Overall Survival Outcomes In Patients Research Articles

Postoperative adjuvant IMRT for patients with HCC and portal vein tumor thrombus: An open-label randomized controlled trial

AimsTo investigate the impact of postoperative intensity modulated radiation therapy (IMRT) in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) after partial hepatectomy +/− thrombectomy. MethodsFrom July 2013 to June 2016, consecutive patients with HCC and PVTT who underwent partial hepatectomy were randomly assigned to 2 groups: a control group and an adjuvant IMRT group. Survival outcomes in the 2 groups were studied. ResultsThe 52 patients in this study were equally randomized into 2 groups with comparable clinicopathological data. The median disease-free survival (DFS) and overall survival (OS) were 9.1 ± 1.6 months, 18.9 ± 1.8 months for the adjuvant RT group and 4.1 ± 0.5 months, 10.8 ± 1.3 months for the control group, respectively. The 1-, 2- and 3-years overall survival rates were significantly better in the adjuvant IMRT group (76.9%, 19.2%, and 11.5%; respectively) than the control group (26.9%, 11.5% and 0%, respectively; p = 0.005). ConclusionsPostoperative IMRT significantly improved the overall survival outcomes in patients with HCC and PVTT after partial hepatectomy +/− thrombectomy.

Novel predictive models of early death less than one year in patients with metastatic RCC treated with first-line tyrosine kinase inhibitors.

552 Background: Although the IMDC model can provide useful information on overall survival outcomes in patients with metastatic renal cell carcinoma (mRCC), this model maybe invaluable in patients who experience early death less than one year after initial systemic therapy. Here, we aimed to develop a new prognostic model which can predict early death in patients with mRCC receiving first line tyrosine kinase inhibitors (TKI). Methods: We retrospectively evaluated a total of 498 patients treated with first line line TKI among 537 patients with mRCC at our institution. The primary endpoint was the rate of early death within 1 year after first line TKI administration. We selected statistically significant factors predicting early death by performing multiple logistic regression. Modified IMDC model 1 based on existing IMDC model and model 2 composed of new variables were generated. The prediction accuracy was evaluated by calculating the concordance index (C-index). Area under curve (AUC) and net reclassification index (NRI) using ROC curve analysis were used to compare the predictive power between the models. Results: Overall mortality was 59.0% (n = 294) in 498 patients, and early mortality was 19.7% (n = 98) within 1 year after first line TKI administration. The C-index of the IMDC model for early death was 0.655. Five variables were selected: previous nephrectomy, BMI, multiple metastases, previous metastasectomy and serum albumin level. The C-index of the model 1, which includes five new variables plus variables in the IDMC model, is 0.823, showing a significant improvement over the IDMC model. In model 2, hemoglobin and neutrophil levels were added in new five variables, and the C-index was 0.822. For the IMDC model, there was a significant NRI difference in both models 1 and 2, but no significant difference in NRI between models 1 and 2. (-0.0368 [95% CI = -0.1416 - 0.0681]; p = 0.491). Conclusions: In this study, we suggest modified IMDC models for predicting ‘early death less than one year in patients with mRCC treated with first line TKI. These novel models can provide better treatment strategies and counseling in patients with mRCC who were treated by first line TKI.

PT318 - Impact of cytoreductive nephrectomy on overall survival outcomes in patients with metastatic renal cell carcinoma and brain and/or bone metastases

PT318 - Impact of cytoreductive nephrectomy on overall survival outcomes in patients with metastatic renal cell carcinoma and brain and/or bone metastases

Prognostic value of the mRNA expression of members of the HSP90 family in non-small cell lung cancer.

The aim of the present study was to investigate the potential prognostic value of members of the heat shock protein (HSP)90 family in non-small cell lung cancer (NSCLC) patients. The mRNA expression profiles of 1,926 NSCLC patients, which was available from the Kaplan-Meier plotter database, were included in the study. High expression of HSP90AA1 mRNA was significantly associated with a poorer rate of overall survival (OS) for all NSCLC patients [hazard ratio (HR), 1.21; 95% confidence interval (CI): 1.06–1.37; P=0.004], as well as for patients with adenocarcinoma (ADE; HR, 1.3; 95% CI: 1.02–1.65; P=0.034), but no significant correlation was identified for squamous cell carcinoma (SCC) patients (HR, 1.08; 95% CI: 0.85–1.38; P=0.51). High expression of HSP90AB1 and HSP90B1 mRNA was significantly associated with poorer rates of OS in lung SCC and ADE patients combined, as well as in lung ADE patients alone. By contrast, high expression of tumor necrosis factor receptor-associated protein 1 (TRAP1) mRNA was significantly associated with improved OS rates in all NSCLC patients combined (HR, 0.88; 95% CI: 0.77–0.99; P=0.041), as well as ADE patients. In stratified survival analysis, a high expression of HSP90AA1, HSP90AB1 and HSP90B1 predicted poor prognosis in stage I NSLCC patients, suggesting that these genes may serve as stage-independent prognostic indicators. As an elevated expression of HSP90AA1, HSP90AB1, HSP90B1 and TRAP1 was associated with poorer OS outcomes in patients with NSCLC, these HSP90 members may be potential prognostic biomarkers and drug targets for the treatment of NSCLC.

Distinct roles of histamine H1- and H2-receptor signaling pathways in inflammation-associated colonic tumorigenesis.

Inflammatory bowel disease (IBD) is a well-known risk factor for the development of colorectal cancer. Prior studies have demonstrated that microbial histamine can ameliorate intestinal inflammation in mice. We tested the hypothesis whether microbe-derived luminal histamine suppresses inflammation-associated colon cancer in Apcmin/+ mice. Mice were colonized with the human-derived Lactobacillus reuteri. Chronic inflammation was induced by repeated cycles of low-dose dextran sulfate sodium (DSS). Mice that were given histamine-producing L. reuteri via oral gavage developed fewer colonic tumors, despite the presence of a complex mouse gut microbiome. We further demonstrated that administration of a histamine H1-receptor (H1R) antagonist suppressed tumorigenesis, while administration of histamine H2-receptor (H2R) antagonist significantly increased both tumor number and size. The bimodal functions of histamine include protumorigenic effects through H1R and antitumorigenic effects via H2R, and these results were supported by gene expression profiling studies on tumor specimens of patients with colorectal cancer. Greater ratios of gene expression of H2R ( HRH2) vs. H1R ( HRH1) were correlated with improved overall survival outcomes in patients with colorectal cancer. Additionally, activation of H2R suppressed phosphorylation of mitogen-activated protein kinases (MAPKs) and inhibited chemokine gene expression induced by H1R activation in colorectal cancer cells. Moreover, the combination of a H1R antagonist and a H2R agonist yielded potent suppression of lipopolysaccharide-induced MAPK signaling in macrophages. Given the impact on intestinal epithelial and immune cells, simultaneous modulation of H1R and H2R signaling pathways may be a promising therapeutic target for the prevention and treatment of inflammation-associated colorectal cancer. NEW & NOTEWORTHY Histamine-producing Lactobacillus reuteri can suppress development of inflammation-associated colon cancer in an established mouse model. The net effects of histamine may depend on the relative activity of H1R and H2R signaling pathways in the intestinal mucosa. Our findings suggest that treatment with H1R or H2R antagonists could yield opposite effects. However, by harnessing the ability to block H1R signaling while stimulating H2R signaling, novel strategies for suppression of intestinal inflammation and colorectal neoplasia could be developed.

Prognostic value of end-of-induction PET response after first-line immunochemotherapy for follicular lymphoma (GALLIUM): secondary analysis of a randomised, phase 3 trial.

Initial results from the ongoing GALLIUM trial have shown that patients with follicular lymphoma have a longer progression-free survival after first-line immunochemotherapy with obinutuzumab than with rituximab. The aim of this secondary analysis was to evaluate the prognostic value of PET-CT responses after first-line immunochemotherapy in the GALLIUM study. GALLIUM is an open-label, parallel-group randomised, phase 3 trial, which recruited previously untreated patients with CD20-positive follicular lymphoma (grades 1-3a; disease stage III/IV, or stage II with largest tumour diameter ≥7 cm) who were aged 18 years or older and met the criteria for needing treatment. Eligible patients were randomly assigned in a 1:1 ratio to receive intravenous administration of obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1, then day 1 of subsequent cycles) or rituximab (375 mg/m2 on day 1 of each cycle), in six 21-day cycles with cyclophosphamide, doxorubicin, vincristine, and prednisone (known as CHOP; oral administration) followed by two 21-day cycles of antibody alone, or eight 21-day cycles cyclophosphamide, vincristine, and prednisone (known as CVP; oral administration), or six 28-day cycles with bendamustine, followed by maintenance antibody every 2 months for up to 2 years. The primary endpoint of the trial, investigator-assessed progression-free survival, has been reported previously. This secondary analysis reports PET and CT-based responses at end-of-induction therapy and explains their relation with progression-free and overall survival outcomes in patients with available scans. As per protocol, during the trial, PET scans (mandatory in the first 170 patients enrolled at sites with available PET facilities, and optional thereafter), acquired at baseline and end of induction (PET population), were assessed prospectively by investigators and an independent review committee (IRC) applying International Harmonisation Project (IHP) 2007 response criteria, and retrospectively by the IRC only applying current Lugano 2014 response criteria. IRC members (but not study investigators) were masked to treatment and clinical outcome when assessing response. The landmark analyses excluded patients who died or progressed (contrast enhanced CT-based assessment of progressive disease, or started next anti-lymphoma treatment) before or at end of induction. GALLIUM is registered at ClinicalTrials.gov, number NCT01332968. 1202 patients were enrolled in GALLIUM between July 6, 2011, and Feb 4, 2014, of whom 595 were included in the PET population; 533 (IHP 2007; prospective analysis), and 508 (Lugano 2014; retrospective analysis) were analysed for progression-free survival (landmark analysis). At end of induction, 390 of 595 patients (65·5% [95% CI 61·6-69·4]) achieved PET complete response according to IHP 2007 criteria, and 450 (75·6% [95% CI 72·0-79·0]) obtained PET complete metabolic response according to Lugano 2014 criteria. With a median of 43·3 months of observation (IQR 36·2-51·8), 2·5-year progression-free survival from end of induction was 87·8% (95% CI 83·9-90·8) in PET complete responders and 72·0% (63·1-79·0) in non-complete responders according to IRC-assessed IHP 2007 criteria (hazard ratio [HR] 0·4, 95% CI 0·3-0·6, p<0·0001). According to Lugano 2014 criteria, 2·5-year progression-free survival in complete metabolic responders was 87·4% (95% CI 83·7-90·2) and in non-complete metabolic responders was 54·9% (40·5-67·3; HR 0·2, 95% CI 0·1-0·3, p<0·0001). Our results suggest that PET is a better imaging modality than contrast-enhanced CT for response assessment after first-line immunochemotherapy in patients with follicular lymphoma. PET assessment according to Lugano 2014 response criteria provides a platform for investigation of response-adapted therapeutic approaches. Additional supportive data are welcomed. F Hoffmann-La Roche.

Prognostic Value of Chronic Hepatitis B Virus Infection in Patients with Breast Cancer in a Hepatitis B Virus Endemic Area

In addition to hepatocellular carcinoma, chronic hepatitis B virus (HBV) infection has been reported to be associated with increased morbidity and mortality in other cancers. However, the impact of chronic HBV infection on the prognosis of breast cancer (BC) remains unknown. The aim of our study was to evaluate the prognostic value of HBV infection for BC in an endemic area of HBV in China. The study included a total of 1904 patients with early breast cancer who underwent mastectomy or breast conserving surgery. 212 patients (11.1%) were identified with chronic HBV infection due to serum hepatitis B surface antigen (HBsAg) positive. HBsAg-positive patients had inferior overall survival (OS) (84.9% vs. 90.4%, P = 0.005) and hepatic metastasis-free survival (HMFS) (92.5% vs. 97.1%, P=0.016) at five years than HBsAg-negative patients. Chronic HBV infection was an independent predictor of poor OS outcome in patients with BC (multivariate analysis; HR, 1.52; P = 0.038), but not for HMFS. Subgroup analysis showed that chronic HBV infection was an unfavorable independent prognostic factor for OS in patients with stage II/III BC (HR, 1.59; P = 0.025), with respective 5-year OS and HMFS rates of 81.9% and 90.5% compared with 88.5% and 96.3% in HBsAg-negative patients. In stage I patients, there was no significant difference in 5-year OS (95.8% vs 97.1%; P = 0.629) and HMFS (100% vs 99.0%; P = 0.447). In conclusion, chronic HBV infection predicts a worse prognosis in patients with stage II/III BC, but not stage I BC. Funding Statement: This work was supported by the National Natural Science Foundation of China (grant numbers 81672598, 81772961). Declaration of Interests: The authors state that there is no conflict of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of the Sun Yat-sen University Cancer Center in accordance with the ethical principles of the Helsinki Declaration of the World Medical Association. The clinical staging was carried out in accordance with the 7th edition of the Tumor TNM Staging System developed by Union for International Cancer Control (UICC) and American Joint Committee on Cancer(AJCC) on Cancer Staging.

Varices on computed tomography are surrogate of clinically significant portal hypertension and can predict survival in compensated cirrhosis patients.

To investigate prognostic value of varices on computed tomography (CT) and redefine surrogate criteria for clinically significant portal hypertension (CSPH). We retrospectively enrolled 241 patients with compensated cirrhosis who underwent hepatic venous pressure gradient (HVPG) measurement from 2008 to 2013. Using CT and upper endoscopy findings obtained within 3months from HVPG measurement, patients were classified into three groups: presence of standard surrogate for CSPH, defined as presence of varices on upper endoscopy and/or splenomegaly associated with thrombocytopenia (Group 1, n=139); varices on CT without standard surrogate for CSPH (Group 2, n=41); and free from both (Group 3, n=61). HVPG value and overall survival (OS) rates were compared among three patient groups. Revised surrogate for CSPH was defined as presence of standard surrogate and/or presence of varices on CT (i.e. both Group 1 and Group 2). Mean HVPG value in Group 2 was significantly higher than that in Group 3 (10.3mmHg vs 6.5mmHg, P<0.001), but significantly lower than that in Group 1 (10.3mmHg vs 13.1mmHg, P<0.001). Seven-year OS rates in Group 2 was similar to those in Group 1 (57.0% vs 62.7%, P=0.591), but significantly poorer than those in Group 3 (57.0% vs 84.0%, P=0.015). The presence of revised surrogate for CSPH was a significant predictive factor for OS (P=0.025, Hazard ratio=2.71 [1.14-6.45]) on multivariate analysis whereas standard surrogate for CSPH was not (P=0.849). The presence of varices on CT was a significant sign for CSPH, predicting poor OS outcome in patients with compensated cirrhosis.

Adjuvant pegylated interferon therapy improves the survival outcomes in patients with hepatitis-related hepatocellular carcinoma after curative treatment: A meta-analysis.

Background:Hepatocellular carcinoma (HCC) is one of the most common cancers and the second leading cause of cancer-related deaths in men worldwide. Surgical resection of HCC remains the mainstay treatment procedure. As a result of hepatitis viral infection, the postoperative survival outcome in patients with HCC is not satisfactory. Recently, studies have reported that due to its treatment effect on hepatitis infection, pegylated interferon (Peg-IFN)-based therapy could improve the survival outcome after the treatment of hepatitis-related HCC. However, the postoperative effect of this regimen on the survival outcomes in patients with hepatitis-related HCC remains debatable. The present study conducted a meta-analysis to evaluate the effects of adjuvant Peg-IFN-based therapy on the survival outcomes in patients with hepatitis-related HCC after the curative treatment.Methods:A systematic search was conducted to identify studies on the survival outcomes in patients with hepatitis-related HCC after a curative treatment with adjuvant Peg-IFN. PubMed, EmBase, and Cochrane Library databases were searched until September 20, 2017. The retrieved studies were independently assessed by 2 reviewers, to identify the potentially eligible studies and extract data of interest. STATA software (Version 10.0, STATA Corporation, College Station, Texas) software was used for all statistical analyses.Results:The pooled results showed that adjuvant Peg-IFN-based therapy improved the 3- and 5-year recurrence-free survival (RFS) rates of patients with hepatitis-related HCC (3-year RFS, HR = 0.80; 95% CI: 0.64–0.99, P = .04; P = .81 for heterogeneity; 5-year RFS, HR = 0.82; 95% CI: 0.67–0.99, P = .04; P = .84 for heterogeneity). For the 5-year overall survival (OS) outcomes of Peg-IFN therapy for hepatitis-related HCC after the curative treatment, the pooled results showed a significant difference between the 2 groups (HR = 0.67; 95% CI: 0.47–0.97, P = .03; P = .99 for heterogeneity).Conclusions:Adjuvant Peg-IFN-based therapy could improve the RFS and OS outcomes in patients after curative treatment of hepatitis-related HCC, with no severe adverse effects.

Chemotherapy and radiotherapy for advanced pancreatic cancer.

Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options. Over the past few decades, many anti-cancer therapies have been tested in the locally advanced and metastatic setting, with mixed results. This review attempts to synthesise all the randomised data available to help better inform patient and clinician decision-making when dealing with this difficult disease. To assess the effect of chemotherapy, radiotherapy or both for first-line treatment of advanced pancreatic cancer. Our primary outcome was overall survival, while secondary outcomes include progression-free survival, grade 3/4 adverse events, therapy response and quality of life. We searched for published and unpublished studies in CENTRAL (searched 14 June 2017), Embase (1980 to 14 June 2017), MEDLINE (1946 to 14 June 2017) and CANCERLIT (1999 to 2002) databases. We also handsearched all relevant conference abstracts published up until 14 June 2017. All randomised studies assessing overall survival outcomes in patients with advanced pancreatic ductal adenocarcinoma. Chemotherapy and radiotherapy, alone or in combination, were the eligible treatments. Two review authors independently analysed studies, and a third settled any disputes. We extracted data on overall survival (OS), progression-free survival (PFS), response rates, adverse events (AEs) and quality of life (QoL), and we assessed risk of bias for each study. We included 42 studies addressing chemotherapy in 9463 patients with advanced pancreatic cancer. We did not identify any eligible studies on radiotherapy.We did not find any benefit for chemotherapy over best supportive care. However, two identified studies did not have sufficient data to be included in the analysis, and many of the chemotherapy regimens studied were outdated.Compared to gemcitabine alone, participants receiving 5FU had worse OS (HR 1.69, 95% CI 1.26 to 2.27, moderate-quality evidence), PFS (HR 1.47, 95% CI 1.12 to 1.92) and QoL. On the other hand, two studies showed FOLFIRINOX was better than gemcitabine for OS (HR 0.51 95% CI 0.43 to 0.60, moderate-quality evidence), PFS (HR 0.46, 95% CI 0.38 to 0.57) and response rates (RR 3.38, 95% CI 2.01 to 5.65), but it increased the rate of side effects. The studies evaluating CO-101, ZD9331 and exatecan did not show benefit or harm when compared with gemcitabine alone.Giving gemcitabine at a fixed dose rate improved OS (HR 0.79, 95% CI 0.66 to 0.94, high-quality evidence) but increased the rate of side effects when compared with bolus dosing.When comparing gemcitabine combinations to gemcitabine alone, gemcitabine plus platinum improved PFS (HR 0.80, 95% CI 0.68 to 0.95) and response rates (RR 1.48, 95% CI 1.11 to 1.98) but not OS (HR 0.94, 95% CI 0.81 to 1.08, low-quality evidence). The rate of side effects increased. Gemcitabine plus fluoropyrimidine improved OS (HR 0.88, 95% CI 0.81 to 0.95), PFS (HR 0.79, 95% CI 0.72 to 0.87) and response rates (RR 1.78, 95% CI 1.29 to 2.47, high-quality evidence), but it also increased side effects. Gemcitabine plus topoisomerase inhibitor did not improve survival outcomes but did increase toxicity. One study demonstrated that gemcitabine plus nab-paclitaxel improved OS (HR 0.72, 95% CI 0.62 to 0.84, high-quality evidence), PFS (HR 0.69, 95% CI 0.58 to 0.82) and response rates (RR 3.29, 95% CI 2.24 to 4.84) but increased side effects. Gemcitabine-containing multi-drug combinations (GEMOXEL or cisplatin/epirubicin/5FU/gemcitabine) improved OS (HR 0.55, 95% CI 0.39 to 0.79, low-quality evidence), PFS (HR 0.43, 95% CI 0.30 to 0.62) and QOL.We did not find any survival advantages when comparing 5FU combinations to 5FU alone. Combination chemotherapy has recently overtaken the long-standing gemcitabine as the standard of care. FOLFIRINOX and gemcitabine plus nab-paclitaxel are highly efficacious, but our analysis shows that other combination regimens also offer a benefit. Selection of the most appropriate chemotherapy for individual patients still remains difficult, with clinicopathological stratification remaining elusive. Biomarker development is essential to help rationalise treatment selection for patients.

Multidisciplinary clinic approach improves overall survival outcomes of patients with metastatic germ-cell tumors

To report our experience utilizing a multidisciplinary clinic (MDC) at Indiana University (IU) since the publication of the International Germ Cell Cancer Collaborative Group (IGCCCG), and to compare our overall survival (OS) to that of the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program. We conducted a retrospective analysis of all patients with metastatic germ-cell tumor (GCT) seen at IU from 1998 to 2014. A total of 1611 consecutive patients were identified, of whom 704 patients received an initial evaluation by our MDC (including medical oncology, pathology, urology and thoracic surgery) and started first-line chemotherapy at IU. These 704 patients were eligible for analysis. All patients in this cohort were treated with cisplatin-etoposide-based combination chemotherapy. We compared the progression-free survival (PFS) and OS of patients treated at IU with that of the published IGCCCG cohort. OS of the IU testis cancer primary cohort (n = 622) was further compared with the SEER data of 1283 patients labeled with 'distant' disease. The Kaplan-Meier method was used to estimate PFS and OS. With a median follow-up of 4.4 years, patients with good, intermediate, and poor risk disease by IGCCCG criteria treated at IU had 5-year PFS of 90%, 84%, and 54% and 5-year OS of 97%, 92%, and 73%, respectively. The 5-year PFS for all patients in the IU cohort was 79% [95% confidence interval (CI) 76% to 82%]. The 5-year OS for the IU cohort was 90% (95% CI 87% to 92%). IU testis cohort had 5-year OS 94% (95% CI 91% to 96%) versus 75% (95% CI 73% to 78%) for the SEER 'distant' cohort between 2000 and 2014, P-value <0.0001. The MDC approach to GCT at high-volume cancer center associated with improved OS outcomes in this contemporary dataset. OS is significantly higher in the IU cohort compared with the IGCCCG and SEER 'distant' cohort.

Impact of socioeconomic status on anal cancer survival.

e18060 Background: Despite an increase in incidence of anal cancer over recent decades, improvements in awareness and therapy have improved survival outcomes. We hypothesized that the gains in outcomes were not shared equally by patients of disparate socioeconomic status (SES). We investigated whether area-based median household income (MHI) predicts survival of patients with anal cancer, after controlling for known predictors. Methods: Patients diagnosed with squamous cell carcinoma of the anus (SCCA) as the first primary malignancy from 2004 to 2013 in the Surveillance Epidemiology and End Results (SEER) registry were included. SES was defined by census-tract MHI, and divided into quintiles. Multivariable Cox Proportional Hazards models were used to evaluate the effect of (MHI) on cancer-specific (CSS) and overall survival (OS). A multivariable logistic regression was used to assess whether these same measures predicted receipt of radiation. Results: A total of 9,550 cases of SCCA were included; median age was 58 years, 63% were female, 85% were white, and 38% were married. In multivariable analyses, patients living in areas with lower MHI had worse OS and CSS compared to those in the highest income areas. Mortality HR’s in order of lowest to highest income were 1.32 (95%CI 1.18-1.49), 1.31 (95%CI 1.16-1.48), 1.19 (95%CI 1.06-1.34), 1.16 (95%CI 1.03-1.30); CSS HR similarly range from 1.34-1.22 from lowest to highest income. Other significant predictors of increased cancer specific mortality included older age, black race (HR 1.44, 95%CI 1.26-1.64), male gender, un-married, earlier year of diagnosis, higher grade, and later stage. Income level, however, was not associated with odds of initiating radiation in multivariable analysis (OR 0.87 for lowest to highest income level, 95%CI 0.63-1.20). Conclusions: SES measured by area-based MHI independently predicts cancer-specific and overall survival outcomes in patients with anal cancer, despite similar rates of initiating radiation therapy. Black race remains a predictor of anal cancer outcomes despite controlling for income. Further investigation is warranted to understand the mechanisms in which socioeconomic inequalities affect cancer care and outcomes.

Ablation of miR-10b Suppresses Oncogene-Induced Mammary Tumorigenesis and Metastasis and Reactivates Tumor-Suppressive Pathways.

The invasive and metastatic properties of many human tumors have been associated with upregulation of the miRNA miR-10b, but its functional contributions in this setting have not been fully unraveled. Here, we report the generation of miR-10b-deficient mice, in which miR-10b is shown to be largely dispensable for normal development but critical to tumorigenesis. Loss of miR-10b delays oncogene-induced mammary tumorigenesis and suppresses epithelial-mesenchymal transition, intravasation, and metastasis in a mouse model of metastatic breast cancer. Among the target genes of miR-10b, the tumor suppressor genes Tbx5 and Pten and the metastasis suppressor gene Hoxd10 are significantly upregulated by miR-10b deletion. Mechanistically, miR-10b promotes breast cancer cell proliferation, migration, and invasion through inhibition of the expression of the transcription factor TBX5, leading to repression of the tumor suppressor genes DYRK1A and PTEN In clinical specimens of breast cancer, the expression of TBX5, HOXD10, and DYRK1A correlates with relapse-free survival and overall survival outcomes in patients. Our results establish miR-10b as an oncomiR that drives metastasis, termed a metastamiR, and define the set of critical tumor suppressor mechanisms it overcomes to drive breast cancer progression. Cancer Res; 76(21); 6424-35. ©2016 AACR.

Lymphocyte Trends During Neoadjuvant Chemoradiation Predict Pathologic Complete Response at Time of Surgical Resection of Locally Advanced Rectal Cancers

While achieving complete pathologic tumor response (ypCR) following neoadjuvant chemoradiation (NCRT) is achievable in up to 25% of patients with locally-advanced rectal cancer, preoperative factors predicting which patients will achieve ypCR at time of definitive surgery are still poorly-elucidated. A number of studies have reported a correlation between peripheral lymphocyte counts and responses to various oncologic therapies and overall survival outcomes in patients with an array of malignancies including rectal cancer. The aim of this study is to determine whether lymphocyte trends at four weeks after initiation of NCRT are associated with complete treatment response in locally-advanced rectal cancers. Patient, tumor, and treatment data was abstracted on patients with T2 N1-2 and T3-4 N0-2 rectal cancers treated with NCRT and subsequent surgical resection at our institution from January 2009 through December 2013, allowing for two-year follow-up. Neoadjuvant chemoradiation for all patients consisted of completion of 4500 cGy to entire pelvis with boost to 5040 cGy to gross disease with concurrent 5-FU or capecitabine chemotherapy. Pathologic evaluation of final surgical specimens following NCRT was recorded as follows: complete response (ypCR), partial response (ypPR) or stable/progressive disease. Univariate analysis was performed to determine whether relative (%) lymphocyte counts at four weeks after initiation of NCRT (4wk RLC) and/or the ratio of 4wk total lymphocyte count (4wk TLC) to pre-treatment baseline total lymphocyte count (bTLC) were associated with the rates of ypCR. Frequencies were compared using the chi-square test. Thirty-one patients were identified who underwent NCRT followed by surgical resection for locally-advanced rectal cancer during the specified time period. Of the 31 post-NCRT surgical specimens reviewed, ypCR was observed in 10 patients (32%) and ypPR was found in 18 patients (58%). When analyzed as a continuous variable, greater 4wk RLC was predictive of ypCR (OR = 1.27, P = 0.065). Area under the ROC curve as a predictor for ypCR for 4wk RLC was 0.71 and for 4wk TLC: bTLC ratio was 0.69. Of patients with 4wk RLC ≤ 9, 3/19 (16%) achieved ypCR compared to 7/12 (58%) with RLC > 9 (P = 0.021). Of patients with 4wk TLC: bTLC ≤ 0.43, 3/17 (18%) achieved ypCR compared to 7/14 (50%) with 4wk TLC: bTLC > 0.43 (P = 0.055). When assessing lymphocyte trends at four weeks after initiation of NCRT, both RLC as well as percent decrease of TLC from baseline were associated with tumor ypCR at time of definitive surgery in patients with locally-advanced rectal cancers. This study underlines the importance of understanding the role of the host immune response in rectal tumor control. Further work characterizing which tumors have the highest response to immune modulation may guide patient selection in future studies investigating immune checkpoint inhibitors.

Prognostic impact of clinical tumor size on overall survival for subclassifying stages I and II vaginal cancer: A SEER analysis

PurposeThis study accessed the Surveillance, Epidemiology and End Results (SEER) database to determine if tumor size is an independent predictor of overall survival (OS) for patients with stages I and II vaginal cancer (VC). Materials and methodsWe identified in the SEER database, patients with available tumor size having stage I or II squamous cell histology from January 2004 through December 2012 with minimum follow-up of six months. Univariate analyses (UA) and multivariable analyses (MVA) evaluated the effect of several prognostic factors, including tumor size, regarding OS. Results529 SEER patients were found with recorded tumor sizes, of which 293 (55.4%) were stage I and 236 (44.6%) stage II. UA found the following significant prognostic factors of worse OS: tumor size >2cm (HR=1.80, p=0.02) and older age at diagnosis (p<0.001) in stage I; and tumor size >2cm (HR=2.13, p=0.04) and older age at diagnosis (p<0.001) in stage II. Estimates of 5-year OS in patients with tumor size ≤2cm vs. >2cm were 79.2% vs. 66.1% in stage I (p=0.0187) and 80.9% vs. 51.2% in stage II (p=0.0369). MVA confirmed about double risk of death for patients with tumor size >2cm (HRs: 1.88 in stage I and 2.06 in stage II). ConclusionsTumor size seems to predict OS outcome in patients with stages I/II VC. Further confirmatory investigations are recommended to firmly establish its incorporation into currently accepted staging criteria for these patients.

Comparing overall survival (OS) outcomes in patients with newly diagnosed chronic lymphocytic leukemia (CLL) with normal life expectancy.

7 Background: CLL is an orphan hematologic malignancy but also accounts for the most common adult leukemia in the Western Hemisphere, with a median age at diagnosis of 72 years. Median OS for symptomatic, treatment-naïve, elderly patients with CLL is approximately 5.3 years (CLL5; Eichhorst, et al. Blood 2009), whereas the life expectancy of a 72 year old (yo) is around 12 years (US Life Tables, 2006). Ibrutinib, an oral, first-in-class, covalent Bruton’s tyrosine kinase inhibitor, significantly improves OS. Early results from a phase 1/2 study in treatment-naïve elderly patients with CLL (PCYC-1102; median age, 71 years) suggest that single-agent ibrutinib extends OS, with survival at 3 years of approximately 97% (Byrd, et al. Blood 2015). Here we compare the OS in newly diagnosed patients with CLL treated with single-agent ibrutinib or chlorambucil with the normal life expectancy of a 72 yo adult. Methods: OS outcomes for patients treated with chlorambucil from the CLL5 study conducted in Germany (Eichhorst, et al. Blood 2009) were compared with long-term OS results from PCYC-1102 (Byrd, et al. Blood 2015). Life expectancy data were obtained from US Life Tables. Results: Results from CLL5 suggest that single-agent chlorambucil has a median OS of 5.3 years (median age, 71 years), with approximately 75% of patients alive at 3 years. The median OS for ibrutinib has not been reached (median follow-up, 3 years), with an estimated progression-free survival of 96% and OS of 97% at 3 years. Life expectancy for a 72 yo healthy person at 3 years is approximately 95%. Naïve comparisons suggest that single-agent ibrutinib may be altering the natural history of CLL, providing a longer OS versus chlorambucil and a similar OS as expected in a 72 yo in the general population. Conclusions: Treatment outcomes in CLL are fundamentally changing with the advent of new targeted therapies. This indirect naïve comparison between ibrutinib-treated patients and a general population suggests we may be moving from palliative care for elderly patients with CLL to chronic care management. Implications for chronic care management of patients with CLL will be discussed.

Role of Pre-therapeutic (18)F-FDG PET/CT in Guiding the Treatment Strategy and Predicting Prognosis in Patients with Esophageal Carcinoma.

Objective(s):The present study aimed to evaluate the role of pre-therapeutic 18fluorine-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) and maximum standardized uptake value (SUVmax) in guiding the treatment strategy and predicting the prognosis of esophageal carcinoma, using the survival data of the patients.Methods:The present retrospective, cohort study was performed on 40 consecutive patients with esophageal carcinoma (confirmed by endoscopic biopsy), who underwent pre-operative 18F-FDG PET-CT staging between January 2009 and June 2014. All the patients underwent contrast-enhanced CT and non-contrasted 18F-FDG PET-CT evaluations. The patients were followed-up over 12 months to assess the changes in therapeutic strategies. Survival analysis was done considering the primary tumor SUVmax, using the Kaplan–Meier product-limit method.Results:In a total of 40 patients, 18F-FDG PET-CT scan led to changes in disease stage in 26 (65.0%) cases, with upstaging and downstaging reported in 10 (25.0%) and 16 (40.0%) patients, respectively. The management strategy changed from palliative to curative in 10 out of 24 patients and from curative to palliative in 7 out of 16 cases. Based on the 18F-FDG PET-CT scan alone, the median survival of patients in the palliative group was 4.0 (95% CI 3.0-5.0) months, whereas the median survival in the curative group has not been reached, based on the 12-month follow-up. Selection of treatment strategy on the basis of 18F-FDG PET/CT alone was significantly associated with the survival outcomes at nine months (P=0.03) and marginally significant at 12 months (P=0.03). On the basis of SUVmax, the relation between survival and SUVmax was not statistically significant.Conclusion:18F-FDG PET/CT scan had a significant impact on stage stratification and subsequently, selection of a stage-specific treatment approach and the overall survival outcome in patients with esophageal carcinoma. However, pre-treatment SUVmax failed to stablish its usefulness in the assessment of patient prognosis and survival outcome.

Impact of Age-Adjusted Charlson Comorbidity score on outcomes for patients with early-stage endometrial cancer

ObjectivesTo determine the impact of Age-Adjusted Charlson Comorbidity (AAC) index score on survival outcomes for patients with early stage endometrial cancer. MethodsAfter IRB-approval, AAC score at time of hysterectomy was retrospectively tabulated by physician chart review for 671 patients with 2009 FIGO stage I–II endometrioid adenocarcinoma. Patients were grouped based on their AAC scores as follows: 0–1 (n=204), 2–3 (n=293) and >3 (n=174). Kaplan–Meier and log-rank test methods and univariate and multivariate modeling with Cox regression analysis was used to determine significant predictors of each survival endpoint. ResultsAfter a median follow-up of 85months, 225 deaths were recorded (34 from EC and 191 from other causes) with a 7-year Overall (OS) and Disease-specific survival (DSS) of 77.6% and 94.0%, respectively. Based on AAC grouping, the 7-year OS, DSS, and Recurrence-free survival (RFS) were: 92.9%, 96.8%, and 94.9% for AAC 0–1; 81.7%, 95.3%, and 89.8% for AAC 2–3: and 56%, 88.2%, and 84.9% for AAC>3 (p<0.0001, p=0.005 and p=0.013, respectively). On multivariate analyses, higher AAC score, tumor grade, lower uterine segment involvement, and lymphovascular space invasion were significantly independent predictors for shorter OS, while for DSS and RFS, higher tumor grade and lymphovascular space invasion were significant predictors of worse outcome, but higher AAC score was not. ConclusionsComorbidity score is as important as pathological features for predicting overall survival outcomes in patients with early-stage endometrioid endometrial carcinoma. Higher AAC scores accurately predicted for worse OS. Comorbidity score should be considered in prospective clinical trials of endometrial carcinoma.

The Ratio of the Absolute Lymphocyte Count to the Absolute Monocyte Count Is Associated with Prognosis in Hodgkin's Lymphoma: Correlation with Tumor-Associated Macrophages

Although most patients with classical Hodgkin's lymphoma (cHL) have a long survival duration, the current risk stratification is imperfect. A recent study suggested a prognostic role for the peripheral blood absolute lymphocyte count/absolute monocyte count (ALC/AMC) ratio at diagnosis in cHL. It is intriguing to investigate the significance of the ALC/AMC ratio in relation to tumor-associated macrophages (TAMs), yet another prognostic factor for cHL. We examined the prognostic impact of the ALC, AMC, and ALC/AMC ratio in 312 cHL patients (median age, 37 years) using receiver operating characteristic curve analysis for optimal cutoff values, and compared these with TAM content. The median follow-up was 65 months (range, 0.1-245 months). On univariate analysis, a low ALC/AMC ratio (<2.9) was correlated with a poorer overall survival (OS) outcome. A subgroup analysis of patients with limited-stage disease showed that the ALC/AMC ratio was significantly correlated with the OS time. Multivariate analysis showed the ALC/AMC ratio to be an independent prognostic factor for OS outcome. A Spearman correlation test of TAM content showed a negative correlation with the ALC/AMC ratio and a positive correlation with the peripheral blood macrophage percentage. This study suggests that the ALC/AMC ratio may be a simple, inexpensive, and independent prognostic factor for OS outcome in patients with cHL and may have a role in the stratification of cHL patients in addition to the International Prognostic Score and TAM content.

Excellent Ten-Year Results following Accelerated Partial Breast Irradiation with Multicatheter Interstitial Brachytherapy in Unsuitable Patients as Categorized by the American Society of Therapeutic Radiology and Oncology Consensus Panel

Purpose: We report ten-year local control and overall survival outcomes in patients with early stage breast cancer who fit criteria for the “unsuitable” category (e.g., high risk) as defined by the current American Society of Therapeutic Radiology and Oncology (ASTRO) Consensus Panel (CP) guidelines, following breast conserving therapy with accelerated partial breast irradiation (APBI) employing multicatheter interstitial brachytherapy (MIB).