Outcomes of a Clinical Pathway for Borderline Resectable Pancreatic Cancer.

BACKGROUND: Without prospective data establishing a consensus multimodality approach to borderline resectable pancreatic adenocarcinoma, institutional treatment regimens vary. This study investigated the outcomes of the clinical pathway at the author's institution, which consists of neoadjuvant gemcitabine, docetaxel, capecitabine, and stereotactic radiotherapy followed by surgery. METHODS: The study reviewed all cases that met the National Comprehensive Cancer Network (NCCN) diagnostic criteria for borderline resectable pancreatic adenocarcinoma from 1 January 2006, to 31 December 2013. Pancreatectomy rates, margin status, pathologic response, disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) were retrospectively examined. Standard statistical methods and Kaplan-Meier survival analysis were used for statistical comparisons. RESULTS: Of 121 patients who met criteria, 101 entered the clinical pathway, and 94 (93.1 %) completed neoadjuvant chemotherapy and radiation therapy. Of the 101 patients, 55 (54.5 %) underwent pancreatectomy, with 53 patients (96.4 %) having microscopically negative margins (R0) and 2 patients (3.6 %) having microscopically positive margins (R1). Vascular resection was required for 22 patients (40 %), with rates of 95.5 % for R0 (n = 21) and 4.5 % for R1 (n = 1). A pathologic response to treatment was demonstrated by 45 patients (81.8 %) and a complete response by 10 patients (14.5 %). Pancreatectomy resulted in a median DFS of 23 months (95 % conflidence interval [CI] 14.5-31.5), a median DSS of 43 months (95 % CI, 25.7-60.3), and a median OS of 33 months (95 % CI, 25.0-41.0) versus a median DSS and OS of 14 months (95 % CI, 10.9-17.1) for patients without pancreatectomy (DSS: P = 3.5 × 10(-13); OS: P = 4.7 × 10(-10)). CONCLUSIONS: The study demonstrated high rates for neoajduvant therapy completion (93.1 %) and pancreatectomy (54.5 %). After pancreatectomy, DSS was significantly improved (43 months), with a pathologic response demonstrated by 81.8 % and a complete response by 14.5 % of the patients. The results support further study of this borderline resectable pancreatic adenocarcinoma clinical pathway.

Florida Initiative for Quality Cancer Care: improvements in breast cancer quality indicators during a 3-year interval.

BACKGROUND: The Florida Initiative for Quality Cancer Care (FIQCC), composed of 11 practice sites across Florida, conducted its initial evaluation of adherence to breast cancer quality of care indicators (QCI) in 2006, with feedback provided to encourage quality improvement efforts at participating sites. In this study, our objective was to reassess changes over time resulting from these efforts. STUDY DESIGN: Quality care indicators were derived from the Quality Oncology Practice Initiative, the National Comprehensive Cancer Network, the American College of Surgeons, and expert panel consensus. Medical records were reviewed for breast cancer patients first seen by medical oncologists in 2009 at the FIQCC sites, using the same performance indicators as in 2006. Statistical comparisons of 2006 vs 2009 data across sites were made by Pearson chi-square exact test using Monte Carlo estimation. RESULTS: Charts of 602 patients in 2006 and 636 patients in 2009 were compared. Performance on medical oncology QCI improved over time for documentation of clinical trial participation discussion (p = 0.001), documentation of consent for chemotherapy (p = 0.047), definitive surgery done after neoadjuvant chemotherapy (p = 0.017), and planned dose of chemotherapy consistent with published regimens (p = 0.02). Improvements in surgical QCI were seen for documentation of specimen orientation (p < 0.001), inking of margins (p < 0.0001), and performance of sentinel lymph node biopsy (p = 0.035). CONCLUSIONS: The 2006 FIQCC study identified several medical and surgical oncology QCI improvement needs. Quality improvement efforts resulted in better performance for numerous metrics, therefore speaking to the benefits of reassessment of adherence to performance indicators to guide QCI efforts.

Degree of variability in performance on breast cancer quality indicators: findings from the Florida initiative for quality cancer care.

PURPOSE: The Florida Initiative for Quality Cancer Care (FIQCC) comprises 11 Florida practice sites that participate in comprehensive reviews of quality of care specific to patients with cancer. Here, we examined site adherence to performance indicators to assess quality of care for patients with breast cancer (BC). METHODS: Quality indicators were scripted on the basis of accepted guidelines from the Quality Oncology Practice Initiative, National Comprehensive Cancer Network, American College of Surgeons, and site-specific expert panel consensus. Comprehensive chart reviews, including both medical and surgical oncology quality measures, were conducted for patients with BC first seen in 2006 by a medical oncologist at one of the sites. Statistical comparisons were made by the Pearson χ(2) exact test, using Monte Carlo estimation. RESULTS: Charts of 622 patients were reviewed. Of the 34 indicators, seven for medical oncology and four for surgical oncology fell below the 85% level of adherence. A statistically significant difference (P < .001) in variation of performance across the sites was found for the following medical and surgical oncology indicators: documentation of menopausal status, family history, informed consent, planned chemotherapy regimen and flow sheet, American Joint Committee on Cancer staging, HER2/neu status, reporting of margin orientation and inking of the margins, histological grade, having a sentinel lymph node biopsy for invasive BC, and obtaining a mammogram within 14 months of definitive surgery. CONCLUSION: The FIQCC has identified how multiple aspects of BC care can be improved. Findings are being used at the participating institutions to guide quality improvement efforts.

Combination of farnesyltransferase and Akt inhibitors is synergistic in breast cancer cells and causes significant breast tumor regression in ErbB2 transgenic mice.

The Akt activation inhibitor triciribine and the farnesyltransferase inhibitor tipifarnib have modest to little activity in clinical trials when used as single agents. In this article, preclinical data show that the combination is more effective than single agents both in cultured cells and in vivo. Combination index data analysis shows that this combination is highly synergistic at inhibiting anchorage-dependent growth of breast cancer cells. This synergistic interaction is also observed with structurally unrelated inhibitors of Akt (MK-2206) and farnesyltransferase (FTI-2153). The triciribine/tipifarnib synergistic effects are seen with several cancer cell lines including those from breast, leukemia, multiple myeloma and lung tumors with different genetic alterations such as K-Ras, B-Raf, PI3K (phosphoinositide 3-kinase), p53 and pRb mutations, PTEN, pRB and Ink4a deletions, and ErbB receptor overexpression. Furthermore, the combination is synergistic at inhibiting anchorage-independent growth and at inducing apoptosis in breast cancer cells. The combination is also more effective at inhibiting the Akt/mTOR/S6 kinase pathway. In an ErbB2-driven breast tumor transgenic mouse model, the combination, but not single agent, treatment with triciribine and tipifarnib induces significant breast tumor regression. Our findings warrant further investigation of the combination of farnesyltransferase and Akt inhibitors.