History Of Other Cancers Research Articles

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

Background: Venous thromboembolism (VTE) is a well-established complication of malignancy associated with high morbidity. Many validated scoring systems exist to predict risk of VTE in patients with solid tumors. However, there are no models that can prospectively identify patients at high risk for the development of VTE in acute myeloid leukemia (AML). The purpose of this study was to determine risk factors for the development of VTE in a large cohort of AML patients and to develop a risk stratification model to predict VTE risk in this patient population. Methods: Adult patients presenting to the University of Wisconsin-Madison with newly-diagnosed AML from 1/1/2010 through 12/31/2021 were included in this retrospective cohort study. The primary end point was VTE within one year of diagnosis. Univariate logistic regression models were used to assess the association of each variable with development of VTE. Multivariate analysis was then completed using 16 candidate variables including demographics (sex, race, age at diagnosis), comorbidities (hypertension, diabetes, coronary artery disease, asthma/COPD), body mass index (BMI), Eastern Cooperative Oncology Group performance status (ECOG PS), history of solid organ or hematologic malignancy, smoking status, indwelling venous catheter, history of VTE, and baseline laboratory values (white blood cell count, hemoglobin, platelet count). Non-normally distributed continuous candidates were log10-transformed, then stepwise selection was used on a training set to choose predictive variables to construct a risk score to predict VTE within one year of AML diagnosis. Results: 326 patients with AML were included in the analysis. The median age at diagnosis was 60 years (range 19-92 years), 55% of the study population was male, and 94% were Caucasian race. 59 patients (18%) experienced VTE within one year of diagnosis. Age at diagnosis (OR 0.98, 95% CI, 0.963-0.998, p=0.033), BMI (OR 1.058, 95% CI, 1.02-1.10, p=0.005), hypertension (OR 0.522, 95% CI, 0.29-0.96, p=0.035) and platelets (OR 3.16, 95% CI, 1.44-6.94, p = 0.004) were individually associated with VTE. In a subgroup analysis of 278 patients with next generation sequencing data available, mutations in DNA methylation genes (DNMT3A, DNMT1, IDH1, IDH2, TET2) were associated with an increased risk of VTE (OR 1.911, 95% CI 1.017-3.591, p=0.0442, Table 1). A multivariate logistic regression model identified six independent predictors of VTE including platelet count &amp;gt;150,000 (OR 1.64, 95% CI 0.65-4.14, p=0.2953), BMI &amp;gt;25 (OR 3.10, 95% CI 1.22-7.86, p=0.0173), hypertension (OR 2.17, 95% CI 1.03-4.55, p=0.0410), history of other cancer (OR 1.72, 95% CI, 0.74-4.01, p=0.2109), diabetes (OR 2.05, 95% CI 0.73-5.73, p=0.1718), and ECOG PS (OR 1.33, 95% CI, 0.66-2.65, p=0.4263). Subsequently, a risk score was constructed from the multivariable model (3*platelets&amp;gt;150 + 8*BMI&amp;gt;25 + 5*NoHTN + 3*NoOtherCancer + 4*Diabetes + 1*ECOG0). Patients were categorized into three groups: low (score&amp;lt;9), moderate (9score&amp;lt;12), and high (score) risk of developing VTE (Table 2). Rates of VTE within one year of AML diagnosis were 3.2%, 16.4%, and 23.6% in the low, moderate, and high risk groups respectively. The model had an external AUC=0.704 when applied to our test set. Conclusions: Our study demonstrates a high rate of early VTE in patients with AML at 18%, highlighting the importance of identifying those at higher risk which would allow for early screening, patient education, and consideration of thromboprophylaxis. On multivariable analysis, we found that normal or elevated platelet count &amp;gt;150, BMI 25, and diabetes were associated with an increased risk of early VTE. Surprisingly, higher ECOG PS, history of malignancy, and hypertension were associated with a decreased risk of early VTE in our cohort. A risk prediction model incorporating these findings was able to identify patients with low, moderate, and high risk of VTE. This model may help with clinical decision making, such as the consideration of thromboprophylaxis for patients with a moderate or high risk score. However, prospective validation of this model in a larger cohort of patients is needed. In summary, we propose a risk prediction model for the development of VTE in AML that can now be validated in order to provide optimal supportive care for this patient population.

Diagnostic Performance of PSMA-Based 18F-DCFPyL PET/CT in Prostate Cancer Patients After Definitive Treatment With PSA Level ≤0.2 ng/mL.

The aim of this study was to investigate the role of 18F-DCFPyL PET/CT in the evaluation of prostate cancer (PC) patients after definitive treatment and with low-level prostate-specific antigen (PSA) level of ≤0.2 ng/mL. This retrospective study was conducted in PC patients who received definitive treatments with PSA level of ≤0.2 ng/mL and underwent 18F-DCFPyL PET/CT within a 1-week interval of PSA examination, and without interval treatment change or history of other cancer. Patient and tumor characteristics at initial diagnosis, treatment regimens, and findings on 18F-DCFPyL PET/CT were collected. Patients with minimal 6-month (median, 11 months; range, 6-21 months) follow-up or definitive biopsy results of the suspected PET/CT findings were included. Imagine findings were reached with consensus among experienced board-certified nuclear medicine physicians. Comprehensive follow-up and/or biopsy results were used as definitive determination of presence or absence of disease. Comparisons between groups of positive and negative 18F-DCFPyL PET/CT were done by using descriptive statistics. A total of 96 18F-DCFPyL PET/CTs from 93 patients met the inclusion criteria. The median Gleason score (GS) of positive group is 8 (range, 6-10), whereas negative group is 7 (range, 6-10). The median age of positive group is 71 (range, 50-90), whereas negative group is 69 (range, 45-88). There were 49 positive (51%) and 47 negative 18F-DCFPyL PET/CTs (49%). Detection rates at PSA level of ≤0.1 and 0.2 ng/mL were 58.7% (27/46) and 44% (22/50), respectively. The scan-based sensitivity, specificity, positive predictive value, and negative predictive value are 100%, 95%, 96%, and 100% in group with PSA level of ≤0.1 ng/mL, and 100%, 97%, 95%, and 100% in group with PSA level of 0.2 ng/mL, respectively. Sites of involvement on positive 18F-DCFPyL PET/CTs were prostate bed, pelvic lymph nodes, bone, chest and supraclavicular lymph nodes, lung, and adrenal glands. The SUVmax value on positive lesions ranged from 1.9 to 141.4; the smallest positive lymph node was 0.4 cm. High GS of 8-10, known metastatic status (M1), presence of extraprostatic extension, presence of seminal vesicle invasion, and very high-risk PC are significantly associated with positive 18F-DCFPyL PET/CT results (P < 0.05). Of all analyzed treatment regimes, upfront surgery (radical prostatectomy with or without pelvic lymph node dissection) had strong correlation with negative PET/CT results (P < 0.001). If patients received ADT only, or ADT plus chemotherapy, the PET/CT results were most likely positive (P = 0.026). For other treatment regimes, there were no statistical differences between the groups (P > 0.05). In the presence of low PSA level in PC patients after definitive treatment, 18F-DCFPyL PET/CT is most beneficial in detection of disease in patients with GS of 8 or higher at the time of diagnosis, and the ones who have history of ADT only, or ADT plus chemotherapy. There is excellent negative prediction value of 18F-DCFPyL PET/CT. However, there is no cutoff PSA level for 18F-DCFPyL PET/CT indication and no correlation between PSA level and SUVmax of positive lesions on 18F-DCFPyL PET/CT.

Predictors of quality of life and mental health in breast cancer survivors in Northern Iran

Background and purposeThe global incidence of breast cancer is the highest among all cancers and is the primary reason for cancer-related fatalities. Our study aimed to assess the predictors of quality of life (QOL) and mental health in breast cancer survivors in Northern Iran.MethodsThis cross-sectional study was done on 96 female breast cancer survivors between the ages of 20 and 65 and was based on convenience samples. We gathered information through demographic and fertility data, a QOL survey, and the Hospital Anxiety and Depression Scale (HADS). A significance level of P < 0.05 was set for the analysis.ResultsIn this study, results showed that 11.5% of women had the optimal quality of life, 31.3% favorable quality of life, and 57.3% undesirable quality of life. The average HADS score was 20.14 ± 3.07, with anxiety scores of 10.21 ± 2.31 and depression scores of 9.93 ± 1.64. On multiple linear regression, marital relationship and the number of children were predictors of quality of life (β=-17.624, p = 0.023 and β=-7.427, p = 0.016, respectively), as well as the husband’s education and having no history of other cancers in the woman, were the most important predictors of HADS (β = 0.763, p = 0.039 and β=-0.528, p = 0.016, respectively).ConclusionIt is crucial to provide exceptional care to breast cancer patients during treatment and post-recovery. Emotional and psychological support is a fundamental requirement for their well-being.

Anatomipatology: PT1 Nomo High Grade Clinical Case

Summary: The first publication dates back to the years 1841 by RAYES then the first histological description in 1875 by WINSIG t BLIX…… Tumors of the upper excretory tract are rare but not exceptional tumors and represent 5 to 10% of UC. Their incidence is estimated at 2/100,000 hts. The natural history differs slightly from that of VT, we note 60% of VTEUS which are infiltrating against 15% of VT. The contributing factors are: occupational exposure to certain industrial dyes, aromatic amines, aristolochic acid (inducing nephropathy with Chinese herbs or Balkan wheat flour=Balkan nephropathy), lynch syndrome or HNCC (hereditary non polyposis colonic cancer). The factors indicating a possible tumor falling within a lynch syndrome are age less than 60 years, a family history of cancer or a personal history of other cancers linked to an HNCC (colorectal, endometrium). The diagnosis is based on uroscanner or uro-MRI, in situ urinary cytology, URRS plus biopsy. They can be of pyelo-calicielles or ureteral location, the prognostic factor are the stage, the tumor grade, but also the location which can thus influence the treatment. NUT remains the reference treatment with a collar on a case-by-case basis without forgetting conservative treatment: end urology and segmental resection in certain lesions classified as low risk. Thanks to more recent endourology and imaging studies, clinical and new treatment options, lead to an extension of therapeutic tools. We report a clinical case at the Mohammed V Raba military instruction hospital.

Prospective prevalence estimation of BRCA1, BRCA2, and other germline mutations associated with hereditary pancreatic cancer (HPC) using a comprehensive gene panel in an unselected cohort of Mexican patients with pancreatic ductal adenocarcinoma (PDAC).

10609 Background: Prevalence of pathogenic or likely pathogenic germline variants (PGVs) in patients with PDAC varies across populations. There is limited information on the prevalence of PGVs among Mexican patients with PDAC. We prospectively tested an unselected cohort of newly diagnosed PDAC patients using a comprehensive gene panel in order to estimate the prevalence of BRCA1/2, and other germline mutations associated with HPC. Methods: The protocol was approved by the ethics committee at each institution: INCMNSZ, INCAN, and CM ABC Observatorio. Key inclusion criteria: age &gt; 18 years and PDAC diagnosed within 6 months of inclusion. Patients were enrolled consecutively, regardless of age, personal or family history of cancer, known hereditary cancer syndrome, or stage of the disease. Written informed consent was obtained before any procedure. Clinical variables including family history of cancer were collected. We used the 84-gene Invitae Multi-Cancer Panel. Genetic testing had no cost for patients. Patient characteristics and family history were summarized using descriptive statistics (IBM SPSS Statistics Version 25). The trial was registered on Clinical Trials (NCT05305001). Results: From August 2020 to June 2022, 119 patients with newly diagnosed PDAC were identified. Of these, 107 patients were included: 58% women, median age was 63 y/o, clinical stages at diagnosis were: I (24%), II (22%), III (6%), and IV (48%). All patients had Hispanic ancestry except one (Ashkenazi Jewish). Only 7.5% (n = 8) had a personal history of other cancer, mainly breast cancer (N = 3); 62% had a family history of any cancer, while 47.6% had a first-degree relative (FDR) with any cancer. 11% (n = 12) had family history of pancreatic cancer (PC), and 9% (n = 10) had an FDR with PC. Five patients met clinical criteria for hereditary cancer syndrome: familial pancreatic cancer (4) and Lynch syndrome (1). PGVs were identified in 17.8% (n = 19) of patients. The prevalence of PGVs in genes associated with autosomal dominant risk of PC was 11.2%: CDKN2A(5.6%), ATM (3.7%), BRCA2 (0.93%), and MSH6 (0.93%). Two patients had a PGV associated with autosomal dominant predisposition to other cancers ( CHECK2 and NF1). Six patients (5.6%) had PGVs associated with autosomal recessive predisposition to rare syndromes with increased cancer risk other than PDAC (MUTYH, RECQL4, FH and WRN). Variants of uncertain significance were present in 42% of patients. Conclusions: In Mexican patients with PDAC, the prevalence of PGVs on BRCA1/2 is &lt; 1%. The prevalence of PGVs in other susceptibility genes is 11%. Our results support the role of universal germline testing in Mexican patients with PDAC using a comprehensive gene panel. Selective testing for BRCA1/2 is discouraged.

Optimizing prognostic factors of five-year survival in gastric cancer patients using feature selection techniques with machine learning algorithms: a comparative study

BackgroundGastric cancer is the most common malignant tumor worldwide and a leading cause of cancer deaths. This neoplasm has a poor prognosis and heterogeneous outcomes. Survivability prediction may help select the best treatment plan based on an individual’s prognosis. Numerous clinical and pathological features are generally used in predicting gastric cancer survival, and their influence on the survival of this cancer has not been fully elucidated. Moreover, the five-year survivability prognosis performances of feature selection methods with machine learning (ML) classifiers for gastric cancer have not been fully benchmarked. Therefore, we adopted several well-known feature selection methods and ML classifiers together to determine the best-paired feature selection-classifier for this purpose.MethodsThis was a retrospective study on a dataset of 974 patients diagnosed with gastric cancer in the Ayatollah Talleghani Hospital, Abadan, Iran. First, four feature selection algorithms, including Relief, Boruta, least absolute shrinkage and selection operator (LASSO), and minimum redundancy maximum relevance (mRMR) were used to select a set of relevant features that are very informative for five-year survival prediction in gastric cancer patients. Then, each feature set was fed to three classifiers: XG Boost (XGB), hist gradient boosting (HGB), and support vector machine (SVM) to develop predictive models. Finally, paired feature selection-classifier methods were evaluated to select the best-paired method using the area under the curve (AUC), accuracy, sensitivity, specificity, and f1-score metrics.ResultsThe LASSO feature selection algorithm combined with the XG Boost classifier achieved an accuracy of 89.10%, a specificity of 87.15%, a sensitivity of 89.42%, an AUC of 89.37%, and an f1-score of 90.8%. Tumor stage, history of other cancers, lymphatic invasion, tumor site, type of treatment, body weight, histological type, and addiction were identified as the most significant factors affecting gastric cancer survival.ConclusionsThis study proved the worth of the paired feature selection-classifier to identify the best path that could augment the five-year survival prediction in gastric cancer patients. Our results were better than those of previous studies, both in terms of the time required to form the models and the performance measurement criteria of the algorithms. These findings may be very promising and can, therefore, inform clinical decision-making and shed light on future studies.

Predicting the future risk of lung cancer: development, and internal and external validation of the CanPredict (lung) model in 19·67 million people and evaluation of model performance against seven other risk prediction models

Lung cancer is the second most common cancer in incidence and the leading cause of cancer deaths worldwide. Meanwhile, lung cancer screening with low-dose CT can reduce mortality. The UK National Screening Committee recommended targeted lung cancer screening on Sept 29, 2022, and asked for more modelling work to be done to help refine the recommendation. This study aims to develop and validate a risk prediction model-the CanPredict (lung) model-for lung cancer screening in the UK and compare the model performance against seven other risk prediction models. For this retrospective, population-based, cohort study, we used linked electronic health records from two English primary care databases: QResearch (Jan 1, 2005-March 31, 2020) and Clinical Practice Research Datalink (CPRD) Gold (Jan 1, 2004-Jan 1, 2015). The primary study outcome was an incident diagnosis of lung cancer. We used a Cox proportional-hazards model in the derivation cohort (12·99 million individuals aged 25-84 years from the QResearch database) to develop the CanPredict (lung) model in men and women. We used discrimination measures (Harrell's C statistic, D statistic, and the explained variation in time to diagnosis of lung cancer [R2D]) and calibration plots to evaluate model performance by sex and ethnicity, using data from QResearch (4·14 million people for internal validation) and CPRD (2·54 million for external validation). Seven models for predicting lung cancer risk (Liverpool Lung Project [LLP]v2, LLPv3, Lung Cancer Risk Assessment Tool [LCRAT], Prostate, Lung, Colorectal, and Ovarian [PLCO]M2012, PLCOM2014, Pittsburgh, and Bach) were selected to compare their model performance with the CanPredict (lung) model using two approaches: (1) in ever-smokers aged 55-74 years (the population recommended for lung cancer screening in the UK), and (2) in the populations for each model determined by that model's eligibility criteria. There were 73 380 incident lung cancer cases in the QResearch derivation cohort, 22 838 cases in the QResearch internal validation cohort, and 16 145 cases in the CPRD external validation cohort during follow-up. The predictors in the final model included sociodemographic characteristics (age, sex, ethnicity, Townsend score), lifestyle factors (BMI, smoking and alcohol status), comorbidities, family history of lung cancer, and personal history of other cancers. Some predictors were different between the models for women and men, but model performance was similar between sexes. The CanPredict (lung) model showed excellent discrimination and calibration in both internal and external validation of the full model, by sex and ethnicity. The model explained 65% of the variation in time to diagnosis of lung cancer R2D in both sexes in the QResearch validation cohort and 59% of the R2D in both sexes in the CPRD validation cohort. Harrell's C statistics were 0·90 in the QResearch (validation) cohort and 0·87 in the CPRD cohort, and the D statistics were 2·8 in the QResearch (validation) cohort and 2·4 in the CPRD cohort. Compared with seven other lung cancer prediction models, the CanPredict (lung) model had the best performance in discrimination, calibration, and net benefit across three prediction horizons (5, 6, and 10 years) in the two approaches. The CanPredict (lung) model also had higher sensitivity than the current UK recommended models (LLPv2 and PLCOM2012), as it identified more lung cancer cases than those models by screening the same amount of individuals at high risk. The CanPredict (lung) model was developed, and internally and externally validated, using data from 19·67 million people from two English primary care databases. Our model has potential utility for risk stratification of the UK primary care population and selection of individuals at high risk of lung cancer for targeted screening. If our model is recommended to be implemented in primary care, each individual's risk can be calculated using information in the primary care electronic health records, and people at high risk can be identified for the lung cancer screening programme. Innovate UK (UK Research and Innovation). For the Chinese translation of the abstract see Supplementary Materials section.