Effect of concomitant variant histology on the prognosis of patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy

ObjectiveTo evaluate the prognostic effect of concomitant variant histology (CVH) on survival outcomes in patients with upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy.Materials and methodsData on 417 patients with UTUC treated with radical nephroureterectomy without preoperative adjuvant therapy were retrospectively reviewed with a focus on CVH. Clinicopathological features and prognostic factors were compared between patients with pure UTUC and patients with UTUC with CVH. The primary end points were cancer-specific survival (CSS), disease recurrence-free survival (DFS), and overall survival (OS).ResultsUTUC with CVH was present in 90 (21.6%) of 417 patients. At a median follow-up of 26 months, 153 (36.7%) had died of UTUC, 161 (38.6%) had experienced a relapse, and 176 (42.2%) had died of other causes. UTUC with CVH was significantly associated with advanced tumor stage, high tumor grade, tumor diameter, lymphovascular invasion, lymph node metastasis, positive surgical margins, and tumor architecture compared with pure UTUC (all P<0.01). The estimated 5-year CSS, DFS, and OS rates were 64.9%, 61.1%, and 62.1%, respectively, in the pure UTUC group, compared with 36.3%, 34.3%, and 26.5%, respectively, in the UTUC with CVH group (P<0.001). Multivariate analysis demonstrated that CVH was an independent predictor of CSS (hazard ratio [HR] = 1.594; 95% CI: 1.125–2.259; P = 0.009), DFS (HR = 1.549; 95% CI: 1.077–2.152; P = 0.017), and OS (HR = 1.685; 95% CI: 1.212–2.343; P = 0.002).ConclusionsApproximately one-fifth of the specimens of patients with UTUC were observed to exhibit CVH. CVH was an independent prognostic factor for CSS, DFS, and OS in patients with UTUC on both univariate and multivariate analyses. Genitourinary pathologists should look for potential CVH components in UTUC specimens and report this in routine pathological practice. The presence of CVH should identify patients as candidates for consultation regarding early adjuvant therapy and intensive surveillance protocols.     

Prognostic value of FOXA1 in breast cancer: A systematic review and meta-analysis

BackgroundDespite some published papers analyzing the prognostic role of forkhead-box A1 (FOXA1) in breast cancer, it has not yet been considered as an established prognostic factor in clinical practice. The present meta-analysis evaluated the prognostic value of FOXA1 in breast cancer.MethodsPubMed, Web of Science and Embase databases were searched for relevant published literature that evaluated the correlation between FOXA1 and breast cancer. Either a fixed or random effect model was applied to estimate the pooled hazard ratio (HR) for FOXA1 prognosis in breast cancer.ResultA total of nine articles comprising 6386 breast cancer patients met the inclusion criteria. Among these nine studies, five studies and four studies investigated the prognostic association with disease-free survival (DFS), and overall survival (OS), respectively. Meta-analysis results suggested that high FOXA1 expression was positively associated with DFS (pooled HR: 0.43, 95% CI: 0.23–0.81; P < 0.05) and OS (pooled HR: 0.39, 95% CI: 0.26–0.60; P < 0.05) in breast cancer patients. No publication bias was discovered by Begg's test in this meta-analysis.ConclusionThe results from this meta-analysis indicated that elevated FOXA1 expression level was associated with better outcome in breast cancer.     

Early lymphocyte recovery predicts superior outcomes after unmanipulated haploidentical blood and marrow transplant for acute myeloid leukemia

We investigated whether early lymphocyte recovery, after unmanipulated haploidentical blood and marrow transplant (HBMT), affected clinical outcomes in 134 patients with acute myeloid leukemia (AML). Lymphocyte recovery was based on the absolute lymphocyte count on day 30 (ALC‐30). Patients with high ALC‐30 (≥294 cells/μL) had higher overall survival (OS) (77.6% vs 59.7%, P=.020) and higher leukemia‐free survival (LFS) (74.6% vs 53.7%, P=.016) than those with low ALC‐30 values. Multivariate analysis demonstrated that a high ALC‐30 was associated with improved overall survival (HR: 0.443, 95% CI: 0.233–0.841; P=.013) and LFS (HR: 0.499, 95% CI: 0.275–0.906; P=.022). Our results suggest that the ALC‐30 can predict a superior outcome after unmanipulated HBMT.     

Prognostic significance of serum lactate dehydrogenase in patients undergoing radical cystectomy for bladder cancer

BackgroundTo investigate the prognostic significance of preoperative serum lactate dehydrogenase (LDH) in patients undergoing radical cystectomy for bladder cancer (BCa).Patients and methodsA cohort of 263 patients undergoing open or laparoscopic radical cystectomy between 2011 and 2016 was studied. Baseline characteristics, hematological variables, follow-up data were collected. Kaplan-Meier curves and Cox proportional hazard regression model were applied to assess the relationship between LDH and overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS).ResultsAfter a median 34.2 (22.9–45.8) months follow-up, all-cause death, cancer-specific death, and disease recurrence occurred in 66 patients, 50 patients, and 91 patients. The elevation of serum LDH was associated with several unfavorable parameters, including advanced age, continent cutaneous urinary diversion, increased neutrophil-to-lymphocyte ratio, decreased lymphocyte-to-monocyte ratio. Patients with a higher serum LDH (> 220 U/L) had a worse OS (P < 0.001), CSS (P < 0.001) and DFS (P < 0.001). Multivariate Cox analysis suggested that elevated LDH was an independent predictor for OS (hazard ratio [HR]: 3.113, 95% confidence interval [CI]: 1.524–6.358; P = 0.002), CSS (HR: 4.564, 95% CI: 2.008–10.373; P < 0.001), DFS (HR: 2.051, 95% CI: 1.125–3.739; P = 0.019). Medical history of diabetes, high pT stage, and positive lymph node also were adverse predictors for oncological outcomes of BCa patients in multivariate analysis.ConclusionsPreoperative serum LDH is an independent prognostic biomarker for OS, CSS, and DFS in patients undergoing radical cystectomy for BCa, which can be incorporated into prognostic models.     

Prognosis of invasive micropapillary carcinoma compared with invasive ductal carcinoma in breast: A meta-analysis of PSM studies

BackgroundInvasive micropapillary carcinoma (IMPC) is a rare histological subtype of breast cancer. The outcome of IMPC remains controversial; we conducted a meta-analysis of propensity score matching (PSM) studies to evaluate the prognostic difference between IMPC and invasive ductal carcinoma (IDC).MethodsWe searched PubMed, EMBASE and the Cochrane library for PSM studies comparing survival data between IMPC and IDC. The summarized odds ratios (ORs) and 95% confidence interval (95% CI) are calculated by STATA software utilizing fixed-effect or random-effect models, depending on the heterogeneity of the eligible studies.ResultsEight PSM studies including 2102 IMPC patients are included in the meta-analysis. Compared with IDC, IMPC has a similar overall survival (OS) (estimated OR = 0.87, 95% CI: 0.61–1.25), but a shorter relapse free survival (RFS) (estimated OR = 1.31, 95% CI: 1.06–1.61); the shorter RFS might owe to the significantly higher loco-regional recurrence rate of IMPC (estimated OR = 3.60, 95% CI: 1.99–6.52). Funnel plots and Egger’s tests are used to evaluate publication bias and the p value for OS and RFS are 0.036 and 0.564 respectively.ConclusionsOur results demonstrate that compared with IDC, IMPC exhibits a similar, even favorite OS, but a shorter RFS; and the shorter RFS might owe to the significantly higher loco-regional recurrence rate of IMPC. These results could contribute to the individualized therapy and follow-up strategies for IMPC patients.     

Low ERCC1 expression is associated with prolonged survival in patients with bladder cancer receiving platinum-based neoadjuvant chemotherapy

PurposeExcision repair cross-complementation group 1 enzyme (ERCC1) plays a key role in the removal of platinum induced DNA adducts and cisplatin resistance. Prognostic role of ERCC1 expression in the neoadjuvant setting in bladder cancer has not been reported before. We evaluated the prognostic role of ERCC1 expression in bladder cancer receiving platinum-based neoadjuvant chemotherapy.Materials and methodsThirty-eight patients with muscle invasive bladder cancer who received neoadjuvant platinum-based chemotherapy were included. Clinical and histopathologic parameters along with immunohistochemical ERCC1 staining were examined and correlated with response rates and survival.ResultsPathologic complete response rates were similar between patients with low and high ERCC1 expression. Median disease-free survival (DFS) was 9.3 vs. 20.5 months (P = 0.186) and median overall survival (OS) was 9.3 vs. 26.7 months (P = 0.058) in patients with high ERCC1 expression compared with those with low expression, respectively. In multivariate Cox regression analysis: pathological complete response (pCR) after chemotherapy (hazard ratio (HR) 0.1, 95% CI 0.012–0.842, P = 0.034) and high ERCC1 expression (HR 3.7, 95% CI 1.2–11.2, P = 0.019) were significantly associated with DFS. Patient age (>60 vs. ≤60 years) (HR 3.4, 95% CI 1.2–9.4, P = 0.018), the presence of pCR (HR 0.11, 95% CI 0.014–0.981, P = 0.048) and high ERCC expression (HR 6.1, 95 CI 1.9–19.9, P = 0.002) were significantly associated with OS.ConclusionsOur results showed that high ERCC1 expression was independently associated with shorter disease-free and overall survival in patients with bladder cancer who received neoadjuvant platinum-based chemotherapy. ERCC1 may represent a potential predictive marker for platinum-based treatment in bladder cancer.     

Lymph node ratio as best prognostic factor in triple‐negative breast cancer patients with residual disease after neoadjuvant chemotherapy

Although lymph node status (ypN) is one of the most important prognostic factors of survival, the lymph node ratio (LNR) has emerged as an equitable factor. We aimed to compare the prognostic value of both ypN and LNR in patients with residual triple‐negative breast cancer (TNBC) after neo‐adjuvant chemotherapy (NAC). This was a retrospective cohort study of patients treated in a tertiary care center during the period 2000‐2014. We stratified the population based on LNR (≤0.20, 0.20‐0.65, and >0.65) and ypN (N1, N2, and N3) status. The overall survival (OS) and progression‐free survival (PFS) were estimated with Kaplan‐Meier curves and the log‐rank + test. We further compared patient mortality and disease recurrence using multivariate Cox regression analysis. We evaluated 169 patients with a median follow‐up of 87 months. At 2 years of follow‐up, patients with low‐risk LNR compared to those with moderate and high risk had a higher PFS (54% vs 31% vs 18%, respectively; P < .001) and OS (74% vs 64% vs 45%, respectively; P < .001). Moreover, ypN1 patients compared to ypN2 and ypN3 showed similar results in PFS (53% vs 35% vs 19%, respectively; P = .001) and OS (73% vs 69% vs 43%, respectively; P < .001). Compared to the low‐risk population, patients with moderate (hazard ratio [HR]: 3.50; 95% confidence interval [CI]: 1.41‐8.71) and high risk (HR: 6.90; 95% CI: 2.29‐20.77) had a worse PFS. Regarding OS, moderate‐risk (HR: 2.85; 95% CI: 1.10‐7.38) and high‐risk patients (HR: 6.48; 95% CI: 2.13‐19.76) showed considerably worse outcomes. On the other hand, ypN staging was not associated with PFS or OS in the multivariate analysis. The LNR is a better prognostic factor of survival than ypN. The LNR should be considered in the stratification of risk after NAC in patients with TNBC.     

Association between lymphovascular invasion and oncological outcome in node-negative upper tract urothelial carcinoma with different stage

ObjectivesTo evaluate the prognostic impact of lymphovascular invasion (LVI) on node-negative upper tract urothelial carcinoma (UTUC) in patients treated with radical nephroureterectomy (RNU).Materials and methodsA retrospective study was performed in single tertiary referral center of middle Taiwan between 2001 and 2015. Seven hundred and twenty-eight patients were diagnosed of UTUC and underwent RNU with ipsilateral bladder cuff excision including 303 and 195 patients with N0 and Nx status respectively. LVI status was assessed as a prognostic factor for cancer-specific (CSS) and overall survival (OS) using univariate and multivariate Cox regression analysis.ResultsLVI was observed in 82 patients (16.5%). LVI presentation associated with smoking status, advanced tumor stage, high tumor grade, positive surgical margin, and consequence lung/liver/bone metastasis. In the multivariate analysis, LVI was failed to predict CSS, OS, and disease-free survival (DFS) (hazard ratio [HR] [95% confidence interval [CI]: 1.07 [0.55–2.09], 1.05 [0.62–1.79], 1.15 [0.69–1.92], in CSS, OS, DFS, respectively). In the subgroup analysis of pT1-2 disease, the CSS, OS, and DFS were associated with LVI status (HR [95% CI]: 2.29 [0.44–11.84], 3.17 [1.16–8.67], 2.66 [1.04–6.79], in CSS, OS, DFS, respectively). In contrast, there was no difference in pT3 disease.ConclusionIn conclusion, LVI status was not associated with survival outcomes of node-negative UTUC in our study. The subgroup analysis showed different prognostic impacts of LVI status in node-negative UTUC with T1-2 and T3 stage. Further evidence to clarify the prognostic effect is needed to make LVI became a practical factor in clinical decision-making.     

Prognostic role of caveolin in breast cancer: A meta-analysis

IntroductionRecent studies have shown that Caveolin play a potential role as a prognostic biomarker of cancers. The aim of the present study was to clarify whether caveolin could be a prognostic factor for patients with breast cancer.Materials and methodsAll eligible studies were identified using Medline and EMBASE system. The patients' clinical characteristics and survival outcome were extracted. The meta-analysis was performed to clarify the prognostic role of caveolin and the correlation between the caveolin expression and clinical characteristics.ResultsAfter full text review, 19 articles were identified as eligible articles. We found that negative stromal Caveolin-1 (Cav-1) expression could predict the poor prognosis of breast cancer. The combined HR (95% CI) for OS was 4.12[2.05, 8.28], while the combined HR (95% CI) for DFS/PFS was 3.69[2.57, 5.31]. The combined HR (95% CI) of tumor epithelial Cav-1 for OS was 0.78[0.54, 1.12], and the combined HR (95% CI) for DFS/PFS was 1.32[0.76, 2.29]. The combined HR (95% CI) of tumor epithelial Cav-2 for CSS was 2.04[0.91, 4.56]. Odds ratios (ORs) showed that the stromal Cav-1 expression was associated with the AJCC stage, T status, lymph metastasis, distant metastasis, and histological grade (G grade) and many biomarkers. We found ORs of Cav-1 and Cav-2 expression in tumor epithelial cells varied in clinical characteristics and biomarkers.ConclusionOur results indicated that negative expression of stromal Cav-1 was associated with poor prognosis of breast cancer, while the detection of Cav-1 and Cav-2 in tumor epithelial cells was not.     

Neutropenia in kidney and liver transplant recipients: Risk factors and outcomes

No studies have directly compared the key characteristics and outcomes of kidney (KTx) and liver transplantation (LTx) recipients with neutropenia. In this single‐center, retrospective, cohort study, we enrolled all adult patients who received a KTx or LTx between 2000 and 2011. Neutropenia was defined as 2 consecutive absolute neutrophil count (ANC) values <1500/mm³ in patients without preexisting neutropenia. The first neutropenia episode occurring during the first year post‐transplantation was analyzed. A total of 663 patients with KTx and 354 patients with LTx met the inclusion criteria. Incidence of neutropenia was 20% in KTx and 38% in LTx, respectively. High‐risk CMV status and valganciclovir (VGCV) use were significant predictors of neutropenia for KTx recipients, but only VGCV use vs nonuse in LTx recipients. Neutropenia was associated with worse survival in KTx recipients (adjusted HR 1.95, 95% CI 1.18‐3.22, P<.01), but not in LTx recipients (adjusted HR 0.75, 95% CI 0.52‐1.10, P=.15). Sixteen acute rejection episodes were associated with preceding neutropenia in KTx recipients (HR 1.77, 95% CI 1.16‐2.68, P=.007) and 24 acute rejection episodes in LTx recipients (HR 1.41, 95% CI 0.97‐2.04, P=.07). Incidence of infection was similar in patients with and without neutropenia among KTx and LTx recipients.     

Anatomic versus non-anatomic resection of hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis

The efficacy of anatomical resection (AR) and non-anatomical resection (NR) in the treatment of hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remains unknown. This study compared the safety and outcomes of these surgical procedures. A systematic literature search was conducted. The main outcomes were overall survival (OS), disease-free survival (DFS). Overall hazard ratio (HR) was calculated from Kaplan–Meier plots and outcomes using random-effects models. There was no significant difference in postoperative complications between the AR and NR groups (risk ratio [RR]: 0.92, 95% confidence interval [CI]: 0.72–1.17, p = 0.496). OS was higher with AR at 1 year (RR: 0.66, 95% CI: 0.45–0.98, p = 0.037), 3 years (RR: 0.64, 95% CI: 0.50–0.82, p = 0.000), and 5 years (RR: 0.76, 95% CI: 0.65–0.89, p = 0.001). AR was associated with a higher OS rate (HR: 0.62, 95% CI: 0.47–0.82, p = 0.001). AR was associated with improved DFS at 1 year (RR: 0.65, 95% CI: 0.52 to 0.82, p = 0.000), 3 years (RR: 0.75, 95% CI: 0.66 to 0.86, p = 0.000), and 5 years (95% CI: 0.75 to 0.94, p = 0.002). Compared with NR, AR had significant advantages on overall HR of DFS (HR: 0.64, 95% CI: 0.45 to 0.91, p = 0.012). In conclusion, AR was associated with higher rates of OS and DFS in HCC patients with MVI. Thus, for well-presented liver function HCC patients which are predicted to have positive MVI, AR is recommended.     

The pretreatment neutrophil‐lymphocyte ratio may predict prognosis of patients with liver cancer: A systematic review and meta‐analysis

Background

At present, several studies have reported that the pretreatment neutrophil‐lymphocyte ratio (NLR) may be associated with the prognosis of liver cancer. Nevertheless, their conclusions remain controversial. Thus, we performed a meta‐analysis of 54 studies to evaluate the prognostic value of NLR.

Method

Databases including PubMed, Embase, Cochrane Library, and Web of Science were searched to July 2017.

Result

A total of 54 studies including 12 979 patients were included in this meta‐analysis. Elevated NLR had a close relationship with the overall survival (OS) (HR 1.52; 95% CI 1.39‐1.67), recurrence‐free survival (RFS) (HR 1.84; 95% CI 1.48‐2.30), and disease‐free survival (DFS) (HR 1.71; 95% CI 1.39‐2.11) of liver cancer, respectively. In addition, elevated NLR was associated with the presence of tumor vascular invasion (OR 2.35; 95% CI 1.93‐2.86), multiple tumors (OR 1.38; 95% CI 1.15‐1.66), alpha‐fetoprotein ≥ 400 ng/mL (OR 1.51; 95% CI 1.15‐1.98), presence of HbsAg (+) (OR 0.68; 95% CI 0.51‐0.90), and cirrhosis (OR: 0.59; 95% CI 0.44‐0.80).

Conclusion

This meta‐analysis indicated that elevated NLR may be an effective and noninvasive indicator for prognosis of patients with liver cancer.     

Influence of age as a continuous variable on the prognosis of patients with pT1-2N1 breast cancer

PurposeTo assess the influence of age as a continuous variable on the prognosis of pT1-2N1 breast cancer and examine its decision-making value for postmastectomy radiotherapy (PMRT).MethodsWe retrospectively evaluated 5438 patients with pT1-2N1 breast cancer after mastectomy in 11 hospitals. A multivariable Cox proportional hazards regression model with penalized splines was used to examine the relationship between age and oncologic outcomes.ResultsThe median follow-up was 67.0 months. After adjustments for confounding characteristics, nonsignificant downward trend in locoregional recurrence (LRR) risk was observed with increasing age (P-non-linear association = 0.640; P-linear association = 0.078). A significant non-linear association was found between age and disease-free survival (DFS) and overall survival (OS) (P-non-linear association <0.05; P-linear association >0.05, respectively). The DFS and OS exhibited U-shaped relationships, with the hazard ratios (HRs), reaching a nadir at 50 years old. A decreased risk of LRR with PMRT vs. no PMRT (HR = 0.304, 95% CI: 0.204–0.454) was maintained in all ages. The HR of PMRT vs. no PMRT for DFS and OS gradually increased with age. In patients ≤50 years old, PMRT was independently associated with favorable LRR, DFS, and OS, all P < 0.05). In patients >50 years old, PMRT was independently associated with reduced LRR (P = 0.004), but had no effect on DFS or OS.ConclusionsAge was an independent prognostic factor for pT1-2N1 breast cancer; PMRT provided survival benefits for patients ≤50 years old, but not for patients >50 years old.     

Efficacy of anthracycline/taxane‐based neo‐adjuvant chemotherapy on triple‐negative breast cancer in BRCA1/BRCA2 mutation carriers

This study aims to estimate the pathologic complete response (pCR) rate after neo‐adjuvant chemotherapy and to compare disease‐free survival (DFS) and overall survival (OS) between pCR and non‐pCR groups of patients with triple‐negative breast cancer (TNBC) and deleterious BRCA1 or BRCA2 mutation. We carried out a retrospective analysis of 53 patients including 46 BRCA1, 6 BRCA2, and 1 combined BRCA1 and BRCA2 mutation. All patients had been diagnosed with triple‐negative breast cancer (TNBC) between 1997 and 2014. Neo‐adjuvant therapy consisted of regimens that were based on anthracycline or an anthracycline‐taxane doublet. DFS included any relapse or second cancer. The Kaplan‐Meier method and the log‐rank test were used to compare pCR and non‐pCR groups. A pCR was observed in 23 (42.6% [95% CI, 29.2%‐56.8%]) of the TNBC included. The pCR rate was 38.3% [95% CI, 26%‐55%] among BRCA1 mutation carriers, and 66% among the 6 BRCA2 mutation carriers. Median follow‐up was 4.4 years (range 0.62‐16.2 years) and did not differ between the groups (P = .25). Fifteen relapses and six second cancers were recorded during the follow‐up period. Eleven deaths occurred, all of which were in the non‐pCR group. DFS (P < .01) and OS (P < .01) were significantly better in the pCR group than the non‐pCR group. This study shows a high pCR rate after neo‐adjuvant therapy in BRCA‐mutated triple‐negative breast cancer, and the survival results confirm the prognostic value of pCR in this group. These outcomes should be considered as a basis of comparison to be used by future studies about new therapies in this domain.     

Whether histologic subtyping affect the oncological outcomes of patients with papillary renal cell carcinoma: evidence from a systematic review and meta-analysis

BackgroundWhether the histologic subtype (type 1 and type 2) of papillary renal cell carcinoma (pRCC) is a tool to predict the prognosis is of great debate. This study is aimed to evaluate the prognostic significance of histologic subtype in patients with pRCC after surgery through a systematic review and meta-analysis.MethodsWe searched PubMed, the Web of Science, Cochrane library and EMBASE databases to identify studies published until January 20, 2021 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were deemed eligible if they compared the overall survival (OS), cancer specific survival (CSS), recurrence-free survival (RFS) or disease-free survival (DFS) between patients with type 1 or type 2 pRCC. And the corresponding hazard ratios (HRs) and 95% conference intervals (CIs) were collected for meta-analysis and further subgroup analysis.ResultsOverall 22 studies with a total of 4,494 patients were considered eligible and included for the systematic review and meta-analysis. The pooled results showed that type 2 pRCC was associated with a worse OS (pooled HR 1.61, 95% CI: 1.10–2.36, P=0.02) and CSS (pooled HR 1.59, 95% CI: 1.00–2.51, P=0.05). However, the subgroup analysis yielded the same result as the initial analysis only when the HRs were extracted from univariate analysis. In studies with multivariate analysis, type 2 pRCC was not statistically associated with a worse OS (pooled HR 1.22, 95% CI: 0.97–1.53, P=0.27), CSS (pooled HR 1.16, 95% CI: 0.67–2.00, P=0.60), and DFS (pooled HR 1.33, 95% CI: 0.93–1.91, P=0.12) compared to type 1 pRCC.DiscussionHistologic subtype is not an independent prognostic factor for patients with pRCC, although the result needs to be taken with caution. And studies with retrospective study design, larger sample size and longer follow-up period are required to verify these results.     

Microsatellite and RAS/RAF Mutational Status as Prognostic Factors in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Background

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to prolonged survival for selected patients with colorectal (CRC) peritoneal metastases (PM). This study aimed to analyze the prognostic role of micro-satellite (MS) status and RAS/RAF mutations for patients treated with CRS.

Methods

Data were collected from 13 Italian centers with PM expertise within a collaborative group of the Italian Society of Surgical Oncology. Clinical and pathologic variables and KRAS/NRAS/BRAF mutational and MS status were correlated with overall survival (OS) and disease-free survival (DFS).

Results

The study enrolled 437 patients treated with CRS-HIPEC. The median OS was 42.3 months [95% confidence interval (CI), 33.4–51.2 months], and the median DFS was 13.6 months (95% CI, 12.3–14.9 months). The local (peritoneal) DFS was 20.5 months (95% CI, 16.4–24.6 months). In addition to the known clinical factors, KRAS mutations (p = 0.005), BRAF mutations (p = 0.01), and MS status (p = 0.04) were related to survival. The KRAS- and BRAF-mutated patients had a shorter survival than the wild-type (WT) patients (5-year OS, 29.4% and 26.8% vs 51.5%, respectively). The patients with micro-satellite instability (MSI) had a longer survival than the patients with micro-satellite stability (MSS) (5-year OS, 58.3% vs 36.7%). The MSI/WT patients had the best prognosis. The MSS/WT and MSI/mutated patients had similar survivals, whereas the MSS/mutated patients showed the worst prognosis (5-year OS, 70.6%, 48.1%, 23.4%; p = 0.0001). In the multivariable analysis, OS was related to the Peritoneal Cancer Index [hazard ratio (HR), 1.05 per point], completeness of cytoreduction (CC) score (HR, 2.8), N status (HR, 1.6), signet-ring (HR, 2.4), MSI/WT (HR, 0.5), and MSS/WT-MSI/mutation (HR, 0.4). Similar results were obtained for DFS.

Conclusion

For patients affected by CRC-PM who are eligible for CRS, clinical and pathologic criteria need to be integrated with molecular features (KRAS/BRAF mutation). Micro-satellite status should be strongly considered because MSI confers a survival advantage over MSS, even for mutated patients.

     

Prognostic Significance of Post-Operative Morbidity Severity Score After Potentially Curative D2 Gastrectomy for Carcinoma

Background

Survival and relapse after gastric cancer surgery are largely attributed to tumor biology and surgical radicality; yet, other prognostic factors have been reported, including respiratory sepsis and anastomotic leakage, but not global morbidity severity score (MSS). The hypothesis tested was that MSS would be associated with both disease-free (DFS) and overall survival (OS).

Methods

Consecutive 373 patients undergoing potentially curative surgery for gastric adenocarcinoma between 2004 and 2016 in a UK cancer network were studied. Complications were defined prospectively as any deviation from a pre-determined post-operative course within 30 days of surgery and classified according to the Clavien-Dindo severity classification (CDSC). Primary outcome measures were DFS and OS.

Results

Post-operative complications were identified in 127 (34.0%) patients, which was associated with 9 (2.4%) post-operative deaths. Five-year DFS and OS were 35.9 and 38.5% for patients with a post-operative complication compared with 59.5 and 61.5% in controls (p?<?0.001, p?=?0.001, respectively). On multivariable DFS analysis, post-operative morbidity [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.06–2.50, p?=?0.026] was independently associated with poor survival. On multivariable OS analysis, post-operative morbidity HR 2.25 (95% CI 1.04–4.85, p?=?0.039) and CDSC HR 1.76 (95% CI 1.35–2.29, p?<?0.001) were independently associated with poor survival. These associations were also observed in patients with TNM stage I and II disease with morbidity HR 7.06 (95% CI 1.89–26.38, p?=?0.004) and CDSC HR 2.93 (95% CI 1.89–4.55, p?<?0.001) offering independent prognostic value.

Conclusion

Post-operative CDSC was an important independent prognostic factor after potentially curative gastrectomy for carcinoma associated with both DFS and OS. Prehabilitation strategies to minimize complications are warranted.

     

The impact of molecular status on survival outcomes for invasive micropapillary carcinoma of the breast

Invasive micropapillary carcinoma (IMPC) is an uncommon variant of breast cancer. Previous studies demonstrated this subtype is often hormone receptor (HR)‐positive, resulting in survival outcomes similar to invasive ductal carcinoma. However, many of these studies were conducted prior to HER2 testing availability. We aim to determine the impact of molecular marker status (including HER2 status) on IMPC survival outcomes. The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy‐proven IMPC from 2007 to 2012. Only patients with known HR and HER2 status were included. Cox multivariate regression was used to determine prognostic factors. In total, 865 patients were included; median follow‐up was 2.5 years. Overall, 651 patients (75.3%) had HR + HER2? disease, 128 (14.8%) had HR + HER2+ disease, 41 (4.7%) had HR‐HER2 + disease, and 45 (5.2%) had triple negative disease. Patients with triple negative disease were more likely to have poorly differentiated histology (66.7%), lymphovascular invasion (73.3%), stage 3 disease (37.8%), undergone mastectomy (68.9%), and positive surgical margins (15.6%). On Cox multivariate regression, those with triple negative disease had worse overall survival (hazard ratio [HR] 7.28, P < 0.001). Other adverse prognostic factors included African‐American descent (HR 2.24, P = 0.018), comorbidity score of 1 (HR 2.50, P = 0.011), comorbidity score ≥2 (HR 3.27, P = 0.06), and ≥3 positive lymph nodes (HR 3.23, P = 0.007). Similar to invasive ductal carcinoma, triple negative disease in IMPC results in worse survival outcomes. This is the largest and first study to characterize molecular status (including HER2 status) in patients with IMPC and its impact on survival outcomes.     

C-reactive protein and neutrophil-lymphocyte ratio are prognostic in metastatic clear-cell renal cell carcinoma patients treated with nivolumab

ObjectiveTo evaluate the impact of markers of systemic inflammation such as C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) on outcomes of metastatic clear-cell renal cell carcinoma (m-ccRCC) patients treated with nivolumab.Patients and methodsWe retrospectively evaluated m-ccRCC patients treated with nivolumab and collected known prognostic factors and survival data. We used Kaplan-Meier survival analysis and cox proportional hazards regression analysis to study prognostic factors for overall survival (OS) and progression-free survival (PFS) since start of nivolumab. Harrell's C-index was used to evaluate the models.ResultsWe included 113 patients. Median OS and PFS after initiation of nivolumab was 15 (interquartile range 7–28) and 4 months (interquartile range 3–11), respectively.Elevated baseline CRP was associated with worse OS (HR per 25 mg/l 1.35, 95% CI 1.16–1.52, P < 0.001) and PFS (HR per 25 mg/l 1.19, 95% CI 1.08–1.35, P = 0.001), independent from the international metastatic renal cell carcinoma database consortium (IMDC) prognostic criteria, increasing the model's C-index from 0.72 to 0.77 for OS and 0.59 to 0.62 for PFS.Elevated NLR was associated with worse OS (HR 1.10, 95% CI 1.04–1.17, P = 0.002) and PFS (HR 1.06, 95% CI 1.01–1.11, P = 0.03) independent from the other IMDC prognostic criteria. The model's C-index decreased from 0.72 to 0.70 for OS and increased from 0.59 to 0.60 for PFS.ConclusionsElevated baseline CRP and NLR predict worse OS and PFS on nivolumab in m-ccRCC patients. Including baseline CRP in the IMDC prognostic model improves its discriminatory power to predict OS and PFS since start of nivolumab.