Implementation and Evaluation of a Breast Cancer Disease Model Using Real-World Claims Data in Germany from 2010 to 2020.

Breast cancer is the leading cause of cancer-related mortality among women in Germany and worldwide. This retrospective claims data analysis utilizing data from AOK Baden-Wuerttemberg, a major statutory German health insurance provider, aimed to construct and assess a real-world data breast cancer disease model. The study included 27,869 female breast cancer patients and 55,738 age-matched controls, analyzing data from 2010 to 2020. Three distinct breast cancer stages were analyzed: Stage A (early breast cancer without lymph node involvement), Stage B (early breast cancer with lymph node involvement), and Stage C (primary distant metastatic breast cancer). Tumor subtypes were estimated based on the prescription of antihormonal or HER2-targeted therapy. The study established that 77.9% of patients had HR+ breast cancer and 9.8% HER2+; HR+/HER2- was the most common subtype (70.9%). Overall survival (OS) analysis demonstrated significantly lower survival rates for stages B and C than for controls, with 5-year OS rates ranging from 79.3% for stage B to 35.4% for stage C. OS rates were further stratified by tumor subtype and stage, revealing varying prognoses. Distant recurrence-free survival (DRFS) analysis showed higher recurrence rates in stage B than in stage A, with HR-/HER2- displaying the worst DRFS. This study, the first to model breast cancer subtypes, stages, and outcomes using German claims data, provides valuable insights into real-world breast cancer epidemiology and demonstrates that this breast cancer disease model has the potential to be representative of treatment outcomes.

Distant recurrence in the cerebellar dentate nucleus through the dentato-rubro-thalamo-cortical pathway in supratentorial glioma cases.

BACKGROUND: Distant recurrence can occur by infiltration along white matter tracts or dissemination through the cerebrospinal fluid (CSF). This study aimed to clarify the clinical features and mechanisms of recurrence in the dentate nucleus (DN) in patients with supratentorial gliomas. Based on the review of our patients, we verified the hypothesis that distant DN recurrence from a supratentorial lesion occurs through the dentato-rubro-thalamo-cortical (DRTC) pathway. METHODS: A total of 380 patients with supratentorial astrocytoma, isocitrate dehydrogenase (IDH)-mutant (astrocytoma), oligodendroglioma, IDH mutant and 1p/19q-codeleted (oligodendroglioma), glioblastoma, IDH-wild type (GB), and thalamic diffuse midline glioma, H3 K27-altered (DMG), who underwent tumor resection at our department from 2009 to 2022 were included in this study. Recurrence patterns were reviewed. Additionally, clinical features and magnetic resonance imaging findings before treatment, at the appearance of an abnormal signal, and at further progression due to delayed diagnosis or after salvage treatment of cases with recurrence in the DN were reviewed. RESULTS: Of the 380 patients, 8 (2.1%) had first recurrence in the DN, 3 were asymptomatic when abnormal signals appeared, and 5 were diagnosed within one month after the onset of symptoms. Recurrence in the DN developed in 8 (7.4%) of 108 cases of astrocytoma, GB, or DMG at the frontal lobe or thalamus, whereas no other histological types or sites showed recurrence in the DN. At the time of the appearance of abnormal signals, a diffuse lesion developed at the hilus of the DN. The patterns of further progression showed that the lesions extended to the superior cerebellar peduncle, tectum, tegmentum, red nucleus, thalamus, and internal capsule along the DRTC pathway. CONCLUSION: Distant recurrence along the DRTC pathway is not rare in astrocytomas, GB, or DMG at the frontal lobe or thalamus. Recurrence in the DN developed as a result of the infiltration of tumor cells through the DRTC pathway, not dissemination through the CSF.

PD1 and TIM3 Expression is Associated with Very Early Hepatocellular Carcinoma Recurrence After Percutaneous Thermal Ablation.

Purpose: Percutaneous thermal ablation (PTA) is a cornerstone in the management of early-stage hepatocellular carcinoma (HCC). However, intrahepatic distant recurrence (IDR) occurs in the majority of patients after PTA. The aim of this study was to evaluate the immune signature associated with very early IDR. Patients and Methods: Thirty-one patients (26 men, 5 women; mean age:72.4 ± 8.6; age range:57-86 years) who underwent PTA for HCC were included in this study. After PTA for HCC, patients were followed and later divided into two groups: a "very early recurrence" group in case of IDR within 12 months after PTA, and a "prolonged recurrence-free" group in case of no recurrence before 12 months of follow-up. Freshly harvested intratumoral and nontumoral liver tissues and peripheral blood were obtained before PTA and explored by multiparametric flow cytometry. Results: The frequency of PD1+CD4+ T cells was higher in the early recurrence group than in the prolonged recurrence-free group in the peripheral blood (24.3%, IQR: 22.3-36.5 vs 14.0%, IQR: 11.5-16.4, p<0.0001), in the nontumoral liver (37.9%, IQR: 36.0-50.0 vs 22.5%, IQR: 18.0-29.9, p=0.0004), and in the tumor (37.6%, IQR: 32.3-39.3 vs 24.0%, IQR: 20.0-30.3, p=0.0137). Similarly, the frequency of TIM+CD8+ T cells was higher in the very early recurrence group in the peripheral blood (p=0.0021), non-tumoral liver (p=0.0012), and tumor (p=0.0239). Conclusion: The expression of immune checkpoint molecules, such as PD1 and TIM3 on T cells identified HCC patients at risk of very early IDR after PTA who would likely benefit from adjuvant immunotherapy. Thus, our study contributes to a better understanding of the potential association of PTA with adjuvant immunotherapies.

Performance of a novel spectroscopy-based tool for adjuvant therapy decision-making in hormone receptor-positive breast cancer: a validation study.

PURPOSE: Digistain Index (DI), measured using an inexpensive mid-infrared spectrometer, reflects the level of aneuploidy in unstained tissue sections and correlates with tumor grade. We investigated whether incorporating DI with other clinicopathological variables could predict outcomes in patients with early breast cancer. METHODS: DI was calculated in 801 patients with hormone receptor-positive, HER2-negative primary breast cancer and ≤ 3 positive lymph nodes. All patients were treated with systemic endocrine therapy and no chemotherapy. Multivariable proportional hazards modeling was used to incorporate DI with clinicopathological variables to generate the Digistain Prognostic Score (DPS). DPS was assessed for prediction of 5- and 10-year outcomes (recurrence, recurrence-free survival [RFS] and overall survival [OS]) using receiver operating characteristics and Cox proportional hazards regression models. Kaplan-Meier analysis evaluated the ability of DPS to stratify risk. RESULTS: DPS was consistently highly accurate and had negative predictive values for all three outcomes, ranging from 0.96 to 0.99 at 5 years and 0.84 to 0.95 at 10 years. DPS demonstrated statistically significant prognostic ability with significant hazard ratios (95% CI) for low- versus high-risk classification for RFS, recurrence and OS (1.80 [CI 1.31-2.48], 1.83 [1.32-2.52] and 1.77 [1.28-2.43], respectively; all P < 0.001). CONCLUSION: DPS showed high accuracy and predictive performance, was able to stratify patients into low or high-risk, and considering its cost and rapidity, has the potential to offer clinical utility.

Characteristics and post-metastasis survival of recurrent metastatic breast cancer over time - An Australian population-based record linkage study, 2001-2016.

AIM: To assess population-level characteristics and post-metastasis survival of people with recurrent metastatic breast cancer (rMBC) during a period when new publicly-subsidised adjuvant and metastatic systemic therapies became available. METHODS: Record linkage study of females in NSW Cancer Registry (NSWCR) diagnosed with non-metastatic breast cancer (BC) in 2001-2002 (C1) and 2006-2007 (C2). We identified first rMBC from NSWCR, administrative hospital records, dispensed medicines and radiotherapy services (2001-2016). We used death registrations to estimate cumulative incidence of BC death. RESULTS: The analysis included 2267 women with rMBC (C1:1210, C2:1057). Compared to C1, C2 had access to adjuvant HER2-targeted therapy and were more likely to have received adjuvant chemotherapy (C1:38%, C2:47%) and aromatase inhibitors (C1:52%, C2:73%, of those dispensed endocrine therapy). Five-year probability of BC death was 65% (95%CI:62-68%) in C1 and 63% (95%CI:60-66%) in C2. Regional disease (T4 or N + ) at initial BC diagnosis (C1:62%, C2:68%), and age ≥ 70 years at first metastasis (C1:27%, C2:31%) were more common in C2 and had poorer prognosis. Five-year probability of BC death was lower in C2 than C1 for treatment-defined HER2-positive BC (C1:72% 95%CI:63-79%; C2:52% 95%CI 45-60%) and those dispensed chemotherapy alone (C1:76% 95%CI:69-82, C2:67% 95%CI:59-74%, p = 0.01), but not treatment-defined hormone receptor-positive HER2-negative BC (C1:60% 95%CI 56-63%, C2:64% 95%CI 60-68%). CONCLUSIONS: Despite less favourable prognostic characteristics in C2, BC-related survival following rMBC was similar between the two cohorts; and improved for women with HER2-positive tumours. These findings support the real-world benefits of newer treatments for rMBC.

Predictors and outcomes of recurrent retroperitoneal liposarcoma: new insights into its recurrence patterns.

BACKGROUND: The clinical profiles of recurrent retroperitoneal liposarcoma (RLS) need to be explored. The recurrence patterns of RLS are controversial and ambiguous. METHODS: A total of 138 patients with recurrent RLS were finally recruited in the study. The analysis of overall survival (OS) and recurrence-free survival (RFS) was performed by Kaplan‒Meier analysis. To identify independent prognostic factors, all significant variables on univariate Cox regression analysis (P ≤ 0.05) were subjected to multivariate Cox regression analysis. The corresponding nomogram model was further built to predict the survival status of patients. RESULTS: Among patients, the 1-, 3-, and 5-year OS rates were 70.7%, 35.9% and 30.9%, respectively. The 1-, 3- and 5-year RFS rates of the 55 patients who underwent R0 resection were 76.1%, 50.8% and 34.4%, respectively. The multivariate analysis revealed that resection method, tumor size, status of pathological differentiation, pathological subtypes and recurrence pattern were independent risk factors for OS or RFS. Patients with distant recurrence (DR) pattern usually had multifocal tumors (90.5% vs. 74.7%, P < 0.05); they were prone to experience changes of pathological differentiation (69.9% vs. 33.3%, P < 0.05) and had a better prognosis than those with local recurrence (LR) pattern. R0 resection and combined organ resection favored the survival of patients with DR pattern in some cases. CONCLUSIONS: Patients with DR pattern had better prognosis, and they may benefit more from aggressive combined resection than those with LR pattern. Classifying the recurrence patterns of RLS provides guidance for individualized clinical management of recurrent RLS.

CD44v6 downregulation as a prognostic factor for distant recurrence in resected stage I lung adenocarcinomas.

CD44 and CD44 variant isoforms have been reported as contributing factors to cancer progression. In this study, we aimed to assess whether CD44 and its variant isoforms were correlated with the prognostic factors for distant metastasis in stage I lung adenocarcinomas using tissue microarray and immunohistochemistry. In this single-center retrospective study, we analyzed the data of 490 patients with stage I lung adenocarcinoma resected between 1999 and 2016. We constructed tissue microarrays and performed immunohistochemistry for CD44s, CD44v6, and CD44v9. The risk of disease recurrence and its associations with clinicopathological risk factors were assessed. CD44v6 expression was significantly associated with recurrence. Patients with CD44v6-negative tumors had a significantly increased risk of developing distant recurrence than patients with CD44v6-positive tumors (5-year cumulative incidence of recurrence (CIR), 10.7% vs. 4.6%; P = 0.009). However, CD44v6-negative tumors were not associated with an increased risk of locoregional recurrence compared to CD44v6-positive tumors (5-year CIR, 6.0% vs. 4.0%; P = 0.39). The overall survival (OS) of patients with CD44v6-negative tumors was significantly lower than that of patients with CD44v6-positive tumors (5-year OS: 87% vs. 94%, P = 0.016). CD44v6-negative tumors were also associated with invasive tumor size and lymphovascular invasion. Even in stage I disease, tumors with negative-CD44v6 expression had more distant recurrences than those with positive-CD44v6 expression and were associated with poor prognosis in resected stage I lung adenocarcinomas. Thus, CD44v6 downregulation may be a prognostic factor for distant metastasis in stage I lung adenocarcinomas.

Patterns of recurrence in patients undergoing curative treatment for maxillary alveolus squamous cell carcinoma.

The aim of this paper was to examine patterns of recurrence in patients undergoing curative treatment for maxillary alveolus squamous cell carcinoma (MASCC). Clinicopathological data on 41 patients undergoing curative resection for MASCC between February 2006 and May 2020 were retrospectively gathered. Outcomes included local, regional, or distant failure as first site of treatment recurrence. Univariate analysis identified significant clinicopathological variables for type of recurrence. Multivariate regression analysis generated predictive models. Ten of 41 patients developed regional recurrence, and nine manifested contralateral recurrence following ipsilateral neck dissection. In three patients the ipsilateral neck was pN0. Nodal metastasis was predictive of regional recurrence, particularly with extranodal tumour extension (ENE). Multivariate analysis with regional recurrence confirmed that ENE was independently predictive. Nodal disease and ENE in patients with MASCC was found to be predictive of contralateral regional recurrence. Management of the neck in MASCC that extends to the palatal aspect should therefore be considered as midline disease.

Therapeutical strategies for recurrent endometrial cancer.

OBJECTIVE: A comprehensive overview of therapeutical strategies for recurrent endometrial cancer with illustrative case report. METHODOLOGY: A review providing basic overview of therapeutical options for different forms of recurrent endometrial cancer including surgical treatment, systemic treatment and radiotherapy. It includes a case report presenting a treatment of patient with an endometrial cancer recurrence in the abdominal wall. CONCLUSION: Therapeutical strategies in patients with endometrial cancer recurrence include surgical treatment, radiotherapy and systemic treatment depending on previous therapy, type and site of recurrence or dissemination, performance status and wishes of the patient. Decision about choice of treatment should be individually discussed and evaluated by multidisciplinary oncogynecological commission board.

MGMT Methylated High Grade Glioma with Distant Recurrence and Stable Original Tumor Site: Case Series.

We present three cases of O6-Methylguanine-DNA Methyl-transferase (MGMT) methylated high grade gliomas with distant recurrence. All three patients had a radiographic stability of original tumor site at time of distant recurrence indicating impressive local control with Stupp protocol in patients with a MGMT methylated tumors. All patients had a poor outcome after distant recurrence. For one patient Next Generation Sequencing (NGS) was available for both original and recurrent tumor and did not reveal any difference other than high tumor mutational burden in the distant recurrent tumor. Understanding risk factors of distant recurrence in MGMT methylated tumors and investigating correlations between recurrences will help plan therapeutic strategies to prevent distant recurrence and improve survival of these patients.

A prospective cohort study of clinical characteristics and outcomes in Chinese patients with estrogen receptor-negative/progesterone receptor-positive early breast cancer.

PURPOSE: This study aimed to examine the clinical characteristics and outcomes of patients with estrogen receptor-negative (ER-)/progesterone receptor-positive (PR+) early breast cancer. We also aimed to investigate the benefits of adjuvant endocrine therapy (ET) in this patient population. METHODS: Patients with early breast cancer diagnosed at West China Hospital were divided into the ER-/PR+, ER+, and ER-/PR- groups. The chi-square test was used to analyze differences in clinical and pathological features among the groups. Multivariable Cox and Fine-Gray regression models were used to compare mortality and locoregional recurrence (LRR)/distant recurrence (DR), respectively. We performed a subgroup analysis to determine which ER-/PR+ patients can benefit more from ET. RESULTS: From 2008 to 2020, we enrolled 443, 7104, and 2892 patients into the ER-/PR+, ER+, and ER-/PR- groups, respectively. The ER-/PR+ group showed more unfavorable clinical features and aggressive pathological characteristics than the ER+ group. The mortality, LRR, and DR rates were higher in the ER-/PR+ than in the ER+ group. Most clinical features and pathological characteristics were similar between the ER-/PR+ and ER-/PR- group and their outcomes were comparable. In the ER-/PR+ group, patients who received ET showed significantly lower LRR and mortality rates than those who did not; however, no difference was observed in DR. Subgroup analysis suggested that ER-/PR+ patients age ≥ 55 years, and postmenopausal status can benefit from ET. CONCLUSION: ER-/PR+ tumors have more aggressive pathological characteristics and more unfavorable clinical features than ER+ tumors. ET can reduce the LRR and mortality rates in ER-/PR+ patients. Postmenopausal and age ≥ 55 years ER-/PR+ patients can benefit from ET.

Molecular risk factors for locoregional recurrence in resected non-small cell lung cancer.

BACKGROUND: Locoregional recurrence is of high risk and is associated with a poor prognosis in terms of OS for non-small cell lung cancer (NSCLC). Local control is essential for radical cure of NSCLC. Previous studies have investigated the clinicopathological risk factors for locoregional recurrence, but the genomic biomarkers associated with locoregional recurrence have been inadequately studied. METHODS: A total of 118 patients who underwent tumor resection with mutation-detected tumor specimens were included. Tumor samples at surgery and pretreatment/postoperative blood samples were collected for mutational profiling. RESULTS: Among 48 patients with disease recurrence, 46% developed locoregional recurrence (LR) and 75% developed distant metastasis (DM). The 3-year actuarial risk of LR and DM was 25% and 43%, respectively. The first sites of failure were locoregional only (29%), locoregional and distant (10%), and distant only (61%). Patients with LR showed significantly higher ctDNA level than those with only DM at the time of initial recurrence. On multivariate analysis of baseline risk factors, the presence of allele frequency heterogeneity and baseline ctDNA shedding were found to be independently associated with a higher risk of LR. Patients with disruptive TP53 mutations had significantly lower LR-free survival as compared to patients with wild-type TP53 or nondisruptive mutations. EGFR mutations showed a favorable prognostic value for LR and is not induced by EGFR tyrosine kinase inhibitor therapy. Both disruptive TP53 mutation and EGFR mutation remained the significant prognostic factor after adjustment for histological type, pathologic nodal stage and adjuvant therapy. CONCLUSIONS: Nearly half of disease recurrences after surgery for NSCC involved locoregional sites. We identified genomic biomarkers from baseline tumor and ctDNA samples which showed promising prognostic value for LR only. This can help identify patients who had a higher risk of locoregional recurrence regardless of the risk of distant metastasis.

Ten-year distant-recurrence risk prediction in breast cancer by CanAssist Breast (CAB) in Dutch sub-cohort of the randomized TEAM trial.

BACKGROUND: Hormone receptor (HR)-positive, HER2/neu-negative breast cancers have a sustained risk of recurrence up to 20 years from diagnosis. TEAM (Tamoxifen, Exemestane Adjuvant Multinational) is a large, multi-country, phase III trial that randomized 9776 women for the use of hormonal therapy. Of these 2754 were Dutch patients. The current study aims for the first time to correlate the ten-year clinical outcomes with predictions by CanAssist Breast (CAB)-a prognostic test developed in South East Asia, on a Dutch sub-cohort that participated in the TEAM. The total Dutch TEAM cohort and the current Dutch sub-cohort were almost similar with respect to patient age and tumor anatomical features. METHODS: Of the 2754 patients from the Netherlands, which are part of the original TEAM trial, 592 patients' samples were available with Leiden University Medical Center (LUMC). The risk stratification of CAB was correlated with outcomes of patients using logistic regression approaches entailing Kaplan-Meier survival curves, univariate and multivariate cox-regression hazards model. We used hazard ratios (HRs), the cumulative incidence of distant metastasis/death due to breast cancer (DM), and distant recurrence-free interval (DRFi) for assessment. RESULTS: Out of 433 patients finally included, the majority, 68.4% had lymph node-positive disease, while only a minority received chemotherapy (20.8%) in addition to endocrine therapy. CAB stratified 67.5% of the total cohort as low-risk [DM = 11.5% (95% CI, 7.6-15.2)] and 32.5% as high-risk [DM = 30.2% (95% CI, 21.9-37.6)] with an HR of 2.90 (95% CI, 1.75-4.80; P < 0.001) at ten years. CAB risk score was an independent prognostic factor in the consideration of clinical parameters in multivariate analysis. At ten years, CAB high-risk had the worst DRFi of 69.8%, CAB low-risk in the exemestane monotherapy arm had the best DRFi of 92.7% [vs CAB high-risk, HR, 0.21 (95% CI, 0.11-0.43), P < 0.001], and CAB low-risk in the sequential arm had a DRFi of 84.2% [vs CAB high-risk, HR, 0.48 (95% CI, 0.28-0.82), P = 0.009]. CONCLUSIONS: Cost-effective CAB is a statistically robust prognostic and predictive tool for ten-year DM for postmenopausal women with HR+/HER2-, early breast cancer. CAB low-risk patients who received exemestane monotherapy had an excellent ten-year DRFi.

CDKN2A/B co-deletion is associated with increased risk of local and distant intracranial recurrence after surgical resection of brain metastases.

Background: While genetic alterations in brain metastases (BMs) have been previously explored, there are limited data examining their association with recurrence after surgical resection. This study aimed to identify genetic alterations within BMs associated with CNS recurrence after surgery across multiple cancer types. Methods: A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and gene sequencing data available. Local and remote CNS recurrence were the primary study outcomes. Next-generation sequencing of the coding regions in over 500 oncogenes was performed in brain metastasis specimens. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with CNS recurrence. Results: A total of 90 patients undergoing resection of 91 BMs composed the cohort. Genes most frequently mutated in the cohort included TP53 (64%), CDKN2A (37%), TERT (29%), CDKN2B (23%), NF1 (14%), KRAS (14%), and PTEN (13%), all of which occurred across multiple cancer types. CDKN2A/B co-deletion was seen in 21 (23.1%) brain metastases across multiple cancer types. In multivariate Cox proportional hazard analyses including patient, tumor, and treatment factors, CDKN2A/B co-deletion in the brain metastasis was associated with increased risk of local (HR 4.07, 95% CI 1.32-12.54, P = 0.014) and remote (HR 2.28, 95% CI 1.11-4.69, P = 0.025) CNS progression. Median survival and length of follow-up were not different based on CDKN2A/B mutation status. Conclusions: CDKN2A/B co-deletion detected in BMs is associated with increased CNS recurrence after surgical resection. Additional work is needed to determine whether more aggressive treatment in patients with this mutation may improve outcomes.

Estimation of an Image Biomarker for Distant Recurrence Prediction in NSCLC Using Proliferation-Related Genes.

This study aimed to identify a distant-recurrence image biomarker in NSCLC by investigating correlations between heterogeneity functional gene expression and fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) image features of NSCLC patients. RNA-sequencing data and 18F-FDG PET images of 53 patients with NSCLC (19 with distant recurrence and 34 without recurrence) from The Cancer Imaging Archive and The Cancer Genome Atlas Program databases were used in a combined analysis. Weighted correlation network analysis was performed to identify gene groups related to distant recurrence. Genes were selected for functions related to distant recurrence. In total, 47 image features were extracted from PET images as radiomics. The relationship between gene expression and image features was estimated using a hypergeometric distribution test with the Pearson correlation method. The distant recurrence prediction model was validated by a random forest (RF) algorithm using image texture features and related gene expression. In total, 37 gene modules were identified by gene-expression pattern with weighted gene co-expression network analysis. The gene modules with the highest significance were selected (p-value < 0.05). Nine genes with high protein-protein interaction and area under the curve (AUC) were identified as hub genes involved in the proliferation function, which plays an important role in distant recurrence of cancer. Four image features (GLRLM_SRHGE, GLRLM_HGRE, SUVmean, and GLZLM_GLNU) and six genes were identified to be correlated (p-value < 0.1). AUCs (accuracy: 0.59, AUC: 0.729) from the 47 image texture features and AUCs (accuracy: 0.767, AUC: 0.808) from hub genes were calculated using the RF algorithm. AUCs (accuracy: 0.783, AUC: 0.912) from the four image texture features and six correlated genes and AUCs (accuracy: 0.738, AUC: 0.779) from only the four image texture features were calculated using the RF algorithm. The four image texture features validated by heterogeneity group gene expression were found to be related to cancer heterogeneity. The identification of these image texture features demonstrated that advanced prediction of NSCLC distant recurrence is possible using the image biomarker.

Preventing metastatic recurrence in low-risk ER/PR + breast cancer patients-a retrospective clinical study exploring the evolving challenge of persistence with adjuvant endocrine therapy.

PURPOSE: In the genomic era, more women with low-risk breast cancer will forego chemotherapy and rely on adjuvant endocrine therapy (AET) to prevent metastatic recurrence. However, some of these patients will unfortunately relapse. We sought to understand this outcome. Preliminary work suggested that early discontinuation of AET, also known as non-persistence, may play an important role. A retrospective analysis exploring factors related to our breast cancer patients' non-persistence with AET was performed. METHODS: Women who underwent Oncotype-DX® testing between 2011 and 2014 with minimum 5 years follow-up were included. 'Low risk' was defined as Oncotype score < 26. Outcomes of recurrence and persistence were determined by chart review. Patient, tumor and treatment factors were collected, and persistent versus non-persistent groups compared using multivariable ANOVA and Fisher Chi square exact test. RESULTS: We identified six cases of distant recurrence among low-risk patients with a median follow-up of 7.7 years. Among them, five of six patients (83%) were non-persistent with AET. The non-persistence rate in our cohort regardless of recurrence was 57/228 (25%). Non-persistent patients reported more severe side effects compared with persistent patients (p = 0.002) and were more likely to be offered a switch in endocrine therapy, rather than symptom-relief (p = 0.006). In contrast, persistent patients were 10.3 times more likely to have been offered symptom-alleviating medications compared with non-persistent patients (p < 0.001). A subset analysis revealed that patients who persisted with therapy had a higher Oncotype-DX® score than patients who discontinued early (p = 0.028). CONCLUSION: Metastatic recurrence in low-risk breast cancer patients may be primarily due to non-persistence with endocrine therapy. Further work is needed to optimize care for patients who struggle with side effects. To our knowledge, these are the first published data suggesting that Oncotype-DX® score may influence persistence with AET.

Vulvar carcinoma and its recurrences - principles of surgical treatment.

OBJECTIVE: A comprehensive overview of the surgical treatment of vulvar cancer, including recurrent forms. METHODOLOGY: A review work providing a basic overview of the pathogenesis, dia-gnosis and surgical treatment of vulvar cancer with a focus on the possibilities of treatment of its recurrences. It includes an illustrative case report presenting a patient with invasive squamous cell carcinoma of the vulva with iterative local recurrences and subsequent development of tumor triplicity and distant metastatic involvement. CONCLUSION: Surgical treatment remains the main modality of vulvar cancer therapy, even in the case of locally advanced or recurrent findings. In these cases, multidisciplinary cooperation of operational fields is necessary. The discipline of treated patients with participation in regular dispensary care plays an important role in the early detection of recurrences. (Chemo) radiotherapy remains a possible alternative to the surgical solution; in clinical practice, radiotherapy has an irreplaceable place in adjuvant therapy. Regional and distant recurrences are characterized by a poor  prognosis.

Patterns of recurrence amongst patients undergoing resection of oral squamous cell carcinoma with curative intent.

This study was aimed to identify key clinicopathological variables that predict recurrence in those undergoing curative resection of oral squamous cell carcinoma (OSCC) with emphasis on initial treatment failure patterns. Between February 2006 to May 2020, clinicopathological data on 833 patients who underwent curative resection of OSCC were gathered. Outcomes of interest included local, regional, distant, and overall recurrence. Univariate analysis was performed to identify significant clinicopathological variables for each recurrence type, and a multivariate regression analysis was utilised to generate predictive models. A total of 187 patients (22.4%) developed recurrent disease; 79 local, 63 regional, and 46 distant. For local recurrence: tumour depth of invasion (DOI) >5--10 mm, tumour DOI >10 mm and modified Glasgow Prognostic Score (mGPS) 2 were independently predictive (c-index 0.708). For regional recurrence: primary OSCC of hard palate/maxilla, pN1, pN3b, and non-cohesive invasive front were independently predictive (c-index 0.738). For distant recurrence: pN1 pN2a, pN2b, pN2c, pN3b, and tumour DOI >10 mm were independently predictive (c-index 0.809). For recurrence at any site; pN1, pN2a, pN2b, pN2c, pN3b, tumour DOI >5-10 mm, tumour DOI >10 mm, mGPS 2, and involved surgical margins were independently predictive (c-index 0.750). Recurrence events after curative treatment for OSCC are relatively predictable on the basis of available clinicopathological characteristics. It seems likely that trials of adjuvant systemic therapy in high-risk OSCC will continue to be designed with emerging therapeutic agents. Trials should focus on those of highest risk of relapse and this study adds clarity to the selection of the correct target population.

Breast cancer mortality of older patients with and without recurrence analysed by novel multi-state models.

INTRODUCTION: In older patients with breast cancer, the risk of dying from other causes than breast cancer strongly increases after the age of 70. The aim of this study was to assess contributions of breast cancer mortality versus other-cause mortality after locoregional or distant recurrence in a population-based cohort of older patients analysed by multi-state models. METHODS: Surgically treated patients ≥70 years diagnosed with stage I-III breast cancer in 2003-2009 were selected from the Netherlands Cancer Registry. A novel multi-state model with locoregional and distant recurrence that incorporates relative survival was fitted. Other-cause and breast cancer mortality were indicated as population and excess mortality. RESULTS: Overall, 18,419 patients were included. Ten-year cumulative incidences of locoregional and distant recurrence were 2.8% (95%CI 2.6-3.1%) and 12.5% (95%CI 11.9-13.1%). Other-cause mortality increased from 23.9% (95%CI 23.7-24.2%) in patients 70-74 years to 73.8% (95%CI 72.2-75.4%) in those ≥80 years. Ten-year probabilities of locoregional or distant recurrence with subsequent breast cancer death were 0.4-1.3% and 10.2-14.6%, respectively. For patients with a distant recurrence in the first two years after diagnosis, breast cancer death probabilities were 95.3% (95%CI 94.2-96.4%), 93.1% (95%CI 91.6-94.6%), and 88.6% (95%CI 86.5-90.8%) in patients 70-74, 75-79, and ≥80 years. CONCLUSION: In older patients without recurrence, prognosis is driven by other-cause mortality. Although locoregional recurrence is a predictor for worse outcome, given its low incidence it contributes little to breast cancer mortality after diagnosis. For patients who develop a distant recurrence, breast cancer remains the dominant cause of death, even at old age.

Propensity score-based analysis of stereotactic body radiotherapy, lobectomy and sublobar resection for stage I non-small cell lung cancer.

We applied two propensity score-based analyses to simultaneously compare three treatment modalities-stereotactic body radiotherapy (SBRT), lobectomy, or sublobar resection (SLR)-for stage I non-small cell lung cancer (NSCLC), with the aim of clarifying the average treatment effect (ATE) and formulating a risk-adapted approach to treatment selection. A retrospective review of 823 patients aged ≥65 years who underwent SBRT, lobectomy, or SLR for stage I NSCLC was conducted. The following two analyses using machine learning-based propensity scores were performed: (i) propensity score weighting (PSW) to assess the ATE in the entire cohort, and (ii) propensity score subclassification (PSS) to evaluate treatment effects of subgroups. PSW showed no significant difference in the 5-year overall survival (OS) between SBRT and SLR (60.0% vs 61.2%; P = 0.70) and significant difference between SBRT and lobectomy (60.0% vs 77.6%; P = 0.026). Local (LR) and distant recurrence (DR) rates were significantly lower in lobectomy than in SBRT, whereas there was no significant difference between SBRT and SLR. PSS identified four subgroups with different patient characteristics: lobectomy-oriented (5-year cumulative incidences of non-lung cancer death, 7.5%), SLR-oriented (14.2%), SBRT-oriented (23.8%) and treatment-neutral subgroups (16.1%). Each subgroup showed different survival trends regarding the three treatments. The ATE of SBRT was not significantly different from that of SLR, but it was inferior to lobectomy. Four subgroups with different risks of non-lung cancer death and different survival trends for each treatment were identified. These would help decision-making for patients with stage I NSCLC.