tbuckley/cabot-search huggingface dataset:
A phase 1B study of a MUC1 pulsed autologous dendritic cell (DC) vaccine as adjuvant therapy in patients (Pts) with resected pancreatic or biliary tumors
Authors: O. J. Finn, T. Whiteside, J. McKolanis, A. J. Moser, H. Zeh, K. Lee, D. Bartlett, A. Schmotzer, R. K. Ramanathan
Journal: Journal of Clinical Oncology (2004)

2578 Background: MUC1 is a transmembrane hypoglycosylated protein overexpressed on adenocarcinomas and a target of specific immune responses. Pts with cancer do not spontaneously generate MUC1-specific T helper cells and as a result make only IgM antibodies against MUC1. In preclinical studies, MUC1 peptide pulsed DC vaccine in MUC1 transgenic (Tg) mice elicited strong immunity, tumor rejection and induction of MUC1 specific CD4+ and CD8+ T cells (J Immunol. 2001;166:6555–63) Methods: The objectives are to evaluate induction of MUC1-specific immunity and to evaluate toxicity of the vaccine, in pts following potentially curative surgery. 90 ml of peripheral blood is withdrawn for DC generation in IL-4 and GMCSF. Immature DCs are pulsed with 100 μg of MUC1–100mer peptide to process and present in MHC class II molecules to T helper cells, then matured and injected subcutaneously or intradermally in the upper arm once every 3 weeks for a total of 3 doses. A booster dose is given 6 months later. For immune assays, peripheral blood lymphocytes are obtained pre-vaccination, prior to each vaccine dose and 7 days post vaccination and 4 weeks after the third vaccination. Development of MUC1-specific T helper cells is evaluated in ELISA assays by the ability of vaccinated patients to switch their anti-MUC1 serum antibodies from IgM to IgG isotypes. The target accrual is 12 patients Results: 8 patients are enrolled and 27 vaccine doses have been given without any toxicity. DC generation from peripheral blood has been successful with 0.5 x106-3.2 x106 cells generated for each vaccine dose, with the target being 1.0 x106 DC's per vaccine dose. ELISA assays have been performed on serum samples obtained from seven patients. Two patients have shown isotype switching after the second injection, suggesting activation of helper T cells. This is now being confirmed by ELISPOT assays. Conclusions: Vaccine administration in the first 8 patients has been extremely safe, with preliminary evidence of immune activity. Supported by grants: Lustgarten foundation (LF01–055), NCI - PO1 CA073743, NIH/NCCR/GCRC #5M01 RR 00056. No significant financial relationships to disclose.
Capecitabine: Single institution experience from North India in metastatic breast cancer
Authors: A. K. Vaid, S. Gupta, D. Doval, V. Talwar, S. Shrestha, K. Pavithran, J. B. Sharma, D. Lokanathan
Journal: Journal of Clinical Oncology (2004)

815 Background: Capecitabine (C) is a fluropyrimidine carbamate derivative, which is an easily administered, tumor activated and tumor selective cytotoxic agent. C has shown promising efficacy in Metastatic breast cancer (MBC) compared to CMF in untreated or paclitaxel in pretreated patients (pts). Methods: : In this retrospective study we evaluated the efficacy the activity and toxicity of C in MBC pts whose case records were available for the same. Case was considered evaluable for toxicity if received at least 1 cycle and for response if received at least 3 cycles of C. Results: 31 pts (between Jan 2000-June 2003) were evaluated. There were 30 female and 1 male patients. The median age was 55 years (range 26–69 years). Pre-treatment included anthracyclines in 83% and taxanes in 87% pts. Out of 31 pts 27 received only C, 3 pts received C+docetaxel and 1 patient C+vinorelbine. 31 and 26 pts were evaluable for toxicity and response respectively. The median number of cylces administered were 6 (range 1–13). Median dose was 2000 mg/m2 /day (range 1000–2500 mg/m2) in two divided doses orally for 14 days with 7 days rest (=1 cycle). Toxicity was low with grade \({1}/{2}\) hand-foot syndrome (51.61%), nausea/vomiting (3.22%), diarrhea (19.35%), neutropenia (22.58%), thrombocytopenia (16.12%) and mucositis (27.58%). Grade 3/4 toxicity was seen as hand-foot syndrome (16.12%),diarrhea (6.45%), neutropenia (9.67%),thrombocytopenia (3.22%) and mucositis (6.45%). Out of 26 pts evaluable for response there were 3 CR (11.53%), and 9PR (34.61%). Another 11 pts (42.30%) had disease stabilization (overall tumor control rate of 88.46%). 3 pts (11.53%) had progressive disease. The median duration of CR was 51 wks (range 48–91 wks) of PR was 31 wks (range 15–88 wks) and of stable disease was 21 wks (range 12–58 wks). Conclusions: Capecitabine has shown good response rate with low toxicity in pts of MBC who were heavily pretreated with anthracyclines and taxanes. There was additional benefit of treatment on out patient basis. Our results suggest that C should be considered as one of the treatment options in anthracyclin and taxane refractory MBC Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer
Improving shared decision making in chronic lymphocytic leukemia through multidisciplinary education.
Authors: Courtney Williams, Karina I. Halilova, Uma Borate, Bradford E. Jackson, Emily Sherene Van Laar, Maria Pisu, Thomas Wayne Butler, Randall S. Davis, Amitkumar N. Mehta, Sara J. Knight, Monika M. Safford, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2017)

154 Background: New treatments for chronic lymphocytic leukemia (CLL) with excellent response rates and varying toxicity profiles have emerged in recent years, creating an opportunity for a patient’s personal preferences to contribute to treatment decisions. Methods: We conducted a prospective, quasi-experimental pre- and post-evaluation of a multi-level educational program and its impact on knowledge of CLL as well as on shared decision-making. We educated patients, patient navigators, and providers (nurses and physicians) using a combination of print, video, in-person lectures, and online case-based education tailored to each learner group. Patients were evaluated for change in patient activation, distress levels, desired role in decision-making, perception of decision-making, satisfaction with oncologist explanation of treatment choice, and knowledge of CLL. Patient navigators and providers were evaluated for change in CLL knowledge and perception of shared decision-making. Results: Forty-one patients and 87 providers participated in the educational program. We observed trends toward improved patient activation with 68% before education vs. 76% after education reporting a high (score of 3 or 4) Patient Activation Measure (PAM) . The percentage of patients desiring and perceiving shared decision-making trended upward from 47% to 67% and 35% to 49%, respectively. There was a trend toward an increase in the percentage of patients understanding that CLL is incurable (80% to 90%) and reporting awareness of signs of progression (64% to 76%). Patients satisfaction with their oncologist’s explanation of therapy increased significantly from 83% to 95% (p = 0.03). Conclusions: This modestly sized project demonstrated trends toward improvements in patient engagement, prognostic awareness, knowledge of signs of progression, and shared decision-making; these promising findings should be tested in larger samples. However, there remains an opportunity for further improvement in shared decision-making.
Overt acute hepatitis B is more severe in female patients
Authors: Ming‐Ling Chang, Yun‐Fan Liaw
Journal: Hepatology (2017)

1Liver Research UnitChang Gung Memorial Hospital, Chang Gung University College of MedicineTaipeiTaiwan *ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO:Yun‐Fan Liaw, M.D.199, Tung Hwa North Road,Taipei, 105, TaiwanE‐mail: [email protected]Tel: 886‐3‐3281200, ext. 8120
Phase II study of cabozantinib for patients with advanced <i>RET</i>-rearranged lung cancers.
Authors: Alexander E. Drilon, Camelia S. Sima, Romel Somwar, Roger Smith, Michelle S. Ginsberg, Gregory J. Riely, Charles M. Rudin, Marc Ladanyi, Mark G. Kris, Naiyer A. Rizvi
Journal: Journal of Clinical Oncology (2015)

8007 Background: RET rearrangements are found in 1-2% of non-small cell lung cancers and are drivers of growth in vitro and in vivo. Cabozantinib is a multi-tyrosine kinase inhibitor with activity against RET. Methods: This is a single-institution, open-label, phase II trial. Eligible patients (pts) had stage IV RET-rearranged lung cancer, KPS > 70%, and measurable disease (RECIST v1.1). Cabozantinib was administered at 60 mg daily until progression or unacceptable toxicity. Study endpoints included response at 12 weeks, objective response, progression-free survival (PFS), overall survival (OS), and toxicity. Simon two-stage minimax design: H0 10% vs HA 30% overall response rate (ORR). Five responses of a maximum of 25 patients were required to meet the primary endpoint. Results: Twenty pts were treated. The median age was 56 (range 38-80 years). All pts had adenocarcinoma and 60% (12/20) were female. The median number of prior chemotherapy lines was 1 (range 0-5). There were no complete responses. The rate of any partial response (PR) at 12 weeks was 33% (5/15, 95% CI 12-62%). ORR was 28% (5/18, 95% CI 10-53%) with 5 confirmed PRs. Stable disease rate was 72% (13/18, 95% CI 51-93%) including 2 unconfirmed PRs. Median PFS was 7 mo (95% CI 3 mo-not reached). Median OS was not reached. Toxicities were mostly grade 1 or 2 and included fatigue, diarrhea, palmar-plantar erythrodysesthesia, transaminitis, and thrombocytopenia. At least 1 dose reduction was required in 60% (12/20) of pts. Eight patients remain on treatment between 1 and 23 mo. Conclusions: Cabozantinib is active in patients with RET-rearranged lung cancers and responses can be durable. This study has met its primary endpoint. A larger, confirmatory, multi-center trial is now warranted. Clinical trial information: NCT01639508.
Phase II study of liposomal daunorubicin and ifosfamide (IDx) as first line chemotherapy in soft tissue sarcoma
Authors: P. M. Deckert, J. M. Siehl, E. Thiel, A. Schmittel, G. Hütter, H. Szelényi, U. Keilholz
Journal: Journal of Clinical Oncology (2004)

9011 Background: Anthracycline/ifosfamide combination is the most effective chemotherapy in soft tissue sarcoma. To improve tolerability and potentially efficacy of this combination we combined liposomal daunorubicin (L-Dauno) with high dose continuous infusion ifosfamide. Methods: In a single-arm phase II study 40 patients were enrolled with a median age of 57 years (19 to 78 years). Treatment regimen was L-Dauno 100 mg/m2 and ifosfamide 5 g/m2 over 24 h every 4 weeks with G-CSF support. Initially, 5 patients were included after failure of a doxorubicin/ifosfamide regimen, but none of these responded. Subsequently, 35 patients were treated first line. Results: A total of 115 cycles (range 1 to 7) were given. Toxicity was tolerable with 5 episodes (4,8 % of cycles) of ifosfamide related CNS toxicity grade II and 9 episodes (8,6 % of cycles) of neutropenic fever. Treatment had to be terminated due to a pseudo-allergic reaction to L-Dauno in one patient. One patient had ifosfamide related acute renal failure and was further treated with L-Dauno alone. No other non-hematological toxicity exceeding grade II was observed. Eleven (31,4 %) out of 35 patients without pretreatment achieved a PR, all after 2 treatment cycles, 6 patients (17,1 %) had stable disease and 12 patients (34,3 %) progressed; 6 patient were not evaluable (2 treatment unrelated early deaths, 2 lost to follow up, 1 adjuvant treatment, 1 to early to evaluate). Median time to progression was 10 months, median overall survival 16 months. PR with respect to histology was: 4/7 PNET, 1/6 leiomyosarcoma, 2/4 liposarcoma, 1/2 synovial sarcoma, 1/3 pleomorphic sarcoma, 1/1 malignant histiocytoma and 1/2 carcinosarcoma. Four of the responding patients received a consolidating high-dose-chemotherapy with subsequent stem cell support. Conclusions: IDx is a well tolerated and highly active chemotherapy regimen for first line treatment of soft tissue sarcoma, even in elderly patients. Randomized studies with this regimen are warranted. No significant financial relationships to disclose.
Prognostic significance and therapeutic implications of c-MET in esophageal squamous cell cancer.
Authors: Ching Tzao, Chun-Ya Wang, Ban-Hen Chen, Guang-Huan Sun
Journal: Journal of Clinical Oncology (2014)

4036 Background: c-MET is a receptor tyrosine kinase (RTK) that has been shown to be overexpressed and may serve as a potential therapeutic target in a variety of human cancers. We aimed to study if c-MET expression correlates with patients’ outcome with therapeutic implications in esophageal squamous cell cancer (ESCC). Methods: Expression of c-MET was analyzed by immunohistochemistry in tumors from 97 resected ESCC with correlative analysis with clinicopathologic variables. Cytotoxicity (MTT), cell migration, and assays for cell cycle and apoptosis were conducted in KYSE-510 and KYSE-170 ESCC cell lines in response to two c-Met inhibitors, SU11274 and PHA665752. Expression of cell cycle regulators, cyclin A and B1, tumor suppressors including Rb, p53 p21 and p27, and intrinsic apoptotic factors were determined by immunoblotting. Mice inoculated with KYSE 170 ESCC cell line were used to test effects of c-MET inhibitors in vivo. Results: Expression of c-Met within resected ESCC correlated positively with T status (P = 0.008), N status (P < 0.001), M status (P = 0.048) and stage (P < 0.001). Patients with low expression of c-Met showed better survival compared to those with high expression (P= 0.0001). SU11274 and PHA665752 significantly inhibited viability and migration of KYSE-170 and 510-ESCC cells with decreased expression of phosphorylated c-MET (p-c-MET). When treated with c-MET inhibitors, p27and p53 was upregulated with a concomitant decrease in cyclin-dependent kinase 6 (Cdk6) in KYSE-170 cells, whereas cyclin A and B1 in was decreased in KYSE-170 cells with an induction of G1 or G2 cell cycle arrest. Apoptosis was induced by c-Met inhibitors with upregulation of pro-apoptic factors, Bcl-2-associated X protein (BAX) and BCL2-interacting killer (BIK) in KYSE-170 cells. Growth was significantly suppressed in murine tumors of KYSE-170 when treated with c-MET inhibitors with decreased expression in p-c-MET. Conclusions: c-MET expression may serve as a predictor for poor prognosis in resected ESCC. c-MET inhibitors, SU11274 and PHA665752 had significant anticancer effects in ESCC cell lines in vitro and in vivo, suggesting that c-MET may serve as a potential therapeutic target for ESCC.
A needs-based curriculum for hematology/oncology mid-level providers.
Authors: Adam Binder, Denise Odea, Adriana Kaczaraj Malone
Journal: Journal of Clinical Oncology (2017)

121 Background: Mid-level providers, both nurse practitioners and physician assistants have comprehensive clinical training, however, they do not undergo in depth sub-specialty training prior to working within a sub-specialty practice. In addition, at our institution, often they are not integrated into academic culture resulting in dissatisfaction with educational opportunities. As a result, we set out to develop a needs based curriculum in order to provide focused learning opportunities for our mid-level providers and improve their satisfaction with the educational environment. Methods: An initial survey was sent to all mid-level providers within the division of hematology and oncology at a single institution. The survey evaluated attendance to currently available lecture series, satisfaction with the educational environment, and an assessment on practitioner comfort level in managing 19 clinical conditions commonly seen in oncology patients. All responses were voluntary and anonymous. A lecture series was developed focusing on topics in which providers felt least comfortable. Follow up survey was to be conducted after 6 months and 1 year of the educational lecture series. Results: On average 11 providers attended each lecture. After 6 months of lectures, there was a suggestion that more practitioners were satisfied with educational opportunities at our institution (pre-intervention 0% (N = 15) satisfaction, at 6 months 43.75% (N = 7)). There was no suggested change in comfort level in managing the specific clinical conditions. Mid-level providers, in addition to attending the focused educational lecture series, were more likely to attend other educational lectures within the institution. Conclusions: At interim analysis, our educational intervention seems to have improved mid-level provider satisfaction with educational opportunities provided to them. In addition, there has been an unintended effect of improving their attendance at other lecture series offered, implying that they feel more integrated into the academic community. To date there is no suggestion that the curriculum is improving providers comfort level in managing the pre-defined clinical scenarios.
Racial differences in survival based on tumor differentiation and stage in patients who have undergone surgery for colon cancer
Authors: D. Alexander, C. Chatla, E. Funkhouser, N. Jhala, W. Grizzle, U. Manne
Journal: Journal of Clinical Oncology (2004)

3609 Background: In the United States, studies indicate that African-Americans have poorer survival compared to Caucasians after diagnosis of colonic adenocarcinoma (CAC). In this study, we evaluated differences in survival based on pathologic stage and histologic grade of the tumor, between African-Americans and Caucasians who have undergone surgical resection as their only treatment for CAC. Methods: All 169 African-Americans and 229 randomly selected non-Hispanic Caucasians who underwent surgery between 1981–1993 for first primary sporadic CAC at the University of Alabama at Birmingham and affiliated Veterans Affairs Hospitals were included. We evaluated differences in survival by tumor stage and within each histologic grade of the tumor. None of these patients received pre- or post- surgery adjuvant therapies. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI), adjusting for demographic and tumor characteristics. Results: Analysis based on tumor stage revealed disparity in survival between African-American and Caucasian patients within stage II, III, and IV CAC; however, this association was statistically significant only in stage II patients. Among patients with stage II CAC, African-Americans have a 2.53 (95% CI: 1.31, 4.86) times greater risk of death from CAC within five years after surgery, compared to Caucasians. Among patients with poorly differentiated tumors, African-Americans are 3.1 (95% CI: 1.4, 7.1) times more likely to die from CAC at any given point in time after surgical resection, compared to Caucasians. There were no statistically significant differences in survival between African-Americans and Caucasians with moderate or well differentiated tumors. Conclusions: Our findings suggest that decreased survival among African-Americans may not be attributable to under-staging at diagnosis or disparate treatment options, but may be due to differences in biologic features like degree of differentiation or other genetic abnormalities between these two ethnic groups of CAC patients who have undergone surgery. No significant financial relationships to disclose.
In Reply:
Authors: Charles M. Balch, Seng-Jaw Soong, Renee Desmond
Journal: Journal of Clinical Oncology (2005)

We appreciate the comments by Berd, Mastrangelo, and Sato in regard to our article 1 published in the Journal of Clinical Oncology in 2001.The following are our responses to the concerns raised in their comments.First, we would like to clarify that the survival times for patients with stage III melanoma in our study were actually calculated from either the data of documented lymph node metastasis or the date or lymphadenectomy, not from the onset of primary melanoma diagnosis.Thus, the survival curves/rates presented in our article for stage III melanoma should be comparable to those reported in published studies using similar starting dates.Our calculation of survival times from the onset of the primary melanoma diagnosis applied only to stage I/II melanoma that consisted of more than 85% of the study population.Perhaps that should have been made clearer in our article.As Berd, Mastrangelo, and Sato correctly pointed out in their letter, some of our parenthetical remarks (eg, "from the onset of primary melanoma") were indeed inadvertently misplaced.However, this does not affect any of our survival rate calculations and the conclusions that we made in the article.Our multivariate prognostic factor analysis for stage III melanoma was also based on the survival times that were calculated from either the date of documented lymph node metastasis or the date of lymphadenectomy.Therefore, the conclusion that we made in our article about ulceration as one of the key prognostic factors in stage III melanoma is perfectly valid.In subsequent studies, 2 we further examined potential prognostic factors separately for the group of patients with micrometastasis (clinically occult node metastasis) and the group with macrometastasis (clinically apparent node metastasis).In our multivariate prognostic factor analyses, ulceration was clearly a significant factor in both groups.This further validated the prognostic importance of ulceration in both major subgroups of our stage III melanoma patients.Our data showed that the 5-year survival rates for stage IIIB and IIIC patients varied from 59% to 24%, depending on various substages of patients. 3 The overall 5-year survival rate of 44% quoted by Berd, Mastrangelo, and Sato for their study of stage IIIB and IIIC melanoma patients seems reasonable, and their patient population may vary in prognostic factors that influence survival rates of their patients.