Identification of a family of cAMP-binding guanine nucleotide exchange factors by Gregory M. Springett.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 1998.Vita.Includes bibliographical references (leaves 137-139).Ph.D

Outcomes Of Adjuvant Radiotherapy And Lymph Node Resection In Elderly Patients With Pancreatic Cancer Treated With Surgery And Chemotherapy

Background: We sought to determine the effects of post-operative radiation therapy (PORT) and lymph node resection (LNR) on survival in patients ≥70 years with pancreatic cancer treated with surgery and chemotherapy. Methods: An analysis of patients ≥70 years with surgically resected pancreatic cancer who received chemotherapy from the SEER database between 2004-2008 was performed to determine association of PORT and LNR on survival. Results: We identified 961 patients who met inclusion criteria. There was a trend towards increased survival associated with PORT in all patients (P=0.052) and N1 patients (P=0.060) but no benefit in N0 patients (P=0.161). There was no difference in OS based on number of lymph nodes removed in all (P=0.741), N0 (P=0.588), and N1 (P=0.070) patients. MVA for all patients revealed that higher T stage, N1, and high grade tumors were prognostic for increased mortality, while there was decreased mortality with PORT and mild benefit with increased lymph nodes resected (P=0.084). Conclusions: PORT demonstrated no benefit in survival of pancreatic cancer patients ≥70 who are resected and treated with adjuvant chemotherapy. Future investigation will need to address age as a stratification factor for pancreatic cancer in the adjuvant setting

Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma

360 Background: Limited data is available for neoadjuvant treatment of borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer. We update our institutional outcomes with a neoadjuvant chemotherapy and stereotactic body radiotherapy (SBRT) approach. Methods: We performed an IRB-approved analysis of all BRPC and LAPC patients treated with our departmental treatment protocol. After staging, medically fit patients underwent chemotherapy for 2-3 months, with regimen at the discretion of the treating medical oncologist (FOLFIRINOX, GTX, gem/abraxane, or gemcitabine alone). Patients then received SBRT delivered in 5 consecutive daily fractions with median radiation doses of 30 Gy to tumor and 40 Gy dose painted to tumor-vessel interfaces. This was followed by restaging imaging for possible resection. Overall survival (OS), event free survival (EFS), and locoregional control (LRC) rates were estimated and compared by Kaplan-Meier and log-rank methods. Results: We identified 159 patients, 110 BRPC and 49 LAPC, with 14.0 months median overall follow-up. The resection and margin negative (R0) rate for BRPC patients who completed neoadjuvant therapy was 50.9% and 96.4%, respectively. Estimated median OS was 14.4 months for BRPC patients and 11.3 months for LAPC patients (p=0.402). Median OS was 34.2 months for surgically resected patients vs 14.0 months for unresected patients (p&lt;0.001). Five of 21 (23.8%) LAPC patients receiving FOLFIRINOX chemotherapy underwent R0 resection. In LAPC, FOLFIRINOX recipients underwent R0 resection more often than other chemotherapy recipients (5 of 21 vs. 0 of 28, p=0.011). There was a trend for improved survival in those resected LAPC patients (p=0.09). For those not undergoing resection, one year LRC was 78.4%. Grade ≥3 potentially radiation related toxicity rate was 6.9%. Conclusions: This data underscores the feasibility, safety, and effectiveness of neoadjuvant SBRT and chemotherapy for BRPC and LAPC. Compared with other chemotherapies, FOLFIRINOX induced greater tumor response in LAPC, permitting for R0 resection in a subset of LAPC patients and trend towards improved OS. </jats:p

Longitudinal cohort study to determine effectiveness of a novel simulated case and feedback system to improve clinical pathway adherence in breast, lung and GI cancers

OBJECTIVES: This study examined whether a measurement and feedback system led to improvements in adherence to clinical pathways. DESIGN: The M-QURE (Moffitt—Quality, Understanding, Research and Evidence) Initiative was introduced in 2012 to enhance and improve adherence to pathways at Moffitt Cancer Center (MCC) in three broad clinical areas: breast, lung and gastrointestinal (GI) cancers. M-QURE used simulated patient vignettes based on MCC's Clinical Pathways to benchmark clinician adherence and monitor change over three rounds of implementation. SETTING: MCC, located in Tampa, Florida, a National Cancer Institute Comprehensive Cancer Center. PARTICIPANTS: Three non-overlapping cohorts at MCC (one each in breast, lung and GI) totalling 48 providers participated in this study, with each member of the multidisciplinary team (composed of medical oncologists, radiation oncologists, surgeons and advanced practice providers) invited to participate. INTERVENTIONS: Each participant was asked to complete a set of simulated patient vignettes over three rounds within their own cancer specialty. Participants were required to complete all assigned vignettes over each of the three rounds, or they would be excluded from this study. PRIMARY OUTCOME MEASURE: Increased domain and overall provider care adherence to clinical pathways, as scored by blinded physician abstractors. RESULTS: We found significant improvements in pathway adherence between the third and first rounds of data collection particularly for workup and treatment of cancer cases. By clinical grouping, breast improved by 13.6% (p<0.001), and lung improved by 12.1% (p<0.001) over baseline, whereas GI showed a decrease of 1.4% (p=0.68). CONCLUSIONS: Clinical pathway adherence improved in a short timeframe for breast and lung cancers using group-level measurement and individual feedback. This suggests that a measurement and feedback programme may be a useful tool to improve clinical pathway adherence

Patterns of recurrence and long-term outcomes in patients who underwent pancreatectomy for intraductal papillary mucinous neoplasms with high grade dysplasia: implications for surveillance and future management guidelines.

BACKGROUND: While intraductal papillary mucinous neoplasms (IPMNs) with high-grade dysplasia (HGD) are thought to represent non-invasive, high-risk lesions, its natural history following resection is unknown. METHODS: A retrospective review of HGD-IPMN patients (1999-2015) was performed. Recurrence patterns and clinical outcomes following pancreatectomy were analyzed and the indications for surgery were explored based on current guidelines. RESULTS: HGD was diagnosed in 100 of 314 patients (32%) following pancreatectomy for IPMN. IPMNs were classified as main duct, branch duct, or mixed in 15, 58 and 27 patients, respectively. Following resection, 25 patients had low-risk residual disease in the remnant pancreas. With a median follow-up of 35 months (range 1-129), 9 patients developed progressive or recurrent disease, 4 of whom underwent additional pancreatectomy. Three patients developed invasive adenocarcinoma. Median time to recurrence was 15 months (range 7-72). Based on the management algorithm from the international consensus guidelines, resection was indicated in 76 patients (76%). Other indications for surgery included mixed-duct IPMN(13), increased cyst size(7) and other(4). CONCLUSION: The prognosis of HGD-IPMN following resection is good; however, HGD may be a marker for developing IPMN recurrence or adenocarcinoma. Current guidelines regarding surgical indications for IPMN can miss a significant number of patients with HGD