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Background 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). Methods 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. Results 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%. Conclusions 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.

Background Primary leiomyosarcoma (LMS) of the gastrointestinal (GI) tract is rare. Limited literature exists regarding the clinical characteristics and outcome for patients with localised and metastatic disease. Methods A retrospective chart review was performed for patients greater than 18 years of age diagnosed with GI LMS at The Royal Marsden Hospital between 1 January 2000–1 May 2020. Descriptive statistics were performed. Patients were censored at data cut-off date of 27 June 2020. Results Forty-six patients with a median age at diagnosis of 54 years (range 25–85) were identified. Fifteen percent (n = 7) of patients previously received abdominal radiation for an unrelated cancer. All patients with localised disease (n = 36) had resection with oncological margins. For patients who underwent potentially curative surgery, median recurrence-free survival (mRFS) was 13 months (0.4–183 months), and half of these patients (n = 18) developed recurrent disease post resection (distant n = 16, local n = 2). Median overall survival (mOS) was 27 months for patients with distant recurrence. Twenty-one percent (n = 10) of patients presented with synchronous metastatic disease and their mOS was 19 months. Median progression-free survival (mPFS) for patients treated with conventional chemotherapy ranged from 2.0 to 8.0 months. Conclusion The risk of recurrence is significant, and recurrence-free survival was short even with complete oncologic resection. The relationship of prior abdominal radiotherapy to the development of GI LMS warrants further investigation. Outcomes with systemic therapy for metastatic disease were poor and there is a need for the development of more effective systemic therapies.

Administration of chemotherapy before breast surgery has the potential to reduce the risk of distant recurrence by targeting micrometastasis as well as allowing a more minimalistic approach to surgical intervention. We performed a systematic review to determine the optimum timing of surgery post breast cancer neoadjuvant chemotherapy (NACT).The primary outcome was to determine whether the timing of surgery post NACT impacted overall survival (OS) and disease-free survival (DFS). We compared patient outcomes between those who had surgery within 8 weeks of completion of NACT to those that had surgery after 8 weeks. An outcome comparison between4 weeks and 4-8 weeks was also performed. Secondary outcome included complete pathological response (pCR) post NACT. A meta-analysis was performed using the Mantel-Haenszel method.Five studies, including 8794 patients were eligible for inclusion. Patients that had surgery within 8 weeks of completion of NACT had a statistically significant improved OS(OR 0.47, 95% c. i 0.34-0.65) and DFS(OR 0.71 (95% c. i 0.52-0.98, P = 0.04). There were no survival advantages associated with having surgery less than 4 weeks post completion of NACT (OR 0.78, 95% c. i 0.46-1.33, P = 0.37). There was no difference in pCR rate between those that had surgery4 weeks and 4-8 weeks (OR 1.01, 95% c. i 0.80-1.28, P = 0.93).This meta-analysis shows that the optimum timing of surgery post completion of NACT is 4-8 weeks as it is associated with increased OS and DFS.

Background Chemotherapy improves overall survival after surgery and radiotherapy for newly diagnosed high-risk IDH-mutant low-grade gliomas (LGGs), but a proportion of patients treated with temozolomide (TMZ) will develop recurrent tumors with TMZ-induced hypermutation. We aimed to determine the prevalence of TMZ-induced hypermutation at recurrence and prognostic implications. Methods We sequenced recurrent tumors from 82 patients with initially low-grade IDH-mutant gliomas who underwent reoperation and correlated hypermutation status with grade at recurrence and subsequent clinical outcomes. Results Hypermutation was associated with high-grade disease at the time of reoperation (OR 12.0 95% CI 2.5-115.5, P = .002) and was identified at transformation in 57% of recurrent LGGs previously exposed to TMZ. After anaplastic (grade III) transformation, hypermutation was associated with shorter survival on univariate and multivariate analysis (HR 3.4, 95% CI 1.2-9.9, P = .024), controlling for tumor grade, subtype, age, and prior radiotherapy. The effect of hypermutation on survival after transformation was validated in an independent, published dataset. Hypermutated (HM) tumors were more likely to develop discontiguous foci of disease in the brain and spine (P = .003). To estimate the overall incidence of high-grade transformation among low-grade IDH-mutant tumors, data from a phase II trial of TMZ for LGG were analyzed. Eight-year transformation-free survival was 53.8% (95% CI 42.8-69.2), and 61% of analyzed transformed cases were HM. Conclusions TMZ-induced hypermutation is a common event in transformed LGG previously treated with TMZ and is associated with worse prognosis and development of discontiguous disease after recurrence. These findings impact tumor classification at recurrence, prognostication, and clinical trial design.

Background: The 21-gene recurrence score (RS) provides prognostic information for distant recurrence (DR) and predictive information for chemotherapy (CT) benefit in early breast cancer, whereas clinicopathologic features provide only prognostic information. We used patient-specific meta-analysis (PSMA) methods (Crager et al, J Appl Stat 2014 [PMID: 26664111]; Tang et al. J Clin Oncol 2011 [PMID: 22010013]) to develop an online tool that assesses individualized estimates of DR risk and absolute CT benefit. We also externally validated this new tool for estimating DR risk in an independent cohort.Methods: The PSMA included 10,004 women with hormone-receptor positive, HER2-negative, node-negative breast cancer from the NSABP B-14 (n=577) trial receiving endocrine therapy (ET) alone and TAILORx trial receiving ET alone (n=4854) or CT plus ET (n=4573). The baseline risk used TAILORx event rates with ET alone. A patient-specific estimator of absolute CT benefit was computed by combining PSMA of the individualized relative CT effect from the TAILORx and NSABP B-20 (n=550 HER2-negative) trials and risk estimates with ET alone. External validation of DR risk estimation was performed in an independent cohort of 1098 women enrolled in the Clalit Health Service registry who had a 21-gene RS performed, of whom 222 (20%) received CT in addition to ET as per the recommendation of their treating physician guided by the RS. Results: The new tool is more informative for DR risk than RS or clinicopathologic factors alone (p Citation Format: Joseph A Sparano, Michael R Crager, Gong Tang, Robert J Gray, Salomon M Stemmer, Steve Shak. Development and validation of a tool integrating the 21-gene recurrence score and clinicopathlogic features to individualize prognosis for distant recurrence and prediction of absolute chemotherapy benefit in early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS4-10.

Background:Clinical risk criteria (CRC) has been used in two well-known gene-expression trials (TAILORX and MINDACT) to predict the risk of distant recurrence (DR). The definition of clinical low-risk patients was (1) node-negative associated with (grade 1 with tumor ≤3cm, grade 2 with tumor≤2cm, or grade 3 with tumor ≤1cm) and N1 with grade 1 and tumor ≤2cm. Recurrence Index for distant recurrence (RI-DR) is a clinical-genomic model, based on genomic profiling derived from Asian women. The primary purpose of this study is to access the clinical utility of RI-DR and CRC in Asian breast cancer patients. Methods:A total of 208 patients (N0 70.2%, N1 29.8%) with luminal-like breast cancer were enrolled in a retrospective study across Taiwan medical centers. Kaplan-Meier method was used to calculate the survival rates and the log rank test was applied for the survival difference between two or more independent groups. The primary endpoint was the recurrence-free interval (RFI). Results:With a median follow-up of 49.05 [IQR 29.72-71.96], the 5-year RFI was significantly poorer in the high-risk group than the low-risk group (87.2% [95% CI, 80.0-95.0] versus 95.2% [89.75-100] by the RI-DR, p = 0.011; and 86.9% [79.8-94.6] versus 97.0% [92.9-100] by the clinical risk, p = 0.03). Combined the CRC and RI-DR together, clinical high (CH) and RI-DR high (RH)had the poorest 5-year RFI (85.2%, [76.6-94.8]); clinical low (CL) and RI-DR low (RL) had the best 5-year RFI (98.0% [94.08, 100]). Among CL-risk patients, RL group has a trend towards less recurrence than RH group (1/66 [1.51%] versus 2/19 [10.52%], p= 0.15). Similar trend was observed in CH-risk patients (RL: 2/41 (4.88%) versus RH: 12/82 [14.63%], p = 0.17) (Table 1). Conclusions:The present study provides robust evidences that clinical-risk criteria and RI-DR testing could partition patients into good and poor prognosis in early-stage luminal breast cancer. RI-DR has a trend to identify low- and high-risk patients if clinical risk criteria have been applied in clinical practice. Analyses of Clinical Risk Criteria and Recurrence Index TogetherNo. of PatientsNo. of Events5-year RFI % (95% CI)Log rank, P valueClinical-Clinical-HighRI-DR high821285.20 [76.55, 94.81]0.17RI-DR low41291.30 [80.15, 100]Clinical-LowRI-DR high19294.12 [83.57, 100]0.15RI-DR low66197.96 [94.08, 100] Citation Format: Skye Hung-Chun Cheng, Liang-Chih Liu, Ling-Ming Tseng, Chuan-Hsun Chang, Chiun-Sheng Huang, Ji-An Liang, Yu-Chen Hsu, Chia-Ming Hsieh, Jun-Ru Wei. Clinical risk criteria and recurrence index for distant recurrence for patients with early stage luminal breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-40.

Background: A majority of breast cancer tumors express estrogen receptor (ER) and/or progesterone receptor (PR); however, the percentage of cancer cells expressing these receptors can range from 0-100%. The prognostic and therapeutic impact of the percentage of cells expressing hormone receptors in breast cancer is not fully understood. Methods: A retrospective analysis of 411 breast cancer patients who were treated at the University of Nebraska Medical Center between 2010 and 2017 was performed. Patient tumors were evaluated for percentage of cells expressing ER and PR in conjunction with clinical outcomes. Results: Patient tumors demonstrated a highly bimodal pattern of ER and PR staining with a majority of tumors demonstrating either a high percentage (> 80% of cells) or lack of cells (0%) staining for ER or PR. An increase in the percentage of ER positivity correlated with decreased local recurrence and improved overall survival. An increase in the percentage of PR positivity demonstrated a trend towards decreased local recurrence and improved overall survival, but was not statistically significant. Conclusions: Results based on both continuous and categorical evaluation of ER expression revealed that increasing expression correlated with improved patient outcomes. Similar evaluation of PR expression demonstrated a trend towards improved patient outcomes though not statistically significant. These findings suggest that the degree of hormone receptor positivity and not a Boolean representation of positivity could provide additional prognostic value in the treatment and management of breast cancer. J Clin Med Res. 2021;13(1):9-19 doi: https://doi.org/10.14740/jocmr4398

Background No consensus exists regarding adequacy of margins after mastectomy. To determine if pathological margin proximity is associated with local (LR) or distant recurrence after mastectomy for early invasive breast cancer or ductal carcinoma in situ. Methods A systematic review of literature published from 1980 to 2019 and meta-analysis was conducted. Unpublished data were sought from authors (PROSPERO (CRD42019127541)). Thirty-four studies comprising 34,833 breast cancer patients were included in the quantitative synthesis. Eligible studies reported on patients undergoing curative mastectomy for cancer allowing estimation of outcomes in relation to margin status/width. The association between pathological margin status and local (LR) and distant recurrence was considered using random effects modelling. PRISMA guidelines were followed. Results Positive margins were associated with increased LR on multivariable analyses (HR, 2·64, (95%CI 2·01–3·46)) and LR was higher regardless of the distance of tumour from the margin defined as positive. After skin-sparing mastectomy, positive margins were associated with increased LR (HR 3·40, (95%CI 1·9–6·2)). In the 4 studies reporting distant recurrence, patients with involved margins had a higher risk (HR 1·53, (95%CI 1·03–2·25)). Conclusions Failure to achieve clear margins after mastectomy may increase the risks of local and distant recurrence. Adequate margin clearance should be recommended to minimize recurrence after mastectomy in National and International Guidelines.

Eccrine porocarcinoma is a rare aggressive cutaneous malignancy. Complete surgical excision is the standard of care, although there are high rates of local and distant recurrence. We present a unique case of locally recurrent and metastatic subungal porocarcinoma successfully treated with intralesional interleukin-2.

Background/objective Natural history and outcomes for truncal/extremity (TE) soft tissue sarcoma (STS) is derived primarily from studies investigating all histiotypes as one homogenous cohort. We aimed to define the recurrence rate (RR), recurrence patterns, and response to radiation of TE leiomyosarcomas (LMS). Methods Patients from the US Sarcoma Collaborative database with primary, high-grade TE STS were identified. Patients were grouped into LMS or other histology (non-LMS). Primary endpoints were locoregional recurrence-free survival (LR-RFS), distant-RFS (D-RFS), and disease specific survival (DSS). Results Of 1215 patients, 93 had LMS and 1122 non-LMS. In LMS patients, median age was 63 and median tumor size was 6 cm. In non-LMS patients, median age was 58 and median tumor size was 8 cm. In LMS patients, overall RR was 42% with 15% LR-RR and 29% D-RR. The 3yr LR-RFS, D-RFS, and DSS were 84%, 65%, and 76%, respectively. When considering high-risk (>5 cm and high-grade, n = 49) LMS patients, the overall RR was 45% with 12% LR-RR and 35% D-RR. 61% received radiation. The 3yr LR-RFS (78vs93%, p = 0.39), D-RFS (53vs63%, p = 0.27), and DSS (67vs91%, p = 0.17) were similar in those who did and did not receive radiation. High-risk, non-LMS patients had a similar overall RR of 42% with 15% LR-RR and 30% D-RR. 60% of non-LMS patients received radiation. There was an improved 3yr LR-RFS (82vs75%, p = 0.030) and DSS (77vs65%,p = 0.007) in non-LMS patients who received radiation. Conclusions In our cohort, patients with LMS have a low local recurrence rate (12–15%) and modest distant recurrence rate (29–35%). However, LMS patients had no improvement in local control or long-term outcomes with radiation. The value of radiation in these patients merits further investigation.

Background Biological factors are emphasized in borderline resectable pancreatic cancer (BRPC), and CA19-9 is an important factor for biological borderline resectability (b-BR). The aim of this study was to investigate the cut-off value of CA19-9 for biological borderline resectability and “biological downstaging” in chemoradiation therapy (CRT) for pancreatic cancer (PC). Methods A total of 407 patients with anatomically resectable PC (a-R) and BRPC (a-BR) received preoperative gemcitabine-based CRT. The b-BR was determined, according to the CA19-9 value prior to preoperative CRT (pre-CA19-9), as the subgroup of a-R cases in which the survival was comparable with that in a-BR cases. “Biological downstaging” was determined based on prognostic analyses regarding the CA19-9 value after preoperative CRT (post-CA19-9) in association with the survival of R cases (a-R cases without the b-BR factor). Results The 5-year survival of a-R patients with pre-CA19-9 > 120 U/mL was comparable with that of a-BR patients (44% vs 34%, p = 0.082). The survival of b-BR patients with post-CRT CA19-9 ≤ 37 U/mL (normalized) was comparably favorable with that of R patients (56% vs 65%, p = 0.369). The incidence of distant recurrence was higher in b-BR patients without post-CA19-9 normalization than in those with post-CA19-9 normalization (70% vs 50%, p = 0.003), while the incidence of local recurrence was comparable between these two groups (12% vs 13%, p = 0.986). Conclusions Biological BRPC was determined to be an anatomically resectable disease with pre-CA19-9 > 120 U/mL, and post-CA19-9 normalization indicated “biological downstaging” in b-BR in the preoperative CRT strategy.

Treatment of soft tissue sarcomas (STS) should only be initiated once the diagnosis is fully established. Resection of tumors of unknown nature should be avoided. Nevertheless, specialized centers continue to face numbers of unplanned excisions (UPE) in STS.To compare oncologic and functional outcomes, number of surgeries, length of hospital stay and treatment costs of UPE versus planned excision (PE) in STS.A retrospective single tertiary center study was performed on 201 patients. Survival, local and distant recurrence rates were compared between PE (n = 137) and UPE (n = 64). In a subgroup analysis of 60 patients, functional outcome (MSTS and TESS scores), and socio-economic impact (number of surgeries, length of hospital stay and treatment costs) in "functional planned excision" (fPE) group (n = 30) and "functional unplanned excision" (fUPE) group (n = 29) were compared.There was no significant difference in oncological outcome between PE and UPE. In the subgroup analysis, we found a non-significant difference in functional outcome. Patients in the fUPE had significantly more surgeries (3.5 vs. 1.4; p 0.00001) and costs of their management was 64% higher than fPE (p = 0.048). Hospital stay was longer after fUPE but not statistically significant (18.3 days vs. 11.8 days; p = 0.13).Even though oncological and functional outcomes are comparable after PE and UPE of STS, the number of surgeries, length of hospital stay and treatment costs were higher in patients with UPE. Our data underscore the importance of specialized STS treatment centers including multidisciplinary management.

Magee Equations™ are multivariable models that can estimate oncotype DX® Recurrence Score, and Magee Equation 3 has been shown to have chemopredictive value in the neoadjuvant setting as a standalone test. The current study tests the accuracy of Magee Decision Algorithm™ using a large in-house database. According to the algorithm, if all Magee Equation scores are 25 (also “do not send”). All other cases could be considered for testing (labeled “send”). Of the 2196 ER+, HER2-negative cases sent for oncotype testing, 1538 (70%) were classified as “do not send” and 658 (30%) as “send”. The classification accuracy in the “do not send” group was 95.1%. Of the 75 (4.9%) discordant cases (expected score ≤25 by decision algorithm but the actual oncotype score >25), 26 received endocrine therapy alone. None of these 26 patients experienced distant recurrence (average follow-up of 73 months). The Magee Decision Algorithm accurately identifies cases that will not benefit from oncotype testing. Such cases constitute ~70% of the routine clinical oncotype requests, an estimated saving of $300,000 per 100 test requests. The occasional discordant cases (expected ≤25, but actual oncotype score >25) appears to have an excellent outcome on endocrine therapy alone.

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.

PURPOSE/OBJECTIVE(S) 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. MATERIALS/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 8.9 months (1.6-21.4 months). Twenty (66.7%) patients had an unmethylated MGMT promotor status and ten (33.3%) patients had a methylated promoter status. Nineteen patients (63.3%) had progression, with median PFS of 7.6 months (range 1.6 to 12.7 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). No distant infratentorial progression was noted. CONCLUSION Concurrent chemoradiation with TTFields for patients with newly diagnosed glioblastoma may increase the incidence of distant recurrence. This finding is suggestive of improved local control of primary site. Further data are needed to validate this finding. AUTHOR DISCLOSURE A. Ali: None. M.Z. Niazi: None. V. Bar-Ad: None. M. Werner-Wasik: Advisory Board; ASTRA Zeneca. Stock; Illumina. leading operations of the committee; NRG Oncology. D.W. Andrews: None. C. Farrell: None. J. Evans: None. K. Judy: None. J. Glass: None. N. Martinez: None. I. Alnahhas: None. I. Chervoneva: None. W. Shi: Independent Contractor; Wenyin Shi. Research Grant; Novocure, Brainlab, Regeneron. Consultant; Varian, Brainlab, Zai lab.

Introduction/Background* This study was aimed to validate the performance of the KGOG-1024 risk model predicting the risk of distant failure after chemoradiation in patients with locally advanced cervical cancer. Methodology In the retrospective cohort of 297 patients who received concurrent chemoradiation for advanced cervical cancer, an individual risk was calculated using the KGOG 1024 risk model for each patients. The cohort was categorized into three risk groups (low, intermediate, and high-risk groups) according to a calculated risk. The mean of the calculated and the observed risk were compared within each group. Result(s)* Low, intermediate, and high-risk groups were classified into 79, 143, and 68 patients. (27.2%, 49.3%, and 23.5%) Risk of recurrence prediction was quite similar between calculated and observed. (26.7% calculated and 25.6% observed) In low risk group, FIGO stage (p=0.004) and old age (p=0.04) was related of the risk of recurrence using univariate analysis. Conclusion* The KGOG-1024 risk assessment model accurately predicted a distant recurrence after chemoradiation in patients with locally advanced cervical cancer, especially in intermediate-risk group. The model may be helpful in identifying patients who may benefit from adjuvant systemic treatment after chemoradiation.

Nowadays, the most common type of cancer in women worldwide is Breast Cancer (BC). BC may be detected at early stage itself using Mammograms, probably before it's spread. Recurrent BC could occur months or years after initial treatment. Cancer may occur in the same place or spread to different areas due to local or distant recurrence. Early-stage treatment is done not only to cure BC but additionally facilitate in preventing its recurrence/ repetition. In predicting the early stage of BC, a machine learning (ML) technique has been used by most of the researcher. so, the present study we focus on a review of different ML techniques which predicts the recurrence of BC and identified the issues over the past decades. Also summarized the obtained results by the researcher for evaluating their predictive model performance. The study scope, results, merits, and demerits of earlier studies have been discussed. Later, gives deep insights of learning technique and then recommended a possible solution for further improvement for BC recurrence prediction.

Introduction The increasing number of patients has created a pressure on the services provided that aim to ensure the maximum level of care, particularly MDT meetings. Using the CTS5 calculator can readily reduce the number of patients needing discussion for EET. This is will prevent delays in decisions made for patients and more importantly, an evidence-based tool will be used for more accurate results. Method A retrospective data collection was undertaken from the Breast MDT records, initially dating from January to December 2018. Then when the optional use of CTS5 was established, data were retrieved from August to October 2019. As per guidance for the use of the CTS5 calculator; Women were deemed low risk if their 5–10-year risk is less than 5%, intermediate if between 5–10%, and high risk if their 5–10-year risk is more than 10%. Finally, a prospective data collected from January to March 2020 where an agreement was made for all involved Surgeons to use the CTS5 calculator. Results Before Introducing the CTS5 Calculator, in 2018, the number of patients was 1523 from which 66 were for EET 4.3%. When CTS5 Calculator was first introduced, 1st of August - 31st October 2019, the percentage reduced to 4.1% and from January to March 2020, a further reduction 3.9% was noticed. Conclusions The CTS5 calculator is an effective evidence-based tool used to predict the risk of 5-10 years recurrence in breast cancer patients. Implementing it will reduce the number of patients needing discussion in Breast MDTs, sparing meetings’ and patients’ time.

Background Few currently available biomarker panels can predict the risk of long-term distant recurrence (DR) in endocrine-responsive breast cancer (ERBC) patients based on lymph-node (LN) status. A new model, DGM-CM6 (Distant Genetic Model-Clinical variable Model 6), has been developed for the prediction of DR risk in our previous studies. To interrogate the prognostic value of our DGM-CM6 model for ERBC patients stratified by LN status, we retrospectively studied 752 operable breast cancer patients treated in a cancer center from 2005 to 2014. Patients and Methods Of 752 tumors, a total of 499 ERBC patients was identified from both IHC method (n=490) and PAM50 method (n=404). ERBC patients were classified by high and low-risk groups using the cutoff ( Results Significant differences were observed between DGM-CM6 low- and high-risk patients with 10-year DRFS in LN- (ERBC identified by IHC: P = 0.011; by PAM50: P< 0.0001) and LN+ (ERBC identified by IHC: P = 0.015; by PAM50: P = 0.019) by log-rank test. Compared to risk prediction by intrinsic subtype, DGM-CM6 performed better in LN- patients and equally good in LN+ patients. Further multivariate analysis confirmed the independent strength of DGM-CM6 model in the prediction of high- vs. low- risk groups in DRFS (P < 0.0001, HR: 6.76; 95% CI, 1.8-25.42) and OS (P = 0.01, HR: 6.06; 95% CI:1.55-23.47), respectively. Conclusion DGM-CM6 model can be used to predict low- and high-risk of 10-year distant recurrence in both LN- and LN+ ERBC patients. This model needs a large scale of clinical trials to validate its clinical utility. Table 1. Multivariate cox regression analyses for the prognosis of predicted risk groups after adjusted for other clinical variables in the distant recurrence (DR, p=0.005) and overall survival (OS, p=0.01) respectively. Results shows that there is no interaction between chemotherapy and risk groups (DR: p=0.163; OS: p=0.195). Abbreviations: DR, distant recurrence; OS: overall survival.GroupsDROSHR [95% CI]pvHR [95% CI]pvRisk: high vs.low6.76 [1.8;25.42]0.005 ***6.06 [1.55;23.74]0.01 ***Age: 50yrs0.86 [0.51;1.44]0.5630.68 [0.38;1.19]0.175LN: Pos. vs. Neg.1.64 [0.88;3.05]0.1161.6 [0.79;3.22]0.189Stage: II vs. I1.35 [0.76;2.4]0.31.45 [0.76;2.77]0.264Stage: III vs. I2.08 [0.59;7.3]0.2531.59 [0.34;7.46]0.557Grade: 2 vs. 12.14 [0.77;5.97]0.1461.81 [0.63;5.25]0.272Grade: 3 vs. 11.2 [0.4;3.62]0.7481.21 [0.38;3.86]0.752PAM50: Normal vs. LumA0.6 [0.13;2.64]0.4960.7 [0.16;3.16]0.645PAM50: LumB vs. LumA1.58 [0.84;2.98]0.1591.29 [0.65;2.59]0.469PAM50: Her2 vs. LumA0.81 [0.25;2.68]0.7311.01 [0.29;3.47]0.986RT: Yes vs. No0.88 [0.47;1.66]0.7010.71 [0.36;1.41]0.326CT: Yes vs.No0.36 [0.11;1.12]0.0770.3 [0.09;1]0.05 *Interaction: CT vs. Risk0.36 [0.09;1.51]0.1630.36 [0.08;1.68]0.195 Citation Format: Lei Lei, Skye Hung-Chun Cheng, Xiao-Jia Wang, Yin-Yuan Mo, Yun-Yun Zhou. A new model to predict 10-year distant recurrence risk for operable endocrine-responsive breast cancer population [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-14.

We previously reported that CD133 expression correlated with the recurrence pattern of glioblastoma (GBM). Subventricular zone (SVZ) involvement may also be associated with distant recurrence in GBM. Therefore, we herein investigated whether the combined analysis of SVZ involvement and CD133 expression is useful for predicting the pattern of GBM recurrence. We retrospectively analyzed 167 cases of GBM. Tumors were divided into four groups based on spatial relationships between contrast-enhanced lesions (CEL) and the SVZ or cortex (Ctx) on MRI. The initial recurrence pattern (local/distant) was obtained from medical records. To identify factors predictive of recurrence, we examined CD133 expression by immunohistochemical, clinical (age, sex, KPS, Ki-67 labeling index, surgery, and MRI characteristics), and genetic (IDH1, MGMT, and BRAF) factors. The CD133 expression rate was higher in SVZ-positive tumors than in SVZ-negative tumors (P = 0.046). Distant recurrence was observed in 21% of patients, and no significant difference was noted in recurrence patterns among the four groups. However, strong CD133 expression was associated with a shorter time to distant recurrence in univariate, multivariate, and propensity-matched scoring analyses (P

This study investigated the impact of gross extrathyroidal extension into major neck structures on the prognosis of papillary thyroid carcinoma according to changes in the American Joint Committee on Cancer (AJCC)/Tumor-Node-Metastasis staging system. Overall, 183 patients with gross extrathyroidal extension into major neck structures were enrolled. The 10-year disease-specific survival (DSS) of patients in each stage showed appropriate correlation and stratification with the AJCC eighth edition. However, the 10-year DSS rate in stage III was better than the expected 10-year DSS rate, according to the AJCC eighth edition. Patients in stage III were subcategorized into three new groups: stage IIIA, patients with only recurrent laryngeal nerve invasion; stage IIIB, patients with superficial invasion of the aerodigestive tract; and stage IIIC, patients with intraluminal invasion of the aerodigestive tract. The prognostic differences among these three groups and stage IVA were examined. Although the DSS rate of patients in stage IIIA was excellent, that of patients with T4a disease was worse due to the progression of aerodigestive tract infiltration. Of the four groups, the time to locoregional recurrence was the shortest for patients in stage IVA. The distant recurrent-free survival for patients in stages IIIC and IVA tended to be worse than those for patients in stages IIIA and IIIB. These results indicate that the progression of aerodigestive tract infiltration has an impact on the incidence of distant recurrence, and the presence of T4b disease has an impact on the incidence of distant and locoregional recurrences.

Managing patients with incidental gallbladder cancer requires stratifying patients risk for recurrence and an appreciation for the recurrence patterns characterizing this malignancy. Although standard management includes reresection to remove sites at risk of harboring residual disease and to achieve negative resection margin status, the decision to perform surgery is tempered by an early and frequent distant recurrence, the most common cause of surgical failure. High-risk patients may benefit from neoadjuvant chemotherapy before reresection. The goal of curative-intent reresection is achieving R0 margin status and optimal staging while limiting morbidity and mortality.

Background The information of Oncotype DX applied in Asian breast cancer patients is limited. A recurrence index for distant recurrence (RI-DR) has been developed for early-stage breast cancer (EBC) from tumor samples in Chinese patients. In this study, we compared the prognostic performance of the Oncotype DX (ODx) recurrence score (RS) with the RI-DR for any recurrence risk type. Materials and methods One hundred thirty-eight (138) patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative EBC who were previously tested with ODx were included for testing with the RI-DR. The cutoff score to partition the low- and high-risk patients was 26 for RS and 36 for RI-DR. The primary endpoint was recurrence-free survival (RFS). Results The concordance between the RI-DR and RS was 83% in N0 patients and 81% in node-positive patients when the RS score cutoff was set at 26. With a median follow-up interval of 36.8 months, the 4-year RFS for the high- and low-risk groups categorized by the RS were 61.9% and 95.0%, respectively (hazard ratio: 10.6, 95.0% confidence interval [CI]: 1.8–62.9). The 4-year RFS in the high- and low-risk groups categorized by the RI-DR were 72.6% and 98.5%, respectively (hazard ratio: 18.9, 95% CI: 1.8–138.8). Conclusion This paper illustrated the performance of RI-DR and ODx RS in breast cancer women in Taiwan. There was high concordance between the RI-DR and RS. The RI-DR is not inferior to the RS in predicting RFS in EBC patients. This study will fill the gap between the current and best practice in Chinese patients., Utilization of Oncotype DX is uncommon in Asia due to lack of clinical data. We compare a clinical-genomic model, developed from Taiwan, to Oncotype 21-gene panel in Chinese patients.

Background Colon cancer outcomes are now inferior to rectal cancer outcomes. The sigmoid colon is the most common site of colonic cancer. The aim of this review was to investigate the oncological outcomes for sigmoid cancer. Methods A systematic review and meta-analysis was performed. We included any study of the oncological outcomes for sigmoid cancer such as local recurrence, distant recurrence and disease free survival. A systematic search was conducted in Medline from inception to November 2016. Study quality was evaluated with the Newcastle-Ottawa Scale. The study was registered on PROSPERO (CRD42017069326). Results The search terms returned 1323 results. We identified a total of 17 eligible studies including 5953 patients. The pooled local recurrence rate was 10.5% in 15 studies with 5148 patients (95% CI 0.07–0.14) and heterogeneity measured by I2 was 94%. The pooled distant recurrence rate was 19.5% (7 studies, 2040 patients, 95% CI (0.14–0.25), I2 90%). The pooled disease free survival at 5 years was 80.4% (5 studies, 2336 patients, 95% CI 78.6%–82.1%, I2 11.5%.). The median Newcastle-Ottawa score was 4 out of 9. R1 and R2 resections were excluded or not described in 16/17 studies. Two studies described R1 and R2 rates of 15–20%. Conclusion The pooled local recurrence rate of sigmoid cancer of 10.5% is higher than contemporary rates of local recurrence of rectal cancer. A large number of papers fail to describe or include R1 resections of sigmoid cancer, which are frequently described as palliative.

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.

Purpose: Despite technological improvement and advances in biology-driven patient stratification, many patients still fail radiotherapy resulting in loco-regional and distant recurrence. Tumor heterogeneity remains a key challenge to effective cancer treatment, and reliable stratification of cancer patients for prediction of outcomes is highly important. Intratumoral heterogeneity is manifested at the different levels, including different tumorigenic properties of cancer cells. Since John Dick et al. isolated leukemia initiating cells in 1990, the populations of tumor initiating or cancer stem cells (CSCs) were identified and characterized also for a broad spectrum of solid tumor types. The properties of CSCs are of considerable clinical relevance: CSCs have self-renewal and tumor initiating potential, and the metastases are initiated by the CSC clones with the ability to disseminate from the primary tumor site. Conclusion: Evidence from both, experimental and clinical studies demonstrates that the probability of achieving local tumor control by radiation therapy depends on the complete eradication of CSC populations. The number, properties and molecular signature of CSCs are highly predictive for clinical outcome of radiotherapy, whereas targeted therapies against CSCs combined with conventional treatment are expected to provide an improved clinical response and prevent tumor relapse. In this review, we discuss the modern methods to study CSCs in radiation biology, the role of CSCs in personalized cancer therapy as well as future directions for CSC research in translational radiooncology.

As a cancer-related long noncoding RNA, functionality of GASL1 has only been characterized in liver cancer. Our study aimed to investigate the possible involvement of GASL1 in postoperative recurrence of gastric adenocarcinoma. A total of 112 gastric adenocarcinoma patients with a tumor located in the distal third who received gastrectomy distal resection in The Second Hospital of Dalian Medical University from January 2012 to January 2015 were included in this study. Patients were followed up for 3 years. Another 56 healthy people were also included to serve as a control group. Blood was extracted from each subject on the day of discharge, on the day of diagnosis of recurrence or at the end of follow-up. The GASL1 expression vector was transfected into gastric adenocarcinoma cell lines. It was observed that plasma levels of GASL1 were significantly lower, while plasma levels of transforming growth factor-β1 (TGF-β1) were significantly higher in patients than in healthy controls on the day of discharge. Patients with distant recurrence showed significantly lower plasma levels of GASL1 and significantly higher plasma levels of TGF-β1 compared with patients with local recurrence and patients without recurrence. During follow-up, plasma levels of GASL1 and TGF-β1 were negatively correlated in patients with distant recurrence but not in other groups of patients. GASL1 overexpression inhibited, while TGF-β1 treatment promoted cell migration and invasion. Overexpression of GASL1 led to downregulated and GASL1 knockdown led to upregulated TGF-β1. However, TGF-β1 showed no significant effects on GASL1 expression. We conclude that GASL1 may participate in the distant recurrence of gastric adenocarcinoma through the interactions with TGF-β1.

RAZOR (Randomized Open versus Robotic Cystectomy) trial is a phase 3 randomized control trial comparing robot-assisted laparoscopic radical cystectomy with open radical cystectomy for the treatment of bladder cancer published by Parekh et.al. Three-year follow-up analysis of this trial showed that there was no difference in overall survival, progression-free survival, and local or distant recurrence in both the group. The present report will discuss this landmark trial in brief in the context of the advantage and feasibility of robotic radical cystectomy in the developing world.

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.

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.

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.

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.

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