tbuckley/cabot-search huggingface dataset:
Capecitabine (X) is resource saving compared with i.v. bolus 5-FU/LV in adjuvant chemotherapy for Dukes' C colon cancer patients: Medical resource utilization (MRU) data from a large phase III trial (X-ACT)
Authors: J. J. McKendrick, J. Cassidy, S. Chakrapee-Sirisuk, G. Fountzilas, T. Iveson, S. Jelic, H. Karnicka-Mlodkowska, R. Ostojic, W. Scheithauer, C. Twelves
Journal: Journal of Clinical Oncology (2004)

3578 Background: Treatment resource use has important implications for the total costs of therapy and quality of life / clinical outcomes. Treatment convenience impacts patient satisfaction and compliance. The X-ACT trial aimed to replace intravenous (i.v.) 5-FU/LV with oral X, an effective 1st line treatment in metastatic colorectal cancer. Methods: MRU was measured in the trial, which compared 6 months of twice-daily oral X 1,250mg/m2 d1–14 every 3 weeks (n=993) with i.v. 5-FU/LV (n=974; Mayo Clinic regimen). Information was collected on visits for study drug administration, hospital use, visits to providers and medication for adverse events (AEs). Hospitalizations linked to specific AEs were designated by the investigator as being study treatment-related or not. Results: Patients on 5-FU/LV typically made 30 visits to the clinic for treatment administration, while X patients made 8 visits, one at the beginning of each cycle. Treatment-related hospitalizations were lower (91 vs 100) in the X arm but the total number of associated days hospitalized was nearly identical (961 vs 959). On average, all patients made approximately 1 additional visit to general practitioners or specialists during the treatment period. In terms of medications to treat adverse events, patients on 5-FU/LV required more days of therapy for higher cost drugs such as anti-diarrheals, analgesics, and anti-fungals; patients on X used more low-cost vitamins and emollients. Conclusions: Adjuvant chemotherapy with oral X yields substantial savings in MRU due to the avoidance of administration costs of i.v. therapy. The indirect cost savings in terms of the value of patient time are substantial. Other potential cost factors, including hospital use, ambulatory encounters, and other medications, did not differ significantly between the regimens. If this trial meets its primary endpoint of equivalence in disease-free survival, X is likely to be cost-effective from a societal perspective compared with the Mayo Clinic regimen in the adjuvant treatment of Dukes' C colon cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche Roche Roche
A randomized phase II study of carboplatin and paclitaxel (CP) versus gemcitabine and vinorelbine (GV) in performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC): West Japan Thoracic Oncology Group 00
Authors: Y. Iwamoto, H. Saito, K. Nakagawa, T. Kashii, N. Katakami, T. Nakano, T. Kurata, M. Ando, M. Fukuoka
Journal: Journal of Clinical Oncology (2007)

18060 Background: Although doublet chemotherapy is a standard treatment regimen for PS 0–1 patients with advanced non- small cell lung cancer (NSCLC), the optimal chemotherapy for PS 2 patients with advanced NSCLC still remains to be established. We conducted a randomized phase II study to compare the efficacy and safety of a platinum-doublet regimen (CP) versus a non-platinum doublet regimen (GV) in PS 2 patients with advanced NSCLC. Methods: Chemotherapy-naive patients with stage IIIB (malignant effusion) and IV NSCLC were eligible for this study. The patients were randomly assigned to carboplatin area under the curve of 6 plus paclitaxel 200 mg/m 2 on day 1 every 3 weeks (the CP arm) or gemcitabine 1000 mg/m 2 plus vinorelbine 25 mg/m 2 on days 1 and 8 every 3 weeks (the GV arm). The primary endpoint was the 1-year survival rate while the secondary endpoints were the response rate, the time to progression and the quality-of-life (QOL). The sample size was 41 assessable patients in each arm. Results: Of the 89 patients enrolled, 84 were assessable for efficacy and toxicity: 41 patients (median age 65 years, male/female 30/11, stage IIIB/IV 7/34) in the CP arm and 43 patients (median age 67 years, male/female 31/12, stage IIIB/IV 7/36) in the GV arm. The overall response and 1-year survival rates were 29.3% (95% CI, 16.1 to 45.5%) and 22% (95% CI, 9.3 to 34.6%) for the CP and 20.9% (95% CI, 10 to 36%) and 27.9% (95% CI, 14.5 to 41.3%) for the GV arm, respectively. The median survival time and time to progression were 5.9 and 2.9 months, respectively, for the CP arms and 6 and 2.6 months for the GV arm. The selected Grade 3/4 toxicity in the CP and GV arms included neutropenia (67.5% vs 65.1%, respectively), anemia (12.5% vs 30.2%), thrombocytopenia (7.5% vs 11.6%), febrile neutropenia (17.1% vs 11.6%), infection (29.3% vs 23.3%), pneumonitis (4.9% vs 11.6%), liver dysfunction (2.5% vs 9.3%), and neuropathy (5.1% vs 0%). The QOL improved after each treatment and it was similar between the two arms. Conclusions: Both CP and GV appear to be active in PS 2 patients with advanced NSCLC . The toxicity profiles were different between the two arms. [Table: see text]
Polar Extremes in the Clinical Use of Stem Cells
Authors: George Q. Daley
Journal: New England Journal of Medicine (2017)

The U.S. biotechnology and pharmaceutical industries arguably lead the world in innovation while operating under stringent regulations set by the Food and Drug Administration (FDA). Although flexible pathways exist to accelerate the development or approval of treatments for serious illnesses or unmet medical needs, regulatory systems around the globe are under assault from forces seeking to relax rigorous, time-honored standards of safety and efficacy. Recent regulatory revisions in Japan allow regenerative medicine products to be marketed on the basis of only preliminary evidence of safety and reduced thresholds for determining therapeutic efficacy. In the United States, the 21st Century Cures . . .
A randomized, placebo-controlled, phase I/II study of tivantinib (ARQ 197) in combination with cetuximab and irinotecan in patients (pts) with <i>KRAS</i> wild-type (WT) metastatic colorectal cancer (CRC) who had received previous front-line systemic therapy.
Authors: Cathy Eng, Lowell L. Hart, Aleksey Severtsev, Oleg Gladkov, Lothar Mueller, Mikhail V. Kopp, Vladimir Ivanovich Vladimirov, Robert M. Langdon, Bogdan Kotiv, Sandro Barni, Ching Hsu, Ellen Bolotin, Reinhard Von Roemeling, Brian E. Schwartz, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2013)

3508 Background: Tivantinib (ARQ 197) selectively inhibits the MET receptor tyrosine kinase, which is implicated in tumor cell migration, invasion, and metastasis. Resistance to EGFR inhibitors has been associated with activation of alternative pathways including MET. Methods: Pts with advanced KRAS WT CRC that progressed on or after 1 prior line of chemotherapy and no previous treatment with an EGFR inhibitor were eligible. Pts were randomized 1:1 to receive cetuximab (500 mg/m 2 ) and irinotecan (180 mg/m 2 ) on days 1 and 15 every 28 days, plus oral tivantinib (360 mg twice daily [BID]) or placebo. The primary endpoint was progression-free survival (PFS); additional endpoints include safety, objective response rate, overall survival (OS) and exploratory biomarker analyses. Results: Between Jul 2010 and Feb 2012, 122 pts were randomized; 117 pts were eligible for analysis (60 tivantinib, 57 placebo). Mean age was 57 years (range, 27-79 years); ECOG PS 0/1 55%/45%; and 81% received prior oxaliplatin. Median PFS was 8.3 months in the tivantinib arm vs 7.3 months in the placebo arm (hazard ratio [HR] = 0.85; 95% CI, 0.55-1.33; P = 0.38). Objective response rate (95% CI) was 45% (33%-58%) in the tivantinib arm and 33% (23%-46%) in the placebo arm. Median OS has not yet been reached but is trending in favor of tivantinib vs placebo (HR = 0.67). Among pts with prior oxaliplatin therapy, median PFS was 8.4 months for tivantinib and 7.2 months for placebo (HR = 0.67; 95% CI, 0.44-1.00; P= 0.1). The most common grade 3/4 adverse events (≥ 10%) were neutropenia, diarrhea, and nausea. Correlation of clinical outcomes with additional factors including mutation status and immunohistochemical analysis of tumor MET expression will be presented. Conclusions: Outcomes in this trial trended towards improvement with tivantinib (360 mg BID) plus cetuximab and irinotecan, particularly in the subgroup who had previous oxaliplatin. Further studies are needed to identify the CRC population most likely to benefit from addition of tivantinib to standard therapy. Clinical trial information: NCT01075048.
Phase I trial of vorinostat in combination with erlotinib in advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations after erlotinib progression
Authors: N. Reguart, A. F. Cardona, D. Isla, F. Cardenal, R. Palmero, E. Carrasco-Chaumel, C. Rolfo, B. Massuti, T. Moran, R. Rosell
Journal: Journal of Clinical Oncology (2009)

e19057 Background: Vorinostat (SAHA) is a histone deacetylase inhibitor that induces differentiation, growth arrest and apoptosis of malignant cells. In vitro, there is a synergistic interaction of vorinostat in combination with gefitinib in NSCLC cell lines. Moreover, vorinostat increases levels of E-cadherin, p21, and downregulates expression of phospho-AKT and phospho-ERK1/2. These molecular findings could reverse resistance to erlotinib in mutant patients. Methods: We conducted a standard 3+3 Phase I trial of oral erlotinib 150 mg QD in combination with oral vorinostat (dose level 1 [DL1], 300 mg QD on days 1–7 every 21 days; DL2, 400 mg QD on days 1–7 every every 21 days, and; DL3, 400 mg QD on days 1–7 and 15–21 in a 28-day cycle). Cycles were repeated for a maximum of 6 cycles until progressive disease (PD) or intolerable toxicity. Pts with advanced NSCLC with EGFR mutations (Exon 19 and 21) after erlotinib progression and ECOG ≤2 were eligible. The main objectives were to determine the maximum tolerated dose (MTD), drug activity and safety of the combination regimen. Results: Thirteen patients have been enrolled up to date, with 9 patients available for this interim analysis (median age, 59 years; range 41–77). One patient (DL3 cohort) experienced a dose limiting toxicity (Grade 3 diarrhoea). The MTD has not been reached. The most common drug-related toxicities of any grade in the first cycle of treatment were anemia (77.8%), skin alterations (66.7%), diarrhoea (66.7%), xerostomy (55.6%), asymptomatic changes in liver function tests (55.6%), and asthenia (55.6%). There were no Grade ≥3 drug-related adverse events during first cycle of treatment and the global analysis of cycles showed asthenia (11.1%), somnolence (11.1%) and hyporexia (11.1%). Four pts discontinued treatment, all due to PD. Of 9 evaluable pts for efficacy, 6 had stable disease as best response (median duration of treatment 6.0 months, range 4–12). Final data will be presented at ASCO meeting. Conclusions: Although accrual continues to determine the MTD, the combination of vorinostat and erlotinib appears to be well tolerated and effective in this group of advanced NSCLC pts with EGFR mutations after erlotinib progression. No significant financial relationships to disclose.
Comparison of chemoradiotherapy (CRT) with carboplatin/paclitaxel (CP) versus cisplatin/5-FU (CF) for esophageal or junctional cancer: Experience from the Princess Margaret Cancer Centre.
Authors: Hao-Wen Sim, Bryan Chan, Akina Natori, Charles Henry Lim, Di Maria Jiang, Eric Xueyu Chen, Geoffrey Liu, Gail Elizabeth Darling, Carol Jane Swallow, Savtaj Singh Brar, James D. Brierley, Jolie Ringash, Rebecca Wong, John Kim, Patrik Rogalla, Sara Hafezi-Bakhtiari, James Conner, Jennifer J. Knox, Raymond Woo-Jun Jang, Elena Elimova
Journal: Journal of Clinical Oncology (2017)

126 Background: The optimal CRT regimen for neoadjuvant or definitive treatment of locoregional esophageal or gastroesophageal junctional (GEJ) cancer is uncertain. There has been no direct comparison between concurrent Cisplatin/5-FU (CF) as per the CALGB 9781 trial (50.4 Gy) or Carboplatin/Paclitaxel (CP) as per the CROSS trial (41.4 Gy). Methods: A retrospective analysis comparing CF and CP was performed in all patients (pts) with locoregional esophageal or GEJ cancer treated in 2012-2014. Overall survival (OS) and disease-free survival (DFS) were assessed via uni- and multivariable Cox proportional hazards regression, adjusting for age, performance status and Charlson comorbidity index. Pathological complete response (pCR) rates were compared using Fisher’s exact test. Results: 64/86 (74%) pts were male. Median age was 64 years (range: 34-84). Primary sites were esophageal (56%, with 60% squamous histology) and GEJ (44%, with 11% squamous). 22 pts received CRT in 2012 (100% CF), 33 pts in 2013 (58% CF, 42% CP) and 31 pts in 2014 (16% CF, 84% CP). Surgery was undertaken in 19 (41%) CF and 27 (68%) CP pts. Median follow-up was 38 months. We found no significant OS difference between CF and CP overall (HR 0.82, 95% CI: 0.43-1.56, p = 0.55) or in the subgroup having surgery (n = 46; HR 2.01, 95% CI: 0.62-6.55, p = 0.25). However, in the subgroup without surgery (n = 40), CF (n = 27) was superior to CP (n = 13)(HR 0.11, 95% CI: 0.03-0.38, p &lt; 0.001). OS was similar by histology (adenocarcinoma/squamous) in all-comers (p = 0.96), and in CF (p = 0.66) and CP subgroups (p = 0.66). DFS results were similar to OS. There was a non-significant numerical difference in pCR rates between CF (31%) and CP (18%) (p = 0.45). Conclusions: Survival is similar for CF and CP CRT regimens in patients undergoing trimodality therapy. pCR rates were comparable but lower than previously reported. In contrast, in the absence of surgical resection, CP given for CRT results in significantly inferior outcomes. Clinicians may prefer CP for surgical candidates given its toxicity profile. However, when treating with definitive CRT, CF may be preferable to CP as a standard regimen.
A hand-held portable imaging system for effective fluorescence-guided surgery of a pancreatic patient-derived orthotopic xenograft (PDOX) in nude mice.
Authors: Yukihiko Hiroshima, Ali Maawy, Fuminari Uehara, Shinji Miwa, Shuya Yano, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
Journal: Journal of Clinical Oncology (2014)

e15219 Background: Fluorescence-guided surgery (FGS) has made great progress in animal models. We focus in this report on a small (105 gram) hand-held imaging system for FGS that could readily translate to the clinic for FGS. Methods: Mouse models of human pancreatic cancer for FGS included (1) MiaPaCa-2-expressing green fluorescent protein (GFP), (2) BxPC3 labeled with anti-CEA antibody conjugated with Alexa 488, (3) pancreatic cancer patient-derived orthotopic xenograft (PDOX) labeled with anti-CA19-9 antibody conjugated with Alexa 488. Results: Each device could clearly detect the primary MiaPaCa-2-GFP tumor and any residual tumor after FGS. In the BxPC3 model labeled with Alexa 488-conjugated anti-CEA, each device could detect the primary tumor, but the MVX10 could not clearly detect the residual tumor remaining after FGS while the other devices could. In the PDOX model labeled with Alexa 488 conjugated with anti CA19-9, only the portable hand-held device could distinguish the residual tumor from the background, and complete resection of the residual tumor was achieved under fluorescence navigation. Conclusions: The efficacy of FGS in a PDOX model of pancreatic cancer with a hand-held imaging system further demonstrates the potential of the clinical-suitability of FGS.
Greater than 3-year follow-up of concomitant gemcitabine, capecitabine, and radiation therapy in locally advanced or incompletely resected pancreatic cancer.
Authors: William H. Sherman, Kyung Chu, John Allendorf, John A Chabot, Beth Schrope, Robert Fine
Journal: Journal of Clinical Oncology (2012)

e14708 Background: When either gemcitabine (G) or capecitabine (X) are combined with RT, the median survival is less than 12 months. Approximately 30% of patients progress during the 9 week period of treatment and re-assessment. The benefit of RT in the post-op setting has been questioned. Co-administration of G and X is synergistic against pancreatic cancer cells and both are radiation sensitizers. They were combined with RT. Methods: A retrospective analysis was done on 48 patients treated with GTX (G, docetaxel (T) and X) followed by radiation therapy with concomitant G and X. RT was delivered by conformal fields or IMRT in 180 cGy fractions to 5040 cGy. X, 1,000 mg/m 2 was given days 1 to 10 and days 16 to 25 of RT and G, 750 mg/m 2 over 90 minutes, was given on days 5, 10, 20 and 25 of RT. The end-points were toxicity and local disease control. Results: 14 patients with positive margin of resection were treated adjuvantly and 34 patients with arterial involvement were treated neo-adjuvantly. No patient developed evidence of metastasis within the 9 weeks after starting RT. There were no bowel perforations, pancreatitis or delayed strictures. The therapy was well tolerated. Grade 3/4 toxicities were: thrombocytopenia 29%, leucopenia 38%, anemia 43%, enteritis 10% and infection 8%. 2 patients had GI bleeding from telangectasias more than 6 months after completing RT. The group of 14 treated adjuvantly had survival of 100% at 1 year, 86% at 2 years. 7 (57%) are beyond 3 years and have not relapsed. 34 patients treated neo-adjuvantly had one year survival of 85%. Of the 34 patients, 16 (47%) are alive with a median survival of 24 months (95% CI 20.7, 31.7.) 22 had resections with a median OS of 25.7 M (range 8.8 to 74.8 M.) 13 have not relapsed (13.6 to 74.8 M.) On pathology, there were 3 CR’s (14%,) 6 (27%) with scattered microscopic disease and 13 (59%) with macroscopic residual disease. Conclusions: G and X can be combined safely with radiation therapy to achieve local control of pancreatic cancer. Our results suggest that the aforementioned therapy, when combined with surgery, increases the long-term disease-free survival over results reported in the literature.
OPTICAL COHERENCE TOMOGRAPHY ANALYSIS OF CLINICAL AND SUBCLINICAL PLAQUE RUPTURE
Authors: Tomoyuki Yamaguchi, Takashi Kubo, Takashi Tanimoto, Takashi Yamano, Kohei Ishibashi, Yasutsugu Shiono, Makoto Orii, Kunihiro Shimamura, Hironori Kitabata, Yasushi Ino, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2012)
Case 10-2017 — A 6-Month-Old Boy with Gastrointestinal Bleeding and Abdominal Pain
Authors: Lauren M. Allister, Ruth Lim, Allan M. Goldstein, Jochen K. Lennerz
Journal: New England Journal of Medicine (2017)

A 6-month-old boy presented with gastrointestinal bleeding and intermittent abdominal pain. Tachycardia and pallor were present. The hemoglobin level was 5.7 g per deciliter, and the hematocrit 17.5%. A diagnosis was made.
Development and implementation of an electronic measurement process for survivorship care plan dissemination and compliance.
Authors: Patricia Leighton, Stephanie Hoopes, Jo Maria Weathers, Leann Perkins, Douglas McCormick, Regina A Franco, Mark Allen O'Rourke
Journal: Journal of Clinical Oncology (2017)

67 Background: Cancer programs must comply with survivorship care plan (SCP) delivery by 2018 to maintain or achieve Commission on Cancer (CoC) accreditation. Barriers to measuring and tracking SCP compliance include insufficient staffing to facilitate the documentation and input of data, lack of electronic medical record automation methods, lack of interoperability and electronic health record reporting processes. In June 2016, The Greenville Health System-GHS Cancer Institute Center for Integrative Oncology and Survivorship-CIOS developed a process to record, measure and track the number of SCP delivery visits delivered to Cancer Survivors. Methods: A patient who attends an SCP visit sees a provider in collaboration with a nurse navigator. The provider explains the elements within the patient’s SCP document. A copy is provided to the patient. The SCP document is embedded within the providers note for the SCP visit. To document the visit and delivery of the SCP, the nurse navigator clicks the “complete SCP visit” button located in the patient’s EMR. The SCP button also identifies the name of the provider and whether the SCP was complete or incomplete. This action in the EMR enables the creation of reports that record and document SCP delivery. Results: Four weeks were chosen during the initial implementation period to evaluate use of the SCP delivery button. For each visit provided, the SCP delivery button was clicked documenting the delivery of the SCP. The weekly data for #SCP deliveries documented and total #SCP visits are: Week 1, 17 of 22 (77%); Week 2, 16 of 17 (94%); Week 3, 13 of 13 SCP (100%); Week 4, 12 of 12 SCP (100%). Of the 64 SCP’s, 42 were complete and 22 incomplete. Conclusions: The development of the electronic measurement process for survivorship care plan delivery has significantly increased efficiency of reporting and has decreased time spent on chart audits.
Attenuation of the volume-outcome relationship for gastrointestinal cancer surgery over time: Is a push towards continued regionalization justified?
Authors: Nabil Wasif, Yu-Hui Chang, Amit Mathur, Barbara A. Pockaj, Richard J. Gray, David Etzioni
Journal: Journal of Clinical Oncology (2017)

131 Background: Research demonstrating a volume-outcome relationship has resulted in regionalization of complex cancer surgery to high volume hospitals. A simultaneous national trend towards improved surgical outcomes brings into question whether the potential benefits of regionalization are still relevant. We hypothesize that the difference in adjusted post-operative mortality between low and high volume hospitals has decreased over time. Methods: The National Cancer Database (NCDB) was used to identify patients with colon, esophageal, and pancreatic cancer undergoing curative intent surgery from 2003-2011. Hospitals were divided into low ( &lt; 25 th percentile), medium (25 th -75 th ) and high ( &gt; 75 th percentile) volume groups depending on annual volume of cancer-specific surgery. Year-specific hospital averaged observed/expected (O/E) ratios were calculated for 90-day mortality. Poisson regression was used to model hospital averaged O/E ratios over time. Results: Our study population included 343,929 patients with colon (88%), esophageal (5%) and pancreatic (7%) cancer. There were significant (p &lt; 0.05) improvements in adjusted 90-day mortality from 2003 and 2011 for all volume categories and cancer types, except in high volume hospitals for esophageal cancer. In 2003, high volume hospitals had significantly better outcomes compared to low volume hospitals for all cancer types, as suggested by lower O/E ratios for 90 day mortality (p &lt; 0.05). However, by 2011 the difference in O/E ratios for 90 day mortality was no longer significantly lower for high compared to low volume hospitals (p &gt; 0.05); this was true for all three cancer types (Figure1). Conclusions: During the period of our study, 90-day mortality following gastrointestinal cancer surgery improved in low, medium and high volume hospitals. However, by 2011 the difference in adjusted post-operative mortality between low and high volume hospitals was not significantly different, likely due to global improvements in operative and peri-operative care. This attenuation of the volume-outcome curve has important implications for policy pertaining to regionalization of cancer care in the US.