Kaplan-Meier Statistics Research Articles

Metal-Free Custom-Made Zirconia Implants-A Prospective 5-Year Follow-Up Single-Arm Clinical Trial.

Dental implants made of zirconia (ZrO2) are a potential alternative for titanium implants in dentistry because of their good biocompatibility, mechanical properties and excellent aesthetic results. However, solid long-term scientific data to prove clinical success of ZrO2 implants are scarce. The aim of this study was to describe and to examine the clinical performance of custom-made two-piece ZrO2 implants, to identify possible influencing factors: a) manipulation of the implant after placement and b) the occlusal scheme on the survival rate, and to evaluate the performance of the implant-supported crown. This follow-up study collected and examined the 5-year data to answer the main question: What are the survival and the success rates of custom-made ZrO2 implants in the maxillary premolar region after 5 years? Of the 31 included patients in this prospective 5-year follow-up single-arm clinical trial, 30 received a custom-made ZrO2 implant to replace a missing single maxillary premolar, which was subsequently restored with a lithium disilicate crown. Parameters regarding clinical performance, marginal bone-level (MBL) changes, and patient-related outcome measures (PROMs) were assessed preoperatively, at the baseline, as well as 1 and 5 years after crown placement. Chances of survival and success of the implant were calculated and displayed using Kaplan-Meier statistics. Kaplan-Meier survival analysis was also performed with stratification based on the variables "manipulation of the implant prior to impression taking" and "occlusal scheme" and compared using log-rank tests. Bone-level moderation in time was compared using a paired samples t-test. Patient's expectations and satisfaction after 5 years were compared as a measure of fulfilled expectations, using a Wilcoxon signed-rank test. Performance of the implant-supported crowns was evaluated using validated criteria. Survival and success probabilities after 5 years were, respectively, 75.8% (95% CI [60.0%; 91.0%]) and 71.0% (95% CI [54.0%; 88.0%]) for the custom-made ZV3 implants. No significant differences in survival rate were found after stratification on "manipulation of the implant" and on "occlusal scheme." Mean bone-level alteration between baseline and the first follow-up was +0.06 mm (95% CI [-0.23 mm; 0.12 mm]; SD = 0.42 mm) and between baseline and the second follow-up was +0.04 mm (95% CI [-0.35 mm; 0.26 mm]; SD = 0.54 mm). Patients' satisfaction for patients with implants still in function after 5 years was 91.7% (IQR = [90.5%-97.3%]), indicating satisfaction with the treatment. Pooled satisfaction in patients with successful implants after 5 years was significantly higher than patients' expressed expectations before treatment. None of the crowns failed, and no interventions were required. Survival rate of these particular ZV3 implants in our study was lower than expected and clinically not acceptable. Hence, ZV3 implant placement as applied in this study cannot be recommended for clinical practice. Further research on the different appearances of mechanical failure in ZrO2 implants would be highly recommended before a larger prospective randomized clinical trial is conducted to evaluate treatment with custom-made ZrO2 dental implants.

Tumor-Associated Tractography Derived from High-Angular-Resolution Q-Space MRI May Predict Patterns of Cellular Invasion in Glioblastoma.

The invasion of glioblastoma cells beyond the visible tumor margin depicted by conventional neuroimaging is believed to mediate recurrence and predict poor survival. Radiomic biomarkers that are associated with the direction and extent of tumor infiltration are, however, non-existent. Patients from a single center with newly diagnosed glioblastoma (n = 7) underwent preoperative Q-space magnetic resonance imaging (QSI; 3T, 64 gradient directions, b = 1000 s/mm2) between 2018 and 2019. Tumors were manually segmented, and patterns of inter-voxel coherence spatially intersecting each segmentation were generated to represent tumor-associated tractography. One patient additionally underwent regional biopsy of diffusion tract- versus non-tract-associated tissue during tumor resection for RNA sequencing. Imaging data from this cohort were compared with a historical cohort of n = 66 glioblastoma patients who underwent similar QSI scans. Associations of tractography-derived metrics with survival were assessed using t-tests, linear regression, and Kaplan-Meier statistics. Patient-derived glioblastoma xenograft (PDX) mice generated with the sub-hippocampal injection of human-derived glioblastoma stem cells (GSCs) were scanned under high-field conditions (QSI, 7T, 512 gradient directions), and tumor-associated tractography was compared with the 3D microscopic reconstruction of immunostained GSCs. In the principal enrollment cohort of patients with glioblastoma, all cases displayed tractography patterns with tumor-intersecting tract bundles extending into brain parenchyma, a phenotype which was reproduced in PDX mice as well as in a larger comparison cohort of glioblastoma patients (n = 66), when applying similar methods. Reconstructed spatial patterns of GSCs in PDX mice closely mirrored tumor-associated tractography. On a Kaplan-Meier survival analysis of n = 66 patients, the calculated intra-tumoral mean diffusivity predicted the overall survival (p = 0.037), as did tractography-associated features including mean tract length (p = 0.039) and mean projecting tract length (p = 0.022). The RNA sequencing of human tissue samples (n = 13 tumor samples from a single patient) revealed the overexpression of transcripts which regulate cell motility in tract-associated samples. QSI discriminates tumor-specific patterns of inter-voxel coherence believed to represent white matter pathways which may be susceptible to glioblastoma invasion. These findings may lay the groundwork for future work on therapeutic targeting, patient stratification, and prognosis in glioblastoma.

The role of 18fluorine-fluorodeoxyglucose positron emission tomography in the diagnosis, follow-up, and regulation of treatment in patients with cardiac sarcoidosis.

Abstract Background Cardiac sarcoidosis (CS) is a potentially fatal disease, commonly presenting with arrhythmias, heart failure, or sudden death. Diagnostic challenges persist, particularly due to limited sensitivity of endomyocardial biopsy (20-25%). Alternative diagnostic approaches, such as criteria-based diagnosis, have emerged. 18fluorine-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) has gained prominence in diagnosing CS, monitoring treatment, and serving as a follow-up tool, although its precise role and efficacy remain unclear. Purpose This retrospective cohort study sought to characterize patients with CS who underwent at least one 118F-FDG-PET scan. Primary objectives were to explore the impact of 18F-FDG-PET on both the diagnosis and management of CS. Additionally, this study aimed to investigate any differences in patient outcomes based on the results of their first follow-up 18F-FDG-PET scan. Methods Medical records of 69 patients with CS who underwent at least one 18F-FDG-PET scan were analyzed. The study calculated the proportion of 18F-FDG PET scans influencing CS treatment and diagnosis, with 56 patients undergoing at least two scans. Among these, 53 patients were categorized into two groups based on their first follow-up scan results (group 1:no change/progress, group 2:regress). Statistical analyses included independent t-tests, the Mann-Whitney test, and Fisher's exact test. Outcome measures included death, heart transplantation or aborted cardiac death, with survival analyzed by Kaplan-Meier statistics. Results Among 69 patients, 204 18F-FDG-PET scans were conducted, with 47% directly influencing treatment decisions. Twenty-five patients were diagnosed with CS through 18F-FDG-PET. While no significant differences were observed regarding demographics and clinical features, the results suggested potential differences in event-free survival (p=0.084;Figure 1) and sex (p=0.08) between the groups. Conclusions 18F-FDG-PET has emerged as a pivotal tool in regulating treatment, diagnosing, and monitoring CS patients, playing a fundamental role in assessing treatment response. However, further studies are needed.

Taurolidine-containing solution for reducing cardiac implantable electronic device infection-early report from the European TauroPace™ registry.

Infection is a significant complication of cardiac implantable electronic device (CIED) therapy. The European TauroPace™ Registry investigates the safety and efficacy of TauroPace™ (TP), an antimicrobial solution containing taurolidine, designed to prevent CIED infections. This multicenter study included patients undergoing CIED procedures at participating centers where TP was used as a disinfectant for external hardware surfaces and an antiseptic for irrigating surgical sites. All patients eligible for CIED placement with adjunctive TP as the standard of care were included. Other aspects of CIED procedures adhered to current guidelines. Data on CIED-related infective endocarditis, CIED pocket infection, device and procedure-related complications, adverse events, and all-cause mortality were prospectively collected for 12 months. In cases of revision, the previous procedure was censored, and a new procedure was created. Binomial and Kaplan-Meier statistics were employed to analyze event rates. From January 2020 to November 2022, TP was used in 822 out of 1170 CIED procedures. Among patients who completed the 3-month follow-up, no CIED pocket infections were observed, and one case of CIED-related infective endocarditis was reported. In the 12-month follow-up cohort, two additional local pocket CIED infections were observed, resulting in a total of three major CIED infections within 1 year after the CIED placement procedure. The 3-month and 12-month major CIED infection rates were 0.125% and 0.51%, respectively. During the observation a complication rate of 4.4% was reported. No adverse events related to TP were observed. TP appears to be effective and safe in preventing CIED infections. gov Identifier: NCT04735666.

Identification of Cuproptosis-Associated Prognostic Gene Expression Signatures from 20 Tumor Types.

We investigated the mRNA expression of 124 cuproptosis-associated genes in 7489 biopsies from 20 different tumor types of The Cancer Genome Atlas (TCGA). The KM plotter algorithm has been used to calculate Kaplan-Meier statistics and false discovery rate (FDR) corrections. Interaction networks have been generated using Ingenuity Pathway Analysis (IPA). High mRNA expression of 63 out of 124 genes significantly correlated with shorter survival times of cancer patients across all 20 tumor types. IPA analyses revealed that their gene products were interconnected in canonical pathways (e.g., cancer, cell death, cell cycle, cell signaling). Four tumor entities showed a higher accumulation of genes than the other cancer types, i.e., renal clear cell carcinoma (n = 21), renal papillary carcinoma (n = 13), kidney hepatocellular carcinoma (n = 13), and lung adenocarcinoma (n = 9). These gene clusters may serve as prognostic signatures for patient survival. These signatures were also of prognostic value for tumors with high mutational rates and neoantigen loads. Cuproptosis is of prognostic significance for the survival of cancer patients. The identification of specific gene signatures deserves further exploration for their clinical utility in routine diagnostics.

The Impact of Social Determinants of Health on Peripheral T Cell Lymphoma Outcomes: Treatment Center-Type Emerges as a Powerful Prognostic Indicator

BackgroundPrognostic models in peripheral T cell lymphoma (PTCL) have identified biological factors including age, performance status, LDH, and bone marrow involvement as prognostic for survival. The association of nonbiological factors, termed social determinants of health (SDH), on PTCL outcomes remains unexplored. MethodsTo evaluate the impact of actionable SDH on PTCL mortality across race groups, we conducted a retrospective cohort study that included all White, Hispanic, Asian/Pacific Islander (PI) and Black adult patients with PTCL (AITL, ALCL, NKTCL and PTCL, NOS), diagnosed from 2000 to 2020, in California. We utilized Chi2 and Wilcoxon rank-sum tests for descriptive metrics and Kaplan-Meier statistics for mortality estimation. Regression models included patient- (age, sex, race, stage, Charlson Comorbidity Index, histology, treatment type, treatment at an academic center, payer), and neighborhood-level factors (socioeconomic (SES) quintile, proportion without a high school diploma, and rural/urban). Risk factors significant in univariate regression at a P-value < .10 were incorporated into the multivariable model. FindingsOur analysis included 6158 patients: 51.8% White, 25.8% Hispanic, 14.7% Asians/PI, and 7.6% Black. Hispanics exhibited the longest median survival (33 months) followed by Whites, Blacks, and Asian/PI (25, 20, and 14 months, respectively; P = .011). Risk factors independently associated with inferior lymphoma-specific survival (LSS) included Asian/PI compared with NH White race (HR, 1.23; 95% CI, 1.10-1.34; P = .0002), AITL and ALCL compared with PTCL, NOS histology (AITL HR, 1.14; 95% CI, 1.02-1.25; P = .011; ALCL HR, 1.15; 95% CI, 1.04-1.26; P = .004), academic compared to nonacademic facility-type (HR 0.71; 95% CI, 0.64-0.77; P < .01), Medicare compared with uninsured status (HR 1.48, 95% CI, 1.25-1.73; P < .01), and the lowest 3 education quartiles compared to the highest education quartile (Q2 HR 1.13; 95% CI, 1.01-1.25; P = .021; Q3 HR 1.14; 95% CI, 1.02-1.26; P = .018; Q4 HR 1.22; 95% CI, 1.08-1.36; P < .001). In the least resourced patients, histology, treatment, treatment facility-type, payer and education were independently prognostic for LSS. Treatment at an academic institution was associated with a striking improvement in LSS (academic institution: yes = 101 months, no = 17 months; P < .01). InterpretationThese data identify treatment facility-type, payer and education, as an independent actionable SDH for PTCL mortality. Treatment center-type had the strongest prognostic association with LSS in our PTCL cohort, conferring a risk reduction of PTCL mortality by nearly 30%. Interventions targeted at improving access to academic centers may improve outcomes for all PTCL patients.

6-month survival of patients with acute myeloid leukemia who received modified chemotherapy at Wahidin Sudirohusodo Hospital

Background and aim. Standard chemotherapy for AML is daunorubicin combined with cytarabine. However, the combination chemotherapy also has side effects that are quite dangerous for AML patients. The purpose of this study is to assess the survival rates of AML patients treated at Wahidin Sudirohusodo Hospital in Makassar using modified chemotherapy regimens. Methods and material. This study was conducted at Wahidin Sudirohusodo Hospital in Makassar using a prospective cohort design. The study population included AML patients aged 18 years or older who had undergone modified chemotherapy for six months. Data on life expectancy, chemotherapy modifications, age, gender, and AML subtype were collected. Data were analyzed using SPSS version 22.0. Survival analysis was performed using the Kaplan-Meier curve, log-rank, and statistic test. Results. The cohort consisted of 25 males (51%) and 24 females (49%) with a mean age of 42 years. The 6-month survival rates were 68% for females and 50% for males. Age-based survival rates were 61.3% for patients &lt;45 years, and 55.6 for those &gt;45 years. Survival rates by AML subtype were 40% for M1, 63.3% for M2, 0% for M3, 60% for M4, and 66.7% for M5. The survival curve for the therapy regimen showed a significant relationship (p &lt;0.05), with 86.7% survival for daunorubicin and 47.1% for cytarabine. Conclusions. Administration of daunorubicin and cytarabine chemotherapy is a variable that significantly determines the 6-month survival of AML patients.

Use of chemotherapy and loco-regional therapy in stage IA triple-negative breast cancer and their association with oncologic outcomes: A cancer registry study.

We aimed to evaluate the role of adjuvant chemotherapy and loco-regional therapy for stage IA (pT1, pN0) triple-negative breast cancer (TNBC) in a real-world setting. We identified patients with pT1, pN0 TNBC diagnosed between 2009 and 2021 within the Baden-Württemberg cancer registry (BWCR), Germany. Overall survival (OS) was assessed using Kaplan-Meier statistics and multivariate Cox regression models (adjusted for age, use of chemotherapy, local therapy (breast conserving therapy [breast conserving surgery + radiotherapy] vs. mastectomy), and tumor histologic subtype). A total of 1231 patients with a median follow-up of 45.9 months were identified: 1.0% (12 of 1231) with pT1mi stage, 9.5% (117 of 1231) with pT1a, 23.7% (292 of 1231) with pT1b, and 65.8% (810 of 1231) with pT1c. Multivariate Cox regression analysis revealed no significant influence for the use of chemotherapy on OS in pT1b patients (HR 0.90, 95% CI 0.43-1.90). For pT1c patients with Grade 1-2 tumors, the use of chemotherapy was not significantly associated OS (HR 1.01, 95% CI 0.48-2.11) but breast conserving therapy was associated with improved OS (HR 0.41, 95% CI 0.18-0.93). For pT1c patients with Grade 3 tumors, the use of chemotherapy (HR 0.51, 95% CI 0.33-0.78) as well as breast conserving therapy (HR 0.42, 95% CI 0.23-0.76) was associated with OS. This data suggests that OS in stage IA TNBC is strongly influenced by local therapy rather than the use of chemotherapy, except for pT1c patients with Grade 3 tumors. Larger studies with longer-term follow-up are welcomed to fully inform this discussion.

Electron beam radiotherapy for the management of squamous cell carcinoma of the anal margin.

Squamous cell carcinoma of the anal margin (SCCAM) is an uncommon lesion that comprises one-third to a quarter of all anal squamous cell carcinoma. Treatment involves surgery or exclusive radiotherapy for small tumours, whereas the preferred treatment for larger tumours is chemoradiotherapy. In our department, selected patients with SCCAM are treated with electron beam radiotherapy using one perineal field. The present study evaluates this strategy. All consecutive patients with SCCAM and treated with electron beam radiotherapy from 2012 to 2022 were included. Data were retrospectively extracted from the medical records and analysed descriptively. Local control (LC) and overall survival (OS) were analysed using Kaplan-Meier statistics. Forty patients were evaluated. Primary radiotherapy was delivered in 35 (87.5%) patients. Five (12.5%) patients had postoperative radiotherapy. Median prescription dose was 60.0 (range 45.0-60.2) Gy in 28 (range 10-30) fractions delivered with 8 (range 4-18) MeV using a standard circular aperture and bolus. At a median follow-up of 73 (range 9-135) months, 7 (17.5%) patients were diagnosed with local recurrences. The 5-year LC rate was 84.3% (95% CI: 71.4%-97.2%). Analysis of LC according to T-stage revealed a 5-year LC of 100% (95% CI: 100%-100%) in T1 tumours compared to 57.0% (95% CI: 27.4%-86.6%) in T2 tumours (p < 0.001). 5-year OS was 91.6% (95% CI: 83.0%-100%). Late grade 3 toxicity included ulceration in the skin and subcutis in 2 (5.0%) patients. Electron beam radiotherapy enables the delivery of 'eye-guided' radiotherapy directly to the tumour. LC is good in patients with T1 tumours. Patients with T2 tumours have less satisfactory LC and should be treated with chemoradiotherapy. Electron beam radiotherapy enables the delivery of "eye-guided" RT directly to the tumour. LC is excellent in patients with T1 tumours. Patients with T2 tumours have less satisfactory LC and should be treated with chemoradiotherapy.

Midterm Survival Results of Preserflo in a Real-World Setting.

Preserflo surgery is a safe procedure, effective in reducing intraocular pressure into the "low teens," surgical survival is greatest in cases of high baseline intraocular pressure (above 21mm Hg) and when performed as a standalone procedure. To evaluate midterm surgical survival and safety profile of Preserflo filtering surgery. In this retrospective, cohort study, consecutive patients who underwent standardized Preserflo implantation with mitomycin C from December 2019 to April 2021 were included. Clinical data were retrieved from patient charts. The primary outcome was surgical survival at 24 months in accordance with World Glaucoma Association guidelines. Survival was evaluated using Kaplan-Meier statistics. Analysis was performed at the eye level and as intention to treat. Ninety-five eyes were included in this study (18 cases combined with cataract surgery). More than half of cases (n=51) were primary open angle glaucoma, with over a fifth having a prior filtering glaucoma procedure. Intraocular pressure at 24 months was significantly decreased from baseline (22.4±6.28 vs. 12.0±3.43mm Hg), as well as the need for IOP-lowering medication [2.88 (±0.92) vs. 0.79 (±1.3), P <0.001 all comparisons]. Standalone Preserflo achieved a qualified survival (irrespective of medication) of 71% (95% CI, 62%-83%) and 44% (95% CI, 27%-75%) in the combined procedure subgroup ( P <0.05 when considering absolute survival). Eyes with baseline intraocular pressure ≥21mm Hg showed a greater qualified survival when compared with eyes with baseline ≤18mm Hg [80% (95% CI, 65%-100%) vs. 50% (95% CI, 32%-76%); P <0.05]. Intra and early operative complications were few, self-limited, and did not require surgical management. The reoperation rate was low (18%). Preserflo filtering surgery was effective in reducing intraocular pressure into the "low teens" and presents an adequate surgical survival and safety profile. Surgical survival appeared greatest when performed as standalone and when preoperative intraocular pressure was high.

Defining the Genomic Landscape of Diffuse Sclerosing Papillary Thyroid Carcinoma: Prognostic Implications of RET Fusions.

Diffuse sclerosing papillary thyroid carcinoma (DSPTC) is an aggressive histopathologic subtype of papillary thyroid carcinoma. Correlation between genotype and phenotype has not been comprehensively described. This study aimed to describe the genomic landscape of DSPTC comprehensively using next-generation sequencing (NGS), analyze the prognostic implications of different mutations, and identify potential molecular treatment targets. Tumor tissue was available for 41 DSPTC patients treated at Memorial Sloan Kettering Cancer Center between 2004 and 2021. After DNA extraction, NGS was performed using the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets platform, which sequences 505 critical cancer genes. Clinicopathologic characteristics were compared using the chi-square test. The Kaplan-Meier method and log-rank statistics were used to compare outcomes. The most common mutation was RET fusion, occurring in 32% (13/41) of the patients. Other oncologic drivers occurred in 68% (28/41) of the patients, including 8 BRAFV600E mutations (20%) and 4 USP8 mutations (10%), which have not been described in thyroid malignancy previously. Patients experienced RET fusion-positive tumors at a younger age than other drivers, with more aggressive histopathologic features and more advanced T stage (p=0.019). Patients who were RET fusion-positive had a significantly poorer 5-year recurrence-free survival probability than those with other drivers (46% vs 84%; p=0.003; median follow-up period, 45 months). In multivariable analysis, RET fusion was the only independent risk factor for recurrence (hazard ratio [HR], 7.69; p=0.017). Gene-sequencing should be strongly considered for recurrent DSPTC due to significant prognostic and treatment implications of RET fusion identification. The novel finding of USP8 mutation in DSPTC requires further investigation into its potential as a driver mutation.

The introduction of video-enabled directly observed therapy (video-DOT) for patients with drug-resistant TB disease in Eswatini amid the COVID-19 pandemic – a retrospective cohort study

BackgroundVideo-enabled directly observed therapy (video-DOT) has been proposed as an additional option for treatment provision besides in-person DOT for patients with drug-resistant TB (DRTB) disease. However, evidence and implementation experience mainly originate from well-resourced contexts. This study describes the operationalization of video-DOT in a low-resourced setting in Eswatini facing a high burden of HIV and TB amid the emergence of the COVID-19 pandemic.MethodsThis is a retrospectively established cohort of patients receiving DRTB treatment during the implementation of video-DOT in Shiselweni from May 2020 to March 2022. We described intervention uptake (vs. in-person DOT) and assessed unfavorable DRTB treatment outcome (death, loss to care) using Kaplan-Meier statistics and multivariable Cox-regression models. Video-related statistics were described with frequencies and medians. We calculated the fraction of expected doses observed (FEDO) under video-DOT and assessed associations with missed video uploads using multivariable Poisson regression analysis.ResultsOf 71 DRTB patients eligible for video-DOT, the median age was 39 (IQR 30–54) years, 31.0% (n = 22) were women, 67.1% (n = 47/70) were HIV-positive, and 42.3% (n = 30) were already receiving DRTB treatment when video-DOT became available. About half of the patients (n = 37; 52.1%) chose video-DOT, mostly during the time when COVID-19 appeared in Eswatini. Video-DOT initiations were lower in new DRTB patients (aHR 0.24, 95% CI 0.12–0.48) and those aged ≥ 60 years (aHR 0.27, 95% CI 0.08–0.89). Overall, 20,634 videos were uploaded with a median number of 553 (IQR 309–748) videos per patient and a median FEDO of 92% (IQR 84–97%). Patients aged ≥ 60 years were less likely to miss video uploads (aIRR 0.07, 95% CI 0.01–0.51). The cumulative Kaplan-Meier estimate of an unfavorable treatment outcome among all patients was 0.08 (95% CI 0.03–0.19), with no differences detected by DOT approach and other baseline factors in multivariable analysis.ConclusionsImplementing video-DOT for monitoring of DRTB care provision amid the intersection of the HIV and COVID-19 pandemics seemed feasible. Digital health technologies provide additional options for patients to choose their preferred way to support treatment taking, thus possibly increasing patient-centered health care while sustaining favorable treatment outcomes.

Use of chemotherapy and loco-regional therapy for stage IA triple-negative breast cancer and their association with oncologic outcomes: A cancer registry study.

524 Background: We aimed to evaluate the role of adjuvant chemotherapy and loco-regional therapy for stage IA (pT1, pN0) triple-negative breast cancer (TNBC) in a real-world setting. Methods: We identified patients with pT1, pN0 TNBC diagnosed between 2009 and 2021 within the clinical cancer registry of Baden-Wuerttemberg, Germany. Overall survival (OS) was assessed using Kaplan-Meier statistics and multivariate Cox regression models (adjusted for age, use of chemotherapy, local therapy (breast conserving therapy [breast conserving surgery + radiotherapy] vs. mastectomy), and tumor histologic subtype). Results: A total of 1191 patients with a median follow-up of 43.8 months were identified: 0.9% (11 of 1191) with pT1mi stage, 10.0% (119 of 1191) with pT1a, 24.0% (286 of 1191) with pT1b, and 65.0% (775 of 1191) with pT1c. Use of adjuvant chemotherapy was 9.1% (1 of 11) in pT1mi stage, 41.2% (49 of 119) in pT1a, 66.8% (191 of 286) in pT1b, and 69.8% (541 of 775) in pT1c. Multivariate Cox regression analysis revealed no significant influence for the use of adjuvant chemotherapy on OS in pT1a and pT1b patients (for pT1a HR 1.27, 95% CI 0.19 to 8.50, for pT1b HR 1.07, 95% CI 0.50 to 2.30) but for patient age in the pT1b group (HR 4.71, 95% CI 2.26 to 9.8, for age ≥70 vs. &lt;70 years). For pT1c patients, there was significant influence for the use of adjuvant chemotherapy on OS (HR 0.55, 95% CI 0.38 to 0.8), for local therapy (HR 0.41, 95% 0.25 to 0.69, for breast conserving therapy vs. mastectomy only), and patient age (HR 2.33, 95% CI 1.61 to 3.39 for age ≥70 vs. &lt;70 years). Notably, for pT1c patients aged &lt;70years, local therapy (HR 0.32, 95% CI 0.15-0.69), in favor of breast conserving therapy) but not use of chemotherapy (HR 1.11, 95% CI 0.56-2.19) was associated with OS. Conclusions: This data suggests that OS in stage IA TNBC is strongly influenced by local therapy and patient age, but not use of chemotherapy. Larger studies with longer-term follow-up are welcomed to fully inform this discussion.

Characteristics of hospital admission during checkpoint-inhibition therapy.

e14510 Background: Immune checkpoint inhibitors (ICI) have enriched the therapeutic armamentarium in outpatient oncology care; however, data on necessity of hospitalizations associated with immune-related adverse event (irAEs) are scarce. Here, we retrospectively characterize hospitalizations of patients (pts) undergoing ICI. Methods: Between 12/2019 and 06/2022, 237 pts were included. Clinical data and characteristics of ICI were collected during a 6-month observation period after the initiation of therapy. Descriptive Statistics and Kaplan-Meier statistics were administered. Results: 30 out of 237 pts were hospitalized (HA+). Most common underlying tumor entities in the overall cohort were malignant melanoma (59.5%), renal cell carcinoma (13.1%), and non-small cell lung carcinoma (12.7%). Hospitalized pts exhibited an increased rate of pulmonary and cerebral metastases. We observed a significantly higher hospitalization rate during dual ICI with Nivolumab and Ipilimumab. The predominant irAEs for hospitalization were colitis (26.7), followed by hypophysitis (13.3%), leading to a median hospitalization of 7 days (range 1-34). Most pts were treated on the general ward (76.7%). Interdisciplinary consultations were frequent, especially to gastroenterology (46.7%) and neurology (26.7%). Although a trend towards an overall survival in the HA+ subgroup was identified, no statistically significant difference was found among the subgroups. Conclusions: The hospitalization rate of 12.6% is comparable to the literature. There was a disproportionate admission of patients with immune-related colitis and hypophysitis compared to the prevalence described under ICI. We observed a high need for interdisciplinary consults in line with the heterogeneity of immune-mediated side effects. When compared to non-hospitalized pts, there was no survival disadvantage in the cohort of hospitalized patients.

Machine learning with electrocardiograms to optimize mortality risk stratification in patients with suspected acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute (NHLBI) and National Center for Advancing Translational Sciences (NCATS). Background The importance of risk stratification in patients with suspected acute coronary syndrome (ACS) extends beyond diagnosis and immediate treatment. It influences the precision of care delivery and the allocation of resources to those at highest risk of adverse events. Purpose We sought to evaluate the prognostic value of electrocardiogram (ECG) feature-based machine learning models to risk-stratify long-term mortality in those with suspected ACS. Methods This was a multicenter prospective observational cohort study of consecutive, non-traumatic patients evaluated at the emergency department for suspected ACS. The derivation cohort included 4,015 patients from a University Medical Center (age 59±16 years, 47% women, 80% training with 10-fold cross-validation and 20% testing). Ascertainment of all-cause death was based on numerous data sources, including the Centers for Disease Control and Prevention’s National Death Index registry. We trained six machine learning methods for survival analysis using 73 morphological ECG features from presenting prehospital 10-second 12-lead ECGs. We used predicted risk scores in a variational Bayesian Gaussian mixture model to define three risk groups corresponding to low, moderate, and high-risk and compared the resulting classification performance against the HEART score. The external testing cohort included 3,095 patients from a University (age 59±15 years, 44% women). Results The mortality rate was 20.3% in the derivation cohort after an average follow-up period of 3.53 years (IQR 1.75 - 5.32). Extra Survival Trees outperformed other forecasting models during cross-validation. In the internal testing cohort, the derived risk groups were significantly predictive of survival (Kaplan-Meier log-rank test statistic = 121.14, p&amp;lt;0.001), outperforming the classification performance using the HEART score (Figure 1). Our machine learning-based risk stratification model detected &amp;gt;90% of death events missed by low-risk HEART score (Figure 2). Ruling-out the low-risk group, it achieved a negative predictive value of 93.4% with a sensitivity of 85.9% (compared to 89.0% and 75.0%, respectively, for the HEART score). This classification performance generalized well to our external testing cohort. Compared to those in the low-risk group, patients at moderate (OR = 3.62 [1.35-9.74]) and high (OR = 6.12 [2.38-15.75]) risk had significantly higher odds of 30-day cardiovascular death (n=109, 3.5%). Conclusions Using only features from the 10-second 12-lead ECG, we derived and externally validated a machine learning model that stratifies the mortality risk of patients during long-term follow up. This model outperformed current standard of care based on the HEART score. Future work should validate the potential of this decision-support tool in influencing treatment plans and resource allocation.Figure 1.Clustering performanceFigure 2.Sankey diagram

Oncologic Outcomes for Different Axillary Staging Techniques in Patients with Nodal-Positive Breast Cancer Undergoing Neoadjuvant Systematic Treatment: A Cancer Registry Study

BackgroundTargeted approaches such as targeted axillary dissection (TAD) or sentinel lymph node biopsy (SLNB) showed false-negative rates of < 10% compared with axillary lymph node dissection (ALND) in patients with nodal-positive breast cancer undergoing neoadjuvant systemic treatment (NAST). We aimed to evaluate real-world oncologic outcomes for different axillary staging techniques.MethodsWe identified nodal-positive breast cancer patients undergoing NAST from 2016 to 2021 from the state cancer registry of Baden-Wuerttemberg, Germany. Invasive disease-free survival (iDFS) was assessed using Kaplan–Meier statistics and multivariate Cox regression models (adjusted for age, ypN stage, ypT stage, and tumor biologic subtype).ResultsA total of 2698 patients with a median follow-up of 24.7 months were identified: 2204 underwent ALND, 460 underwent SLNB (255 with ≥ 3 sentinel lymph nodes [SLNs] removed, 205 with 1–2 SLNs removed), and 34 underwent TAD. iDFS 3 years after surgery was 69.7% (ALND), 76.6% (SLNB with ≥ 3 SLNs removed), 76.7% (SLNB with < 3 SLNs removed), and 78.7% (TAD). Multivariate Cox regression analysis showed no significant influence of different axillary staging techniques on iDFS (hazard ratio [HR] for SLNB with < 3 SLNs removed 0.96, 95% confidence interval [CI] 0.62–1.50; HR for SLNB with ≥ 3 SLNs removed 0.86, 95% CI 0.56–1.3; HR for TAD 0.23, 95% CI 0.03–1.64; ALND reference), and for ypN+ (HR 1.92, 95% CI 1.49–2.49), triple-negative breast cancer (HR 2.35, 95% CI 1.80–3.06), and ypT3-4 (HR 2.93, 95% CI 2.02–4.24).ConclusionThese real-world data provide evidence that patient selection for de-escalated axillary surgery for patients with nodal-positive breast cancer undergoing NAST was successfully adopted and no early alarm signals of iDFS detriment were detected.

Immunohistochemical evaluation of tumor hypoxia and angiogenesis: Pathological significance and prognostic role in head and neck squamous cell carcinomas

Objectives: Tumor hypoxia and angiogenesis have been implicated in therapeutic resistance of head and neck squamous cell carcinomas (HNSCCs). Immunohistochemical evaluation of hypoxia-inducible factor-1 alpha (HIF-1 α), a hypoxia transcription factor, and vascular endothelial growth factor (VEGF), a hypoxia-responsive pro-angiogenic factor, can be exploited for prognostication and guiding treatment intensification or de-escalation decisions in HNSCC patients. The purpose of the study is to evaluate the immunohistochemical expression patterns of HIF-1 α and VEGF and the microvessel density (MVD) for angiogenesis in HNSCC and assess their pathological significance and prognostic role. Materials and Methods: In this cross-sectional study, immunohistochemical expression of HIF-1 α, VEGF, and MVD through Cluster of Differentiation (CD31) was evaluated in paraffin-embedded tumor resection tissue of 44 patients with HNSCC. Associations among HIF-1 α, VEGF, and MVD with clinicopathological variables were assessed. Statistical Analysis: For assessment of association between HIF-1α, VEGF and MVD by CD 31 immunohistochemical markers and other clinicopathological variables Pearson’s chi-square test and Fisher’s exact tests were used. Analysis of survival was done using Kaplan-Meier statistics. Also, the univariate and multivariate analysis were performed using the Cox proportional hazard regression model for the calculation of hazard ratios. Results: Nuclear expression of HIF-1 α showed significant association with MVD (P = 0.007) and cytoplasmic expression of HIF-1 α with histologic grade (P = 0.03). Overexpression of HIF-1 α was more frequent in T3/T4 stage. In addition to cytoplasmic staining, VEGF showed a unique nuclear expression pattern in four cases of advanced disease with nodal metastasis. Logistic regression analysis showed tumors with nuclear overexpression of HIF-1 α to have increased MVD (P = 0.05), and tumors with higher MVD to have a presence of lymphovascular invasion (P = 0.014). Multivariate analysis showed HIF-1 α nuclear overexpression to be significantly associated with decreased survival of patients (P = 0.05). Conclusions: Immunohistochemical overexpression of HIF-1 α and MVD quantification can serve as cost-effective tools for prognostication and treatment modification of HNSCC patients in resourcelimited settings.

The natural history of neurolymphomatosis

BackgroundNeurolymphomatosis is a lymphoid malignancy of the peripheral nervous system and its natural history is poorly understood.MethodsWe performed PubMed search and extracted clinical data for Kaplan-Meier statistics to determine outcome parameters over time. Kruskal-Wallis test was performed to compare prognostic factors.ResultsOur search identified 559 patients and their median age was 61 years. Median overall survival (OS) was 12.0 (range 10.0–15.0) months. Diffuse large B-cell lymphoma was the most frequent histology, involving the brachial plexus, cranial nerves, and sciatic nerve. None had molecular profiling. There was a progressive lengthening of OS in successive decades, from 0.5 (95% CI 0.0–0.8) to 26.4 (95% CI 18.0–34.8) months between 1951 and 2022 (r2 = 0.0528, p < 0.00001). Time from first treatment (treatment 1) to progression increased from 2.0 to 36.0 (95% CI 6.5–50.7) months (r2 = 0.0961, p = 0.00236). Time from symptom onset to diagnosis remained unchanged (r2 = 0.0000556, p = 0.939). Patients were most frequently treated with methotrexate, rituximab, and/or radiation either alone or in combination. Primary neurolymphomatosis had a better prognosis than secondary neurolymphomatosis. No OS difference was noted between B- and T-cell disease, but low-grade B-cell performed better than Burkitt’s lymphoma.DiscussionBetter outcome for patients with neurolymphomatosis is noted over time. But timely diagnosis remains a major problem that needs improvement.

Abstract 2408: Comprehensive genomic profiling of ctDNA reveals distinct genomic signatures and therapeutic implications for immunotherapy response in advanced head and neck cancer

Abstract Background: Head and Neck Cancer (HNC) is highly prevalent malignancy in Southeast Asia. We investigated comprehensive genomic profiling (CGP) of ctDNA, aimed to compare genomic landscapes between responders (R) and non-responders (NR) to immunotherapy among advanced HNC patients. Methods: An observational study, ctDNA was evaluated in 69 advanced HNC patients both at the baseline (BL) and during follow up (FL). OncoIndx® CGP was used to identify patient-specific genomic alterations in the ctDNA cohort. Raw sequence alignment and variant calling were performed using iCare® software. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier statistics. Results: Total 250 mutations, encompassing pathogenic (P), likely pathogenic (LP), and variants of unknown significance (VUS), were identified at BL. In FL samples a slight decrease in the overall number of mutations was observed. Loss-of-function (LOF) KMT2C, MSH6 mutations, and activating HNF1α mutations were consistently present at comparable frequencies in BL and FL samples, exhibiting ubiquity across immunotherapy R and NR populations (F test, P 0.00063, OR 13). The variants did not demonstrate statistically significant association with PFS and OS. Most prevalent variants at follow-up emerged from tumor suppressor genes TP53, BRIP1, STAT5B, NF1, suggesting their potential role as therapy-resistant variants. PFS and OS were notably lower for patients with TP53 + BRCA pathway variants compared to their wild-type counterparts (median PFS TP53 + BRCA pathway mutated 2.7 months vs wt 9.1 months, HR = 4.1; median OS TP53 + BRCA pathway mutated 4.7 months vs 12.8 months for wt, HR 7.7). Similarly STAT5B carriers compared to the wild-type STAT5B-bearing population. Multivariate analysis further confirmed the independent role of TP53 + BRCA pathway and STAT5B variants as determinants for worst outcome (P 0.006, HR2.5). Population with prevalent TP53 and STAT5B LOF variants exhibited a strong negative correlation with the PD-L1 score compared to the population with their wild-type counterparts (P 0.03). Average scores for genome-wide homologous recombination deficiency (HRD), bTMB, and loss of LOH were low at BL and FL and did not correlate with the PD-L1 score. Interestingly, bTMB was low for the cohort, Tumor fraction (TF) emerged as an independent prognosticator for OS and PFS. Conclusions: ctDNA revealed distinct genomic signatures in R and NR populations at BL and FL. Significant prevalence of TP53, BRIP1, STAT5B, and NF1 in the NR population suggest a potential role in conferring immunotherapy resistance. Genomic signatures, TMB and TF impacted survival of immunotherapy responders. Integrating CGP into SOC protocol may help in identifying therapy resistance in advanced HNC patients who did not respond to initial treatment. Citation Format: Atul Bharde, Vanita Noronha, Mrunal Ratnaparkhi, Vijay Patil, Bhagwat Jadhav, Sangeeta Prajapati, Anuradha Choughule, Pratik Chandrani, Sumit Haldar, Fauzul Moubeen, Nandini Menon, Kanchan Hariramani, Madhura Basavalingegowda, Aarthi Ramesh, Jayant Khandare, Pankaj Chaturvedi, Gowhar Shafi, Kumar Prabhash. Comprehensive genomic profiling of ctDNA reveals distinct genomic signatures and therapeutic implications for immunotherapy response in advanced head and neck cancer [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 2408.

Incidence of amyotrophic lateral sclerosis in Chile

Objective This study aimed to estimate amyotrophic lateral sclerosis (ALS) incidence and survival rates in the Metropolitan region of Chile. Methods We conducted a cohort study of ALS cases in the Metropolitan Region from 2016 to 2019. A total of 219 ALS patients were recruited from Corporación ELA-Chile registry, in collaboration with neurologists from Sociedad de Neurología, Psiquiatría y Neurocirugía de Chile. We calculated incidence rates by sex and age and determined median survival from onset and diagnosis. Survival analysis used the Kaplan–Meier statistic, estimating hazard ratios for age, sex, time from symptom onset and from diagnosis using a Weibull regression model. All analyses were done using R 4.1.0. Results Overall, ALS diagnosis incidence was 0.97 cases per 100,000 inhabitants, peaking in the 70–79 age group and declining thereafter. The male-to-female ratio was 1.23. The median time to death from diagnosis was 2.3 years (95% confidence interval [CI]: 1.9–2.5), and from the first symptom, it was 3.1 years (95% CI: 2.8–3.5). Conclusions This is the first population-based study reporting ALS incidence and survival rates in Chile’s Metropolitan region. Incidence resembled other Latin American studies. Median survival from diagnosis and from the first symptom were in line with previous findings. Our results corroborated lower ALS rates in Latin America, consistent with prior research.