Worse 5-year Disease-free Survival Research Articles

Invasive lobular carcinoma of the breast; clinicopathologic profile and response to neoadjuvant chemotherapy over a 15-year period

IntroductionInvasive lobular carcinoma (ILC) accounts for 5–15% of invasive breast cancers. Typical ILC is oestrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative. Atypical biomarker profiles (ER- and HER2+, ER+ and HER2+ or triple negative) appear to differ from typical ILCs. This study compared subtypes of ILC in terms of clinical and pathological parameters, and response to neoadjuvant chemotherapy (NACT) according to biomarker profile. MethodsAll patients with ILC treated in a single centre from January 2005 to December 2020 were identified from a prospectively maintained database. Clinicopathologic and outcome data was collected and analysed according to tumour biomarker profile. ResultsA total of 582 patients with ILC were treated. Typical ILC was observed in 89.2% (n = 519) and atypical in 10.8% (n = 63). Atypical ILCs were of a higher grade (35% grade 3 vs 9.6% grade 3, p < 0.001).A larger proportion of atypical ILC received NACT (31.7% vs 6.9% p < 0.001). Atypical ILCs showed a greater response to NACT (mean RCB (Residual Cancer Burden Score) 2.46 vs mean RCB 3.41, p = 0.0365), and higher pathological complete response rates (15% vs 0% p = 0.017). Despite this, overall 5-year disease-free survival (DFS) was higher in patients with typical ILC (91% vs 83%, p = 0.001). ConclusionsAtypical ILCs have distinct characteristics. They are more frequently of a higher grade and demonstrate a superior response to NACT. Despite the latter, atypical ILCs have a worse 5-year DFS which should be taken into consideration in terms of prognostication and may assist patient selection for NACT.

Prognostic value of tumor necrosis based on the evaluation of frequency in invasive breast cancer

BackgroundTumor necrosis (TN) was associated with poor prognosis. However, the traditional classification of TN ignored spatial intratumor heterogeneity, which may be associated with important prognosis. The purpose of this study was to propose a new method to reveal the hidden prognostic value of spatial heterogeneity of TN in invasive breast cancer (IBC).MethodsMultiphoton microscopy (MPM) was used to obtain multiphoton images from 471 patients. According to the relative spatial positions of TN, tumor cells, collagen fibers and myoepithelium, four spatial heterogeneities of TN (TN1-4) were defined. Based on the frequency of individual TN, TN-score was obtained to investigate the prognostic value of TN.ResultsPatients with high-risk TN had worse 5-year disease-free survival (DFS) than patients with no necrosis (32.5% vs. 64.7%; P < 0.0001 in training set; 45.8% vs. 70.8%; P = 0.017 in validation set), while patients with low-risk TN had a 5-year DFS comparable to patients with no necrosis (60.0% vs. 64.7%; P = 0.497 in training set; 59.8% vs. 70.8%; P = 0.121 in validation set). Furthermore, high-risk TN “up-staged” the patients with IBC. Patients with high-risk TN and stage I tumors had a 5-year DFS comparable to patients with stage II tumors (55.6% vs. 62.0%; P = 0.565 in training set; 62.5% vs. 66.3%; P = 0.856 in validation set), as well as patients with high-risk TN and stage II tumors had a 5-year DFS comparable to patients with stage III tumors (33.3% vs. 24.6%; P = 0.271 in training set; 44.4% vs. 39.3%; P = 0.519 in validation set).ConclusionsTN-score was an independent prognostic factor for 5-year DFS. Only high-risk TN was associated with poor prognosis. High-risk TN “up-staged” the patients with IBC. Incorporating TN-score into staging category could improve its performance to stratify patients.

Tumor Deposit Is an Independent Factor Predicting Early Recurrence and Poor Prognosis in Gastric Cancer

BackgroundAccurate prognostic estimation is crucial; however, the prognostic value of tumor deposits in gastric cancer remains controversial. This study aimed to investigate their prognostic significance. MethodsClinicopathological and prognostic data of 1012 gastric cancer patients who underwent R0 or R1 surgery from 2010 to 2017 at the Osaka International Cancer Institute were retrospectively reviewed. ResultsOverall, 6.3% patients had tumor deposits, which were associated with Borrmann type, surgical procedure, type of gastrectomy, extent of lymphadenectomy, tumor size, histology, pT, pN, pM, pStage, lymphatic invasion, vascular invasion, preoperative chemotherapy, and postoperative chemotherapy. Tumor deposit-positive patients had worse 5-year disease-free survival (32.60% vs. 92.45%) and overall survival (41.22% vs. 89.37%) than tumor deposit-negative patients. Subgroup analysis regarding pStage II–III also showed significant differences between patients with and without tumor deposits for 5-year disease-free survival (34.15% vs. 80.98%) and overall survival (43.17% vs. 75.78%). Multivariable analysis showed that older age, undifferentiated histology, deeper tumor invasion, lymph node metastasis, distant metastasis, and presence of tumor deposits were significantly correlated with early tumor recurrence and shorter survival time; these factors were identified as independent prognostic factors. The 5-year disease-free survival of tumor deposit-positive patients was significantly worse than that of patients in the pStage III group and comparable to that of patients in the pT4, pN3, and pM1 groups. The 5-year overall survival of tumor deposit-positive patients was comparable to that of the pT4, pN3, pM1, and pStage III groups. ConclusionsTumor deposits are strong and independent predictors of tumor recurrence and poor survival.

The association between fasting blood glucose and prognosis in gastrointestinal stromal tumor patients after curable resection.

Blood glucose has been demonstrated to serve as prognostic indicators in various malignancies. This study aimed to explore the relationship between fasting blood glucose (FBG) levels and the prognosis in patients with gastrointestinal stromal tumor (GIST) undergoing complete resection. Data were retrospectively collected from 256 patients with primary GIST underwent complete surgical resection or endoscopic excision. Patients were stratified into euglycemic group and hyperglycemic group. Patients' characteristics between groups were compared. Cox regression model was conducted to identify independent prognostic factors of disease-free survival (DFS). Both univariate analysis and multivariate analyses revealed that FBG ≥ 100mg/dl was associated with poor outcomes. Patients with FBG ≥ 100mg/dl tended to have more adverse features, more likely to suffer recurrence and a worse 5-year DFS than patients with FBG < 100mg/dl. Moreover, FBG levels helped distinguishing between patients with different survival outcomes in different risk categories defined by modified NIH systems. Our data provided the evidence that FBG is a useful prediction marker prognosis in patients with GIST undergoing curative surgery.

Ki67 increase after core needle biopsy associated with worse disease outcome in HER2-negative breast cancer patients

Ki67 would change after core needle biopsy (CNB) in invasive breast cancer. However, whether Ki67 alteration (ΔKi67) influences disease outcomes remains unclear. Here we aim to evaluate the prognostic value of ΔKi67. Patients with paired CNB and open excision biopsy (OEB) samples between January 2009 and June 2016 were retrospectively analyzed. ΔKi67 was calculated as the absolute difference between Ki67 level in CNB and OEB samples, and the median value of 5% was adopted to category patients into high- and low ΔKi67 groups. Disease-free survival (DFS) and overall survival (OS) were compared between different ΔKi67 groups. Overall, 2173 invasive breast cancer patients were included. Median Ki67 was higher in OEB than CNB samples: 25.00% versus 20.00% (P < 0.001). Axillary nodal status, STI, histological grading, and molecular subtype were independently associated with ΔKi67 (P < 0.05). In the whole population, patients with low ΔKi67 showed superior 5-year DFS (89.6% vs 87.0%, P = 0.026), but similar OS (95.8% vs 94.3%, P = 0.118) compared to those with high ΔKi67. HER2 status at surgery was the only significant factor interacting with ΔKi67 on both DFS (P = 0.026) and OS (P = 0.007). For patients with HER2-negative disease, high ΔKi67 was associated with worse 5-year DFS (87.2% vs 91.2%, P = 0.004) as well as impaired 5-year OS (93.9% vs 96.8%, P = 0.010). ΔKi67 had no significant impact on survival of HER2-positive patients. Ki67 increase after CNB was significantly associated with worse disease outcomes in HER2-negative, but not in HER2-positive patients, which warrants further study.

Effects of perioperative blood transfusion in gastric cancer patients undergoing gastrectomy: A systematic review and meta-analysis.

The short-term and long-term effects of perioperative blood transfusion (PBT) on patients with gastric cancer are still intriguing. This systematic review and meta-analysis aimed to investigate the effects of blood transfusion on clinical outcomes in patients with gastric cancer undergoing gastrectomy. We searched PubMed, Web of Science, Embase, and The Cochrane Library on December 31th 2021. The main outcomes were overall survival (OS), disease-free survival (DFS), disease-specific survival (DFS), and postoperative complications. A fixed or random-effects model was used to calculate the hazard ratio (HR) with 95% confidence intervals (CIs). Fifty-one studies with a total of 41,864 patients were included for this review and meta-analysis. Compared with patients who did not receive blood transfusions (NPBT), PBT was associated with worse 5-year OS (HR = 2.39 [95%CI: 2.00, 2.84]; p < 0.001; Multivariate HR = 1.43 [95%CI: 1.24, 1.63]; p < 0. 001), worse 5-year DFS (HR = 2.26 [95%CI: 1.68, 3.05]; p < 0.001; Multivariate HR = 1.45 [95%CI: 1.16, 1.82]; p < 0. 001), and worse 5-year DSS (HR = 2. 23 [95%CI: 1.35, 3.70]; p < 0.001; Multivariate HR = 1.24 [95%CI: 0.96, 1.60]; p < 0.001). Moreover, The PBT group showed a higher incidence of postoperative complications [OR = 2.30 (95%CI:1.78, 2. 97); p < 0.001] than that in the NPBT group, especially grade III-V complications, according to the Clavien-Dindo classification. [OR = 2.50 (95%CI:1.71, 3.63); p < 0.001]. In patients who underwent gastrectomy, PBT was associated with negative survival effects (OS, DFS, DSS) and a higher incidence of perioperative complications. However, more research was expected to further explore the impact of PBT. Meanwhile, strict blood transfusion management should be implemented to minimize the use of PBT.

Overexpression of AKR1B10 Predicts Poor Prognosis in Gastric Cancer Patients Undergoing Surgical Resection.

Aldo-keto reductase family 1 member B10 (AKR1B10) is associated with several cancers, but the prognostic role in gastric cancer (GC) remains unclear. We enrolled 359 GC patients who underwent a gastrectomy with D2 lymph node dissection. AKR1B10 expression was scored using an immunoreactive scoring system based on immunohistochemistry. Adjuvant chemotherapy with S-1 or oxaliplatin plus capecitabine was administered to pathological stage II or III disease patients. There were 117 (32.6%) and 242 (67.4%) patients with AKR1B10 overexpression and low expression, respectively. Patients overexpressing AKR1B10 had worse 5-year disease-free survival (DFS) and overall survival (OS) rates than those with low expression of AKR1B10. Pathological T3-T4 stage, pathological stage III, lymph node ratio ≥25%, and AKR1B10 overexpression were independent prognostic factors for worse DFS and OS in univariate and multivariate analyses. For 162 stage II or III patients who received adjuvant chemotherapy after surgical resection and 59 patients with signet ring cell carcinoma histology, AKR1B10 overexpression was also associated with inferior DFS and OS. AKR1B10 was not associated with clinical survival in stage I GC patients. In conclusion, AKR1B10 overexpression may be an independent prognostic factor for worse survival in GC patients who underwent gastrectomy with D2 lymph node dissection.

Extensive Intraductal Component in Breast Cancer: What Role in Disease-Free Survival?

IntroductionExtensive intraductal component (EIC) associated to early breast cancer could increase the risk locoregional recurrence, but its impact on distant metastases is still unclear. The aim of the present study was to assess the role of EIC on 5-year survival outcomes in patients affected by early breast cancer treated with breast-conserving surgery. MethodsA total of 414 consecutive patients with a minimum follow-up of 60 mo were collected from January 2007 to December 2015. Disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival at 5 y were assessed considering the presence or absence of EIC and other clinical and pathological features. ResultsAbsence of EIC was independently associated with worse 5-year DFS (hazard ratio [HR] 1.68, P = 0.008) and 5-year DMFS (HR 1.93, P = 0.007), whereas 5-year locoregional recurrence-free survival was not affected (HR 1.50, P = 0.16). Five-year DFS was increased by EIC in T1 patients (P = 0.03) but not in T2 stage. Moreover, EIC was associated to better DFS in G2 (P = 0.03) and G3 patients (P = 0.01) but not in G1 cases. ConclusionsOur results suggest that EIC is independently correlated with increased 5-year DFS and in particular with 5-year DMFS.

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.

Metaplastic Breast Cancer: Mesenchymal Subtype Has Worse Survival Outcomes

Background: Metaplastic breast carcinoma (MBC) is a rare type of breast cancer that accounts for 0.2–1% of all breast cancers. To date, there are only few institutional studies comparing survival rates between different subtypes. In this retrospective cohort study, we aim to evaluate factors effecting survival rates of different subtypes of MBC. Methods: This retrospective cohort study observed 118 nonmetastatic MBC patient records extracted from 15,244 breast cancer cases between December 2000 and December 2020. In order to analyze factors effecting survival rates of mesenchymal subtype of MBC, all cases are classified as mesenchymal (n = 45) and other (n = 48). Twenty-five cases could not be sub-classified due to the missing data. Univariate and multivariate logistic regression analyses were performed to define factors associated with survival rates. Results: Of the 15,244 cases, 118 (0.8%) were nonmetastatic MBC. 105 were triple negative and 12 were nonluminal HER2. There was no significant difference between mesenchymal and other subgroups for age, median tumor size, AJCC staging, and type of surgery. Of the five local recurrences with known subgroup, four of them had mesenchymal subtype. It is demonstrated that mesenchymal subtype was significantly associated with worse 5-year disease-free survival and disease-specific survival (HR: 2.35 [1.01–5.48], p = 0.049, and HR: 3.16 [1.06–9.47], p = 0.040 with 95% CI, respectively). Conclusion: This study is one of the few studies presenting the survival outcomes of subtypes of MBCs. Nonetheless, it is the only study demonstrating that mesenchymal subtype had worse survival outcomes. Further studies are needed to determine the outcome of different subtypes of MBCs.

Down-regulated expression of miR-99a is associated with lymph node metastasis and predicts poor outcome in stage IB cervical squamous cell carcinoma: a case-control study.

Background Lymph node metastasis (LNM) accounts for the most important route of metastasis for cervical cancer. Yet, the status of LNM is different in patients with similar clinico-pathological variables. It has been revealed that microRNAs are widely involved in the occurrence and development of various malignancies, and the tumor-suppressive or promoting effects of microRNA-99 (miR-99) family have been previously reported. This study sought to investigate the predictive value of miR-99a for lymphogenous spread and its effect on the survival of patients with early-stage cervical squamous cell cancer (CSCC).MethodsPatients with stage IB squamous cervical cancer who were treated surgically between October 2015 and November 2018 were enrolled. A total of 21 formalin-fixed paraffin-embedded tissues of pathologically confirmed positive lymph nodes were retrieved, and an additional 21 tissues of negative lymph nodes from patients well-matched on baseline characteristics were collected as the control group. TaqMan real-time quantitative polymerase chain reaction was used to examine the expression levels of miR-99a in the samples. Differential expression levels of miR-99a were compared between the 2 groups using independent sample t-test. Furthermore, the associations between miR-99a expression level and clinico-pathological parameters of these 42 patients was evaluated by Chi-square test or Fisher’s exact-probability method, and their effects on survival were assessed using Kaplan-Meier product-limit method.ResultsThere were no significant differences in baseline clinico-pathological parameters between the 2 groups (P>0.05). The expression levels of miR-99a in the node-positive group and control group were 1.61±3.09 and 16.77±30.40, respectively (P=0.029). Downregulated expression of miR-99a was closely related to depth of invasion (DOI) and lymph-vascular space invasion (P<0.05). Univariate analysis revealed that downregulated miR-99a and deeper DOI were associated with worse 5-year disease-free survival, while multivariate analysis showed that only the expression level of miR-99a was an independent factor for disease-free survival (HR =0.120; 95% CI: 0.015–0.979; P=0.048). Patients with downregulated miR-99a tended to have more unfavorable overall survival, but the difference did not reach statistical significance.Conclusions MiR-99a plays an inhibitory role in the pathogenesis of lymph node metastasis and may serve as a novel prognostic biomarker for patients with CSCC.

Prognostic value of tumor deposits for long-term oncologic outcomes in patients with stage III colorectal cancer: a systematic review and meta-analysis.

The presence of tumor deposits (TDs) in colorectal cancer is associated with a poor prognosis. In patients with the concomitant presence of both TDs and lymph nodes (LNs), there is no staging option except for the number of positive LNs alone. Therefore, to determine the prognostic value of TDs in patients with stage III colorectal cancer, meta-analyses of survival outcomes of patients with TDs were performed comparing different subgroups based on the lymph node status. PubMed, EMBASE, and the Cochrane Library were searched. Data were pooled, and overall effect size was calculated using random-effect models. Outcome measures were 5-year overall survival (OS) and 5-year disease-free survival (DFS). We included in the analysis 18 nonrandomized studies and 1 prospective study that examined 90,455 patients. N1c patients (TD + LN-) had worse 5-year DFS than TDs-negative stage III patients (TD-LN +) with a RR of 1.30 (95% CI 1.06-1.61, I2 = 47%). In subgroup analysis, N1c patients had worse 5-year DFS (RR = 1.60, 95% CI = 1.25-2.05, I2 = 40%) compared with TDs-negative N1 patients (TD-N1) whereas N1c patients had better 5-year OS (RR = 0.72, 95% CI = 0.62-0.83, I2 = 0%) and 5-year DFS (RR = 0.75, 95% CI = 0.57-0.99, I2 = 0%) compared with TDs-negative N2 patients (TD-N2). These results may suggest that current nodal staging for colorectal cancer needs modification. The presence of TDs may have more adverse oncologic outcomes than TDs-negative N1 patients. More studies are warranted to further verify these results.

Association of tumor-infiltrating lymphocytes before and after neoadjuvant chemotherapy with pathological complete response and prognosis in patients with breast cancer.

PurposeTo evaluate the predictive and prognostic value of tumor‐infiltrating lymphocytes (TILs) before and after neoadjuvant chemotherapy (NAC) in patients with breast cancer.Patients and methodsConsecutive breast cancer patients treated with NAC between August 2008 and November 2019 were retrospectively analyzed. TIL levels were evaluated of invasive tumor samples, and high expression was defined as TILs >10%. Total pathological complete response (pCR) was defined as no invasive tumor in the breast or lymph nodes. Univariate and multivariate analyses were used to assess factors associated with pCR rate, disease‐free survival (DFS), and overall survival.ResultsA total of 461 patients were included. The mean pre‐NAC TIL level was higher among patients with pCR than among patients without pCR (24.28% ± 2.34% vs. 11.34% ± 0.60%, respectively, p < 0.0001). The multivariate analysis demonstrated that a high pre‐NAC TIL level was an independent risk factor for a higher pCR (odds ratio = 3.92, 95% CI = 2.23–6.90, p < 0.001). Patients with high pre‐NAC TIL levels had a better 5‐year DFS than those with low pre‐NAC TIL levels (84.5% vs. 68.9%, HR = 0.50, 95% CI = 0.31–0.81, p = 0.005). The multivariate analysis showed that pre‐NAC TIL (HR = 0.48; 95% CI = 0.29–0.81, p = 0.006) but not post‐NAC TIL (HR = 0.89, 95% CI = 0.50–1.59, p = 0.699) was significantly associated with DFS among patients without pCR. Furthermore, patients with low pre‐ and post‐NAC TIL levels had a worse 5‐year DFS than those with high pre‐NAC TIL levels (HR = 2.09, 95% CI = 1.23–3.56, p = 0.007).ConclusionsPre‐NAC TIL level can predict pCR and DFS in patients with breast cancer receiving NAC. For patients without pCR, pre‐NAC TIL, and TIL category change, but not post‐NAC TIL, were significantly associated with DFS.

Prognostic Value of NLRP3 Inflammasome and TLR4 Expression in Breast Cancer Patients.

Inflammasome complexes play a pivotal role in different cancer types. NOD-like receptor protein 3 (NLRP3) inflammasome is one of the most well-studied inflammasomes. Activation of the NLRP3 inflammasome induces abnormal secretion of soluble cytokines, generating advantageous inflammatory surroundings that support tumor growth. The expression levels of the NLRP3, PYCARD and TLR4 were determined by immunohistochemistry in a cohort of primary invasive breast carcinomas (BCs). We observed different NLRP3 and PYCARD expressions in non-tumor vs tumor areas (p<0.0001). All the proteins were associated to more aggressive clinicopathological characteristics (tumor size, grade, tumor proliferative activity etc.). Univariate analyses were carried out and related Kaplan-Meier curves plotted for NLRP3, PYCARD and TLR4 expression. Patients with higher NLRP3 and TLR4 expression had worse 5-year disease-free survival (DFS) compared to patients with lower NLRP3 and TLR4 expression (p =0.021 and p = 0.009, respectively). In multivariate analysis, TLR4 was confirmed as independent prognostic factors for DFS (HR = 2.03, 95% CI 1.16–3.57, p = 0.014), and high NLRP3 expression showed a slight association with DFS (HR = 1.75, 95% CI 0.98–3.15, p = 0.06). In conclusion, we showed TLR4 expression as independent prognostic factors and we highlighted for the first time that high expression of NLRP3 is linked to a poor prognosis in BC patients. These results suggest that NLRP3 and TLR4 could be two new good prognostic factor for BC patients.

Prognostic impact of sterilized lymph nodes in esophageal squamous cell carcinomas after neoadjuvant chemoradiotherapy

BackgroundThe prognostic importance of sterilized lymph nodes (SLN) remains unclear in patients with esophageal squamous cell carcinomas (ESCC) treated by neoadjuvant chemoradiotherapy (nCRT). This study aimed to determine whether SLN predicted disease-free survival (DFS) in ESCC. MethodsWe enrolled 246 eligible patients who were divided into SLN (+) and SLN (-) group according to the presence or absence of fibrosis, necrosis, calcifications and/or foreign body giant cell reactions in the negative lymph nodes specimens. The prognostic value of SLN was determined using univariate and multivariate analyses. The prognostic strength of counting SLN as positive lymph nodes was evaluated using the difference of Akaike information criterion (ΔAIC). ResultsA total of 61 SLN were identified in 38 (15.4%) patients. There was no significant difference in baseline characteristics between SLN (+) and SLN (-) group. The most frequently detected SLN in the thoracic cavity and abdominal cavity were those along bilateral recurrent laryngeal nerve (21/38,55.3%) and left gastric artery (13/24,60.9%), respectively. The univariate and multivariate analyses showed SLN was an independent prognostic factor for worse DFS in the whole cohort (HR = 2.05, 95%CI = 1.08–3.90, P = 0.029). The SLN (+) group additionally correlated with worse 5-year DFS than SLN (-) group in the ypT0, ypN0 and pCR subgroups. Counting SLN as positive lymph nodes showed better prognostic strength than ignoring them. ConclusionSLN was of prognostic significance for worse DFS in patients with ESCC, particularly in patients with good response to nCRT.

Validation of tumour-free distance as novel prognostic marker in early-stage cervical cancer: a retrospective, single-centre, cohort study.

The aim of the present study was to assess the prognostic value of tumour-free distance (TFD), defined as the minimum distance of uninvolved stroma between the tumour and peri-cervical stromal ring, in early-stage cervical cancer. Patients with pathologic FIGO 2009 stage IA1-IIA2 cervical cancer, treated by primary radical surgical treatment between 01/2000 and 11/2019, were retrospectively included. Adjuvant treatment was administered according to the presence of previously established pathologic risk factors. TFD was measured histologically on the hysterectomy specimen. Pre-operative TFD measured at MRI-scan from a cohort of patients was reviewed and compared with pathology TFD. 395 patients were included in the study. 93 (23.5%) patients had TFD ≤ 3.0 mm and 302 (76.5%) had TFD > 3.0 mm. TFD ≤ 3.0 mm together with lymph vascular space involvement represented the strongest predictor for lymph node metastasis at multivariate analysis. TFD ≤ 3.0 mm was associated with worse 5-year disease-free survival (DFS) and overall survival (OS), compared with TFD > 3.0 mm (p = 0.022 and p = 0.008, respectively). DFS difference was more evident in the subgroup of patients with low-risk factors who did not receive adjuvant treatment (p = 0.002). Cohen's kappa demonstrated an agreement between TFD measured at pre-operative MRI-scan and histology of 0.654. Pathologic TFD ≤ 3.0 mm represents a poor prognostic factor significantly associated with lymph node metastasis and it may be considered a novel marker to select candidates for adjuvant treatment. The possibility to obtain this parameter by radiological imaging makes it a potential easy-measurable pre-operative marker to predict the presence of high-risk pathologic factors in early-stage cervical cancer.

Prognostic factors in patients with complete response of the tumour (ypT0) after neoadjuvant chemoradiotherapy and radical resection of rectal cancer.

There are only a few studies on the prognosis of patients with complete response of the tumour (ypT0) after neoadjuvant chemoradiotherapy (NCRT) and radical resection of rectal cancer. The aim of the study was to identify prognostic factors with regard to oncological outcome in ypT0 patients after NCRT and radical resection. All ypT0 patients with rectal cancer after NCRT and radical resection between January 2010 and June 2019 were included. Cox univariate and multivariate regression analyses were used to determine the prognostic factors of these patients. Seventy-six patients with ypT0 rectal cancer were included. In nine patients (11.8%), lymph node metastasis was identified. Age, gender, elevated carcinoembryonic antigen (CEA) and ypN+ were risk factors associated with a worse 5-year disease-free survival (DFS) rate in univariate analysis (P = 0.08, 0.14, 0.007 and 0.003, respectively). In multivariate analysis, ypN+ and elevated CEA before NCRT were independent risk factors for worse 5-year DFS (P = 0.005 and 0.021, respectively). Elevated CEA before NCRT, post-operative chemotherapy and ypN+ were risk factors associated with worse overall survival in univariate analysis (P = 0.14, 0.002 and 0.17, respectively). However, in multivariate analysis, none of these three factors were independent risk factors for worse overall survival (P = 0.20, 0.34 and 0.06, respectively). ypN+ and elevated CEA before NCRT were found to be independent risk factors for an unfavourable DFS in ypT0 patients with complete response of the tumour after neoadjuvant chemoradiotherapy for rectal cancer.

The prognostic value of the tumor-stroma ratio in squamous cell lung cancer, a cohort study

ObjectivesThe tumor-stroma ratio (TSR) is based on the relative amount of stroma in the primary tumor and has proven to be an independent prognostic factor in various solid tumors. The prognosis of patients and adjuvant treatment decision making in lung squamous cell carcinomas (SqCC) is based on the TNM classification. Currently, no other prognostic biomarkers are available. In this study we evaluated the prognostic value of the TSR in lung SqCC. Material and MethodsPatients undergoing lung surgery because of lung SqCC between 2000 and 2018 at the Leiden University Medical Center were included. The TSR was scored on hematoxylin & eosin stained tissue sections. Based on the amount of tumor-stroma, two groups were defined: ≤50% was classified as a stroma-low tumor and >50% as stroma-high. The prognostic value of the TSR was determined with survival analysis. ResultsA total of 174 stage I-III patients were included. Of them, 79 (45%) were stroma-low and 95 (55%) stroma-high. Separately analyzed for tumor stages, the TSR showed to be an independent prognostic biomarker in stage II (n = 68) for 5-year overall survival (HR=3.0; 95% CI, 1.1–8.6; p = 0.035) and 5-year disease free survival (DFS) (HR=3.6; 95% CI, 1.3–9.9; p = 0.014). Patients with a stroma-high tumor had a worse 5-year DFS in the whole cohort (HR 1.6; 95% CI, 1.0–2.4; p = 0.048), but no independent prognostic value was found. ConclusionIn stage II lung SqCC patients, stroma-low tumors have a better prognosis compared to stroma-high tumors. Moreover, adjuvant chemotherapy could be spared for these stroma-low patients.

Combining fluorine-18 fluorodeoxyglucose positron emission tomography and pathological risk factors to predict postoperative recurrence in stage I lung adenocarcinoma.

The aim of this study was to investigate the predictive value of qualitative assessment of tumor fluorine-18 fluorodeoxyglucose (F-FDG) uptake on PET and pathological risk factors for postoperative tumor recurrence in patients with stage I lung adenocarcinoma. Eighty-seven patients with stage I lung adenocarcinoma who had undergone F-FDG-PET and sequential surgical treatment without adjuvant chemotherapy were enrolled into this retrospective study. Qualitative assessment visually compared tumor F-FDG uptake with liver uptake. Tumors with one or more risk factors of tumor size of at least 4 cm, poorly differentiated, visceral pleural invasion, and lymphovascular invasion were defined as pathological high-risk tumors. Patients with pathological high-risk tumors had a significantly (P=0.015) higher standardized uptake value. A multivariable Cox's proportional hazard analysis showed that tumor F-FDG uptake>liver uptake (adjusted hazard ratio: 3.54; 95% confidence interval: 1.36-9.21, P=0.010) and pathological high-risk tumors (adjusted hazard ratio: 2.34; 95% confidence interval: 1.13-4.87, P=0.023) were significant independent predictors of postoperative tumor recurrence. Patients with tumor F-FDG uptake>liver uptake and pathological high-risk tumors had significantly (P=0.001) worse 5-year disease-free survival (38.8%) and significantly (P=0.011) worse overall survival (68.5%). Tumor F-FDG uptake>liver uptake and pathological high-risk tumors were significant independent predictors of postoperative tumor recurrence in stage I lung adenocarcinoma. Combining the two factors improves the prediction of disease-free and overall survivals, which could offer a feasible prediction model for clinically recommending adjuvant chemotherapy.

Prognostic value of advanced lung cancer inflammation index in head and neck squamous cell carcinoma

The advanced lung cancer inflammation index (ALI) is a useful tool for prediction of outcome in several malignancies. However, to date, its significance in head and neck cancer patients has not been evaluated. We retrospectively analyzed data from 93 patients who were diagnosed with head and neck squamous cell carcinoma (HNSCC) and treated with surgical resection and postoperative radiotherapy between 2002 and 2012. The aim of this study was to investigate whether the preoperative ALI is a prognostic indicator for disease-free survival and overall survival in HNSCC patients. A low ALI was significantly associated with a worse 5-year disease-free survival (47.0 vs. 83.5%, p < 0.001), and overall survival (44.4 vs. 73.6%, p = 0.008). Multivariate analysis showed that low ALI was independently associated with disease-free survival (p < 0.001) and overall survival (p = 0.02). The ALI could serve as an easily available prognostic indicator for disease-free and overall survival prediction in patients with HNSCC.