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PURPOSE Large-scale analysis of real-world evidence is often limited to structured data fields that do not contain reliable information on recurrence status and disease sites. In this report, we describe a natural language processing (NLP) framework that uses data from free-text, unstructured reports to classify recurrence status and sites of recurrence for patients with breast and hepatocellular carcinomas (HCC). METHODS Using two cohorts of breast cancer and HCC cases, we validated the ability of a previously developed NLP model to distinguish between no recurrence, local recurrence, and distant recurrence, based on clinician notes, radiology reports, and pathology reports compared with manual curation. A second NLP model was trained and validated to identify sites of recurrence. We compared the ability of each NLP model to identify the presence, timing, and site of recurrence, when compared against manual chart review and International Classification of Diseases coding. RESULTS A total of 1,273 patients were included in the development and validation of the two models. The NLP model for recurrence detects distant recurrence with an area under the curve of 0.98 (95% CI, 0.96 to 0.99) and 0.95 (95% CI, 0.88 to 0.98) in breast and HCC cohorts, respectively. The mean accuracy of the NLP model for detecting any site of distant recurrence was 0.9 for breast cancer and 0.83 for HCC. The NLP model for recurrence identified a larger proportion of patients with distant recurrence in a breast cancer database (11.1%) compared with International Classification of Diseases coding (2.31%). CONCLUSION We developed two NLP models to identify distant cancer recurrence, timing of recurrence, and sites of recurrence based on unstructured electronic health record data. These models can be used to perform large-scale retrospective studies in oncology.

IntroductionTriple 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 MethodsOne 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).ResultsTILs ≥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.ConclusionIn 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.

PURPOSE Although the prognosis of patients with thin primary cutaneous melanomas (T1, ≤ 1.0 mm) is generally excellent, some develop recurrence. We sought to develop and validate a model predicting recurrences in patients with thin melanomas. METHODS A Dutch population-based cohort (n = 25,930, development set) and a cohort from an Australian melanoma treatment center (n = 2,968, validation set) were analyzed (median follow-up 6.7 and 12.0 years, respectively). Multivariable Cox models were generated for local, regional, and distant recurrence-free survival (RFS). Discrimination was assessed using Harrell's C-statistic for each outcome. Each nomogram performance was evaluated using calibration plots defining low-risk and high-risk groups as the lowest and top 5% of the nomogram risk score, respectively. The nomograms' C-statistics were compared with those of a model including the current American Joint Committee on Cancer staging parameters (T-stage and sentinel node status). RESULTS Local, regional, and distant recurrences were found in 209 (0.8%), 503 (1.9%), and 203 (0.8%) Dutch patients, respectively, and 23 (0.8%), 61 (2.1%), and 75 (2.5%) Australian patients, respectively. C-statistics of 0.79 (95% CI, 0.75 to 0.82) for local RFS, 0.77 (95% CI, 0.75 to 0.78) for regional RFS, and 0.80 (95% CI, 0.77 to 0.83) for distant RFS were obtained for the development model. External validation showed C-statistics of 0.80 (95% CI, 0.69 to 0.90), 0.76 (95% CI, 0.70 to 0.82), and 0.74 (95% CI, 0.69 to 0.80), respectively. Calibration plots showed a good match between predicted and observed rates. Using the nomogram, the C-statistic was increased by 9%-12% for the development cohort and by 11%-15% for the validation cohort, compared with a model including only T-stage and sentinel node status. CONCLUSION Most patients with thin melanomas have an excellent prognosis, but some develop recurrence. The presented nomograms can accurately identify a subgroup at high risk. An online calculator is available at www.melanomarisk.org.au .

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 (3.40cm IQR 2.2–5.5 versus 3.0cm 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.

International audience; Background: Few patients with pancreatic adenocarcinoma (PAC) are eligible for surgery. Patients with early relapse have a poor prognosis and might be better candidates for a medical approach. Clinical and pathological parameters only partially predict recurrence and are only obtained after surgery. PAC subtypes based on gene expression were proposed, and we assessed if they could predict the risk and type of recurrence independently of clinicopathological parameters. Methods: Patients with curative-intent surgery for PAC without pretreatment were selected and divided into two independent cohorts defined as discovery (n = 381) and validation (n = 149) cohorts. Transcriptomic analyses were performed on formalin-fixed paraffin-embedded surgical samples to characterise tumour and stroma compartments using previously defined signatures. We associated molecular and clinicopathological characteristics with general, distant, and local recurrences using Cox regression analyses. Results: We found that tumour biology predicted distant recurrence contrary to local recurrence, which was directly related to resection margin status. Pure basal-like and stroma-activated subtypes were strongly associated with distant recurrence, independently of clinicopathological factors (hazard ratios [HRs] = 5.85, p < 0.001 and HR = 1.75, p = 0.007, respectively). By dissecting tumoural and stromal compartments, we demonstrated that the basal-like tumour component positively correlated with distant recurrence in both cohorts (HR = 1.45, p < 0.001 and HR = 1.90, p < 0.001), whereas the inactive structural stroma component was protective against distant recurrence (HR = 0.68, p < 0.001 and HR = 0.72, p < 0.001). Conclusions: In addition to suggesting a different mechanism for local and distant relapse (incomplete resection and high metastatic potential, respectively), our results show the potency of molecular phenotype to predict patient outcome regarding distant recurrences.

Triple‐negative breast cancer (TNBC) is a type of breast cancer that has a higher risk of distant recurrence and metastasis, leading to a relatively aggressive biological behaviour and poor outcome. So far, the clinical management of TNBC is challenging because of its heterogeneity and paucity of specific targeted therapy. Recently, various studies have identified a lot of differently expressed long non‐coding RNAs (lncRNAs) in TNBC. Those lncRNAs have been reported to play important roles in the multistep process of TNBC tumorigenesis. Here, we review the biological characteristics of lncRNAs, and present the current state of knowledge concerning the expression, function and regulation of lncRNAs in TNBC. Accumulating studies explored the potential lncRNAs‐based therapeutics in TNBC, including the techniques of genetic modification using antisense oligonucleotides, locked nucleic acid and RNA nanotechnology. In current review, we also discuss the future prospects of studies about lncRNAs in TNBC and development of lncRNA‐based strategies for clinical TNBC patients., In current review, we accumulated literature to the understanding of lncRNAs biogenesis and function, as well as the latest findings of novel lncRNAs‐based therapeutics in TNBC. We also present the current state of knowledge concerning the expression and regulation of lncRNAs in TNBC, and discuss the future development of lncRNA‐based strategies for clinical TNBC patients.

BACKGROUND Patterns of recurrence help to inform surveillance of patients with resected gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS Patients with GEP-NETs in British Columbia, Canada (2004-2015) were reviewed. Associations between tumor characteristics, recurrence and survival were analyzed. RESULTS Among 759 patients, 41%, 25%, and 17% had grade 1, 2, and 3 disease, respectively. 387 patients had R0/R1 resections, of which 30% recurred (median 25 months). 5-year incidence of recurrence was 22% (grade 1), 46% (grade 2), and 59% (grade 3) (p

Distant recurrence of breast cancer results in high lifetime risks and low 5-year survival rates. Early prediction of distant recurrent breast cancer could facilitate intervention and improve patients' life quality. In this study, we designed an EHR-based predictive model to estimate the distant recurrent probability of breast cancer patients. We studied the pathology reports and progress notes of 6,447 patients who were diagnosed with breast cancer at Northwestern Memorial Hospital between 2001 and 2015. Clinical notes were mapped to Concept unified identifiers (CUI) using natural language processing tools. Bag-of-words and pre-trained embedding were employed to vectorize words and CUI sequences. These features integrated with clinical features from structured data were downstreamed to conventional machine learning classifiers and Knowledge-guided Convolutional Neural Network (K-CNN). The best configuration of our model yielded an AUC of 0.888 and an F1-score of 0.5. Our work provides an automated method to predict breast cancer distant recurrence using natural language processing and deep learning approaches. We expect that through advanced feature engineering, better predictive performance could be achieved.

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 of1 mm was associated with decreased overall survival, and overall, loco-regional and distant recurrence-free survival compared to negative RM (log rank p-value0.05). 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.

Use of genomic assays to determine distant recurrence risk in patients with early stage breast cancer has expanded and is now included in the American Joint Committee on Cancer staging manual. Algorithmic alternatives using standard clinical and pathology information may provide equivalent benefit in settings where genomic tests, such as OncotypeDx, are unavailable. We developed an artificial neural network (ANN) model to nonlinearly estimate risk of distant cancer recurrence. In addition to clinical and pathological variables, we enhanced our model using intraoperatively determined global mammographic breast density (MBD) and local breast density (LBD). LBD was measured with optical spectral imaging capable of sensing regional concentrations of tissue constituents. A cohort of 56 ER+ patients with an OncotypeDx score was evaluated. We demonstrated that combining MBD/LBD measurements with clinical and pathological variables improves distant recurrence risk prediction accuracy, with high correlation (r = 0.98) to the OncotypeDx recurrence score. This article is protected by copyright. All rights reserved.

Purpose/Objectives Before definitive stereotactic body radiation therapy (SBRT) for presumably node-negative, early-stage NSCLC, many patients are staged with PET/CT alone. In patients undergoing PET/CT prior to SBRT, the role of invasive nodal staging (INS) with endobronchial ultrasound (EBUS) or mediastinoscopy is uncertain. We sought to characterize the impact of nodal staging modality on outcomes. Materials/Methods Patients receiving definitive SBRT for T1-2N0 NSCLC deemed node-negative by either PET/CT plus INS (EBUS or mediastinoscopy) or PET/CT alone were identified. Patients with initially equivocal or positive nodes on PET/CT were excluded from this analysis. All patients received 3–5 fraction SBRT according to institutional guidelines. Control was assessed by at least one follow-up CT in all patients. Multivariable logistic regression (MVA) was performed to identify variables independently associated with use of INS. Results We identified 651 eligible patients at our institution from 2005–2016. INS was performed in 15.2% of patients (n = 99) with EBUS (n = 78) or mediastinoscopy (n = 21). Median follow-up was 19.4 months (0.2–135.1). Median survival was 28.5 months (0.6–140). Factors predictive of increased likelihood of INS after negative PET/CT on MVA were age (OR for decreasing age 1.033; 95% CI 1.058–1.010), Caucasian race (OR vs. non-white 1.852; 1.044–3.289), male sex (1.629; 1.031–2.575), central location (1.978; 1.218–3.211) and squamous histology (2.564; 1.243–5.287). Nodal and/or distant control at 2 years was similar between PET/CT alone (78%, 95% CI 74–82%) and INS + PET/CT (75%, 95% CI 65–85%) (p = 0.877) as well as on MVA. Overall survival did not differ based on staging modality. Conclusions In patients with early-stage NSCLC deemed node-negative by PET/CT, addition of INS did not appreciably alter patterns of failure or survival after definitive SBRT. This study does not question the established value of INS for equivocal or suspicious nodes.

Efficient prediction of cancer recurrence in advance may help to recruit high risk breast cancer patients for clinical trial on-time and can guide a proper treatment plan. Several machine learning approaches have been developed for recurrence prediction in previous studies, but most of them use only structured electronic health records and only a small training dataset, with limited success in clinical application. While free-text clinic notes may offer the greatest nuance and detail about a patient’s clinical status, they are largely excluded in previous predictive models due to the increase in processing complexity and need for a complex modeling framework. In this study, we developed a weak-supervision framework for breast cancer recurrence prediction in which we trained a deep learning model on a large sample of free-text clinic notes by utilizing a combination of manually curated labels and NLP-generated non-perfect recurrence labels. The model was trained jointly on manually curated data from 670 patients and NLP-curated data of 8062 patients. It was validated on manually annotated data from 224 patients with recurrence and achieved 0.94 AUROC. This weak supervision approach allowed us to learn from a larger dataset using imperfect labels and ultimately provided greater accuracy compared to a smaller hand-curated dataset, with less manual effort invested in curation.

Recent studies on medulloblastomas (MB) suggest that a large fraction of tumors appearing as late recurrence turn out to be secondary malignancies, e.g., malignant gliomas, after thorough molecular investigation. Here, we report of a patient with a group 4 MB that developed a distant recurrence after more than 18 years. The recurrent tumor was confirmed by histology and genome-wide DNA methylation profiling. Our case not only illustrates the potential of very late recurrences after seemingly cured group 4 MB, but also illustrates that detailed molecular analyses are indispensable in patients with a history of a previous malignancy.

Background: EndoPredict has been previously validated as a prognostic test in women with ER-positive, HER2-negative disease who received endocrine therapy only as part of the ABCSG6 and -8 trials. Here, we further evaluate the prognostic value of EndoPredict in this cohort with longer-term follow-up and compare 10-year distant recurrence (DR) and 5-15 years late recurrence according to nodal status. Methods: This analysis included 1702 patients with ER-positive, HER2-negative disease who received endocrine therapy only. Prognostic value of EPclin score and EPclin risk category (high, low) on the risk of distant recurrence adjusted for patient and disease characteristics was evaluated using multivariable Cox proportional hazard models. Kaplan-Meier estimators were used to estimate DR according EPclin class and were compared using log rank test. Analyses were performed for the overall cohort, by nodal status, and for patients who were distant recurrence free at year 5 (late recurrence). Results: The median follow-up was 9.6 years (range 0-16.6), an increase of 4.2 years over previous reports. Reanalysis with longer follow-up confirms that EPclin is a significant predictor of DR after adjusting for clinical factors, regardless of nodal status (Table 1). Overall, 62.6% of patients had low risk EPclin scores and 10-year DR was significantly improved relative to those with high risk scores (p Conclusion: This reanalysis of previous EndoPredict data with a longer follow-up confirms that EPclin can identify a large group of patients at low risk of distant recurrence after 10 years who might be sufficiently treated with 5 years adjuvant endocrine therapy only, independent of nodal status. Replication of these results for the late distant recurrence between years 5-15 also shows that EPclin scores may also be informative in selecting patients who may safely forgo extended endocrine therapy. Table 1.Multivariate analysis 0-15 year DR5-15 year DRCohortHR*p-valueHR*p-valueAll patients2.55 Table 2.DR according to EPclin score Low risk EPclinHigh risk EPclin CohortHR*%0-10 year DR (95% CI)%0-10 year DR (95% CI)Log-rank p-valueAll patients N=17024.7762.60.96 (0.94, 0.97)37.40.80 (0.77, 0.84) Citation Format: Filipits M, Dubsky P, Rudas M, Greil R, Balic M, Fitzal F, Bago-Horvath Z, Singer C, Hlauschek D, Kronenwett R, Bernhisel R, Lancaster J, Gnant M. Prediction of distant recurrence using EndoPredict among women with ER-positive, HER2-negative breast cancer with a maximum follow-up of 16 years [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-05.

Introduction Lymphoedema develops after surgery in 30% patients. In a prospective, multi-centre UK study, we used a validated perometer arm measurement to determine 1) the factors predicting lymphoedema development and 2) the effect of a lymphoedema diagnosis on QoL and survival. Methods Participants (n = 1100) undergoing axillary clearance at 9 centres underwent arm volume measurements pre and post-surgery by perometry, and completed FACT-B+4 and Lymphoedema checklist questionnaires. Relative arm volume increase (RAVI) of >10% diagnosed lymphoedema. Predictors of lymphoedema development were determined using logistic regression, and changes in QoL were assessed using Generalised Estimating Equation (GEE) analyses. Results Median patient age was 56 (range 22 to 90) years; 78% received radiotherapy and 65% chemotherapy. Lymphoedema was detected in 21.4% of women by perometry and 24.4% underwent sleeve application by 24 months. Initial decreases in QoL scores post-surgery were greater in patients with lymphoedema and took longer to return to baseline values (FACT-B p=0.014, TOI p=0.008, ARM subscale p RAVI at 1 month (p25-≤30 and >30, p=0.05), ER status (p=0.05) and number of positive nodes (p Local recurrence was 1.7%. One hundred and twenty-nine patients had died of breast cancer (n=88) or had distant recurrence (n=41) across the study. Lymphoedema (RAVI≥10%) by 9 months was an independent predictor of post 9 months distant disease-free cancer survival (Table). Distant Disease Free Survival (DDFS) after Lymphoedema diagnosis Single variableMultivariableVariable (between 3 and 9 months)nHazard ratio (HR) (95% CI)p-valueHR (95% CI)p-valueRAVI ≥ 10% Yes: 105 vs No9552.30 (1.39-3.81)0.0011.73 (1.01-2.96)0.047ER Status Negative: 1719532.94 (1.92-4.49) Conclusions Lymphoedema is associated with lasting quality of life deficits and early distant relapse. Women at low risk of lymphoedema (75%) can be reassured using the scoring model. Early Arm measurements at 1 month post-surgery a useful measurement time to determine lymphoedema risk and enable patients to be reassured (75%) or plan for lymphoedema monitoring. Citation Format: Bundred NJ, Foden P, Riches K, Morris J, Evans A, Todd C, Bramley M, Skene A, Purushotham A, Keeley V. Prediction model for lymphoedema, and effect of Lymphoedema diagnosis on quality of life (QoL) and distant recurrence from breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-07-01.

New evidence and systemic therapies demand an updated analysis of chemotherapy for soft tissue sarcoma. We completed a meta-analysis of chemotherapy in localized STS, assessing OS, PFS, and local and distant recurrence (local recurrence-free survival [LRFS] and distant recurrence-free survival [DRFS]). Ten studies, totaling 3157 patients, were included. A pooled analysis for 5-year OS, progression-free survival, LRFS, and DRFS showed no benefit of chemotherapy over locoregional therapy alone for all-comers or site-specific STS. We make recommendations to improve outcome reporting and quality indices.

Purpose:Multigene assays provide useful prognostic information regarding hormone receptor (HR)-positive breast cancer. Next-generation sequencing (NGS)-based platforms have numerous advantages including reproducibility and adaptability in local laboratories. This study aimed to develop and validate an NGS-based multigene assay to predict the distant recurrence risk.Experimental Design:In total, 179 genes including 30 reference genes highly correlated with the 21-gene recurrence score (RS) algorithm were selected from public databases. Targeted RNA-sequencing was performed using 250 and 93 archived breast cancer samples with a known RS in the training and verification sets, respectively, to develop the algorithm and NGS–Prognostic Score (NGS-PS). The assay was validated in 413 independent samples with long-term follow-up data on distant metastasis.Results:In the verification set, the NGS-PS and 21-gene RS displayed 91.4% concurrence (85/93 samples). In the validation cohort of 413 samples, area under the receiver operating characteristic curve plotted using NGS-PS values classified for distant recurrence was 0.76. The best NGS-PS cut-off value predicting distant metastasis was 20. Furthermore, 269 and 144 patients were classified as low- and high-risk patients in accordance with the cut-off. Five- and 10-year estimates of distant metastasis–free survival (DMFS) for low- versus high-risk groups were 97.0% versus 77.8% and 93.2% versus 64.4%, respectively. The age-related HR for distant recurrence without chemotherapy was 9.73 (95% CI, 3.59–26.40) and 3.19 (95% CI, 1.40–7.29) for patients aged ≤50 and >50 years, respectively.Conclusions:The newly developed and validated NGS-based multigene assay can predict the distant recurrence risk in ER-positive, HER2-negative breast cancer.

We analyzed oncologic outcomes according to pre-/post-LPLN enlargement. Rectal cancer patients who underwent resection post-PCRT during 2008-2012 were enrolled. Magnetic resonance imaging pre-/post-PCRT were re-evaluated. LNs with short axis (SA) ≥7 mm pre-PCRT and ≥4 mm post-PCRT were defined as enlarged nodes. Of 798 patients enrolled, recurrence occurred in 55 (6.9%) local, 17 (2.1%) lateral, and 179 (22.4%) distal regions. Patients with LPLN SA ≥7 mm pre-PCRT showed worse local recurrence-free survival (RFS), lateral RFS, and distant RFS (p 0.001, 0.002, and 0.005, respectively). LN shrinkage post-PCRT to SA4 mm showed better 5-year local RFS (83.5% vs. 78.3%, p = 0.045), but distant RFS was similar irrespective of LN shrinkage to4 mm. Among patients with pre-PCRT SA ≥7 mm, node shrinkage to SA4 mm after PCRT presented with lower incidence of local recurrence but did not benefit in distant recurrence. Lateral node sampling did not improve local recurrence control, resulting in a 5-year local RFS of 75.4% in patients undergoing lateral node sampling and 83.2% in those not undergoing lateral node sampling (p = 0.722). Four (66.7%) patients had lateral recurrence in the same area of the enlarged nodes identified pre-PCRT. For patients assessed with pre-PCRT nodes ≥7 mm, response to PCRT did not guarantee better outcomes.

espanolObjetivo Los sarcomas uterinos son tumores raros con mal pronostico debido a las altas tasas de recurrencia. El papel actual de la 18F-FDG PET/TC en la vigilancia posterior a la terapia aun no esta establecido. Material y metodos Cuarenta y una mujeres con sarcoma uterino se sometieron a 73 estudios 18F-FDG PET/TC para la reestadificacion en la presunta recurrencia o durante el seguimiento en pacientes asintomaticos. Los resultados histopatologicos y/o el seguimiento clinico/de imagenes durante al menos 12 meses se consideraron el estandar de referencia. Se calculo la precision diagnostica y el impacto clinico de la 18F-FDG PET/TC. Resultados treinta y tres estudios 18F-FDG PET/TC fueron positivos, mientras que los 40 estudios restantes fueron negativos. La sensibilidad general, la especificidad, el valor predictivo positivo (VP+), el valor predictivo negativo (VP-) y la precision de la 18F-FDG PET/TC fueron del 88%, 98%, 97%, 91% y 93%. Considerando pacientes con sospecha clinica o radiologica de recidiva (n = 47) y durante el seguimiento (n = 26) la sensibilidad y especificidad, VP+, VP− y precision de 18F-FDG PET/TC fueron del 89%, 100%, 100%, 86% y 94%, y 80%, 95%, 80%, 95% y 92% respectivamente. La 18F-FDG PET/TC tuvo un impacto clinico positivo en 9/73 (12%) estudios y cambio el manejo clinico en 8/41 (20%) pacientes. Conclusion La 18F-FDG PET/TC es un metodo preciso para la deteccion y localizacion de recidivas a distancia en pacientes con sarcoma uterino con buena sensibilidad y especificidad e impacto significativo en la toma de decisiones clinicas. EnglishPurpose Uterine sarcomas are rare tumors with poor prognosis due to the high recurrence rates. The current role of 18F-FDG PET/CT in the post-therapy surveillance is not established yet. Materials and Methods Forty-one women with uterine sarcoma underwent 73 18F-FDG PET/CT for restaging in suspected recurrence or during follow-up in asymptomatic patients. Histopathology results and/or clinical/imaging follow-up for at least 12 months were considered the reference standard. The diagnostic accuracy and clinical impact of 18F-FDG PET/CT was calculated. Results Thirty-three 18F-FDG PET/CT were positive, while the remaining 40 studies were negative. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 18F-FDG PET/CT were 88%, 98%, 97%, 91% and 93%, respectively. Considering patients with clinical or radiological suspicion of recurrence (n = 47) and those during follow-up (n = 26), sensitivity, specificity, PPV, NPV and accuracy of 18F-FDG PET/CT were 89%, 100%, 100%, 86% and 94%, and 80%, 95%, 80%, 95% and 92%, respectively. 18F-FDG PET/CT had a positive clinical impact in 9/73 (12%) studies and changed the clinical management in 8/41 (20%) patients. Conclusions 18F-FDG PET/CT seems to be an accurate method for detection and localization of local and distant recurrence in patients with uterine sarcoma with good sensitivity and specificity and significant impact on clinical decision making.

Background Recurrence of periampullary cancer after pancreatoduodenectomy is common. The aim of this study was to investigate patterns of recurrence, incidence, and factors associated with local and distant recurrences. Methods This retrospective, single-centre study included consecutive patients with periampullary cancer who underwent resection with curative intent from January 2012 to January 2018. Survival, patterns of recurrence, and factors associated with recurrences were analysed. Results Median overall survival (OS) and disease-free survival among 398 included patients was 58.4 and 49.5 months respectively. Twenty-three patients (5.8 per cent) developed isolated local recurrences (LR), 50 (12.6 per cent) developed LR along with distant metastasis (DM), and 103 (25.9 per cent) developed isolated DM. Median OS was 40.4 months for patients with isolated LR versus 23 months for those with DM (P Conclusion Isolated LR is associated with better survival than DM and occurs most commonly along the superior mesenteric artery.

Introduction With the increasing reliance on targeted therapies and immunotherapy, no standard management strategy is today available for the treatment of locally, distant, or both renal cell carcinoma (RCC) recurrences, and their surgical treatment seems to play a crucial role. We report the 20-year experience of our center evaluating the short- and long-term outcomes of patients undergone surgical resection of RCC recurrences, and the possible role of repeated surgical resections of RCC recurrences. Materials and methods From January 1999 to January 2019, 40 patients underwent surgical resection of isolated locally recurrent RCC (iLR-RCC-group), locally recurrent RCC associated with the presence of distant recurrence (LR-DR-RCC-group), and distant-only recurrent RCC (DR-RCC-group). Data regarding pre-, intra-, post-operative course, and follow-up, prospectively collected in an institutional database, were retrospectively analyzed and compared. Results iLR-RCC-group was composed of 9 patients, LR-DR-RCC-group of 6 patients, and DR-RCC-group of 25 patients. The recurrence rate was 55.6% (5/9 patients) in iLR-RCC-group, 50% (3/6 patients) in LR-DR-RCC-group, and 44% (11/25) patients in DR-RCC-group, p = 0.830. 3/5 (60%) patients in iLR-RCC-group, 2/3 (66.7%) patients in LR-DR-RCC-group, and 7/11 (63.6%) patients in DR-RCC group underwent to almost one further local treatments of their recurrences, respectively (p = 0.981). No differences in the mean disease-free survival (p = 0.384), overall survival (OS) (p = 0.881), and cancer-specific survival (p = 0.265) were reported between the three groups. In DR-RCC-group, patients who underwent further local treatments of new recurrences presented a longer OS: 150.7 versus 66.5 months (p = 0.004). Conclusions A surgical resection of RCC recurrences should be always taken in consideration, also in metastatic patients and/or in those who have already undergone surgery of previous RCC recurrence, whenever radicality is still possible, because this approach may offer a potentially long survival.

Dermatofibrosarcoma protuberans is a rare form of soft tissue sarcoma that tends to invade and recur locally. The most common site of this disease is head, neck and extremities; however, the involvement of the breast has been reported. We present a case with a dermatofibrosarcoma of the breast that is composed of low-grade spindle cells which are positive for CD43. She was treated by wide surgical excision followed by adjuvant external beam irradiation at a dose of 60 Gray. After a follow-up of 24 months, no local-regional or distant recurrence was detected.

Lung cancer remains the leading cause of cancer-related death worldwide, with estimated 5-year survival rates for patients with pathological N0 (pN0) non-small cell lung cancer (NSCLC) as low as 56% (1,2). Although these staggering low survival rates could be attributed to a multitude of patient-related and tumor-related factors, recent evidence suggests that these outcomes are most likely related to tumor recurrence and metastasis (1,3-5). In this regard, identification of clinically relevant predictors for tumor recurrence is an integral step towards improving patient prognosis, with a goal of defining a relevant patient cohort that would benefit from possible additional therapies (either induction or adjuvant therapy).

There are few data on the long-term outcomes of patients with phyllodes tumors following breast-conserving surgery with or without radiation therapy (RT). We reviewed 69 patients diagnosed from 2000 to 2015 with surgical specimens available for central pathology assessment for outcome in relation to histopathologic subtype, margin width, and utilization of RT. Median follow-up was 63 months (interquartile range, 35-131 months). Forty-eight patients had benign, 13 borderline, and eight malignant phyllodes tumors, with local recurrence rates of 4%, 0%, and 38%, respectively (P ≤ .04 comparing malignant lesions to both benign and borderline lesions). None of the eight patients who received RT suffered a local recurrence. Two of the 26 (8%) patients with benign phyllodes tumors who did not receive RT with margins that were positive or

Background: BCI is a gene expression assay for patients with early stage HR+ breast cancer that provides 2 results: BCI Predictive, based on the HoxB13/IL17BR (H/I) ratio, reports a prediction of high vs low likelihood of benefit from EET; BCI Prognostic, based on the algorithmic combination of H/I and a set of proliferation-based genes, reports the risk of late distant recurrence (DR). Clinical actionability is distinct based on the 4 possible combinations of prognostic and predictive results. To better characterize patients classified by BCI as having a high risk of late DR but a low likelihood of benefit from EET, we assessed clinicopathologic and molecular correlates in this subset. Methods: The BCI Clinical Database for Correlative Studies is a de-identified database containing >50 clinicopathologic and molecular variables from cases submitted for BCI in clinical practice (N=19,126). Clinicopathologic variables abstracted from pathology reports were available for a subset of these cases. Molecular proliferation status (molecular grade index [MGI]) and clinicopathologic parameters were examined in the 4 possible BCI result categories of BCI Prognostic (High vs Low risk) and BCI Predictive (High vs Low H/I). Chi-squared tests and ANOVA were used to compare BCI results within subsets. Results: Analyses included 3843 LN- pts with clinicopathologic data: Median age was 59.1y (range 26-89y; 74% ≥50y); 30.9%, 51.7%, and 17.4% were Grade 1, 2, and 3, respectively; 27.8%, 48.9%, 21.7%, and 1.6% were T1a/b, T1c, T2, and T3, respectively. BCI categorized 41.4% of pts as having Low risk/Low likelihood of benefit, 31.3% with High risk/High benefit, 18.0% with High risk/Low benefit, and 9.3% with Low risk/High benefit. Patients with High Risk/Low Benefit had increased median proliferation scores (MGI), and a greater proportion of pts with grade 2/3 tumors and high Ki67 scores compared to pts with Low Risk/Low Benefit (P Conclusion: In characterizing the molecular and clinical correlates in BCI cases with a high risk of late DR but low likelihood of benefit from EET, we found that higher proliferative status was associated with classification of high risk of DR. Future studies might investigate whether patients with this molecular pattern might benefit from combinatorial therapy (e.g., CDK 4/6 inhibitors) with EET. This study highlights the importance of predictive biomarkers for individualized EET therapy recommendation. Citation Format: Royce M, Poage G, Israel MA, Schnabel CA, Holmes FA. Clinicopathologic and molecular correlates of breast cancer index (BCI) results in patients with HR+, LN- breast cancer that are high risk of late distant recurrence (DR) / low likelihood of benefit from extended endocrine therapy (EET) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-18.

Objectives: Despite complete surgical resection, 30–40% of patients with stage I–IIA non-small-cell lung cancer (NSCLC) have recurrences. We aimed to elucidate the effect of lymphovascular invasion (LVI) on the prognosis and patterns of recurrence in patients with pathologically confirmed T1–2N0 NSCLC. Methods: We evaluated 381 patients who underwent complete resection and were diagnosed with pathologic T1–2N0 NSCLC between March 2000 and January 2012. Local recurrence, nodal recurrence, and distant metastasis were defined and analyzed. Results: LVI was present in 72 patients (18.9%). The 5-year disease-free survival (DFS) for all patients was 69.9%. Patients with LVI showed a significant decrease in 5-year DFS (47.3 vs. 74.4%, p < 0.001). LVI was a significant prognostic predictor in multivariate analysis (p = 0.003). The patients with LVI showed a significantly increased 5-year cumulative incidence of nodal recurrence (22.5 vs. 8.7%, p < 0.001) and distant metastasis (30.4 vs. 14.9%, p = 0.004). However, no difference was shown between the two groups in the 5-year cumulative incidence of local recurrence (p = 0.416). Conclusions: LVI is a negative prognostic factor in patients with stage I–IIA NSCLC. The presence of LVI significantly increases the risk of nodal and distant recurrence.

INTRODUCTION: Current standard of care for glioblastoma (GBM) includes concurrent chemoradiation and maintenance temozolomide (TMZ) along with Tumor Treating Fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. Secondary analysis of EF14 trial demonstrated TTFields treatment may increase the rate of distant recurrence. We report our experience evaluating areas of progression in our pilot clinical trial of concurrent chemoradiation with TTFields. METHODS: This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with KPS ≥ 60 with newly diagnosed GBM were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions), standard concurrent TMZ (75 mg/m2 daily), and TTFields. Maintenance therapy included standard TMZ and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. Incidence and location of progression was documented. Distant recurrence was defined as recurrence more than 2 cm from primary enhancing lesion. RESULTS: A total of 30 patients were enrolled on the trial. Twenty were male, and ten were female, with median age 58 years (19-77 years). Median KPS was 90 (70-100). Median follow-up was 11.6 months (1.7-22.1 months). Twenty (66.7%) patients had an unmethylated MGMT promotor status and ten (33.3%) patients had a methylated promoter status. Twenty patients (66.7%) had progression, with median PFS of 9.1 months (range 1.6 to 12.9 months). Five patients (26%) of patient presented with distant recurrence, with median distance from primary lesion of 5.1 cm (2.26-9.12 cm). One infratentorial progression was noted. Another patient transferred care and location of progression is unknown. CONCLUSIONS: Concurrent chemoradiation with TTFields for patients with newly diagnosed glioblastoma may have increased incidence of distant recurrence. This finding is suggestive of improved local control of primary site. Further data are needed to validate this finding.

Despite careful selection, the recurrence rate after upfront surgery for pancreatic adenocarcinoma can be very high. We aimed to construct and validate a model for the prediction of early distant recurrence (&lt, 12 months from index surgery) after upfront pancreaticoduodenectomy. After exclusions, 147 patients were retrospectively enrolled. Preoperative clinical and radiological (CT-based) data were systematically evaluated, moreover, 182 radiomics features (RFs) were extracted. Most significant RFs were selected using minimum redundancy, robustness against delineation uncertainty and an original machine learning bootstrap-based method. Patients were split into training (n = 94) and validation cohort (n = 53). Multivariable Cox regression analysis was first applied on the training cohort, the resulting prognostic index was then tested in the validation cohort. Clinical (serum level of CA19.9), radiological (necrosis), and radiomic (SurfAreaToVolumeRatio) features were significantly associated with the early resurge of distant recurrence. The model combining these three variables performed well in the training cohort (p = 0.0015, HR = 3.58, 95%CI = 1.98–6.71) and was then confirmed in the validation cohort (p = 0.0178, HR = 5.06, 95%CI = 1.75–14.58). The comparison of survival curves between low and high-risk patients showed a p-value &lt, 0.0001. Our model may help to better define resectability status, thus providing an actual aid for pancreatic adenocarcinoma patients’ management (upfront surgery vs. neoadjuvant chemotherapy). Independent validations are warranted.