Difference In Risk Of Recurrence Research Articles

Oncologic outcomes after Total Mesometrial Resection (TMMR) or treatment according to current international guidelines in FIGO (2009) stages IB1-IIB cervical cancer: an observational cohort study

According to international guidelines, standard treatment (ST) with curative intent in cervical cancer (CC) comprises radical hysterectomy and pelvic lymphadenectomy in early stages (International Federation of Gynecology and Obstetrics (FIGO) 2009 IB1, IIA1), adjuvant chemoradiation is recommended based on risk factors upon final pathology. Definitive chemoradiation is recommended in locally advanced stages (FIGO 2009 IB2, IIA2, IIB). Total mesometrial resection (TMMR) with therapeutic lymph node dissection (tLND) without adjuvant radiation has emerged as a promising treatment. Here we compare oncologic outcome by TMMR+tLND or ST. In this observational cohort study, women treated according to international guidelines were identified in the population-based registries from Sweden and women treated with TMMR were identified in the Leipzig Mesometrial Resection (MMR) Study Database (DRKS 0001517) 2011-2020. Relevant clinical and tumour related variables were extracted. Recurrence-free survival (RFS) and overall survival (OS) by ST or TMMR was analysed with log-rank test, cumulative incidence function and proportional hazard regression yielding hazard ratios (HR) with 95% confidence intervals (CI), adjusted for relevant confounders. Between 2011 and 2020, 1007 women were included in the final analysis. 733 women were treated according to ST and 274 with TMMR. RFS at five years was 77.9% (95% CI 74.3-81.1) and 82.6% (95% CI 77.2-86.9) for the ST and TMMR cohorts respectively (p=0.053). In early-stage CC, RFS was higher after TMMR as compared to ST, 91.2% vs 81.8% (p=0.002). In the adjusted analysis, TMMR was associated with a lower hazard of recurrence (HR 0.39; 95% CI 0.22-0.69) and death (HR 0.42; 95% CI 0.21-0.86) compared to ST. The absolute difference in risk of recurrence at 5 years was 9.4% (95% CI 3.2-15.7) in favor of TMMR. In locally advanced CC, no significant differences in RFS or OS was observed. Compared to ST, TMMR without radiation therapy was associated with superior oncologic outcomes in women with early-stage cervical cancer whereas no difference was observed in locally advanced disease. Our findings together with previous evidence suggest that TMMR may be considered the primary option for both early-stage and locally advanced cervical cancer confined to the Müllerian compartment. This study was supported by grants from Centre for Clinical Research Sörmland (Sweden) and Region Stockholm (Sweden).

The impact of existing total anti-toxin B IgG immunity in outcomes of recurrent Clostridioides difficile infection

Late anti-toxin-B humoral immunity acquired after treatment is important for preventing recurrent Clostridioides difficile infection. We prospectively-measured anti-toxin-B IgG and neutralization titers at diagnosis as potential early predictors of recurrence. High anti-toxin-B-IgG/neutralizing antibodies were associated with short-lasting protection within 6-weeks, however, no difference in recurrence risk was observed by 90-days post-infection.

Charlson-Deyo Comorbidity Index as a Novel Predictor for Recurrence in Non-Muscle-Invasive Bladder Cancer.

To test the association between the Charlson-Deyo Comorbidity Index (CCI) and the recurrence of non-muscle-invasive bladder cancer (NMIBC). NMIBC (Ta, T1, TIS) patients who underwent transurethral resection of bladder tumor (TURB) between 2010 and 2018 were identified within a retrospective data repository of a large university hospital. Kaplan-Meier estimates and uni- and multivariable Cox regression models tested for differences in risk of recurrence according to low vs. high comorbidity burden (CCI ≤ 4 vs. >4) and continuously coded CCI. A total of 1072 NMIBC patients were identified. The median follow-up time of the study population was 55 months (IQR 29.6-79.0). Of all 1072 NMIBC patients, 423 (39%) harbored a low comorbidity burden vs. 649 (61%) with a high comorbidity burden. Overall, the rate of recurrence was 10% at the 12-month follow-up vs. 22% at the 72-month follow-up. In low vs. high comorbidity burden groups, rates of recurrence were 6 vs. 12% at 12 months and 18 vs. 25% at 72 months of follow-up (p = 0.02). After multivariable adjustment, a high comorbidity burden (CCI > 4) independently predicted a higher risk of recurrence (HR 1.42, 95% confidence interval (CI) 1.06-1.92, p = 0.018). After multivariable adjustment, the hazard of recurrence increased by 5% per each one-unit increase on the CCI scale (HR 1.05, 95% CI 1.00-1.10, p = 0.04). Comorbidities in NMIBC patients are common. Our data suggest that patients with higher CCI have an increased risk of BC recurrence. As a consequence, patients with a high comorbidity burden should be particularly encouraged to adhere to NMIBC guidelines and conform to follow-up protocols.

Variation in Rates of Post-Mastectomy Radiotherapy Among Women with Early Invasive Breast Cancer in England and Wales: A Population-Based Cohort Study

AimsThis study examined whether patterns of post-mastectomy radiotherapy (PMRT) among women with early invasive breast cancer (EIBC) varied within England and Wales and explored the role of different patient factors in explaining any variation. Materials and methodsThe study used national cancer data on women aged ≥50 years diagnosed with EIBC (stage I–IIIa) in England and Wales between January 2014 and December 2018 who had a mastectomy within 12 months of diagnosis. A multilevel mixed-effects logistic regression model was used to calculate risk-adjusted rates of PMRT for geographical regions and National Health Service acute care organisations. The study examined the variation in these rates within subgroups of women with different risks of recurrence (low: T1-2N0; intermediate: T3N0/T1-2N1; high: T1-2N2/T3N1-2) and investigated whether the variation was linked to patient case-mix within regions and organisations. ResultsAmong 26 228 women, use of PMRT increased with greater recurrence risk (low: 15.0%; intermediate: 59.4%; high: 85.1%). In all risk groups, use of PMRT was more common among women who had received chemotherapy and decreased among women aged ≥80 years. There was weak or no evidence of an association between use of PMRT and comorbidity or frailty, for each risk group. In women with an intermediate risk, unadjusted rates of PMRT varied substantially between geographical regions (range 40.3–77.3%), but varied less for the high-risk (range 77.1–91.6%) and low-risk groups (range 4.1–32.9%). Adjusting for patient case-mix reduced the variation in regional and organisational PMRT rates to a small degree. ConclusionsRates of PMRT are consistently high across England and Wales among women with high-risk EIBC, but variation exists across regions and organisations for women with intermediate-risk EIBC. Effort is required to reduce unwarranted variation in practice for intermediate-risk EIBC.

Development and validation of MRI-based radiomics model to predict recurrence risk in patients with endometrial cancer: a multicenter study.

To develop a fusion model based on clinicopathological factors and MRI radiomics features for the prediction of recurrence risk in patients with endometrial cancer (EC). A total of 421 patients with histopathologically proved EC (101 recurrence vs. 320 non-recurrence EC) from four medical centers were included in this retrospective study, and were divided into the training (n = 235), internal validation (n = 102), and external validation (n = 84) cohorts. In total, 1702 radiomics features were respectively extracted from areas with different extensions for each patient. The extreme gradient boosting (XGBoost) classifier was applied to establish the clinicopathological model (CM), radiomics model (RM), and fusion model (FM). The performance of the established models was assessed by the discrimination, calibration, and clinical utility. Kaplan-Meier analysis was conducted to further determine the prognostic value of the models by evaluating the differences in recurrence-free survival (RFS) between the high- and low-risk patients of recurrence. The FMs showed better performance compared with the models based on clinicopathological or radiomics features alone but with a reduced tendency when the peritumoral area (PA) was extended. The FM based on intratumoral area (IA) [FM (IA)] had the optimal performance in predicting the recurrence risk in terms of the ROC, calibration curve, and decision curve analysis. Kaplan-Meier survival curves showed that high-risk patients of recurrence defined by FM (IA) had a worse RFS than low-risk ones of recurrence. The FM integrating intratumoral radiomics features and clinicopathological factors could be a valuable predictor for the recurrence risk of EC patients. An accurate prediction based on our developed FM (IA) for the recurrence risk of EC could facilitate making an individualized therapeutic decision and help avoid under- or over-treatment, therefore improving the prognosis of patients. • The fusion model combined clinicopathological factors and radiomics features exhibits the highest performance compared with the clinicopathological model and radiomics model. • Although higher values of area under the curve were observed for all fusion models, the performance tended to decrease with the extension of the peritumoral region. • Identifying patients with different risks of recurrence, the developed models can be used to facilitate individualized management.

Meta-Analysis of Rates and Risk Factors for Local Recurrence in Surgically Resected Patients With NSCLC and Differences Between Asian and Non-Asian Populations

IntroductionPostoperative radiotherapy (PORT) reduces local failure in patients with NSCLC, without a clear overall survival benefit. It is unknown whether the subsets of patients benefit. Two recent large randomized controlled trials, PORT-C (People’s Republic of China) and Lung ART (Europe), reported widely different locoregional recurrence (LR) rates in the control arms, at 18.3% and 28.1% (46% of which were mediastinal recurrences), respectively. We performed a meta-analysis of patients with pathologic (p) N0 to N2 disease to evaluate the risk factors for LR and to explore possible differences in recurrence risk between Asian population (AP) and non-Asian population (NAP). MethodsWe identified all original studies of curative NSCLC surgical resection which reported risk of LR between January 1, 2000, and January 10, 2021, excluding studies with less than 10 LR, patients with metastatic disease, or any neoadjuvant therapy. A total of 87 studies were identified with pN0 to N2 disease; of these, 56 were of high quality (HQ) on the basis of the Newcastle-Ottawa Scale. For each risk factor, we derived pooled relative risk (RR) and 5-year rate estimates using random-effects models. ResultsOverall, the three significant highest pooled RRs (95% confidence intervals) for LR were pN2 versus pN0 (3.01, 1.39–6.55), lymphovascular invasion (1.92, 1.58–2.33), and advanced pT3–4 stage versus pT1 (1.86, 1.53–2.25). For HQ studies, the highest RRs for LR were lymphovascular invasion (1.94, 1.57–2.40), sublobar versus lobar resection (1.86, 1.46–2.36), and pN1 versus pN0 (1.84, 1.37–2.47), but pN2 versus pN0 was no longer significant (3.0, 0.57–15.61), on the basis of only two eligible studies. The RRs for LR were consistent for most factors in AP and NAP, although the RR for male versus female sex was higher in AP (1.44, 1.21–1.72) than in NAP (1.09, 0.99–1.19). Where reported, the pooled rate of LR at 5 years was lower in AP (12.0%) than in NAP (22.7%), despite similar overall 5-year recurrence rates (both LR and distal) in both populations: 38.0% in AP and 37.3% in NAP. Nevertheless, a lower 5-year mortality rate was noted in AP (24.3%) than in NAP (45.9%). ConclusionsThere is little high-quality evidence to support the hypothesis that pN2 disease is a risk factor for LR, but LR seems to be lower in Asians. Prospective evaluation of LR factors and rates may be necessary before further prospective evaluation of PORT, because it may not depend on nodal status alone. Recurrence rates may differ in Asians. The impact of mutational status and modern treatment including targeted therapies and immune checkpoint inhibitors is inadequately studied.

Abstract 5787: Modelling the spatial heterogeneity of CD45-positive tumor infiltrating lymphocytes in early-stage, estrogen receptor-positive breast cancer

Abstract The frequency of lymphocytes infiltrating tumors is a known prognostic in estrogen receptor (ER) negative cancers. ER+ disease is putatively believed to be immune cold, however, there exists a subset of ER+ tumors with high immune infiltrate and with a significant spatial heterogeneity. The clinic impact of such infiltrate - especially between the Oncotype Dx Recurrence Score risk categories - remains unclear. Moreover, the distribution of tumor and stromal tissues, while noted as significantly heterogenous, is still ill-defined and not yet clinically used prognostically, despite evidence to support its utility. Using a cohort (n=450) of serial sections taken from early-stage, ER+/HER2- breast tumors of the Irish arm of the TAILORx clinical trial, we aimed to investigate the tumor architecture and spatial distribution of tumor immune infiltrate and proliferating tumor cells using digital image analysis. Antibodies against Ki67 (proliferation marker) and CD45 (leukocyte common antigen), and a routine Haematoxylin and Eosin stain were applied to serial sections of 450 full-face tumors via chromogenic immunohistochemistry, as outlined previously [1]. Digital image analysis was performed using open-source software, QuPath [2]. Pixel classifiers were trained and validated against an expert pathologist in order to define observed lymphocytes as tumor or stromal-infiltrating, and to establish a classifier to quantify the tumor-stroma ratio (TSR) and infiltrating tumor area. Distances of CD45-positive cells from tumor were computed, along with autocorrelation statistics [3,4] of CD45 and Ki67 hotspots; firstly in order to quantify spatial heterogeneity, and secondly to examine whether Ki67 as a component gene in the Oncotype Dx assay has a foundation in tumor biology or is being confounded by potentially Ki67-positive lymphocytes. Subdividing by Oncotype Dx risk categories, no significant difference in TSR was observed (p=0.09799), neither for intermediary risk patients receiving hormone therapy alone or in combination with chemotherapy (p=0.3873). While there was an observed trend overall (p=0.092), no significance was found for recurrence between intermediary risk subcategories (HT alone: p=0.393, HT+CT: p=0.288). However, in the cohort as a whole, median TSR was 0.3215 (range 0 - 5.023), with statistically significant differences in recurrence risk observed (cohort high v low by median TSR. HR: 6.356, 95CI: 2.263-17.84, p<0.0001). Citation Format: Zak Kinsella, Anna Blümel, Mairi Lucas, Andreas Lindner, Claudia A. Gonzalez, Arman Rahman, Joanna Fay, Tony O'Grady, Verena Murphy, John Crown, Cathy Kelly, William Gallagher, Darran O'Connor. Modelling the spatial heterogeneity of CD45-positive tumor infiltrating lymphocytes in early-stage, estrogen receptor-positive breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5787.

A simple procedure to identify children with B‐lineage acute lymphoblastic leukemia who can be successfully treated with low or moderate intensity: Sequential versus single‐point minimal residual disease measurement

Sequential monitoring of minimal residual disease (MRD) by molecular techniques or multicolor flow cytometry (MFC) has emerged over the past two decades as the primary tool to optimize treatment in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The aim of our study was to compare the prognostic power of repeated MFC-MRD measurement with single-point MRD assessment in children with BCP-ALL treated with the reduced-intensity protocol ALL-MB 2008. Data from consecutive MFC-MRD at day 15 and day 36 (end of induction, EOI) were available for 507 children with Philadelphia-negative BCP-ALL. They were stratified into standard risk (SR, n=265), intermediate risk (ImR, n=211), and high risk (HR, n=31) according to the initial clinical characteristics defined in the ALL-MB 2008 protocol. Quantitative (relative to quantitative thresholds) and kinetic (logarithmic reduction) assessments of MFC-MRD at both time points effectively separated patients into three groups with different risk of recurrence. On the other hand, starting with low (for the SR group) and moderate (for the ImR group) induction therapy, a single MFC-MRD measurement at EOI proved sufficient to unequivocally identify patients in whom this therapy is highly effective and distinguish them from those who cannot be successfully treated with such therapy. Therefore, initiating treatment with low or moderate treatment from the start, together with careful consideration of initial clinical risk factors and just one EOI-MFC-MRD measurement is simple, inexpensive, and entirely sufficient for treatment optimization. Furthermore, for a large proportion of patients, this approach allows better adjustment, in particular also reduction of therapy intensity than sequential MRD measurements.

Fibrin Glue–Coated Collagen Complex Patch: A Novel Material for Surgical Repair of Spontaneous Temporal Bone Cerebrospinal Fluid Leak and Encephalocele

To compare outcomes of surgical repair of temporal bone encephalocele and cerebrospinal fluid (CSF) leak using fibrin glue-coated collagen (FGCC) complex patch versus other materials for repair of dura. Retrospective chart review. Tertiary care hospital. Fifty-two adult patients undergoing transmastoid (TM), middle fossa (MF) or combined approach repair of spontaneous MF CSF leak between 2016 and 2020. Exposure of bony defect via TM approach, MF craniotomy, or combined TM/MF, and repair of the associated dura defect with FGCC complex patch, or other materials (acellular collagen matrix, bovine collagen, autologous fascia, fibrin tissue sealant). Successful repair without recurrent CSF leak or encephalocele throughout follow-up. Cost of materials used in duraplasty. Sixty-four percent of patients were female. Mean (standard deviation) age at repair was 61.4 (12.1) years. Mean (standard deviation) body mass index was 35.0 (8.3) kg/m 2 . Forty-nine (94%) patients had successful repair without known recurrence of CSF leak or encephalocele over a median follow-up interval of 11.7 months. Average duraplasty material cost was significantly lower with FGCC in comparison with other nonautologous materials (FGCC+: $1259.94, FGCC-: $1652.58; p = 0.004). No significant differences in recurrence risk (FGCC+: 6.9%, FGCC-: 6.9%; p > 0.999) or operative time (FGCC+: 153.7 min, FGCC-: 155.4 min; p = 0.88) were detected based on material used for duraplasty. All materials studied demonstrate effective and sustained means of repair for MF CSF leak and encephalocele, including in the presence of multiple defects. Use of FGCC for duraplasty produces noninferior surgical results to other nonautologous materials in repair of spontaneous CSF leaks of the temporal bone and may be more cost-effective.

Artificial intelligence-assisted evaluation of tumor infiltrating CD3+ and CD8+ T cells for prognostication and prediction of benefit from adjuvant chemotherapy in early stage colorectal cancer (CRC): A retrospective analysis of the QUASAR trial.

204 Background: High CD3+ (all) and CD8+ (cytotoxic) T cell densities in the core (CT) and invasive margin (IM) of primary CRCs have been shown to be associated with superior prognosis at all stages of disease. Their predictive effect on benefit from adjuvant chemotherapy in early stage CRC has not been tested. Methods: FFPE samples from participants (pts) in the QUASAR trial (adjuvant fluorouracil/folinic acid vs observation in stage 2/3 CRC) were analysed for CD3 and CD8 immunohistochemistry (IHC). Pathologists annotated the core and peritumor areas on digital slide images. Artificial intelligence (AI) algorithms delineated the CT and IM, and calculated the densities (cells/mm2) of each marker in each region (CD3-CT, CD3-IM, CD8-CT, CD8-IM). Pts were randomly partitioned into test and validation sets (1:1). In the test set, each measure’s prognostic effect on recurrence-free interval (RFI) (primary endpoint), colorectal cancer mortality (CCM) and overall survival (OS) in each trial arm was assessed. Maximum likelihoods methods were used to develop optimal cut-points. Analyses were repeated in the validation set. Analysis of 425 pts in each set would give > 95% power (α = 0.05, 2-sided) to detect a twofold difference in recurrence risk. In predictive analyses, 2-year recurrence rate was the primary outcome; biomarker-treatment interactions were assessed. Results: Tumor tissue from 868 pts (797 [92%] stage 2; 531 [61%] colon) was analysed, with evaluable results for CD3-CT in 851 (98.0%), CD3-IM in 833 (96.0%), CD8-CT in 849 (97.0%) and CD8-IM in 820 (94.5%) pts. In the test set, optimal cut-points of 318, 798, 81 and 186 cells/mm2 were defined for CD3-CT, CD3-IM, CD8-CT and CD8-IM respectively. The recurrence rate in the high-risk group was twice that in the low-risk group for all measures (CD3-CT: rate ratio [RR] 2.00, [95%CI 1.33-2.94], p = 0.0008; CD3-IM: 2.38, [1.59-3.57], p < 0.00001; CD8-CT: 2.17, [1.59-3.57], p = 0.0001; CD8-IM: 2.13 [1.43-3.23], p = 0.0001), which was closely replicated in the validation set (CD3-CT: RR 1.96, [1.30-2.94], p = 0.002; CD3-IM: 1.79, [1.18-2.70], p = 0.005; CD8-CT: 1.72, [1.18-2.56], p = 0.005; CD8-IM: 1.72 [1.15-2.56], p = 0.008). In multivariate analyses, prognostic effects were similar in colon and rectal cancers, and in stage 2 and 3 disease. CD3/8 counts were not predictive of benefit from adjuvant chemotherapy, with similar efficacy in the high and low risk groups. Conclusions: AI-assisted CD3 and CD8 counts were strongly associated with tumor recurrence rates. With no biomarker-treatment interactions, proportional reductions in recurrence with chemotherapy were similar in high and low-risk disease. Hence, numbers of high-risk patients needed to treat to prevent one recurrence were about half the number for low-risk patients.

Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study

BackgroundMultiple clinical trials demonstrate consistent but modest benefit of adjuvant extended endocrine therapy (EET) in HR + breast cancer patients. Predictive biomarkers to identify patients that benefit from EET are critical to balance modest reductions in risk against potential side effects of EET. This study compares the performance of the Breast Cancer Index, BCI (HOXB13/IL17BR, H/I), with expression of estrogen (ER), progesterone (PR), and androgen receptors (AR), and Ki67, for prediction of EET benefit.MethodsNode-positive (N+) patients from the Trans-aTTom study with available tissue specimen and BCI results (N = 789) were included. Expression of ER, PR, AR, and Ki67 was assessed by quantitative immunohistochemistry. BCI (H/I) gene expression analysis was conducted by quantitative RT-PCR. Statistical significance of the treatment by biomarker interaction was evaluated by likelihood ratio tests based on multivariate Cox proportional models, adjusting for age, tumor size, grade, and HER2 status. Pearson’s correlation coefficients were calculated to evaluate correlations between BCI (H/I) versus ER, PR, AR, Ki67 and AR/ER ratio.ResultsEET benefit, measured by the difference in risk of recurrence between patients treated with tamoxifen for 10 versus 5 years, is significantly associated with increasing values of BCI (H/I) (interaction P = 0.01). In contrast, expression of ER (P = 0.83), PR (P = 0.66), AR (P = 0.78), Ki67 (P = 0.87) and AR/ER ratio (P = 0.84) exhibited no significant relationship with EET benefit. BCI (H/I) showed a very weak negative correlation with ER (r = − 0.18), PR (r = − 0.25), and AR (r = − 0.14) expression, but no correlation with either Ki67 (r = 0.04) or AR/ER ratio (r = 0.02).ConclusionThese findings are consistent with the growing body of evidence that BCI (H/I) is significantly predictive of response to EET and outcome. Results from this direct comparison demonstrate that expression of ER, PR, AR, Ki67 or AR/ER ratio are not predictive of benefit from EET. BCI (H/I) is the only clinically validated biomarker that predicts EET benefit.

A Radiation-Free Approach Based on the Whole-Body-MRI Has Shown a High Level of Accuracy in the Follow up of Lymphoma Patients. a Single Center Retrospective Study

Introduction: lymphoproliferative disorders are a heterogeneous group of oncological diseases characterized by a variable prognosis and different risk of recurrence that can occur even after years from the last line of treatment. Therefore, it is mandatory to follow up all the patients in complete remission (CR) of disease. For this purpose, the most recent guidelines do not recommend the use of imaging methods that are recommended at diagnosis including multidetector computed tomography with intravenous iodinated contrast enhancement (CE-CT) and 2-[18F]-fluoro-2-deoxy-D-glucose-positron-emission tomography (18F-FDG PET- CT) because of the potential damage from ionizing radiation especially in young patients. Whole body magnetic resonance imaging with diffusion-weighted imaging (WB-MRI-DWI) is an emerging method that, without using contrast medium and ionizing radiation, can provide similar results, if not superior in some histological subtypes, to 18F-FDG PET-CT in detecting lymphomatous localizations. This method could potentially be suitable for the follow-up of lymphoma patients. In this retrospective single center study, we aimed to assess the accuracy of WB-MRI-DWI during follow-up of lymphoma patients in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Materials and methods: 191 lymphoma patients who underwent at list one WB-MRI-DWI in our center during follow-up between February 2010 and February 2022 were enrolled. Seventy-five were Hodgkin Lymphomas, 47 diffuse large B cell lymphomas (DLBCL), 33 follicular lymphomas (FL); 10 Marginal zone lymphomas, 7 primitive mediastinal B cell lymphomas (PMBCL), 6 mantle cell lymphomas, 3 Burkitt lymphomas and 10 with more rare histotypes). Twenty-seven patients have been identified as relapsed by WB-MRI-DWI. Results: In our cohort of patients the calculated sensitivity of WB-MRI-DWI in lymphoma surveillance was 100% (95% CI: 99.4-100.0), while specificity was 98.6% (95% CI: 97.4-99.3). The positive predictive value (PPV) was 79% (95% CI: 75.9-81.9) and the negative predictive value (NPV) 100% (95% CI: 99.4-100.0). Conclusion: despite some limitations of the whole body magnetic resonance including the possibility of poor patient compliance and the identification of some false positives (6.3% of the total), WB-MRI-DWI is an investigation with excellent sensitivity that can identify recurrence of the disease and at the same time it could eliminate the risk of ionizing radiation.

Risk of adenoma recurrence after polypectomy in patients younger than 50 years vs. 50 years old and over with diminutive or small adenomas

Current studies have shown that polyp recurrence occurs after colonic adenomas polypectomy (AP), but the difference in recurrence risk between patients in patients older than 50 years and younger than 50 years has not been clearly studied. 490 patients after AP were enrolled in the study. The patients were classified according to age (<50 years old or ≥50 years old), and then further categorized according to the baseline adenoma characteristics: Group 1: 1-2 non-advanced adenomas (NAAs) 1-5 mm in size; Group 2: ≥3 NAAs, 1-5 mm; Group 3: 1-2 NAAs, 6-9 mm; Group 4: ≥3 NAAs, 6-9 mm; and Group 5: advanced adenomas. During a mean follow-up interval of 2.52 years (2.51 years for ≥50 years old and 2.55 years for patients <50 years old), NAA recurrence was detected in 147 patients (30.0%). Overall, the hazard ratio (HR) for NAA recurrence after AP was higher in patients ≥50 years old than that in patients <50 years old (HR, 1.774, P = 0.003). For patients <50 years old, HRs (Group 2-5 vs. G1, respectively) for NAA recurrence were 0.744 (P = 0.773), 3.885 (P = 0.007), 5.337 (P = 0.003), and 3.334 (P = 0.015). For patients ≥50 years old, HRs (Group 2-5 vs. G1, respectively) for NAA recurrence were 1.033 (P = 0.965), 1.250 (P = 0.405), 2.252 (P = 0.015), and 1.887 (P = 0.009). For G1, the risk of NAA recurrence was significantly higher in patients ≥50 years old (HR, 2.932, P = 0.011) than that in patients <50 years old; for G2-G5, the risk was similar in the two age groups (P > 0.05). For patients <50 years old with less than 3 NAAs that are 1-5 mm in size, the recurrence rate of NAA is less than that of patients ≥50 years old with the same index colonoscopy findings. When the adenomas are ≥5 mm, or their number exceeds 3, they have similar recurrence risk as that for patients ≥50 years old.

Educational differences in mortality but not in risk of recurrence following first-time pulmonary embolism: A Danish nationwide register-based study

BackgroundSeveral studies agree that high socioeconomic position is protective against risk of PE. However, socioeconomic impact on outcomes from PE is not known. In this paper we aimed to compare differences in risk of recurrence and mortality within the first year following a first-time PE across level of education. MethodsUsing Danish national registers, patients ≥18 years of age hospitalized with a first-time PE between 1998 and 2018 were registered. Based on International Standard Classification of Education system 2011 patients were divided into four levels of education. Risk of recurrence and death across educational level were assessed by cumulative incidence curves and multivariable adjusted absolute risk regression analyses. ResultsIn total, 22,708 patients with basic education (60 % women, median age 73 years), 19,809 with high school/vocational education (43 % women, median age 67 years), 7257 with short/medium higher education (54 % women, median age 65 years) and 2410 with long higher education (34 % women, median age 64 years) were hospitalized for PE. Risk of recurrence was not influenced by increasing educational level (relative absolute risk (RAR) 0.97, [95 % confidence interval (CI), 0.85–1.11], RAR 1.01 [95 % CI, 0.85–1.19], RAR 0.81 [95 % CI, 0.60–1.09]) compared to basic education, however, risk of death decreased with increasing level of education (RAR 0.93 [95 % CI, 0.90–0.96], RAR 0.88 [95 % CI, 0.83–0.92], RAR 0.83 [95 % CI, 0.76–0.89]). ConclusionSignificant educational differences exist in mortality following PE, warranting a need for socially differentiated efforts targeted towards patients with low educational status.

Classification of pyroptosis patterns and construction of a novel prognostic model for prostate cancer based on bulk and single-cell RNA sequencing.

BackgroundEmerging evidence suggests an important role for pyroptosis in tumorigenesis and recurrence, but it remains to be elucidated in prostate cancer (PCa). Considering the low accuracy of common clinical predictors of PCa recurrence, we aimed to develop a novel pyroptosis-related signature to predict the prognosis of PCa patients based on integrative analyses of bulk and single-cell RNA sequencing (RNA-seq) profiling.MethodsThe RNA-seq data of PCa patients was downloaded from several online databases. PCa patients were stratified into two Classes by unsupervised clustering. A novel signature was constructed by Cox and the Least Absolute Shrinkage and Selection Operator (LASSO) regression. The Kaplan-Meier curve was employed to evaluate the prognostic value of this signature and the single sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to analysis tumor-infiltrating immune cells. At single-cell level, we also classified the malignant cells into two Classes and constructed cell developmental trajectories and cell-cell interaction networks. Furthermore, RT-qPCR and immunofluorescence were used to validate the expression of core pyroptosis-related genes.ResultsTwelve prognostic pyroptosis-related genes were identified and used to classify PCa patients into two prognostic Classes. We constructed a signature that identified PCa patients with different risks of recurrence and the risk score was proven to be an independent predictor of the recurrence free survival (RFS). Patients in the high-risk group had a significantly lower RFS (P<0.001). The expression of various immune cells differed between the two Classes. At the single-cell level, we classified the malignant cells into two Classes and described the heterogeneity. In addition, we observed that malignant cells may shift from Class1 to Class2 and thus have a worse prognosis.ConclusionWe have constructed a robust pyroptosis-related signature to predict the RFS of PCa patients and described the heterogeneity of prostate cancer cells in terms of pyroptosis.

Development and External Validation of a Novel Model for Predicting Postsurgical Recurrence and Overall Survival After Cytoreductive R0 Resection of Epithelial Ovarian Cancer.

PurposeTreatment of epithelial ovarian cancer is evolving towards personalization and precision, which require patient-specific estimates of overall survival (OS) and progression-free survival (PFS).Patients and MethodsMedical records of 1173 patients who underwent debulking surgery in our center were comprehensively reviewed and randomly allocated into a derivation cohort of 879 patients and an internal validation cohort of 294 patients. Five hundred and seventy-seven patients from the other three cancer centers served as the external validation cohort. A novel nomogram model for PFS and OS was constructed based on independent predictors identified by multivariable Cox regression analysis. The predictive accuracy and discriminative ability of the model were measured using Harrell’s concordance index (C-index) and calibration curve.ResultsThe C-index values were 0.82 (95% CI: 0.76–0.88) and 0.84 (95% CI: 0.78–0.90) for the PFS and OS models, respectively, substantially higher than those obtained with the FIGO staging system and most nomograms reported for use in epithelial ovarian cancer. The nomogram score could clearly classify the patients into subgroups with different risks of recurrence or postoperative mortality. The online versions of our nomograms are available at https://eocnomogram.shinyapps.io/eocpfs/ and https://eocnomogram.shinyapps.io/eocos/.ConclusionA externally validated nomogram predicting OS and PFS in patients after R0 reduction surgery was established using a propensity score matching model. This nomogram may be useful in estimating individual recurrence risk and guiding personalized surveillance programs for patients after surgery, and it could potentially aid clinical decision-making or stratification for clinical trials.

Integration of Deep Learning Radiomics and Counts of Circulating Tumor Cells Improves Prediction of Outcomes of Early Stage NSCLC Patients Treated With Stereotactic Body Radiation Therapy

We develop a deep learning (DL) radiomics model and integrate it with circulating tumor cell (CTC) counts as a clinically useful prognostic marker for predicting recurrence outcomes of early-stage (ES) non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). A cohort of 421 NSCLC patients was used to train a DL model for gleaning informative imaging features from computed tomography (CT) data. The learned imaging features were optimized on a cohort of 98 ES-NSCLC patients treated with SBRT for predicting individual patient recurrence risks by building DL models on CT data and clinical measures. These DL models were validated on the third cohort of 60 ES-NSCLC patients treated with SBRT to predict recurrent risks and stratify patients into subgroups with distinct outcomes in conjunction with CTC counts. The DL model obtained a concordance-index of 0.880 (95% confidence interval, 0.879-0.881). Patient subgroups with low and high DL risk scores had significantly different recurrence outcomes (P = 3.5e-04). The integration of DL risk scores and CTC measures identified 4 subgroups of patients with significantly different risks of recurrence (χ2 = 20.11, P = 1.6e-04). Patients with positive CTC measures were associated with increased risks of recurrence that were significantly different from patients with negative CTC measures (P = 0.0447). In this first-ever study integrating DL radiomics models and CTC counts, our results suggested that this integration improves patient stratification compared with either imagining data or CTC measures alone in predicting recurrence outcomes for patients treated with SBRT for ES-NSCLC.

Bladder cancer recurrence in papillary urothelial neoplasm of low malignant potential (PUNLMP) compared to G1 WHO 1999: a population-based study

Objective Papillary urothelial neoplasm of low malignant potential (PUNLMP) and stage TaG1 non-muscle invasive bladder cancer (NMIBC) represent separate categories in current WHO 1999 grade definitions. Similarly, PUNLMP and Ta low-grade are separate entities in the WHO 2004/2016 grading system. However, this classification is currently questioned by reports showing a similar risk of recurrence and progression for both categories. Patients and methods In this population-based study, risk estimates were evaluated in patients diagnosed with PUNLMP (n = 135) or stage TaG1 (n = 2176) NMIBC 2004–2008 with 5-year follow-up registration in the nation-wide Bladder Cancer Data Base Sweden (BladderBaSe). The risk of recurrence was assessed using multivariable Cox regression with adjustment for multiple confounders (age, gender, marital status, comorbidity, educational level, and health care region). Results At five years, 28/135 (21%) patients with PUNLMP and 922/2176 (42%) with TaG1 had local recurrence. The corresponding progression rates were 0.7% (1/135) and 4.0% (86/2176), respectively. A higher relative risk of recurrence was detected in patients with TaG1 tumours compared to PUNLMP (Hazard Ratio 1.6, 95% CI 1.2–2.0) at 5-year follow-up, while progression events were too few to compare. Conclusions The difference in risk of recurrence between primary stage TaG1 and PUNLMP stands in contrast to the recently adapted notion that treatment and follow-up strategies can be merged into one low-risk group of NMIBC.

Association of histological subtype with risk of recurrence in craniopharyngioma patients: a systematic review and meta-analysis.

It is controversial whether there is a different risk of recurrence between two histological subtypes in craniopharyngioma (CP) patients. Some reported that adamantinomatous craniopharyngioma (ACP) had a higher risk of recurrence than papillary craniopharyngioma (PCP), but others reported that there is no significant difference between them. So, we conducted this systematic review and meta-analysis to determine the association between the histological subtype of CP and the rate of recurrence. A comprehensive literature search was undertaken in PubMed, EMBASE, and Web of Science for all English articles published up to November 2020. Recurrence data stratified by ACP and PCP were extracted from studies meeting inclusion criteria. A pooled analysis of the association between the histological subtype of craniopharyngioma and rates of recurrence was performed. Thirteen articles containing 974 patients were included. When stratified by two pathological subtypes, the total recurrence rate of ACP was 26.0% and PCP was 14.1%, which showed ACP associated with a higher risk of tumor recurrence than PCP (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.36, 3.30, P = 0.00). This is the first meta-analysis focusing on histological subtypes of CP. PCP associates with a lower risk of recurrence than ACP, indicating that ACP could act as one of recurrence risk factors for CP patients. Nevertheless, large sample size and well-designed multicenter studies in which the other clinical variables are controlled to determine the histological subtype of CP as an independent recurrence risk factor are needed.

Change in Practice of Radioactive Iodine Administration in Differentiated Thyroid Cancer: A Single-Centre Experience

Objective: Our study aimed to analyse temporal trends in radioactive iodine (RAI) treatment for thyroid cancer over the past decade; to analyse key factors associated with clinical decisions in RAI dosing; and to confirm lower activities of RAI for low-risk patients were not associated with an increased risk of recurrence. Methods: Retrospective analysis of 1,323 patients who received RAI at a quaternary centre in Australia between 2008 and 2018 was performed. Prospectively collected data included age, gender, histology, and American Joint Committee on Cancer stage (7th ed). American Thyroid Association risk was calculated retrospectively. Results: The median activities of RAI administered to low-risk patients decreased from 3.85 GBq (104 mCi) in 2008–2016 to 2.0 GBq (54 mCi) in 2017–2018. The principal driver of this change was an increased use of 1 GBq (27 mCi) from 1.3% of prescriptions in 2008–2011 to 18.5% in 2017–2018. In patients assigned as low risk per ATA stratification, lower activities of 1 GBq or 2 GBq (27 mCi or 54 mCi) were not associated with an increased risk of recurrence. In patients assigned to intermediate- or high-risk categories who received RAI as adjuvant therapy, there was no difference in risk of recurrence between 4 GBq (108 mCi) and 6 GBq (162 mCi). Conclusions: Our data demonstrate an evolution of RAI activities consistent with translation of ATA guidelines into clinical practice. Use of lower RAI activities was not associated with an increase in recurrence in low-risk thyroid cancer patients. Our data also suggest lower RAI activities may be as efficacious for adjuvant therapy in intermediate- and high-risk patients.