tbuckley/cabot-search huggingface dataset:
Palliative reoperation for recurrent periampullary adenocarcinoma: Primum non nocere?
Authors: Brian A. Boone, Arthur J. Moser, Brady K. Mock, Paul J. Johnson, Igor Dvorchik, Herbert J. Zeh, J. Wallis Marsh
Journal: Journal of Clinical Oncology (2013)

257 Background: A majority of patients with periampullary cancer develop local or metastatic recurrence despite successful R0 resection. Many of these patients present with unresectable, symptomatic recurrence and selective surgical palliation is often considered. While the literature has addressed palliative surgery in primary periampullary cancer, no study has evaluated outcomes in recurrent disease. We examined the outcomes of surgical palliation for recurrent periampullary cancer. Methods: This is a retrospective study of patients who underwent palliative reoperation for recurrent periampullary cancer from 1990-2011. Morbidity and mortality was followed to 90 days. Complications were graded according to the Clavien-Dindo classification. Kaplan Meier was used to evaluate survival. Results: Fourteen patients underwent palliative reoperation following successful primary resection for periampullary adenocarcinoma. Indications for reoperation were small bowel obstruction (n=10, 71%), gastric outlet obstruction (2, 14.3%), spinal compression (1, 7.1%) and symptomatic pleural effusion (1, 7.1%). For patients undergoing abdominal reoperation, 2 (17%) underwent incomplete resection, 5 (42%) underwent bypass and 5 (42%) underwent lysis of adhesions. Median estimated blood loss was 100 mL. Median length of stay was 12 days. Postoperative complications affected 8 (57%) patients, with 75% ≥ Grade 3 complications. 3 (38%) patients died during their operative stay. 30 day and 90 day postoperative mortality were 43% and 86% respectively. Median survival was 45 days (range: 4-100). There was improved median survival in patients with an interval of more than 9 months prior to undergoing reoperation (57 vs. 11 days, p &lt;0.05). There was no difference in survival based on pancreatic versus ampullary cancer (45 vs. 43 days, p=0.096), or local versus metastatic site of recurrence (57 vs. 34 days, p=0.30). Conclusions: Palliative reoperation for periampullary cancer recurrence is associated with high morbidity and dismal survival. Non-operative palliation should be strongly considered in patients who have undergone prior resection and present with symptomatic recurrence.
Tolerance of full-dose sorafenib (S) combined with irinotecan (I; weekly, two on, one off) and cetuximab (C) in previously treated patients with advanced colorectal cancer (CRC).
Authors: A. Dasari, M. A. Rudek, J. Arcaroli, R. W. Powell, M. A. Carducci, D. Laheru, J. J. Wright, M. Hidalgo, W. A. Messersmith, N. S. Azad
Journal: Journal of Clinical Oncology (2011)

522 Background: The epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways are qualified targets in CRC, and are both inhibited by S. Preclinical evidence suggests S may also overcome cetuximab resistance. We previously reported (2008 GI Symposium, abstr#435) excessive toxicity of this combination with I 120 mg/m 2 days (d) 1,8,15,22 every 42 d; the study was amended with an alternative I dose/schedule and the phase I results are presented. Methods: Patients (pts) with advanced, pretreated CRC irrespective of KRAS mutation status with ECOG PS 0-2 and good organ function were eligible. The original dose/schedule of I was combined with C 400 mg/m 2 IV d1 and 250 mg/m 2 weekly; and S PO daily with dose level (DL) 1 = 200mg QD, DL2=200 mg BID and DL 3=400 mg BID. 2/4 pts had DLTs: grade (g) 3 fatigue and febrile neutropenia. The dose/schedule were amended to I 100 mg/m 2 d1, 8 of 21d cycles (c) without changing S or C. As with the original design, there was a C/S lead-in for 2 weeks in c1, thus c1 (DLT window) was 5 weeks (w). Results: In the original design, 5 subjects were recruited; after the study amendment, 13 additional pts were recruited (3, 3 and 7 pts respectively at amended DL1, DL2 and DL3). Overall, median age was 56.5 yrs, M: F 12:6 and colon: rectal cancer 16:2. All patients are evaluable and 3 are still on treatment (10+ - 20+ w). At the amended I dose/schedule, there were no further DLTs. Any c g3 toxicities included constitutional (fatigue:2, dehydration:1), gastrointestinal (nausea:1, vomiting:2, diarrhea:1), metabolic (hypomagnesemia:2 including one with tetany; hypokalemia:3), elevated ALT:1 and neutropenia:1. G 4 toxicities included neutropenia:1, thrombocytopenia:1. Two pts (one KRAS MT) had partial response with one pt (KRAS WT) on treatment for &gt;44 w. 10 pts had stable disease (5–20+ w). PK/PD analysis is ongoing. Conclusions: The recommended phase II dose is I 100 mg/m 2 d1,8; C 400 mg/m 2 IV d1 and 250 mg/m 2 weekly; and S 400 mg PO BID. The regimen is tolerable in advanced, pretreated CRC. Due to the limited responses and current phase III studies with S in CRC, there are no plans to open the phase II portion at this time. No significant financial relationships to disclose.
Late effects of pelvic radiation treatment (EAGLE study).
Authors: Sophia Emily Taylor, Ann Muls, Jervoise Andreyev, John Green, Damian Farnell, Lesely Smith, SAM H. Ahmedzai, Sara Pickett, Catherine Ferguson, Deborah Fitzsimmons, Susan Cambell, Raymond O'Shea, Annmarie Nelson, John Staffurth
Journal: Journal of Clinical Oncology (2016)

159 Background: Radiotherapy treatment for prostate cancer can cause severe long –term bowel problems, including limiting travel, work or socialising. Around half of patients suffer from late effects, appearing more than six months after radiotherapy. These symptoms often remain unmonitored in follow up care, despite the existence of effective treatment if referred to gastroenterology departments. This study focuses on the early identification and treatment of neglected late effect symptoms. Methods: Novel healthcare interventions are often difficult to embed in local clinical settings. Implementation research methodology will be used to evaluate experiences of a multi-component intervention aimed at prompting referrals to an enhanced gastroenterology service, making real time adjustments as needed, with the ultimate aim of successfully embedding the intervention into practice across the UK. The intervention, introduced in three UK centres, comprises a brief, standardised clinical assessment of relevant symptoms and rapid referral to a gastroenterological service, with staff trained to use a validated investigation and treatment algorithm. Evaluation of the intervention and its acceptability within local practices will be conducted using longitudinal mixed methods research. All prostate cancer patients attending follow up clinics, meeting the eligibility criteria will be invited to be screened (n = 300) and offered a referral to gastroenterology if appropriate. A cost effectiveness analysis of health-related quality of life and resource utilisation data will be undertaken and contrasts made between participants and a comparison group. Results: Interim results will focus on interview data from healthcare professionals and how they are working locally to embed practice, sharing learning points with other locations whilst working towards a sustainable service. Conclusions: This study evaluates the effectiveness of an enhanced assessment and treatment service spanning oncology and gastroenterology services in improving the outcome of men with prostate cancer after radiotherapy. Successful implementation will act as examples of best practice for a network of centres of excellence in this area.
Non-Random Lentiviral Vector Insertions in Bone Marrow Progenitors from Fanconi Anemia Patients
Authors: Ali Nowrouzi, Africa Gonzales-Murillo, Anna Paruzynski, Ariana Jacome, Paula Rio, Susana Navarro, José Carlos Segovia, Nadine Krenzer, Christof von Kalle, Guillermo Guenechea, Juan A. Bueren, Manfred Schmidt
Journal: Blood (2008)
Ensuring evidence-based cancer medicine by influencing prescribing behavior.
Authors: William J. Hrushesky, Dinah Huff, Sharon Davis, Laura Rose Bobolts, Marc L. Fishman, William S. Shimp, Jurgen Wilhelm Kogler, Val Fishman, Robert Walton
Journal: Journal of Clinical Oncology (2013)

212 Background: Oncology Analytics, Inc. (OA) promotes evidence-based, guidelines-compliant cancer therapeutic decision-making on behalf of healthcare payers. The OA web-based 1,300 protocol treatment request system screens several hundred applications each month. Evidence-based requests are automatically approvable within seconds (Auto); those needing medical director (MD) review, within hours (Non-Auto). Some 10% of all requests require real-time consultation between OA board-certified medical oncologists/hematologists and the prescribing cancer specialist. Three-quarters of these non-compliant residual requests are rescinded by the treating oncologist. The remainder are either approved because of additional information while about 1% are recommended for an adverse determination. Methods: We hypothesize that OA’s presence in a cancer market gradually improves the likelihood of evidence-based oncologist prescribing behavior. We tested this over 44 consecutive months of rapid growth, from May 2009 through December 2012, within a single southeastern US market. Since Auto requests are evidence- and guidelines-based, and Non-Auto requests are either not supported by evidence or have evidence support but with less toxic or less costly alternatives available, we reasoned that any sustained directional change in the ratio of Auto to Non-Auto represents a characteristic change in cancer specialist behavior over that span. The monthly ratios of Auto to Non-Auto were analyzed for trends by least squares and the slopes of each were contrasted by ANCOVA. Results: During the first six months, Auto-processed requests approximately equaled Non-Auto-processed request numbers, for a baseline ratio of one. Over the next 38 months, this ratio rose to approximately 1.4, meaning that 40% more requests were eventually approved automatically each month than those requiring MD review. The slopes of this relationship between Auto and Non-Auto approvals are statistically distinct (F = 43.34; p&lt;0.001). Conclusions: This progressive quality improvement reflects malleability of cancer doctor prescribing behavior, results in substantial savings, occurs quickly, persists and grows over time.
Use of progression-free survival (PFS) as an endpoint in advanced non-small cell lung cancer (NSCLC) trials: FDA perspective.
Authors: S. M. Malik, A. Ibrahim, R. Sridhara, R. L. Justice, R. Pazdur
Journal: Journal of Clinical Oncology (2010)

e18001 Background: According to SEER data, 1 in 14 people will be diagnosed with lung cancer during their lifetime. Most patients (pts) present with metastatic disease and systemic therapy remains the most important treatment modality. Until recently, chemotherapeutic agents were the only approved treatment options offering a modest benefit. Advances in the identification of molecular alterations have led to the development of targeted therapies. The appropriate population in which targeted therapy is of clinical benefit and the role of targeted therapies in such patients are still evolving. Methods: The criteria for disease progression and tumor response can be difficult to evaluate, and may potentially introduce bias. Furthermore, primary lung tumors and regional nodal disease frequently have ill-defined borders which can be difficult to accurately and reproducibly measure radiographically. Results: The basis for regular approval of drugs approved for advanced or metastatic NSCLC has been overall survival (OS) (see Table). Conclusions: Studies have demonstrated that Overall Response Rate (ORR) and PFS may not reliably predict for a corresponding effect on survival in NSCLC (Thatcher et al. Lancet, 2005; Pirker et al. Lancet 2009). Evaluation of new drugs for the treatment of lung cancer should be based on studies assessing appropriate clinical trial endpoints and regulatory approval should include a risk/benefit assessment. An improvement in OS in randomized controlled trials has been the standard for establishing clinical benefit for drug approvals in advanced NSCLC. Drugs Approval endpoints First-line Vinorelbine monotherapy OS, ORR Vinorelbine + cisplatin OS, ORR Docetaxel + cisplatin OS, TTP, ORR Gemcitabine + cisplatin OS TTP, ORR Bevacizumab* + paclitaxel/carboplatin OS Paclitaxel + cisplatin TTP, ORR, OS Pemetrexed in combination with cisplatin*,** OS Pemetrexed as maintenance therapy* OS Second-line NSCLC Docetaxel OS, TTP, ORR Erlotinib OS, TTP. ORR Pemetrexed*,** Durable ORR, decreased toxicity Third-line NSCLC Erlotinib OS, TTP, ORR Gefitinib** Durable ORR * Limited to nonsquamous non-small cell lung cancer. ** Accelerated approval. No significant financial relationships to disclose.
The impact of survivorship care plans on knowledge among breast cancer survivors.
Authors: Kaleigh Bulloch, Melinda Irwin, Anees B. Chagpar, Nina Ruth Horowitz, Brigid K. Killelea, Lajos Pusztai, Maysa M. Abu-Khalaf, Michael DiGiovanna, Gina G. Chung, Erin Wysong Hofstatter, Arthur Louis Levy, Tara Beth Sanft
Journal: Journal of Clinical Oncology (2013)

124 Background: Despite the Institute of Medicine’s recommendation that all cancer survivors be provided with a survivorship care plan (SCP), there is limited information as to whether SCPs improve knowledge. The purpose of this study was to examine the impact of SCPs on patient knowledge regarding tumor stage, cancer treatment and potential risk of long-term side effects, surveillance recommendations, and perceived knowledge of their therapy. Methods: 75 English-speaking women over the age of 18 were enrolled in this prospective study. The participants’ treatment progress was tracked through the electronic medical record and used to create the SCP, which was given to them at the completion of treatment (defined as the time patients had completed radiation and/or chemotherapy treatments and initiated on hormonal therapy, if applicable). Knowledge of stage, treatments, potential side effects, and surveillance recommendations were assessed before receiving the SCP and again two months later. Accuracy of responses was compared using the McNemar test. Results: The median patient age was 56.8 ± 12.5 and 47.1% were stage I, 37.3% were stage II, and 15.7% were stage III. Participants were statistically more accurate in identifying their stage after receiving their SCP than at baseline (72.6% vs. 92.2%, p = 0.0016). While many patients were more accurate in the identification of the cancer treatment they received after SCP, the only significant improvement was in identifying 5-Fluorouracil as chemotherapy received (65.5% vs. 89.7%, p=0.0196). Patients were more accurate in identifying potential side effects but were only statistically more accurate at identifying leukemia as a risk factor (36.0% vs. 46.9%, p=0.0348). At baseline and follow up patients perceived that they had a high level of understanding as it related to their cancer stage (60.4%, and 66.7%), treatment (69.4%, and 71.4%), and surveillance recommendations (61.4%, and 54.6%). Conclusions: SCPs appear to improve patient knowledge in several important areas including basic and specific treatment details, surveillance recommendations, and potential side effects. Delivery of a SCPs is one strategy to improve knowledge of treatments received.
Genetic and phenotypic characterization of families with familial pancreatic cancer and screening of high-risk individuals.
Authors: Carmen Guillen, Julie Earl, Evelina Mocci, Carme Guerrero, Jose Montans, Mirari Marquez, Enrique Vazquez Sequeiros, Cristina Gonzalez Gordaliza, Alfonso Sanjuanbenito, Maria Jesus MuÃƒÂ‘oz, Jesus Solera, Francisco X Real, Nuria Malats, Alfredo Carrato
Journal: Journal of Clinical Oncology (2015)

242 Background: The prognosis of patients diagnosed with Pancreatic Cancer (PC) is dismal with a 5-year survival rate of around 5%. Familial Pancreatic Cancer (FPC) is an autosomal dominant rare syndrome defined as families with two or more first-degree relatives with pancreatic cancer that do not fulfill the criteria of any other inherited tumor syndrome. The Spanish familial pancreatic cancer registry, Pan-Gen-FAM was established in 2009 in order to identify and manage families at high risk of developing PC. Methods: Information on the family history of cancer is collected in order to determine the phenotype of individual families and patients are offered genetic testing of known FPC associated genes pertinent to their familial syndrome. An individualized clinical screening program is devised for the early detection of a pancreatic tumor consisting of periodic monitoring by imaging techniques (EUS and MRI) and the evaluation of minimally-invasive tumor biomarkers approaches including Circulating Tumor Cells (CTC) and circulating free DNA in blood. Results: To date the registry includes 125 individuals representing some 41 families. Of 17 families tested so far BRCA2 germline mutations were detected in 5 families and a BRCA1 mutation in 1 family. 43 individuals underwent clinical screening. More pancreatic abnormalities were found by EUS (41%) than by MRI (31%). The most frequent abnormal findings were parenchymal changes associated with chronic pancreatitis. Eight cystic lesions were identified. One lesion was identified as a well differentiated neuroendocrine tumor and another was shown to have benign cytology and whilst carcinoma was found in a third patient, this patient underwent a subsequent partial pancreatectomy. The remaining patients with cystic lesions are undergoing close clinical observation. Seventy three patients underwent CTC determinations and all patients tested negative. Conclusions: Periodic screening of high risk individuals by EUS and RMI can detect small tumors and premalignant lesions. We hypothesize that these persons will have a higher probability of long-term survival than sporadic cases.
Patient surveys for cancer populations: Initial experiences with Cancer CAHPS.
Authors: Manasi Tirodkar, Mark W Friedberg, Shelley Fuld Nasso, Lindsey M Roth, Aaron Smith-McLallen, Ellen L. Stovall, Sarah Hudson Scholle
Journal: Journal of Clinical Oncology (2016)

281 Background: Patient experiences are an important component of quality, but information on how well oncology providers meet the specific needs of patients with cancer is limited. This study reports on the patient experiences among patients undergoing drug therapy treatment for cancer in diverse outpatient settings. Methods: We assessed patient experiences using a modified version of the CAHPS Survey for Cancer Caredeveloped by the American Institutes for Research.The survey has five composites and an overall rating of providers. We used claims data from an insurance plan in Southeastern Pennsylvania to identify all patients who had a paid claim for drug therapy treatment at 26 practices from January 1 through July 31, 2014. The survey was sent to 2,302 patients who met this criteria and 701 patients returned a completed survey for a response rate of 31%. We calculated scores of 0-100 on the composites after adjusting for age, education, self-rating of mental health and response tendency (a measure of level of optimism/pessimism). Results: In general, cancer patients rated their providers highly on patient experience, particularly on access and communication. However, cancer patients rated their providers lower on shared decision-making and helping patients manage their symptoms and care at home. The scaled, adjusted scores on the five composites were: Access (score=91; 95% CI=90-92); Affective communication (score=90; 95% CI=88-91); Exchanging information/keeping patients up to date (score=89; 95% CI=88-90); Shared decision-making (score=78; 95% CI=76-80); Enabling patient self-management (score=69; 95% CI=67-71). We encountered several challenges in fielding the survey related to attributing patients to specific practice sites, identifying patients who had died, and concerns raised by patients/family respondents about the length or content of the survey. Conclusions: Our findings suggest the need for strong efforts to engage cancer patients in decision-making and provide supportive care. Methodology for sampling patients using claims data needs to be more accurate and the survey could be edited for length and comprehension.
TH17 cells and early pancreatic tumorigenesis.
Authors: Florencia McAllister, Jennifer M Bailey, Janivette Alsina, Christopher Nirschl, Jeffrey Roeser, Danielle Blake, Rachana Lankapali, Cynthia Sears, Elizabeth M. Jaffee, Jay Kolls, Charles G. Drake, Drew M. Pardoll, Steven D. Leach
Journal: Journal of Clinical Oncology (2013)

144 Background: Chronic pancreatitis increases the risk of developing pancreatic ductal adenocarcinoma (PDAC), one of the deadliest human cancers. Activating Kras mutations have been detected in 30% of early pancreatic intraepithelial neoplasias (PanINs), increasing to 100% in PDAC. We hypothesized that inflammatory cells recruited to the pancreas in response to chronic injury can interact with epithelial cells harboring activated Kras G12D and affect the progression of PanIN lesions. Methods: We used the the transgenic Mist1:CreERT2; LSL-Kras G12D (KC iMist1 ) adult mice in which the LSL Kras G12D allele is activated specifically in the acinar compartment. This model leads to the formation of PanINs with a classic "ductal" phenotype and the progression of lesions is accelerated by the induction of chronic pancreatitis with recurrent cerulein injections. Results: We have found that TH17 cells, a subtype of CD4+ T-helper cells known to play an active role in inflammation, are recruited to the pancreas during chronic pancreatitis and further increased upon Kras G12D activation. The differentiation of CD4+T cells into TH17 requires IL-6 and TGF-B, factors that are increased in the pancreatic tumor microenvironment. Stat3, a key transcription factor that determines the differentiation of TH17 lineage, is activated in the pancreatic dysplastic epithelium and in the stroma. We have discovered that PanINs from KC iMist1 mice overexpress the IL-17 Receptor (IL-17RA) by immunofluorescence and furthermore we confirmed this finding on human PanIN tissue arrays. Intrapancreatic injections of adenovirus encoding IL-17A, the main cytokine produced by TH17 cells, into KC iMist1 mice led to an increase in the progression of PanIN lesions by 6 weeks when compared with mice injected with control adenovirus. Finally, we transplanted IL-17-/- bone marrow into KC iMist1 mice and showed a significant decrease in metaplasia and PanINs formation when compared with mice transplanted with WT bone marrow. Conclusions: We found that TH17 cells, recruited to the pancreas in the presence of chronic pancreatitis, can accelerate the progression of early pancreatic tumorigenesis, setting the basis for future translational studies targeting TH17 cells.