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Preoperative AminoIndex Cancer Screening (AICS) abnormalities predict postoperative recurrence in patients undergoing curative resection for non-small cell lung cancer.

ABSTRACT: BACKGROUND:AminoIndex™ Cancer Screening (AICS (lung)) was developed as a screening test for lung cancer using a multivariate analysis of plasma-free amino acid (PFAA) profiles. According to the developed index composed of PFAA, the probability of lung cancer was categorized into AICS (lung) ranks A, B, and C in order of increasing risk. The aim of the present study was to investigate the relationship between the preoperative AICS (lung) rank and surgical outcomes in patients who underwent curative resection for non-small cell lung cancer (NSCLC). METHODS:Preoperative blood samples were collected from 297 patients who underwent curative resection for NSCLC between 2006 and 2015. PFAA concentrations were measured. The relationship between the preoperative AICS (lung) rank and clinicopathological factors was examined. The effects of the preoperative AICS (lung) rank on postoperative outcomes were also analyzed. RESULTS:The AICS (lung) rank was A in 93 patients (31.3%), B in 82 (27.6%), and C in 122 (41.1%). The AICS (lung) rank did not correlate with any clinicopathological factors, except for age. Based on follow-up data (median follow-up period of 6?years), postoperative recurrence was observed in 22 rank A patients (23.7%), 15 rank B (18.3%) and 49 rank C (40.2%). In the univariate analysis, preoperative AICS (lung) rank C was a worse factor of recurrence-free survival (p?=?0.0002). The multivariate analysis identified preoperative AICS (lung) rank C (HR: 2.17, p?=?0.0005) as a significant predictor of postoperative recurrence, particularly in patients with early-stage disease or adenocarcinoma. CONCLUSION:Preoperative AICS (lung) rank C is a high-risk predictor of postoperative recurrence in patients undergoing curative resection for NSCLC.

SUBMITTER: Higashiyama M

PROVIDER: S-EPMC7659101 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Preoperative AminoIndex Cancer Screening (AICS) abnormalities predict postoperative recurrence in patients undergoing curative resection for non-small cell lung cancer.

Higashiyama Masahiko M Miyazaki Ryohei R Yamamoto Hiroshi H Anayama Takashi T Kikuchi Shinya S Hirohashi Kentaro K Okami Jiro J Maniwa Tomohiro T Kimura Toru T Orihashi Kazumasa K Imamura Fumio F

BMC cancer 20201112 1

<h4>Background</h4>AminoIndex™ Cancer Screening (AICS (lung)) was developed as a screening test for lung cancer using a multivariate analysis of plasma-free amino acid (PFAA) profiles. According to the developed index composed of PFAA, the probability of lung cancer was categorized into AICS (lung) ranks A, B, and C in order of increasing risk. The aim of the present study was to investigate the relationship between the preoperative AICS (lung) rank and surgical outcomes in patients who underwen ...[more]

PMID: 33183251

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Project description:BACKGROUND:High-quality randomized controlled trials have demonstrated the benefit of radiotherapy (RT) in patients with radical resected gastric cancer (GC), however, utilization rates of postoperative RT remain remarkably low. Patterns, incidences, and time of recurrence provide biological bases for clinical monitoring of GC patients and guiding potential complementary therapies. Thus, the aim of this study is to understand the location of locoregional recurrence which may allow individualized RT strategies and minimize radiation-related toxic effects. METHODS:A relatively large sample of GC patients in a single institution who had undergone curative D2 resection was retrospectively reviewed and the relevant recurrence patterns were illustrated. Independent recurrence-related risk factors were analyzed by logistic regression analysis. New logistic regression models were further developed to predict the probability of recurrence. RESULTS:Overall, among 776 GC patients who had continuous and complete follow-up data, 300 cases relapsed after curative resection. Lymphovascular invasion, lymph node metastases, and tumor stage were indicators for early recurrence. Peritoneal, regional, local, and distant recurrence initially occurred in 51 (6.6%), 151 (19.4%), 56 (7.2%), and 164 (21.1%) patients, respectively. Among patients with regional recurrence, the most common sites were lymph node stations 16a2, 8, 12, 16b1, and 9. Remnant stomach recurrence was not so prominent that it seemed reasonable to be excluded from an irradiation field for patients with negative surgical/pathologic margins. CONCLUSIONS:For GC patients who underwent radical D2 resection, distant and regional recurrences were still common. Besides, optimizing regional control of lymph nodes outside the D2 dissected area was crucial for rational design of the RT field. Furthermore, the new logistic regression models might act as useful tools to evaluate recurrence risk and determine which patients should receive postoperative chemoradiotherapy.

Project description:Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined.To define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction.Nomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015.The discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves.In total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63-5.70; P <?.001), positive nodal status (HR, 4.78; 95% CI, 1.47-15.50; P =?.01), stage III/IV (HR, 1.80; 95% CI, 0.95-3.39; P =?.07), cortisol-secreting tumor (HR, 2.38; 95% CI, 1.27-4.48; P =?.01), and capsular invasion (HR, 1.96; 95% CI, 1.02-3.74; P =?.04). Factors selected as predicting OS were tumor size of at least 12 cm (HR, 1.78; 95% CI, 1.00-3.17; P =?.05), positive nodal status (HR, 5.89; 95% CI, 2.05-16.87; P =?.001), and R1 margin (HR, 2.83; 95% CI, 1.51-5.30; P =?.001). The discriminative ability and calibration of the nomograms revealed good predictive ability as indicated by the C statistics (0.74 for RFS and 0.70 for OS).Independent predictors of survival and recurrence risk after curative-intent surgery for ACC were selected to create nomograms predicting RFS and OS. The nomograms were able to stratify patients into prognostic groups and performed well on internal validation.

Project description:Liver resection is the most effective treatment for intrahepatic cholangiocarcinoma. Recurrent disease is frequent; however, recurrence patterns are ill-defined and prognostic models are lacking.A primary cohort of 189 patients who underwent resection for intrahepatic cholangiocarcinoma was used for recurrence patterns analysis within and after 24 months. Based on independent factors for disease-free survival identified in Cox regression analysis, preoperative and postoperative models were developed using a recursive partitioning method. Models were externally validated using a multicenter cohort of 522 resected patients (Association Française de Chirurgie intrahepatic cholangiocarcinoma study group).Recurrence within 24 months most often involved the liver (82.7%), and most recurrences after 24 months were strictly extrahepatic (61.1%). In multivariable analysis of the primary cohort, independent preoperative factors for disease-free survival were tumor size and multifocality (based on imaging); tumor size, multifocality, vascular invasion, and lymph node metastases (based on pathology) were independent postoperative factors. The preoperative model allowed patient classification into low-risk and high-risk groups for recurrence. In the validation cohort (n = 522), high-risk patients had a greater likelihood of recurrence (hazard ratio = 2.17; 95% CI, 1.74-2.72; p < 0.001). The postoperative model included tumor size, vascular invasion, and positive nodal disease on pathology and classified patients in low-, intermediate-, and high-risk groups in the primary cohort. As compared with low-risk patients in the validation cohort, intermediate- and high-risk patients were more likely to experience recurrence (hazard ratio = 1.9; 95% CI, 1.41-2.47; p < 0.001 and hazard ratio = 2.99; 95% CI, 2.08-4.31; p < 0.001, respectively).Recurrence patterns are time dependent. Both models as developed and validated in this study classified patients in distinct recurrence risk groups, which can guide treatment recommendations.

Project description:ObjectivesTo explore the role of preoperative gadoxetic acid-enhanced MRI in stratifying the risk of early recurrence in patients with LR-5 hepatocellular carcinoma (HCC) by LI-RADS v2018 after curative resection.MethodsBetween July 2015 and August 2018, this study evaluated consecutive treatment-naïve at-risk LR-5 HCC patients who underwent gadoxetic acid-enhanced MRI examination within 2 weeks before curative resection. The Cox regression analysis was performed to identify potential predictors of early recurrence. Disease-free survival (DFS) rates were analyzed and compared by using the Kaplan-Meier method and log-rank tests.ResultsFifty-three of 103 (51.5%) patients experienced early recurrence. Three MRI findings were significantly associated with early recurrence: corona enhancement (hazard ratio [HR]: 2.116; p = 0.013), peritumoral hypointensity on hepatobiliary phase (HBP) (HR: 2.262; p = 0.007), and satellite nodule (HR: 2.777; p = 0.005). An additional risk factor was AFP level > 400 ng/mL (HR: 1.975; p = 0.016). Based on the number of MRI predictors, LR-5 HCC patients were stratified into three subgroups: LR-5a (60/103; no predictor), LR-5b (26/103; one predictor), and LR-5c (17/103; two or three predictors), with low, medium, and high risk of early recurrence, respectively. The 2-year DFS rate of LR-5a, LR-5b, and LR-5c patients was 65.0%, 38.5%, and 5.9%, respectively, while the corresponding median DFS was undefined, 17.1 months, and 5.1 months, respectively (p < 0.001).ConclusionsIn at-risk LR-5 HCC patients, corona enhancement, peritumoral hypointensity on HBP, and satellite nodule could be used to preoperatively stratify the risk of early recurrence after hepatectomy.Key points• Corona enhancement, peritumoral hypointensity on HBP, satellite nodule, and serum AFP level > 400 ng/mL were significant predictors of early recurrence in patients with LR-5 HCC after hepatectomy. • Based on the number of predictive MRI findings, LR-5 HCC patients could be preoperatively stratified into three subgroups: LR-5a, LR-5b, and LR-5c, with significantly different risk of early recurrence and disease-free survival. • Preoperative risk stratification is essential for the identification of patients at increased risk of postoperative early recurrence, which may contribute to risk-based personalized management for LR-5 HCC patients.

Project description:BackgroundIn patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA (ctDNA) analysis, as a marker of minimal residual disease, is a powerful prognostic factor in patients with nonmetastatic colorectal cancer (CRC). Serial analysis of ctDNA in patients with resectable CRLM could inform the optimal use of perioperative chemotherapy. Here, we performed a validation study to confirm the prognostic impact of postoperative ctDNA in resectable CRLM observed in a previous discovery study.Methods and findingsWe prospectively collected plasma samples from patients with resectable CRLM, including presurgical and postsurgical samples, serial samples during any pre- or postoperative chemotherapy, and serial samples in follow-up. Via targeted sequencing of 15 genes commonly mutated in CRC, we identified at least 1 somatic mutation in each patient's tumor. We then designed a personalized assay to assess 1 mutation in plasma samples using the Safe-SeqS assay. A total of 380 plasma samples from 54 patients recruited from July 2011 to Dec 2014 were included in our analysis. Twenty-three (43%) patients received neoadjuvant chemotherapy, and 42 patients (78%) received adjuvant chemotherapy after surgery. Median follow-up was 51 months (interquartile range, 31 to 60 months). At least 1 somatic mutation was identified in all patients' tumor tissue. ctDNA was detectable in 46/54 (85%) patients prior to any treatment and 12/49 (24%) patients after surgery. There was a median 40.93-fold (19.10 to 87.73, P < 0.001) decrease in ctDNA mutant allele fraction with neoadjuvant chemotherapy, but ctDNA clearance during neoadjuvant chemotherapy was not associated with a better recurrence-free survival (RFS). Patients with detectable postoperative ctDNA experienced a significantly lower RFS (HR 6.3; 95% CI 2.58 to 15.2; P < 0.001) and overall survival (HR 4.2; 95% CI 1.5 to 11.8; P < 0.001) compared to patients with undetectable ctDNA. For the 11 patients with detectable postoperative ctDNA who had serial ctDNA sampling during adjuvant chemotherapy, ctDNA clearance was observed in 3 patients, 2 of whom remained disease-free. All 8 patients with persistently detectable ctDNA after adjuvant chemotherapy have recurred. End-of-treatment (surgery +/- adjuvant chemotherapy) ctDNA detection was associated with a 5-year RFS of 0% compared to 75.6% for patients with an undetectable end-of-treatment ctDNA (HR 14.9; 95% CI 4.94 to 44.7; P < 0.001). Key limitations of the study include the small sample size and the potential for false-positive findings with multiple hypothesis testing.ConclusionsWe confirmed the prognostic impact of postsurgery and posttreatment ctDNA in patients with resected CRLM. The potential utility of serial ctDNA analysis during adjuvant chemotherapy as an early marker of treatment efficacy was also demonstrated. Further studies are required to define how to optimally integrate ctDNA analyses into decision-making regarding the use and timing of adjuvant therapy for resectable CRLM.Trial registrationACTRN12612000345886.

Dataset Information

Preoperative AminoIndex Cancer Screening (AICS) abnormalities predict postoperative recurrence in patients undergoing curative resection for non-small cell lung cancer.

Publications

Preoperative AminoIndex Cancer Screening (AICS) abnormalities predict postoperative recurrence in patients undergoing curative resection for non-small cell lung cancer.

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