Is the TNM Staging System for Breast Cancer Still Relevant in the Era of Biomarkers and Emerging Personalized Medicine for Breast Cancer – An Institution's 10‐year Experience

We have previously demonstrated that TNM status and age were significant predictors of overall survival (OS) in our study population of Caucasian patients with invasive breast carcinoma (2000–2004 study period). However, estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) biomarker expression was not predictive of OS when using the five‐group ER/PR/HER2 subtype classification system recommended by St. Gallen International Consensus Panel in 2011. The current study reassessed the relevance of tumor biomarkers (ER/PR/HER2) in our study population using a recently proposed biologic TNM (bTNM) classification system in which the inclusion of triple negative ER/PR/HER2 phenotype (TNP) could improve the prognostic accuracy of TNM for staging, prognosis and treatment of breast cancer patients. Seven hundred eighty‐two Caucasian women diagnosed with invasive ductal carcinoma from 1998 to 2008 were grouped according to their TNM stage and TNP versus non‐TNP ER/PR/HER2 phenotype. OS was measured comparing these categories using Kaplan Meier curves and Cox regression analysis. TNM stage (Stage II = HR 1.41, 95% CI 1.01–1.97; Stage III = HR 3.96, 95% CI 2.68–5.88; Stage IV = HR 27.25, 95% CI 16.84–44.08), and age (HR 1.05, 95% CI 1.04–1.06) were significant predictors of OS. TNP significantly worsened prognosis/survival only in higher TNM stages (Stage III = HR 3.08, 95% CI 1.88–5.04, Stage IV = HR 24.36, 95% CI 13.81–42.99), but not in lower stages (I and II). Our data support the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes and show that biomarkers primarily improve the accuracy of TNM staging in advanced stages of breast cancer. We suspect that type of ER/PR/HER2 classification system(s) (St. Gallen, TNP, etc.), characteristics of populations studied (Caucasians, minorities, etc.), and the time period chosen for a study are major factors that determine impact of biomarkers on the prognostic accuracy of TNM. We propose systematic analyses of these factors before biomarkers are fully incorporated into the TNM staging system (bTNM).     

BS10THE PROGNOSTIC SIGNIFICANCE OF THE OVEREXPRESSION OF THE GROWTH FACTOR CRIPTO IN PATIENTS WITH BREAST CANCER

Purpose To determine the prognostic significance and long term survival of breast cancer patients with overexpression of the epidermal growth factor Cripto. Methodology 120 formalin fixed paraffin embedded breast cancer specimens were constructed on a tissue microarray and detection of Cripto carried out by immunohistochemical staining. Patients were treated between 1989 and 1995 and the median follow up was 125 months. We examined the association of Cripto positivity with age, menopausal status, grade and size of tumour, lymph node status, tumour type, ER/PR/HER2 status, Ki67 and Nottingham Prognostic Index (NPI). Results 48% of patients were Cripto positive. We demonstrated a significant association between overexpression of Cripto and NPI (p < 0.01), grade of tumour (p < 0.01), progesterone receptor (p = 0.02), Ki 67 (p = 0.02), tumour type (p = 0.04) and most importantly overall survival (p = 0.0003). Cox regression analysis revealed Cripto to be an independent prognostic variable for survival – HR 2.79 (95% CI 1.20–6.50). Conclusion Overexpression of Cripto is associated with high grade poor prognostic breast cancer and a significantly decreased patient survival. Future research is required to confirm these findings and to develop an anti‐Cripto humanised antibody for clinical use.     

Prognostic Significance of Survivin in Breast Cancer: Meta‐analysis

Survivin, an inhibitor of apoptosis protein, is a potentially prognostic factor and therapeutic target in breast carcinoma, but no consensus exists based on heterogeneous data. The aim of this present study is to clarify the prognostic relevance of survivin in breast cancer patients. Relevant articles were screened in PubMed and EMBASE databases. Patients’ clinical characteristics, overall survival (OS), disease/recurrence‐free survival (DFS/RFS) and positive expressed survivin rates were extracted for further analysis. Statistics extracted from Kaplan–Meier survival curves were calculated indirectly with methods developed by Parmar, Williamson, and Tierney. Multivariate Cox hazard regression analysis data were used directly in Stata 11.0. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to evaluate the prognostic role of survivin in breast cancer. Online literature search identified 23 articles containing 3,259 breast cancer patients. Our meta‐analysis of all included studies about survival outcomes showed positive correlation between poor prognosis and survivin expression. Pooled HRs (95% CIs) for OS and DFS/RFS were 1.37 (1.12–1.68) and 1.34 (1.02–1.76), respectively. Subgroup analyses considering methods used to detect survivin (immunohistochemistry or not) and localization of survivin (whole, nuclear or cytoplasm of the cell) were also conducted, and all the above analyses supported the stability of the prognostic role of survivin. In addition, our study revealed a significant association between survivin expression and lymph node metastasis (OR: 2.74; 95% CI: 1.27–5.93) or stage of breast cancer (OR: 2.01; 95% CI: 1.29–3.13). Positive expression of survivin demonstrated a significantly higher risk of recurrence and decreased OS rates in breast cancer.     

Partial Breast Irradiation or Whole Breast Radiotherapy for Early Breast Cancer: A Meta‐Analysis of Randomized Controlled Trials

Abstract: The purpose of the study was to compare treatment outcomes in patients with breast cancer treated with partial breast irradiation (PBI) and of those treated with whole breast‐radiation therapy (WBRT). We conducted a systematic review and meta‐analysis of published randomized clinical trials comparing PBI versus WBRT. Primary outcome was overall survival and secondary outcomes were locally, axillary, supraclavicular, and distant recurrences. A search of the literature identified three trials with pooled total of 1,140 patients. We found no statistically significant difference between partial and whole breast radiation arms associated with death (OR 0.912, 95% CI 0.674–1.234, p = 0.550), distant metastasis (OR 0.740, 95% CI, 0.506–1.082, p = 0.120), or supraclavicular recurrences (pooled OR 1.415, 95% CI 0.278–7.202, p = 0.560). However, PBI was statistically significantly associated with an increased risk of both local (pooled OR 2.150, 95% CI, 1.396–3.312; p = 0.001) and axillary recurrences (pooled OR 3.430, 95% CI, 2.058–5.715; p < 0.0001) compared with whole breast‐radiation. Partial breast irradiation does not seem to jeopardize survival and may be used as an alternative to whole breast‐radiation. Nevertheless the issue of loco‐regional recurrence needs to be further addressed.     

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.     

Role of Lentivirus‐Mediated Overexpression of Programmed Death‐Ligand 1 on Corneal Allograft Survival

To investigate the role of lentivirus‐mediated overexpression of programmed death‐ligand 1 (PD‐L1) on rat corneal allograft survival. A fully allogeneic rat cornea transplant model was used for in vivo studies. Lentiviral (LV) vectors are efficient tools for ex vivo genetic modification of cultured corneas. LV vector encoding for PD‐L1 (LV.PD‐L1) and LV vector encoding for eGFP (LV.eGFP, as control) were constructed and tested. PD‐L1 or eGFP expression was increased on corneal cells upon LV.PD‐L1 and LV.eGFP transduction, respectively. Both allogeneic controls and allogeneic LV.eGFP transduced corneas were uniformly rejected (MST: 13.8 ± 1.7 days and 12.3 ± 1.9 days, respectively). In contrast, allogeneic LV.PD‐L1 transduced corneas showed a high percentage (83%) of graft survival (MST > 30 days, n = 5, 15 days, n = 1). Graft opacity of PD‐L1 transduced corneas was present but was significantly reduced compared to control or eGFP expressing corneas. Flow cytometric analysis revealed that percentages of CD3⁺CD8⁺CD161⁺ and CD3⁺CD8⁺CD161^– lymphocytes were decreased in animals receiving LV.PD‐L1 transduced corneas compared to animals grafted with LV.eGFP transduced corneas. Moreover, reduced expression of proinflammatory cytokines (IFN‐γ and IL‐6) in PD‐L1 transduced corneas compared to allogeneic controls was also observed. Local PD‐L1 gene transfer in cultured corneas is a promising approach for the prolongation of corneal allograft survival and attenuation of graft rejection.     

HP40PA SYSTEMATIC REVIEW AND META‐ANALYSIS OF THE RANDOMISED CONTROLLED TRIALS ON ADJUVANT INTRAPERITONEAL CHEMOTHERAPY FOR ADVANCED GASTRIC CANCER

Purpose The purpose of this systematic review and meta‐analysis was to determine the effectiveness and safety of adjuvant intraperitoneal chemotherapy for patients with advanced gastric cancer. Methodology Studies eligible for this systematic review included those in which patients with gastric cancer were randomly assigned to receive surgery combined with intraperitoneal chemotherapy versus surgery without intraperitoneal chemotherapy. The end‐points of the meta‐analysis were overall survival, incidence of recurrence, morbidity and mortality. Results Thirteen reports of RCTs were included for appraisal and data extraction. Ten reports were judged fair‐quality and subjected to the meta‐analysis. A significant improvement in survival was associated with hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) alone (HR = 0.60; 95% CI = 0.43 to 0.83; p = 0.002) or combined with early postoperative intraperitoneal chemotherapy (EPIC) (HR = 0.45; 95% CI = 0.29 to 0.68; p = 0.0002). Survival improvement was marginally significant (p = 0.06) with normothermic intraoperative intraperitoneal chemotherapy, but not significant with EPIC alone or delayed postoperative intraperitoneal chemotherapy. Intraperitoneal chemotherapy was also found to be associated with higher risks for intra‐abdominal abscess (RR = 2.37; 95% CI = 1.32 to 4.26; p = 0.003) and neutropenia (RR = 4.33; 95% CI = 1.49 to 12.61; p = 0.007). Conclusions The present meta‐analysis indicates that HIIC with or without EPIC after resection of advanced gastric primary cancer is associated with an improved overall survival. However, increased risks of intra‐abdominal abscess and neutropenia are demonstrated.     

Role of endocrine responsiveness and HER2/neu overexpression in inflammatory breast cancer treated with multimodality preoperative therapy

We analyzed the role of endocrine responsiveness and HER2/neu overexpression in inflammatory breast cancer treated with multimodality preoperative therapy. Thirty-eight patients (estrogen receptor [ER] and/or progesterone receptor [PgR] >or=10% of the cells 21, premenopausal 14, Ki-67 expression >or=20% of the cells 30, HER2/neu overexpressed 11) were treated with six courses of epirubicin, cisplatin and fluorouracil (FU) as continuous infusion, perioperative FU as continuous infusion, mastectomy and loco-regional radiotherapy. In endocrine-responsive patients, endocrine treatment (letrozole, either alone or if premenopausal with triptorelin) was given preoperatively and as adjuvant treatment. There were 32 objective responders (84.2%; 95% CI 70.0-94.6%), three of whom had pathologic complete remission. At the multivariate analysis disease-free survival was significantly worse in patients with ER and PgR absent tumors compared with the positive expression cohort (hazards ratio [HR]: 5.91; 95% CI 1.69-20.7; p = 0.005), in particular if HER2/neu overexpression was detected (HR: 16.5; 95% CI 4.24-64.5; p < 0.0001). New multimodality and targeted strategies should be explored in endocrine nonresponsive breast cancer.     

Loss of ARID1A expression is associated with poor prognosis in invasive micropapillary carcinomas of the breast: A clinicopathologic and immunohistochemical study with long‐term survival analysis

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive and a rare subtype of breast cancer. In this study, we aimed to investigate differences between pure and mixed IMPCs of the breast in terms of clinicopathologic features, and also to analyze the significance of expressions of ARID1A and bcl‐2 regarding prognosis. Sixty‐nine of IMPCs consisting of 21 pure and 48 mixed type diagnosed at Pathology Department of Istanbul Medical Faculty between 2000 and 2011, who had complete follow‐up data, were collected to analyze ARID1A and bcl‐2 expressions immunohistochemically with prognosis. The median follow‐up period was 94 months. No significant difference was found between pure and mixed type IMPC, as well as in luminal subgroups in terms of prognostic and clinicopatologic features. ARID1A and human epidermal growth factor receptor‐2 (Her‐2) status were found to be independent prognostic factors of both overall survival (OS) (HR=6.1, 95% CI 1.4‐26.6, P=.02; HR=15.9, 95% CI 3.5‐71.5, P<.0001, respectively) and disease free survival (DFS) (HR=4, 95% CI 1.1‐14.9, P=.04; HR=7.2, 95% CI 2‐25.4, P=.002, respectively) in multivariate analysis using Cox regression. The loss of ARID1A expression was significantly related with 10 year‐OS (P=.001) and 10 year‐DFS (P=.05). Statistically significant effect of ARID1A expression was also stated on DFS and OS in Luminal B group (P=.05 and P=.001 respectively). Pure and mixed type IMPCs are similar in terms of clinicopathologic and prognostic features. The loss of ARID1A expression and Her‐2 positivity have significant adverse effect clinical outcomes of IMPC patients.     

Heterogeneity of Breast Cancer Clinical Characteristics and Outcome in US Black Women—Effect of Place of Birth

Breast cancer mortality in black women is disproportionately high; reasons for this phenomenon are still unclear. In addition to socioeconomic factors, the biology of the tumor may play a role. We analyzed 1,097 incident invasive breast cancer cases diagnosed between 2000 and 2010 in black US women from Long Island and Brooklyn. Thirty‐five percent of women had an estrogen receptor (ER) negative tumor, 46% a progesterone receptor (PR) negative tumor. ER, PR negative tumors were diagnosed at an earlier age (55.8 versus 55.3 years), at a later stage (p = 0.06), were larger in size (p = 0.04), and more frequently treated with neo‐adjuvant chemotherapy (p = 0.06) than ER, PR positive tumors. Determinants of shorter survival were: ER, PR negativity (HR: 2.2, 95% CI: 1.4–3.4), age, and stage at diagnosis (HR: 2.0; 95% CI: 1.5–2.7). ER, PR negative breast cancer born outside of the US experienced a significantly worse survival than ER, PR negative women who were born in the US. ER, PR negative tumors in black women born outside the US, mainly in the Caribbean, are biologically more aggressive than the same size and age‐matched tumors in black women born in the US. Our study suggests that environmental exposures in the country of origin may impact on host cancer interactions and cancer outcome.     

Prognostic Value of Breast Cancer Subtypes,Ki‐67 Proliferation Index,Age, and Pathologic Tumor Characteristics on Breast Cancer Survival in Caucasian Women

Estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) status are well‐established prognostic markers in breast cancer management. The triple negative breast carcinoma subtype (ER‐/PR‐/HER2‐) has been associated with worse overall prognosis in comparison with other subtypes in study populations consisting of ethnic minorities and young women. We evaluated the prognostic value of breast cancer subtypes, Ki‐67 proliferation index (Ki‐67PI), and pathologic tumor characteristics on breast cancer survival in Caucasian women in our institution, where greater than 90% of the total patient population is white. From 628 new invasive breast cancer cases in our data base (2000‐late 2004), 593 (94%) were identified in Caucasian women. ER/PR/HER2 breast cancer subtypes were classified based on St. Gallen International Expert Consensus recommendations from 2011. ER/PR/HER2 status and its effect on survival were analyzed using a Kaplan–Meier curve. ER/PR/HER2 status, grade, tumor‐node‐metastasis status (TNM)/anatomic stage, and age were analyzed in terms of survival in a multivariate fashion using a Cox regression. Ki‐67PI was analyzed between ER/PR/HER2 groups using the Kruskal–Wallis, Mann–Whitney U‐tests, and 2 × 5 ANOVA. Our results showed that patients with stage IIB through stage IV breast carcinomas were 2.1–16 times more likely to die than patients with stages IA‐B and IIA disease, respectively (95% CI 1.17–3.81 through 9.68–28.03, respectively), irrespective of ER/PR/HER2 subtype. Similar effect was seen with T2, N2/N3, or M1 tumors in comparison with T1, N0/N1, and M0 tumors. Chances of dying increase approximately 5% for every year increase in age. There was a significant main effect of Ki‐67PI between ER/PR/HER2 subtypes, p < .001, but Ki‐67PI could not predict survival. In summary, TNM status/anatomic stage of breast carcinomas and age are predictive of survival in our patient population of Caucasian women, but breast carcinoma subtypes and Ki‐67 proliferation index are not.     

Influence of the subtype on local recurrence risk of breast cancer with or without radiation therapy

PurposeTo investigate if intrinsic subtypes of breast cancer predict different risks of ipsilateral breast tumor recurrence (IBTR) following breast-conserving surgery (BCS) with and without postoperative radiation therapy.Patients and methodsWe randomized 381 women with a unifocal T1N0M0 breast cancer to BCS alone (197 women) or BCS plus postoperative radiation therapy (XRT) (184 women). All available histopathological material was re-analyzed with modern immunohistochemical methods (223 women). After 20 years of complete follow-up we analyzed the risk of IBTR by intrinsic breast cancer subtypes (luminal A, luminal B/HER2-negative, luminal B/HER2-positive, HER2-positive and triple negative). We used Cox regression analyses to estimate hazard ratios (HR) with 95% confidence intervals (CI).ResultsIn a multivariate analysis the luminal B/HER2-negative subtype, compared with the luminal A subtype, was associated with a higher risk of IBTR overall (HR 3.04; 95% CI 1.38–6.71) and in both the XRT-group (HR 5.08 95% CI 1.31–19.7) and the non-XRT-group (HR 2.58 95%CI 1.07–6.20); (p for interaction = 0.37). The risk of IBTR in the XRT- and non-XRT group, stratified by intrinsic subtype, revealed an absolute risk difference at 20 years to the benefit of XRT of 14% (95% CI 1.0%–26%) for luminal A, 17% (95% CI -6.0% to 39%) for luminal B/HER2 negative and 22% (95% CI -7.0–51%) for the high-risk group.ConclusionsAmong breast cancer patients treated with BCS, the luminal B/HER2-negative subtype predicts an about 3-fold higher risk for IBTR compared to other intrinsic subtypes independent of postoperative radiation therapy.     

Comparative Diagnostic Utility of Low‐Dose Breast‐Specific Gamma Imaging to Current Clinical Standard

To retrospectively compare low‐dose (7–10 mCi) to high‐dose (15–30 mCi) breast‐specific gamma imaging (BSGI) in the detection of breast cancer. A retrospective review of 223 consecutive women who underwent BSGI exam between February 2011 and August 2013 with subsequent pathologic analysis was performed. Women were divided into low‐dose and high‐dose groups. The results of BSGI and pathology were compared, and the sensitivity, positive predictive value (PPV), and negative predictive value (NPV) were determined. A subgroup analysis was performed to evaluate specificity using benign follow‐up imaging to establish true‐negative results. There were 223 women who met inclusion criteria with 109 patients with 153 lesions in the low‐dose group and 114 patients with 145 lesions in the high‐dose group. Pathologic correlation demonstrates sensitivities of 97.6% (95% CI = 90.9–99.6%) and 94.6% (95% CI = 84.2–98.6%; p = 0.093), PPVs of 62.1% (95% CI = 53.2–70.3%) and 50.5% (95% CI = 40.6–60.3%, p = 0.089), and NPVs of 90.5% (95% CI = 68.2–98.3%) and 92.5% (95% CI = 78.5–98.0%, p = 0.781) in the low‐dose and high‐dose groups, respectively. Subgroup analysis included 72 patients with 98 lesions in the low‐dose group and 116 patients with 132 lesions in the high‐dose group, with a specificity of 53.7% (95% CI = 39.7–67.1%) and 66.3% (95% CI = 56.2–75.2%%, p = 0.143), respectively. Low‐dose BSGI demonstrated high sensitivity and NPV in the detection of breast cancer comparable to the current standard dose BSGI, with moderate specificity and PPV in a limited subgroup analysis, which was associated with a substantial number of false‐positives.     

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.     

Outcome of HCV/HIV‐Coinfected Liver Transplant Recipients: A Prospective and Multicenter Cohort Study

Eighty‐four HCV/HIV‐coinfected and 252‐matched HCV‐monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty‐six (43%) HCV/HIV‐coinfected and 75 (30%) HCV‐monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42–64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420–3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV‐coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32–6.76), donor risk index (HR, 9.48; 95% CI, 2.75–32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03–0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV‐infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5‐year prognosis (69%[95% CI, 54–80]) to that of HCV‐monoinfected recipients. In conclusion, 5‐year survival in HCV/HIV‐coinfected liver recipients was lower than in HCV‐monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.     

Breast cancer patients with brain metastases or leptomeningeal disease: 10‐year results of a national cohort with validation of prognostic indexes

Development of brain metastasis (BM) and leptomeningeal (LM) disease in breast cancer (BC) patients indicates poor prognosis and impairs patients’ quality of life. Prognostic survival scores for BM can help predict expected survival in order to choose the most appropriate treatment. The aim of our study was to analyze national data for BC patients treated with radiation therapy for BM/LM disease and validate the applicability of different survival prognostic scores. We retrospectively evaluated medical records of 423 BC patients with BM/LM disease receiving radiation therapy between April 2005 and December 2015. Patients were classified by BC Recursive Partitioning Analysis (B‐RPA), Breast Graded Prognostic Assessment (Breast‐GPA), Modified Breast Graded Prognostic Assessment (MB‐GPA), and Simple Survival score for patients with BM from BC (SS‐BM). Overall survival (OS) was calculated from the development of BM/LM disease to death or last follow‐up date. After a median follow‐up of 7.5 years, the median OS was 6.9 months (95% CI 5.5‐7.8, range 0‐146.4) and 1‐ and 2‐year survival rates were 35% and 17%, respectively. Survival analysis showed significant differences in median OS regarding biologic subtypes (P < 0.0001), as follows: 3.2 (95% Confidence Interval (CI) 2.5‐3.9), 3.9 (95% CI 2.3‐5.6), 7.1 (95% CI 4.3‐9.8), 12.1 (95% CI 8.3‐15.9), and 15.4 (95% CI 8.8‐22.1) months for primary triple‐negative BC (TNBC), Luminal B HER2‐negative, Luminal A, HER2‐enriched, and Luminal B HER2‐positive tumors, respectively. Good Karnofsky Performance Status (KPS), single metastasis, and absence of LM or extracranial disease all demonstrated better OS in univariate and multivariate analysis. All four employed prognostic indexes provided good prognostic value in predicting survival. SS‐BM and MB‐GPA showed the best discriminating ability (Concordance indexes C were 0.768 and 0.738, respectively). This study presents one of the largest single‐institution series validating prognostic scores for BC patients with BM/LM. SS‐BM and MB‐GPA proved to be useful tools in the clinical decision‐making process.     

Impact of PD‐L1 expression and human papillomavirus status in anti‐PD1/PDL1 immunotherapy for head and neck squamous cell carcinoma—Systematic review and meta‐analysis

Programmed cell death‐1 (PD‐1) pathway inhibition in head and neck squamous cell carcinoma (HNSCC) has demonstrated inconsistent efficacy regarding human papillomavirus (HPV) status and PD‐L1 expression. This study compared outcomes in HNSCC in the context of PD‐L1 and HPV expression. Outcomes: PD‐L1 and HPV expression; overall survival (OS), and tumor response (ORR). 1088 patients received PD‐1/L1 inhibitors. Four methodologies were identified in determining PD‐L1 expression, most commonly using the Dako PD‐L1 IHC 22C3 pharmaDx assay. Using a 1% threshold, ORR was greater for PD‐L1 expressers vs non‐expressers (18.9%, CI 16.1‐21.8 v 8.8% CI 5.3‐13.7, P = 0.009), as was OS at 6 months (60.6%, CI 49.2‐71.4 v 49.0%, CI 39.1‐59.0, P = 0.04) but not at 12 or 18 months. No advantages were identified for HPV expressers. Patients expressing PD‐L1 may have a better tumor response and OS. No impact on survival or response was observed based on HPV status.     

Clinicopathological risk factors of Stage II colon cancer: results of a prospective study

Aim Adjuvant 5‐fluorouracil based chemotherapy has demonstrated benefit in Stage III colon cancer but still remains controversial in Stage II. The aim of this study was to analyse the prognostic impact of clinicopathological factors that may help guide treatment decisions in Stage II colon cancer. Method Between 1996 and 2006 data from patients diagnosed with colorectal cancer at Hospital Universitari Bellvitge and its referral comprehensive cancer centre Institut Català d′Oncologia/L’Hospitalet were prospectively included in a database. We identified 432 patients with Stage II colon cancer operated on at Hospital Universitari Bellvitge. The 5‐year relapse‐free survival (RFS) and colon‐cancer‐specific survival (CCSS) were determined. Results The 5‐year RFS and CCSS were 83% and 88%, respectively. Lymphovascular or perineural invasion was associated with RFS [hazard ratio (HR) 1.84; 95% CI 1.01–3.35]. Gender (women, HR 0.48; 95% CI 0.23–1) and lymphovascular or perineural invasion (HR 3.51; 95% CI 1.86–6.64) together with pT4 (HR 2.79; 95% CI 1.44–5.41) influenced CCSS. In multivariate analysis pT4 and lymphovascular or perineural invasion remained significantly associated with CCSS. We performed a risk index with these factors with prognostic impact. Patients with pT4 tumours and lymphovascular or perineural invasion had a 5‐year CCSS of 61%vs the 93% (HR 5.87; 95 CI 2.46–13.97) of those without any of these factors. Conclusion pT4 and lymphatic, venous or perineural invasion are confirmed as significant prognostic factors in Stage II colon cancer and should be taken into account in the clinical validation process of new molecular prognostic factors.     

Prognostic value of pathologic fracture in patients with high grade localized osteosarcoma: A systemic review and meta‐analysis of cohort studies

Consensus has not been reached regarding the ability of pathologic fracture to predict local recurrence and survival in osteosarcoma. We aim to review the available evidence to examine the association between pathologic fracture and osteosarcoma prognosis. A comprehensive literature search for relevant studies published until March 2014 was performed using PubMed, Cochrane and Web of Science. The studies investigating pathologic fracture of osteosarcoma patients were systematically analyzed. The overall relative risk (RR) was estimated using a fixed‐effect model or random‐effect model according to heterogeneity between the trials. We included nine cohort studies involving 2,187 patients (311 with pathologic fracture and 1,876 without fracture) for the analysis of survival rate and local recurrence. Studies were assessed for quality using the Newcastle–Ottawa Assessment Scale. In the fixed‐effects model, the meta‐analysis showed that pathologic fracture in osteosarcoma patients predicted poor 3‐year overall survival (OS) (RR = 1.86, 95% CI: 1.37–2.53, p < 0.001) and 5‐year OS (RR = 1.34, 95% CI: 1.06–1.70, p = 0.016). Similarly, pathologic fracture was significantly correlated with worse 3‐year event free survival (EFS) (RR = 1.52, 95% CI: 1.21–1.92, p < 0.001) and 5‐year EFS (RR = 1.24, 95% CI: 1.03–1.49, p = 0.021), whereas no significant association was noted with local recurrence (RR = 1.30, 95% CI: 0.84–2.02, p = 0.233). The meta‐analysis confirmed that pathologic fracture in osteosarcoma was a prognostic marker for both OS and EFS but not for local recurrence. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:131–139, 2015.