Self-efficacy as a crucial psychological predictor of treatment adherence among elderly people living with HIV: analyses based on the health belief model.

Medication adherence to antiretroviral therapy (ART) among elderly people living with HIV (PLWH) is of serious concern. Our study aimed to understand the medication adherence of elderly PLWH under ART based on the health belief model (HBM). A baseline survey with a total of 529 elderly PLWH was conducted in Sichuan. Logistic and linear regression analysis, mediation analysis, and path analysis based on prior evidence were used. Only self-efficacy showed direct associations with medication adherence in the last four days (ORm = 1.37, 95%CI: 1.11, 1.70) and the last month (ORm = 1.39, 95%CI: 1.18, 1.63) in the multivariate analysis. Self-efficacy mediated the relations between perceived benefits, perceived barriers, cues to action and medication adherence. Inner relations existed within the HBM. In addition to the direct effects, perceived benefits (ß = 0.149, p = 0.031; ß = 0.093, p = 0.005), perceived barriers (ß = -0.070, p = 0.008; ß = -0.062, p = 0.012), and cues to action (ß = 0.184, p = 0.013; ß = 0.135, p = 0.014) showed indirect effects on medication adherence in the last four days and the last month, respectively. HBM may be effective in predicting medication adherence of elderly PLWH, and self-efficacy may be a crucial predictor and mediator. Efforts should be focused on how to enhance elderly PLWH's self-efficacy without neglect of other medication beliefs.

Patient-reported symptom burden in routine oncology care: Examining racial and ethnic disparities.

BACKGROUND: Racial and ethnic disparities are well-documented in cancer outcomes such as disease progression and survival, but less is known regarding potential disparities in symptom burden. AIMS: The goal of this retrospective study was to examine differences in symptom burden by race and ethnicity in a large sample of cancer patients. We hypothesized that racial and ethnic minority patients would report greater symptom burden than non-Hispanic and White patients. METHODS AND RESULTS: A total of 5798 cancer patients completed the Edmonton Symptom Assessment Scale-revised (ESAS-r-CSS) at least once as part of clinical care. Two indicators of symptom burden were evaluated: (1) total ESAS-r-CSS score (i.e., overall symptom burden) and (2) number of severe symptoms (i.e., severe symptomatology). For patients completing the ESAS-r-CSS on multiple occasions, the highest score for each indicator was used. Zero-inflated negative binomial regression analyses were conducted, adjusting for other sociodemographic and clinical characteristics. Symptomology varied across race. Patients who self-identified as Black reported higher symptom burden (p = .016) and were more likely to report severe symptoms (p < .001) than self-identified White patients. Patients with "other" race were also more likely to report severe symptoms than White patients (p = .032), but reported similar total symptom burden (p = .315). Asian and Hispanic patients did not differ from White or non-Hispanic patients on symptom burden (ps > .05). CONCLUSION: This study describes racial disparities in patient-reported symptom burden during routine oncology care, primarily observed in Black patients. Clinic-based electronic symptom monitoring may be useful to detect high symptom burden, particularly in patients who self-identify their race as Black or other. Future research is needed to reduce symptom burden in racially diverse cancer populations.

A phase 1/2 trial of ibrutinib in combination with pembrolizumab in patients with mismatch repair proficient metastatic colorectal cancer.

BACKGROUND: MMR proficient (pMMR) colorectal cancer (CRC) is usually unresponsive to immunotherapy. Recent data suggest that ibrutinib may enhance the anti-tumour activity of anti-PD-1 immunotherapy. In this study, we evaluated the safety and efficacy of ibrutinib plus pembrolizumab in refractory metastatic CRC. METHODS: This was a phase 1/2 study in patients with refractory metastatic pMMR CRC. The primary endpoints for phases 1 and 2 were maximum tolerated dose (MTD) and disease control rate, respectively. The secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 40 patients were enrolled. No dose-limiting toxicity was observed, and MTD was not identified. The highest tested dose of ibrutinib, 560 mg once daily, was combined with a fixed dose of pembrolizumab 200 mg every 3 weeks for the phase 2 portion. The most common grade 3/4 treatment-related adverse events were anaemia (21%), fatigue (8%) and elevated alkaline phosphatase (8%). Among 31 evaluable patients, 8 (26%) achieved stable disease, and no objective response was observed. The median PFS and OS were 1.4 and 6.6 months, respectively. CONCLUSION: Ibrutinib 560 mg daily plus pembrolizumab 200 mg every 3 weeks appears to be well tolerated with limited anti-cancer activity in metastatic CRC. CLINICALTRIALS. GOV IDENTIFIER: NCT03332498.

Constitutively Activated DAP12 Induces Functional Anti-Tumor Activation and Maturation of Human Monocyte-Derived DC.

Dendritic cells (DCs) are professional antigen presenting cells with a great capacity for cross-presentation of exogenous antigens from which robust anti-tumor immune responses ensue. However, this function is not always available and requires DCs to first be primed to induce their maturation. In particular, in the field of DC vaccine design, currently available methodologies have been limited in eliciting a sustained anti-tumor immune response. Mechanistically, part of the maturation response is influenced by the presence of stimulatory receptors relying on ITAM-containing activating adaptor molecules like DAP12, that modulates their function. We hypothesize that activating DAP12 in DC could force their maturation and enhance their potential anti-tumor activity for therapeutic intervention. For this purpose, we developed constitutively active DAP12 mutants that can promote activation of monocyte-derived DC. Here we demonstrate its ability to induce the maturation and activation of monocyte-derived DCs which enhances migration, and T cell stimulation in vitro using primary human cells. Moreover, constitutively active DAP12 stimulates a strong immune response in a murine melanoma model leading to a reduction of tumor burden. This provides proof-of-concept for investigating the pre-activation of antigen presenting cells to enhance the effectiveness of anti-tumor immunotherapies.

Impact of Axillary Dissection Among Patients With Sentinel Node-Positive Breast Cancer Undergoing Mastectomy.

BACKGROUND: Results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial supports omission of completion axillary lymph node dissection (CLND) after breast-conservation surgery with a positive sentinel lymph node biopsy (SLNB). We hypothesized that CLND also does not impact outcomes in women with clinically node-negative (cN0), pathologically node-positive breast cancer undergoing mastectomy. MATERIALS AND METHODS: A single-institution retrospective review was performed of patients with SLN-positive breast cancer treated from July 1999 through May 2018. Clinicopathologic and outcome data were collected. Patients with SLNBs were compared with those receiving SLNB and CLND. The Kruskal-Wallis, chi-square, and Fisher exact tests were used to assess for differences between continuous and categorical variables. The log-rank test was used for time-to-event analyses, and Cox proportional hazards models were fit for locoregional and distant recurrence and overall survival (OS). RESULTS: Of 329 patients with SLN-positive breast cancer undergoing mastectomy, 60% had CLND (n=201). Median age at diagnosis was 53 years (interquartile range [IQR], 46-62 years). The median number of SLNs sampled was 3 (IQR, 2-4), and the median number of positive SLNs was 1 (IQR, 1-2). Patients receiving CLND had higher tumor grades (P=.02) and a higher proportion of hormone receptor negativity (estrogen receptor, 19%; progesterone receptor, 27%; both P=.007). A total of 44 patients (22%) had increased N stage after CLND. Median follow-up was 51 months (IQR, 29-83 months). No association was found between CLND and change in OS and locoregional or distant recurrence. Completion of postmastectomy radiotherapy was associated with improved OS (P=.04). CONCLUSIONS: CLND is not significantly correlated with reduced recurrence or improved OS among patients who have cN0, SLN-positive breast cancer treated with mastectomy. CLND was significantly correlated with receipt of adjuvant systemic therapy. Completion of postmastectomy radiotherapy was associated with improved OS.

Is it Wise to Omit Sentinel Node Biopsy in Elderly Patients with Breast Cancer?

BACKGROUND: The Society of Surgical Oncology's Choosing Wisely® guidelines recommend against routine sentinel lymph node biopsy (SLNB) in clinically node-negative (cN0), hormone receptor (HR)-positive breast cancer patients aged ≥ 70 years. We examined the effect of SLNB on treatment and outcomes in this population. MATERIALS AND METHODS: A single-institution retrospective review of consecutive cN0 women ≥ 70 years of age who received SLNB was performed. We collected clinicopathologic characteristics and treatment data. Patients were compared according to SLN status with subset analysis of HR-positive patients. Outcomes were analyzed using the Kaplan-Meier method and univariable analysis, and were compared using log-rank tests. RESULTS: Of 500 patients, 345 (69%) were SLN-negative. Median age was 74 years (range 70-96). Most tumors were T1 (72%), N0 (69%), invasive ductal (77%), without lymphovascular invasion (88%), estrogen receptor-positive (88%) and progesterone receptor-positive (75%), and human epidermal growth factor receptor 2 (HER2)-negative (88%) treated with lumpectomy (71%). Median number of SLNs obtained was 2 (range 0-12) and median number of positive SLNs was 0 (range 0-8). Characteristics of the HR-positive subset were similar. In both the overall cohort and the HR-positive subset, SLN status significantly affected the use of adjuvant chemotherapy, although no significant effect on recurrence was observed. SLN-negative patients had better overall survival and less distant recurrence (both p < 0.0001). Adjuvant hormone therapy significantly improved overall survival. CONCLUSIONS: SLNB can be safely omitted in elderly patients with T1, HR-positive, invasive ductal carcinoma tumors, but may still provide important information affecting treatment. Patients who are candidates for adjuvant systemic chemotherapy should still be considered for SLNB.

Surgeon Bias in the Management of Positive Sentinel Lymph Nodes.

BACKGROUND: The standard of care for clinically node-negative (cN0) patients following positive sentinel lymph node biopsy (SLNB) was completion axillary lymph node dissection (CALND). Publication of ACOSOG Z0011 in 2010 changed this standard for patients undergoing lumpectomy. Clinicians have since expanded this practice to mastectomy patients, and ongoing prospective studies are seeking to validate this practice. Here, we evaluate patient and tumor characteristics that led surgeons to forego a second surgery for CALND in cN0 mastectomy patients with positive SLNB. PATIENTS AND METHODS: A single institution, retrospective review of cN0 patients with invasive primary breast cancer and positive SLNB from 2010 to 2016 was performed. Patients with T4 disease, positive preoperative axillary biopsy, prior neoadjuvant therapy or axillary surgery were excluded. Patients with positive SLNB undergoing CALND were compared with patients for whom CALND was omitted. Statistical analysis was performed using Kruskal-Wallis tests for continuous variables and χ2 tests or Fischer exact tests for categorical variables. RESULTS: Of 259 patients with positive SLNB, 180 (69.4%) patients underwent mastectomy. CALND was performed at the time of mastectomy in 54 (30%) patients, at time of second operation in 22 (12.2%) patients, and not performed in 104 (57%) patients. Delayed CALND was significantly associated with younger age, larger tumors, increased number of positive sentinel nodes, invasive lobular carcinoma, extranodal extension, and lymphovascular invasion. CONCLUSIONS: The management of cN0 patients with positive SLNB that do not meet ACOSOG Z0011 criteria is evolving and is influenced by tumor and patient characteristics in an attempt to balance the morbidity of CALND with the low rate of local regional recurrence.

Aberrant Epidermal Growth Factor Receptor RNA Splice Products Are Among the Most Frequent Somatic Alterations in Clear Cell Renal Cell Carcinoma and Are Associated with a Poor Response to Immunotherapy.

BACKGROUND: Accumulating evidence suggests that alternative RNA splicing has an important role in cancer development and progression by driving the expression of a diverse array of RNA and protein isoforms from a handful of genes. However, our understanding of the clinical significance of cancer-specific RNA splicing in renal cell carcinoma (RCC) is limited. OBJECTIVE: To characterize and validate a novel oncogene RNA splicing event discovered in patients with RCC and to correlate expression with clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: Using DNA and RNA sequencing, we identified a novel epidermal growth factor receptor (EGFR) splicing alteration (EGFR_pr20CTF) in RCC tumor tissue. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We confirmed the frequency and specificity of the EGFR_pr20CTF variant by analyzing cohorts of patients from our institution (n = 699) and The Cancer Genome Atlas (TCGA; n = 832). Furthermore, we analyzed its expression in tumor tissue and a human kidney cancer cell line using reverse transcriptase-polymerase chain reaction. Variant expression was also correlated with survival and response to systemic therapy. RESULTS AND LIMITATIONS: EGFR_pr20CTF expression was identified in 71.7% (n = 71/99) of patients with RCC in our institutional cohort and in 56.7% (n = 279/492) of patients in the TCGA cohort. EGFR_pr20CTF was found to be specific to clear cell renal cell carcinoma (ccRCC), occurring in <0.2% of non-RCC tumors (n = 2/1091). High levels of EGFR_pr20CTF correlated with lower survival at 48 mo following immunotherapy (p = 0.036). The average survival in patients with high EGFR_pr20CTF expression was <16 mo. CONCLUSIONS: The EGFR_pr20CTF RNA splice variant occurs frequently, is specific to patients with advanced ccRCC, and is associated with a poor response to immunotherapy. PATIENT SUMMARY: Cancer-specific RNA alternative splicing may portend a poor prognosis in patients with advanced clear cell renal cell carcinoma. Further investigation will help clarify whether EGFR_pr20CTF can be used as a biomarker for this patient population.

Utility of Taking Additional Margins When Performing Breast-Conserving Surgery with Intraoperative Radiation Therapy for Early Breast Cancer.

INTRODUCTION: Intraoperative radiation therapy (IORT) is an alternative to external beam radiation therapy (EBRT) after lumpectomy, in which radiation is delivered before the final margin analysis. Practices vary regarding excision of close or positive margins pre- and post-IORT. MATERIALS AND METHODS: In a retrospective cohort of women with hormone receptor-positive, clinically node-negative breast cancer undergoing lumpectomy with IORT and selective EBRT at our institution from 2011 to 2015, we compared the impact of pre- and post-IORT margin excisions on in-breast tumor recurrence. Additional pre-IORT margins were taken at surgical team discretion. Re-excisions post-IORT were performed for positive/close margins. We describe rate of invasive or in situ malignancy in additional pre-IORT and post-IORT re-excised specimens and compare IBTR using Chi-squared tests. RESULTS: There were 195 cases in 193 women (2 bilateral breast cancer). Pre-IORT, ≥1 additional margin was obtained in 139 (71%). The final margin on the initial lumpectomy was positive in 13 (9%) and ≤2 mm in 72 (52%). Additional pre-IORT margins contained in situ/invasive cancer in 16 (12%). Thirty-one patients (16%) underwent post-IORT re-excision and nine (29%) contained invasive/in situ malignancy. Twenty-three (12%) received EBRT. In 45.6-month mean follow-up, 13 had IBTR (7%) with no difference by additional pre-IORT margin excision (5 vs. 11%, p = 0.150), post-IORT margin re-excision (10 vs. 6%, p = 0.464), or EBRT (0 vs. 8%, p = 0.172). Adjuvant endocrine therapy was associated with lower IBTR (4 vs. 17%, p = 0.003). CONCLUSIONS: Taking additional pre-IORT margins and re-excising close/positive margins post-IORT improved margin clearance rates but had an unclear effect on IBTR. Adjuvant endocrine therapy significantly reduced IBTR.

A Phase 2 Multi-institutional Study of Nivolumab for Patients With Advanced Refractory Biliary Tract Cancer.

Importance: Currently, there is no established second-line systemic treatment for biliary tract cancer (BTC). Preclinical data have demonstrated that the presence of tumor-infiltrating CD8 T cells and programmed cell death 1 ligand 1-expressing tumor cells in the tumor microenvironment of BTC supports the rationale of using programmed cell death 1 protein blockade immunotherapy in BTC. Objective: To evaluate anticancer activity of nivolumab in patients with advanced refractory BTC. Design, Setting, and Participants: In this single-group, multicenter phase 2 study of nivolumab, 54 patients with histologically confirmed BTC whose disease progressed while undergoing treatment with at least 1 line but no more than 3 lines of systemic therapy were enrolled between October 5, 2016, and December 26, 2018. Analysis was performed on an intention-to-treat basis. Interventions: Nivolumab, 240 mg, was delivered intravenously every 2 weeks for 16 weeks, and then 480 mg was delivered intravenously every 4 weeks until disease progression or unacceptable toxic effects occurred. Main Outcomes and Measures: The primary end point was investigator-assessed objective response rate, and the secondary end points were progression-free survival, overall survival, and incidence of adverse events. Results: A total of 54 patients (27 men and 27 women; median age, 65 years [range, 28-86 years]) enrolled, and 46 (22 men and 24 women; median age, 65 years [range, 28-86 years]) were examined for objective response with radiologic imaging. The investigator-assessed objective response rate was 22% (10 of 46), including 1 unconfirmed partial response, with a disease control rate of 59% (27 of 46). Central independent review found an objective response rate of 11% (5 of 46), including 1 unconfirmed partial response, with a disease control rate of 50% (23 of 46). All patients who responded to treated (hereafter referred to as responders) had mismatch repair protein-proficient tumors. The median duration of investigator-assessed response was not reached, with a median follow-up of 12.4 months. Among the intention-to-treat population, median progression-free survival was 3.68 months (95% CI, 2.30-5.69 months) and median overall survival was 14.24 months (95% CI, 5.98 months to not reached). Programmed cell death 1 ligand 1 expression in tumors was associated with prolonged progression-free survival (hazard ratio, 0.23; 95% CI, 0.10-0.51; P < .001). The most common treatment-related grade 3 or 4 toxic effects were hyponatremia (3 of 54 [6%]) and increased alkaline phosphatase (2 of 54 [4%]). Conclusions and Relevance: This study found that nivolumab was well tolerated and showed modest efficacy with durable response in patients with refractory BTC. Further studies are warranted to verify the findings and evaluate biomarkers for improved treatment selection for patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02829918.

Evaluation of 2014 margin guidelines on re-excision and recurrence rates after breast conserving surgery: A multi-institution retrospective study.

INTRODUCTION: A 2014 consensus statement from the Society of Surgical Oncology and American Society for Radiation Oncology supported "no ink on tumor" as an adequate margin for breast conserving therapy (BCT). This study evaluates this statement in a multi-institution cohort. METHODS: A retrospective review of BCT cases at 3 comprehensive cancer centers was performed. Women age >18 receiving BCT for T1-2 breast cancer from 2008-2012 were included. Pre-2014, all sites considered 2 mm adequate. Estimated re-excision rates using the 2014 guidelines were calculated and factors predictive of re-excision were analyzed. RESULTS: 542 patients (545 lumpectomies) were eligible. Using a ≥2 mm margin standard, 32.8% of patients underwent re-excision compared to 14.1% after 2014 (p < 0.0001). Tumor size (p= 0.003), grade (p=0.015), and lymphovascular invasion (p=0.021) were predictive of re-excision. Patients with additional intraoperative margins excised were less likely to require reoperation (p=0.002). Local recurrence was unaffected by re-excision after mean followup of 66 months. CONCLUSIONS: The 2014 margin guidelines markedly reduce re-excision rates. There is no difference in local recurrence for patients after re-excision for a close margin versus without Powered.

Reduced-intensity fludarabine/melphalan confers similar survival to busulfan/fludarabine myeloablative regimens for patients with acute myeloid leukemia and myelodysplasia.

Optimal conditioning chemotherapy for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains uncertain. Myeloablative regimens such as fludarabine/busulfan are favored over reduced-intensity fludarabine/melphalan (Flu/Mel); however, it is not known if Flu/Mel is inferior. We analyzed hematopoietic cell transplantation recipients with AML and MDS who received fludarabine with once-daily intravenous busulfan targeted to either area under the curve (AUC) 5300 µM*L/min (Flu/Bu 5300) (n = 246) or AUC 3500 µM*L/min (Flu/Bu 3500) (n = 81), or Flu/Mel (n = 69). Flu/Bu regimens were compared separately to Flu/Mel. After 2-year follow-up, no differences in overall or relapse-free survival were found between Flu/Bu 5300 or 3500 versus Flu/Mel though relapse rates were significantly higher; 33.1% (p = 0.024), 44.6% (p = 0.002), versus 19.4%, respectively. Flu/Bu 5300 (p = 0.008) and Flu/Bu 3500 (p < 0.001) groups were prognostic for relapse compared to Flu/Mel. Flu/Mel yields lower relapse rates and similar survival benefit when compared to Flu/Bu 3500 or 5300 µM*L/min.

A Phase II Study of Ibrutinib in Advanced Neuroendocrine Neoplasms.

BACKGROUND: Ibrutinib is an orally administered inhibitor of Bruton's tyrosine kinase (Btk). Preclinical data suggest that mast cells are recruited within neuroendocrine neoplasms (NENs) where they stimulate angiogenesis and tumor growth. Ibrutinib inhibits mast cell degranulation and has been associated with regression of tumors in a mouse insulinoma model. METHODS: A prospective, phase II trial evaluated patients with advanced gastrointestinal (GI)/lung NENs and pancreatic NENs (pNENs) who had evidence of progression within 12 months of study entry on at least one prior therapy. Patients received ibrutinib 560 mg daily until unacceptable toxicity, progression of disease, or withdrawal of consent. The primary endpoint was objective response rate. RESULTS: Twenty patients were enrolled on protocol from November 2015 to December 2017 (15 advanced GI/lung NENs and 5 pNENs). No patient reached an objective response. Median PFS was 3.0 months. A total of 44 drug-related adverse events (AEs) were captured as probably or definitely associated with ibrutinib. Five patients experienced probably or definitely related grade 3 AEs, and 1 patient experienced a probably related grade 4 AE. Five patients discontinued treatment prior to radiographic assessment. CONCLUSIONS: Ibrutinib does not show significant evidence of activity in well-differentiated gastroenteropancreatic and lung NENs.

Completion of adjuvant therapy in patients with resected pancreatic cancer.

BACKGROUND: Adjuvant chemotherapy is the standard of care for resected pancreatic ductal adenocarcinoma (PDAC). It is estimated that only 40-80% eligible patients initiate intended adjuvant chemotherapy. Completion rates are largely unknown. METHODS: A retrospective analysis of outcomes of patients with resected PDAC over an 8-year period at H. Lee Moffitt Cancer Center (MCC) was performed. RESULTS: From a total of 309 patients, 299 were included for further analysis. 242 (81%) initiated adjuvant therapy (AT) and 195 (65%) completed the intended course. The median time-to-initiation of AT was 53 days (7.6 weeks). The most common reasons for early discontinuation of AT (n = 47) were toxicity (n = 29), disease recurrence (n = 9), patient decision (n = 4), unrelated comorbidities (n = 3), and death (n = 1). Completion of AT was an independent predictor of overall survival (OS) and recurrence-free survival (RFS) on multivariable analysis (OS: HR 0.41, CI 0.27-0.61, p < 0.001; RFS: HR 0.52, CI 0.36-0.76, p < 0.001). Factors associated with early termination of AT were vascular resection (OR 0.29, CI 0.13-0.67, p = 0.004) and administration of AT with local oncologist as opposed to MCC (OR 0.41, CI 0.21-0.82, p = 0.010). CONCLUSION: Completion of AT is associated with improved survival in patients with resected PDAC. Factors associated with an inability to complete AT include vascular resection and administration of AT with local care team in the patient's community.

High hnRNP AB expression is associated with poor prognosis in patients with colorectal cancer.

Heterogeneous ribonucleoprotein AB (hnRNP AB) is a member of the heterogeneous nuclear ribonucleoprotein family, which serves important functions in gene expression and signal transduction. However, the expression and clinicopathological significance of hnRNP AB in colorectal cancer (CRC) remain to be elucidated. To investigate the expression and clinical significance of hnRNP AB in CRC, hnRNP AB expression levels were analysed in two independent cohorts of patients with CRC. The results of reverse transcription-quantitative PCR, immunohistochemistry and western blot analysis demonstrated that hnRNP AB was upregulated in CRC tissues compared with the corresponding adjacent normal tissues. Immunohistochemical analyses indicated that a high expression of hnRNP AB was significantly associated with preoperative carcinoembryonic antigen (CEA; P<0.001) and carbohydrate antigen 19-9 (P=0.014) levels, tumour size (P=0.022) and infiltration (P=0.026), lymph node metastasis (P<0.001) and Tumour-Node-Metastasis stage (P<0.001). Univariate and multivariate Cox survival analyses revealed that hnRNP AB expression and preoperative CEA levels were significant independent factors affecting overall survival in patients with CRC (P<0.05). According to the Kaplan-Meier model, patients with CRC with high hnRNP AB expression exhibited significantly poorer prognosis compared with those with low hnRNP AB expression (P<0.001). In conclusion, the results of the present study demonstrated that hnRNP AB expression may serve an important role in the progression of CRC and that hnRNP AB may be considered a predictor of prognosis for patients with CRC.

OCT4B1 Promoted EMT and Regulated the Self-Renewal of CSCs in CRC: Effects Associated with the Balance of miR-8064/PLK1.

Cancer stem cells (CSCs) are the main cause of tumor generation, recurrence, metastasis, and therapy failure in various malignancies including colorectal cancer (CRC). Accumulating evidence suggests that tumor cells can acquire CSC characteristics through the epithelial-mesenchymal transition (EMT) process. However, the molecular mechanism of CSCs remains unclear. OCT4B1 is a transcript of OCT4, which is initially expressed in embryonic stem and carcinoma cells, and is involved in the regulation and maintenance of an undifferentiated state of stem cells. In this study, three-dimensional (3D) microspheres were confirmed as CRC stem cells. Compared with that of parental cells, their self-renewal ability was significantly increased, and OCT4B1 expression was increased and promoted the EMT process. The knockdown of OCT4B1 decreased the self-renewal of CSCs and reversed EMT. Moreover, OCT4B1 induced the expression of Polo-like kinase 1 (PLK1), which is a key regulator of EMT in tumor cells. Further examination showed that OCT4B1 regulated the miR-8064/PLK1 balance to exert its function. Taken together, our data suggest that OCT4B1 may be involved in regulating the self-renewal of colorectal CSCs through EMT, which is at least partially due to the miR-8064/PLK1 balance. This study indicates that OCT4B1 is a potential therapeutic target for CRC by targeting CSCs.

Outcomes of selective whole breast irradiation following lumpectomy with intraoperative radiation therapy for hormone receptor positive breast cancer.

BACKGROUND: For low risk breast cancer, the TARGIT-A randomized trial supported lumpectomy with intraoperative radiation therapy (IORT) and selective whole breast radiation (WBXRT). Selection criteria for WBXRT vary. METHODS: Women with hormone-receptor positive, clinically node-negative breast cancer were categorized retrospectively as suitable for IORT alone or also needing WBXRT by TARGIT-A or expanded TARGIT criteria (TARGIT-MCC). We evaluated local recurrence (LR) by selection criteria and receipt of WBXRT. RESULTS: Among 194 cases followed a median of 44 months, 54 (27.8%) met TARGIT-MCC criteria for WBXRT (34 met TARGIT-A criteria). Thirty patients were recommended and 21 (10.8%) received WBXRT. Of 13 patients with LR, none received WBXRT. LR was 10.5% in patients meeting TARGIT-MCC criteria who did not receive WBXRT versus 0% after WBXRT (p = 0.299). CONCLUSIONS: Selective WBXRT may have mitigated LR. Nearly all LR were in patients not recommended WBXRT. Further work should refine criteria for WBXRT after IORT. SUMMARY: Prior work among women with early breast cancer supported lumpectomy with intraoperative radiation therapy and selective adjuvant radiation using a risk-adapted approach. An expanded set of criteria for adjuvant radiation appear to further mitigate local recurrence risk. Local recurrence after lumpectomy with IORT could be further minimized by identification of additional high-risk features, as well as greater adherence to adjuvant endocrine therapy.

Association of multidimensional comorbidities with survival, toxicity, and unplanned hospitalizations in older adults with metastatic colorectal cancer treated with chemotherapy.

BACKGROUND: Studies of older patients with colorectal cancer(CRC) have found inconsistent results about the correlation of various comorbidities with overall survival(OS) and treatment tolerance. To refine our understanding, we evaluated this correlation using the Cumulative Illness Rating Scale-Geriatric(CIRS-G) and heat maps to identify subgroups with the highest impact. METHODS: We retrospectively reviewed 153 patients aged 65 years and older with stage IV CRC undergoing chemotherapy. We calculated CIRS-G scores, and a Total Risk Score(TRS) derived from a previous heat map study. The association between CIRS-G scores/TRS and OS, unplanned hospitalizations, and chemotoxicity was examined by the Cox proportional hazards model. RESULTS: Median age was 71 years. Median MAX2 score of chemotherapies was 0.134(0.025-0.231). The most common comorbidities were vascular(79.8%), eye/ear/nose/throat(68%), and respiratory disease(52.4%). Median OS was 25.1 months(95% confidence interval: 21.2-27.6). In univariate analysis, ECOG PS ≥ 2(HR 1.86(1.1-3.17), p = 0.019), poorly differentiated histology(HR 2.03(1.27-3.25), p = 0.003), primary site(rectum vs colon)(HR 0.58 (0.34-0.98), p = 0.04), age at diagnosis(HR per 5y 1.20 (1.04-1.39), p = 0.012), and number of CIRS-G grade 4 comorbidities(HR 1.86 (1.1-3.17), p = 0.019) were associated with OS. In multivariate analysis, the number of CIRS-G grade 4 comorbidities lost significance, although it retained it in the subgroup of patients with colon cancer. Conversely, the TRS was associated with OS in patients with rectal cancer. No association of comorbidity with unplanned hospitalization or chemotoxicity was observed. CONCLUSIONS: In older adults with metastatic CRC, the number of CIRS-G grade 4 comorbidities was associated with worse OS but no specific CIRS-G category was independently associated with OS, unplanned hospitalization, or toxicities.

Semiautomated Measure of Abdominal Adiposity Using Computed Tomography Scan Analysis.

BACKGROUND: The obesity epidemic has prompted the need to better understand the impact of adipose tissue on human pathophysiology. However, accurate, efficient, and replicable models of quantifying adiposity have yet to be developed and clinically implemented. We propose a novel semiautomated radiologic method of measuring the visceral fat area (VFA) using computed tomography scan analysis. MATERIALS AND METHODS: We obtained a cohort of 100 patients with rectal adenocarcinoma, with a median age of 60.9 y (age range: 35-87 y) and an average body mass index of 28.8 kg/m2 ± 6.56 kg/m2. The semiautomated quantification method of adiposity was developed using a commercial imaging suite. The method was compared to two manual delineations performed using two different picture archiving communication systems. We quantified VFA, subcutaneous fat area (SFA), total fat area (TFA), and visceral-to-subcutaneous fat ratio (V/S ratio) on computed tomography axial slices that were at the L4-L5 intervertebral level. RESULTS: The semiautomated method was comparable to manual measurements for TFA, VFA, and SFA with intraclass correlation (ICC) of 0.99, 0.97, and 0.96, respectively. However, the ICC for the V/S ratio was only 0.44, which led to the identification of technical outliers that were identified using robust regression. After removal of these outliers, the ICC improved to 0.99 for TFA, VFA, and SFA and 0.97 for the V/S ratio. Measurements from the manual methodology highly correlated between the two picture archiving communication system platforms, with ICC of 0.98 for TFA, 0.98 for VFA, 0.96 for SFA, and 0.95 for the V/S ratio. CONCLUSIONS: This semiautomated method is able to generate precise and reproducible results. In the future, this method may be applied on a larger scale to facilitate risk stratification of patients using measures of abdominal adiposity.