tbuckley/cabot-search huggingface dataset:
A retrospective analysis of patients with complete response (CR) after FOLFOX4: Single institute experience
Authors: M. Ozaka, E. Shinozaki, M. Suenaga, S. Matuzaka, K. Chin, N. Mizunuma, K. Hatake
Journal: Journal of Clinical Oncology (2008)

15100 Background: FOLFOX4 is one of the standard therapies for patients with metastatic colorectal cancer (mCRC) in Japan. Past clinical studies show the complete response (CR) rate was 4 percent. We had both highly chemo-sensitive patients who achieved CR and chemo-resistant patients who had progressive disease (PD), after FOLFOX4. By comparing both groups, we investigated the clinical pathological characteristics of patients after FOLFOX4 therapy. Methods: CR and PD patients were chosen retrospectively from 427 mCRC patients who underwent FOLFOX4 therapy in our single institute. Results: Twelve (3%) patients achieved CR, twenty (4.7%) had PD. Among CR patients, eleven had recurrent disease after colorectomy, nine had a single recurrent site. Median amount of tumor lesion prior to treatment was five, and the median size of largest measurable lesion was 20.0 mm. All PD patients had recurrent disease after colorectomy, nineteen with multiorgan recurrence, and the largest measurable tumor size was 41.0 mm. The median CEA prior to treatment was significantly lower in CR patients compared to PD patients, 9.9 ng/ml and 63.8 ng/ml. The median time to confirming CR was 6.7 months (range: 3–12 months), median number of treatment courses was 12 (range: 5–18), and all patients were given standard dose of FOLFOX4. All CR patients experienced at lowest Grade 1 (CTCAE v. 3.0) neuropathy. Treatment was discontinued in seven patients after confirming CR, among which five had recurrence, median time before recurrence was 3.5 months (range: 2.9–8.5 months). Of four patients where treatment has continued, no recurrence has been reported. Conclusions: Our study suggests that CEA level, tumor size, and number of recurrent site could be predictive factor of treatment effect. No significant financial relationships to disclose.
Abstract 17901: A Comparison of Temporal Trends in In-hospital Adherence to Secondary Prevention Measures Among Patients Undergoing Coronary Artery Bypass Graft Surgery, Percutaneous Coronary Intervention or No Intervention: Insights From the GWTG-CAD
Authors: Dharam J Kumbhani, Gregg C Fonarow, Christopher P Cannon, Adrian F Hernandez, Eric D Peterson, W F Peacock, Warren K Laskey, Maria Grau-Sepulveda, Lee H Schwamm, Deepak L Bhatt
Journal: Circulation (2012)

Objectives: Prior studies have noted that in-hospital adherence to secondary prevention measures varied among patients undergoing CABG vs. PCI vs. no-intervention for CAD. We sought to study temporal trends in the in-hospital management of patients with CAD in a large national database between 2003 and 2008. Methods: Using data from the national GWTG-CAD registry, we sought to compare adherence with 6 performance measures (aspirin within 24 hours, discharge on aspirin and beta-blockers, patients with low ejection fraction discharged on angiotensin converting enzyme inhibitor /angiotensin receptor blocker, smoking cessation counseling, use of lipid lowering medications) in eligible CAD patients who underwent CABG, PCI or no-intervention. Temporal trends between the groups were compared using Cochrane-Mantel-Haenszel row means scores statistics. Results: A total of 113,971 patients with CAD were treated at 193 hospitals between 2003 and 2008 (61% PCI, 13% CABG, 26% no-intervention). Overall adherence with a...
Successful re-challenge with panitumumab (PAN) in patients (pts) with GI cancers who developed hypersensitivity reactions (HSR) to cetuximab (CET)
Authors: V. Potter, M. J. Davies, J. Peccerillo, M. W. Saif
Journal: Journal of Clinical Oncology (2008)

20744 Background: Monoclonal antibodies (Mabs) targeting epidermal growth factor receptor (EGFR) are effective in treatment of metastatic colorectal cancer (mCRC). CET, a human-murine chimeric Mab targets EGFR. Even with premedication, CET can cause an HSR in select pts. In case of severe HSR, further therapy with CET is contraindicated, thus preventing these pts from receiving potentially beneficial anti-EGFR therapy. PAN is a fully human Mab also targets EGFR. To date, no human antihuman Ab have been detected, and unlike CET, HSR are infrequent, and no premedication is required. Safety of PAN in pts with a previous severe HSR with CET is not fully known. We present 3 pts with GI cancers who tolerated PAN without HSR after experiencing severe HSR to CET. Methods: 3 pts were challenged with standard dose of PAN (6mg/kg) after experiencing grade (g) 3 HSR to standard dose of CET and monitored very closely. 1st pt, a 58-yr-old M with mCRC developed g3 HSR during 8th dose of CET. 2nd pt, a 58-yr-old F with mCRC develpoed g3 HSR during 12th dose of CET. 3rd pt, a 61-yr-old M with pancreatic cancer experienced g3 HSR during loading dose of CET. Charts were reviewed to find prior allergy, including H1 blocker use, drug allergy, bee sting allergy, eczema, allergic reactive airways disease, or food allergy. Results: All pts were Caucasians with average age of 59 yr and no history of prior allergy. No pt received any premedication. 1st pt received PAN for 2 mths, 2nd pt was treated for 6 mths, and 3rd pt who was rechallenged 1 week after HSR to CET had a partial response after 6 mths. Conclusions: HSR are serious complications associated with modern Abs. In order to reduce incidence and severity of such reactions, newer generations of Mabs contain less or no mouse-specific protein sequences. Identification of individuals likely to develop severe and sometimes life-threatening HSR is challenging. Our report of 3 pts successfully treated with PAN after they had severe HSR to CET warrant further investigation. Summary of safety and response to re-challenge with PAN Case Age/Sex Diagnosis CET Dose Grade of HSR Time Interval Between CET and PAN PAN Dose Tolerance Duration of PAN Therapy 1 58/M CRC 250mg/kg G3 1 month 6mg/kg No HSR 2 months 2 58/F CRC 250mg/kg G3 3 months 6mg/kg No HSR 6 months 3 61/M Pancreatic cancer 400mg/kg G3 1 week 6mg/kg No HSR 6 months M: male, F: female No significant financial relationships to disclose.
Pretreatment albumin may help select patients for intrahepatic Y-90 microsphere transarterial radioembolization (TARE) for malignancies of the liver.
Authors: Kelly Elizabeth Orwat, Samuel Lewis Cooper, Michael Ashenafi, M. Bret Anderson, Marcelo Guimaraes, David T. Marshall
Journal: Journal of Clinical Oncology (2015)

453 Background: Systemic therapies for unresectable liver malignancies may provide a survival benefit, but eventually prove intolerable or ineffective. TARE provides an additional liver-directed treatment option to improve local control for these patients, but there is limited data on patient factors associated with survival. Methods: All patients that received TARE at the Medical University of South Carolina from March 2006 through May of 2014 were included in this analysis of overall survival (OS) and toxicity. Kaplan-Meier estimates of OS from date of first procedure are reported. Potential prognostic factors for OS were evaluated using log rank tests and Cox proportional hazards models. Results: In 114 patients that received TARE at our institution, median follow-up was 6.4 months [range 0-86], with the following tumor histology: colorectal (CR) n=55, hepatocellular (HC) n=20, cholangiocarcinoma (CC) n=16, neuroendocrine (NE) n=12, breast (BR) n=6, other n=5. At least 1 line of systemic therapy prior to TARE was noted in 79% of patients. Median OS was 6.6 months and 1-year OS was 30.7%. The percentage of patients who died within 3 months of TARE were 46.2% for patients with albumin &lt; 3 but only 20.3% for patients with albumin ≥ 3. Grade ≥ 2 toxicity was observed in 22 patients (19.3%) including 9 (7.9%) with Grade 3 and 1 (0.9%) with Grade 4 toxicity. A single patient with a pre-existing pulmonary arteriovenous malformation experienced Grade 3 pneumonitis that resolved with steroids. No deaths were attributed to radiation-induced liver disease. Conclusions: TARE is a relatively safe and effective treatment for unresectable intrahepatic malignancies. Patients with NE or BR histology as well as those with better hepatic synthetic function were associated with significantly better survival. Our data suggest that patients with albumin below 3 may not benefit from TARE. [Table: see text]
Safety and efficacy of HiDAC induction in de novo AML patients age 60 and older.
Authors: M. L. Arellano, L. Pan, L. Lima, M. Tighiouart, L. T. Heffner, A. A. Langston, M. McLemore, J. Neely, E. F. Winton, H. J. Khoury
Journal: Journal of Clinical Oncology (2010)

6587 Background: High dose (>1.5 gm/m2) Ara-C (HiDAC) given during induction is effective and well-tolerated in patients with AML <60. We report safety and efficacy of HiDAC in AML patients ≥60. Methods: Retrospective analysis of newly diagnosed de novo AML ≥ 60 who underwent induction with 6 daily doses of cytarabine 2 gm/m2 and 3 daily doses of daunorubicin 45 mg/m2, which was repeated in patients achieving CR. Subsequent consolidations consisted of either 2 additional courses of 6 daily doses of cytarabine 2 gm/m2 or hematopoietic stem cell transplantation (HSCT). Study end points were toxicities, remission, relapse-free (RFS) and overall survival (OS). Kaplan-Meier curves were used to obtain RFS and OS. Results: 59 patients (30 M/29 F) with a median age 68 (range 60-86) received HiDAC induction between July 1996 and February 2005. 4 (7%) had favorable cytogenetics, 36 (61%) intermediate, 15 (25%) unfavorable, and 4 (7%) unknown. Median WBC was 20,000/mcL (700- 279,000/mcL). Overall, 41/59 (69%) achieved CR. Induction-related toxicities are listed in the table and contributed to the death of 11/59 (19%) by day 60. Eighteen primary resistant patients after 1-2 inductions received alternative therapies and expired. 33/ 41 patients in CR, received additional 1 (N=6), 2 (N=11), or 3 (N=10) courses of HiDAC consolidation of which 6 received HSCT (5 auto and 1 allogeneic matched sibling donor). 8/41 patients in CR received other consolidations (N=5), refused/was unable to receive further therapy (N=1), and returned to referring MD (N=1). Median follow-up for surviving patients was 55 (17-114) months. Median OS was 12(1-114) for the cohort and for those in CR, median RFS was 14 months (1-113) and OS was 27 months (2-114). Conclusions: In a group of 59 unselected de novo AML patients age 60 and older, HiDAC induction was well- tolerated, had comparable early mortality rates to those observed with standard 7+3 induction in this age group, and was associated with high rates (69%) of durable remissions. Induction toxicity No. of patients (%) n = 59 (%) Neutropenic fever 17 (29) Pneumonia/pneumonitis/hypoxia 15 (25) Arrhythmia 10 (17) Acute renal failure 5 (8) Cerebellar 3 (5) Congestive heart failure 2 (3) Hepatic 1 (2) No significant financial relationships to disclose.
Pulmonary uptake of technetium 99m macroaggregated albumin: a predictor of gastrointestinal toxicity during hepatic artery perfusion.
Authors: W D Kaplan, S E Come, R W Takvorian, S M Laffin, R S Gelman, G R Weiss, M B Garnick
Journal: Journal of Clinical Oncology (1984)

Hepatic artery infusion of 5-fluoro-2-deoxyuridine (5-FUdR) provides high hepatic drug levels but little systemic toxicity, since, by this route of administration, the drug is detoxified by the hepatocytes. Slow infusion of technetium 99m- (99mTc) labeled macroaggregated albumin (MAA) through the hepatic artery is an aid in catheter placement, in predicting response of liver metastases to therapy, and in identifying extra-hepatic flow in the gastroduodenal or splenic arteries as an indicator of systemic toxicity. Marked pulmonary uptake of this tracer after slow radionuclide hepatic angiography was noted in four patients who showed major gastrointestinal (GI) toxicity. A retrospective examination of pulmonary accumulation of 99mTcMAA as a predictor of GI toxicity is the subject of this paper. Two groups of patients were evaluated. The first group consisted of 14 consecutive patients in whom continuous infusion of drug was administered by an external pump by way of a percutaneous catheter. Patients received baseline and follow-up (seven to 27 days) slow-infusion tracer studies (2 to 4 mCi 99mTcMAA at 10 to 21 mL/h). The second group included 14 consecutive patients who were receiving intraarterial chemotherapy by a totally implantable pump system. All received baseline slow-infusion studies (2 to 4 mCi 99mTcMAA at approximately 0.5 to 1.0 mL/min). The percentage of the injected dose in the lung was determined. Patients with greater than 20% of tracer in the lung after radionuclide hepatic angiography had significantly greater severe GI toxicity than patients with baseline values of less than 20%. Our findings support the existence of hepatic arteriovenous (A-V) communications in some patients and suggest that they are present pretherapy. Presence of these A-V communications, which can result in a vascular bypass of normal hepatic parenchyma and the subsequent decrease in hepatic detoxification of chemotherapeutic agents, is the likely cause of GI toxicity. Pulmonary uptake of tracer injected in the hepatic artery may be useful in quantifying the degree of shunting and facilitate the monitoring of potential systemic toxicity.
Gemcitabine-based transcatheter arterial chemoembolization for unresectable cholangiocarcinoma in thirty-eight patients: Single institutional experience
Authors: T. C. Gamblin, D. A. Geller, J. W. Marsh, B. Carr
Journal: Journal of Clinical Oncology (2006)

14152 Background: Survival for patients with unresectable cholangiocarcinoma is reported to be 5–8 months. Systemic chemotherapy has been disappointing and not shown to significantly improve survival. Transcatheter arterial chemoembolization (TACE) has been shown to prolong survival in hepatocellular carcinoma patients but experience with cholangiocarcinoma is limited. We report our experience with the well-tolerated drug gemcitabine. Methods: Thirty-eight patients with unresectable cholangiocarcinoma were treated with one or more cycles of gemcitabine-based TACE between 2001 and 2005 at our institution. Follow-up imaging was performed on all patients after each TACE procedure. Regimens of TACE included: gemcitabine only (16), gemcitabine followed by cisplatin (2), gemcitabine followed by oxaliplatin (5), gemcitabine and cisplatin (12), and gemcitabine and cisplatin followed by oxaliplatin (3). Actual survival is reported, as 35 of 38 have died from disease (92%). Results: Patients were 57.5 years of age (range 36–87) and a median of 3 treatments (range 1–10) were administered. Median survival from time of first treatment was 10.3 months. Patients receiving gemcitabine followed by cisplatin or oxaliplatin had improved survival (mean 16.5 and 10.5 months respectively) when compared to gemcitabine alone (mean 6 months). Patients receiving gemcitabine and cisplatin as a combination had improved survival (mean 13.4 months) compared to single agent gemcitabine. Patients who progressed on gemcitabine and cisplatin and then received oxaliplatin also showed improved survival (mean 14.3 months) compared to gemcitabine only. Neutropenia, thrombocytopenia and hyperbilirubinemia were the most common toxicities observed. Three patients in the entire series exhibited grade 3 thrombocytopenia while seven patients had grade 3 and one had grade 4 bilirubin levels. Conclusions: This series provides evidence in favor of TACE rather than historically reported alternatives such as systemic chemotherapy or chemotherapy/RT. Our results suggest that gemcitabine based TACE is well tolerated and perhaps best delivered as a combination therapy for patients with unresectable cholangiocarcinoma. No significant financial relationships to disclose.
A single arm phase II study of neoadjuvant transarterial regional therapy (TACE) using preloaded Irinotecan Beads in patients with resectable colorectal liver metastases (CRLM).
Authors: Robert Peter Jones, Hassan Zakria Malik, Stephen W. Fenwick, Thomas Gruenberger, Stefan Stremitzer, Myrddin Rees, Graham Plant, Joan Figueras, Maite Albiol, Rene Adam, Sameh Awad, Monica Terlizzo, Elizabeth O'Grady, Graeme John Poston
Journal: Journal of Clinical Oncology (2015)

3588 Background: Perioperative chemotherapy confers 3-year progression free survival advantage following CRLM resection. Good pathologic response is associated with improved overall survival. Chemoembolisation using DEBIRI gives sustained delivery of drug directly to tumor, thereby maximising response and reducing systemic exposure. This study examined the safety and feasibility of neoadjuvant DEBIRI before CRLM resection and subsequent early disease free survival (DFS). Methods: Patients with resectable CRLM received segmental DEBIRI (median dose 100 mg Irinotecan, range 25-200) 1 month before surgery, with radiological endpoint of near stasis during the procedure. Primary study end-point: tumor resectability. Secondary end-points: safety; radiologic response (RECIST); pathologic tumor response; disease-free survival. Results: 40 patients received DEBIRI-TACE. All proceeded to surgery, 38 underwent hepatectomy (2 peritoneal disease, resectability rate 95%). 30-day post-operative mortality 5% (n = 2), neither death TACE related (1 intraoperative pneumomediastinum, 1 aspiration pneumonia). 66 lesions (median 2 per patient) resected. RECIST at 1 month demonstrated 60% stable disease/partial response (24/40). Histologic major or complete pathologic response in 77.3% of targeted lesions (51/66). Correlation between radiologic and histologic response was poor. At 12-month follow-up, 18/40 (45.0%) of patients had disease recurrence (56% intrahepatic, 44% extrahepatic) (55% 1 year DFS). 2 patients died of recurrent disease (95% 1 year overall survival). Conclusions: Resection after neoadjuvant DEBIRI-TACE for CRLM is feasible and safe. Single treatment with DEBIRI-TACE resulted in tumor pathologic response and 1 year DFS similar to that seen after neoadjuvant systemic chemotherapy. RECIST at 1 month did not correlate with pathologic response or 1 year DFS. Clinical trial information: NCT00844233.
A phase I study of weekly irinotecan (CPT), cisplatin (CIS) and flavopiridol (F)
Authors: M. A. Shah, J. Kortmansky, M. Gonen, A. Tse, R. Lefkowitz, D. Kelsen, D. Colevas, J. Winkelman, S. Yi, G. Schwartz
Journal: Journal of Clinical Oncology (2004)

4027 Background: F is a cyclin dependent kinase inhibitor which potentiates CPT- and CIS-induced apoptosis, with pathologic cures in colon cancer xenografts(Motwani, et.al. Clin Cancer Res 2001). We translated our preclinical studies into a phase I trial of CPT 100mg/m2 followed 7 hours later by F given over 1-hour weekly for 4 out of 6 weeks (Shah et al, ASCO 2003). To build on this, we have now performed a phase I trial of the combination of CPT, CIS and F. Methods: 26 patients (pts) have been enrolled: median age 54 (range 35–72), KPS 90%(80–90%), 1–2 prior regimens (0–4), and 17 males/7 females. The initial design was CPT 60 mg/m2 and escalating CIS (10 → 30mg/m2) administration, followed 7 hours later by F 50 mg/m2 given weekly for 3 weeks on, 1 week off. In cohort one (CIS 10 mg/m2), we noted dose limiting grade 3/4 neutropenia by week 3. In view of this, we changed the schedule to a 2 on, 1 off cycle. CIS dose escalation then successfully proceeded without dose limiting toxicity(DLT) until full cytotoxic doses (CPT 65mg/m2, CIS 30mg/m2) with F 50mg/m2 were achieved. Results: Neutropenia was again the only DLT, especially in heavily pretreated pts. There appears to be an increased incidence of thromboembolic phenomenon, unrelated to dose: deep vein thromboses(2 pts), pulmonary embolism, arterial clot, and stroke(1 pt each). We observed encouraging antitumor activity: 5 out of 7 pts with gastroesophageal cancers demonstrated a partial response(PR). We also noted a minor response and a PR in 2 out of 3 pts with cholangiocarcinoma. Conclusions: 1) Neutropenia, in heavily pretreated pts was dose limiting. 2) Thromboembolic phenomenon may be a complication of therapy. 3) Encouraging antitumor activity was noted. 4)Dose escalation of F will continue in pts minimally pretreated (0 or 1 prior therapies) and with a reduced dose of CPT in heavily (>2 prior therapies) pretreated pts. 5) PK data will be presented. (Supported by R01-CA67819) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Pharmaceuticals; Pfizer Aventis Pharmaceuticals Pfizer
Use of pemetrexed with or without platin in malignant pleural mesothelioma in Italy
Authors: M. Marangolo, B. Castagneto, M. Pacini, F. Russo, L. Bertelli, A. Santoro
Journal: Journal of Clinical Oncology (2008)

19103 Background: This study evaluated the effects of pemetrexed(P)single agent or combined with cisplatin(CI)or carboplatin(CA)in patients with malignant pleural mesothelioma.The results of Italian patients within the Expanded Access Program of P are presented. Methods: Chemotherapy-naive or previously-treated patients not eligible for curative surgery and with adequate organ function, received P 500 mg/m2combined with CI 75 mg/m2(P/CI,option 1),as single agent(P,option 2)or combined with CA at an AUC of 5 mg/mL-min(P/CA,option 3),all given i.v. every 21 days together with folic acid and vitamin B12. Results: A total of 1032 patients(275 P/CI,375 P and 382 P/CA)were treated(mean age 64.1years).886(253 P/CI, 292 P and 341 P/CA)were eenrolledvaluable for efficacy (48.6% with performance status ≥90). 26.8The following table shows the results of best response [n, (%)]. The one-year survival rate was 67.5%(95% C.I.46.2–88.9)with P/CI,75.0%(66.9–83.0)with P and 73.9%(59.3–88.4)with P/CA.The median number of cycles was 4.0 with P and 6.0 with other regimens.The relative dose intensity of P was greater than 96% with all options. Grade 3/4 neutropenia occurred in 20.2% of patients on P/CI,in 15.4% on PA and in 28.6% on P/CA,and was reported in 24.0% of naïve and 18.4% of previously-treated patients.Rates of grade 3/4 anemia were 10.6% with P/CI,11.6% with PA and 16.7 with P/CA. Conclusions: In this non-randomized study, the combination arms had a higher response rate compared to P alone, but no additional one-year survival benefit. Toxicity with P/CA was worse compared to P/CI or P alone. Table of Contents Chemo-naïve N(%) Previously treated N(%) P/CI N(%) P N(%) P/CA N(%) Resp. Rate 113 (20.9) 34 (10.0) 64 (25.3) 22 (7.5) 62 (18.2) 95%CI 17.5–24.6 7.0–13.7 20.1–31–1 4.8–11.2 14.2–22.7 Stable dis. 270 (49.9) 157 (46.0) 122 (48.2) 136 (46.6) 170 (49.9) Dis. Progr. 140 (25.9) 138 (40.5) 58 (22.9) 124 (42.5) 98 (28.7) No significant financial relationships to disclose.
Civil Rights Laws as Tools to Advance Health in the Twenty-First Century
Authors: Angela K. McGowan, Mary M. Lee, Cristina M. Meneses, Jane Perkins, Mara Youdelman
Journal: Annual Review of Public Health (2015)

To improve health in the twenty-first century, to promote both access to and quality of health care services and delivery, and to address significant health disparities, legal and policy approaches, specifically those focused on civil rights, could be used more intentionally and strategically. This review describes how civil rights laws, and their implementation and enforcement, help to encourage health in the United States, and it provides examples for peers around the world. The review uses a broad lens to define health for both classes of individuals and their communities--places where people live, learn, work, and play. Suggestions are offered for improving health and equity broadly, especially within societal groups and marginalized populations. These recommendations include multisectorial approaches that focus on the social determinants of health.