Residual Disease Group Research Articles

TP53 Signature Can Predict Pathological Response From Neoadjuvant Chemotherapy and Is a Prognostic Factor in Patients With Residual Disease.

The TP53 signature that predicts the mutation status of TP53 has been shown to be a prognostic factor and predictor of neoadjuvant chemotherapy (NAC) response. The current study sought to investigate the utility of the TP53 signature for predicting pathological complete response (pCR) and its prognostic significance among patients with residual disease (RD). The study followed a retrospective cohort study design. Patients with T1-3/N0-1 from a cohort of those with HER2-negative breast cancer who received NAC were selected. Ability to predict pCR was evaluated using odds ratio, positive and negative predictive values, sensitivity, and specificity. Prognostic factors in the RD group were explored using the Cox proportional hazards model with distant recurrence-free survival (DRFS). Four independent cohorts were used for validation. A total of 333 eligible patients were classified into the TP53 mutant signature (n = 154) and wild-type signature (n = 179). Among the molecular and pathological factors, the TP53 signature had the highest predictive power for pCR. In 4 independent cohorts (n = 151, 85, 104, and 67, respectively), pCR rate in TP53 mutant signature group was significantly higher than that in the wild-type group. Univariate and multivariate analyses on DRFS in the RD group identified the TP53 signature and nodal status as independent prognostic factors, with the former having a better hazard ratio than the latter. After comparing DRFS between 3 groups (pCR, RD/TP53 wild-type signature, and RD/TP53 mutant signature groups), the RD/TP53 mutant signature group showed significantly worse prognosis compared with others. The RD/TP53 wild-type signature group did not exhibit inferior DRFS compared with the pCR group. Our results showed that the TP53 mutant signature can predict pCR and that combining pathological response and TP53 mutant signature allows for the identification of subgroups with truly poor prognosis.

Serum squamous cell carcinoma antigen is a predictive factor of outcomes in patients with locally advanced unresectable esophageal squamous cell carcinoma treated by definitive chemoradiotherapy

Aim: Definitive chemoradiotherapy (dCRT) is the standard treatment for locally advanced unresectable esophageal squamous cell carcinoma (LU-ESCC). This study aimed to describe the results of dCRT for T4 ESCC and evaluate the pretherapeutic predictive factors of the outcomes. Methods: A total of 133 patients with T4 ESCC who received dCRT were grouped into those who achieved a complete response (CR) or those who had residual disease (RD). The clinicopathologic variables were compared between the groups and the overall survival (OS) was evaluated. The predictive factor of RD was assessed and the prognostic factor for OS was identified. Results: Among the 133 patients, 31 (23%) achieved CR. The CR group had a significantly better OS than the RD group (89.9 months vs. 10.7 months; hazard ratio = 0.096; 95% confidence interval: 0.05-0.19; P < 0.001). Multivariate analysis showed that a supracarinal tumor (OR = 3.21; P = 0.016), higher pretherapeutic serum SCC-Ag level (> 1.6 ng/mL) (OR = 2.86; P = 0.018), and metastatic node invasion (OR = 3.19; P = 0.048) were independent predictors of RD. The increased level of pretherapeutic serum squamous cell carcinoma antigen (> 1.6 ng/mL) (OR = 1.61; P = 0.022) was an independent predictor of poor survival. Conclusions: Among the patients who underwent dCRT for LU-ESCC, 23% achieved CR, and the long-term outcome of these patients was favorable. Increased levels of pretherapeutic serum squamous cell carcinoma antigen were also found to be predictive of treatment failure.

Residual disease in lymph nodes has no influence on survival in patients with incidental gallbladder cancer - institution experience with literature review.

BackgroundA better appreciation of the course and factors that influence incidental gallbladder cancer (iGBC) is needed to develop treatment strategies aimed to improve outcomes. The purpose of the study was to determine the influence of residual disease in the liver and lymph nodes on overall survival in re-resected patients with iGBC.Patients and methodsPatients undergoing radical re-resection for iGBC from January 2012 to December 2018 were retrospectively identified. Patients with a 5-year follow-up and submitted to complete resection with stage I, II and III disease were analysed. The influence of residual disease (RD) in liver and lymph nodes on survival was assessed using the Kaplan-Meier curves. In addition, the rest of the group was assessed based on type of primary/secondary procedure, number of harvested lymph nodes and RD in liver and/or lymph nodes.ResultsIn this retrospective study 48 out of 58 (83%) patients underwent re-resection. Among the group with a 5-year follow-up (re-operation between 2012–2014), 22 patients out of 28 (79%) were re-resected. Survival analysis showed that patients with no RD in the liver and lymph nodes had statistically significant better 5-year survival than those with RD. Comparing 5-year survival rate in patients with RD in the liver or lymph nodes against no RD group, patients with RD in the liver had statistically significantly worse 5-year survival, while lymph node metastases did not show any statistically significant different in 5-year survival. Besides, a statistically significant better prognosis was found in stage II disease compared to stage III, as expected.ConclusionsThe most important predictors of a 5-year survival in our study were RD in liver and stage of the disease. Lymph node metastases did not have any impact on the overall 5-year survival rate.

Kinetic information from dynamic contrast-enhanced MRI enables prediction of residual cancer burden and prognosis in triple-negative breast cancer: a retrospective study

This study aimed to evaluate the predictions of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for prognosis of triple-negative breast cancer (TNBC), especially with residual disease (RD) after preoperative chemotherapy. This retrospective analysis included 74 TNBC patients who received preoperative chemotherapy. DCE-MRI findings from three timepoints were examined: at diagnosis (MRIpre), at midpoint (MRImid) and after chemotherapy (MRIpost). These findings included cancer lesion size, washout index (WI) as a kinetic parameter using the difference in signal intensity between early and delayed phases, and time-signal intensity curve types. Distant disease-free survival was analysed using the log-rank test to compare RD group with and without a fast-washout curve. The diagnostic performance of DCE-MRI findings, including positive predictive value (PPV) for pathological responses, was also calculated. RD without fast washout curve was a significantly better prognostic factor, both at MRImid and MRIpost (hazard ratio = 0.092, 0.098, p < 0.05). PPV for pathological complete remission at MRImid was 76.7% by the cut-off point at negative WI value or lesion size = 0, and 66.7% at lesion size = 0. WI and curve types derived from DCE-MRI at the midpoint of preoperative chemotherapy can help not only assess tumour response but also predict prognosis.

Anatomic location of residual disease after initial cholecystectomy independently determines outcomes after re-resection for incidental gallbladder cancer.

This study aimed to elucidate the impact of anatomic location of residual disease (RD) after initial cholecystectomy on survival following re-resection of incidental gallbladder cancer (IGBC). Patients with pT2 or pT3 gallbladder cancer (36 with IGBC and 171 with non-IGBC) who underwent resection were analyzed. Patients with IGBC were classified as follows according to the anatomic location of RD after initial cholecystectomy: no RD (group 1); RD in the gallbladder bed, stump of the cystic duct, and/or regional lymph nodes (group 2); and RD in the extrahepatic bile duct and/or distant sites (group 3). Timing of resection (IGBC vs. non-IGBC) did not affect survival in either multivariate or propensity score matching analysis. RD was found in 16 (44.4%) of the 36 patients with IGBC; R0 resection following re-resection was achieved in 32 patients (88.9%). Overall survival (OS) following re-resection was worse in group 3 (n = 7; 5-year OS, 14.3%) than in group 2 (n = 9; 5-year OS, 55.6%) (p = 0.035) or in group 1 (n = 20; 5-year OS, 88.7%) (p < 0.001). There was no survival difference between groups 1 and 2 (p = 0.256). Anatomic location of RD was independently associated with OS (group 2, HR 2.425, p = 0.223; group 3, HR 9.627, p = 0.024). The anatomic location of RD independently predicts survival following re-resection, which is effective for locoregional disease control in IGBC, similar to resection for non-IGBC. Not all patients with RD have poor survival following re-resection for IGBC.

Residual cancer burden index and tumor-infiltrating lymphocyte subtypes in triple-negative breast cancer after neoadjuvant chemotherapy.

There is a need to refine the prognosis of triple-negative breast cancer (TNBC) patients after neoadjuvant chemotherapy (NAC) and to study the influence of the tumor microenvironment. We evaluated the prognostic value of pathological and immune markers in TNBC with residual disease (RD) after NAC. In a series of 186 TNBC patients treated by NAC, we assessed the prognostic value of the Residual Cancer Burden (RCB) index. In 109 patients with RD, we studied the impact of clinicopathological features and tumor immune response in the residual tumor on overall survival (OS) and distant recurrence-free interval (DRFI). In the whole group, the OS and DRFI, at 3years, were statistically different between the different classes of RCB (P = 0.0004 and P < 0.0001, respectively). In univariate analysis of the RD group, low RCB index and high ratios of stromal tumor-infiltrating lymphocytes (TILs), CD3 + TILs, CD4 + TILs, CD8 + TILs, and IDO1-positive cells were significant favorable prognostic factors for DRFI at 3years. In the final multivariate model, CD4 + TILs and RCB index showed a statistically independent prognostic significance for DRFI [Hazard Ratio (HR) 2.88 (95%CI 1.34-6.17), P = 0.007 and HR 12.04 (95%CI 2.78-52.23, P < 0.0001), respectively]. The CD4 + TIL levels influenced survival in the different RCB classes with a significant effect observed in RCB-II and RCB-III classes (P = 0.05 and P = 0.05, respectively). These results suggest that the combination of pathological (RCB index) and tumor micro-environmental features (CD4 + TILs) help refining the prognosis of TNBC patients with RD following NAC.

Abstract P6-17-04: 3-year relapse-free survival of stage II-III HER2-neu positive breast cancer treated with pertuzumab and trastuzumab-containing neoadjuvant therapy compared to trastuzumab-containing therapy

Abstract Background: Pertuzumab (P) in combination with trastuzumab (H) based chemotherapy is FDA-approved as a standard neoadjuvant treatment for patients with clinical stage II-III HER2-positive (HER2+) breast cancer (BC). The goal of this study was to evaluate the pathologic complete response (pCR) rate for neoadjuvant HP-containing regimens compared to H-containing regimens and report the 3-year relapse-free survival (RFS) for patients who had a pCR compared to those with residual disease (RD). Methods: All patients with stage II-III non-inflammatory HER2+ BC who received neoadjuvant H-containing or HP-containing therapy and underwent definitive breast and axillary surgery were identified from 2005 to 2016 through an institutional database. Medical records were examined for patient demographics, breast cancer stage, pathology results, surgical outcomes, and treatment details. pCR was defined as ypT0/is, ypN0. RFS was defined as the interval from surgery to date of last followup or death from any cause. Descriptive statistics, Cox proportional hazards, and Kaplan-Meier estimates were used for statistical analysis. Results: Patient characteristics and results by pCR or RD status are shown in the table below. The median age was 51 (22-84) years for the HP group and 50 (21-87) years for the H group. The median follow-up time was 1.9 (0-4.2) years for the HP group and 5.3 (0.1-12) years for the H group. For the HP group, the 3-year RFS was 98% (95% CI: 95, 100) for the pCR group and 90% (95% CI: 83, 97) for the RD group; HR 0.17 (0.04, 0.82), p=0.012. For the H group, the 3-year RFS was 91% (95% CI: 88,94) for the pCR group and 75% (95% CI: 71-79) for the RD group; HR 0.31 (0.22, 0.44), p&amp;lt;0.0001. Among the 520 patients who achieved pCR and the 502 patients who had RD, the effect of HP vs. H was statistically significant (pCR: HR 0.24 (0.06, 1.00); p=0.015) (no pCR: HR 0.46 (0.22, 0.94); p=0.017). Conclusion: Patients who achieve pCR have an improved 3-year RFS compared to patients who have RD. Treatment with HP-containing neoadjuvant regimens is associated with a high 3-year RFS. VariableHP (n=215)H (n=807) pCR n=121RD n=94pCR n=399RD n= 408Age at Diagnosis&amp;lt;5043%46%46%51% ≥5057%54%54%49%Menopausal StatusPremenopausal46%50%53%57% Postmenopausal54%50%47%43%Clinical Stage at DiagnosisIIA40%29%34%29% IIB29%31%23%28% IIIA14%15%17%16% IIIB0%5%5%9% IIIC17%20%21%18%Clinical Nodal StatusNode (+)63%76%69%73% Node (-)37%24%31%27%Nuclear Grade1II25%32%22%28% III75%65%78%72%HR statusHR(+)52%74%52%67% HR(-)48%26%48%33%Adjuvant therapyTrastuzumab88%80%100%100% Trastuzumab and Pertuzumab3%5%0%0% Unknown9%15%20%0%11 patient in the HP pCR group had nuclear grade 1; 2 patients in the HP RD group had nuclear grade 1 tumors 2 2 patients received adjuvant TDM-1 on the NSABP B50 protocol Citation Format: Murthy RK, Raghavendra AS, Hess KR, Barcenas CH, Lim B, Moulder SL, Giordano SH, Mittendorf EA, Thompson A, Ueno NT, Valero V, Litton JK, Tripathy D, Chavez-Macgregor M. 3-year relapse-free survival of stage II-III HER2-neu positive breast cancer treated with pertuzumab and trastuzumab-containing neoadjuvant therapy compared to trastuzumab-containing therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-04.