Clinical significance of axillary nodal ratio in stage II/III breast cancer treated with neoadjuvant chemotherapy

Purpose Neoadjuvant chemotherapy may modify the yield of involved axillary lymph nodes. The purpose of this study was to identify the clinical significance of the involved nodal ratios in patients with stage II/III breast cancer treated with neoadjuvant chemotherapy. Methods Two hundred and five stage II and III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this prospective study. The patients received three cycles of neoadjuvant chemotherapy followed by curative surgery, either breast-conserving surgery or mastectomy with axillary lymph node dissection, and received three additional cycles of docetaxel/doxorubicin chemotherapy as adjuvant. Adjuvant radiotherapy and hormonal therapy were given after adjuvant chemotherapy when indicated. Results The median follow-up duration was 28.9 months. The overall response rate (RR) for neoadjuvant chemotherapy was 77.6%. The mean nodal ratio was 0.29 (range, 0–1.0; nodal ratio ≤0.25, 121 [59.0%] vs. >0.25, 84 [41.0%]). Relapse free survival (RFS) of the patients who had a nodal ratio >0.25 was significantly shorter (Hazard Ratio (HR) = 2.701, P = 0.001). A nodal ratio >0.25 was also associated with a shorter overall survival (OS) (HR = 4.109, P = 0.006). However, RFS and OS were not different according to the absolute number of involved nodes (ANIN) (P = 0.166, P = 0.248, respectively). In multivariate analysis, the nodal ratio was an independent prognostic factor for RFS and OS (HR = 4.246, P < 0.001; HR = 7.764, P < 0.001). Conclusion Axillary nodal ratios have an independent prognostic value in stage II/III breast cancer treated with neoadjuvant chemotherapy. Nodal ratio might be a useful tool to identify the patients at high risk of relapse in the neoadjuvant setting.     

Topoisomerase II alpha protein and responsiveness of breast cancer to adjuvant chemotherapy with CEF compared to CMF in the NCIC CTG randomized MA.5 adjuvant trial

Overexpression of topoisomerase II protein (topo 2α) is postulated to be more closely associated with responsiveness to anthracycline-containing chemotherapy than human epidermal growth factor receptor type 2 (HER2) gene amplification or alterations in the topoisomerase II alpha gene (TOP2A). The authors used tissue microarrays from 477 of 710 premenopausal women with node-positive breast cancer randomized to CEF or CMF adjuvant chemotherapy in the NCIC Clinical Trials Group Mammary 5 (MA.5) trial. No significant interaction was found between treatment and continuous topo 2α level in either relapse-free (RFS) or overall survival (OS). In 136 patients (28.5%) whose tumors showed topo 2α overexpression by immunohistochemistry based on a cut-off of 13%, CEF was superior to CMF for RFS (adjusted HR 0.45; 95% CI 0.25–0.82; P = 0.009) and OS (adjusted HR 0.50; 95% CI 0.26–0.96; P = 0.04). When tumors lacked topo 2α overexpression, CEF was not superior for RFS (adjusted HR 0.88; 95% CI 0.64–1.22; P = 0.46) or OS (adjusted HR 0.95; 95% CI 0.66–1.38; P = 0.80). Interaction between topo 2α and treatment was borderline significant for RFS (P = 0.04) and OS (P = 0.05) and not substantially more significant than between TOP2A gene alteration (P _interaction = 0.09 for RFS and 0.02 for OS) or HER2 overexpression (P _interaction = 0.002 for RFS and 0.009 for OS). Topo 2α protein overexpression based on the cut-off identified in this study, TOP2A gene alterations and HER2 protein overexpression were each associated with responsiveness to anthracycline-containing chemotherapy. The topo 2α protein analysis was exploratory and will require further validation.     

Shorter survival-times following adjuvant endocrine therapy in oestrogen- and progesterone-receptor positive breast cancer overexpressing HER2 and/or with an increased expression of vascular endothelial growth factor

Purpose: To investigate the possible correlation between expression of HER2 and vascular endothelial growth factor (VEGF), and to determine the predictive value of these factors in patients receiving adjuvant endocrine therapy including the group with a breast cancer (BC) positive for both oestrogen receptor (ER) and progesterone receptor (PgR). Material and methods: By enzyme immuno-sorbent assays (ELISA) tumour levels of HER2 and VEGF proteins were determined in 679 consecutive primary BC patients, median age 63 years, median follow-up time 92 months. A total of 404 patients received adjuvant endocrine therapy, mainly tamoxifen, out of them 295 had an ER and PgR positive BC. In 160 patients, HER2 status was also determined by immunohistochemistry (IHC) using the monoclonal antibody CB11. Results: Overexpression of HER2 by IHC was found in 15% of the patients. Overexpression of HER2 by ELISA correlated with HER2 by IHC (P < 0.001) and a higher VEGF expression (P = 0.004). Patients receiving adjuvant endocrine therapy with high VEGF (RFS P = 0.0087, BCCS P = 0.0012) or over-expressing HER2 (RFS P = 0.0116, BCCS P = 0.0036) had significantly shorter survival. Factors retaining statistical significance in multivariate analyses for recurrence-free survival (RFS) were nodal status (P < 0.001), tumour size (P = 0.005) and VEGF (P = 0.032) and for breast cancer corrected survival (BCCS) nodal status (P < 0.001), tumour size (P = 0.001), ER status (P = 0.022), and VEGF (P = 0.016). Both factors were significantly correlated with survival in the group with a BC positive for both ER and PgR; VEGF (RFS P = 0.0177, BCCS P = 0.0321) and HER2 (RFS P = 0.0143, BCCS P = 0.0311). In multivariate analyses, nodal status (P < 0.001) and VEGF (P = 0.021) were independent factors for RFS. Nodal status (P < 0.001) and tumour size (P = 0.016) retained independent factors for BCCS. Combined analysis identified a high-risk group (HER2 positive and high VEGF) with significantly reduced survival. Conclusion: The results from this retrospective analysis suggest that overexpression of HER2 and higher VEGF expression may add information on patient’s outcome after adjuvant endocrine therapy in ER and PgR positive BC.     

Hepatic resection for synchronous hepatic metastasis from gastric cancer

Background

The role of surgical resection for synchronous hepatic metastases arising from gastric adenocarcinoma has not been established. This study was designed to explore the clinicopathologic features and surgical results of these patients.

Methods

Twenty-five (4.8%) of 526 patients diagnosed with synchronous hepatic metastatic gastric cancer received hepatectomy and gastrectomy at the same time; 2 cases underwent repeat hepatectomy after intrahepatic recurrence. Clinicopathologic parameters of the hepatic metastases and the surgical results for all 25 patients were analysed.

Results

The 1-, 3-, and 5-year overall survival (OS) and recurrence-free survival (RFS) rates after resection were 96.0%, 70.4%, and 29.4%, respectively, and 56.0%, 22.3%, and 11.1%, respectively. Five patients survived for more than 5 years after surgery, and no mortality has occurred within 30 days after resection. Univariate analysis revealed that patients with multiple hepatic metastases suffered poorer OS (P = 0.026) and RFS (P = 0.035) than those with solitary hepatic metastasis. Postoperative adjuvant chemotherapy was a significant indicator of a favourable OS (P = 0.022). Number of metastatic lesions remained significant in the multivariate analysis of OS and RFS (P = 0.039, P = 0.049, respectively). None of variables of the primary lesion was a significant prognostic factor for those patients.

Conclusions

Gastric cancer patients with a solitary synchronous liver metastasis may be good candidates for hepatic resection. Postoperative adjuvant chemotherapy may provide a benefit by aiding in OS.     

G-protein-coupled estrogen receptor GPR30 and tamoxifen resistance in breast cancer

Recently, we have shown that the new G-protein-coupled estrogen receptor GPR30 plays an important role in the development of tamoxifen resistance in vitro. This study was undertaken to evaluate the correlation between GPR30 and tamoxifen resistance in breast cancer patients. GPR30 protein expression was evaluated by immunohistochemical analysis in 323 patients with primary operable breast cancer. The association between GPR30 expression and tamoxifen resistance was confirmed in a second cohort of 103 patients treated only with tamoxifen. Additionally, we evaluated GPR30 expression in 33 primary tumors and in recurrent tumors from the same patients. GPR30 expression was detected in 56.7% of the breast cancer specimens investigated and it correlated with overexpression of HER-2 (P = 0.021), EGFR (P = 0.024) and lymph node status (P = 0.047). In a first cohort, survival analysis showed that GPR30 was negatively correlated with relapse-free survival (RFS) only in patients treated with tamoxifen (tamoxifen with or without chemotherapy). GPR30 expression was associated with shorter RFS (HR = 1.768; 95% CI, 1.156–2.703; P = 0.009). In a subset of patients treated only with tamoxifen, multivariate analysis revealed that GPR30 expression is an independent unfavorable factor for RFS (HR = 4.440; 95% CI, 1.408–13.997; P = 0.011). In contrast, GPR30 tended to be a favorable factor regarding RFS in patients who did not receive tamoxifen. In 33 paired biopsies obtained before and after adjuvant therapy, GPR30 expression significantly increased only under tamoxifen treatment (P = 0.001). GPR30 expression in breast cancer independently predicts a poor RFS in patients treated with tamoxifen.     

Nuclear IRS-1 predicts tamoxifen response in patients with early breast cancer

Insulin receptor substrate-1 (IRS-1) is a cytoplasmic scaffolding protein that is phosphorylated by insulin-like growth factor-I receptor and recruits downstream effectors. Recent evidence suggests that IRS-1 has a nuclear localization and function. Here we investigated whether nuclear and cytoplasmic IRS-1 levels are associated with clinico-pathological characteristics and clinical outcome in breast cancer patients. Tissue microarrays from 1,097 patients with stage I–II breast cancer were stained by immunohistochemistry for IRS-1. Nuclear and cytoplasmic IRS-1 were scored separately according to the Allred score. Nuclear IRS-1 showed a positive association with estrogen receptor (ER) (r = 0.09, P = 0.003) and progesterone receptor (PR) (r = 0.08, P = 0.008) status and a negative correlation with lymph node involvement (r = −0.10, P = 0.001). Cytoplasmic IRS-1 did not correlate with ER or PR but showed a positive correlation with tumor size (r = 0.10, P = 0.001) and S-phase fraction (r = 0.16, P < 0.001). In univariate analysis, tamoxifen-treated patients with tumors showing positive nuclear IRS-1 had a better recurrence-free survival (RFS) (P = 0.009) and overall survival (OS) (P = 0.0007), while no association was shown between cytoplasmic IRS-1 and RFS or OS in the same group of patients. In multivariate analysis of patients receiving tamoxifen, negative nuclear IRS-1 showed a significantly reduced RFS (P = 0.046) and OS (P = 0.018). Combining both PR and nuclear IRS-1, tamoxifen-treated patients with PR+/IRS-1+ tumors had a better RFS (P = 0.0003) and OS (P < 0.0001) when compared with patients with PR−/IRS-1− tumors. In conclusion, nuclear IRS-1 may be a useful marker to predict tamoxifen response in patients with early breast cancer, particularly when assessed in combination with PR.     

Real-world Data for High-risk Stage II Colorectal Cancer – The Role of Tumor Side in the Adjuvant Setting

BackgroundThe impact of sidedness in the high-risk stage II colorectal cancer (CRC) setting is uncertain. Although controversial, available data suggest a possible modest benefit of adjuvant chemotherapy (CT) in the adjuvant scenario. The aim of this study is to analyze the overall survival (OS) and recurrence-free survival (RFS) according to the tumor side.Patients and MethodsIn this single-center retrospective cohort, we analyzed patients treated between January 2011 and December 2018. We evaluated OS and RFS of high-risk patients according to the tumor side and considering adjuvant CT exposure and clinical and molecular features.ResultsA total of 1047 patients with stage II CRC were evaluated. Of these, 540 had high-risk criteria and microsatellite stability (MSS) or unknown status. One hundred fifty-seven (29%) patients had right-sided tumors, and 352 (65.2%) had left-sided tumors. Most patients received adjuvant CT, and the majority of them had T3 stage tumors, ≥ 12 lymph node resection, left tumor, MSS, and moderate differentiation. OS did not differ according to tumor side (5-year OS rates: 81.9% for right-sided tumors vs. 83% for left-sided tumors; hazard ratio, 0.91; 95% confidence interval, 0.55-1.53; P = .744). Adjuvant CT was associated with a superior RFS and OS, with 5-year OS rates of 87.7% versus 76.1% in the no-adjuvant group (hazard ratio, 0.46; 95% CI, 0.28-0.73; P = .001).ConclusionThe tumor side did not influence the outcomes in this study. Adjuvant CT was associated with improved RFS and OS in patients with high-risk stage II CRC, with a total gain of 11.6% in 5-year OS.     

Nomograms for Predicting Overall and Recurrence-free Survival From Pathologic Stage IA and IB Lung Cancer After Lobectomy

BackgroundStage I non–small-cell lung cancer (NSCLC) is potentially curable with surgical resection. Significant proportions of patients may still experience recurrence and death despite undergoing curative surgery. This study describes predictive nomograms for recurrence-free (RFS) and overall survival (OS) after lobectomy.Patients and MethodsA total of 301 patients with the American Joint Committee on Cancer pathologic stage IA and IB NSCLC who underwent open, thoracoscopic, or robotic lobectomy from January 2011 to April 2017 were analyzed. Multivariate Cox proportional hazards regression models were used to create nomograms for OS and RFS. Kaplan-Meier survival curves were calculated for OS and RFS comparing high-risk and low-risk cohorts based on nomogram scores.ResultsHistology (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.10-0.56; P = .002), lymphovascular invasion (HR, 0.46; 95% CI, 0.29-0.74; P = .001), smoking status (HR, 3.46; 95% CI, 1.25-9.55: P = .02), and total lymph nodes removed (HR, 1.05; 95% CI, 1.01-1.10; P = .021) were significant predictors for OS in a multivariate model. Lymphovascular invasion (HR, 0.55; 95% CI, 0.36-0.83; P = .0040), smoking status (HR, 2.56; 95% CI, 1.16-5.62; P = .02), total lymph nodes removed (HR, 1.04; 95% CI, 1.00-1.08; P = .029), and tumor size (HR, 1.30; 95% CI, 1.30-1.68; P = .047) were significant predictors of RFS in a multivariate model.ConclusionNomograms can predict OS and RFS for pathologic stage IA and IB NSCLC after lobectomy regardless of operative approach. The risk for death and recurrence after stratification by the nomogram scores may provide guidance regarding adjuvant therapy and surveillance.     

Endocrine therapy in obese patients with primary breast cancer: another piece of evidence in an unfinished puzzle

Obesity, defined as a body mass index (BMI) ≥30 is an independent risk factor in breast cancer and is correlated with shorter survival and enhanced recurrence rates. The present subgroup analysis of the German BRENDA-cohort aimed to investigate the correlation between BMI, recurrence-free survival (RFS) and adjuvant endocrine therapy. In this subgroup analysis, 4,636 patients were retrospectively examined using multivariate analyses. Overall 3,759 (81.1%) patients had a BMI <30 (non-obese) and 877 (18.9%) a BMI ≥30 (obese). In the group of all 3,896 (84.0%) patients with hormone-receptor-positive (HR+) breast carcinomas a significant reduction in RFS was demonstrated for those who were obese (P = 0.002; HR = 1.45 (95% CI: 1.15–1.83)), also after adjustment for Nottingham Prognostic Index (NPI) (P = 0.028; HR = 1.30 (95% CI: 1.03–1.65)). In hormone-receptor-negative (HR−) patients BMI had no influence on RFS (P = 0.380; HR = 1.20 (95% CI: 0.80–1.81)). Considering menopausal status, a significantly shorter RFS was seen in postmenopausal obese than in non-obese patients (P < 0.001; HR = 1.61 (95% CI: 1.24–2.09)), whereas the premenopausal patient group only showed a trend towards a shorter RFS (P = 0.202; HR = 1.44 (95% CI: 0.82–2.53)). The group of HR+ postmenopausal patients with normal or intermediate weight showed a non-significant statistical trend towards a survival benefit for aromatase inhibitors (AI) compared to tamoxifen (RFS: P = 0.486; HR = 1.29 (95% CI: 0.63–2.62), while obese patients tended to benefit more from tamoxifen (RFS: P = 0.289; HR = 0.65 (95% CI: 0.29–1.45)). In accordance with recently published results we demonstrated a negative effect of a high BMI on outcome in primary breast cancer. Furthermore the efficacy of AI seems dependent on BMI in contrast to tamoxifen. Prospective studies to optimise the therapy of obese breast cancer patients are urgently needed.     

Adjuvant Radiation Field Extent and Sites of Failure in Node Positive Endometrioid Endometrial Cancer

PurposeIn patients with node-positive endometrial cancer, adjuvant radiation therapy with chemotherapy decreases local-regional recurrence compared with chemotherapy alone. However, the optimal radiation field borders and extent of nodal coverage have not been well studied. In a multi-institutional cohort, survival outcomes and sites of failure were analyzed for patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IIIC endometrioid endometrial cancer treated with pelvic radiation therapy (PRT) versus extended-field radiation therapy (EFRT), which encompassed high para-aortic lymph nodes.Methods and MaterialsIn a multi-institutional retrospective study, 143 patients with FIGO stage IIIC1 or IIIC2 endometrioid endometrial cancer treated with adjuvant radiation therapy from 2000 to 2016 were identified. Patient subgroups were classified by substage and radiation field extent: stage IIIC1 received EFRT, stage IIIC1 received PRT, and stage IIIC2 received EFRT. Recurrence-free survival (RFS), overall survival (OS), and out-of-field recurrence were calculated by the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards model. Sites of failure were categorized as within or outside the radiation field.ResultsThe median follow-up was 59 months; 87% of patients received chemotherapy. The 5-year RFS and OS rates were 73% and 87%, respectively. By subgroup, 5-year RFS rates were 79% for stage IIIC1 EFRT, 73% for stage IIIC1 PRT, and 69% for stage IIIC2 EFRT (P = .4). On multivariate analysis, the recurrence risk was highest for stage IIIC2 EFRT, although this result was not statistically significant (adjusted hazard ratio, 2.0; P = .4). In-field vaginal and nodal recurrences were observed in 2 patients (1%) and 4 patients (3%), respectively. Of 78 patients with stage IIIC1 cancer treated with PRT, 5 (6%) had isolated para-aortic nodal relapse outside the radiation field; 3 were long-term survivors (more than 6 years after salvage therapy). For patients with para-aortic recurrence, 86% had lymphovascular invasion, 71% had myometrial invasion of ≥50%, and 57% had grade 3 disease.ConclusionsAdjuvant chemoradiation therapy resulted in excellent survival outcomes for patients with FIGO stage IIIC endometrioid endometrial cancer. For patients with positive pelvic nodes, isolated para-aortic relapse outside the PRT field was uncommon and amenable to salvage therapy.     

Determining the role of adjuvant therapy in Invasive Intraductal Papillary Mucinous Neoplasms; a systematic review and meta-analysis

BackgroundConflicting evidence exists regarding the role of adjuvant therapy for Invasive Intraductal Papillary Mucinous Neoplasms (i-IPMN). This meta-analysis assessed whether adjuvant therapy improves Overall Survival (OS) in patients with resected i-IPMN.MethodsA systematic review and meta-analysis was performed. The primary endpoint was the effect of adjuvant therapy on OS. Secondary endpoint evaluated adjuvant therapy with regard to nodal disease, positive resection margins, tumour grade and differentiation. A meta-analysis of pooled hazard ratios (HRs) with an inverse variance and a random-effects model was performed. Risk of bias was determined with the GRADE approach and MINORS criteria.ResultsTen articles with a total of 3252 patients were included. No statistically significant difference in the OS was noted with adjuvant therapy for i-IPMN in the entire cohort (HR = 1; 95% CI = 0.75–1.35; P = 0.98). However, a survival benefit was noted in a subgroup of patients with an aggressive disease phenotype; nodal involvement (HR = 0.56; 95% CI = 0.39–0.79; P = 0.001) and advanced staged tumours (≥stage 2, HR = 1.42; 95% CI = 1.11–1.82; P = 0.005)ConclusionsThe concurrent evidence base for adjuvant therapy for i-IPMN is limited. After acknowledging the limitations of the data, the current literature suggests that adjuvant therapy should be reserved for patients with resected i-IPMN that have adverse tumour biology.     

Does Prophylactic Paraortic Lymph Node Irradiation Improve Outcomes in Women With Stage IIIC1 Endometrial Carcinoma?

PurposeTo evaluate the impact of prophylactic paraortic lymph node (PALN) radiation therapy (RT) on clinical outcomes in patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 endometrial cancer (EC).Methods and MaterialsA multi-institutional retrospective study included patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 EC lymph node assessment, status postsurgical staging, followed by adjuvant chemotherapy and RT using various sequencing regimens. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. Univariable and multivariable analysis were performed by Cox proportional hazard models for RFS/OS. In addition, propensity score matching was used to estimate the effect of the radiation field extent on survival outcomes.ResultsA total of 378 patients were included, with a median follow-up of 45.8 months. Pelvic RT was delivered to 286 patients, and 92 patients received pelvic and PALN RT. The estimated OS and RFS rates at 5 years for the entire cohort were 80% and 69%, respectively. There was no difference in the 5-year OS (77% vs 87%, P = .47) and RFS rates (67% vs 70%, P = .78) between patients treated with pelvic RT and those treated with pelvic and prophylactic PALN RT, respectively. After propensity score matching, the estimated hazard ratios (HRs) of prophylactic PALN RT versus pelvic RT were 1.50 (95% confidence interval, 0.71-3.19; P = .28) for OS and 1.24 (95% confidence interval, 0.64-2.42; P = .51) for RFS, suggesting that prophylactic PALN RT does not improve survival outcomes. Distant recurrence was the most common site of first recurrence, and the extent of RT field was not associated with the site of first recurrence (P = .79).ConclusionsProphylactic PALN RT was not significantly associated with improved survival outcomes in stage IIIC1 EC. Distant metastasis remains the most common site of failure despite routine use of systemic chemotherapy. New therapeutic approaches are necessary to optimize the outcomes for women with stage IIIC1 EC.     

Prognostic Impact of the Findings on Thin-Section Computed Tomography in Patients with Subcentimeter Non–Small Cell Lung Cancer

IntroductionSubcentimeter NSCLC is not always an early-stage disease despite its small tumor size. We investigated the prognostic impact of such cancers on the basis of the findings of thin-section computed tomography (CT).MethodsWe evaluated the clinicopathological features and prognosis of 328 surgically resected clinical-N0 NSCLCs 1.0 cm or less in size. Consolidation-to-tumor ratio (CTR) was evaluated for all, and tumors were classified into three groups, namely, pure ground glass opacity (GGO) (CTR = 0 [n = 139]), part solid (0 < CTR < 1.0 [n = 123]), and pure solid (CTR = 1.0 [n = 66]).ResultsPathological nodal involvement was observed in seven patients, with all cases found exclusively in pure solid subcentimeter NSCLC (10.9%). Furthermore, a multivariate analysis revealed that the presence of GGO was an independently significant clinical factor in overall survival (OS) and recurrence-free survival (RFS) (OS: p = 0.0340; RFS: p = 0.0018). Histological examination revealed that 134 of the 139 cases of pure GGO (97%), 99 of the 123 cases of part solid tumor (81%), and 16 of the 66 cases of pure solid tumor (25%) were lepidic predominant lung adenocarcinoma. Evaluation of the oncological outcomes on the basis of CTR revealed that 5-year OS and RFS rates were significantly better in patients with nonsolid tumors (OS and RFS = 100%) or part solid tumors (OS = 97.5% and RFS=94.9%), whereas the OS and RFS rates of patients with pure solid subcentimeter NSCLC were 87.6% and 79.3%, respectively (OS: p = 0.0015; RFS: p < 0.0001).ConclusionsThe findings of thin-section CT are extremely important when considering the prognosis of subcentimeter NSCLC. Radiologically determined solid subcentimeter NSCLCs should be treated as invasive tumors regardless of their small size.     

Transarterial chemoembolization plus immune checkpoint inhibitor as postoperative adjuvant therapy for hepatocellular carcinoma with portal vein tumor thrombus: A multicenter cohort study

PurposeThis study aimed to assess the efficacy and safety of postoperative adjuvant transarterial chemoembolization (PA-TACE) plus immune checkpoint inhibitor (ICI) for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).Patients and methodsThis study was conducted on three centers from June 2018 to December 2020. Patients were divided into the PA-TACE (n = 48) and PA-TACE plus ICI groups (n = 42). The recurrence-free survival (RFS) and overall survival (OS) curves were depicted by Kaplan-Meier method, and the differences between the two groups were compared using log-rank test. Univariate and multivariate Cox analyses were performed to identify independent risk factors for RFS and OS. Adverse events (AEs) were assessed according to the Common Terminology Criteria for AEs (CTCAE) version 5.0.ResultsThe median RFS of the PA-TACE plus ICI group was significantly longer than the PA-TACE group (12.76 months vs. 8.11 months; P = 0.038). The median OS of the PA-TACE plus ICI group was also significanfly better than the PA-TACE group (24.5 months vs. 19.1 months; P = 0.032). PA-TACE plus ICI treatment was an independent prognostic factor for RFS (HR: 0.54, 95% CI: 0.32–0.9, P = 0.019) and OS (HR: 0.47, 95% CI: 0.26–0.86, P = 0.014). Only one patient experienced grade ≥3 immune-related AEs in the PA-TACE plus ICI group.ConclusionsPA-TACE plus ICI treatment had better efficacy in preventing recurrence and prolonging survival than PA-TACE alone for HCC patients with PVTT after R0 resection. This novel treatment modality may be an appropriate option for HCC with PVTT.     

Is postoperative adjuvant chemoradiotherapy efficacious and safe for gastric cancer patients with D2 lymphadenectomy? A meta-analysis of the literature

BackgroudAdjuvant chemoradiotherapy (CRT) for patients with gastric cancer after D2 lymphadenectomy remains controversial. The objective of the present meta-analysis was to analyze efficacy and safety of postoperative CRT and establish a consensus on whether it is suitable for the patients.MethodsWe searched PubMed, Ovid, Cochrane, and Web of Science. Statistical analysis was carried out by STATA version 12.0 software. The quality of evidence was assessed by Jadad and the Newcastle–Ottawa quality assessment scale.ResultsSix studies involving 2135 patients were included for the meta-analysis. The results showed that, compared with non-CRT, postoperative adjuvant CRT was associated with a significant improvement in 5-year overall survival (OS) (HR = 0.79, 95% CI 0.68–0.92, P = 0.002) and 5-year relapse-free survival (RFS) (HR = 0.81, 95% CI 0.70–0.93, P = 0.004). However, there were no differences in distant metastasis (RR = 0.93, 95% CI 0.82–1.06, P = 0.304) and treatment-related toxicity between the two groups.ConclusionsFrom the results of our study, postoperative adjuvant CRT may be associated with longer 5-year OS and 5-year RFS in patients with D2 lymphadenectomy, but might not improve 5-year disease-free survival compared to non-CRT. Methodologically high-quality comparative studies are needed for further evaluation.     

Prognostic Significance of Carbonic Anhydrase IX (CA-IX), Endoglin (CD105) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in Breast Cancer Patients

The aim of this study was to examine the prognostic significance of carbonic anhydrase IX (CA-IX), an endogenous marker for tumor hypoxia; endoglin (CD105), a proliferation-associated and hypoxia-inducible glycoprotein and 8-hydroxy-2′-deoxyguanosine (8-OHdG), an oxidative DNA lesion, in breast cancer patients. Immunohistochemical expressions of CA-IX, CD105 and 8-OHdG, analyzed on paraffin-embedded tumor tissues from forty female breast cancer patients, were used to assess their prognostic implication on overall survival (OS) and relapse-free survival (RFS). Patients with high CA-IX expression (above cut-off value) had a higher occurrence of relapse (P = 0.002). High CA-IX expression was significantly associated with shorter RFS (P < 0.001, hazard ratio (HR) 0.21) and shorter OS (P < 0.001, HR 0.19). Lymph node negative patients with high CA-IX expression had worse RFS (P = 0.031, HR 0.14) and OS (P = 0.005, HR 0.05). Patients with grade I&II tumors and high CA-IX expression showed shorter RFS (P = 0.028, HR 0.28) and OS (P = 0.008, HR 0.20). Worse OS (P = 0.046, HR 0.28) was found in subgroup of patients with grade II tumors and high CA-IX expression. Among all three markers, only high CA-IX expression was strong independent prognostic indicator for shorter OS (HR 4.14, 95% CI 1.28–13.35, P = 0.018) and shorter RFS (HR 3.99, 95% CI 1.38–11.59, P = 0.011). Elevated expression of CA-IX was an independent prognostic factor for decreased RFS and OS and a significant marker for tumor aggressiveness. CD105 had week prognostic value; whereas, 8-OHdG, in this study, did not provide sufficient evidence as a prognostic indicator in breast cancer patients.     

Smoking reduces survival in young females with lung adenocarcinoma after curative resection

The aim of this study was to investigate effects of smoking on the overall survival of young female lung adenocarcinoma patients after curative resection. A total of 282 surgically treated young females (younger than 40) with histologically confirmed primary lung adenocarcinoma were studied retrospectively. Overall survivals (OS) and related prognostic factors were analyzed. The 5-year OS of current-smokers and non-smokers were 20 and 36.6%, respectively (P = 0.03). As for patients with stage I disease, the 5-year OS of current-smokers and non-smokers were 50 and 68.8%, respectively, (P = 0.02). Smoking (RR = 3.15, CI 1.726–8.786) was identified as an independent prognostic factor. Current-smokers (21.4 vs. 14.5%, P = 0.03) and non-smokers (37.9 vs. 28.8%, P = 0.02) all benefited from adjuvant chemotherapy. Among young female patients with adenocarcinoma, current-smokers have a lower survival rate than non-smokers, especially patients with stage I disease.     

Aberrant Expression of CD13 Identifies a Subgroup of Standard-Risk Adult Acute Lymphoblastic Leukemia With Inferior Survival

BackgroundThe standard-risk (SR) subgroup of acute lymphoblastic leukemia in adults (aALL) is a heterogeneous category, with a 20% to 40% relapse rate and a wide range of relapse-free survival (RFS) and overall survival (OS). There is a need to identify at the outset those patients with SR-aALL who are likely to have shorter RFS and OS, so they can be treated more aggressively.Patients and MethodsFlow cytometric data of 81 patients with SR-aALL treated with a standardized protocol were retrospectively analyzed. Thirty-two patients (40%) relapsed; the median RFS and OS were 12.5 months (range, 1-136 months) and 30 months (range, 3-235 months), respectively. Twenty-six patients survived ≥ 48 months.ResultsExpression of myeloid antigen CD13, using the conventional ≥ 20% threshold and a lower ≥ 5% threshold, was seen in 17 (29%) of 59 and 29 (49%) of 59 patients, respectively, whereas dual expression of CD13 and CD33 was seen in 8 patients. CD13 positivity at ≥ 20% and ≥ 5% threshold was associated with a shorter RFS (P = .0158 and P < .0001, respectively) and OS (P = .0072 and P < .0001, respectively). Dual expression of CD13 (at ≥ 5% or ≥ 20% threshold) and CD33 was associated with inferior OS (P = .0038 and P = .0032, respectively) and RFS (P = .0705 and P = .2516, respectively). For ≥ 20% and ≥ 5% threshold of positivity, 16 of 42 and 28 of 42 who survived < 48 months were positive, compared with 1 of 17 and 1 of 17 who survived ≥ 48 months (P = .0133 and P < .0001, respectively).ConclusionAberrant expression of CD13 in ≥ 5% of blasts of patients with SR-aALL is an adverse prognostic factor, delineating a subgroup of patients with SR-aALL that should be considered for more aggressive treatment.     

Preoperative Elevation of C-Reactive Protein Is a Predictor for Adverse Oncologic Survival Outcomes for Renal Cell Carcinoma: Analysis from the International Marker Consortium Renal Cancer (INMARC)

BackgroundWe sought to analyze the usefulness of pretreatment C-reactive protein (CRP) as a predictor of survival and oncological outcomes in patients with renal cell carcinoma (RCC).MethodsRetrospective international analysis of patients with RCC with pretreatment CRP values from 2006 to 2017. A CRP of more than >5 mg/L was deemed elevated. The cohort was subdivided into 2 groups for analysis (normal CRP ≤5 mg/L; elevated CRP >5). Primary outcome was overall survival (OS) and secondary outcome was recurrence-free survival (RFS). Kaplan–Meier analyses (KMA) and multivariable analyses (MVA) were used to delineate survival outcomes and their predictors.ResultsWe analyzed 2445 patients (1641 male/804 female; normal CRP 1056/elevated CRP 1389; mean follow-up 36 months). Patients with elevated CRP had a higher incidence of hypertension (P = .001), higher body mass index (P < .001), and larger tumor size (6.0 cm vs 3.9 cm; P < .001). MVA for RFS demonstrated elevated CRP (hazard ratio [HR], 1.85; P = .005), tumor size (HR, 1.1; P < .001), and high tumor grade (HR, 3.1; P < .001) to be independent risk factors. For normal vs elevated CRP, KMA for RFS of stages 1–4 RCC revealed a 5-year RFS of 93% vs 88% (P = .001), 95% vs 83% (P = .163), 84% vs 62% (P = .001), and 58% vs 60% (P = .513), respectively. KMA MA KMA for OS of stages 1–4 RCC revealed a 5-year OS of 98% vs 81% (P = .001), 94% vs 80% (P = .103), 94% vs 65% (P = .001), and 99% vs 38% (P < .001), respectively.ConclusionsPretreatment CRP was an independent predictor of RFS and OS in an international multicenter cohort of patients with RCC.     

Angiogenesis and Blood Vessel Invasion as Prognostic Indicators for Node-Negative Breast Cancer

This study was undertaken to determine the value of angiogenesis and blood vessel invasion (BVI) using both Factor VIII-related antigen and elastica van Gieson staining in predicting 20-year relapse-free survival (RFS) and 20-year overall survival (OS) rates in Japanese patients with node-negative breast cancer. Two hundred and sixty patients were studied. We investigated nine factors, including angiogenesis (average microvessel count (AMC)), BVI, proliferating cell nuclear antigen (PCNA), p53, c-erbB-2, clinical tumor size (T), histological grade, tumor necrosis, and lymphatic vessel invasion (LVI). Twenty-five patients (9.6%) had recurrence and 17 patients (6.5%) died of breast cancer. Univariate analysis showed that BVI, AMC, T, histological grade, PCNA, p53, and tumor necrosis were significantly predictive of RFS or OS. Multivariate analysis showed that AMC, BVI, and T were significant independent factors for RFS or OS. Moreover, the combination of AMC/BVI was an especially significant factor for RFS or OS (P<0.0001, P=0.0003, respectively). When stratified by T, a significant impact of AMC or BVI on RFS was seen in patients with T1, T2, and T3 carcinomas. Multivariate analysis in patients with T2 carcinoma showed that both AMC and BVI were significant independent factors for RFS (P=0.0231, P=0.0388, respectively) and OS (P=0.0331 and P=0.0479, respectively). AMC, BVI, and T were independent prognostic indicators. As the combined impact of AMC/BVI is especially strong, AMC/BVI is useful in selecting high-risk node-negative breast cancer patients who may be eligible to receive aggressive adjuvant chemotherapy.