Early Cancer Recurrence Research Articles

272P - Competing nomogram for late-period breast cancer-specific death in patients with early-stage hormone receptor-positive breast cancer

BackgroundMore than half of early breast cancer recurrences occur after 5 years from the initial diagnosis. An individualized estimate of the risk of late-period breast cancer-specific death (LP-BCSD) after 5 years of endocrine therapy (ET) can improve decision-making for extended endocrine therapy (EET). MethodsA total of 147,059 eligible patients with breast cancer who survived 5+ years after diagnosis between 1990 and 2007 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analyses based on the competing risk regression model were used to evaluate predictive factors for high risk of LP-BCSD or LP-non-BCSD. Significant factors were used to build a nomogram to individualize estimates of LP-BCSD or LP-non-BCSD. ResultsThe 5- and 10-year LP-BCSD rates were 5.67% and 10.06%, respectively, and the 5- and 10-year LP-non-BCSD rates were 6.72% and 15.50%, respectively. Young age, black race, single marital status, poor differentiation, large tumor size, lymph node metastasis, and ER+/PR- status were independent predictive factors for high risk of LP-BCSD. Age was the most important factor for predicting high risk of LP-non-BCSD. The nomograms, which were based on significant factors identified by the competing risk regression model. A risk score system based on the competing risk nomogram was established to describe the relative risk of LP-BCSD and LP-non-BCSD. ConclusionsThis study explored the novel endpoint of LP-BCSD for further clinical trials. The risk score system is highly useful for patient counseling, especially in discussing EET options with elderly or comorbid patients. Legal entity responsible for the studyJianfei Fu. FundingScience & Technology Division of Jinhua Zhejiang Province. DisclosureAll authors have declared no conflicts of interest.

111P - Combined genomic and epigenomic assessment of cell-free circulating tumour DNA (cfDNA) for cancer diagnosis and recurrence-risk assessment in early-stage lung cancer

BackgroundCirculating tumor DNA (ctDNA) analysis has been successfully applied to therapy selection and treatment monitoring in advanced cancer patients. However, it is not yet established whether ctDNA can be used clinically for early cancer detection or recurrence prediction in early stage lung cancer patients. MethodsWe analyzed pre-operative plasma samples from 55 early stage NSCLC patients (stages I-IIIA) using next-generation sequencing assay incorporating somatic and epigenomic analysis, and a bioinformatic classifier to filter non-tumor derived variants.Table: 111PTable: 111PCell typeStageSomatic mutationEpigenetic patternTotal numberRecurrence+, n (%)Site of recurrenceAdenocarcinomastage 1ctDNA-methylation-91 (11)Lungn=17methylation+62 (33.3)Stump, bonectDNA+21 (50)lungstage 2ctDNA-methylation-00 (0)n=2methylation+00(0)ctDNA+11 (100)multiplestage 3ctDNA-methylation-00 (0)n=4methylation+20 (0)ctDNA+22 (100)brain, multipleSqaumous cell carcinomastage1ctDNA-methylation-00 (0)n=7methylation+30 (0)ctDNA+41 (25)multiplestage2ctDNA-methylation-00 (0)n=9methylation+00 (0)ctDNA+92 (22.2)multiple, lungstage3ctDNA-methylation-00 (0)n=4methylation+10 (0)ctDNA+31 (33.3)Mediastinal LNs ResultsSomatic mutation analysis alone detected ctDNA in 42% (23/55) of patients, whereas combined mutational and epigenomic analysis detected ctDNA in 67% (37/55). ctDNA detection rate varied by pathological subtypes; using combined approach, ctDNA was detected in all squamous cell carcinoma patients, while only 55% (12/22) in adenocarcinoma (ADC) (p=0.006). Within the ADC subgroup, ctDNA detection rates using the combined approach were dependent on disease stage: 47% (8/17) in stage I, 100% (2/2) in stage II, and 100% (2/2) in stage IIIA. Importantly, within 2 years of follow-up, pre-operative ctDNA status was correlated with tumor recurrence after resection; among 17 stage I ADC patients, three of eight (38%) ctDNA-positive cases showed recurrence, while only one of nine (11%) ctDNA-negative cased did (p=0.29). Interestingly, patients with somatic mutation in their ctDNA have shown higher recurrence rate. ConclusionUtilizing a plasma-only sequencing assay incorporating somatic genomic and epigenomic analysis, ctDNA detection rate in early stage lung cancer (stage I-III) can far outperform the detection rate of somatic sequence variant detection alone. And, the presence of pre-operative ctDNA in patients with early stage lung adenocarcinoma may identify those who are more likely to have disease recurrence.Legal entity responsible for the study: Guradant Health, Inc. FundingGuardant Health, Redwood City, CA, USA. DisclosureI. Kim: Full / Part-time employment, Officer / Board of Directors: Guardant Health. M. Shultz: Officer / Board of Directors: Guardant Health. A. Jaimovich: Officer / Board of Directors: Guardant Health. J. Odegaard: Officer / Board of Directors: Guardant health, Inc. S. Olsen: Officer / Board of Directors: Guardant Health, Inc. A. Talasaz: Officer / Board of Directors: Guardant health. J. Kim: Research grant / Funding (self): Guardant health, Inc. All other authors have declared no conflicts of interest.

Clinical Outcomes in Early Breast Cancer With a High 21-Gene Recurrence Score of 26 to 100 Assigned to Adjuvant Chemotherapy Plus Endocrine Therapy

A high 21-gene recurrence score (RS) by breast cancer assay is prognostic for distant recurrence of early breast cancer after local therapy and endocrine therapy alone, and for chemotherapy benefit. To describe clinical outcomes for women with a high RS who received adjuvant chemotherapy plus endocrine therapy in the TAILORx trial, a population expected to have a high distant recurrence rate with endocrine therapy alone. In this secondary analysis of data from a multicenter randomized clinical trial, 1389 women with hormone receptor-positive, ERBB2-negative, axillary node-negative breast cancer, and a high RS of 26 to 100 were prospectively assigned to receive adjuvant chemotherapy in addition to endocrine therapy. The analysis was conducted on May 12, 2019. The adjuvant chemotherapy regimen was selected by the treating physician. Freedom from recurrence of breast cancer at a distant site, and freedom from recurrence, second primary cancer, and death (also known as invasive disease-free survival [IDFS]). Among the 9719 eligible women, with a mean age of 56 years (range 23-75 years), 1389 (14%) had a recurrence score of 26 to 100, of whom 598 (42%) had an RS of 26 to 30 and 791 (58%) had an RS of 31 to 100. The most common chemotherapy regimens included docetaxel/cyclophosphamide in 589 (42%), an anthracycline without a taxane in 334 (24%), an anthracycline and taxane in 244 (18%), cyclophosphamide/methotrexate/5-fluorouracil in 52 (4%), other regimens in 81 (6%), and no chemotherapy in 89 (6%). At 5 years, the estimated rate of freedom from recurrence of breast cancer at a distant site was 93.0% (standard error [SE], 0.8%), freedom of recurrence of breast cancer at a distant and/or local regional site 91.0% (SE, 0.8%), IDFS 87.6% (SE, 1.0%), and overall survival 95.9% (SE, 0.6%). The estimated rate of freedom from recurrence of breast cancer at a distant site in women with an RS of 26 to 100 treated largely with taxane and/or anthracycline-containing adjuvant chemotherapy regimens plus endocrine therapy in the prospective TAILORx trial was 93% at 5 years, an outcome better than expected with endocrine therapy alone in this population. ClinicalTrials.gov identifier: NCT00310180.

Predictors of postoperative early recurrence of extrahepatic bile duct cancer.

Resected bile duct cancers often relapse during postoperative follow-up. The aim of this study was to detect predictors of early recurrence in patients with extrahepatic bile duct cancer. Consecutive cases (n = 162) of extrahepatic bile duct cancer in which R0 or R1 resection was achieved in Kobe University Hospital between 2000 and 2016 were divided into three groups [early recurrence (ER), within 6months of surgery, late recurrence (LR), and no recurrence (NR)] and their clinicopathological features were compared. Twenty-two patients (14%) developed ER and 69 (43%) developed LR after surgery. The rates of lymph node metastasis and residual cancer status were similar in all three groups. Liver metastasis was more common in the ER group than in the LR group (59% vs. 32%, p = 0.02). ER had a significantly worse prognosis than LR and NR (7% vs. 44% vs. 85% at 1year, p < 0.01, respectively). Multivariate analysis showed that age > 75years, serum CA19-9 > 1008U/ml and perineural invasion were independent predictors of early recurrence. High serum CA19-9 values (>1008U/ml) were an independent predictor of early recurrence. Neoadjuvant therapy and aggressive adjuvant therapy may be beneficial for patients who show highly elevated CA19-9 values before surgery.

Prognostic Determinants of Salvage Image-Guided Brachytherapy for Vaginal Recurrence of Endometrial Cancer

In PORTEC-1, the 5-year survival after vaginal relapse from early stage endometrial cancer was 65% for patients in the observation arm. In this study, we evaluated clinical outcomes and toxicity in patients with vaginal relapse of endometrial cancer treated with salvage image-guided brachytherapy (BT). Retrospective review identified 62 patients with early stage endometrial cancer and biopsy-proven vaginal recurrence treated with external beam (EBRT) and image-guided BT with definitive intent between 10/04 and 05/17. All patients had prior hysterectomy without adjuvant radiotherapy (RT) and >3 months follow-up (FU). Rates of vaginal control (VC), recurrence-free survival (RFS) and overall survival (OS) were estimated by Kaplan-Meier method. Univariate analysis was performed by Cox proportional hazards or log-rank test. Late toxicity was graded by CTCAE. Median FU was 31.8 months (r: 3.2 – 160.5). Baseline characteristics are summarized in table 1. The median time to recurrence after hysterectomy was 18.2 months (range [r]: 1.6 – 158). Median tumor size was 2.3 cm (r: 0.3-7.5). Median prescribed dose and HR-CTV D90 in EQD2 were 75.4 Gy and 75.3 Gy, respectively. Twenty patients had disease relapse at a median of 14.2 months after completion of BT (6 with vaginal failure only, 2 vaginal and distant, and 12 distant only). The 3-year rates of VC, RFS, and OS were 86%, 70% and 80%. respectively. Tumor grade at hysterectomy was a strong determinant of outcome, with 3-year RFS rates of 80% for grade 1 tumors, 78% for grade 2, and 13% for grade 3 (p<0.01). Age, stage at diagnosis, nodal involvement and BT modality were not associated with RFS (all p>0.2). Median HR-CTV D90 was 75.7 Gy for patients with vaginal failure and 75.2 Gy for those without (p=0.9). Age, BT modality, tumor grade, tumor size and cumulative prescribed dose were not prognostic for VC (all p>0.5). Late grade 3 toxicity included 2 patients with proctitis and 1 with urinary incontinence; all received interstitial BT. One cylinder patient had grade 3 vaginal stenosis. Salvage RT with image-guided BT results in excellent clinical outcomes for patients with grade 1 or 2 tumors and vaginal relapse. Those with grade 3 tumors or non-endometrioid histologies have high rates of distant recurrence and poor survival. Adjuvant treatment should be considered for all high risk patients given the low rates of salvage.Abstract 2796; Table 1Baseline characteristics for 62 patientsn (%)FIGO 2009 stage at diagnosis • IA• 56 (90%) • IB• 5 (8%) • II• 1 (2%)Histology • Endometrioid• 55 (89%) • Serous• 5 (8%) • Carcinosarcoma• 2 (3%)Grade • 1• 40 (65%) • 2• 13 (21%) • 3• 9 (14%)Median age at recurrence67 years (r: 41-86)Site(s) of recurrence • Vaginal only• 55 (89%) • Vaginal + nodal• 7 (11%)Image-guided BT modality • Intracavitary (cylinder)• 26 (42%) • Interstitial• 36 (58%)Median central EBRT dose• 45Gy (r: 44 – 54)Median BT dose• 25Gy (r: 16 – 35)Median D2cc OAR • Bladder• 65.8 Gy (r: 50.7 – 87.2) • Rectum• 64.7 Gy (r: 52.1 – 86.9) • Sigmoid• 53.7 Gy (r: 44.7 – 75.5)Chemotherapy use11 (18%) Open table in a new tab

ASO Author Reflections: The Strengths and Weaknesses of Intraoperative Radiotherapy for Early Breast Cancer and Ipsilateral Tumor Recurrence.

ASO Author Reflections: The Strengths and Weaknesses of Intraoperative Radiotherapy for Early Breast Cancer and Ipsilateral Tumor Recurrence.

Impact of therapeutic delay in colorectal cancer on overall survival and cancer recurrence – is there a safe timeframe for prehabilitation?

IntroductionInterest in adoption of a prehabilitation programme in management of colorectal cancer is increasing, but current waiting time targets leave no opening for intervention. Prompt treatment following diagnosis is demanded but defending evidence is lacking. We aimed to investigate the impact of prolonged therapeutic delay on overall and cancer-free survival in patients with primary colorectal cancer. MethodsRetrospective analysis was performed in a detailed dataset of patients with primary colorectal cancer who underwent curative surgical treatment between January 2010 and December 2016. Groups were made according to therapeutic delay ≤35 days or >35 days. Endpoints were overall and cancer-free survival, assessed with Kaplan-Meier survival curves, log-rank tests and Cox proportional hazard analyses. ResultsA total of 790 patients were included of whom 559 had a colonic tumour and 231 a rectal tumour. Median therapeutic delay was 32 days (IQR 26-43 days). Multivariate analysis showed therapeutic delay >35 days was not associated with poorer overall survival (HR = 1.202, p = 0.249) or earlier cancer recurrence (HR = 1.256, p = 0.212). Similar results were found when stratifying analyses for colonic and rectal cancer, and when defining prolonged delay as >49 days. ConclusionProlonged treatment delay does not lead to poorer overall or cancer-free survival in patients with primary colorectal cancer who underwent curative surgical treatment. This allows professionals to push current national waiting time targets in order to adopt a prehabilitation programme without jeopardizing outcomes.

Time from incident primary cancer until recurrence or second primary cancer: Risk factors and impact in general practice.

Specialised follow-up care after cancer treatment is changing towards increased involvement of general practice. To ensure timely detection of new cancer events, knowledge is warranted on the timing of cancer recurrence (CR) and second primary cancer (SPC), including risk factors for CR. This population-based register study included 67,092 patients diagnosed with malignant melanoma, bladder, lung, ovarian, endometrial, colorectal and breast cancer in Denmark in 2008-2016. The time from primary cancer to CR or SPC and risk factors for prolonged time to CR were analysed and stratified on sex and primary cancer type. Cancer recurrence proportions ranged from 6% to 35%. The risk of CR increased profoundly within the first 3years and then levelled off, except for breast cancer. A total of 3%-6% of patients had SPC, with monotonously increasing cumulative incidence proportions. Besides primary tumour characteristics, lower educational level, living alone and comorbidity were associated with earlier CR. For example, in female malignant melanoma, HRs and 95% confidence intervals were 0.47 (0.37-0.61) for high educational level, 1.40 (1.16-1.68) for living alone and 2.38 (1.53-3.70) for high comorbidity. The results may inform stratified risk assessment in decision of frequency, location and duration of post-cancer follow-up care.

Genomic testing in early stage invasive male breast cancer: An NCDB analysis from 2008 to 2014.

Genomic assays, or tissue gene profiling tests, are widely used to predict recurrence of early stage invasive breast cancer and guide systemic therapy. The purpose of our study was to examine the current national trends of genomic testing in male breast cancer (MBC) and its association with systemic therapy. The National Cancer Database (NCDB) includes 6227 cases of pathologic T1/T2 and N0/N1 MBC from 2008 to 2014 with known genomic testing status. Results of the tests were grouped as low, intermediate, and high risk of recurrence scores (RRS). Statistical analysis included multivariate logistic regression and Chi-square tests. A supplemental analysis in female breast cancer was provided as reference. Of the 6227 cases of MBC age 18-90, 1478 (23.74%) underwent genomic testing. Testing was significantly associated with age, race, tumor grade, year of diagnosis, receptor status, and nodal status. Distribution of RRS in MBC was 59.3% low, 27.4% intermediate, and 13.3% high. RRS in men were significantly associated with tumor grade and size, but not nodal status. Those with a low RRS were 7-times more likely to be treated with hormone therapy alone (AOR 7.18, CI 5.78-8.91, P<0.001). Those with a high RRS were five times more likely to receive a combination of hormone and chemotherapy (AOR 5.16, CI 3.60-7.40, P<0.001). Rates of testing and distribution of RRS in men and women with early stage invasive breast cancer are similar. Treatment patterns in MBC varied significantly based on genomic testing results, even when adjusted for other clinicopathologic features. Further investigation is required to determine the prognostic and predictive nature of genomic testing in male breast cancer.

Wearable-Based Mobile Health App in Gastric Cancer Patients for Postoperative Physical Activity Monitoring: Focus Group Study.

BackgroundSurgical cancer patients often have deteriorated physical activity (PA), which in turn, contributes to poor outcomes and early recurrence of cancer. Mobile health (mHealth) platforms are progressively used for monitoring clinical conditions in medical subjects. Despite prevalent enthusiasm for the use of mHealth, limited studies have applied these platforms to surgical patients who are in much need of care because of acutely significant loss of physical function during the postoperative period.ObjectiveThe aim of our study was to determine the feasibility and clinical value of using 1 wearable device connected with the mHealth platform to record PA among patients with gastric cancer (GC) who had undergone gastrectomy.MethodsWe enrolled surgical GC patients during their inpatient stay and trained them to use the app and wearable device, enabling them to automatically monitor their walking steps. The patients continued to transmit data until postoperative day 28. The primary aim of this study was to validate the feasibility of this system, which was defined as the proportion of participants using each element of the system (wearing the device and uploading step counts) for at least 70% of the 28-day study. “Definitely feasible,” “possibly feasible,” and “not feasible” were defined as ≥70%, 50%-69%, and <50% of participants meeting the criteria, respectively. Moreover, the secondary aim was to evaluate the clinical value of measuring walking steps by examining whether they were associated with early discharge (length of hospital stay <9 days).ResultsWe enrolled 43 GC inpatients for the analysis. The weekly submission rate at the first, second, third, and fourth week was 100%, 93%, 91%, and 86%, respectively. The overall daily submission rate was 95.5% (1150 days, with 43 subjects submitting data for 28 days). These data showed that this system met the definition of “definitely feasible.” Of the 54 missed transmission days, 6 occurred in week 2, 12 occurred in week 3, and 36 occurred in week 4. The primary reason for not sending data was that patients or caregivers forgot to charge the wearable devices (>90%). Furthermore, we used a multivariable-adjusted model to predict early discharge, which demonstrated that every 1000-step increment of walking on postoperative day 5 was associated with early discharge (odds ratio 2.72, 95% CI 1.17-6.32; P=.02).ConclusionsIncorporating the use of mobile phone apps with wearable devices to record PA in patients of postoperative GC was feasible in patients undergoing gastrectomy in this study. With the support of the mHealth platform, this app offers seamless tracing of patients’ recovery with a little extra burden and turns subjective PA into an objective, measurable parameter.

LncRNA FOXD2-AS1 Functions as a Competing Endogenous RNA to Regulate TERT Expression by Sponging miR-7-5p in Thyroid Cancer.

Long non-coding RNA FOXD2 Adjacent Opposite Strand RNA 1 (FOXD2-AS1) has been widely reported to be implicated in the progression and recurrence of several cancers. The clinical significance and functional role of FOXD2-AS1 in thyroid carcinoma remain unknown. FOXD2-AS1 expression was evaluated by analyzing thyroid cancer RNA sequencing dataset from The Cancer Genome Atlas (TCGA). In vitro and in vivo assays were performed to assess the biological roles of FOXD2-AS1 in thyroid cancer cells. Western blot, luciferase, immunoprecipitation (IP), and RNA immunoprecipitation (RIP) assays were used to identify the underlying miRNA and mRNA target mediating the biological roles of FOXD2-AS1 in thyroid cancer cells. FOXD2-AS1 was upregulated in thyroid carcinoma tissues and cells. High expression of FOXD2-AS1 significantly correlated with clinical stage, recurrence of thyroid carcinoma. Silencing FOXD2-AS1 inhibited cancer stem cell-like phenotypes and attenuates the anoikis resistance in vitro. Downregulating FOXD2-AS1 represses the tumorigenesis of thyroid carcinoma cells in vivo. FOXD2-AS1 acts as a competitive endogenous RNA (ceRNA) for miR-7-5p, up-regulating the expression of telomerase reverse transcriptase (TERT), which further promotes the cancer stem cells features and anoikis resistance in thyroid cancer cells. Our findings indicate that FOXD2-AS1 functions as an oncogenic regulator in the development of thyroid cancer, contributing to early recurrence of thyroid cancer.

Wound fluid enhances cancer cell proliferation via activation of STAT3 signal pathway in vitro.

Wound healing begins immediately after surgery with a modification of the microenvironment via a well‑orchestrated interaction between cells, cytokines and growth factors. Some of these growth factors and cytokines have mitogenic effects on cancer cells, which may lead to enhanced cancer cell proliferation and early metastatic events. The present study aimed to investigate the effects of wound fluid (WF) on the head and neck squamous carcinoma cell lines FaDu and HLaC78 in vitro. WF was harvested from 7 patients who had undergone a planned neck dissection. The presence of cytokines and growth factors was evaluated with the dot blot assay. Proliferation and cell viability were investigated via MTT assay and Ki-67 staining. Cell invasion was measured via tree‑dimensional invasion assay. Western blotting was used to investigate STAT 3 activation. WF contained several cytokines and growth factors responsible for pro‑ and anti‑inflammation, chemotaxis, proliferation and angiogenesis. The proliferation effect of WF on FaDu and HLaC78 was concentration dependent. Media with 40% WF resulted in the highest proliferation effect. FaDu and HLaC78 exhibited enhanced motility after cultivation with 40% WF compared with cultivation with expansion medium. Cultivating cancer cells with WF had no advantageous effect on cell viability after the paclitaxel treatment. Western blot analysis revealed enhanced activation of the STAT3 signaling pathway by WF in both FaDu and HLaC78. In conclusion, surgery leads to excessive release of mitogenic factors. The contact of non‑resected cancer cells and these factors may have a negative impact on patient outcome. Future investigations should specifically focus on the inhibition of mitogenic factors following cancer surgery in order to prevent early metastasis and cancer recurrence.

Stratification of Postsurgical Computed Tomography Surveillance Based on the Extragastric Recurrence of Early Gastric Cancer.

To stratify the postsurgical computed tomography (CT) surveillance based on a risk-scoring system for predicting extragastric recurrence after surgical resection of early gastric cancer (EGC). Postsurgical CT surveillance should not be routinely performed in all patients because of the low incidence of extragastric recurrence and potential risk of radiation exposure. Data from 3162 patients who underwent surgical resection for EGC were reviewed to develop a risk-scoring system to predict extragastric recurrence. Risk scores were based on the predictive factors for extragastric recurrence, which were determined using Cox proportional hazard regression model. The risk-scoring system was validated by Uno censoring adjusted C-index. External validation was performed using an independent dataset (n = 430). The overall incidence of extragastric recurrence was 1.4% (44/3162). Five risk factors (lymph node metastasis, indications for endoscopic resection, male sex, positive lymphovascular invasion, and elevated macroscopic type), which were significantly associated with extragastric recurrence, were incorporated into the risk-scoring system, and the patients were categorized into 2 risk groups. The 10-year extragastric recurrence-free survival differed significantly between low- and high-risk groups (99.7% vs 96.5%; P < 0.001). The predictive accuracy of the risk-scoring system in the development cohort was 0.870 [Uno C-index; 95% confidence interval (95% CI), 0.800-0.939]. Discrimination was good after internal (0.859) and external validation (0.782, 0.549-1.000). This risk-scoring system might be useful to predict extragastric recurrence of EGC after curative surgical resection. We suggest that postsurgical CT surveillance to detect extragastric recurrence should be avoided in the low-risk group.

ZNF671 DNA methylation as a molecular predictor for the early recurrence of serous ovarian cancer.

Serous ovarian cancer is the most frequent type of epithelial ovarian cancer. Despite the use of surgery and platinum‐based chemotherapy, many patients suffer from recurrence within 6 months, termed platinum resistance. Currently, the lack of relevant molecular biomarkers for the prediction of the early recurrence of serous ovarian cancers is linked to the poor prognosis. To identify an effective biomarker for early recurrence, we analyzed the genome‐wide DNA methylation status characteristic of early recurrence after treatment. The patients in The Cancer Genome Atlas (TCGA) dataset who showed a complete response after the first therapy were categorized into 2 groups: early recurrence serous ovarian cancer (ERS, recurrence ≤12 months, n = 51) and late recurrence serous ovarian cancer (LRS, recurrence >12 months, n = 158). Among the 12 differently methylated probes identified between the 2 groups, we found that ZNF671 was the most significantly methylated gene in the early recurrence group. A validation cohort of 78 serous ovarian cancers showed that patients with ZNF671 DNA methylation had a worse prognosis (P < .05). The multivariate analysis revealed that the methylation status of ZNF671 was an independent factor for predicting the recurrence of serous ovarian cancer patients both in the TCGA dataset and our cohort (P = .049 and P = .021, respectively). Functional analysis revealed that the depletion of ZNF671 expression conferred a more migratory and invasive phenotype to the ovarian cancer cells. Our data indicate that ZNF671 functions as a tumor suppressor in ovarian cancer and that the DNA methylation status of ZNF671 might be an effective biomarker for the recurrence of serous ovarian cancer after platinum‐based adjuvant chemotherapy.

Laparoscopic Mobilization of the Splenic Flexure as the First Step of Restorative Colorectal Resection.

Background: Mobilization of the colonic splenic flexure (SFM) is an essential surgical step of the restorative rectal resections. However, the surgical procedures are technically complex thereby overcoming the learning curve may not be an easy process. Looking for improved expertise and better outcomes, in 2016, we have decided to routinely perform SFM as a first step of all the laparoscopic or robotic sigmoid and rectal resections. The aim of this paper is to describe the technique of laparoscopic splenic flexure mobilization and to discuss the advantages of using it as the first surgical step in colorectal rectal resection analyzing our last 12 months experience (2018). Method: A detailed description of the laparoscopic surgical technique for SFM is performed. There are four routes for SFM: two from medial to lateral, one starting from the splenic vein the other one from the promontory, a superior to inferior approach and a lateral to medial approach. However, the combination of different maneuvers for an easier, safer approach decreases the morbidity and is saving surgical time. Results: Between January and December 2018, 47 patients had SPM as a first step of the performed colorectal procedure in our institution. There were 30 patients with rectal cancer, 10 with sigmoidal tumors, five with sigmoidal resection for diverticulitis and Hartmann reversal was indicated in two. The robotic approach has been used in 40% (16 patients). No intraoperative incidents were associated with the SFM. No colorectal fistula was encountered. No early cancer recurrence, deaths or major complication were encountered. The mean follow-up for these patients is 7 months (range, 4-12 months). Conclusions: In our perspective, the routine mobilization of the splenic flexure as a first step of the colorectal restorative resections associate many advantages and these strategies should be largely used. There is a learning curve involved in such procedure and it can easily be overcome in high volume centers.

Isolated solitary muscle recurrence of early stage non-small cell lung cancer detected by 18F-FDG PET/CT.

Isolated solitary muscle recurrence of early stage non-small cell lung cancer detected by 18F-FDG PET/CT.

Port site recurrence and unusual diffuse subcutaneous metastases of unexpected early stage ovarian cancer after laparoscopic surgery: a case report.

Port site recurrence is a rare but well-documented adverse event peculiar to laparoscopic surgery. We report an unusual outcome of unexpected early stage ovarian cancer in which port site recurrence occurred after laparoscopic surgery and was followed by diffuse subcutaneous metastases. A 31-year-old Japanese woman with a large tumor in her abdomen visited our hospital. Because no intratumoral solid component was detected on diagnostic imaging, the tumor was diagnosed as a benign ovarian tumor and the patient underwent left ovarian laparoscopic cystectomy. Contrary to our expectations, however, the ovarian tumor was a mucinous carcinoma. We performed additional surgery, but the tumor recurred in the umbilical area, and multiple subcutaneous metastases later appeared. The curative effect of chemotherapy and radiation was limited. This atypical metastatic distribution of an extremely small amount of cancer might have been caused by the laparoscopic procedure. Protection against tumor cell dissemination is necessary during all forms of laparoscopic surgery.

Factors associated with early recurrence after curative resection for panrceatic cancer.

Introduction: Adjuvant chemotherapy is recommended after curative resection of pancreatic cancer. But early recurrence before the end time of the chemotherapy is sometimes observed, which exhibited poor prognosis. We sought to find the factors which affect the early relapse of pancreatic cancer. Method: We searched curatively resected cases of pancreatic adenocarcinoma among 2006-2014 in our faculty retrospectively. We defined early recurrence as relapse within 6 months after surgery, and patients were classified into early recurrence (group A), late recurrence (group B) and no recurrence group(group C). Result: A total of 86 patients were identified and 55 cases were eligible, 10 in group A, 31 in group B and 14 in group C. Clinical characteristics among the groups was not significant except the profile of lymph node metastasis. Postoperative complication (worse than Clavien-Dindo grade 2) and later initiation of adjuvant chemotherapy (more than 30 days after the surgery) were significantly corelated to group A when compared with group B. Cox regression analysis showed significant association The lymph node metastasis (N1a:HR 0.183 [95% CI 0.076-0.438]; P < 0.01, N1b: HR 0.325 [95% CI 0.137-0.773]; P = 0.011) and the initiation date of adjuvant chemotherapy (HR 10.146 [95% CI 2.066-49.825]; P < 0.01) were also associated with disease-free survival. Conclusion: We detected the lymph node metastasis and delay of adjuvant chemotherapy as possible factors which support to predict early recurrence of pancreatic cancer. However, additional study with extended number and follow-up are needed to validate our findings.

Early local recurrence and one-year mortality of rectal cancer after restricting the neoadjuvant therapy regime

IntroductionTo reduce the risk of local recurrence after rectal cancer surgery, neoadjuvant radiotherapy (RT) can be applied. However, as this causes morbidity and increases mortality, new Dutch guidelines withhold RT in low-risk patients. The aim of this study is to investigate if early local recurrence and one-year mortality in rectal cancer patients has changed since this more restricting indication for neoadjuvant RT was introduced in 2014. MethodsThis retrospective study included all consecutive patients treated with a mesorectal excision for primary rectal cancer in the Amphia Hospital, the Netherlands, between January 2011 and July 2016. Data were extracted from the electronic patient records. Survival data were collected from the Municipal Personal Records Database. ResultsBetween 2011 and July 2016, 407 resections of primary rectal cancer without synchronic metastases were performed, 225 under the old guidelines and 182 under the new guidelines. Significantly fewer patients received neoadjuvant treatment under the new guidelines (89% vs 41%, p < 0.001). Both clinical tumour stage (p = 0.001) and clinical lymph node stage (p < 0.001) were lower in the new group, but no difference in pathologic TN-stage was found. There was no difference in one-year local recurrence (2.2% in both groups, p = 0.987), nor in one-year mortality (5.3% vs 3.8%, p = 0.479). ConclusionIntroducing a new guideline and thereby restricting the indication for neoadjuvant RT in rectal cancer patients did not increase the early local recurrence rate or decreased one-year mortality in our hospital.

Different risk factors between early and late cancer recurrences in patients without additional surgery after noncurative endoscopic submucosal dissection for early gastric cancer

Cancer recurrence is observed in some patients without additional radical surgery after endoscopic submucosal dissection (ESD) that does not fulfill the curability criteria for early gastric cancer (EGC), categorized as "noncurative resection" or "curability C-2" in the guidelines. However, time to cancer recurrence is different in such patients. Thus, we aimed to identify the risk factors of early and late cancer recurrences in these patients. Between 2000 and 2011, this multicenter study analyzed 905 patients who were followed up without additional radical surgery after ESD for EGC categorized as curability C-2. We evaluated the risk factors for early and late cancer recurrences, separately, after ESD. The cut-off value was defined at 2 years. Time to cancer recurrence in the enrolled patients showed a bimodal pattern, and the 5-year cancer recurrence rate was 3.2%. Multivariate Cox analyses revealed that lymphatic invasion (hazard ratio [HR], 8.56; P= .003) was the sole independent risk factor for early cancer recurrence. Regarding late cancer recurrence, vascular invasion (HR, 4.50; P= .039) was an independent risk factor, and lymphatic invasion tended to be a risk factor (HR, 3.63; P= .069). This multicenter study with a large cohort demonstrated that lymphatic invasion is mainly associated with early cancer recurrence; however, vascular invasion was a risk factor only for late recurrence in patients without additional treatment after ESD for EGC categorized as curability C-2. This finding may contribute to decision making for treatment strategies after ESD, especially for patients with a relatively short life expectancy.