Prognostic Factor For Relapse-free Survival Research Articles

Features and prognostic significance of soluble TIM-3 and its ligands Gal-9 and CEACAM1 levels in the diagnostic bone marrows of adult acute myeloid leukemia patients.

Prognostic significance of soluble immune checkpoint molecule TIM-3 and its ligands in the plasma has been illustrated in various solid tumors, but such study in newly diagnosed acute myeloid leukemia (AML) remains absent. Soluble TIM-3, Gal-9 and CEACAM1 levels in the bone marrow plasma samples collected from 90 adult AML patients at diagnosis and 12 healthy donors were measured by enzyme-linked immunosorbent assays (ELISA), and 16 AML patients were simultaneously tested cell membrane TIM-3 expression by multi-color flow cytometry. AML patients had significantly elevated soluble TIM-3 levels and similar soluble Gal-9 and CEACAM1 levels compared with healthy donors (p = 0.0003, 0.26 and 0.96). In the whole cohort, high soluble TIM-3 level was the sole independent adverse prognostic factor for relapse-free survival (RFS) (p = 0.0060), and it together with adverse ELN genetic risk were independent poor prognostic factors for event-free survival (EFS) (p = 0.0030 and 0.0040); High soluble CEACAM1 level were significantly related to lower RFS (p = 0.028). In addition, high soluble Gal-9 level had significant association with lower RFS in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the first complete remission (p = 0.037). Furthermore, soluble TIM-3 level tended to have positive correlation with the percentage of non-blast myeloid TIM-3+ cells in nucleated cells in AML (r = 0.48, p = 0.073). Therefore, the high soluble TIM-3 level in the diagnostic BM plasma predicted poor outcome in adult AML patients, and high sGal-9 level was associated with relapse after allo-HSCT.

The prognostic value of lymph node response to neoadjuvant therapy among breast cancer subtypes

Objectives. The aim of this study was to assess the prognostic value of persistent node involvement after neoadjuvant chemotherapy among breast cancer subtypes. Materials and methods. A total of 258 patients with T1-T4 and N0-N3 breast cancer treated by neoadjuvant chemotherapy followed by tumor excision and axillary lymph-node dissection between January 2015 and December 2019 were selected from the Coltea Clinical Hospital database and retrospectively evaluated. Association between nodal involvement (ypN) binned into four classes (0, 1-3, 4-9 and >10), relapse free-survival and overall survival among the whole population and according to breast cancer subtypes was analyzed using Statistical Package for Social Science Version 29.0.2.0. Outcomes. After a median follow-up of 20.7 months (range 1-97 months) post neoadjuvant chemotherapy nodal involvement was significantly associated with disease free survival in the whole population (X2(3)= 23.161, p <.001) and between breast cancer subgroups (X2(3) = 27.871, p= <.001). After univariate cox regression analyses by breast cancer subtypes nodal involvement was statistically significant only in the Luminal B(HER-) (X2(3)=14.867, p=.002) and triple-negative breast cancer (X2(3)= 9.867, p=.020). In Luminal B(HER2-) breast cancers all nodal involvement subgroups were associated with impaired relapse free survival compared to ypN0 tumors (1-3 nodes, HR= 4.871, 95%CI [1.32-17.94], p=.017; 4-9 nodes, HR=5.126, 95%CI [1.341-19.59], p=.017; >10 nodes, HR=8.744, 95%CI [2.379-32.13], p=.001). In triple negative breast cancers, relapse-free survival was associated with an adverse prognosis in patients with more than 10 nodes involved when compared with ypN0 (HR=16.57, 95%CI [3.25-84.30], p=<.001). There was no statistically significant association in the univariate cox regression analyze between post neoadjuvant chemotherapy nodal involvement and overall survival neither in the whole population (X2(3)=.992, p=.803) nor among breast subtypes (X2(3)=1.191, p= .779). Kaplan Meier analyze of RFS adjusted for BC subtype showed a statistically significant relapse rate in all groups (1-3 (p=.035), 4-9(p=<.001), >10 (p=<.001)) compared with ypN0 group. Kaplan Meier overall survival analyze showed no statistical difference in survival among node groups. Conclusions. Post neoadjuvant chemotherapy lymph node status in breast cancer subtypes represents an important prognostic factor of relapse-free survival and the prognostic value of residual axillary disease should be interpreted according to breast cancer subtype.

Tumor-infiltrating lymphocytes in patients undergoing esophagectomy following neoadjuvant DCF therapy.

Accumulating evidence suggests that expression levels of tumor-infiltrating (TI) cells may play a prognostic role in patients with esophageal cancer who have undergone esophagectomy. However, its effect on patients undergoing neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy followed by esophagectomy for esophageal squamous cell carcinoma (ESCC) remains unclear. Therefore, this study aimed to elucidate the prognostic impact of TI cells in patients who underwent esophagectomy following neoadjuvant DCF therapy. Overall, 81 patients with ESCC who underwent curative esophagectomy following neoadjuvant DCF therapy were included. The number of TI CD8+ cells was determined using light microscopy at ×400 in tumor invasive margins. Receiver operative characteristic curve was used to determine the cutoff values for mortality for continuous variables; the patients were separated into high and low TI CD8+ cell groups and their backgrounds and clinical outcomes were compared. Overall and relapse-free survival were significantly worse in the TI CD8+-low group than that in the TI CD8+-high group (p < 0.01). Multivariate analysis revealed that positive ypN (hazard ratio [HR], 3.12; 95% confidence interval [CI], 1.08-9.02) and low TI CD8+ cell levels (HR, 2.77; 95% CI, 1.31-5.85) were independent prognostic factors for overall survival. Furthermore, positive venous invasion (HR, 2.63; 95% CI, 1.29-5.35) and low TI CD8+ cell levels (HR, 2.77; 95% CI, 1.70-5.46) were significant prognostic factors for relapse-free survival. Low TI CD8+ cell level was a prominent prognostic factor for patients with ESCC undergoing neoadjuvant DCF therapy followed by esophagectomy.

Tumor vascularity on contrast-enhanced computed tomography as a predictive marker of metastatic potential for small nonfunctioning pancreatic neuroendocrine tumors

BackgroundAlthough surgical resection is generally suggested for nonfunctioning pancreatic neuroendocrine tumors, observation can be proposed for carefully selected patients with small tumors. However, the indications for observation remain unclear. MethodsThis retrospective study included 77 patients with nonfunctioning pancreatic neuroendocrine tumors, including small tumors (≤2.0 cm, n = 41), who received pancreatectomy. The ratio of the mean computed tomography value of a tumor in the late arterial/equilibrium phase (computed tomography a/e ratio) was used to evaluate tumor vascularity. Pathologic examinations of small tumors were conducted. The associations among the computed tomography a/e ratio, pathologic findings, and survival outcomes were investigated. ResultsSmall tumors were pathologically categorized by the degree of fibrosis as follows: medullary (n = 20), intermediate (n = 11), and fibrotic (n = 10). The fibrotic type had significantly lower computed tomography a/e ratios than the medullary type (median, 1.42 vs 2.03, P < .001). The median number of vessels with microscopic venous invasion was significantly higher in the fibrotic type than in the medullary type (4.5 vs 0.0, P < .001). The cutoff value of the computed tomography a/e ratio for predicting microscopic venous invasion was determined to be 1.54 by the receiver operating characteristic curve (area under the curve, 0.832; sensitivity, 80.0%; specificity, 83.9%; accuracy, 82.9%). Microscopic venous invasion was an independent prognostic factor for relapse-free survival in overall patients (hazard ratio 5.18, P = .017). ConclusionThe computed tomography a/e ratio may be a useful predictor of the metastatic potential of nonfunctioning pancreatic neuroendocrine tumors and may help decide the indications of observation for small nonfunctioning pancreatic neuroendocrine tumors.

Controlling Nutritional Status (CONUT) score as a prognostic marker for gastrointestinal stromal tumours.

The Controlling Nutritional Status (CONUT) score, regarded as the effective indicator of patient nutrition, has been demonstrated to be related to prognosis of numerous tumours. Nevertheless, the significance of CONUT for gastrointestinal stromal tumour (GIST) remains unclear. This study intended to clarify the association between CONUT and the prognosis of GISTs. Three hundred and fifty-five patients with GISTs undergoing surgical resection at our center were retrospectively assessed. Receiver operating characteristic curve analysis was used to help determine the cut-off value of CONUT score. Relapse-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier curve analysis. Prognostic factors for RFS and OS were examined by Cox proportional hazards models. A total of 355 patients were enrolled in this study. Areas under the curve (AUC) were 0.638 for CONUT score, and the cut-off value of CONUT was shown to be three. Kaplan-Meier curve analysis showed that high CONUT score was linked to poorer RFS and OS. Univariate and multivariate analyses ultimately revealed that CONUT was a risk factor for RFS and OS, independent of demographics and clinicopathological tumour characteristics. CONUT score was an effective and novel predictor for prognosis of GIST patients treated with surgery, indicating its potential as a prognostic marker in the overall management.

Survival impact of immediate complete lymph node dissection for Chinese acral and cutaneous melanoma with micrometastasis in sentinel nodes: a retrospective study

Sentinel node biopsy (SNB) has become a critical part of standard surgical treatment for melanoma with no clinical metastatic evidence. However, for patients with a positive sentinel node, the MSLT-II and DeCOG-SLT trials have shown that immediate complete lymph node dissection (CLND) does not bring further survival benefits. There is still an argument among the Chinese population dominated by acral subtypes on whether CLND can be omitted. Thus, this study aims to investigate the impact of immediate CLND on relapse-free survival (RFS) in Chinese melanoma patients with a positive sentinel node. Patients with acral or cutaneous melanoma of clinical Stages I–II who received SNB procedure and were detected with nodal micrometastasis were retrospectively collected at Fudan University Cancer Center (FUSCC) from January 2017 to December 2021. The clinicopathologic features and prognostic factors for RFS were analyzed. Out of 381 patients who received SNB in the past 5 years, 130 (34%) cases with SN micrometastasis detected were included in this study. Ninety-nine patients underwent immediate CLND while the other 31 patients received observation alone. Among patients who received CLND, the non-SN(NSN)-positive rate was 22.2%. Most of the clinicopathologic factors were balanced well between the CLND and non-CLND groups. However, more patients in the CLND group were detected with BRAF and NRAS mutation (P = 0.006) and received adjuvant PD-1 monotherapy (P = 0.042) as well. There were slightly fewer N1 patients in the CLND group, although the difference did not reach statistical significance (P = 0.075). The study found no significant difference in RFS between the two groups (P = 0.184). Even for patients with the acral subtype (P = 0.925), primary T4 lesion (P = 0.769), or presence of ulceration (P = 0.249), immediate CLND did not bring more survival benefits. Immediate CLND did not bring further RFS benefit for Chinese melanoma patients with SN micrometastasis in real-world clinical practice, even for patients with acral subtype or more tumor burden such as thick Breslow invasion and ulceration.

Long-term Outcomes of Neoadjuvant Chemotherapy With Docetaxel, Cisplatin and S-1 for Stage III Gastric Cancer.

In the previous phase I/II study, we established neoadjuvant chemotherapy (NAC) using bi-weekly docetaxel, cisplatin, and S-1 (DCS) for clinical stage III gastric cancer. This study aimed to clarify long-term outcomes of this treatment. Relapse-free survival (RFS) and overall survival (OS) were calculated by the Kaplan-Meier method and prognostic factors for RFS and OS were identified by univariate analysis. A total of 47 patients with clinical stage III gastric cancer were enrolled in this study. The 5-year RFS and OS rates were 69.8% and 74.3%, respectively, in all registered patients. Moreover, the 5-year OS and RFS rates in patients receiving R0 gastrectomy were 68.0% and 79.4%, respectively. Neutrophil-lymphocyte ratio (NLR) before NAC ≥2.41, prognostic nutritional index (PNI) before NAC ≤50.4, Glasgow prognostic score before NAC classification 2, NLR after NAC ≥1.43, PNI after NAC <48.0, and Grade 1a/1b pathological response significantly worsened RFS. NLR after NAC ≥1.43, PNI before NAC ≤50.4, NLR after NAC ≥1.43, and body weight loss >5 kg after NAC significantly worsened OS. Although bi-weekly DCS therapy as neoadjuvant setting showed acceptable long-term outcomes, poor immune-nutritional status before and after NAC caused worse long-term survival in stage III gastric cancer patients. It is warranted to conduct a well-designed prospective randomized control study to compare long-term outcomes using the bi-weekly DCS regimen between patients with and without immune-nutritional support during peri-NAC.

Potential role of serum vitamin D as a risk factor in pediatric acute lymphoblastic leukemia

Vitamin D deficiency/insufficiency (VDD, VDI) is common in children yet limited experience exists on the association of VDD and hematologic malignancies amongst this population. Therefore, this study aimed to compare serum vitamin D levels in children with acute lymphoblastic leukemia (ALL) and controls. Moreover, vitamin D levels is compared in subjects with and without relapse and evaluated as a prognostic factor for relapse-free survival (RFS). Children with newly diagnosed ALL were recruited as case group. Data on demographic variables as well as the dietary habits were collected by interview. In addition, serum 25(OH)D3 was measured. The case group was followed up for 36 months to assess RFS. Overall, 358 subjects were included in the study (n = 169 cases, n = 189 controls). The mean levels of 25(OH)D3 were 28.05 ± 18.87 and 28.76 ± 12.99 in cases and controls, respectively (p = .68). VDD was found in 15.4% (n = 26) and 4.2% (n = 8) of the case and control groups, respectively (p < .001). Relapse was seen in 18.34% of patients and vitamin D levels of 20 ng/mL or above were associated with longer RFS (p = .044 by log-rank test). In this study, VDD and VDI amongst children with ALL were significantly higher than controls. In addition, lower levels of Vitamin D were associated with increased risk of relapse.

Comparative analysis of adjuvant therapy for stage III BRAF-mut melanoma: A real-world retrospective study from single center in China.

BRAF V600 mutation is the most common oncogenic alternation in melanoma and is visible in around 50% of cutaneous and 10%-15% of acral or mucosal subtypes. Currently, immunotherapy with anti-PD-1 blockade and dual-targeted therapy with Dabrafenib plus trametinib (D + T) target therapy have been approved as adjuvant therapies for Stage III melanoma with BRAF V600 mutation. According to their phase III clinical trials, 3-year recurrence-free survival (RFS) is around 60% for both types of treatment. However, early disease control was slightly more effective with targeted therapy than immunotherapy. With different drug approval deadlines in China, anti-PD1 monotherapy, D + T combination, and Vemurafenib (V) monotherapy have all been used in real clinical practice as adjuvant settings for stage III BRAF-mut melanoma in recent years. We conducted this retrospective study to evaluate the efficacy of different treatments in the Chinese melanoma population. Patients who underwent radical surgery and were diagnosed as Stage III melanoma harboring BRAF V600 mutation by pathological report were retrospectively identified at Fudan University Shanghai Cancer Center from January 2017 to December 2021. Patients with mucosal melanoma, or with follow-up of <6 months, or receiving other adjuvant treatment were excluded. Pearson's chi-squared test or Fisher's exact test was performed for univariable analysis of the different adjuvant groups. Log-rank analysis was used to identify prognostic factors for relapse-free survival (RFS). Ninety-three patients with resected stage III melanoma with BRAF V600E mutation were identified in our study, including 25 patients receiving adjuvant anti-PD-1 immunotherapy (PD-1), 25 receiving adjuvant D + T, 23 receiving V, and 20 patients with observation-only (OBS). There were no statistical differences between treatment groups in baseline characteristics including age, gender, subtypes, primary thickness, ulceration, and nodal involvement. Median relapse-free survival (RFS) time was not reached in the D + T group, 15 months in the V group, 15 months in the PD-1 group, and 10 months in the OBS group, respectively. Compared to OBS, all three other groups showed a tendency to benefit from RFS, while only D + T achieved a statistical difference (p = 0.002). However, compared to D + T, anti-PD-1 monotherapy also showed significantly worse relapse control (p = 0.032). For Chinese stage III melanoma with BRAF mutation, both novel targeted therapy and immunotherapy showed potential benefits in relapse-free survival compared to observation only. Dual-targeted D + T therapy may still be the best choice for adjuvant therapy because anti-PD-1 monotherapy has failed to report equivalent efficacy in real-world practice.

Abstract 1415: The search for molecular biomarkers of relapse in early stage lung adenocarcinoma

Abstract Background: Recurrence cannot be completely prevented by resection or chemotherapy. Molecular biomarkers reported in previous studies have the potential to predict the recurrence risk of lung adenocarcinoma (LUAD), but the results were controversial. Methods: We retrospectively analyzed the molecular characteristics of the 218 early-stage patients with lung adenocarcinoma based on 599 gene-panel target sequencing. All the patients received no neoadjuvant therapy and no EGFR-TKI treatment. The follow-up information on recurrence was complete. Univariate and multivariate analyses were performed using the Cox proportional hazard models to investigate whether the common alterations in EGFR and KRAS were prognostic factors for relapse-free survival(RFS). Results: Among all the enrolled patients, the mutation rates of EGFR and KRAS were 47.6% and 9.3%, respectively. EGFR mutation was not proved to be a prognostics signature of relapse for lung adenocarcinoma regardless univariate and multivariate analysis (univariate: HR, 1.11; 95%CI, 0.82-1.50, P = 0.49; multivariate: HR, 1.18; 95%CI, 0.86-1.64, P = 0.31). The univariate and multivariate analysis identified KRAS alteration as an independent prognostic factor for a shorter RFS (univariate: HR, 1.64; 95%CI, 0.75-2.43, P &amp;lt; 0.05; multivariate: HR, 1.66; 95%CI, 1.19-2.32, P &amp;lt;0.05). For patients in pathological stage I, the patients with KRAS alterations showed significant recurrent risk compared with wild-type patients (HR, 2.02; 95%CI, 1.38-2.96; P &amp;lt;0.0.01). Conclusion: KRAS alterations rather than EGFR alterations were prognostic biomarkers of relapse for early-stage lung adenocarcinoma, especially for patients in pathological stage I. Citation Format: Honggang Ke, Zhongying Jing. The search for molecular biomarkers of relapse in early stage lung adenocarcinoma [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 1415.

Postoperative inflammatory markers predict survival in patients after McKeown esophagectomy for esophageal cancer.

Preoperative C-reactive protein-to-albumin ratio (CAR) and neutrophil-to-lymphocyte ratio (NLR) are correlated with a poor prognosis of various cancers. The significance of postoperative systemic inflammation markers for prognostic stratification of patients with esophageal cancer (EC) has not been established. Therefore, this study aimed to elucidate the impact of postoperative CAR and NLR on survival in patients with EC for prognostic stratification. A total of 235 patients who received curative esophagectomy were analyzed. A Cox proportional hazard model was performed to detect prognostic factors. Multivariate analysis revealed that postoperative CAR ≥ 0.05 (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.01-2.57) and NLR ≥ 3.0 (HR, 2.81; 95% CI, 1.79-4.40) were independent prognostic factors for overall survival. Meanwhile, postoperative CAR ≥ 0.05 (HR, 1.61; 95% CI, 1.07-2.41) and NLR ≥ 3.0 (HR, 1.92; 95% CI, 1.29-2.85) were also significant prognostic factors for relapse-free survival. In addition, the patient group with postoperative CAR ≥ 0.05 and NLR ≥ 3.0 had the worst survival. Postoperative CAR ≥ 0.05 and NLR ≥ 3.0 can predict the poor survival of patients who received curative esophagectomy for EC.

A Novel Frailty Grade Combined with Cachexia Index and Osteopenia in Esophagectomy.

The optimal method for evaluating frailty grade in patients with cancer has not been established in patients undergoing esophagectomy for esophageal cancer. This study aimed to clarify the impact of cachexia index (CXI) and osteopenia on survival in esophagectomized patients for esophageal cancer to develop frailty grade for risk stratification of the prognosis. A total of 239 patients who underwent esophagectomy were analyzed. CXI was calculated as follows: skeletal muscle index × serum albumin/neutrophil-to-lymphocyte ratio. Meanwhile, osteopenia was defined as below the cutoff value of bone mineral density (BMD) calculated by the receiver operating characteristic curve. We evaluated the average Hounsfield unit within a circle in the lower midvertebral core of the 11th thoracic vertebra on preoperative computed tomography as BMD. Multivariate analysis revealed that low CXI (Hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.25-3.04) and osteopenia (HR, 1.86; 95% CI, 1.19-2.93) were independent prognostic factors for overall survival. Meanwhile, low CXI (HR, 1.58; 95% CI, 1.06-2.34) and osteopenia (HR, 1.57; 95% CI, 1.05-2.36) were also significant prognostic factors for relapse-free survival. A frailty grade combined with CXI and osteopenia stratified into four groups by their prognosis. Low CXI and osteopenia predict poor survival in patients undergoing esophagectomy for esophageal cancer. Furthermore, a novel frailty grade combined with CXI and osteopenia stratified the patients into four groups according to their prognosis.

Systemic inflammation score as a preoperative prognostic factor for patients with pT2–T4 resectable gastric cancer: a retrospective study

BackgroundSystemic inflammation has been reported to be associated with cancer progression and metastasis. Systemic inflammation score (SIS), calculated from preoperative serum albumin level and lymphocyte-to-monocyte ratio, has been shown to be a novel prognostic factor for several types of tumors. This study aimed to evaluate the prognostic value of the SIS in patients with pT2–4 resectable gastric cancer (GC).MethodsTotal 97 patients with pT2–4 GC who underwent curative surgery from 322 cases between 2009 and 2015 in Fukushima Medical University Hospital were included. We performed univariate and multivariate analyses to evaluate the usefulness of preoperative SIS and other prognostic factors for relapse-free survival (RFS) and overall survival (OS).ResultsThe higher SIS score was associated with undifferentiated cancer and recurrence. Univariate analysis of RFS identified deeper tumor invasion and higher SIS were significant risk factors and multivariate analysis revealed that both of them were independent prognostic factors for RFS. As for OS, age, tumor invasion, SIS and LNR were significantly correlated with RFS. In multivariate analysis, tumor invasion, SIS and LNR were independent prognostic factors for OS.ConclusionsSIS was an independent prognostic factor for RFS and OS in pT2–4 resectable gastric cancer patients who underwent curative gastrectomy.

Value of the Tumor-Stroma Ratio and Structural Heterogeneity Measured by a Novel Semiautomatic Image Analysis Technique for Predicting Survival in Patients With Colon Cancer.

The tumor-stroma ratio and intratumor stromal heterogeneity have been identified as prognostic factors for several carcinomas. Recent advancements in image analysis technologies and their application to medicine have enabled detailed analysis of clinical data beyond human cognition. This study aimed to investigate the tumor-stroma ratio and intratumor stromal heterogeneity measured using a novel objective and semiautomatic method with image analysis. A retrospective cohort design. Single institution. This study included patients who underwent curative colectomy for colon cancer. The survival analyses between tumor-stroma ratio or intratumor stromal heterogeneity high and low groups after colectomy were assessed in multivariate analyses. Two hundred patients were divided into 2 groups based on the median tumor-stroma ratio and intratumor stromal heterogeneity values. The 5-year overall survival and relapse-free survival rates after colectomy significantly differed between the high and low tumor-stroma ratio or intratumor stromal heterogeneity groups. Multivariate analysis identified low tumor-stroma ratio (HR: 1.90, p = 0.03) and high intratumor stromal heterogeneity (HR: 2.44, p = 0.002) as independent poor prognostic factors for relapse-free survival. The tumor-stroma ratio and intratumor stromal heterogeneity correlated with the duration from curative surgery to recurrence. Furthermore, postoperative recurrence within 2 years was predicted with higher accuracy by using the tumor-stroma ratio or intratumor stromal heterogeneity than by using the pathological stage. In a validation cohort, interobserver agreement was assessed by 2 observers, and Cohen's κ coefficient for the tumor-stroma ratio (κ value: 0.70) and intratumor stromal heterogeneity (κ value: 0.60) revealed a substantial interobserver agreement. This study was limited by its retrospective, single-institution design. Tumor-stroma ratio and intratumor stromal heterogeneity calculated using image analysis software have potential as imaging biomarkers for predicting the survival of patients with colon cancer after colectomy. See Video Abstract at http://links.lww.com/DCR/C114 . ANTECEDENTES:La proporción de estroma tumoral y la heterogeneidad del estroma intratumoral han sido identificados como factores pronósticos para varios tipos de carcinomas. Los avances recientes en cuanto a las tecnologías de análisis de imágenes y sus aplicaciones en la medicina, han permitido un análisis detallado de los datos clínicos más allá del conocimiento humano.OBJETIVO:Investigar la relación del estroma tumoral y la heterogeneidad del estroma intratumoral calculados mediante un nuevo método objetivo y semiautomático para el análisis de imágenes.DISEÑO:Diseño de cohorte retrospectivo.AJUSTES:Institución única.PACIENTES:Pacientes sometidos a colectomía curativa por cáncer de colon.PRINCIPALES MEDIDAS DE RESULTADO:Los análisis de supervivencia entre la relación del estroma tumoral o la heterogeneidad del estroma intratumoral entre los grupos con valores altos y bajos tras la colectomía, fueron evaluados en análisis multivariados.RESULTADOS:Fueron divididos 200 pacientes en dos grupos basados en la mediana de la proporción con respecto a los valores del estroma tumoral y la heterogeneidad del estroma intratumoral. Las tasas de supervivencia general a los 5 años y de supervivencia libre de recaídas después de la colectomía, difirieron significativamente entre los grupos con índice de estroma tumoral o heterogeneidad del estroma intratumoral altos y bajos. El análisis multivariante identificó una proporción de estroma tumoral baja (cociente de riesgos instantáneos: 1.90, p = 0.03) y una heterogeneidad estromal intratumoral alta (cociente de riesgos instantáneos: 2.44, p = 0.002) como factores independientes de mal pronóstico para la supervivencia libre de recaídas. La proporción de estroma tumoral y la heterogeneidad del estroma intratumoral se correlacionaron con la duración de la recurrencia desde la cirugía.Además, la recurrencia posoperatoria dentro de los 2 años se predijo con mayor precisión mediante el uso del índice de estroma tumoral o la heterogeneidad del estroma intratumoral que mediante el uso del estadio patológico. En una cohorte de validación, la concordancia interobservador fue evaluada por dos observadores, y el coeficiente Kappa de Cohen para la proporción de estroma tumoral y la heterogeneidad estromal intratumoral reveló una concordancia interobservador sustancial (valor Kappa: 0.70, 0.60, respectivamente).LIMITACIONES:Este estudio estuvo limitado por su diseño retrospectivo de una sola institución.CONCLUSIONES:La proporción del estroma tumoral y la heterogeneidad del estroma intratumoral calculadas mediante software de análisis de imágenes tienen potencial como biomarcadores de imagen para predecir la supervivencia de los pacientes con cáncer de colon tras la colectomía. Consulte Video Resumen en http://links.lww.com/DCR/C114 . (Traducción-Dr. Osvaldo Gauto ).

Prognostic value of desmoplastic stromal reaction, tumor budding and tumor-stroma ratio in stage II colorectal cancer

Existing high-risk factors are insufficient to accurately predict the postoperative recurrence risk of stage II colorectal cancer (CRC). The discovery of additional prognostic markers may be the key to improving the current status of stage II CRC treatment. The present study aimed to evaluate the relationship among desmoplastic reaction (DR), tumor budding (TBd), the tumor-stroma ratio (TSR) and their prognostic value for relapse-free survival (RFS). In this study, 207 patients with histologically confirmed stage II CRC from January 2012 to August 2018 were retrospectively reviewed from a single center; the cohort was divided into subgroups based on low or high TSR, and low, intermediate or high DR and TBd. Kaplan-Meier curve analysis and log-rank test were applied to examine RFS among subgroups. Univariate and multivariate Cox proportional hazards analyses were used to identify independent factors associated with RFS, and a nomogram was subsequently developed. Abnormal CA242, CEA, T4 stage, presence of hypertension, internal obstruction or perforation (IOP), lymphovascular or/and perineural invasion (PNI), number of nodes examined less than 12, low-frequency microsatellite instability (MSI-L), higher Ki-67 and immature DR were associated with a lower RFS. In multivariable analysis, DR (HR =2.111; 95% CI: 1.184-3.766; P=0.011), LVI (HR =1.919; 95% CI: 1.004-3.669; P=0.049) and PNI (HR =2.724; 95% CI: 1.362-5.448; P=0.005) were prognostic factors for RFS. On this basis, a nomogram that integrated DR and clinicopathologic predictors for predicting RFS passed the calibration and had an area under the curve of 0.826. The prognostic significance of DR outperformed TBd and TSR, therefore, we recommend adding DR as a biomarker in routine pathological reports. The novel nomogram combining these factors may be used as a reliable and effective tool for the prediction of RFS in stage II CRC, thus helping optimize therapeutic regimens under cooperation of oncologists and surgeons. Further multicentric studies are required for validation of this novel, simple and cost-effective prognostic model.

Time-Dependent Prediction of Relapse in Patients with Acute Myeloid Leukemia

Background: Although most patients with newly diagnosed acute myeloid leukemia (AML) obtain a complete remission (CR) following induction chemotherapy, most subsequently relapse. Previous studies have demonstrated the importance of various prognostic factors for relapse-free survival, including age, cytogenetics, prior antecedent hematologic disorder (AHD), and prior cancer-related therapy. However, assessments of treatment response now include additional factors such as measurable residual disease (MRD) status, time to count recovery, and remission type (CR vs. CR with incomplete count recovery [CRi]). Among patients in complete remission, we set out to examine the impact of additional initial response variables on relapse or death at various time points up to 3 years, a time point after which AML relapses become very uncommon. Methods: Of 972 patients who had a confirmed diagnosis of AML or other high-grade myeloid neoplasm (≥10% blasts) underwent initial induction treatment at University of Washington / Fred Hutchinson Cancer Center between November 2008 and December 2018, 656 achieved a morphologic remission (CR or CRi) and were included in our analysis. The primary outcomes were survival without relapse after 1, 2, or 3 years. Multivariable logistic regression models controlled for the following covariates: age, ELN 2017 risk classification, presence of MRD determined by multiparameter flow cytometry at first remission, gender, WBC count at diagnosis, prior AHD and/or therapy-related disease, performance status, treatment-related mortality (TRM) score, induction intensity (high: CLAG-M, FLAG-ida, or similar; intermediate: 7+3 or similar; low: hypomethylating agent with or without venetoclax), CR vs CRi, and count recovery within 30 days. Time to relapse was estimated using relapse-free survival curves. Results: The median age at diagnosis was 60 years (range 18-91). De novo AML was found in 373 patients (57%) with the remainder a mix of antecedent AHD and therapy-related AML. ELN2017 risk classification was favorable in 181 patients (28%), intermediate in 206 (41%), and adverse in 203 (31%). Performance status was 0-1 in 538 patients (82%). Most patients received high or intermediate-intensity induction (88%). After induction, 540 patients (82%) achieved a CR and 116 patients (18%) CRi. MRD following induction therapy was found in 173 patients (26%). In multivariable analysis, age, remission type (CRi), and MRD status were the strongest predictors of being alive without relapse at years 1, 2, and 3 (year 3 summarized in Table 1). In the year 3 model, CR MRD+ after induction was associated with the largest decrease in odds of being alive without relapse (CR MRD+: odds ratio [OR] 0.15, 95% confidence interval [CI] 0.08-0.27). 3-year relapse-free survival (RFS) of 18.5% (95% CI 13.5-25.5%) for MRD+ patients versus 36.4% (95% CI 31.3-42.4%) for MRD- patients (Figure 1). CRi MRD+/MRD- were both also associated with decreased survival with CRi MRD- (OR 0.33, 95% CI 0.16-0.65) and CRi MRD+ (OR 0.40, 95% CI 0.18-0.87). Increasing age was the second strongest predictor across the models (year 3 OR 0.78, 95% CI 0.67-0.89). Conclusions: Our study identified remission category (CR vs CRi), MRD status, and age as the strongest predictors of being alive without relapse at years 1, 2, or year 3 following induction for patients with AML and other high-grade myeloid neoplasms. Patients with older age or those with evidence of residual detectable disease with MRD or CRi and/or MRD have an increased risk of relapse or death in the first 3 years after initial CR. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The prognostic significance of preoperative nutritional/inflammatory markers and clinicopathological features in resectable esophagectomy patients: possibility of nutritional intervention.

Preoperative inflammatory or nutritional biomarkers and clinicopathological features may be survival predictors in resectable esophagealsquamous cell carcinoma. We included 118 patients with resectable squamous esophageal carcinoma (stages I-IV), assessing preoperative CRP- and albumin-based modified Glasgow prognostic score, the modified controlling nutritional status score, C-reactive protein, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, pathologic stage, and tumor location(s), looking for correlation with overall survival and relapse-free survival. Using univariate and Cox analysis, we selected the most reliable prognostic factors. Five-year overall survival and recurrence-free survival were 54.9% and 48.5%, respectively. C-reactive protein values correlated negatively with hypoalbuminemia (P = 0.0036). On univariate analysis, tumor stage, invasion depth, location, nodal involvement, albumin, and modified Glasgow prognostic score were significant prognostic factors for overall and recurrence-free survival. Preoperative C-reactive protein was prognostic factor for overall survival, but not for relapse-free survival (P = 0.017, 0.063, respectively). The Cox proportional hazards model showed the modified Glasgow prognostic score to be an independent prognostic factor for relapse-free survival and overall survival after using the stepwise variable selection procedure. Cox analysis including clinicopathological factors and modified Glasgow prognostic scores showed that only tumor location(s) and pathologic stage were independent prognostic factors for overall survival and recurrence-free survival. Although the modified Glasgow prognostic score is not superior to pathologic stage and tumor location as a biomarker of preoperative nutrition/inflammation and clinicopathological factors, it remains an important prognostic marker in resectable esophageal cancers. Preoperative decreased inflammatory response and improved nutritional status may contribute to prognosis in patients with esophageal cancer.

Clinicopathological characteristics and loss of mismatch repair protein expression in Chinese upper tract urothelial carcinomas.

Expression of DNA mismatch repair (MMR) protein (MLH1, PMS2, MSH2, and MSH6) in upper tract urothelial carcinoma (UTUC) has been explored in Western cohorts, but it is rarely reported in Eastern cohorts. We aimed to assess the loss of MMR protein expression among Chinese UTUC patients and study its clinicopathological implications. We enrolled 175 UTUC patients at our center and tested the expression of MMR proteins by immunohistochemistry. Then, we explored these patients' clinicopathological characteristics. We found loss of MMR proteins in 19 (10.9%) of 175 patients in our cohort (6 MSH2 and MSH6, 2 MSH6 alone, 6 MSH2 alone, 3 MLH1 and PMS2, and 2 PMS2 alone). Loss of MMR proteins was not a significant prognostic factor of relapse-free survival for these patients. In addition, patients with lower T stage or with bladder cancer history were more likely to have loss of MMR protein expression. At last, two metastatic patients (MSH2 and MSH6 loss; MSH2 loss) with loss of MMR protein experienced tumor recession after several cycles of anti-PD-1 immunotherapy. In conclusion, this is the largest Chinese UTUC cohort study to date that explores the loss of MMR protein expression. The rate of MMR loss observed was comparable to that in the Western UTUC cohort, supporting universal UTUC screening in China. Furthermore, a subset of advanced UTUCs with MMR protein loss are probably immunogenic, for whom single or combined immunotherapy may be potential therapeutic options in the future.

Evaluating prognostic significance of preoperative C-reactive protein to albumin ratio in older patients with pathological stage II or III colorectal cancer.

This study was performed to evaluate the prognostic value of preoperative C-reactive protein to albumin ratio (CAR) in older patients with colorectal cancer (CRC) undergoing curative resection. We retrospectively analyzed 244 older patients (aged 75 years or higher) with pathological stage II or III CRC who underwent curative surgery between 2008 and 2016. The optimal value of CAR was calculated and its correlation with the clinicopathological factors and prognosis was examined. The optimal cutoff value of the CAR was 0.085. High preoperative CAR was significantly associated with high carcinoembryonic antigen levels (P=0.001), larger tumor size (P<0.001), and pT factor (P=0.001). On multivariate analysis, high CAR was independent prognostic factor for relapse-free survival (P=0.042) and overall survival (P=0.001). Preoperative elevated CAR could be considered as an adverse predictor of both relapse-free survival and overall survival in older patients with CRC undergoing curative surgery.

Prognostic factors for relapse-free survival in stage IB-IIIA primary lung adenocarcinoma by epidermal growth factor receptor mutation status

BackgroundPathological stage IB-IIIA lung adenocarcinoma with an epidermal growth factor receptor (EGFR) mutation (Mt) has a high recurrence rate even after complete resection. However, there have been few reports on the risk factors for Mt recurrence. This study aimed to analyze the clinicopathological factors related to the relapse-free survival (RFS) of patients with pathological stage IB-IIIA primary lung adenocarcinoma with and without an EGFR mutation.MethodsPatients who underwent curative surgery for Mt (n = 208) harboring the EGFR exon 21 L858R point mutation or EGFR exon 19 deletion mutation and EGFR mutation wild-type lung adenocarcinoma (Wt, n = 358) between January 2010 and December 2020 were included. Patients who received adjuvant EGFR-tyrosine kinase inhibitors were excluded. The prognostic factors for RFS were analyzed using a multivariable Cox regression analysis.ResultsThe 5-year RFS rates in the Mt and Wt groups were 43.5 and 52.3%, respectively (p = 0.907). Prognostic factors for RFS in the Mt group included smoking history (hazard ratio [HR], 1.49; p = 0.049), blood vessel invasion (HR, 1.84; p = 0.023), and lymph node metastasis (HR, 1.96; p = 0.005). However, adjuvant chemotherapy was not a prognostic factor (HR, 1.02; p = 0.906). In contrast, positron emission tomography (PET) max standardized uptake value (SUV) ≥ 6.0 (HR, 1.53; p = 0.042), lymphatic vessel invasion (HR, 1.54; p = 0.036), lymph node metastasis (HR, 1.79; p = 0.002), and adjuvant chemotherapy (HR, 0.60; p = 0.008) were prognostic factors for RFS in the Wt group.ConclusionsPrognostic factors for RFS in stage IB-IIIA primary lung adenocarcinoma differ by epidermal growth factor receptor mutation status. The impact of adjuvant chemotherapy on RFS also differed by EGFR mutation status.