the 41 analyzed cases, we found PVs or likely PVs in 7 (17%). These variants were found in TP53, MUTYH, FANCC, DICER1, FANCA, MYO3A, and MYO5B. Supporting the causality of these PVs, four cases revealed loss of heterozygosity (LOH) of the wild-type allele in the tumor tissue, one patient with a PV in DICER1 had a second somatic variant in DICER1, and a patient with a PV in TP53 had the altered allele amplified in the tumor. For three out of five with available family history, a history of other cancers in relatives was recorded. Among genes with variants of uncertain significance, CHD1L was of particular interest, revealing a stop-gain and a missense variant. A high fraction of young patients with soft tissue sarcoma harbor PVs. Among the genes affected, we substantiate a potential role of MYO5B and propose a potential role for MYO3A.

Germline pathogenic variants in a large convenience cohort of multiple melanoma subtypes.

9595 Background: A heritable component accounts for approximately 10% of melanomas. These estimates derive from populations deemed high risk for a germline pathogenic variant (gPV). The prevalence and clinical features of a broader melanoma patient population are unknown. Methods: Using the MSKCC IMPACT dataset, we identified a convenience cohort of all pts with melanoma who had undergone targeted tumor-normal sequencing (NCT01775072) for gPV in 76-90 genes. gPV were categorized by association with cancer predisposition and penetrance. Results: 701 pts with melanoma and germline sequencing demonstrated 105 pathogenic variants in 29 genes (Table). 14% of pts (n=99) harbored a gPV in a cancer susceptibility gene (gPV+); 49% high/moderately pathogenic, 32% low/recessive, and 19% uncertain. 6% of gPV+ pts had 2 gPVs. 77% of gPVs were involved in DNA damage repair pathways. The genes known to be associated with melanoma risk accounted for 9% of gPVs, inclusive of CDKN2A (2%), CDK 4 (1%), MITF (4%), and BRCA2 (2%). A further 15% were in genes with suggested, as yet undefined, susceptibility for melanoma; BRCA1 (6%), ATM (5%), BAP1 (2%) and PALB2 (2%). gPV+ frequency varied by melanoma subtype: unknown primary (19%, n=18), cutaneous (15%, n=64), mucosal (13%, n=13), acral (7%, n=2) and uveal (4%, n=2) (p=0.039). No significant difference in age, sex, race, stage at diagnosis, personal history of other cancer, or family history (FHx) of melanoma was seen between gPV+ and gPV-, on univariate analysis. 47% of gPV+ pts had either >1 primary melanoma, age<45 years or a FHx of melanoma (n=47), of which 14 pts had >1 risk factor. The presence of >1 melanoma and FHx of melanoma was associated with gPV+ (p=0.016). There was no significant difference in somatic TMB and MAPK pathway alterations between gPV+ and gPV-. In this cohort selected for high-risk melanomas, melanoma was the first presenting cancer for 83% of patients with gPV+. Assessment of biallelic loss to clarify if gPVs may be driving melanoma carcinogenesis is ongoing. Conclusions: This represents the largest cohort of sequenced matched germline and somatic analysis in melanoma. There is a 14% overall gPV prevalence that varies by melanoma subtype. The association of >1 primary melanoma, young age and a family history of melanoma with gPV+ is consistent with prior studies, however, would not capture 53% of gPV+ in this cohort. Melanoma represents the index cancer for the majority of gPVs, informing the need to expand germline testing in patients with melanoma. [Table: see text]

Implementation of Universal Hepatitis C Virus Screening in a Tertiary Cancer Center.

The prevalence of chronic hepatitis C virus (HCV) infection in the United States is ≤1%. Universal HCV screening is recommended nationwide. Here we describe our experience implementing universal HCV screening at a cancer center. In October 2016, universal HCV screening with HCV antibody (anti-HCV) was initiated for all new outpatients. Universal screening was promoted through widespread provider education, orders in the Epic electronic health records (EHRs), SmartSets, and automated EHR reminders. The effort focused on patients with solid tumors, because universal screening in patients with hematologic malignancies was already standard practice. Primary outcomes were the proportion of patients screened and the proportion of patients with reactive anti-HCV test results linked to HCV care. The secondary outcome was the incidence of HCV-associated hepatocellular carcinoma as a second primary malignancy (HCC-SPM) in patients with a history of other cancers before HCC diagnosis. Epic's Reporting Workbench Business Intelligence tools were used. Statistical significance was defined as P<.05 on chi-square analysis. From April 2016 through April 2023, 56,075 patients with solid tumors were screened for HCV, of whom 1,300 (2.3%) had reactive anti-HCV test results. The proportion of patients screened was 10.1% in the 6 months before study implementation and 34.4% in the last 6 months of the study (P<.001). HCV screening was ordered using SmartSets in 39,332 (45.8%) patients and in response to automated EHR reminders in 10,972 (12.8%) patients. Most patients with reactive anti-HCV test results were linked to care (765/1,300; 59%), most with proven HCV infection were treated (425/562; 76%), and most treated patients achieved sustained virologic response (414/425; 97%). The incidence of HCC-SPMs was 15% in historical controls treated from 2011 to 2017 and 5.7% following implementation of universal screening (P=.0002). Universal HCV screening can be successfully implemented in cancer hospitals using an EHR-based multipronged approach to eliminate HCV and prevent HCV-associated HCC-SPMs.

Ki67 as a prognostic factor in male breast cancer (male BC): Results from a large GEICAM Spanish cohort of male BC.

556 Background: Male BC management is based, by default, on evidence produced from female BC. There is a high need to validate gender specific performance of established prognostic biomarkers. We present here descriptive results from a large, country specific, registry of Male BC. Methods: GEICAM/2016-04 (NCT03800355) is a retrospective, observational study including Male BC pts diagnosed from 2000 to 2019 in 51 Spanish sites. Data from BC diagnosis until 10-Mar-2020 was collected from medical charts; biological specimens were obtained. Pts and tumors characteristics, therapies, and outcomes were analyzed. Molecular subtypes were categorized as hormonal receptor positive (HR+)/HER2 negative (HER2−), triple negative (TN) (HR−/HER2−), and HER2+ (any HR). Results: 773 pts were analyzed, at first diagnosis, 721 (93%) had early BC (EBC) (stages I [28%], II [41%], III [21%]), and 52 (7%) de novo metastatic BC; median age was 66 (23-96) years; median body mass index was 28 (18-50) Kg/m2 (overweight), with obesity in 4% as prior medical history. Previous history of other cancers: 20 (3%) pts were diagnosed with prostate cancer (PC) and 20 (3%) pts with skin cancer (melanoma and non-melanoma). BC family history was reported in 212 (35%) pts, 56 (9%) PC, and 35 (6%) ovarian cancer. Germline genetic testing for hereditary risk was performed in 238 (31%) pts, with BRCA1/2 mutations present in 46 (19%) pts (BRCA1 in 6, BRCA2 in 39, and both in 1); BRCA1/2 mutations were observed in 9 (33%) HER2+ pts and 32 (18%) HR+/HER2− pts. Of EBC pts, 322 (45%) were node-positive, 274 (38%) had T2 tumors; 4% had breast conserving surgery, and 42% sentinel lymph node biopsy; 42% received adjuvant radiation therapy; 336 (47%) adjuvant and 44 (6%) neoadjuvant chemotherapy, 609 (84%) adjuvant endocrine therapy, mainly tamoxifen (72%); and 6% pts did not receive any systemic therapy. Morphologically, invasive carcinoma of no special type was reported in 89% pts, and 52% were grade 2. Per local pathological assessment, 97% estrogen receptor positive (ER+), 90% progesterone receptor positive (PgR+), 84% androgen receptor positive; 51% presented Ki67 index expression ≥20%, and 11% HER2+. Frequency according to molecular subtype: 599 (77%) HR+/HER2−, 75 (10%) HER2+, 6 (1%) TN, and 93 (12%) unknown. With a median follow-up of 64 months, medians of invasive disease-free survival (iDFS) and distant DFS (dDFS) were not statistically different in HR+/HER2− vs HER2+ pts and according to levels of Ki67 index expression (&lt;20% vs. ≥20%). In a Cox multivariate model, stage I-II vs III and age were statistically significant (p&lt;0.05) for both iDFS and dDFS. Conclusions: HR+/HER2− is the most common Male BC subtype, with ER and PgR highly positive, and 20% as median Ki67 index. No statistically significant differences were observed in terms of iDFS and dDFS based on level of Ki67 index expression. Clinical trial information: NCT03800355 .

Prevalence of pathogenic genetic variants in patients with gastric cancer ascertained through multi-gene panel testing.

10578 Background: Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. The role of pathogenic/likely pathogenic variants (PVs) in cancer predisposition genes is not well understood. We aimed to assess the prevalence of PVs in GC patients undergoing germline genetic testing (GGT) via multi-gene panel testing (MGPT) at a large commercial laboratory. Methods: Retrospective review of MGPT (&gt;10 genes) in GC patients at a large commercial laboratory (Invitae Corp.) from March 2015 to July 2023 was performed. GC included diffuse type, intestinal type or unspecified type, as provided by ordering clinicians. Association of patient characteristics with positive GGT results was assessed with logistic regression with a significance threshold of p &lt; 0.05. Results: 3,706 GC patients underwent GGT(Table). Overall, 495 (13.4%) patients were found to carry ≥1 PV, including 29 patients with 2 PVs and 3 patients with 3 PVs. GGT was negative in 1,890 (51.0%) patients, 1,199 (32.4%) had a variant of uncertain significance-only and 121 (3.3%) carried a single PV in a gene associated with autosomal recessive inheritance. PVs were identified in 38 genes; 77.7% (385/495) were in a gene previously associated with GC, primarily the homologous recombination repair genes ( BRCA1, BRCA2, PALB2and ATM, 34.9%), the Hereditary Diffuse Gastric Cancer genes ( CDH1and CTNNA1, 19.6%) and mismatch repair genes ( MLH1, MSH2, MSH6, PMS2and EPCAM, 17.4%). Males were more likely to carry a PV than females (OR 1.4, 95% CI 1.1-1.7) and having a personal history of another cancer increased the odds of carrying a PV (OR 1.3, 95% CI 1.0-1.7). Age, number of genes tested and histology were not significantly associated with PV. Conclusions: In this large study of GGT in GC patients, the prevalence of PVs in cancer associated genes was 13.4%, higher than previous estimates of 3-5%. PVs were predominantly in genes associated with GC. Male sex and history of other cancers were associated with a PV. Limitations include incomplete histologic data, varying panel size, and ascertainment bias as patients may have had additional personal/family history that prompted GGT. These results support consideration of GGT in all GC patients as prevalence of PVs is similar to other cancer types for which guidelines recommend universal genetic testing.[Table: see text]

Double lung transplantation in patients with recent history of malignancy.

e20614 Background: Recent history of malignancy has been considered as a contraindication for double lung transplantation (DLT) due to concerns for risk of cancer recurrence and worse outcomes. However, the relationship between the recent malignancy history and lung transplantation mortality remains unclear. Methods: Among patients treated with DLT between 09/2021 and 02/2024 in single institution, patients with a recent history of other cancers were included in this study. All patients had enrolled in cohort C of the DLT registry aimed for lung-limited malignancies (DREAM) study (NCT05671887). Exclusion criteria include extrapulmonary metastatic disease and medical ineligibility for DLT. All patients were followed up with computed tomography every 12 weeks. Results: Four patients were included; three (75%) patients with a histology of NSCLC (squamous cell, stage Ib-IIIb), and one (25%) with prostate adenocarcinoma (stage IIc). The median no-evidence-of-disease (NED) time was 19.5 months (0-41). Patients were aged 57-68, three (75%) were male. The indication for DLT was chronic obstructive pulmonary disease (1/4, 25%), interstitial lung disease (2/4, 50%), and idiopathic pulmonary fibrosis (1/4, 25%). All patients had high oxygen requirements before DLT. The median duration of the waitlist for DLT was sixteen days (3-61). There was no in-hospital mortality and the median hospital stay was 20.5 days (16-32). During a median follow-up of 2.5 months (range 0-9), rejection and post-transplant malignancy did not occur in any of the cases (Table 1). Conclusions: Four patients with history of cancers underwent DLT without significant complications. The median post-transplant follow-up was 2.5 months (0-9). Ongoing DREAM study cohort C will continue to investigate the role of DLT in patients with a recent history of malignancy. Clinical trial information: NCT05671887 . [Table: see text]

PENTAGON (Predicting Clinical Trials in Gynecologic Oncology): A retrospective study assessing study design factors that affect enrollment in gynecologic cancer trials.

e13647 Background: Obstacles to attaining a diverse clinical trial population contribute to poor representation in medicine, increasing health disparities by limiting generalizability and applicability of findings. Our objective is to evaluate trial enrollment trends according to patient and trial demographics for those who have sought care at our multi-center, mixed-setting Gynecologic Oncology practice. Additionally, we aim to determine specific trial criteria that promote or impede enrollment for patients and physicians. Methods: An IRB-approved, retrospective cohort study evaluating all patients who screened positive for a clinical trial through the Gyn Onc practice’s manual screening process was performed. Screening events were new neoplasms, recurrences or progressions, and changes in treatment. Data was collected from July 2022 to December 2023. Demographic information, trials for which each patient was considered, trials patients enrolled on, and trial characteristics were recorded. Results: After adjustment, there were no significant differences between patient factors (age, marital status, race, ethnicity, and number of screening events) and enrollment status. Of trials available, 9% require biopsy and 94.7% are in person. Most studies are interventional (78.9%) and pharmaceutical trials (73.7%). There was a drastic unadjusted estimated increase in enrollment for Medicaid patients compared to other insurances (55.2% vs 32%, p=.031). There was also an increase in enrollment for cervical cancer patients (18.4%, p=.106) compared to other cancer sites (56.5% vs 32.8%, p=.036). There was a positive relationship between distance traveled to the treatment site and clinical trial enrollment. Patients who lived within 20 miles of the clinical trial site had an enrollment percentage of 30.1% (n=93), compared to 46.55% enrollment for those who lived further (n=58). There was a significant increase in enrollment likelihood without an exclusion criterion of previous history of other cancer (50% vs 33.3%, p=.046). Trials that required no history of chemotherapy had an enrollment of 27.3% (compared to 44.1%). Conclusions: Unlike prior reports, we did not demonstrate differences in trial enrollment by race, socioeconomic or insurance status. This suggests that our objective manual screening process enhances equitable clinical trial offerings. It is possible that this objective manual screening process attenuates provider bias and offers clinical trials to historically marginalized and underrepresented groups.

Endoscopic Ultrasonography-Guided Fine-Needle Biopsy for Patients with Resectable Pancreatic Malignancies

Clinicians often use endoscopic ultrasonography to survey pancreatic tumors. When endoscopists conduct this examination and find the tumor to be unresectable, a fine-needle biopsy is subsequently performed for tissue confirmation. However, if the tumor is deemed resectable, the necessity of a pre-operative fine-needle biopsy remains debatable. Therefore, we performed a retrospective analysis of a single-center cohort of patients with pancreatic tumors who underwent an endoscopic ultrasound-guided fine-needle biopsy or aspiration (EUS-FNB or FNA) between 2020 and 2022. This study focused on patients diagnosed with resectable malignant pancreatic tumors. The exclusion criteria included individuals diagnosed with benign pancreatic lesions and those with unresectable tumors. A total of 68 patients were enrolled in this study. Histological examination revealed that pancreatic adenocarcinoma was the predominant type of tumor (n = 42, 61.8%), followed by neuroendocrine tumors (n = 22, 32.3%), and metastasis (n = 4, 5.9%). Notably, 17 patients had a history of other cancers, with 23.5% being diagnosed with a metastatic tumor rather than primary pancreatic cancer. Therefore, EUS-FNA/FNB is crucial in patients with a resectable pancreatic tumor and a history of cancer to differentiate between a primary and a metastatic tumor.

Improved bladder function in radical hysterectomy without worsening oncologic outcome: resection of the posterior layer of the vesicouterine ligament with the procedure limited to the vesical veins.

The classic Okabayashi nerve-sparing radical hysterectomy involves complete resection of the posterior leaf of the vesicouterine ligament, whereas in the simplified nerve-sparing radical hysterectomy, only the vesical veins and some connective tissue of the posterior layer of the vesicouterine ligament are resected. This study aimed to compare bladder function and cervical carcinoma relapse-free survival between these two techniques. We conducted a retrospective, historical control study. All female patients aged >20 years who were diagnosed with cervical cancer stage IB1-IIB and underwent radical hysterectomy with pelvic lymphadenectomy between 2009 and 2022 were enrolled. Patients who had a history of other cancers and those who were treated with non-surgical approaches or non-radical hysterectomy were excluded. The primary outcome was relapse-free survival during the follow-up period. A total of 114 patients who underwent curative-intent radical hysterectomy were included in this study. The median follow-up duration was 60 months. No significant difference was observed in relapse-free survival between the two surgical procedures. The simplified nerve-sparing radical hysterectomy was superior in terms of both motor and sensory bladder function outcomes. Resection of the posterior layer of the vesicouterine ligament, with the procedure limited to the vesical veins, is an effective and safe method for radical hysterectomy. It may be more useful for preserving the bladder function, without leading to unfavorable oncologic outcomes.

Derivation of a Risk Prediction Model for Venous Thromboembolism in Adult Patients with Acute Myeloid Leukemia

Derivation of a Risk Prediction Model for Venous Thromboembolism in Adult Patients with Acute Myeloid Leukemia