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High-risk cutaneous squamous cell carcinoma (hr-cSCC) tumors exhibit aggressive behavior, leading to local recurrence, metastasis, and mortality. The management of hr-cSCC tumors is not well-defined. To clarify the impact of clinical risk factors and management strategies on disease-related outcomes (DROs) in patients with hr-cSCCs. This dual-center retrospective cohort study reviewed patient records from 2007 to 2023, focusing on hr-cSCC tumors classified as high-risk according to two staging systems. 160 adult patients with hr-cSCC were included. Tumors > 2 cm were associated with a higher risk of recurrence, metastasis, and mortality, with greater risk for tumors > 4 cm. Nonsurgical therapies were linked to higher recurrence and mortality rates compared to surgical monotherapy. Patients whose initial treatment was delayed > 60 days following biopsy had increased incidence of DROs. Other variables associated with at least one DRO included female sex, higher tumor grade, lymphovascular invasion, and advanced AJCC-8 stages. Limitations of this study include its retrospective design, narrow demographics, and variable follow-up times. This study identifies increased tumor diameter, non-surgical treatments, delayed treatment > 60 days after biopsy, female sex, tumor grade, lymphovascular invasion, and advanced tumor stage as significant risk factors for DROs in hr-cSCC. Importantly, our study provides new clarifying evidence that delayed surgical treatment of hr-cSCCs > 60 days after biopsy is associated with elevated incidence of DROs. [ABSTRACT FROM AUTHOR]

Introduction Distant recurrence of non‐muscle invasive bladder cancer is a rare condition that is poorly understood and difficult to detect in follow‐up protocols. Case presentation A 73‐year‐old female with a history of T1N0M0 bladder cancer 8 years ago suffered from a left axillary tumor, a left lung tumor, left mediastinal lymph node swelling, and bilateral adrenal gland tumors. Initially, she was diagnosed with metastatic left breast cancer of the left accessory mamma by needle biopsy of an axillary tumor. Subsequent bronchoscopic biopsy of the mediastinal lymph node revealed metastatic urothelial carcinoma, although no recurrence was detected in the urinary tract. She underwent systemic therapy, and all regions shrank without reprogression. Conclusion Non‐muscle invasive bladder cancer should be managed considering distant metastasis. If the origin of the metastatic lesions is unknown, this disease should be considered as a possible origin, even in the absence of urinary tract recurrence.

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. [ABSTRACT FROM AUTHOR]

BackgroundWhile 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.MethodsA 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.ResultsA 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.ConclusionsCDKN2A/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.

Abstract 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

Aims: To compare healthcare resource utilization (HRU) and costs between patients with or without melanoma recurrence and between patients with distant or locoregional melanoma recurrence. Methods: Patients aged ≥65 years with completely resected, stage IIB/IIC or III melanoma were identified from Surveillance, Epidemiology, and End Results-Medicare data and stratified based on whether they experienced a recurrence, and whether it was distant or locoregional (separately for each stage). The index date was the date of recurrence (recurrence group) or a randomly assigned date (non-recurrence group). Patients in the recurrence and non-recurrence groups were propensity score-matched 1:1 based on patient characteristics; HRU and healthcare costs were compared between the 2 groups and between patients with distant or locoregional recurrence during the ≤24 months following index. Results: After matching, 507 pairs of patients with recurrent or non-recurrent stage IIB/IIC melanoma (236 patients with distant recurrence, 271 with locoregional) and 141 pairs of patients with recurrent or non-recurrent stage III melanoma (50 patients with distant recurrence, 91 with locoregional) were included. During the first year following recurrence, unadjusted HRU was generally higher in patients with versus without recurrence and patients with distant versus locoregional recurrence among both stage IIB/IIC and III cohorts. Patients who experienced recurrence incurred $6,474 (stage IIB/IIC) or $6,112 (stage III) per patient per month (PPPM) more in unadjusted, all-cause, total healthcare costs than patients without recurrence (both p < 0.001). Patients with distant recurrence incurred $7,292 (stage IIB/IIC) or $5,436 (stage III) PPPM more in unadjusted, all-cause, total healthcare costs than patients with locoregional recurrence (both p < 0.05). Limitations: Melanoma recurrence was identified using a claims-based algorithm. Conclusions: Economic burden is higher in patients with versus without melanoma recurrence and patients with distant versus locoregional recurrence. There is a high unmet need for adjuvant therapies that may help to prevent or delay recurrence. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • Older patients with breast cancer often die from competing causes. • Competing mortality after recurrence has not been extensively studied so far. • Novel multi-state models were used including time after recurrence. • These models can be applied to different datasets as input for clinical decision tools. [ABSTRACT FROM AUTHOR]

Background/Aims Rectal neuroendocrine tumor (NETs) up to 2cm in size are widely treated with endoscopic resection with a favorable prognosis. However, studies on the clinical outcomes of microscopic incomplete resected rectal NET after macroscopic complete endoscopic resection are still lacking. We aimed to investigate the long-term clinical outcomes of microscopic incomplete resected rectal NETs after macroscopic complete endoscopic resection to optimize the follow-up strategies. Methods This retrospective study included 401 patients diagnosed with rectal NETs who had undergone macroscopic complete endoscopic resection between October 2004 and December 2019 at Seoul national university hospital. Multivariate analysis was performed to analyze factors associated with incomplete resection. Clinical outcomes including local or distant recurrence were compared between the wait-and-see group and the salvage treatment group. Results Among all 401 patients, microscopic complete resection after macroscopic complete endoscopic resection was achieved in 283 (70.6%) patients and salvage treatment was performed in 34 (8.5%) patients. In multivariate analysis, tumor size (adjusted odds ratio 1.13; 95% confidence interval 1.05-1.21, p=0.001) was an independent risk factor for microscopic incomplete resection. During the median follow-up period of 39.3 months, local recurrence occurred in 3 patients, 2 in the wait-and-see group and 1 in the salvage treatment group, while distant recurrence did not occur in any group. Conclusion Considering the clinical outcomes including local or distant recurrences of this study, the ‘wait-and-see’ policy is a safe and efficient strategy for patients with microscopic incompletely resected rectal NETs, as well as in microscopic completely resected rectal NETs after macroscopic complete endoscopic resection. [ABSTRACT FROM AUTHOR]

Abstract Background Clinical treatment of osteosarcoma suffers from high recurrence rate. Therefore, is of great clinical values to develop predictive markers for recurrent osteosarcoma. Cervical carcinoma high-expressed lncRNA 1 (lncRNA CCHE1) participates in several types of malignancies, while its functionality in osteosarcoma is unknown. This study was therefore carried out to explore the involvement of lncRNA CCHE1 in recurrent osteosarcoma. Methods A total of 87 osteosarcoma patients received surgical resection and 38 healthy volunteers were included in this study. The 87 osteosarcoma patients were followed up for 5 years to record the recurrence of osteosarcoma. Plasma levels of lncRNA CCHE1 and ROCK1 on the day of discharge and during follow-up were measured by real-time quantitative PCR and ELISA, respectively. The effects of CCHE1 siRNA silencing on ROCK1 expression were analyzed by real-time quantitative PCR and western blot. Transwell assay was performed to analyze the role of lncRNA CCHE1 and ROCK1 in regulating cell invasion and migration. Results We observed that, on the day of discharge, plasma lncRNA CCHE1 was upregulated in osteosarcoma patients who developed distant recurrence (DR) during follow-up than in osteosarcoma patients who developed local recurrence (LR), patients with non-recurrence (NR) and healthy controls. On the day of discharge, plasma levels of ROCK1 were higher in DR, LR and NR groups in comparison to healthy controls. On the day of discharge, plasma levels of lncRNA CCHE1 were positively correlated with plasma levels of ROCK1 only in patients who developed DR during follow-up, but not in patients who developed LR, NR and control groups. During follow-up, plasma levels of lncRNA CCHE1 were further increased in DR group but slightly decreased in LR and NR groups. LncRNA CCHE1 siRNA silencing inhibited, while ROCK1 overexpression promoted osteosarcoma cell invasion and migration. ROCK1 overexpression attenuated the role of CCHE1. LncRNA CCHE1 siRNA silencing led to inhibited ROCK1 expression in cancer cells. Conclusion Therefore, lncRNA CCHE1 may participate in postoperative distant recurrence of osteosarcoma caner possibly by interacting with ROCK1 to promote cancer cell invasion and migration.

Jiapeng Xu,1,* Yu Zhang,1,* Qing You,1 Hongbing Fu,1 Xiaokai Zhao,2 Kai Lu,2 Ronglin Yan,1 Dejun Yang1 1Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People’s Republic of China; 2Shanghai Yunying Medical Technology Co.Ltd, Shanghai 201600, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ronglin Yan; Dejun YangDepartment of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai 200003, People’s Republic of ChinaEmail yanronglin@smmu.edu.cn; yangdejun@smmu.edu.cnIntroduction: It is worldwide accepted that lncRNA PTCSC3 is a tumor suppressor in glioma and thyroid cancer, whereas its role in the recurrence of gastric cancer is unknown.Patients and Methods: We recruited 80 GC patients (46 males and 34 females, 44 to 68 years, 56.3± 6.7 years) in our study. Two human GC cell lines AGS and SNU-1 were transfected with PTCSC3 and HOXA11-AS expression vectors. Then, qPCR was used to detect the level of relative mRNA. Both invasion and migration assays were performed to detect the effect of the lncRNA on gastric cancer cell motility.Results: In the present study, we showed that PTCSC3 was downregulated in plasma of gastric cancer patients than in plasma of healthy controls. Follow-up study indicated that PTCSC3 was further downregulated in patients with distant-recurrence but not in patients with local recurrence only or non-recurrence. LncRNA HOXA11-AS was upregulated in plasma of gastric cancer cells than in plasma of healthy controls and was inversely correlated with PTCSC3 in plasma of gastric cancer patients. PTCSC3 overexpression mediated the downregulation of HOXA11-AS in gastric cancer cells, while HOXA11-AS overexpression failed to significantly affect PTCSC3. PTCSC3 overexpression led to inhibited, while HOXA11-AS overexpression led to promoted migration and invasion of gastric cancer cells. In addition, HOXA11-AS overexpression reduced the effects of PTCSC3 overexpression.Discussion: Therefore, lncRNA PTCSC3 alleviates in the postoperative distant recurrence of gastric cancer possible by suppression of HOXA11-AS.Keywords: PTCSC3, gastric cancer, distant recurrence, HOXA11-AS

Cervical cancer is one of the most common cancers in women worldwide. Patients diagnosed with early-stage cervical cancer have a good prognosis, however, 10-20% suffer from local or distant recurrent disease after primary treatment. Treatment options for recurrent cervical cancer are limited. Therefore, it is crucial to identify factors that can predict patients with an increased risk of recurrence to optimize treatment to prevent the recurrence of cervical cancer. We aimed to identify biomarkers in early-stage primary cervical cancer which recurred after surgery. Formalin-Fixed, Paraffin-Embedded surgical specimens of 34 patients with early-stage cervical cancer (FIGO 2009 stage 1B1) and 7 healthy controls were analyzed. Targeted gene expression profiling using the PanCancer IO 360 panel of NanoString Technology was performed. The findings were confirmed by performing immunohistochemistry stainings. Various genes, namely GLS, CD36, WNT5a, HRAS, DDB2, PIK3R2, and CDH2 were found to be differentially highly expressed in primary cervical cancer samples of patients who developed distant recurrence. In addition, The relative infiltration score of CD8+ T cells, CD80+CD86+ macrophages, CD163+MRC1+ macrophages, and FOXP3+IL2RA+ regulatory T cells were significantly higher in this group of samples. In contrast, no significant differences in gene expression and relative immune infiltration were found in samples of patients who developed local recurrence. The infiltration of CD8 and FOXP3 cells were validated by immunohistochemistry using all samples included in the study. We identified molecular alterations in primary cervical cancer samples from patients who developed recurrent disease. These findings can be utilized towards developing a molecular signature for the early detection of patients with a high risk to develop metastasis.

Purpose: Examine the association between circulating lipids and breast cancer outcomes in patients enrolled in the Malmö Diet and Cancer Study (MDCS). Patients and methods: Circulating lipid levels were measured in blood sampled upon enrollment in the female MDCS cohort (N = 17,035). We identified all MDCS participants with incident invasive breast cancer diagnosed between 1991 and 2014. Follow-up time began at breast cancer diagnosis and continued until the first event of breast cancer recurrence, death, emigration, or 5 years of follow-up. We estimated the incidence rates of recurrence at 5 years and fit Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI) of breast cancer recurrence as well as all-cause mortality according to cohort-specific tertiles of apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B). Results: We enrolled 850 eligible patients. During the 5 years of follow-up, 90 invasive breast cancer recurrences were diagnosed over 3807 person-years. In multivariable analyses, high baseline levels of Apo B were associated with an increased rate of recurrence (tertile 3 vs. 1, HR = 2.30 [95% CI 1.13–4.68]). However, high baseline levels of Apo B were not associated with all-cause mortality (tertile 3 vs. 1, HR = 1.23 [95% CI 0.68–2.25]). We observed no associations between levels of Apo A-1 and recurrence (tertile 3 vs. 1, HR = 1.34 [95% CI 0.70–2.58]) or all-cause mortality (tertile 3 vs. 1, HR = 1.12 [95% CI 0.61–2.05]). Conclusion: High pre-diagnostic levels of Apo B were associated with an increased risk of recurrence among breast cancer patients. Circulating Apo A-1 was not associated with breast cancer outcomes. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the most common cancers in women worldwide. Patients diagnosed with early-stage cervical cancer have a good prognosis, however, 10-20% suffer from local or distant recurrent disease after primary treatment. Treatment options for recurrent cervical cancer are limited. Therefore, it is crucial to identify factors that can predict patients with an increased risk of recurrence to optimize treatment to prevent the recurrence of cervical cancer. We aimed to identify biomarkers in early-stage primary cervical cancer which recurred after surgery. Formalin-Fixed, Paraffin-Embedded surgical specimens of 34 patients with early-stage cervical cancer (FIGO 2009 stage 1B1) and 7 healthy controls were analyzed. Targeted gene expression profiling using the PanCancer IO 360 panel of NanoString Technology was performed. The findings were confirmed by performing immunohistochemistry stainings. Various genes, namely GLS, CD36, WNT5a, HRAS, DDB2, PIK3R2, and CDH2 were found to be differentially highly expressed in primary cervical cancer samples of patients who developed distant recurrence. In addition, The relative infiltration score of CD8+ T cells, CD80+CD86+ macrophages, CD163+MRC1+ macrophages, and FOXP3+IL2RA+ regulatory T cells were significantly higher in this group of samples. In contrast, no significant differences in gene expression and relative immune infiltration were found in samples of patients who developed local recurrence. The infiltration of CD8 and FOXP3 cells were validated by immunohistochemistry using all samples included in the study. We identified molecular alterations in primary cervical cancer samples from patients who developed recurrent disease. These findings can be utilized towards developing a molecular signature for the early detection of patients with a high risk to develop metastasis. [ABSTRACT FROM AUTHOR]

This study aimed to validate the performance of the Korean Gynecologic Oncologic Group (KGOG)-1024 risk model in predicting the risk of distant failure after chemoradiation in patients with locally advanced cervical cancer (LACC). In a retrospective cohort of 297 patients who received concurrent chemoradiation for advanced cervical cancer, individual risk was calculated using the KGOG-1024 risk model. The cohort was categorized into three risk groups (low-, intermediate-, and high-risk groups) according to the calculated risk. The means of the calculated and observed risks were compared within each group. The study population was classified into low-, intermediate-, and high-risk groups according to the KGOG-1024 risk model (27.2%, 49.3%, and 23.5% of patients, respectively). The calculated and observed 5-year cumulative incidence rates were 12.4% vs. 16.4% in the low-risk group, 23.2% vs. 25.9% in the intermediate-risk group, and 50.7% vs. 36.3% in the high-risk group. Overall, the calculated and observed risk was 26.7% vs. 25.6%. The KGOG-1024 risk assessment model accurately predicted distant recurrence after chemoradiation in patients with LACC, especially in the low- and intermediate-risk groups. The model may be helpful for identifying patients for future trials assessing the possible benefit of adjuvant systemic treatment after chemoradiation. • In locally advanced cervical cancer, the risk of distant failure was predicted. • The model was more accurate in subjects with a low- and intermediate- risk. • The prediction model may be useful in designing more effective trials. [ABSTRACT FROM AUTHOR]

Purpose: Distant recurrence is a devastating occurrence after colorectal cancer resection. This study aimed to identify the risk factors for distant recurrence following surgery. Methods: All consecutive colorectal cancer resections with curative intent were included from a prospectively maintained colorectal cancer database. The primary outcome was to identify predictive factors for distant recurrence of colorectal cancer. Results: A total of 670 eligible cases were identified with 88 (13.1%) developing distant recurrence during the follow-up period. The median time to distant recurrence was 1.2 years with the most common sites of distant recurrence being the lung (44.3%) and liver (44.3%). Predictive factors for distant recurrence in colon cancer included a high tumor, nodal, and overall stage of the primary cancer (p < 0.001 for all). Surgical complications (p = 0.007), including anastomotic leak (p = 0.023), were associated with a higher risk of developing distant recurrence in rectal cancer patients. Independent variables associated with distant recurrence included tumor stage (OR 1.61, p = 0.011), nodal stage (OR 2.18, p < 0.001), and both KRAS (OR 11.04, p < 0.001) and MLH/PMS2 (OR 0.20, p = 0.035) genetic mutations. Among patients with distant recurrence, treatment with surgery conferred the best survival, with patients < 50 years of age having the best overall 5-year survival. Conclusion: Predictive factors for distant recurrence include advanced tumor and nodal stages, and the presence of KRAS and MLH/PSM2 mutations. Clinicians should be cognizant of these risk factors, and instate close surveillance plans for patients exhibiting these features. [ABSTRACT FROM AUTHOR]

Evaluation of recurrence pattern and risk factors for recurrence are essential for good rates of survival after upfront pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). This retrospective study included 167 consecutive patients who underwent upfront PD for resectable PDAC between 2000 and 2018. Postoperative recurrences were classified into three patterns according to initial recurrence site: isolated locoregional, isolated distant, and simultaneous locoregional and distant recurrences. This study found 114 patients who developed postoperative recurrence (68.3%), including 37 patients with isolated locoregional recurrence (32.5%), 67 patients with isolated distant recurrence (58.8%), and 10 patients with simultaneous locoregional and distant recurrences (6.0%). When locoregional recurrence was classified based on the location of recurrent lesions, locoregional recurrence most commonly occurred around the superior mesenteric artery (SMA) (70.2%), followed by around the hepatic artery (25.5%) and in the paraaortic region (14.9%). Multivariate analyses showed that complete circumferential lymphadenectomy around the SMA, including not only the right side, but also the left side, was an independent factor for reduction of locoregional recurrence (P = 0.019, odds ratio [OR]: 2.217). Lymph node metastasis was an independent risk factor for both locoregional (P < 0.001, OR: 3.686) and distant recurrences (P < 0.001, OR: 4.315). Non-completion of postoperative adjuvant therapy was a risk factor for distant recurrence (P < 0.001, OR: 3.748). Based on our data, complete circumferential lymphadenectomy around the SMA might contribute to local control, and multidisciplinary treatment including neoadjuvant therapy might be needed for resectable PDAC with high risk for recurrence. [ABSTRACT FROM AUTHOR]

The prognostic significance of radial margin (RM) involvement in esophagectomy cancer specimens is unclear. Our study investigated survival and recurrence rates between different depths of RM involvement. We retrospectively analyzed 1103 esophagectomies at our institution from 2005 to 2019. Patients were grouped by three-tier stratification: negative RM > 1 mm away, direct RM involvement at 0 mm, and close RM between 0 mm and 1 mm. Survival, loco-regional and distant recurrences were analyzed. 1103 esophageal cancer patients were analyzed. 389 patients had recurrence (35.3%). Median survival (13.2 months) and recurrence rates (71%) were worst with direct RM (p < 0.001) as compared to negative RM (median survival not achieved within 5-years from surgery and 30%). Without nodal involvement, RM involvement of <1 mm was associated with decreased overall survival, and overall, loco-regional and distant recurrence-free survival compared to negative RM (log rank p-value <0.05). In those with persistent nodal disease, only direct RM was associated with decreased overall and loco-regional recurrence-free survival as compared to negative margins (p < 0.05). Direct RM tended to do worse compared to close RM in terms of median survival and trended worse for recurrence. Direct RM (baseline negative RM), but not close RM, was an independent RF in a multivariable Cox model for worse overall survival (HR 2.74; p < 0.001), recurrence-free survival (HR 1.96; p = 0.019), and loco-regional recurrence-free survival (HR 3.19; p = 0.011). RM involvement affects survival and recurrence. Tumor at 0 mm remained an independent RF for worse survival and overall and loco-regional recurrence. [ABSTRACT FROM AUTHOR]

Abstract Background Surveillance imaging is used to detect local and/or distant recurrence following primary treatment of localised soft tissue sarcoma (STS), however evidence supporting optimal surveillance modality or frequency is lacking. We used prospectively collected sarcoma data to describe current surveillance imaging practice in patients with AJCC stage II and III extremity STS and evaluate its cost-effectiveness. Methods From three selected Australian sarcoma referral centres, we identified patients with stage II and III extremity STS treated between 2009 and 2013. Medical records were reviewed to ascertain surveillance imaging practices, including modality, frequency and patient outcomes. A discrete event simulation model was developed and calibrated using clinical data to estimate health service costs and quality adjusted life years (QALYs) associated with alternative surveillance strategies. Results Of 133 patients treated for stage II and III extremity STS, the majority were followed up with CT chest (86%), most commonly at 3-monthly intervals and 62% of patients had the primary site imaged with MRI at 6-monthly. There was limited use of chest-X-ray. A discrete event simulation model demonstrated that CT chest screening was the most cost effective surveillance strategy, gaining additional QALYs at a mean incremental cost of $30,743. MRI alone and PET-CT alone were not cost-effective, whilst a combined strategy of CT + MRI had an incremental cost per QALY gained of $96,556. Conclusions Wide variations were observed in surveillance imaging practices in this high-risk STS cohort. Modelling demonstrated the value of CT chest for distant recurrence surveillance over other forms of imaging in terms of cost and QALYs. Further work is required to evaluate cost-effectiveness in a prospective manner.

Abstract Background Current evidence suggests that patients with Luminal A early breast cancer can skip chemotherapy or extended endocrine therapy, but immunohistochemistry-based biomarker analysis for St Gallen subtyping may not be reproducible. We asked whether RT-qPCR can be used instead to address this clinical question. Methods RNA was extracted from tumor material derived from ER+/HER2- patients receiving adjuvant endocrine treatment for low-risk cancers and was semi-quantified by RT-qPCR with the MammaTyper®. St Gallen subtypes were based on the mRNA expression of ERBB2/HER2, ESR1/ER, PGR/PR and MKI67/Ki67 after dichotomizing at predefined cut-offs. Differences in distant disease-free survival (DDFS) were assessed by Kaplan Meier analysis and Cox regression. Results With a median follow up of 7.8 years, there were ten events in the group of 195 Luminal A-like tumors (5.1%) and 18 events in the remaining 127 tumors (14.1%), consisting mostly of Luminal B-like cases (N = 119). Luminal A-like had significantly better DDFS over the entire follow-up period (HR 0.35, 95% CIs 0.16–0.76, p = 0.0078) with a trend towards reduced probability of recurrences also in the late phase (> 5 years) (HR 0.20, p = 0.052). The survival advantage spanning the entire follow-up period persisted in the pN0 or pN0-N1 subgroups or after correcting for clinicopathological parameters. MKI67 alone significantly predicted for worse DDFS (HR 2.62, 95% CIs 1.24–5.56, p = 0.0088). Conclusions St Gallen Luminal A-like tumors identified by RT-qPCR display markedly low rates of distant recurrence at ten years follow-up. Patients with such tumors could be spared chemotherapy due to the obviously unfavourable benefit/toxicity ratio.

Abstract CanAssist‐Breast (CAB) is an immunohistochemistry (IHC)‐based prognostic test for early‐stage Hormone Receptor (HR+)‐positive breast cancer patients. CAB uses a Support Vector Machine (SVM) trained algorithm which utilizes expression levels of five biomarkers (CD44, ABCC4, ABCC11, N‐Cadherin, and Pan‐Cadherin) and three clinical parameters such as tumor size, grade, and node status as inputs to generate a risk score and categorizes patients as low‐ or high‐risk for distant recurrence within 5 years of diagnosis. In this study, we present clinical validation of CAB. CAB was validated using a retrospective cohort of 857 patients. All patients were treated either with endocrine therapy or chemoendocrine therapy. Risk categorization by CAB was analyzed by calculating Distant Metastasis‐Free Survival (DMFS) and recurrence rates using Kaplan‐Meier survival curves. Multivariate analysis was performed to calculate Hazard ratios (HR) for CAB high‐risk vs low‐risk patients. The results showed that Distant Metastasis‐Free Survival (DMFS) was significantly different (P‐0.002) between low‐ (DMFS: 95%) and high‐risk (DMFS: 80%) categories in the endocrine therapy treated alone subgroup (n = 195) as well as in the total cohort (n = 857, low‐risk DMFS: 95%, high‐risk DMFS: 84%, P 74% of high Ki‐67 and IHC4 score intermediate‐risk zone patients into low‐risk category. Overall the data suggest that CAB can effectively predict risk of distant recurrence with clear dichotomous high‐ or low‐risk categorization.

Distant recurrence, especially liver metastases, occurs in one-third of rectal cancer patients initially treated with curative therapy and is still an unsolved problem. The identification of patients at risk is crucial for enabling individualized treatment. All patients undergoing curative resection for histologically confirmed rectal cancer after neoadjuvant radiochemotherapy between January 2001 and December 2015 were included. Sections were stained for Ki67, CD44, apoptosis and CD133. Patients were categorized based on whether they were found to have (CD44+/Ki67+) or not have (CD44+/Ki67+) still proliferating tumor cells. 218 patients who underwent R0 resection for stage I-III rectal cancer were selected. In 37 (17%) of these patients, CD44+/Ki67+ tumor cells were found. In multivariable Cox regression analysis, patients with CD44+/Ki67+ cells had significantly impaired overall (hazard ratio (HR): 3.84, 95% CI: 1.77–8.31, p = 0.001) and relative survival (HR 3.44, 95% CI: 1.46–8.09). The previous results were confirmed after propensity-score matching. In mediation-analysis, the presence of CD44+/Ki67+ cells was associated with a substantial direct effect on overall (HR 1.92, 95% CI: 1.09–9.28) and relative survival (HR 1.63, 95% CI: 1.31–6.38). The presence of still proliferating CD44+/Ki67+ tumor cells after neoadjuvant radiochemotherapy was associated with impaired oncological long-term outcomes. Characterization of these cells should be performed. [ABSTRACT FROM AUTHOR]

Introduction: Triple negative breast cancer (TNBC) is highly heterogeneous, but still most of the patients are treated by the anthracycline/taxane-based neoadjuvant therapy (NACT). Tumor-infiltrating lymphocytes (TILs) are a strong predictive and prognostic biomarker in TNBC, however are not always available. Peripheral blood counts, which reflect the systemic inflammatory/immune status, are easier to obtain than TILs. We investigated whether baseline white cell or platelet counts, as well as, Neutrophil-to-Lymphocyte Ratio (NLR) or Platelet-to-Lymphocyte Ratio (PLR) could replace baseline TILs as predictive or prognostic biomarkers in a series of TNBC treated by standard NACT. Patients and Methods: One hundred twenty patients uniformly treated by FEC/taxane NACT in a tertiary cancer care center were retrospectively analyzed. The presence of pathological complete response (pCR: ypT0/Tis, ypN0) or the presence of pCR and/small residual disease (ypT0/Tis/T1ab, ypN0) were considered as good responses in data analysis. Baseline/pre-NACT blood count, NLR, PLR and TILs were evaluated as predictors of response, distant recurrence rate and distant recurrence-free survival (DRFS). Results: TILs ≥30% and ≥1.5% were best predictors of pCR and distant recurrence risk, respectively (p = 0.007, p = 0.012). However, in this cohort, pCR status was not significantly associated with recurrence. Only the ensemble of patients with pCR and small residual disease had lower recurrence risk and longer survival DRFS (p = 0.042, p = 0.024, respectively) than the rest of the cohort (larger residual disease). The only parameter which could predict the pCR/small residual disease status was PLR: patients with values lower than 133.25 had significantly higher chance of reaching that status after NACT (p = 0.045). However, no direct correlation could be established between baseline PLR and metastatic recurrence. No correlation either was found between TIL and individual blood counts, or between TILs and NLR or PLR. Conclusion: In this cohort, TILs retained their pCR predictive value; however PLR was a better predictor of the ensemble of responses which had good outcome in terms of less distant recurrences or longer DRFS (pCR or small residual disease). Thus, baseline PLR is worth further, prospective investigation together with baseline TILs, as it might indicate a good TNBC response to NACT when TILs are unavailable. [ABSTRACT FROM AUTHOR]

Objective: We sought to define the prognostic significance of histologic subtype for extremity/truncal liposarcoma (LPS). Background: LPS, the most common sarcoma, is comprised of 5 histologic subtypes. Despite their distinct behaviors, LPS outcomes are frequently reported as a single entity. Methods: We analyzed data on all patients from a single-institution prospective database treated from July 1982 to September 2017 for primary, nonmetastatic, extremity or truncal LPS of known subtype. Clinicopathologic variables were tested using competing risk analyses for association with disease-specific death (DSD), distant recurrence (DR), and local recurrence (LR). Results: Among 1001 patients, median follow-up in survivors was 5.4 years. Tumor size and subtype were independently associated with DSD and DR. Size, subtype, and R1 resection were independently associated with LR. DR was most frequent among pleomorphic and round cell LPS; the former recurred early (43% by 3 years), and the latter over a longer period (23%, 3 years; 37%, 10 years). LR was most common in dedifferentiated LPS, in which it occurred early (24%, 3 years; 33%, 5 years), followed by pleomorphic LPS (18%, 3 years; 25%, 10 years). Conclusions: Histologic subtype is the factor most strongly associated with DSD, DR, and LR in extremity/truncal LPS. Both risk and timing of adverse outcomes vary by subtype. These data may guide selective use of systemic therapy for patients with round cell and pleomorphic LPS, which carry a high risk of DR, and radiotherapy for LPS subtypes at high risk of LR when treated with surgery alone. [ABSTRACT FROM AUTHOR]

• MRI follow-up until the terminal stage was conducted after BCNU wafer implantation. • The recurrence pattern was determined by MRI or the radiation field. • We histologically assessed an autopsy case after wafer implantation. 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU, or Carmustine) wafers are intraoperatively implantable wafers used to achieve local tumor control. There is scarce data about the behavior of wafers in the long-term follow-up of implanted cases. We reviewed the data of 64 patients with newly diagnosed glioblastoma treated by surgery, BCNU wafers, radiation therapy, and temozolomide administration. This cohort included 55 patients who presented first recurrence, and 49 of them showed tumor progression to death. The MR imaging of each patient at the terminal stage and an autopsy case were used to elucidate the tumor progression pattern after the wafer implantation. We subdivided the first recurrence pattern into local, distant, and multifocal based on MR imaging or into infield, outfield, and marginal based on the radiation field. The first recurrence pattern was 33 patients (60%) with local, 13 (24%) with distant, and nine (16%) with multifocal recurrence, or 38 patients (69%) with infield, 13 (24%) with outfield, and four (7%) with marginal. The median and mean time intervals between MR imaging at the terminal stage and death were 2.0 and 2.3 months, respectively. Of note, 13 patients with first distant recurrence had no obvious radiological local tumor progression even at the terminal stage. Long-term follow-up after BCNU wafer implantation revealed that patients with first distant recurrence had long-lasting local tumor control until the terminal stage. [ABSTRACT FROM AUTHOR]

Background: Endocrine therapy resistance is a major cause of distant recurrence (DR) in hormone receptor–positive breast cancer. This study evaluated differences in survival after DR in patients treated with different adjuvant endocrine therapy regimens in the Breast International Group (BIG) 1‐98 trial. Methods: BIG 1‐98 compared 5 years of adjuvant treatment among 4 arms: tamoxifen (T), letrozole (L), tamoxifen followed by letrozole (TL), and letrozole followed by tamoxifen (LT). After a median follow‐up of 8.1 years, 911 of 8010 patients (T, 302; L, 285; TL, 170; and LT, 154) had DR as the site of first recurrence. Univariate and multivariate Cox analyses were performed to determine features associated with post‐DR survival. Results: The median follow‐up time after DR was 59 months (interquartile range, 29‐88 months). Among all patients with DR, 38.1% were 65 years old or older at enrollment, 61.9% had tumors larger than 2 cm, and 69.7% were node positive. Neoadjuvant or adjuvant chemotherapy was administered to 35.6% of the patients. There was no difference in post‐DR survival by treatment arm (median survival, 20.8 months for T, 17.9 months for L, 17.3 months for TL, and 20.8 months for LT; P =.21). In multivariate analysis, older patients (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.15‐1.59) and patients with tumors larger than 2 cm (HR, 1.19; 95% CI, 1.00‐1.41), 4 or more positive nodes (HR, 1.31; 95% CI, 1.05‐1.64), progesterone receptor (PR)–negative tumors (HR, 1.25; 95% CI, 1.02‐1.52), or shorter disease‐free survival (DFS) had significantly worse post‐DR survival. Conclusions: Treatment with adjuvant T, L, or their sequences was not associated with differences in survival after DR. Significant differences in survival were observed by age, primary tumor size, nodal and PR status, and DFS, and this suggests that traditional baseline high‐risk features remain prognostic in the metastatic setting. In the Breast International Group 1‐98 study, no difference was observed in post–distant recurrence survival by adjuvant endocrine treatment arm. Older patients and patients with tumors larger than 2 cm, 4 or more positive nodes, progesterone receptor–negative tumors, or shorter disease‐free survival had significantly worse post–distant recurrence survival. [ABSTRACT FROM AUTHOR]

Background & Aims: Radiation therapy has been refined with increasing evidence of the benefits of stereotactic body radiation therapy (SBRT) in treating hepatocellular carcinoma (HCC). In this study, we aimed to evaluate whether SBRT could serve as an alternative to radiofrequency ablation (RFA) for small HCC with a single lesion ≤5.0 cm., Methods: Patients with a single HCC lesion ≤5.0 cm who received RFA or SBRT were included. Cumulative local/distant recurrence rate, progression-free survival, overall survival, adverse events and subsequent treatments after recurrence were analyzed., Results: A total of 288 patients receiving RFA (n = 166) or SBRT (n = 122) were enrolled. The baseline characteristics between the two groups were comparable. The cumulative local recurrence rate in the SBRT group was significantly lower than that in the RFA group (hazard ratio [HR] 0.30, 95% CI 0.16-0.57, p < 0.001), especially for patients with tumours >2.0 cm (HR 0.20, 95% CI 0.08-0.50, p < 0.001) or adjacent to major vessels (HR 0.29, 95% CI 0.13-0.66, p < 0.001). Cumulative distant recurrence rate, progression-free survival and overall survival were not significantly different between the two groups (all p >0.050). Adverse events were mild and easily reversible. However, more patients in the SBRT group suffered from Child-Pugh score and total bilirubin increases. More treatment options after recurrence or progression might be available for patients in the RFA group compared to those in the SBRT group ( p < 0.001)., Conclusions: Both RFA and SBRT were effective and safe for HCC with a single lesion ≤5.0 cm. SBRT could be an alternative treatment to RFA, especially for tumours >2.0 cm or adjacent to major vessels., Impact and Implications: Stereotactic body radiation therapy (SBRT) may be used as an alternative treatment to thermal ablation for patients with BCLC stage A hepatocellular carcinoma (HCC) who are not candidates for surgical resection, including those with tumours >3 cm and those with 1 to 3 tumours. This study focused on HCC patients with a specific tumour burden, namely a single lesion ≤5.0 cm, demonstrating that SBRT could be an effective and safe alternative to radiofrequency ablation (RFA), especially for those with tumours >2.0 cm or adjacent to major vessels. The findings of this study provided robust empirical evidence supporting the utilization of SBRT in treating small HCC, while also establishing a solid foundation for future prospective clinical investigations., (© 2024 The Author(s).)

To investigate the prognostic value of DGM-CM6 (Distant Genetic Model-Clinical variable Model 6) for endocrine-responsive breast cancer (ERBC) patients, we analyzed 752 operable breast cancer patients treated in a Taiwan cancer center from 2005 to 2014. Among them, 490 ERBC patients (identified by the PAM50 or immunohistochemistry method) were classified by DGM-CM6 into low- and high-risk groups (cutoff

Advances in the treatment of Ewing's sarcoma family of tumors (ESFTs) are a result of improvements in systemic and local therapies. VACA (vincristine, Adriamycin [doxorubicin], cyclophosphamide, dactinomycin) chemotherapy alone versus VACA + IE (VACA with alternate ifosfamide, etoposide) improve survival, but this regimen cannot be given to all patients due to poor tolerance and 5-day schedule chemotherapy in VACA + IE schedule. We reviewed the records of 50 patients treated as per our institutional protocols from 2007 to 2011. Two schedules of chemotherapy followed were vincristine, Adriamycin, cyclophosphamide (VAC) and VAC with alternate ifosfamide, etoposide (VAC + IE). Factors predictive of local failure and distant recurrence were analyzed. A total of 50 patients were analyzed. The median age at diagnosis was 14 years. Thirty-two patients were male, whereas 18 were female. Approximately, 95% of the patients relapsed after a median time gap of 1.6 years. The median 5-year disease-free survival was 30%. Systemic treatment with VAC or VAC + IE–based chemotherapy had equal local control and distant control rates. Smaller tumors had a better local control and lesser systemic failure than those of larger sizes. Successful treatment of Ewing's sarcoma requires optimal systemic and local therapy. Both the chemotherapy regimens showed equal survival rates. Control of both the local and distant diseases is a result of the combined modality approach. Stage at presentation is the most important factor for prognosis. Complete surgery and local radiotherapy are important predictive factors for local and systemic control.

Background: Few studies have focused on risk factors which may predict an intrahepatic local recurrence (LR) on the surgical edge rather than a distant recurrence (DR) in other liver segments after surgery for hepatocarcinoma (HCC). The purpose of this study was to assess the risk factors for both patterns of recurrence. Methods: An international, multicentre, retrospective study was conducted by collecting data on all consecutive patients with a first diagnosis of HCC who were treated between 2010 and 2017. The presence of macrovascular invasion was an exclusion criteria. Results: About 376 patients were enrolled, and, among them, 62 presented LR, while 90 had DR. Baseline characteristics were comparable between the two groups, but the DR group had a much higher rate of HCV infection (48.9% vs 29%, p 0.014) and a higher median nodule size (3.40 cm IQR 2.2–5.5 versus 3.0 cm IQR 2.0–5.0 in the LR group, p 0.025). A positive surgical margin (R1, HR 4.721; 95% CI 1.83–12.17; p 0.001) was the only independent risk factor for LR, while MVI (HR 1.837; 95% CI 1.03–3.77; p 0.039) and satellitosis (HR 2.440, 95% CI 1.43–3.77, p 0.001) were the only predictive factors for DR. Conclusion: MVI and satellitosis are predictive factors of intrahepatic distant recurrence, configuring a probable hallmark of advanced systemic disease, regardless of the treatment. LR has to be considered the expression of surgical failure. [ABSTRACT FROM AUTHOR]

Background: Clinical treatment of osteosarcoma suffers from high recurrence rate. Therefore, is of great clinical values to develop predictive markers for recurrent osteosarcoma. Cervical carcinoma high-expressed lncRNA 1 (lncRNA CCHE1) participates in several types of malignancies, while its functionality in osteosarcoma is unknown. This study was therefore carried out to explore the involvement of lncRNA CCHE1 in recurrent osteosarcoma.Methods: A total of 87 osteosarcoma patients received surgical resection and 38 healthy volunteers were included in this study. The 87 osteosarcoma patients were followed up for 5 years to record the recurrence of osteosarcoma. Plasma levels of lncRNA CCHE1 and ROCK1 on the day of discharge and during follow-up were measured by real-time quantitative PCR and ELISA, respectively. The effects of CCHE1 siRNA silencing on ROCK1 expression were analyzed by real-time quantitative PCR and western blot. Transwell assay was performed to analyze the role of lncRNA CCHE1 and ROCK1 in regulating cell invasion and migration.Results: We observed that, on the day of discharge, plasma lncRNA CCHE1 was upregulated in osteosarcoma patients who developed distant recurrence (DR) during follow-up than in osteosarcoma patients who developed local recurrence (LR), patients with non-recurrence (NR) and healthy controls. On the day of discharge, plasma levels of ROCK1 were higher in DR, LR and NR groups in comparison to healthy controls. On the day of discharge, plasma levels of lncRNA CCHE1 were positively correlated with plasma levels of ROCK1 only in patients who developed DR during follow-up, but not in patients who developed LR, NR and control groups. During follow-up, plasma levels of lncRNA CCHE1 were further increased in DR group but slightly decreased in LR and NR groups. LncRNA CCHE1 siRNA silencing inhibited, while ROCK1 overexpression promoted osteosarcoma cell invasion and migration. ROCK1 overexpression attenuated the role of CCHE1. LncRNA CCHE1 siRNA silencing led to inhibited ROCK1 expression in cancer cells.Conclusion: Therefore, lncRNA CCHE1 may participate in postoperative distant recurrence of osteosarcoma caner possibly by interacting with ROCK1 to promote cancer cell invasion and migration. [ABSTRACT FROM AUTHOR]

Background: Surveillance imaging is used to detect local and/or distant recurrence following primary treatment of localised soft tissue sarcoma (STS), however evidence supporting optimal surveillance modality or frequency is lacking. We used prospectively collected sarcoma data to describe current surveillance imaging practice in patients with AJCC stage II and III extremity STS and evaluate its cost-effectiveness. Methods: From three selected Australian sarcoma referral centres, we identified patients with stage II and III extremity STS treated between 2009 and 2013. Medical records were reviewed to ascertain surveillance imaging practices, including modality, frequency and patient outcomes. A discrete event simulation model was developed and calibrated using clinical data to estimate health service costs and quality adjusted life years (QALYs) associated with alternative surveillance strategies. Results: Of 133 patients treated for stage II and III extremity STS, the majority were followed up with CT chest (86%), most commonly at 3-monthly intervals and 62% of patients had the primary site imaged with MRI at 6-monthly. There was limited use of chest-X-ray. A discrete event simulation model demonstrated that CT chest screening was the most cost effective surveillance strategy, gaining additional QALYs at a mean incremental cost of $30,743. MRI alone and PET-CT alone were not cost-effective, whilst a combined strategy of CT + MRI had an incremental cost per QALY gained of $96,556. Conclusions: Wide variations were observed in surveillance imaging practices in this high-risk STS cohort. Modelling demonstrated the value of CT chest for distant recurrence surveillance over other forms of imaging in terms of cost and QALYs. Further work is required to evaluate cost-effectiveness in a prospective manner. [ABSTRACT FROM AUTHOR]

Background: Studies have demonstrated worse breast cancer‐specific mortality with older age, despite an increasing risk of dying from other causes due to comorbidity (competing mortality). However, findings on the association between older age and recurrence risk are inconsistent. The aim of this study was to assess incidences of locoregional and distant recurrence by age, taking competing mortality into account. Materials and Methods: Patients surgically treated for nonmetastasized breast cancer between 2003 and 2009 were selected from The Netherlands Cancer Registry. Cumulative incidences of recurrence were calculated considering death without distant recurrence as competing event. Fine and Gray analyses were performed to characterize the impact of age (70–74 [reference group], 75–79, and ≥80 years) on recurrence risk. Results: A total of 18,419 patients were included. Nine‐year cumulative incidences of locoregional recurrence were 2.5%, 3.1%, and 2.9% in patients aged 70–74, 75–79, and ≥80 years, and 9‐year cumulative incidences of distant recurrence were 10.9%, 15.9%, and 12.7%, respectively. After adjustment for tumor and treatment characteristics, age was not associated with locoregional recurrence risk. For distant recurrence, patients aged 75–79 years remained at higher risk after adjustment for tumor and treatment characteristics (75–79 years subdistribution hazard ratio [sHR], 1.25; 95% confidence interval [CI], 1.11–1.41; ≥80 years sHR, 1.03; 95% CI, 0.91–1.17). Conclusion: Patients aged 75–79 years had a higher risk of distant recurrence than patients aged 70–74 years, despite the higher competing mortality. Individualizing treatment by using prediction tools that include competing mortality could improve outcome for older patients with breast cancer. Implications for Practice: In this population‐based study of 18,419 surgically treated patients aged 70 years or older, patients aged 75–79 years were at higher risk of distant recurrence than were patients aged 70–74 years. This finding suggests that patients in this age category are undertreated. In contrast, it was also demonstrated that the risk of dying without a recurrence strongly increases with age, and patients with a high competing mortality risk are easily overtreated. To identify older patients who may benefit from more treatment, clinicians should therefore take competing mortality risk into account. Prediction tools could facilitate this and thereby improve treatment strategy. Evidence suggests that age is an independent risk factor for worse breast cancer outcome. This study assessed the incidence of locoregional and distant recurrence by age at diagnosis among patients aged ≥70 years, while taking competing mortality risks into account. [ABSTRACT FROM AUTHOR]

Objective: Despite the benefits of concomitant radiotherapy and cisplatin for locally advanced cervical cancer, recurrence rates remain high. New treatment strategies such as consolidation chemotherapy and different concomitant chemotherapy combinations have been tested in recent years. Identification of the best candidates for each treatment strategy could optimize results.Study Design: A retrospective review of data from 127 patients with locally advanced cervical cancer (International Federation of Gynecology and Obstetrics Stages IIB-IVA), treated at a single institution from 2005 to 2014. Risk factors for loco-regional and systemic recurrence, and prognostic factors for overall survival (OS) were analysed using Cox regression. Survival of patients treated with consolidation chemotherapy was compared with survival of patients not treated with consolidation chemotherapy in the role cohort and in a propensity-score-matched cohort.Results: With a median follow-up time of 48.7 months, loco-regional-recurrence-free survival (LRFS), distant-metastasis-free survival (DMFS) and OS at 5 years were 76.6%, 54.0% and 63.0%, respectively. On multivariate analysis, tumour size ≥6 cm was associated with shorter LRFS [hazard ratio (HR) 5.18; 95% confidence interval (CI) 1.45-18.45; p = 0.011], and adenocarcinoma (HR 2.48; 95% CI 1.10-5.57; p = 0.028) and positive lymph nodes (HR 2.21; 95% CI 1.303-4.72; p = 0.041) were associated with shorter DMFS. Tumour size ≥6 cm was associated with shorter OS (HR 2.64; 95% CI 1.09-6.35; p = 0.031). Twenty-two patients were treated with consolidation chemotherapy; on univariate analysis, these patients had longer OS compared with patients who were not treated with consolidation chemotherapy (p = 0.043). In a propensity-score-matched cohort, patients treated with consolidation chemotherapy had longer DMFS and OS compared with patients who were not treated with consolidation chemotherapy, although the difference was not significant.Conclusions: Different risk factors are associated with loco-regional and distant metastases in patients with locally advanced cervical cancer, and could potentially lead to particular therapeutic strategies. Although the number of patients treated with consolidation chemotherapy in the study cohort was small, they seemed to live longer and to have better control of distant relapse then patients who were not treated with consolidation chemotherapy. [ABSTRACT FROM AUTHOR]