Independent Prognostic Factor For Disease-free Survival Research Articles

Prognostic value of tumour contour irregularity on surgical strategies for T1bN0M0 renal cell carcinoma: A multi-institutional study

PurposeTo determine the prognostic value of tumour contour irregularity degree (CID) in surgical strategy options for T1bN0M0 renal cell carcinoma (RCC). Materials and methodsWe performed a retrospective multi-institutional review of 489 patients with T1bN0M0 RCC treated between January 2009 and June 2019. Cox regression and Kaplan-Meier analyses were performed to analyse the impact of CID on disease-free survival (DFS). ResultsThe median follow-up time was 55 months (interquartile range, 40–81 months) for 55 (11.2 %) patients with metastasis or recurrence. Logistic analysis indicated that CID was associated with World Health Organization/International Society of Urological Pathology (WHO/ISUP) grades III–IV (odds ratio, 1.015; 95 % confidence interval [CI], 1.008–1.023; p < 0.001). After being classified into high CID (≥50 %) and low CID (<50 %) groups, those with a high CID showed a significantly higher ratio of WHO/IUSP grades III–IV (74/277 [26.7 %] vs 25/212 [11.8 %]) and shorter DFS than the low CID group (p < 0.001). Multivariable Cox regression showed that partial nephrectomy (PN; hazard ratio [HR], 1.889; 95 % CI, 1.020–3.499; p = 0.043), high CID (HR, 6.685; 95 % CI, 2.776–16.100; p < 0.001), and WHO/ISUP grade III–IV (HR, 1.950; 95 % CI, 1.100–3.458; p = 0.022) were independent prognostic factors for DFS. The Kaplan-Meier plot showed that PN had a DFS rate comparable to that of radical nephrectomy (RN; p = 0.994). In the low CID group, patients who underwent PN showed comparable DFS to those who underwent RN (p = 0.903). Furthermore, patients with a high CID tended to have worse DFS in the PN versus RN group (p = 0.044). Multivariable Cox regression showed that PN (HR, 2.049; 95 % CI, 1.065–3.942; p = 0.032) and WHO/ISUP grade III–IV (HR, 2.148; 95 % CI, 1.189–3.881; p = 0.011) were independent prognostic factors of DFS in the high CID group. ConclusionsCID is a reliable preoperative parameter which is positively correlated with WHO/ISUP grade and can help with surgical decision-making in patients with T1bN0M0 RCC.

Family history of cancer is a prognostic factor for better survival in operable esophageal squamous cell carcinoma: A propensity score matching analysis.

Patients with a family history of cancer, especially digestive tract cancer and esophageal cancer, a family history of cancer in the first degree, and more than one relative affected by cancer were associated with favorable survival when compared to those without a family history of cancer. A family history of cancer is a favorable independent prognostic factor in ESCC. Patients with a family history of cancer, especially digestive tract cancer and esophageal cancer, a family history of cancer in the first degree, and more than one relative affected by cancer were associated with favorable survival when compared to those without a family history of cancer. A family history of cancer (FH) is closely associated with the risk and survival of many cancers. However, the effect of FH on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) remains unclear. We performed a large cohort study in the Chinese population to obtain insight into the prognostic value of FH in patients with operable ESCC. A total of 1,322 consecutive patients with thoracic ESCC who had undergone esophagectomy between January 1997 and December 2013 were included. The FH group included patients with any degree of FH, while the non-FH group included patients without any degree of FH. In total, 215 patients with FH and 215 without FH were matched using the propensity score matching analysis method to adjust for differences in baseline variables between the two groups. The impact of FH on disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier method and Cox's proportional hazards models. Before matching, 280 (21.2%) patients were included in the FH group and 1,042 (78.8%) in the non-FH group. FH was associated with early pathological T stage (p = 0.001), lymph node-negative status (p = 0.022), and early pathological stage (p = 0.006). After matching, FH was an independent prognostic factor for DFS and OS in ESCC patients. Patients with FH had 35% lower risk of disease progression (hazard ratio [HR] = 0.65, 95% CI: 0.51-0.84, p = 0.001) and 34% lower risk of death (HR = 0.66, 95% CI: 0.51-0.86, p = 0.002) than those without FH. Patients with a family history of digestive tract cancer (FH-DC), a family history of esophageal cancer (FH-EC), FH in first-degree relatives (FH-FD), and more than one relative affected by cancer were associated with favorable DFS and OS as compared to those without FH. FH is a favorable independent prognostic factor in ESCC. Patients with FH, especially those with FH-DC, FH-EC, FH-FD, and more than one relative affected by cancer, had improved survival.

Uncertain resection of highest mediastinal lymph node positive among pN2 non-small cell lung cancer patients: survival analysis of postoperative radiotherapy and driver gene mutations.

The role of postoperative radiotherapy (PORT) in uncertain resection of pN2 non-small cell lung cancer (NSCLC) with highest mediastinal lymph node positive has not been determined. We aim to evaluate the effect of PORT and driver gene mutation status (DGMS) on survival in such patients. 140 selected patients were grouped according to whether they received PORT and their DGMS. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) of each group were evaluated by Kaplan-Meier analyses. COX regression was used to evaluate the effects of various factors on DFS and OS. Of 140 patients, thirty-four patients (24.3%) received PORT, and forty (28.6%) had positive driver gene mutation status (DGp). PORT significantly prolonged LRFS (p = 0.002), DFS (p = 0.019) and OS (p = 0.02), but not DMFS (p = 0.062). By subgroup analysis, in patients with negative driver gene mutation status (DGn), those receiving PORT had notably longer LRFS (p = 0.022) and DFS (p = 0.033), but not DMFS (p = 0.060) or OS (p = 0.215), compared to those not receiving PORT. Cox analysis showed that the number of positive lymph nodes (PLNs) and administration of PORT were independent prognostic factors of DFS, and pathology, PLNs, and DGMS may be prognostic factors of OS (all p < 0.05). Postoperative radiotherapy may improve locoregional recurrence-free and disease-free survival in patients with pN2 NSCLC with positive highest mediastinal lymph nodes, while driver gene mutation status impacted OS significantly. Only patients with positive driver gene mutations experienced significant overall survival benefits from postoperative radiotherapy.

Influence of radiation treatment technique (IMRT vs. 3D-RT) on acute toxicity and prognostic factors for survival for anal cancer

We compared our institutional experience with intensity-modulated radiotherapy (IMRT) and 3D-conformal radiotherapy (3D-RT) for definitive treatment of primary anal cancer. We performed a single-institution retrospective review of all patients with anal squamous cell carcinoma treated with definitive (chemo) radiotherapy with curative intent from 2004 through 2018. We assessed several prognostic factors in respect to relevant survival endpoints. In addition, acute toxicities were determined and compared between IMRT and 3D-RT patients. This study included 94 patients (58 IMRT, 36 3D-RT). Mean follow up for all patients, for IMRT and 3D-RT patients was 61 months (range 6–176), 46 months (range 6–118), and 85 months (range 6–176), respectively. 5-year overall survival (OS) was 86%, disease-free survival (DFS) was 72%, and colostomy-free survival (CFS) was 75% in the IMRT cohort. In the 3D-RT cohort, OS was 87%, DFS was 71%, and CFS was 81% (all p > 0.05). Male gender and Karnofsky Index (KI) were revealed as independent prognostic factors for 5-year OS (p = 0.017; p = 0.023). UICC stage was an independent prognostic factor for DFS and CFS (p = 0.023; p = 0.042). In addition, the pre-treatment leukocyte count was an independent prognostic factor for CFS (p = 0.042). Acute grade ≥ 3 toxicity was not significantly different between IMRT and 3D-RT patients, but the IMRT cohort had favorable outcomes. This study confirmed IMRT as the primary definitive treatment of anal cancer. With similar survival rates, IMRT had the potential to reduce acute toxicity by sparing organs at risk. Promising prognostic factors such as BMI, KI, and leucocyte and hemoglobin levels should be further investigated.

Distinct Prognostic Impact of PET Findings Based on Radiological Appearance in Clinical Stage IA Lung Adenocarcinoma

IntroductionAlthough solid appearance on computed tomography and positive findings on positron emission tomography (PET) have been both associated with poor outcome in lung adenocarcinoma, the extent to which these findings overlap is unknown. This study aimed to determine the differences in prognostic significance of PET findings in part-solid nodules (PSNs) and solid nodules. Materials and MethodsWe retrospectively investigated 417 patients with clinical stage IA adenocarcinoma who underwent curative resection between 2010 and 2017. We compared disease-free survival (DFS), cumulative incidence of disease recurrence (CIR) and clinicopathological characters between PET-positive and negative groups among PSNs and solid nodules, respectively. We used 2.5 as a cut-off value of maximum standardized uptake value (SUV max). ResultsIn PSNs (n = 235), PET-positive group (n = 59) showed more aggressive features in several clinicopathological variables, poorer DFS (P < .001) and higher CIR (P < .001) than PET-negative group (n = 176). In contrast, in solid nodules (n = 182), DFS (P = .521) and CIR (P = .311) were not significantly different between PET-positive (n = 128) and negative groups (n = 54). SUV max was proved to be the independent prognostic factor of DFS by multivariate analysis (HR, 1.155; 95% CI, 1.036-1.287) only in PSNs. ConclusionThese findings showed distinct impact on prognosis of PET findings between PSNs and solid nodules. PET-positive finding was more important prognostic factor in PSNs than in solid nodules among clinical stage IA lung adenocarcinoma.

Abstract B043: Impact of SMAD4 loss in patients with pancreatic ductal adenocarcinoma receiving neoadjuvant therapy

Abstract Introduction: SMAD4, the central mediator of the Transforming Growth-Beta (TGF-Beta) signaling pathway, is inactivated in 50-55% of pancreatic ductal adenocarcinomas (PDACs). SMAD4 loss of expression has been described as a negative prognostic factor in PDAC and associated with increased rate of metastasis and resistance to adjuvant therapy. However, the impact of SMAD4 inactivation in patients receiving neoadjuvant therapy (NAT) is not well characterized. The aim of our study is to investigate if SMAD4 loss is a prognostic factor in a cohort of patients who underwent surgery for PDAC and, more specifically, in patients receiving NAT. Material and methods: We analyzed a single center retrospective series of 204 patients who underwent surgical resection for PDAC between 2004-2021. SMAD4 nuclear expression was semi-quantitively assessed by immunohistochemistry (IHC) on tumor samples and related to clinical variables including overall survival (OS) and disease free survival (DFS). Results: Among the 204 patients, 64 (31,37%) received NAT and 140 (68,63%) did not. In the NAT cohort, 33 (51,47%) tumors were SMAD4-positive and 31 (48,43%) were SMAD4-negative and in the non-NAT group, 84 (60%) and 56 (40%) patients presented SMAD4-positive and -negative tumors, respectively (p=0.28). Both in the NAT and non-NAT cohort of patients, SMAD4 status was not associated with clinico-pathological variables and did not impact OS. However, regarding DFS, in patients without NAT, SMAD4 loss seems to be associated with shorter DFS (p=0.073). In a multivariate analysis including the significant clinico-pathological variables, SMAD4 status showed a tendency to remain an independent prognostic variable (p=0.052). Moreover, in patients that received NAT, univariate analysis indicated that SMAD4 loss was associated with worse DFS (p=0.018). However, in a multivariate analysis, only vascular invasion (p=0.02) and the subtype of administrated NAT (FOLFIRINOX or GEMCITABINE-based) (p=0.0004) were independent prognostic factors for DFS. We therefore evaluated the prognostic significance of SMAD4 loss in a homogenous group of patients receiving FOLFIRINOX-based therapy (n=45). Univariate and multivariate analysis indicated that in these patients, SMAD4 loss was an independent negative prognostic factor (p=0.009) as well as vascular invasion (p=0.003). Conclusion: This study highlights the potential prognostic role of SMAD4 loss in the DFS of PDAC patients, more specifically in patients receiving NAT. Citation Format: Marie-Lucie Racu, Dana Bernardi, Aniss Chaouche, Egor Zindy, Julie Navez, Patrizia Loi, Calliope Maris, Jean Closset, Jean-Luc Van Laethem, Christine Decaestecker, Isabelle Salmon, Nicky D'Haene. Impact of SMAD4 loss in patients with pancreatic ductal adenocarcinoma receiving neoadjuvant therapy [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B043.

Prognostic and clinical significance of HER-2 low expression in early-stage gastric cancer

IntroductionGastric cancer is the most fifth common tumor worldwide. Human epidermal growth factor receptor 2 (HER2) overexpression is associated with poor prognosis and clinical characteristics in gastric cancer. Nevertheless, the biology of HER2-low expression has not reported in gastric cancer.Materials and methodsA total of 157 patients with early-stage gastric cancer were retrospectively analyzed. The associations between HER-2 low expression and clinical characteristics were analyzed by Chi-square test. And the prognostic value of HER-2 low expression and clinical characteristics in disease-free survival (DFS) and overall survival (OS) were analyzed by univariate and multivariate Cox regression analysis.ResultsOf 157 patients with early-stage gastric cancer, 31.8% had HER2-low tumors and 50.3% had HER2-negative tumors. HER2-low expression was associated with age, histological differentiation, tumor location and Ki-67 index. However, HER2-low expression was not associated with DFS or OS in early-stage gastric cancer.ConclusionHER2-low expression might result in distinct biology, but it was not an independent prognostic factor of DFS or OS in early-stage gastric cancer.

SOX9 Expression Is Superior to Other Stem Cell Markers K19 and EpCAM in Predicting Prognosis in Hepatocellular Carcinoma.

Various stem cell markers (eg, epithelial cell adhesion molecule [EpCAM], cytokeratin 19 [K19]) have been reported as predictors of poor prognosis in hepatocellular carcinoma (HCC). However, the data remain limited, particularly in Western populations, and are often contradictory. In this study, the prognostic value of positive SOX9 immunohistochemistry was compared with that of more established markers EpCAM and K19 in a large cohort (n=216) of North American patients. The independent HCC cohort in The Cancer Gene Atlas (n=360) was utilized to validate our findings. Finally, molecular signatures associated with SOX9 -high HCC were determined. We found that the expression of SOX9, but not EpCAM or K19, was associated with worse overall survival and disease-free survival (DFS) and was an independent prognostic factor for DFS in our North American cohort, in which hepatitis C infection was the most common underlying etiology. High SOX9 mRNA level, but not increased expression of EpCAM mRNA or K19 mRNA, was also associated with worse DFS and was an independent prognostic factor for DFS in The Cancer Gene Atlas cohort. This group had underlying causes, including an increased incidence of hepatitis B, significantly different from our initial cohort. High SOX9 mRNA level is associated with molecular pathways important in HCC pathogenesis. Increased SOX9 expression is clinically and biologically relevant for HCC arising in patients with a variety of underlying etiologies. Immunohistochemistry for SOX9 is a reliable proxy for increased SOX9 mRNA and can be used to predict prognosis in HCC cases.

Evaluation of systemic inflammatory and nutritional indexes in locally advanced gastric cancer treated with adjuvant chemoradiotherapy after D2 dissection.

Many studies have shown that the peripheral blood inflammatory index and nutritional index, such as the platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), lymphocyte monocyte ratio (LMR), systemic inflammation response index (SIRI), pan-immune-inflammation value (PIV), systemic immune-inflammation index (SII), and prognostic nutrition index (PNI), are independent prognostic factors for tumors. The present study aimed to investigate the prognostic role of these peripheral blood indexes before treatment in locally advanced gastric cancer (LAGC) treated with adjuvant chemoradiotherapy after D2 dissection. A total of 89 patients with LAGC who underwent D2 gastrectomy and adjuvant chemoradiotherapy at our hospital from 2010-2018 were eligible. Systemic inflammatory indicators before treatment were evaluated. Receiver operating characteristic curve (ROC), Kaplan-Meier analysis, and Cox regression were utilized for prognosis evaluation. The median follow-up time was 29.1 (4.1-115.8) months. The overall survival at 3 years (OS) and the disease-free survival (DFS) were 78.9% and 59.1%, respectively. According to the ROC curve for 3-year DFS, the best cut-off values of pre-treatment NLR, PLR, LMR, SII, SIRI, PIV and PNI were 1.7, 109.3, 2.9, 369.2, 0.58, 218.7, and 48, respectively. Multivariate Cox regression analysis showed that NLR was an independent prognostic factor for DFS (HR 2.991, 95%CI 1.085-8.248, P = 0.034). Kaplan-Meier analysis showed that a higher NLR (>1.70) was significantly associated with a poorer OS (3-year OS: 68.8% vs 92.9%, P = 0.045) and DFS (3-year DFS: 47.5% vs 80.9%, P = 0.005). In terms of the free locoregional recurrence rate (LRR), the prognosis of patients with high NLR was also significantly worse than those with low NLR (70.2% vs 96.0%, P = 0.017). Paraaortic lymph nodes were the most common site of LRR (7/14 patients). The seven cases of paraaortic lymph node metastasis occurred in patients with high NLR. In our retrospective analysis, we found that pretreatment NLR could serve as a prognostic factor for survival in LAGC treated with adjuvant chemoradiotherapy after D2 dissection, especially for the prediction of LRR and paraaortic lymph node metastasis. Prospective studies are needed to confirm our findings.

Clinicopathologic characteristics and prognostic impact of atypical EGFR mutations in completely resected lung adenocarcinoma

IntroductionThis study evaluated the clinicopathologic characteristics and prognostic impact of atypical epidermal growth factor receptor (EGFR) mutations in patients with completely resected lung adenocarcinoma (LUAD) and investigate whether adjuvant chemotherapy could benefit the survival outcomes for these subjects. Material and methodsWe retrospectively reviewed resected LUAD samples from 8437 patients and identified 5358 EGFR-mutated (EGFRm) cases. Of these, 4847 had classical mutations, while 511 had atypical mutations. For further survival analysis, propensity score matching, Kaplan–Meier curve, and Cox regression analyses were conducted. ResultsOf the 511 patients with atypical EGFRm LUAD, 131 patients had compound mutations. The frequency of exon 20 insertion (20-ins), G719X, L861Q, S768I, and de novo T790M were 30.3%, 32.7%, 21.9%, 9.2%, and 11.4%, respectively. These patients included a higher proportion of males than those with classical EGFRm LUAD. Between the 483 matched pairs of the classical and atypical EGFRm patients, no significant difference emerged in disease-free survival (DFS) (p = 0.476). Patients with the L861Q mutation had the poorest DFS among those with atypical EGFRm LUAD (p = 0.005). Cox regression analyses revealed that the L861Q mutation was an independent prognostic factor for DFS in 487 patients with solely atypical EGFRm LUAD. In addition, adjuvant chemotherapy did not improve the DFS for those patients, whether in stage IB (p = 0.638) or II-III (p = 0.505) of the disease. ConclusionThe L861Q mutation is an independent prognostic factor for DFS in patients with atypical EGFRm LUAD after complete resection who would not benefit from adjuvant chemotherapy regardless of disease stage.

Is red blood cell distribution width a prognostic factor for colorectal cancer? A meta-analysis.

BackgroundRDW might be an easy and cost-effective pre-operative prognostic factor for cancer patients. The aim of the current study was to analyze whether red blood cell distribution width (RDW) was a prognostic factor for colorectal cancer (CRC) patients who underwent radical surgery.MethodsWe conducted the searching strategy in three databases including the PubMed, Embase and Cochrane Library from the inception to May 07, 2022, to find eligible studies. In this meta-analysis, we focused on the prognosis. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS).ResultsA total of seven studies involving 7,541 patients were included in this meta-analysis. After pooling up the HRs, red blood cell distribution width-coefficient of variation (RDW-CV) was not an independent prognostic factor of OS (HR = 1.48, I2 = 90%, 95% CI = 0.93 to 2.36, P = 0.10), however, red blood cell distribution width-standard deviation (RDW-SD) was an independent prognostic factor of OS (HR = 1.99, I2 = 0%, 95% CI = 1.59 to 2.49, P < 0.01). As for DFS, we found that RDW-CV (HR = 1.51, I2 = 83%, 95% CI = 0.94 to 2.43, P = 0.09 < 0.10) and RDW-SD (HR = 1.77, I2 = 56%, 95% CI = 0.91 to 3.43, P = 0.09 < 0.10) were both the independent prognostic factors. In terms of CSS, we found that RDW-CV was not an independent prognostic factor (HR = 1.23, I2 = 95%, 95% CI = 0.72 to 2.10, P = 0.46).ConclusionRDW-SD was an independent prognostic factor of OS and DFS, and RDW-CV was an independent prognostic factor of DFS.

Association of body composition with clinical outcome in Chinese women diagnosed with breast cancer.

ObjectiveThis study aims to explore the association of body composition with clinical outcomes in Chinese women diagnosed with breast cancer.MethodA total of 2,948 Chinese female patients with breast cancer have been included in this retrospective study. Body composition mainly includes the measurements of adiposity and muscle mass. Visceral fat area (VFA) is used to measure visceral obesity, while appendicular skeletal muscle mass index (ASMI) is utilized to evaluate sarcopenia. The endpoints of this study are disease-free survival (DFS) and overall survival (OS). The association of the body composition parameters with DFS and OS was statistically analyzed.ResultThe median follow-up time for survivors was 42 months (range, 3 to 70 months). In total, 194 patients (6.9%) had breast cancer recurrence, and 32 patients passed away (1.1%). Among the 2,948 patients included, 1,226 (41.6%) patients were viscerally obese, and 511 (17.3%) patients were sarcopenic. We found that visceral obesity had a significant prognostic impact on DFS (HR, 1.46; 95% CI, 1.10–1.95; p = 0.010) but not on OS (P = 0.173). Multivariate analysis revealed sarcopenia as an independent prognostic factor for DFS (HR, 1.44; 95% CI, 1.02–2.03; p = 0.038) and OS (HR, 2.13; 95% CI, 1.00–4.51; p = 0.049). Body mass index was not significantly associated with both DFS (P = 0.224) and OS (P = 0.544).ConclusionVisceral obesity is associated with a higher risk of disease recurrence, and sarcopenia is significantly associated with increased recurrence and overall mortality among Chinese women with breast cancer. Body composition assessment could be a simple and useful approach in breast cancer management. Further studies can focus on decreasing visceral fat and increasing skeletal muscle mass to improve prognosis in breast cancer survivors.

NANOG regulates epithelial-mesenchymal transition via AMPK/mTOR signalling pathway in ovarian cancer SKOV-3 and A2780 cells.

NANOG engages with tumour initiation and metastasis by regulating the epithelial–mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). However, its role in association with pAMPKα, and its clinical significance in EOC have not been elucidated even though AMPK is known to degrade NANOG in various human cancers. Hence, we investigated the role of pAMPKα and its association with NANOG as potential prognostic biomarkers in EOC. Both NANOG and pAMPKα expression were significantly overexpressed in EOCs comparing nonadjacent normal epithelial tissues, benign tissues, and borderline tumours. NANOG overexpression was significantly associated with poor disease‐free survival (DFS) and overall survival (OS), whereas pAMPKα overexpression was associated with good DFS and OS. Importantly, multivariate analysis revealed that the combination of high NANOG and low pAMPKα expression was a poor independent prognostic factor for DFS and was associated with platinum resistance. In ovarian cancer cell lines, siRNA‐mediated NANOG knockdown diminished migration and invasion properties by regulating the EMT process via the AMPK/mTOR signalling pathway. Furthermore, treatment with AMPK activator suppressed expression of stemness factors such as NANOG, Oct4 and Sox2. Collectively, these findings established that the combination of high NANOG and low pAMPKα expression was associated with EOC progression and platinum resistance, suggesting a potential prognostic biomarker for clinical management in EOC patients.

The Prognostic Role of Baseline Eosinophils in HPV-Related Cancers: a Multi-institutional Analysis of Anal SCC and OPC Patients Treated with Radical CT-RT

Background and AimAnal squamous cell carcinoma (SCC) and oropharyngeal cancer (OPC) are rare tumors associated with HPV infection. Bioumoral predictors of response to chemoradiation (CT-RT) are lacking in these settings. With the aim to find new biomarkers, we investigated the role of eosinophils in both HPV-positive anal SCC and HPV-related oropharyngeal cancer (OPC).MethodsWe retrieved clinical and laboratory data of patients with HPV-positive anal SCC treated with CT-RT in 5 institutions, and patients with locally advanced OPC SCC treated with CT-RT in 2 institutions. We examined the association between baseline eosinophil count (the best cutoff has been evaluated by ROC curve analysis: 100 × 10^9/L) and disease-free survival (DFS). Unadjusted and adjusted hazard ratios by baseline characteristics were calculated using the Cox proportional hazards model.ResultsThree hundred four patients with HPV-positive anal SCCs and 168 patients with OPCs (122 HPV-positive, 46 HPV-negative diseases) were analyzed. In anal SCC, low eosinophil count (< 100 × 10^9/L) correlates to a better DFS (HR = 0.59; p = 0.0392); likewise, in HPV-positive OPC, low eosinophil count correlates to a better DFS (HR = 0.50; p = 0.0428). In HPV-negative OPC, low eosinophil count confers worse DFS compared to high eosinophil count (HR = 3.53; p = 0.0098). After adjustment for age and sex, eosinophils were confirmed to be independent prognostic factors for DFS (HR = 4.55; p = 0.0139).ConclusionEosinophil count could be used as a prognostic factor in anal HPV-positive SCC. The worse prognosis showed in HPV-positive patients with high eosinophil count is likely to derive from an unfavorable interaction between the HPV-induced immunomodulation and eosinophils, which may hamper the curative effect of RT.

Trimodal Therapy in Esophageal Squamous Cell Carcinoma: Role of Adjuvant Therapy Following Neoadjuvant Chemoradiation and Surgery.

Simple SummaryIn this work, we aimed to explore the effectiveness of adjuvant therapy after trimodal therapy (neoadjuvant chemoradiotherapy and esophagectomy) in patients with thoracic esophageal squamous cell carcinoma (ESCC). Overall survival (OS) and disease-free survival (DFS) were both compared for adjuvant and non-adjuvant groups. Propensity score matching was used to eliminate the confounding factors between the two groups. Meanwhile, subgroup analysis based on a neoadjuvant-treated node stage (ypN) was performed to precisely stratify the patients and to guide the clinical decision-making at the point of care. As of now, there is no guideline or recommendation on the treatment of ESCC patients with adjuvant therapy after neoadjuvant chemoradiotherapy followed by surgery. The results of our study indicate that adjuvant therapy after trimodal therapy could shorten OS and DFS in patients with ESCC. Meanwhile, adjuvant therapy is an independently unfavorably prognostic factor for DFS. Therefore, adjuvant therapy is not recommended for ESCC patients after trimodal therapy, especially patients without nodal metastases after neoadjuvant therapy. To our knowledge, this is the first retrospective study using subgroup analysis to examine the effect of adjuvant therapy in ESCC patients after trimodal therapy by comparing overall survival and disease-free survival. The results of our study add useful evidence to recent guidelines.Background: The aim of this study was to determine the role of adjuvant therapy after neoadjuvant chemoradiotherapy and esophagectomy for esophageal squamous cell carcinoma (ESCC). Methods: The study retrospectively reviewed 447 ESCC patients who underwent neoadjuvant chemoradiotherapy and esophagectomy. Patients were divided into an adjuvant therapy group and no adjuvant therapy group. Propensity score matching was used to adjust the confounding factors. Results: 447 patients with clinical positive lymph nodes and no distant metastasis treated with neoadjuvant chemoradiotherapy and esophagectomy were eligible for analysis. After propensity score matching, there were 120 patients remaining in each group. Patients receiving adjuvant therapy had a significantly shorter post-resection overall survival (OS) and disease-free survival (DFS) when compared to patients not receiving adjuvant therapy (log-rank, OS: p = 0.046, DFS: p < 0.001). Receiving adjuvant therapy is not an independently prognostic factor for OS (hazard ratio (HR): 1.270, HR: 0.846–1.906, p = 0.249) but a significantly unfavorable independent prognostic factor for DFS (HR: 2.061, HR: 1.436–2.958, p < 0.001). Conclusions: The results of our study indicate that adjuvant therapy after neoadjuvant chemoradiotherapy and surgery could reduce the OS and DFS in patients with ESCC. Therefore, adjuvant therapy is not recommended for ESCC patients after neoadjuvant chemoradiotherapy and esophagectomy, especially patients without nodal metastases after neoadjuvant therapy.

Glutamine deficiency promotes recurrence and metastasis in colorectal cancer through enhancing epithelial–mesenchymal transition

BackgroundGlutamine is the most abundant amino acid in the body and plays a vital role in colorectal cancer (CRC) cell metabolism. However, limited studies have investigated the clinical and prognostic significance of preoperative serum glutamine levels in patients with colorectal cancer, and the underlying mechanism has not been explored.MethodsA total of 121 newly diagnosed CRC patients between 2012 and 2016 were enrolled in this study. Serum glutamine levels were detected, and their associations with clinicopathological characteristics, systemic inflammation markers, carcinoembryonic antigen (CEA) and prognosis were analysed. In addition, the effect of glutamine depletion on recurrence and metastasis was examined in SW480 and DLD1 human CRC cell lines, and epithelial–mesenchymal transition (EMT)-related markers were detected to reveal the possible mechanism.ResultsA decreased preoperative serum level of glutamine was associated with a higher T-class and lymph node metastasis (P < 0.05). A higher serum level of glutamine correlated with a lower CEA level (r = − 0.25, P = 0.02). Low glutamine levels were correlated with shorter overall survival (OS) and disease-free survival (DFS). Multivariate Cox regression analysis showed that serum glutamine was an independent prognostic factor for DFS (P = 0.018), and a nomogram predicting the probability of 1-, 3- and 5-year DFS after radical surgery was built. In addition, glutamine deficiency promoted the migration and invasion of CRC cells. E-cadherin, a vital marker of EMT, was decreased, and EMT transcription factors, including zeb1and zeb2, were upregulated in this process.ConclusionsThis study elucidated that preoperative serum glutamine is an independent prognostic biomarker to predict CRC progression and suggested that glutamine deprivation might promote migration and invasion in CRC cells by inducing the EMT process.

Circulating DNA in the neoadjuvant setting of early stage colon cancer

Background While circulating tumour (ct)DNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III colon cancer, no study has ever analysed the value of this biomarker in colon cancer patients treated with neoadjuvant chemotherapy. We sought to fill this gap by using prospectively collected plasma samples from 80 stage III colon cancer patients, receiving one cycle of neoadjuvant FOLFOX followed by surgery +/− adjuvant FOLFOX in the PePiTA trial. Material and Methods Samples were collected at baseline, 2 weeks and surgery. NPY and WIF1 were selected as universal methylation markers for ctDNA, and analysed with ddPCR technology. ROC curves were applied for cut-off points, and outcome measures included 5-year disease-free survival (DFS) and 6-year overall survival (OS). Results After a median follow-up of 52.5 months, baseline circulating-free (cf) DNA was an independent prognostic factor for DFS (HR 3.35, 95% CI: 1.15–9.77, p = .03), and a trend towards a similar association was observed for relative cfDNA changes between baseline and surgery (HR 2.57, 95% CI: 0.94–7.05, p = .07). Among 60 ctDNA assessable patients, 25 (42%) had detectable ctDNA at baseline. While detection of ctDNA at any pre-operative timepoint was not associated with outcome, patients with ctDNA increase (change of the worst trending methylation marker ≥11%, or mean ctDNA change of NPY and WIF1 ≥ 0%) between baseline and surgery showed a trend towards worse 5-year DFS (HR 3.66, 95% CI: 0.81–16.44, p = .09). Conclusion This is the first study of ctDNA in the neoadjuvant setting of early-stage colon cancer. Results are hypothesis-generating and should be confirmed in larger series.

Prognostic factors and treatment considerations of submandibular gland carcinomas: A population-based study.

The therapeutic regimen of submandibular gland carcinoma (SGC) has not reached consensus, especially for the neck treatment of patients with cN0. Patients with SGC were identified from the medical database of Shanghai Ninth People's Hospital. Kaplan-Meier analysis, univariate and multivariate Cox regression were employed to evaluate the survival and independent prognostic factors. Two hundred and fifteen patients with SGC were retrospectively reviewed. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 71.5% and 77.8%, respectively. Multivariate analysis revealed that histological grade, cT classification, cN classification, and perineural invasion (PNI) were independent prognostic factors for DFS, while histological grade, cT classification, cN classification, and age were those for OS. The neck dissection showed no significant survival benefit for patients with cN0. Lung was the most common site of distant metastasis (16.7%). Histological grade, cT classification, cN classification, age, and PNI were independent prognostic factors of patient with SGC, which should be the main considerations for making therapeutic regimens. Our study also verifies the neck dissection of patient with cN0 is unnecessary, and postoperative radiotherapy (PORT) is vital for patients with pN+.

Prognostic Value of HPV E6 and APOBEC3B in Upper Urinary Tract Urothelial Carcinoma.

Background APOBEC mutation signature is common in upper urinary tract urothelial carcinoma (UTUC). When virus infection occurs, upregulated APOBEC plays an antiviral role by deoxycytidine deaminase activity. However, the carcinogenic roles of HPV E6 protein and APOBEC mutation signature in UTUC have not been investigated. Aims This study explored the relationship among HPV E6, APOBEC, and clinicopathological characteristics in patients with UTUC and impacts of their expression on the prognosis. Methods The expression of HPV E6 and APOBEC3B of 78 patients with UTUC was detected by immunohistochemistry. Correlation of HPV E6 and APOBEC3B expression levels with clinicopathological characteristics was statistically analyzed. Univariate and multivariate Cox regression analyses were used to evaluate the prognosis of HPV E6 and APOBEC3B for disease-free survival (DFS); survival analysis was performed using Kaplan-Meier methods. Results The expression of APOBEC3B was positively correlated with the expression of HPV E6 (r = 0.383, P = 0.001). HPV E6 was significantly increased in patients with stage I (χ2 = 4.938, P = 0.026) and low-grade urothelial carcinoma (χ2 = 3.939, P = 0.047), as well as in patients without LVI (χ2 = 4.064, P = 0.044). Meanwhile, APOBEC3B was highly expressed in patients with stage I (χ2 = 4.057, P = 0.044) and low-grade urothelial carcinoma (χ2 = 7.153, P = 0.007). Multivariate Cox regression analysis revealed the APOBEC3B expression was the independent prognostic factor for DFS, Kaplan-Meier survival analysis showed that low expression of APOBEC3B and HPV E6 was significantly associated with the poor prognosis of UTUC patients. Conclusion HPV E6 expression is positively associated with APOBEC3B expression, and the high expression of HPV E6 and APOBEC3B is associated with favorable prognosis of patients with UTUC.

Tertiary lymphoid structures favor outcome in resected esophageal squamous cell carcinoma.

Tertiary lymphoid structures (TLSs) are considered to have a good prognosis in multiple solid tumors. However, the prognostic value of TLS in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, we retrospectively enrolled 185 ESCC patients who underwent surgical resection. Hematoxylin and eosin staining was performed to investigate the presence, the abundance, the maturation, and the location of TLSs. We explored the cellular composition of TLSs using traditional immunohistochemistry in serial sections. The prognostic value of TLSs was investigated by univariate and multivariate analyses. A nomogram was constructed to predict the prognosis. TLS‐positive tumors were infiltrated with more CD45+ leukocytes, CD20+ B cells, CD4+ and CD8+ T cells, and CD11c+ dendritic cells（DCs） compared with negative tumors. Kaplan–Meier curves showed that the presence and the abundance of TLSs were associated with longer disease‐free survival (DFS) (p = 0.0130) and overall survival (OS) (p = 0.0164). In addition, patients with tumors containing more CD20+ B cell infiltration had longer DFS (p = 0.0105) and OS (p = 0.0341). Multivariate analyses demonstrated that the presence of TLSs was an independent prognostic factor for DFS (hazard ratio [HR] = 0.384, p < 0.001) and OS (HR = 0.293, p < 0.001). The nomogram that integrated the tumor stage, histologic grade, and TLS presence had higher prognostic accuracy. Our study suggests that ESCC‐related TLSs can be used as a new biomarker for the prognosis of ESCC patients, and further understanding of their formation and mechanism of induction can provide a possible direction and target for immunotherapy of ESCC.