Risk Of Recurrence In Patients Research Articles

Impact of Histologic Risk Factors on Recurrence Rates for Oral Cavity Squamous Cell Carcinoma.

This study assesses the impact of adverse histologic risk factors including worst pattern of invasion (WPOI), predominant pattern of invasion (PPOI), tumor budding, and tumor infiltrating lymphocytes (TILS), on risk of recurrence in patients with early-stage Oral Cavity Squamous Cell Carcinoma (OCSCC). Retrospective chart review was performed at a single institution to identify patients with OCSCC who underwent surgical excision. Inclusion criteria included T1-T2 stage disease based on AJCC seventh edition guidelines, no cervical lymph node involvement, no perineural invasion (PNI), no lymphovascular invasion (LVI), no post-operative adjuvant radiation therapy, and cancer involving only the oral tongue or floor of mouth. Patients were excluded if they had positive final margins. A subset of 35 patients were selected for additional histologic review to determine WPOI, PPOI, TB, and TILS. Bivariable and multivariable cox analysis were performed to determine variables associated with recurrence. One hundred and sixty-one patients met criteria and were included in the analysis. Variables that were significantly associated with recurrence on bivariable analysis included tumors with high risk PPOI (groups 4 and 5; P = .021), TB with 10 or more buds (P = .021), T-stage (P = .001), neck dissection (P = .03), and depth of invasion (DOI) >4 mm (P = .044). Multivariable cox proportional hazards found T-stage (HR: 6.40; 95% CI 1.67, 24.50; P = .007), neck dissection (HR: 0.23; 95% CI 0.07, 0.82; P = .023), and TBs (HR: 1.17; 95% CI 1.05, 1.30; P = .006) to be most predictive of recurrence. TB is a strong predictor of recurrence. WPOI, PPOI, and TILS were not statistically significant risk factors for recurrence.

Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma.

Pheochromocytomas and paragangliomas are endocrine tumors belonging to the family of neural crest cell-derived neoplasms. They have an extremely variable clinical course, characterized by a non-negligible percentage of relapse and/or metastasis after radical surgery. To date, there are no reliable methods to predict the metastatic potential of these neoplasms, despite several clinical, molecular, and histopathological factors that have been extensively studied in the literature as predictors of the recurrence and/or metastasis in these neoplasms with different performances and results. In this review, we aimed to discuss and analyze the most important clinical and histopathological tools for predicting recurrence risk in patients affected by pheochromocytomas or paragangliomas. Thus, we compared the main available predictive models, exploring their applications in stratifying patients’ risks. In conclusion, we underlined the importance of simple and validated tools to better define disease aggressiveness and establish tailored patients’ treatments and follow-ups.

Sirolimus reduces the risk of pneumothorax recurrence in patients with lymphangioleiomyomatosis: a historical prospective self-controlled study

BackgroundSpontaneous pneumothorax has a high incidence and high rate of recurrence in patients with lymphangioleiomyomatosis (LAM). The risk factors for pneumothorax and the effects of sirolimus on pneumothorax in patients with LAM are unknown. In our study, multivariate logistic regression was applied to a cross-sectional cohort to investigate factors associated with pneumothorax in LAM patients. Kaplan–Meier analysis was applied in the historical prospective self-controlled study to determine whether sirolimus reduces the risk of pneumothorax recurrence in patients with LAM.ResultsOf the 399 patients registered with LAM-CHINA at our center between May 10, 2017 and August 31, 2020, 142 had a history of pneumothorax at registration. High CT grade and age at presentation ≤ 35 years were associated with a higher risk of pneumothorax in patients with LAM. Postmenopausal status was correlated with a lower risk of pneumothorax. In the historical prospective self-controlled study, the 5-year probability of pneumothorax recurrence was 80% lower in the sirolimus group than in the control group (hazard ratio for pneumothorax recurrence, 0.20; 95% CI, 0.14 to 0.30, P < 0.001 by log-rank test).ConclusionSirolimus reduced the risk of pneumothorax recurrence in LAM patients.

Margin Status Predicts Outcome in Patients with Cutaneous Squamous Cell Carcinoma of the Scalp: The Westmead Hospital Experience

Background/Objectives: An involved or close resection margin in the setting of cutaneous SCC (cSCC) is associated with the risk of developing recurrence. The scalp poses unique anatomical challenges when obtaining adequate resection margins and further treatment may be required. We aimed to investigate the risk of recurrence in patients with scalp cSCCs and the role of adjuvant radiotherapy.&#x0D; Methods: Eligible patients with cSCC of the scalp treated with curative intent at Westmead hospital, Sydney, were identified and patient, tumor and treatment factors analyzed. Patients were categorized based on margin status and analyzed in terms of treatment delivered, local recurrence and survival.&#x0D; Results: In total, 114 patients with a median age of 70 years with the majority (81%) male, were identified with a median follow up of 5.6 years. Following surgery, 52 patients (46%) had clear margins, 62 (54%) had close (≤2mm) or involved margins, with a significant difference in the 5-year disease specific mortality of 20% and 35%, respectively (p=0.05). Twenty-eight patients (25%) underwent surgery and adjuvant radiotherapy, most with a close/involved margin. There was no significant difference in the risk of developing local recurrence between the group of patients in whom a clear margin was obtained and the group in whom the margin was close/involved (p=0.23).&#x0D; Conclusion: Margin status had a significant impact on disease specific mortality, but was not associated with the risk of developing local recurrence. The addition of adjuvant radiotherapy in select high-risk patients may improve outcome although this was not demonstrated in our study.

Prognostic impact of examined mediastinal lymph node count in clinical N0 non-small cell lung cancer.

The number of examined mediastinal lymph nodes (mLNs) could represent the quality of mediastinal lymphadenectomy for non-small cell lung cancer (NSCLC). This study aimed to evaluate the prognostic impact of the number of examined individual mLNs in patients with resectable NSCLC. We retrospectively evaluated 1420 patients with clinical stage IA-IIB, N0 NSCLC who underwent complete resection by lobectomy, which involved hilar and mLN dissection, between 2008 and 2016. We investigated the threshold number of examined mLNs that had prognostic significance and evaluated their effects on the risk of mLN recurrence. In a respective multivariable analysis according to the number of examined mLNs, examining ≥3 mLNs [reference (ref.) mLNs ≤2] achieved statistical significance and had the best prognosis (hazard ratio, 0.68; P = 0.013). In the multivariable analyses for each pathological N (pN) stage, ≥3 examined mLNs (ref. mLNs ≤2) were an independent prognostic factor in pN1 disease (hazard ratio, 0.32, P = 0.002), but not in pN0 or pN2 disease. The cumulative incidence of mLN recurrence was significantly lower in patients with ≥3 examined mLNs (ref. mLNs ≤2, hazard ratio, 0.27; P = 0.008) in pN1 disease. Patients with ≥3 examined mLNs had higher upstaging rates to pN2 than those with ≤2 examined mLNs. Examining ≥3 mLNs contributed to a favourable prognosis and low mLN recurrence risk in patients with clinical stage I-II, N0 NSCLC. Our findings can serve as a benchmark for the number of required mLNs to be examined.

A predictive model for recurrence after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC) by using preoperative clinical data and CT characteristics

BackgroundThe overall survival for patients with resectable PDAC following curative surgical resection hasn’t been improved significantly, as a considerable proportion of patients develop recurrence within a year. The purpose of this study was to develop and validate a predictive model to assess recurrence risk in patients with PDAC after upfront surgery by using preoperative clinical data and CT characteristics.MethodsThe predictive model was developed based on a retrospective set of 141 pancreatic cancer patients after surgery. A separate set of 77 patients was used to validate model. Between January 2017 and December 2019, all patients underwent multidetector pancreatic CT and upfront surgery. Univariable and multivariate Cox regression was used to determine the risk factors related to recurrence and then establish a nomogram to estimate the 1-year recurrence probability. The Harrell C-index was employed in evaluating the discrimination and calibration of the model.ResultsA total of 218 patients in this retrospective cohort. A recurrence model in nomogram form was developed with predictors including tumor size (hazard ratio [HR], 1.277; 95% CI 1.098, 1.495; P = 0.002), tumor density in the portal vein phase (HR, 0.598; 95% CI 0.424, 0.844; P = 0.003), peripancreatic infiltration (HR, 4.151; 95% CI 2.077, 8.298; P < 0.001), suspicious metastatic lymph node (HR, 2.561; 95% CI 1.653, 3.967; P < 0.001), Neutrophils/Lymphocytes ratio (HR, 1.111; 95% CI 1.016, 1.215; P = 0.020). The predictive nomogram had good discrimination capability with these predictors with an area under curve at 1 year of 0.84 (95%CI 0.77, 0.91) in the development set and 0.82 (95% CI 0.72, 0.92) and 0.84 (95% CI 0.74, 0.94) in the validation set for two radiologists reading respectively.ConclusionsThe model developed based on preoperative clinical data and CT characteristics of resectable pancreatic ductal adenocarcinoma patients, which can helpfully estimate the recurrence-free survival. It may be a useful tool for clinician to select optimal candidates for upfront surgery or neoadjuvant therapy.

SY19-4 Precision oncology for adjuvant treatment of colon cancer

Accurate prediction of recurrence risk is extremely important for tailoring adjuvant chemotherapy for individual colon cancer patients. To date, some multi-gene assay systems have been developed to evaluate recurrence risk in patients with colon cancer. The 12-gene Recurrence Score assay (Oncotype DX) for colon cancer has been validated in stage II and III colon cancer as well as breast cancer. Another micro array based assay system, 55-gene classifier (55GC) for colon cancer has also been validated in resected stage II and stage III treated with adjuvant chemotherapy in Japan.

The risk of recurrence of breast cancer in the presence of deletion polymorphism of the GSTT1 and GSTM1 genes

Objective: The aim of the study was to establish the relationship between the effectiveness of chemotherapy (CMT) in case of breast cancer and the risk of recurrence with polymorphism of glutathione-S-transferase (GSTT1, GSTM1) genes.Methods: The study involved 132 women having breast cancer diagnosed, aged 23 to 79 years (average age 48 ± 13 years). They received chemotherapy treatment (neoadjuvant (NACMT), adjuvant (ACMT)). The detection of deletion (null) genotypes GSTM1 and GSTT1 was carried out using multiplex PCR followed by analysis of the melting curves of the reaction products.Results: Statistically significant connection between the presence of a null genotype GSTM1-0 and a reduced risk of breast cancer recurrence in patients having stage III BC (RR = 0.721; 95% CI: 0.524-0.992, p = 0.034). At the same time, the precense of GSTT1-0 genotype didn't have statistically significant effect on the risk of recurrence (RR = 0.543; 95% CI: 0.274– 1.077, p = 0.015). However, the tendency of the prevalence of GSTT1 0/0 among patients without recurrnece of breast cancer persisted.Conclusions: The lack of activity of the GSTT1 or GSTM1 enzymes in carriers of null genotypes can lead to a decrease in detoxification capacity and, accordingly, to a longer circulation of active metabolites of medicine and reactive oxygen species. It prolongs the time of exposure of chemotherapy drugs on tumor cells. The functionally active enzymes may increase the risk of breast cancer recurrence due to rapid elimination of drugs.

Predicting Late Recurrence of Atrial Fibrillation After Radiofrequency Ablation in Patients With Atrial Fibrillation: Comparison of C2HEST and HATCH Scores.

ObjectiveThis study was aimed to investigate the risk of recurrence in patients with atrial fibrillation (AF) after radiofrequency ablation and predict risk of recurrence using C2HEST and HATCH scores.MethodsWe retrospectively included 322 patients with AF from Second Hospital of Lanzhou University, and 261 patients were included in the analysis finally. They had AF and were admitted for radiofrequency catheter ablation. We compared the ability of C2HEST and HATCH scores to predict recurrence after radiofrequency ablation of AF. The predictive ability of C2HEST and HATCH scores for AF recurrence was estimated by the area under the receiver operating characteristic curve (AUROC). The difference in receiver operating characteristic curve between the two models was compared using the DeLong test.ResultsOf the 261 patients included in the analysis, 83 (31.6%) patients suffered a late recurrence of AF after radiofrequency ablation. The risk of postoperative recurrence of AF increased with increasing C2HEST and HATCH scores. The AUROC of C2HEST and HATCH scores in predicting postoperative recurrence of AF was 0.773 (95%CI, 0.713–0.833) and 0.801 (95% CI, 0.740–0.861), respectively. There was no significant difference between the two models in their ability to evaluate patients for postoperative recurrence of AF (DeLong test p-value = 0.36). Among the risk factors in both models, hypertension and heart failure (HF) contributed the most to postoperative recurrence after AF, and higher blood pressure and lower cardiac ejection fraction (EF) were associated with a higher risk of recurrence.ConclusionBoth C2HEST and HATCH scores were significantly associated with the risk of late recurrence after radiofrequency ablation of AF. Besides hypertension and HF contributed the most to postoperative recurrence after AF.

The effect of delayed primary treatment initiation on adverse events and recurrence in older head and neck cancer patients

Background and purposeAs a result of rapid tumor growth in head and neck squamous cell carcinoma (HNSCC), delay in treatment initiation can result in tumor progression and inferior outcome. Especially older and frail patients are prone to develop adverse events. The aim of this study was to assess the effect of delay on development of adverse events and recurrence in older HNSCC patients. Materials and methodsThis cohort study with prospectively collected data included all newly diagnosed, curatively treated HNSCC patients (≥60 years) between 2015 and 2017. Time-to-treatment interval and geriatric domains were assessed. Adverse events were defined as postoperative complications (Clavien-Dindo classification) and acute radiation-induced toxicity (Common Terminology Criteria of Adverse Events). Multivariable regression models were performed, using adverse events and recurrence as outcome variables. ResultsA total of 245 patients were included. Median time-to-treatment was 26 days for surgery patients and 40 days for radiotherapy patients (p < 0.001). Delayed treatment initiation was not associated with postoperative complications or acute radiation-induced toxicity.Delay was significantly associated with recurrence risk within two years after treatment initiation in a model adjusted for stage and tumor location in patients treated with initial surgery (HR:4.1, 95%CI:1.2–14.0, p = 0.024). For patients treated with radiotherapy, delay was not significantly associated with recurrence risk. ConclusionDelayed treatment initiation was independently associated with increased recurrence risk in patients treated with initial surgery. Delay was not associated with short-term adverse events. These findings highlight the importance of establishing fast-track care pathways to minimize delays and improve especially long-term outcome.

Clinical N3 as an independent risk factor of recurrence for breast cancer patients achieving pathological complete response and near-pathological complete response after neoadjuvant chemotherapy.

e12619 Background: Although achieving pathological complete response (pCR) and near-pathological complete response (near-pCR) after neoadjuvant chemotherapy (NAC) in breast cancer predicts a better outcome, some patients still experience recurrence. The aim of our study was to analyse the predictive factors of recurrence in the pCR and near-pCR population. Methods: We reviewed 1209 breast cancer patients treated with NAC. A total of 292 patients achieving pCR and near-pCR between January 2010 and April 2021 in the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) were included in our analysis. pCR was defined as ypT0N0/ypTisN0. Near-pCR was defined as ypT1mi/1a/1bN0 or ypT0/isN1mi. The Kaplan-Meier method with the log rank test was used to estimate recurrence analysis. Results: Of the 292 patients,173 were pCR and 119 were near-pCR. The median age was 46 years (range 23-75 years). The predominant tumor subtype was human epidermal growth factor receptor type 2 (HER2) positive (49.0%) and triple-negative breast cancer (TNBC) (30.8%). The median duration of follow-up was 53 months (range 9-138 months). A total of 16 (8.9%) patients developed recurrence, with 9 (5.2%) in the pCR group and 16 (13.4%) in the near-pCR group. The vast majority of recurrence occurred within 36 months from onset of NAC. The 5-year recurrence-free survival (RFS) rate of patients achieving pCR was significantly higher than that of patients achieving near-pCR (94.6% vs.85.6%, P=0.008). Clinical N3 (cN3) before NAC was an independent factor of higher risk for recurrence in patients who achieved pCR ( P=0.003) and near-pCR ( P=0.036). Tumor size before NAC, subtype of breast cancer and chemotherapy regimens showed no significant association with RFS both for patients who achieved pCR and near-pCR ( P ≥0.05). Conclusions: cN3 before NAC was an independent factor of higher risk for recurrence in patients who achieved pCR and near-pCR. It is worthwhile to monitor closely for patients with cN3, especially in the first 3 years.

Adjuvant abemaciclib for high-risk early breast cancer (EBC): Factors increasing the rate of treatment discontinuations in monarchE.

527 Background: Adjuvant abemaciclib plus endocrine therapy (ET) demonstrated clinically meaningful improvement in reducing the risk of recurrence in patients (pts) with HR+, HER2– high risk EBC. In monarchE, 25.6% pts discontinued abemaciclib before completing the 2-year treatment period due to reasons other than recurrence. This exploratory analysis evaluates the impact of baseline factors on time to discontinuation for abemaciclib-treated patients with an aim to identify pts at higher risk of discontinuation. Methods: Time to discontinuation(TTD) was defined as time from first dose to the discontinuation of abemaciclib or all treatment due to reasons other than recurrence. These exploratory analyses evaluated the association between TTD and baseline demographics, disease characteristics, and the extent of pre-existing medical comorbidities. Factors with p-value &lt;0.05 in the univariate Cox model were considered as potentially associated with TTD and then fitted into a multivariate Cox model with stepwise variable selection, with entry and retaining p-value threshold of 0.05. Discontinuation rates at selected timepoints (6-month, 12-month, 18-month, 24-month) within each subgroup were estimated using the Kaplan-Meier method. Results: The following variables were significantly associated with higher risk of discontinuation in the multivariate model: Age ≥65 yr, enrolled in North America or EU, ECOG PS=1, post-menopausal, 1-3 positive nodes, or 4 or more pre-existing comorbidities. The majority of discontinuations occurred within the first 6 months of the treatment period; thus, this timepoint was selected to estimate discontinuation rates for factors independently associated with TTD (Table). Complete results on discontinuation rates at other timepoints will be reported in the presentation. Conclusions: This exploratory analysis identified several factors associated with a greater risk of discontinuation. These results illustrate the importance of close monitoring and dose adjustments early on, particularly for patients with an increased risk of discontinuation prior to completing the 2-yr treatment period of abemaciclib. Clinical trial information: NCT03155997. [Table: see text]

Clinical Study on Dynamic Detection of Minimal Residual Disease in Acute Myeloid Leukemia by Multiparameter Flow Cytometry

To investigate the prognostic significance of dynamic detection of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) by 8-color flow cytometry. MRD of 282 AML patients who achieved remission after initial therapy was detected by 8-color flow cytometry. MRD threshold for predicting recurrence was determined by receiver operating characteristic (ROC) curve, and time from MRD-positive to clinical recurrence was analyzed. The differences in overall survival (OS) time and relapse-free survival (RFS) time of patients with different MRD-changes were compared, and the related factors of recurrence in patients with MRD-negative were analyzed by univariate and logistic regression analysis. ROC curve determined that the MFC-MRD threshold for predicting the recurrence of AML was 0.105%, and the recurrence rate of MRD-positive patients was significantly higher than that of MRD-negative patients [52.45% (75/143 cases) vs 35.97% (50/139 cases), P=0.005]. The patients in MRD persistent positive group and negative to positive group recurred earlier than those in positive to negative group and negative-positive fluctuation group (P<0.005). Survival analysis showed that OS and RFS time of patients with MRD persistent positive were significantly shorter than those of patients with MRD persistent negative, positive to negative, and negative-positive fluctuation (P<0.005). There was no significant difference in OS and RFS between MRD negative to positive group and MRD persistent positive group (P>0.005), either between MRD persistent negative group and MRD positive to negative group (P>0.005). Among 139 MRD-negative patients, 50 recurred. Univariate and logistic regression analysis showed that the risk of recurrence increased with the increase of white blood cells level (95%CI: 1.000-1.013, P=0.045). The risk of recurrence in patients without hematopoietic stem cell transplantation (HSCT) was 9.694 times higher than that in patients who received HSCT (95%CI: 1.720-54.651, P=0.010), and in the high-risk group was 5.848 times higher than that in the low-risk group (95%CI: 1.418-24.121, P=0.015). The prognosis of AML patients with different MRD changes is significantly different. No matter MRD-positive or MRD-negative at the initial remission, dynamic detection of MRD after treatment is more helpful to accurately guide treatment.

Efficacy and safety of "second adjuvant" therapy with BRAF/MEK inhibitors after resection of recurrent melanoma following adjuvant PD-1–based immunotherapy.

9575 Background: Both anti-PD-1 antibodies and BRAK/MEK inhibitors (BRAF/MEKi) reduce the risk of recurrence for patients with resected stage III melanoma. For patients with V600 BRAF-mutated melanoma who recur with resectable disease on or after adjuvant, many may be suitable for ‘second adjuvant' treatment after surgery. We sought to examine the efficacy and safety of ‘second adjuvant’ BRAF/MEKi in patients who recurred despite adjuvant PD-1 based immunotherapy. Methods: Patients with V600 BRAF-mutated melanoma treated with adjuvant PD-1 based immunotherapy for resected stage III/IV disease who recurred, underwent resection of recurrence and were then treated with adjuvant BRAF/MEKi were identified retrospectively from 13 centres. Demographics, disease characteristics, treatment details, and outcome data were examined. Results: 55 patients were included; median age at commencement of PD-1 was 53y, most were V600E (91%) and had IIIB (42%) or IIIC (44%) melanoma. PD-1 based adjuvant therapy included nivolumab (71%), nivolumab plus ipilimumab (14%), pembrolizumab (13%) and pembrolizumab plus mRNA-4157 vaccine (2%). Patients had initial recurrence after mean 8.4 months (95% CI 7.4-10.6), mainly while on treatment (65%), in regional nodes (42%), in-transit metastases (ITMs; 38%), both regional nodes and ITMs (7%) and distant metastases (13%). Surgical management included CLND (36%), selected nodal resection (11%), ITM resection (33%) and resection of distant metastasis (13%). A minority had adjuvant radiotherapy (17%). Stage at start of second adjuvant BRAF/MEKi included IIIB (29%), IIIC (53%) IIID (4%) and IV (15%). Patients received dabrafenib and trametinib (95%, N = 52) and encorafenib and binimetinib (5%, N = 3). After a median follow up of 21.4 months (19.7-25.4), 17 (31%) patients have recurred again. Mean duration of treatment was 9 months (95% CI 7.4-10.6); 20% ceased for toxicity, 7% for recurrence and 35% were on treatment at last follow up. The most common toxicity was pyrexia (43%) and 21% patients experienced a severe (G3-4) adverse event. Median RFS was 33.4 months (14.3.7-NR) and median DMFS was not reached. At 12 months, 72% (59-88) of patients were recurrence free and 90% (81-100) were free of distant recurrence. For those whose disease recurred again, most recurred after cessation of second adjuvant BRAF/MEKi (13/17, 76%). 7 (41%) recurred locally and 8 (47%) recurred with new metastatic disease but none had brain metastases. Conclusions: This is the first study examining outcomes of patients receiving second adjuvant targeted therapy for melanoma, after failure of adjuvant PD-1 based immunotherapy. While RFS appears shorter compared to first line trials, second adjuvant treatment with BRAF/MEKi appears safe and active in preventing further recurrence. Further data on sequencing adjuvant therapies are needed.

Whole transcriptome analysis of tumors with discordant oncotype and MammaPrint results in the FLEX trial.

556 Background: Genomic tests, such as MammaPrint (MP) and Oncotype DX Breast Recurrence Score (RS), assess risk of recurrence in patients with early breast cancer (EBC). Using both assays may yield discordant results which leads to uncertainty in treatment recommendations. The assays differ in technology and genes analyzed. RS relies on RT-PCR to query 16 cancer-related genes and 5 controls. MP uses a microarray to query 70 cancer-related genes and 465 normalization controls. Here we explore the genetic basis for discordance by using the FLEX whole transcriptome database to examine differentially expressed genes among patients who received discordant RS and MP results. Methods: Patients with EBC enrolled in the FLEX study (NCT03053193) undergo standard of care MP and BluePrint (BP) tests, and consent to clinically annotated whole transcriptome data collection. MP stratifies risk of recurrence as Low risk and High. RS classifies patients as Low Risk (RS 0-10), Intermediate (RS 11-25), and High Risk (RS 26-100). Due to low representation of BP Basal and BP HER2-type tumors in this data set, we only examined BP Luminal-type tumors (N = 705). We used full genome transcriptomes to compare gene expression among discordant cases. Gene expression data were quantile normalized and analyzed using R package ‘limma’. Genes were considered differentially expressed at a fold change of at least 1.7 and an adjusted p-value of lower than 0.05. To keep the analysis as unbiased as possible, comparisons between RS categories only included tumors within the same MP score range and similarly comparisons of MP categories only contained tumors within the same RS score range. Results: The comparisons between discordant cases, their numbers and the amount of differentially expressed genes (DEGs) are shown below. Sample sizes are shown in parentheses. Of the 49 DEGs found in the RS Intermediate group, several are associated with increased proliferation or increased metastatic potential. SCUBE2 and MMP9 were among the 49 genes and are among the 70-genes assayed by MP. Conclusions: The comparisons highlight the genomic diversity of the RS Intermediate (RS11-25) group, as seen with the high number of DEGs. MP separates cases into more genomically distinct categories, as reflected by fewer DEGs. Clinical trial information: NCT03053193. [Table: see text]

Circulating tumor DNA (ctDNA) as a minimal residual disease (MRD) assessment and recurrence risk in patients undergoing curative intent resection with or without adjuvant chemotherapy in colorectal cancer: A systematic review and meta-analysis.

3623 Background: Minimal residual disease (MRD) assessment may effectively detect cure in patients with colorectal cancer (CRC). Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for MRD in patients. Recent studies have shown the ability to detect MRD using ctDNA assay to assess recurrence risk and patient selection for adjuvant chemotherapy. We performed a systematic review and metanalysis of post operative ctDNA in Stage I-IV (oligometastatic) CRC patients after curative intent resection with or without adjuvant chemotherapy. Methods: We searched PubMed/Medline, EMBASE, Web of Science, Cochrane Library, and Google from inception to February 3, 2022 using keywords related to colorectal cancer, ctDNA, and MRD. The search also includes paper and conference presentations. The search resulted in 427 studies after removing the duplicates. Data were extracted to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. Results: After the initial abstract screening, 48 studies were identified. The final review led to the inclusion of 27 studies representing 3459 patients with evaluable ctDNA, with 623 having +ve post-surgery ctDNA levels. Seven studies had analyses of patients specifically with oligometastatic disease, the rest 20 studies subdivided within stages I-III. The pooled HR for RFS in post-surgical ctDNA +ve vs -ve patients in all stages was 7.16 (95% CI 6.12-8.36) p &lt;0.00001. Subgroup analysis revealed pooled HR = 8.27 (95% CI 6.16-11.09) and 6.07 (95% CI 4.54-8.13) for stage I-III and IV CRC, respectively. Only 11 studies did analysis for post adjuvant chemotherapy patients based on ctDNA status. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA +ve versus -ve patients in all stages was 12.40 (95% CI 9.24-16.64) p &lt;0.00001. Subgroup analysis revealed pooled HR = 13.95 (95% CI 9.08-21.43) and 11.39 (95% CI 5.99-21.66) for stage I-III and IV CRC, respectively. Conclusions: This is the largest and most current meta-analysis done on ctDNA levels as MRD assessment in CRC. Our analysis emphasizes that post operative ctDNA is a strong prognostic marker of RFS. Based on our results ctDNA can be a significant and independent predictor of RFS. Several ctDNA-based randomized adjuvant trials are ongoing internationally to confirm the clinical utility of ctDNA in colorectal cancer. [Table: see text]

PEC-PRO: A new prognostic score from a series of 93 patients with localized perivascular epithelioid cell neoplasms (PEComas) treated with curative intent.

11571 Background: Perivascular Epithelioid Cell Neoplasms (PEComas) encompass a heterogeneous family of mesenchymal tumors. The current understanding of their natural history is limited. Previously described clinicopathological factors aimed to define benign or malignant variants, but there is a lack of prognostic factors associated with recurrence of surgically resected tumors, preventing the development of a prognostic score to better optimize patient’s management. Methods: This is a retrospective analysis of clinicopathological features from patients diagnosed with a localized PEComa, within all centers from the French Sarcoma network and one center in Belgium. We analyzed 12 clinicopathological factors in a Cox proportional hazard framework to derive a multivariate prognostic risk model for progression-free survival (PFS). We built the PEComa PROgnostic score (PEC-PRO) ranging from 0 to 5, based on the coefficients of the multivariate model. Three different prognostic groups were identified: low risk (score = 0), intermediate risk (score = 1) and high risk (score ≥2). Results: Ninety-three patients were analyzed with a median follow-up of 46 months (range, 3-253). At diagnosis, the median age was 54 years (range, 13-84), with female predominance (72%). Most common primary locations were uterus (n = 15;16%) and kidney (n = 15;16%). Median tumor size was 6.2 cm (range, 0.8-30). Among patients with reported surgical margins, 64 (73%) and 23 (27%) had R0 and R1-2 margins, respectively. The median PFS was 26 months (IC95, 2.9-124.4), with 1- and 5-year overall survival (OS) rates of 95.7% and 69.9%, respectively, while the median OS was not reached. Using univariate analyses, male gender, primary tumor size &gt; 5 cm, high nuclear grade and cellularity, high mitotic rate &gt; 1/50 HPF, necrosis, vascular invasion, nodal invasion, and R1-2 margins were associated with a shorter PFS. Among those, male gender (HR = 2.88; IC95 1.12-7.411, p = 0.03), vascular invasion (HR = 3.14; IC95 1.10-8.96, p = 0.034), necrosis (HR = 3.93; IC95 1.35-11.47, p = 0.015), and R1-2 margins (HR 4.47; IC95 1.60-12.46, p = 0.007) remained associated with PFS in the multivariate analysis and were included in the multivariate model. Median PFS in patients with high PEC-PRO score was 16 months as compared to 104 months and not reached for patients with intermediate and low PEC-PRO scores, respectively (p &lt; 0.001). We also confirmed the prognostic relevance of the PEC-PRO score in terms of OS. Conclusions: Using a weighted combination of clinicopathological features, the PEC-PRO score reliably predicts the post-operative recurrence risk in patients with localized PEComas. It has the potential to better improve follow-up strategies and personalize adjuvant treatments. The findings of this retrospective analysis require validation in a prospective trial.

28-gene classifier model for prediction of local recurrence and distant metastasis risk in HER-2 positive operable breast cancer.

e13018 Background: Accurate prediction of postoperative recurrence risk is very important for the formulation of appropriate treatment for breast cancer patients. However, traditional clinicopathological indicators cannot accurately assess the recurrence risk of patients. We aimed to build a novel gene-clinical variable model, which included 28 genetic profiles and clinical variable information, to assess the risk of recurrence in a more individualized and accurate manner. Methods: We retrospectively included a cohort of operable HER-2 positive breast cancer patients treated in Cancer Hospital of the Chinese Academy of Medical Sciences from 2010 to 2016. The genetic and clinical data were used to train and validate the 28-gene classifier model in predicting local recurrence and distant metastasis risk. Results: A total of 260 HER-2 positive breast cancer patients were Included in the study. All patients received standard adjuvant chemotherapy and routine targeted therapy after mastectomy. All patients were followed up for a median of 60.4 months for disease recurrence. Among them, 21 patients had distant metastasis events and 18 patients had local recurrence events. We used the 28 gene-clinical variable model to classify 260 patients into high- and low-risk groups. Kaplan-Meyer survival curves were used to compare the prognostic difference of DFS into high- and low- risk groups. Conclusions: 28 gene-clinical variable model may be a reliable toll to predict local recurrence and distant metastasis risk in HER-2 positive operable breast cancer.

The time-dependent changes in serum carcinoembryonic antigen impact on posthepatectomy outcomes of colorectal liver metastasis

BackgroundOnly a few studies have examined the impact of carcinoembryonic antigen variation in patients before and after curative resection of colorectal liver metastasis . This study examined the correlation between carcinoembryonic antigen levels and patient prognosis. MethodsPatients who underwent curative resection for colorectal liver metastasis between 2000 and 2017 were enrolled. This study examined patients with high preoperative carcinoembryonic antigen levels that normalized after resection of colorectal liver metastasis and the correlation between prognosis and time-dependent changes in carcinoembryonic antigen levels. The similarity in the risk of recurrence in patients with normal preoperative carcinoembryonic antigen levels was evaluated. ResultsA total of 143 consecutive patients were included in the study cohort and classified into the normal preoperative (46 patients), normalized postoperative (57 patients), and elevated preoperative and postoperative (40 patients) carcinoembryonic antigen groups. All clinicopathologic characteristics were comparable between patients grouped according to carcinoembryonic antigen levels. The 5-year disease-free survival and overall survival rates for all patients were 30.4% and 56.0%, respectively. Multivariate analysis confirmed that elevated preoperative and postoperative carcinoembryonic antigen levels (hazard ratio = 1.73, 95% confidence interval: 1.04–2.87) were independently associated with poor disease-free survival; normalization of postoperative carcinoembryonic antigen (hazard ratio = 0.94, 95% confidence interval: 0.57–1.53) was statistically indistinguishable from normal preoperative carcinoembryonic antigen levels. The risk of recurrence was similar to that of patients with normal preoperative carcinoembryonic antigen levels ConclusionPatients with elevated preoperative carcinoembryonic antigen levels that normalized after resection of colorectal liver metastasis were not at risk of poor disease-free survival. Elevated carcinoembryonic antigen levels after surgery are independent prognostic factors for disease-free survival.

Methylation site APC112043544 as a potential biomarker for post-transplant hepatocellular carcinoma recurrence.

Objective: To investigate the prognostic value of DNA methylation of tumor suppressor genes for hepatocellular carcinoma (HCC) recurrence after liver transplantation. Methods: APC gene was selected according to The Cancer Genome Atlas dataset. Tumor tissues and clinical data of 85 HCC patients who received a liver transplantation were retrospectively enrolled and next-generation methylation sequencing was performed. Risk factors were determined using the Cox proportional-hazard-regression model. Results: The APC methylation site (chromosome 5, position 112043544) was an independent predictor of post-transplant HCC recurrence. Patients with hyper-methylated APC112043544 experienced superior recurrence-free survival (p=0.021) and had a decreased proportion of microvascular invasion (p=0.017). APC112043544 also predicted recurrence risk in patients beyond selection criteria. Conclusions: APC112043544 methylation may serve as a potential biomarker for post-transplant HCC recurrence.