5-year Cumulative Incidence Of Recurrence Research Articles

Oncological characteristics of epidermal growth factor receptor–mutated clinical stage IA lung adenocarcinoma with radiologically pure-solid appearance

ObjectivesWe evaluated the clinicopathological and oncological characteristics of epidermal growth factor receptor–mutated clinical stage IA radiological pure-solid lung adenocarcinoma and compared them with those of a ground-glass opacity component. MethodsBetween 2008 and 2020, data from 1014 surgically resected clinical stage 0-IA epidermal growth factor receptor–mutated lung adenocarcinomas were evaluated. Oncological outcomes were assessed using multivariable analysis. Overall survival was estimated using Kaplan–Meier analysis and the log-rank test. The cumulative incidence of recurrence was estimated using the Gray's test. ResultsOf these, 233 (23%) were radiologically pure-solid tumors, which demonstrated a higher proportion of nodal metastasis, micropapillary component, spread through alveolar space, and Ex19 subtype compared with those of tumors with ground-glass opacity (P < .001). Multivariable analysis revealed that the presence of ground-glass opacity was an independently significant factor for overall survival (P = .037) and cumulative incidence of recurrence (P < .001). In cases where the oncological outcomes were stratified by the presence of ground-glass opacity component, the 5-year overall survival was excellent at more than 90% in tumors with ground-glass opacity despite clinical-T categories (P = .2044); however, tumor size significantly affected survival only in pure-solid tumors (T1a, 100%; T1b, 77.7%; T1c, 68.5%; P = .0056). Furthermore, the cumulative incidence of recurrence was low in tumors with ground-glass opacity despite the clinical-T categories, whereas tumor size significantly affected the cumulative incidence of recurrence only in pure-solid tumors (5-year cumulative incidence of recurrence: T1a-b, 18.9%; T1c, 41.3%; P < .001). ConclusionsOncologic behavior and prognosis of radiologically pure-solid tumors were significantly poorer than those of tumors with ground-glass opacity among patients with epidermal growth factor receptor–mutated early-stage lung adenocarcinoma. These findings imply distinct tumorigenesis based on the presence of ground-glass opacity, even in tumors with epidermal growth factor receptor mutations.

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

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

A multicenter propensity score-matched analysis of lymphadenectomy in N1-positve lung cancer.

Selective mediastinal lymph node dissection based on lobe-specific metastases is widely recognized in daily practice. However, the significance of mediastinal lymph node dissection for N1-positive tumors has not been elucidated. We retrospectively reviewed 359 patients with N1-positive lung cancer who underwent lobectomy with systematic mediastinal lymph node dissection (systematic lymph node dissection) (n=150) and lobe-specific mediastinal lymph node dissection (lobe-specific lymph node dissection) (n=209). The operative and postoperative results and their propensity score-matched pairs were compared. The factors affecting survival were assessed using competing risk and multivariable analyses. The cumulative incidence of recurrence and the cumulative incidence of cancer-specific death were not significantly different between systematic and lobe-specific lymph node dissection in entire cohort. In the propensity score-matched cohort (83 pairs), systematic lymph node dissection tended to detect N2 lymph node metastasis more frequently (55.4 vs. 41%, P=0.087). Eleven patients (13.2%) in the systematic lymph node dissection group had a metastatic N2 lymph node 'in the systematic lymph node dissection field' that lobe-specific lymph node dissection did not dissect. The oncological outcomes between patients undergoing systematic lymph node dissection (5-year cumulative incidence of recurrence, 62.1%; 5-year cumulative incidence of cancer-specific death, 27.9%) and lobe-specific lymph node dissection (5-year cumulative incidence of recurrence, 60.1%; 5-year cumulative incidence of cancer-specific death, 23.3%) were similar. The propensity score-adjusted multivariable analysis for cumulative incidence of recurrence revealed that the prognosis associated with systematic lymph node dissection was comparable with the prognosis with lobe-specific lymph node dissection (hazard ratio, 1.17; 95% confidence interval, 0.82-1.67; P=0.37). The extent of lymph node dissection can affect accurate pathological staging; however, it was not associated with survival outcome in the treatment of N1-positive lung cancer.

Recurrence After Complete Resection for Non-Small Cell Lung Cancer in the National Lung Screening Trial

BackgroundThe objective of this study was to evaluate patterns, predictors, and long-term outcomes of recurrent disease after complete resection for early-stage non-small cell lung cancer (NSCLC) using the National Lung Screening Trial (NLST). MethodsThe frequency of recurrence in patients with pathologic stage I-II NSCLC who underwent complete resection (lobectomy or bilobectomy) in the NLST was evaluated. Predictors of increased risk of recurrence were assessed by Fine-Gray competing risks regression. ResultsOf the 497 patients meeting study inclusion criteria, 94 experienced a recurrence—a rate of 4.9 (95% CI, 4.0-6.0) per 100 person-years. The 5-year cumulative incidence of recurrence was 20.1% (95% CI, 16.5%-23.9%). Most patients experienced recurrences at distant sites alone (n = 47 [50.0%]) or at both locoregional and distant sites (n = 30 [31.9%]). The median time from resection to recurrence was 18.8 (10.6-30.7) months. The incidence rate of recurrence was significantly lower among patients with lung cancer detected by low-dose computed tomography screening during one of the three screening rounds of the NLST when compared with patients with lung cancer detected by chest radiography screening and patients with lung cancer not detected by any form of screening (ie, those diagnosed after a negative or missed screening exam and those diagnosed during follow-up after the three screening rounds of the NLST were completed) (P < .001). Median survival (from the date of recurrence) of patients with pathologic stage I and stage II disease who had recurrences at locoregional, distant, or both sites was 63.0, 23.1, and 9.8 months and 28.9, 8.7, and 10.2 months, respectively. ConclusionsIn this analysis of NLST participants with completely resected stage I-II NSCLC, the 5-year cumulative incidence of recurrence was 20%. Nearly 82% of recurrences were at distant sites and associated with poor survival.

Early-Onset Pancreatic Neuroendocrine Tumors: Clinical Presentation, Pathology Features, and Oncological Outcomes.

Early-Onset (EO) pancreatic neuroendocrine tumor (PanNET) is a rare disease, but whether it is clinically different from late-onset (LO) PanNET is unknown. Our study aimed to evaluate clinical differences and disease outcomes between EO-PanNET and LO-PanNET and to compare sporadic EO-PanNET with those with a hereditary syndrome. Patients with localized PanNET who underwent pancreatectomy at Memorial Sloan Kettering between 2000 and 2017 were identified. Those with metastatic disease and poorly differentiated tumors were excluded. EO-PanNET was defined as <50 and LO-PanNET >50 years of age at the time of diagnosis. Family history and clinical and pathology characteristics were recorded. Overall 383 patients were included, 107 (27.9%) with EO-PanNET. Compared with LO-PanNET, EO-PanNET were more likely to have a hereditary syndrome (2.2% vs. 16%, P <0.001) but had similar pathology features such as tumor grade ( P =0.6), size (2.2 Vs. 2.3cm, P =0.5) and stageof disease ( P =0.8). Among patients with EO-PanNET, those with hereditary syndrome had more frequently a multifocal disease (65% vs. 3.3%, P <0.001). With a median follow-up of 70 months (range 0-238), the 5-year cumulative incidence of recurrence after curative surgery was 19% (95% CI 12%-28%) and 17% (95% CI 13%-23%), in EO-PanNET and LO-PanNET ( P =0.3). Five-year disease-specific survival was 99% (95% CI 98%-100%) with no difference with respect to PanNET onset time ( P =0.26). In this surgical cohort, we found that EO-PanNET is associated with hereditary syndromes but has pathologic characteristics and oncological outcomes similar to LO-PanNET. These findings suggest that patients with EO-PanNET can be managed similarly to those with LO-PanNET.

Effects of a ground-glass opacity component on the recurrence and survival of pathological stage IA3 lung adenocarcinoma: a multi-institutional retrospective study.

This study aimed to evaluate the effect of the presence of a radiographically manifested ground-glass opacity (GGO) component on the prognosis of patients with pathological stage IA3 lung adenocarcinoma. Patients diagnosed with pathological stage IA3 lung adenocarcinoma who underwent radical surgery at two medical institutions in China between July 2012 and July 2020 were enrolled. The cumulative incidence of recurrence (CIR) and cumulative incidence of death (CID) in patients with and without a GGO component were compared. Risk curves for the recurrence and tumor-related death overtime were analyzed between the two groups according to life table. In order to validate the prognostic value of GGO components, the recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated. Decision curve analysis (DCA) was performed to evaluate the clinical benefit rate of different models. Among the 352 included patients, the presence of a GGO component was radiographically shown in 166 (47.2%) patients, while 186 (52.8%) displayed solid nodules. Patients exhibiting the absence of a GGO component had higher incidences of total recurrence (17.2% vs. 3.0%, P<0.001), local-regional recurrence (LRR) (5.4% vs. 0.6%, P=0.010), distant metastasis (DM) (8.1% vs. 1.8%, P=0.008), and multiple recurrences (4.3% vs. 0.6%, P=0.028) than the presence-GGO component group. The 5-year CIR and CID were 7.5% and 7.4% in the presence-GGO component group, and 24.5% and 17.0% in the absence-GGO component group, respectively, with statistically significant differences between the two groups (P<0.05). The risk of recurrence in patients with the presence of GGO components showed a single peak at 3 years postoperatively, while patients with the absence of GGO components showed a double peak at 1 and 5 years after surgery, respectively. However, the risk of tumor-related death peaked in both groups at 3 and 6 years postoperatively. Multivariate Cox analysis showed that the presence of a GGO component was a favorable independent risk factor for pathological stage IA3 lung adenocarcinoma patients (P<0.05). Pathological stage IA3 lung adenocarcinoma with or without GGO components are two types of tumors with different invasive abilities. In clinical practice, we should develop different treatment and follow-up strategies.

Abstract 4206: The impact of two decades of multidisciplinary efforts to reduce the risk of recurrence from colorectal cancer - a Danish population-based registry-study

Abstract Purpose: Over the last two decades, several initiatives have aimed at reducing risk of recurrence in patients operated for non-metastatic colorectal cancer (CRC). The focus has been on improving treatment in a multidisciplinary setting and implementing a population-based screening program. However, the combined impact of these initiatives on the risk of recurrence is not well described. Therefore, the primary aim of this study was to determine and compare recurrence rates for three calendar periods 2004-2008, 2009-2013, and 2014-2019 (after implementation of screening) in CRC. Material and Methods: Patients undergoing surgery for UICC TNM stage I-III CRC in the period 2004 to 2019 were included. All patients were identified using the nationwide clinical quality database DCCG, and hereafter linked with data from the Danish Cancer Registry, the Danish National Registry of Patients, and the Danish Pathology Registry. Recurrence status was determined using a validated algorithm defining recurrence based on diagnosis codes of local recurrence or metastases, the receipt of chemotherapy, or a pathological tissue assessment code of recurrence. The algorithm has shown a positive predictive value of 94% and a negative predictive value of 99%. Cumulative risk of recurrence and relapse-free survival (RFS) was reported by grouping the patients in calendar periods. Results: Of 33,470 stage I-III patients, 7,002 developed recurrence within 5 years after primary surgery (incidence rate = 60.4 per 1,000 person years, 95% CI: 59-61.8) with highest incidence among rectal cancer patients. The 5-year cumulative incidence of recurrence decreased for both colon cancers (2004-2009: 26% (95% CI: 25-27%); 2009-2013: 21% (95% CI: 20-22%); 2014-2019: 15% (95% CI: 14-16%)) and rectal cancers (2004-2009: 30% (95% CI: 29-32%); 2009-2013: 25% (95% CI: 24-27%); 2014-2019: 19% (95% CI: 18-20%)). The same pattern was found within each of stages I, II and III when stratifying by the three calendar periods. Screening-detected (SD) patients had lower risk of recurrence when compared to non-screening detected patients. The 5-year cumulative incidence of recurrence remained lower for 2014-2019 compared to previous calendar periods when excluding SD patients. Adjusted RFS improved significantly from 2004-2008 (reference) to 2014-2019 for colon cancer patients across all UICC stages; I) HR=0.49 (95%CI: 0.42-0.57), II) HR=0.56 (0.51-0.62) and III) HR=0.67 (0.62-0.73). The same pattern was seen for rectal cancer patients with HR=0.50 (0.42-0.60), HR=0.60 (0.52-0.69) and HR=0.67 (0.60-0.75) for stage I, II and III, respectively. Conclusion: The national multidisciplinary initiatives to improve the outcome of CRC within the past two decades have borne fruit, as reflected by significant reductions in CRC recurrence risk and prolonged RFS observed for Danish stage I-III CRC patients. Citation Format: Jesper Nors, Kaare A. Gotschalck, Rune Erichsen, Lene H. Iversen, Claus L. Andersen. The impact of two decades of multidisciplinary efforts to reduce the risk of recurrence from colorectal cancer - a Danish population-based registry-study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4206.

Abstract OT1-06-01: Preservation of axillary lymph nodes in breast cancer patients undergoing mastectomy with 1-2 metastatic sentinel lymph nodes: The current status and future perspectives of the multicenter randomized clinical trial SINODAR-ONE

Abstract Introduction: Axillary lymph node dissection (ALND) has always been part of breast cancer (BC) treatment. However, during the past 25 years, the surgical management of the axilla has shifted towards a more conservative approach. Until now, ALND has remained the standard surgical technique when the sentinel lymph node (SLN) is macrometastatic. However, ALND may now be considered overtreatment for early-stage BC. The SINODAR-ONE trial is a prospective non-inferiority multicenter randomized study aimed at assessing the role of ALND in patients undergoing either breast-conserving surgery (BCS) or mastectomy for T1-2 BC presenting 1-2 macrometastatic SLNs. Objectives: The primary endpoint was to evaluate whether sentinel lymph node biopsy (SLNB) only was associated with clinically relevant worsening of the prognosis compared with ALND in terms of overall survival (OS). The secondary endpoint was to evaluate whether there was increased regional (lymph node recurrence) or distant recurrence in terms of recurrence-free survival (RFS) in patients with macrometastatic SLN who did not undergo ALND. Methods: Patients were randomly assigned (1:1 ratio) to either removal of ≥10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). Results: The trial started in April 2015 and ceased in April 2020, involving 889 patients. The majority of the patients (75.2%) underwent BCS; 328 of 439 patients (74.7%) in the standard treatment arm, and 333 of 440 patients (75.7%) in the experimental treatment arm. 218 patients (24.8%) underwent mastectomy. SLN status at randomization was comparable between the two groups of treatment, with a median number of two SLNs removed and a median number of one positive SLN in both arms. The median number of non-SLNs identified at definitive histopathological evaluation was 16 (interquartile range [IQR] 12–21) in the ALND group. Overall, 193 of 439 patients (44.0%) in the standard treatment arm had additional macrometastases in the removed axillary lymph nodes. However, the median number of positive non SLNs was 0 (IQR 0–1) in the ALND group. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with a 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with a 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB only arm, respectively (p = 0.936). Conclusion: The 3-year survival and relapse rates of T1-2 BC patients with 1-2 macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND in patients undergoing BCS. However, given the low number of patients treated with mastectomy, there is no certainty that ALND omission can be extended also to this sub-group. In order to collect further evidence regarding the safety of the experimental treatment in patients candidates for mastectomy, the reopening of the enrollment of these patients as part of a single-arm experimental study started in June 2022. Citation Format: Damiano Gentile, Wolfgang Gatzemeier, Andrea Sagona, Erika Barbieri, Alberto Testori, Valentina Errico, Alberto Bottini, Simone Di Maria Grimaldi, Giulia Caraceni, Luca Boni, Paolo Bruzzi, Bethania Fernandes, Davide Franceschini, Ruggero Spoto, Rosalba Torrisi, Marta Scorsetti, Armando Santoro, Giuseppe Canavese, Corrado Tinterri. Preservation of axillary lymph nodes in breast cancer patients undergoing mastectomy with 1-2 metastatic sentinel lymph nodes: The current status and future perspectives of the multicenter randomized clinical trial SINODAR-ONE [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-06-01.

Risk Factors for Recurrence of Stage I Epidermal Growth Factor Receptor Mutated Lung Adenocarcinoma

BackgroundWe aimed to clarify the risk factors for postoperative recurrence in patients with epidermal growth factor receptor (EGFR)-mutated stage I lung adenocarcinoma, using EGFR wild-type adenocarcinoma as a comparator, to select optimal candidates for adjuvant therapy with EGFR tyrosine kinase inhibitor (TKI). MethodsData of patients with pathologic stage I EGFR-mutated (n = 713) and wild-type (n = 673) adenocarcinoma who did not receive adjuvant therapy were retrospectively analyzed. The cumulative incidence of recurrence (CIR) was estimated using Gray’s method, and multivariable Fine-Gray competing risk models identified independent risk factors associated with recurrence. ResultsThe CIR did not differ significantly between patients with EGFR-mutated and wild-type adenocarcinoma (P = .32). Multivariable analysis revealed that greater size (cm) of invasive tumor (hazard ratio 1.539; 95% CI, 1.077-2.201), lymphovascular invasion (hazard ratio 5.180; 95% CI, 2.208-12.15), pleural invasion (hazard ratio 3.388; 95% CI, 1.524-7.533), and high-grade histologic subtype (hazard ratio 4.295; 95% CI, 1.539-11.99) were independent risk factors for recurrence in patients with EGFR-mutated adenocarcinoma. The 5-year CIR was significantly higher among patients with these factors (tumor size greater than 2 cm, 15.9%; lymphovascular invasion, 26.9%; pleural invasion, 39.3%; and high-grade subtype, 44.4%) than among patients without them (4.4%, 2.2%, 3.9%, and 5%, respectively; P < .001). For patients with EGFR wild-type adenocarcinoma, independent risk factors for recurrence were invasive tumor size, lymphovascular invasion, and pleural invasion, but not histologic subtypes. ConclusionsEven for patients with EGFR-mutated stage I lung adenocarcinoma, recurrence risk is stratified. Adjuvant therapy may be considered if they have high-risk factors for recurrence.

Peritumoral radiomics features on preoperative thin-slice CT images can predict the spread through air spaces of lung adenocarcinoma

The spread through air spaces (STAS) is recognized as a negative prognostic factor in patients with early-stage lung adenocarcinoma. The present study aimed to develop a machine learning model for the prediction of STAS using peritumoral radiomics features extracted from preoperative CT imaging. A total of 339 patients who underwent lobectomy or limited resection for lung adenocarcinoma were included. The patients were randomly divided (3:2) into training and test cohorts. Two prediction models were created using the training cohort: a conventional model based on the tumor consolidation/tumor (C/T) ratio and a machine learning model based on peritumoral radiomics features. The areas under the curve for the two models in the testing cohort were 0.70 and 0.76, respectively (P = 0.045). The cumulative incidence of recurrence (CIR) was significantly higher in the STAS high-risk group when using the radiomics model than that in the low-risk group (44% vs. 4% at 5 years; P = 0.002) in patients who underwent limited resection in the testing cohort. In contrast, the 5-year CIR was not significantly different among patients who underwent lobectomy (17% vs. 11%; P = 0.469). In conclusion, the machine learning model for STAS prediction based on peritumoral radiomics features performed better than the C/T ratio model.

Preservation of Axillary Lymph Nodes Compared with Complete Dissection in T1-2 Breast Cancer Patients Presenting One or Two Metastatic Sentinel Lymph Nodes: The SINODAR-ONE Multicenter Randomized Clinical Trial.

The SINODAR-ONE trial is a prospective noninferiority multicenter randomized study aimed at assessing the role of axillary lymph node dissection (ALND) in patients undergoing either breast-conserving surgery or mastectomy for T1-2 breast cancer (BC) and presenting one or two macrometastatic sentinel lymph nodes (SLNs). The endpoints were to evaluate whether SLN biopsy (SLNB) only was associated with worsening of the prognosis compared with ALND in terms of overall survival (OS) and relapse. Patients were randomly assigned (1:1 ratio) to either removal of ≥ 10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). The trial started in April 2015 and ceased in April 2020, involving 889 patients. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB-only arm, respectively (p = 0.936). The 3-year survival and relapse rates of T1-2 BC patients with one or two macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND.

The prognostic impact of the ground-glass opacity component in nearly pure-solid stage IA non-small-cell lung cancer.

The aim of this study was to assess the clinical effects of a small ground-glass opacity (GGO) component of a radiologically nearly pure-solid tumour on tumour aggressiveness in patients with clinical stage IA non-small-cell lung cancer (NSCLC). Data of 988 patients with clinical stage IA NSCLC who had a consolidation-to-tumour ratio of ≥0.75 on high-resolution computed tomography were retrospectively analysed. The cumulative incidence of recurrence (CIR) was compared between patients with GGO (nearly pure-solid, n = 297) and those without GGO (pure-solid, n = 691). In patients with clinical T1mi + T1a and T1b, the CIR was significantly higher in the pure-solid group than in the nearly pure-solid group (5-year CIR, 15.2% and 19.3% vs 0% and 6.4%; P < 0.001); however, this was not the case for patients with clinical T1c (5-year CIR, 23.1% vs 26.5%; P = 0.580). In the multivariable analysis, pure-solid tumours were independently associated with a higher CIR than nearly pure-solid tumours in patients with clinical T1mi + T1a + T1b (solid tumour size ≤2 cm; subdistribution hazard ratio, 3.25; 95% confidence interval, 1.59-6.63; P = 0.001) but not in those with clinical T1c tumours (2-3 cm; subdistribution hazard ratio, 0.67; 95% confidence interval, 0.39-1.13; P = 0.130). Nearly pure-solid tumours with a small GGO component influence tumour aggressiveness based on solid tumour size, with a threshold of 2 cm in patients with clinical stage IA NSCLC. For tumours sized 2-3 cm, nearly pure-solid tumours had a similar tumour aggressiveness as pure-solid tumours.

The effect of perioperative packed red blood cells transfusion on patient outcomes after liver transplant for hepatocellular carcinoma.

The impact of packed Red Blood Cell (pRBC) transfusion on oncological outcomes after liver transplantation (LT) for Hepatocellular Carcinoma (HCC) remains controversial. We evaluated the impact of pRBC transfusion on HCC recurrence and overall survival (OS) after LT for HCC. Patients with HCC transplanted between 2000 and 2018 were included and stratified by receipt of pRBC transfusion. Outcomes were HCC recurrence and OS. Propensity score matching was performed to account for confounders. Of the 795 patients, 234 (29.4%) did not receive pRBC transfusion. After matching the 1-, 3-, and 5-year cumulative incidence of recurrence was 6.6%, 12.5% and 14.8% for no-pRBC transfusion, and 8.6%, 18.8% and 21.3% (p=0.61) for pRBC transfusion. The OS at 1-, 3-, 5-year was 93.0%, 84.6% and 75.8% vs 92.0%, 79.7% and 73.5% (p=0.83) for no-pRBC transfusion and pRBC transfusion, respectively. There were no differences in recurrence (HR 1.13, 95%CI 0.71-1.78, p=0.61) or OS (HR 1.04, 95%CI 0.71-1.54, p=0.83). Perioperative administration of pRBC in liver transplant recipients for HCC resulted in a nonsignificant increase of HCC recurrence and death after accounting for confounder. Surgeons should continue to exercise cation and optimize patients iron stores medically preoperatively.

Abstract 10047: Ethnic-Specific Trends in Long-Term Post-Stroke Recurrence and Mortality Over 13 Years

Introduction: Estimating trends in long-term outcomes after stroke is important for long-term planning of health resources. Data on trends in long-term post-stroke outcomes are not available among Hispanics. Whether race-ethnic disparities exist and how trends in these outcomes have changed over time comparing non-Hispanic Whites (NHWs) with Mexican Americans (MAs) are also unknown. Thus, we aimed to estimate ethnic-specific trends in risk of 5-year all-cause mortality and recurrence after initial stroke in MAs and NHWs. Methods: We included 3308 patients who had first-ever ischemic stroke ascertained between January 1, 2000 and December 31, 2012 from the Brain Attack Surveillance in Corpus Christi (BASIC) project in Texas. Data on recurrent stroke and death were available through December 31, 2017. Fine-Gray subdistribution hazard models including covariates and an interaction term between calendar year and ethnicity were used to calculate 5-year cumulative incidence of recurrence and death in both ethnic groups in each year. Results: Among the 3308 index stroke patients, 402 (12.15%) recurrences and 1420 (37.61%) deaths were observed during the 5-year follow-up. Adjusted 5-year cumulative incidence of recurrence among MAs declined from 15.76% to 11.28%. Among NHWs, a slight decline from 12.49% to 10.46% was observed. An ethnic disparity in 5-year recurrence was not apparent in 2000 (risk difference 3.27%, [95% CI, -10.41, 9.10]) or during the study duration (Figure). The greatest ethnic disparity in 5-year mortality risk was observed in 2000 but disappeared in 2012, which was driven by the increasing trend in MAs from 23.11% in 2000 to 24.28% in 2012 and the decreasing trend in NHWs from 31.09% to 27.19% accordingly. Conclusions: No apparent ethnic disparity in long-term stroke recurrence was found and long-term survival advantage in MAs presented early in the study gradually disappeared over the 13 years.

Treatment of Anastomotic Recurrence After Esophagectomy

BackgroundIsolated local recurrence after curative esophagectomy for esophageal cancer is a rare event. Although it is potentially curable, management can be challenging. MethodsWe retrospectively reviewed all patients undergoing esophagectomy for esophageal adenocarcinoma (EAC) from 2000 to 2019. Date of recurrence was defined as the date at which the initial abnormal surveillance study result or symptomatic presentation led to further workup and subsequent pathologic diagnosis of recurrence. Overall survival after recurrence was estimated using Kaplan-Meier methods and compared between treatment groups using the log-rank test. ResultsOf the 1370 patients with EAC who underwent esophagectomy in our cohort, 531 (39%) developed recurrence of their disease. The 5-year cumulative incidence of recurrence was 2.7% (95% CI, 2.0%-3.6%) for local, 6.3% (95% CI, 5.2%-7.8%) for regional, and 22.0% (95% CI, 20.0%-24.4%) for distant recurrences. On univariable and multivariable competing-risk regression analysis, advanced pT stage, signet ring histology, and serious complication were independently associated with local recurrence. Patients with local recurrence treated with definitive therapy had a median survival after recurrence of 19.1 months (95% CI, 11.4-33.2 months) compared with 10.6 months (95% CI, 8.5-14.2 months) for chemotherapy or radiotherapy alone and 1.73 months (95% CI, 0.23-15.6 months) for no treatment (P < .001). ConclusionsIsolated local recurrence occurred in only 3% of patients. Advanced T stage, signet cell histology, and serious complication were risk factors for recurrence. Although complex surgical resection is required, in very select cases, more aggressive treatment may be warranted.

Impact of analgesia on cancer recurrence and mortality within 5 years after stage I non-small cell lung cancer resection.

The choice of analgesia after cancer surgery may play a role in the onset of cancer recurrence. Particularly opioids seem to promote cancer cell proliferation and migration. Based on this consideration, we assessed the impact of perioperative analgesia choice on cancer recurrence after curative surgery for stage I non-small cell lung cancer (NSCLC). We retrospectively reviewed the records of all patients undergoing lung resection for stage I NSCLC between January 2005 and December 2012. Patients received analgesia either by peridural (PERI group) or intravenous analgesia with opioids (EV group). Follow-up was concluded in August 2019. Five-year cumulative incidence of recurrence and overall survival were evaluated and adjusted using a propensity score matching method. A total of 382 patients were evaluated, 312 belonging to the PERI group (81.7%) and 70 to the EV group (18.3%). There was no statistically significant difference between the two groups in 5-year cumulative incidence of recurrence (p = 0.679) or overall survival rates (p = 0.767). These results were confirmed after adjustment for propensity score matching for cumulative incidence of recurrence (p = 0.925) or overall survival (p = 0.663). We found no evidence suggesting an association between perioperative analgesia choice and recurrence-free survival or overall survival in patients undergoing surgical resection of stage I NSCLC.

Defining low-risk lesions in early-stage esophageal adenocarcinoma

ObjectiveAs endoscopic approaches become more widely used to treat early-stage esophageal cancer, reliably identifying patients with less-aggressive tumors is paramount. We sought to identify risk factors for recurrence in patients with completely resected T1 esophageal adenocarcinoma. MethodsWe retrospectively analyzed a single-institutional database for all patients with completely resected pathologic T1 esophageal adenocarcinoma (1996-2016). Risk factors for recurrence were identified using competing-risk regression methods. Risk stratification was performed on the basis of known preoperative clinicopathologic factors; this model's discriminative power for overall survival was evaluated using a Cox proportional hazards model. ResultsOf 243 patients, 32 experienced recurrence. At a median follow-up among survivors of 4 years (range, 0.05-19 years), the 5-year cumulative incidence of recurrence was 15%, and median time to recurrence was 2 years (range, 0.26-6.13 years). On univariable analysis, submucosal invasion, N1 disease, poor differentiation, tumor length, lymphovascular invasion, and multicentricity were significantly associated with recurrence. On multivariable analysis, N1 disease (hazard ratio, 2.93; 95% confidence interval, 1.17-7.34; P = .022) and tumor length (hazard ratio, 1.44; 95% confidence interval, 1.12-1.86; P = .004) were independently associated with recurrence. Risk stratification showed that patients without lymphovascular invasion and a with median tumor length of 0.8 cm (range, 0.10-1.70 cm) had a <10% risk of recurrence and improved survival. ConclusionsPathologic T1 tumors have a 5-year cumulative incidence of recurrence of 15%. Nodal involvement and tumor length were independent risk factors for recurrence, whereas tumors <2 cm in length without lymphovascular invasion were associated with a low risk of recurrence.

Comparison of cancer control between segmentectomy and wedge resection in patients with clinical stage IA non–small cell lung cancer

ObjectiveThe study objective was to compare cancer control between segmentectomy and wedge resection in patients with clinical stage IA non–small cell lung cancer. MethodsBetween 2010 and 2015, 457 patients with clinical stage IA (8th edition) non–small cell lung cancer undergoing wedge resection or segmentectomy were identified at 3 institutions. Propensity scores were calculated on the basis of the extent of resection (wedge resection or segmentectomy) and included adjustment for confounding variables, such as age, sex, smoking status, pulmonary functions, laterality, tumor size, maximum standardized uptake value on 18F-fluorodeoxyglucose positron emission tomography, presence of ground-glass opacity on high-resolution computed tomography, histology, and visceral pleural invasion for multivariable analysis and matching. The primary end point was cumulative incidence of recurrence. ResultsIn all cohorts, postoperative recurrence occurred in 36 of 195 patients (18.5%) undergoing wedge resection and 14 of 262 patients (5.3%) undergoing segmentectomy. Cumulative incidence of recurrence was significantly lower in patients undergoing segmentectomy (5-year cumulative incidence of recurrence, 5.3%) than in those undergoing wedge resection (5-year cumulative incidence of recurrence, 19.1%; P < .001). In propensity score–adjusted multivariable analysis, segmentectomy was identified as an independent favorable prognostic factor for cumulative incidence of recurrence (hazard ratio, 0.47; 95% confidence interval, 0.24-0.90; P = .022). In propensity score matching of 163 pairs, cumulative incidence of recurrence was significantly lower in patients undergoing segmentectomy (5-year cumulative incidence of recurrence, 6.6%) than in those undergoing wedge resection (5-year cumulative incidence of recurrence, 13.2%; P = .041). ConclusionsCancer control was better in segmentectomy than in wedge resection. Segmentectomy is the preferred oncologic procedure as sublobar resection to treat clinical stage IA non–small cell lung cancer.

Clinicopathological variables influencing overall survival, recurrence and post-recurrence survival in resected stage I non-small-cell lung cancer

BackgroundTo investigate clinicopathological variables influencing overall survival, overall recurrence, and post-recurrence survival (PRS) in patients who experienced curative-intent surgical resection of stage I non-small-cell lung cancer (NSCLC).MethodsWe investigated a series of 1387 patients with stage I NSCLC who underwent surgical resection from 2008 to 2015. The effect clinicopathological factors on death, recurrence, and PRS were evaluated by Kaplan-Meier estimates and cox regression analysis.ResultsAmong the 1387 stage I patients, 301 (21.7%) experienced recurrence. The 5-year cumulative incidence of recurrence (CIR) for all patients was 20.2% and median PRS was 25.5 months. The older age (P = 0.036), p-stage IB (P = 0.001), sublobar resection(P<0.001), histology subtype (P<0.001), and lymphovascular invasion (LVI) (P = 0.042) were significantly associated with worse overall survival. Among 301 recurrent patients, univariable analysis indicated that p-stage IB (versus IA) (P<0.001), LVI (P<0.001) and visceral pleural invasion (VPI) (P<0.001) were remarkably correlated with the higher incidence of recurrence. Taking the effect of clinicopathological variables on PRS into consideration, smoking history (P = 0.043), non-adenocarcinoma (P = 0.013), high architectural grade of LUAD (P = 0.019), EGFR wild status (P = 0.002), bone metastasis (P =0.040) and brain metastasis (P = 0.042) were substantially related with poorer PRS. Multivariate analysis demonstrated that high architectural grade of LUAD (P = 0.008), brain metastasis (P = 0.010) and bone metastasis (P = 0.043) were independently associated with PRS.ConclusionIn patients with resected stage I NSCLC, the older age, p-stage IB (versus IA), sublobar resection, histology subtype, and LVI were significantly associated with worse overall survival. P-stage IB (versus IA), LVI, and VPI were significantly correlated with the higher incidence of recurrence. High architectural grade of LUAD, brain metastasis and bone metastasis were independent risk factors with PRS.

Surgical site occurrences, not body mass index, increase the long-term risk of ventral hernia recurrence

BackgroundRecurrence rates after ventral hernia repair vary widely and evidence about risk factors for recurrence are conflicting. There is little evidence for risk factors for long-term recurrence. MethodsPatients who underwent ventral hernia repair at our institution and were captured in the American College of Surgeons-National Surgical Quality Improvement Program database between 2002 and 2015 were included. We reviewed all demographic, procedural, and hernia-specific data. ResultsSix hundred and thirty patients were included for analysis with a median follow-up of 4.9 years (inter-quartile range, 2–7.3 years). By univariate analysis, index hernia repairs were more likely to recur if defect size was ≥4 cm (P = .019), no mesh was used (P = .026), or if the repair was for a recurrent hernia (P = .001). Five-year cumulative incidence of recurrence and reoperation was 24.3% and 16.0%, respectively. Patients with a perioperative surgical site occurrence, which included superficial, deep-incisional, and organ space surgical site infections as well as wound disruption, had a 5-year cumulative incidence of recurrence of 54.9% compared with 22.6% for those without surgical site occurrence. By multivariable analysis, non-primary hernia repair (hazard ratio 1.7, 95% confidence interval 1.2–2.4, P = .005) and any postoperative surgical site occurrence (hazard ratio 1.9, 95% confidence interval 1.1–3.6, P = .02) were the only risk factors predictive of recurrence. Patient body mass index had no independent effect on recurrence. Conclusion1 in 4 patients undergoing an open ventral hernia repair will have a recurrence after 5 years, and this risk is doubled among patients who experience any perioperative surgical site occurrence. After controlling for patient comorbidities, including body mass index, hernia size, and mesh position, the most significant risk factor for recurrence after ventral hernia repair was a non-primary hernia and surgical site occurrence.