The clinicopathological evaluation of the breast cancer patients with brain metastases: predictors of survival

We aimed to define the clinicopathologic characteristics of breast cancer (BC) patients with brain metastasis (BM) and to investigate the effect of these parameters on survival. Seventy-nine patients diagnosed with BC and symptomatic BM between 1995 and 2011 were retrospectively evaluated. The relationship between clinicopathological features and outcome was investigated. Triple negative patients had the shortest overall survival (OS) while HR(+)HER2(?) patients had the longest (48.2  vs 88.2 months, 95 % CI; p = 0.33). Multivariate analysis demonstrated that luminal A subtype was the strongest positive predictor of prolonged OS (HR 0.48, 95 % CI 0.28–0.84; p = 0.01), while poor performance status (PS) (ECOG 3–4) at BM was the strongest predictor of shortened OS (HR 1.92, 95 % CI 1.21–3.06; p = 0.006). The patients with early-stage BC at diagnosis had BM later than the advanced-staged patients (47 months for Stage I–II disease, 23.2 months for Stage III–IV disease, 95 % CI; p = 0.002). Median survival after BM was 10.2 months (6.4–14 months, 95 % CI). The patients with liver or skin metastases had significantly shorter survival than the patients with only BM (4.8 vs 17 months, p < 0.001 for liver and 4.8 vs 11.1 months, p = 0.04 for skin). Multivariate analysis demonstrated that regardless of the BC subtype, lack of systemic therapy, and liver involvement were independent factors associated with increased risk of death (HR 4, 95 % CI 1.7–9.1; p = 0.001 and HR 2.2, 95 % CI 1.05–4.9; p = 0.036 respectively). Clinical outcome after BM mostly depends on the ECOG PS and the fact that whether the patient received systemic therapy or not. Systemic therapy prolongs survival especially in HER2 positive patients.     

Clinicopathologic characteristics and prognostic factors for HER2-positive patients with metastatic breast cancer in southern China

Introduction

The aim of the study was to analyze clinicopathologic characteristics and survival and to identify prognostic factors for Chinese patients with HER2-positive metastatic breast cancer.

Material and methods

A total of 243 patients with HER2-positive metastatic breast cancer, treated during the period 2002 to 2009, were followed up from initial disease diagnosis to death or date of last follow-up (December 2011). Cumulative survival curves were created using Kaplan-Meier analysis with the log-rank test. Prognostic factors were analyzed by univariate and multivariate Cox proportional hazards regression analysis.

Results

During follow-up, 205 patients died, with a median OS of 27 months (95% CI: 23.5, 30.5 months), and the 1-, 3-, and 5-year survival rates were 84.4%, 38.6%, and 18.1%, respectively. The median OS of HR+ patients was significantly higher than that of HR– patients (p < 0.001). Surgery (hazard ratio = 0.60, p = 0.002), endocrine therapy (hazard ratio = 0.53, p < 0.01), and anti-HER2 therapy (hazard ratio = 0.63, p = 0.003) were favorable independent prognostic factors for patients with HER2-positive metastatic breast cancer.

Conclusions

These results indicated that surgical intervention, endocrine therapy, and anti-HER2 therapy were good for these HER2 positive patients with metastatic breast cancer, but ECOG performance status < 1 and metastasis to brain were unfavorable independent prognostic factors. HR status was not an independent prognostic factor.     

Differential expression of HER2 and downstream proteins in prediction of advanced tumor phenotypes and overall survival of patients with Epstein-Barr virus-positive vs. negative gastric cancers

This study evaluated the associations of HER2 protein, HER2 gene amplification, and positivity for p-AKT, p-ERK, and p-PLCγ proteins with clinicopathological status and overall survival (OS) of patients who had Epstein-Barr virus-associated gastric cancer (EBVaGC; n = 58) or EBV-negative GC (EBVnGC; n = 329). Tissue samples were subjected to immunohistochemistry and fluorescence in situ hybridization (FISH). Results showed that EBVaGC less expressed HER2 and amplified HER2 gene. p-AKT (p = 0.035) and p-ERK (p = 0.001) were inhibited in EBVaGC than in EBVnGC, while p-PLCγ (p = 0.034) was upregulated. Among EBVaGC patients, p-ERK positivity was associated with Lauren classification (p = 0.023), and p-PLCγ positivity was inversely associated with TNM stage (p = 0.041) and lymph node metastasis (p = 0.041). In contrast, among EBVnGC patients, HER2 expression was associated with distant metastasis (p = 0.043) and p-AKT positivity was associated with intestinal subtype (p < 0.004), lymph node metastasis (p = 0.031), distant metastasis (p < 0.001), and elder age (>60y, p < 0.004). Overall analysis showed that EBVaGC patients presented better OS than EBVnGC patients (p = 0.044). Among EBVaGC patients, p-AKT positivity (p = 0.008) was associated with worse OS; as well as, HER2 high expression (p < 0.001), p-AKT positivity (p = 0.010), and p-PLCγ (p < 0.001) were associated with worse OS in EBVnGC patients. Multivariate analysis showed that distant metastasis (95% CI: 1.559 to 4.028, p < 0.001), HER2 high expression (95% CI: 1.058 to 2.454, p = 0.026), and p-PLCγ positivity (95% CI: 1.056 to 2.435, p = 0.027) were independent prognostic predictors of OS in EBVnGC patients. Our results indicated that p-AKT positive patients presented worse OS than p-AKT negative ones in EBVaGC, as well as, HER2, p-AKT, and p-PLCγ are prognostic biomarkers for OS in EBVnGC patients.     

Co-expression of receptors of the HER family correlates with clinical outcome in non-small cell lung cancer (NSCLC)

HER family receptors play a critical role in lung carcinogenesis. There is a growing body of evidence showing that cooperation between them contributes to a more aggressive tumor phenotype and impacts on their response to targeted therapy. We explored immunohistochemical co-expression of HER family receptors (HER1, HER2, HER3, HER4) and its potential role as prognostic factor in resected non-small cell lung cancer (NSCLC). Expression of HER family receptors was assessed by immunohistochemistry on 125 surgically resected NSCLC. Kaplan–Meier estimates of overall survival (OS), disease-free survival (DFS), and time to recurrence were calculated for clinical variables and HER expression, using the Cox model for multivariate analysis. HER1 and HER3 expression was detected more frequently in squamous cell carcinoma (p?=?0.002 and p?=?<0.001, respectively). HER4 was more often expressed in patients older than 60 years (p?=?0.02) and in tumors of low histological grade (p?=?0.04). Cases which expressed only HER1 had a worse DFS (p?=?0.01) and OS (p?=?0.01) compared to cases expressing HER1 and one or more of the other family members and to cases which did not express HER1 but one of the other HERs. By multivariate analysis, stage was an independent prognostic factor for DFS and OS. Furthermore, different patterns of co-expression of HER family receptors showed a statistically significant correlation with a shorter DFS (p?=?0.03) and OS (p?=?0.02). Our findings suggest that expression of HER1 only is correlated with worse DFS and OS. A better understanding of the functional relationships between these receptors may lead to a useful predictive indicator of response to targeted therapy.     

Pathological complete response and prognosis after neoadjuvant chemotherapy in patients with HER2-low breast cancer

BackgroundThe development of novel human epidermal growth factor receptor 2 (HER2) antibody drug conjugates brings encouraging opportunities for the treatment of HER2-low breast cancer. In this study, we investigated the clinical factors and prognosis of HER2-low breast cancer after neoadjuvant chemotherapy (NAC).MethodsData from patients diagnosed with HER2-zero or HER2-low breast cancer at a single center between January 2017 and December 2021 who underwent NAC followed by surgery were retrospectively reviewed. HER2 status was detected by immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH), and classified as HER2-zero (IHC 0), HER2-low (IHC 1+ or IHC 2+ and FISH–), and HER2-positive (IHC 3+ or IHC 2+ and FISH+). Baseline characteristics were analyzed and compared between the HER2-low and HER2-zero groups. Survival outcomes were analyzed using the Kaplan–Meier method with the log-rank test and Cox proportional-hazards regression analysis.ResultsThe sample comprised 132 patients with HER2-zero [n = 62 (47.0 %)] and HER2-low [n = 70 (53.0 %)] breast cancer. Relative to the HER2-zero group, the HER2-low group contained larger proportions of patients with hormone receptor (HR) positivity (37.1 % vs. 75.7 %, P < 0.001) and low nuclear grades and Ki-67 indices (both P < 0.05). The pathological complete response (pCR) rate was significantly lower in the HER2-low group than in the HER2-zero group (20.0 % vs. 37.1 %, P = 0.03). At the final follow-up [median 20 (range 4–66) months], patients with HER2-low status had significantly favorable disease-free survival (DFS) and overall survival (OS) outcomes relative to those with HER2-zero status (87.1 % vs. 71.0 %, P = 0.02 and 94.3 % vs. 82.3 %, P = 0.02, respectively). HER2-low status and pCR were independent prognostic factors for DFS [hazard ratio (HR) = 0.31, 95 % confidence interval (CI) 0.13–0.75, P = 0.009 and HR = 0.08, 95 % CI 0.01–0.67, P = 0.02, respectively].ConclusionThis analysis revealed that HER2-low status is associated significantly with HR positivity and low nuclear grades, Ki-67 indices, and pCR rate. It is also associated with favorable DFS and OS outcomes after NAC. HER2-low status and pCR are independent prognostic factors for DFS.     

Prognostic role of Amphiregulin and the correlation with androgen receptor in invasive breast cancer

BackgroundIn androgen-sensitive prostate cancer, androgenic stimulation induces the synthesis of amphiregulin (AREG). Research is lacking on the role of AREG in invasive breast cancer and the co-expression with androgen receptor (AR) status.Materials and methodsThe present study investigated the prognostic role of AREG in invasive breast cancer cases (N = 298) and the co-expression with the AR status as analysed by immunohistochemistry (IHC).ResultsThe samples were divided into groups according to AREG expression levels: low/no expression (AREG^low/no) and high expression (AREG^high). As shown by cytoplasmic immunostaining, 46.0% (137/298) of invasive breast cancers were AREG^high, and 54.0% (161/298) of cases were AREG^low/no. Co-expression of the AR and AREG accounted for 62.4% (186/298) of cases. A Kaplan–Meier analysis revealed that AREG^high and AR⁺/AREG^high decreased patients’ overall survival (OS) (P = 0.002 and P = 0.006, respectively) and disease-free survival (DFS) (P < 0.001 and P < 0.001, respectively). In Cox models, AR⁺/AREG^high remained an independent prognostic indicator of OS and DFS in invasive breast cancer (hazard ratio [HR], 0.591, 95% confidence interval [CI], 0.407-0.859, P = 0.006; HR, 0.449, 95% CI, 0.236-0.853, P = 0.014, respectively). AREG^high remained an independent prognostic indicator of OS and DFS in estrogen receptor (ER)-negative tumours (P < 0.05).ConclusionsThis study suggested that AREG and the AR were co-expressed in invasive breast cancer. Thus, AREG and the AR may be valuable prognostic biomarkers in invasive breast cancer and promising therapeutic targets, especially in ER-negative breast cancer.     

Impact of everolimus on survival after liver transplantation for hepatocellular carcinoma

Background/AimsThis study aimed to investigate whether everolimus (EVR) affects long-term survival after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC).MethodsThe data from 303 consecutive patients with HCC who had undergone LT from January 2012 to July 2018 were retrospectively reviewed. The patients were divided into two groups: 1) patients treated with EVR in combination with calcineurin inhibitors (CNIs) (EVR group; n=114) and 2) patients treated with CNI-based therapy without EVR (non-EVR group; n=189). Time to recurrence (TTR) and overall survival (OS) after propensity score (PS) matching were compared between the groups, and prognostic factors for TTR and OS were evaluated.ResultsThe EVR group exhibited more aggressive tumor biology than the non-EVR group, such as a higher number of tumors (P=0.003), a higher prevalence of microscopic vascular invasion (P=0.017) and exceeding Milan criteria (P=0.029). Compared with the PS-matched non-EVR group, the PS-matched EVR group had significantly better TTR (P<0.001) and OS (P<0.001). In multivariable analysis, EVR was identified as an independent prognostic factor for TTR (hazard ratio [HR], 0.248; P=0.001) and OS (HR, 0.145; P<0.001).ConclusionsCombined with CNIs, EVR has the potential to prolong long-term survival in patients undergoing LT for HCC. These findings warrant further investigation in a well-designed prospective study.     

FGFR2, HER2 and cMet in gastric adenocarcinoma: detection,prognostic significance and assessment of downstream pathway activation

Receptor tyrosine kinase pathways are potential therapeutic targets in gastric adenocarcinoma patients. We evaluated HER2 and cMet protein expression, and FGFR2 gene amplification to assess their prognostic significance, and downstream mediators pS6 and pERK for their potential utility as pharmacodynamic biomarkers in patients with gastric adenocarcinoma. Tissue microarrays were constructed from resection samples of 184 patients who underwent surgery for gastric/gastro-oesophageal junction adenocarcinoma. Tissue cores were obtained from the tumour body (TB), luminal surface (LS) and invasive edge (IE), and immunohistochemical and fluorescence in situ hybridisation (FGFR2) analysis was performed. FGFR2 amplification was identified in 2 % of cases and associated with worse survival (P?=?0.005). HER2 overexpression was observed in 10 % of cases and associated with increased survival (P?=?0.041). cMet overexpression was observed in 4 % of cases and associated with worse survival (P?<?0.001). On multivariate analysis, only cMet retained significance (P?=?0.006). pS6 and pERK expression were observed in 73 % and 30 % of tumours, respectively, with no association with survival. HER2 (P?=?0.004) and pERK (P?=?0.001) expression differed between tumour regions with HER2 expression increased in the LS compared with the TB and IE. These findings confirm subpopulations in gastric adenocarcinoma with poor outcome that may benefit from specific therapeutic strategies. However, we found heterogeneous HER2, pS6 and pERK overexpression, which presents challenges for their use as predictive biomarkers in gastric biopsies. The potential downstream pharmacodynamic markers pS6 and pERK were expressed across tumour regions, providing evidence that resections and biopsies would yield comparative results in clinical trials.     

The Role of Steroid Sulfatase as a Prognostic Factor in Patients with Endometrial Cancer

PurposeThe aim of the study was to determine steroid sulfatase (STS) expression in endometrial cancer patients and its correlation with disease prognosis.ResultsSixteen of the 59 patients (27.1%) were positive for STS expression. Disease free survival (DFS) was 129.83±8.67 [95% confidence interval (CI): 112.84–146.82] months in the STS positive group (group A) and 111.06±7.17 (95% CI: 97.01–125.10) months in the STS negative group (group B) (p=0.92). Overall survival (OS) was 129.01±9.38 (95% CI: 110.63–147.38) months and 111.16±7.10 (95% CI: 97.24–125.07) months for the groups A and B, respectively (p=0.45). Univariate analysis revealed that FIGO stage and adjuvant therapy are significantly associated with DFS and OS. However, in multivariate analysis, FIGO stage and adjuvant therapy did not show any statistical significance with DFS and OS. STS was also not significantly associated with DFS and OS in univariate and multivariate analysis.ConclusionSTS expression was not significantly associated with DFS and OS, despite positive STS expression in 27% of endometrial cancer patients. Therefore, the role of STS as a prognostic factor in patients with endometrial cancer remains unclear and requires further research.     

FGFR1 amplification is associated with poor prognosis and smoking in non-small-cell lung cancer

FGFR1 amplification has been identified recently as an important therapeutic target in non-small-cell lung cancer (NSCLC), particularly squamous cell carcinoma (SqCC). However, data from previous studies on the clinical implications of FGFR amplification in NSCLC are inconsistent. We evaluated FGFR1 gene copy number (GCN) in 369 cases of surgically resected NSCLC using five previously reported criteria and investigated associations between clinicopathologic parameters and FGFR1 amplification. FGFR1 amplification was found in 32/369 (8.7 %) of NSCLC and was more frequent in SqCC (18.0 % in SqCC, 3.0 % in adenocarcinoma; p?p?FGFR1 amplification was significantly associated with shorter overall survival (OS, 58.6 vs 80.0 months; p?=?0.033) and shorter disease-free survival (DFS, 58.5 vs 80.0 months; p?=?0.042) in patients with SqCC, but this was not statistically significant on multivariate analysis (OS: hazard ratio [HR]?=?1.79, 95 % confidence interval [CI]?=?0.83–3.87, p?=?0.139; DFS: HR?=?1.73, 95 % CI?=?0.93–3.21, p?=?0.081). The correlation between FGFR1 amplification and protein expression was poor (rho?=?0.08; p?=?0.123). These results suggest that FGFR1 amplification is associated with smoking history and squamous cell carcinoma histology and might indicate poor prognosis.     

Immunohistochemical over-expression of HER2 does not always match with gene amplification in invasive bladder cancer

BackgroundHER2 is a potential target of therapy in urothelial cancer (UC). Pathological case stratification according to HER2 gene amplification or HER2 protein overexpression was critical for patients’ selection in previous unsuccessful clinical trial with HER2 targeting agents.Study designWe evaluated the HER2 overexpression by immunohistochemistry (IHC) together with the amplification of the HER2 gene with chromogenic(CISH) and fluorescent (FISH) in situ hybridization in a cohort of 61 patients covering the whole spectrum of bladder UC variants, using a tissue microarray (TMA) approach.ResultsIHC was available in all the 61 cases while ISH in 37 and FISH in 42. At IHC, 2/61 cases (3%) were scored 3+; 2 (3%) scored 2+; 2 (3%) scored 1+; the remaining 55 (91%) scored 0. At CISH analysis 10/37 cases (27%) were amplified, 6 cases with HER2 amplification showed positive HER2 IHC (3+, 2+, 1+). Seven cases with IHC score 0 were amplified at CISH. FISH analysis revealed an amplification in 5/42 cases (12%). The total number of HER2amplified cases was different between chromogenic and fluorescent ISH with 5 cases amplified using FISH compared to 10 with CISH.ConclusionsIn clinical trials with HER2 targeting agents the candidate patients should be investigated not only by IHC but also by ISH, independently of the IHC results. Since also usual type UC can overexpress HER2 we recommend to extend the patients’ selection to all the histotypes of bladder cancer other than the micropapillary type.     

Effects of an educational intervention on heart failure knowledge,self-care behaviors,and health-related quality of life of patients with heart failure: Exploring the role of depression

ObjectivesTo test effects of an educational intervention on patient-reported outcomes among rural heart failure (HF) patients and to examine whether effects differed between patients with and without depression.MethodsPatients (N = 614) were randomized to usual care (UC) or 1 of 2 intervention groups. Both intervention groups received face-to-face education, followed by either 2 phone calls (LITE) or biweekly calls until they demonstrated content competency (PLUS). Follow-up lasted 24 months. Statistical analyses included linear mixed models and subgroup analyses by depression status.ResultsBoth intervention groups showed improvement in HF knowledge at 3 months (LITE–UC, p = 0.003; PLUS–UC, p < 0.001). Improvement lasted 24 months only in the PLUS group. Compared to UC, both intervention groups exhibited better self-care at 3 months (LITE–UC, p < 0.001; PLUS–UC, p < 0.001) and 12 months (LITE–UC, p = 0.001; PLUS–UC, p = 0.002). There were no differences in health-related quality of life (HRQOL) among groups. In subgroup analyses, similar effects were found among non-depressed, but not among depressed patients.ConclusionThe educational intervention improved HF knowledge and self-care, but not HRQOL. No intervention effects were observed in patients with depressive symptoms.Practice ImplicationsThe simple educational intervention is promising to improve HF knowledge and self-care. Additional strategies are needed for depressed patients.     

Discordance in receptor status between primary and metastatic breast cancer and overall survival: A single-center analysis

BackgroundThe tumor phenotype may change between primary and metastatic breast cancer. We compared the expression of estrogen receptor (ER), progesterone receptor (PR), and HER2 in a series of primary breast carcinomas (PBC) with their metastatic relapses and analyzed the impact of any changes on survival.Materials and methodsIt was a single-center retrospective study, collecting consecutive cases of metastatic breast carcinoma diagnosed in the pathology and medical oncology departments at Habib Bourguiba University Hospital in Sfax, Tunisia. An immunohistochemical study was used to assess ER, PR, and HER2 expression. Overall survival (OS) and post-metastasis survival (PMS) were evaluated using multivariable Cox regression analysis.ResultsOur study included 68 patients. ER and PR status changed in 29.4 % and 39.7 % of cases, respectively. Conversions were mainly from positive to negative status (22 % and 23.5 % for ER and PR, respectively). Differences in HER2 status were observed in 19.6 % of cases, with loss of overexpression in 6 patients (10.7 %). Adjuvant trastuzumab therapy and PBC molecular subtype (HR-, HER2+) were associated with HER2 status discordance (p = 0.02 and 0.03, respectively). On multivariable analysis, HR-negative conversion tumors were significantly associated with a worse OS (p = 0.042) and PMS (p < 0.001), compared to HR-concordant positive tumors.ConclusionThis study establishes that HR and HER2 status discordance between primary and metastatic breast carcinoma has a prognostic impact on patient outcome. Analyzing these receptors' status in all newly diagnosed cases of metastatic breast carcinoma is strongly recommended and would provide information for changing treatment strategies.     

Comparison of Liver Transplantation and Liver Resection for Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus Type I and Type II

PurposeThe aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis.Materials and MethodsA total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involved and divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were compared before and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored.ResultsTwo treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR (p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longer median RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335, respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase (AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS.ConclusionLT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels >200 ng/mL.     

Predictive factors of failure to control bleeding and 6-week mortality after variceal hemorrhage in liver cirrhosis – a tertiary referral center experience

IntroductionMortality from variceal bleeding remains high despite the therapeutic progress in severe cirrhosis. Understanding the predictive factors of failure to control bleeding (FTB) and mortality will lead to better future therapies. Comorbidities are thought to be important prognostic factors for variceal bleeding. The aim of the study was to assess the factors associated with FTB and with 42-day mortality and to evaluate the influence of comorbidities on these patients’ prognosis.Material and methodsWe prospectively included in the study all consecutive patients with cirrhosis and variceal bleeding presenting to the emergency room and we followed them up over 6 weeks. CirCom score and Charlson index were used for the assessment of comorbidities.ResultsOf the 138 patients included in the study, 27 (19.5%) were considered to have FTB. Child C class (74.07% vs. 32.43%, p < 0.001), Meld score (20.5 vs. 16.00, p = 0.004) and creatinine level (1.04 vs. 0.81, p = 0.01) were associated with FTB, but only Child class was independently associated with FTB in multivariate analysis (OR = 2.94, p = 0.006). Mortality at 42 days (21.7%) was influenced by the severity of the disease assessed through Child class (76.66% vs. 30.55% – Child C, p < 0.001) and MELD score (21.00 vs. 16.00, p < 0.001). Creatinine level (1.00 vs. 0.7, p = 0.02) and acute kidney injury (26.66% vs. 7.40%, p = 0.009) were also prognostic factors for the 6-week mortality. Comorbidities did not influence the mortality (CirCom > 1 (16.7% vs. 21.3%, p = 0.76) or Charlson index > 4 (36% vs. 47.2%, p = 0.41).ConclusionsThe severity of cirrhosis is an important prognostic factor for FTB and 42-day mortality. Identifying the factors associated with early mortality may help selecting patients needing more than conventional therapy.     

Induction chemotherapy plus nimotuzumab followed by concurrent chemoradiotherapy for advanced nasopharyngeal carcinoma

IntroductionThis study investigated the best mode for the application of nimotuzumab (Nimo) in combination with chemoradiotherapy to treat nasopharyngeal carcinoma (NPC).Material and methodsData were prospectively collected from 168 patients with NPC from September 2009 to February 2014. One hundred twelve patients received 2–3 cycles of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT), and 56 patients with well-matched propensity scores received IC + CCRT + Nimo. Patients were divided into 3 subgroups according to the application schedule of Nimo: group A, IC + CCRT; group B: IC (combined with Nimo) + CCRT; and group C: IC + CCRT (combined with Nimo). The 5-year overall survival (OS) and progression-free survival (PFS) and adverse events were investigated.ResultsWith a median follow-up of 61.4 months (range: 1.7–96.5 months), the 5-year OS and PFS for group A vs. groups B + C were 74.8 ±4.1% versus 87.0 ±4.6% (p = 0.043) and 72.7 ±4.3% vs. 83.1 ± 5.1% (p = 0.243), respectively. The 5-year OS of group B was significantly improved over that of group A (93.0 ±4.8% vs. 74.8 ±4.1%, p = 0.038); however, there was no benefit to the 5-year PFS (89.3 ±5.9% vs. 72.7 ±4.3%, p = 0.144). The 5-year OS and PFS for group C were 80.4 ±7.9% and 76.4 ±8.5%, respectively, and there was no statistically significant difference from group A (p = 0.257 and p = 0.611, respectively). No significant increase in toxicities was observed with the addition of Nimo.ConclusionsNimo administered with chemoradiotherapy is effective for NPC. Nimo concurrent with IC followed by CCRT could be the optimal mode of sequential treatment.     

Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma

Background

Podocalyxin-like protein (PODXL) is a cell surface transmembrane glycoprotein, the expression of which has been associated with poor prognosis in a range of malignancies. The aim of this study was to investigate the impact of PODXL expression on survival in esophageal and gastric adenocarcinoma.

Methods

The study cohort consists of a consecutive series of 174 patients with esophageal (including the gastroesophageal junction) or gastric adenocarcinoma, surgically treated between 2006 and 2010 and not subjected to neoadjuvant treatment. Immunohistochemical expression of PODXL was assessed in tissue microarrays with cores from primary tumors, lymph node metastases, intestinal metaplasia and adjacent normal epithelium. Survival analyses were performed on patients with no distant metastases and no macroscopic residual tumor.

Results

In the majority of cases, expression of PODXL was significantly higher in cancer cells compared to normal epithelial cells and was significantly associated with lymph node metastases and high grade tumors. In esophageal adenocarcinoma, Kaplan-Meier analyses revealed that patients with PODXL negative tumors had a superior time to recurrence (TTR) and overall survival (OS) compared to patients with PODXL positive tumors. In gastric adenocarcinoma, patients with PODXL negative tumors had a superior TTR and a trend towards an improved OS. In esophageal and gastric adenocarcinoma combined, the prognostic significance of PODXL expression on TTR was confirmed in unadjusted Cox regression analysis (HR?=?5.36, 95 % CI 1.68-17.06, p?=?0.005) and remained significant in the adjusted model (HR?=?3.39, 95 % CI 1.01-11.35, p?=?0.048). Moreover, the impact of PODXL expression on OS was also confirmed in unadjusted analysis (HR?=?2.52, 95 % CI 1.31-4.85, p?=?0.006) and remained significant in the adjusted model (HR?=?2.03, 95 % CI 1.04-3.98, p?=?0.039).

Conclusions

In esophageal and gastric adenocarcinoma, PODXL expression is an independent prognostic biomarker for reduced time to recurrence and poor overall survival. This is the first report on the prognostic role of PODXL in esophageal adenocarcinoma and validates recent findings in gastric cancer.

     

Clinical Significance of CA125 Level after the First Cycle of Chemotherapy on Survival of Patients with Advanced Ovarian Cancer

PurposeTo determine the most powerful cancer antigen 125 (CA125)-related prognostic factor for advanced epithelial ovarian cancer (EOC) and to identify cut-off values that distinguish patients with a poor prognosis from those with a good prognosis.ResultsThe CA125 level after the first chemotherapy cycle was the most significant independent prognostic factor for overall survival (OS). Time to normalization (p=0.028) and relative percentage change between CA125 levels at baseline and after the first chemotherapy cycle (p=0.021) were additional independent prognostic factors in terms of OS. The CA125 level after the first chemotherapy cycle (p=0.001) and time to normalization (p<0.001) were identified as independent prognostic factors for progression free survival (PFS).ConclusionAmong well-established CA125-related prognostic factors, serum CA125 levels after the first cycle of chemotherapy and time to normalization were the most significant prognostic factors for both OS and PFS.     

Sarcopenia as a Predictor of Prognosis in Early Stage Ovarian Cancer

BackgroundTo identify sarcopenia as a predictive prognostic factor of ovarian cancer in terms of survival outcome in patients with early-stage ovarian cancer.MethodsData of Konkuk University Medical Center from March 2002 to December 2017 were reviewed retrospectively. Eighty-two patients who underwent surgery due to early-stage (International Federation of Gynecology and Obstetrics stage I/II) ovarian cancer and had computed tomography (CT) images taken at the initial diagnosis were included. The initial CT scan images were analyzed with SliceOmatic software (TomoVision). A sarcopenia cutoff value was defined as a skeletal muscle index of ≤ 38.7 cm²/m². Overall survival (OS) times were compared according to the existence of sarcopenia, and subgroup analyses were performed.ResultsA Kaplan-Meier analysis showed a significant survival disadvantage for patients with early-stage ovarian cancer when they had sarcopenia (P < 0.001; log-rank test). Sarcopenia remained a significant prognostic factor for OS in early-stage ovarian cancer, in a Cox proportional hazards model regression analysis (HR, 21.9; 95% CI, 2.0–199.9; P = 0.006).ConclusionThis study demonstrated that sarcopenia was predictive of OS in patients with early-stage ovarian cancer. Further prospective studies with a larger number of patients are warranted to determine the extent to which sarcopenia can be used as a prognostic factor in ovarian cancer.