tbuckley/cabot-search huggingface dataset:
A randomized phase II study of gemcitabine (GEM) plus S-1 combination chemotherapy versus GEM monotherapy in patients (pts) with advanced biliary tract cancer (BTC).
Authors: T. Sasaki, H. Isayama, Y. Ito, I. Yasuda, N. Toda, K. Hanada, S. Matsubara, H. Maguchi, Y. Yashima, H. Kamada
Journal: Journal of Clinical Oncology (2011)

250 Background: Our previous phase II study demonstrated that GEM/S-1 combination chemotherapy was tolerable and showed good efficacy in pts with advanced BTC (Sasaki et al, Cancer Chemother Pharmacol 2010). This randomized phase II study compared the response rate of GEM/S-1 combination chemotherapy and GEM monotherapy in pts with advanced BTC. Methods: Pts with advanced BTC who had at least one measurable lesion were randomized into two groups. GEM/S-1: GEM 1,000 mg/m 2 (day 1, 15) and S-1 80 mg/m 2 (day 1-14) repeated every 4 weeks. GEM: GEM 1,000 mg/m 2 (day 1, 8, 15) repeated every 4 weeks. Treatment was continued until disease progression. The primary endpoint was objective response according to RECIST version 1.0. Results: From November 2008 to March 2010, 62 pts were enrolled from 13 institutions. Patient characteristics were: median age 72 (range 47-86); Male/Female 36/26; Performance status 0/1/2 (37/22/3). The primary tumor site was; 30 pts in gallbladders, 16 pts in intrahepatic bile ducts, and 16 pts in extrahepatic bile ducts. Seven pts had previous surgical resection. Response rates of GEM/S-1 and GEM were 16.7% and 9.4%, respectively. The median time-to-progressions of GEM/S-1 and GEM were 5.6 months and 4.1 months, respectively. Conclusions: GEM/S-1 combination chemotherapy is more active than GEM monotherapy in pts with advanced BTC. Updated time-to-progression and overall survival data will be presented at the meeting. No significant financial relationships to disclose.
Phlebotomy Frequency and Quality of Life and Productivity in Patients with Polycythemia Vera: Results from the MPN Landmark Survey in the United States
Authors: Salman Fazal, Carole B. Miller, John O. Mascarenhas, Maureen Thyne, Sara Goldberger, Dilan C. Paranagama, Shreekant V. Parasuraman, Ahmad B. Naim, James Mangan, Ruben A. Mesa
Journal: Blood (2015)
Enrichment of allogeneic tumor antigen-specific T cells from bone marrow (BM) of patients treated with high-dose post-transplant cyclophoshamide (Cy): A novel approach to adoptive immunotherapy.
Authors: K. Noonan, L. Luznik, I. Borrello
Journal: Journal of Clinical Oncology (2011)

2610 Background: Donor lymphocyte infusions (DLI) to treat relapse after allogeneic BMT (alloBMT) has limited efficacy and is associated with substantial graft vs host disease (GVHD). Thus, novel strategies are required that increase the tumor specificity with reduced alloreactivity. High-dose Cy post-BMT effectively reduces GVHD through elimination of allo-reactive T cells and enables immune reconstitution free of ongoing pharmacologic immunosuppression. Since the BM is both the site of disease in most hematologic malignancies and a reservoir of tumor specific T cells, we hypothesized that marrow infiltrating lymphocytes (MILs) collected after alloBMT in patients treated with high-dose Cy could be a source of tumor-specific T cells for adoptive immunotherapy. Methods: BM was obtained from patients 2 -12 months after HLA-matched alloBMT on the clinical trial using high-dose post-transplant Cy as a single agent GVHD prophylaxis. The MILs were activated and expanded with CD3/CD28 antibody-coated beads. Results: Allo-MILs can be reproducibly expanded (574-fold avg expansion; 14-2000) at all time points tested. The activated allo-MILs are not anergic, exhibit anti-HLA-reactivity against third party allo-antigens but do not respond to recipient allo-antigens. Tumor-specific MILs were significantly expanded as determined by reactivity to HL60/K562 myeloid cell lysates (P<0.0001; pre- vs. post-activation). In contrast, no change was observed in cultures pulsed with irrelevant antigens, thus suggesting the specificity of the response. The ability to expand allogeneic antigen-specific MILs was also confirmed with a 15.5 fold expansion of PR-1 specific (HLA) A*0201-restricted CD8+ T-cells using tetramers. Conclusions: We can preferentially enrich tumor specific MILs with minimal allo-reactivity in patients treated with high-dose Cy. A phase I/II trial is planned to assess the safety and feasibility of administering ex vivo expanded allogeneic MILs to patients with relapsed hematologic malignancies after alloHSCT.
A phase II multicenter study on CY-503 in the treatment of patients with unresectable stage IV metastatic melanoma after failure of previous chemotherapy.
Authors: P. Mohr, U. Trefzer, R. Gutzmer, A. Hauschild, M. Weichenthal, K. Witthohn, T. Wilhelm, F. Schenk, K. C. Kaehler, H. Lentzen
Journal: Journal of Clinical Oncology (2010)

e19015 Background: CY-503 is a recombinant mistletoe lectin ( INN: aviscumine) leading to catalytical inactivation of ribosomes, thereby inhibiting protein synthesis. Dependent on dosage immunomodulatory and cytotoxic effects are induced. In patients (pts.) with stage IV metastatic melanoma CY-503 could potentially lead to an antitumoral response. Methods: Pts. with stage IV metastatic melanoma (ECOG performance score 0-1), who had failed from one or more previous systemic chemotherapies, were eligible in this trial. Pts. with severe organ dysfunction or brain metastasis were excluded. Pts. received CY-503 350ng SC twice weekly for a minimum of 8 weeks (2 cycles). Pts. without disease progression were continued. The primary study endpoints were progression free survival (PFS) and overall survival (OS). Tumor assessment included CT and MRI scans every 8 weeks, which were centrally reviewed. Results: Between April 2008 and June 2009, 32 pts. were enrolled, one being ineligible. 31 pts. (16m; 15f) with a median age of 67 years (range: 20-85y) were evaluable. Pts. were belonging to the following stage IV categories: M1a/b/c = 4/5/22, and median number of prior treatments was 2 (range: 1- 6), 7 pts. (23%) were pretreated with ≥ 3 lines. (84%) received at least 8 weeks of treatment; 4 pts. withdrew prior to 8 weeks due to clinically overt disease progression, and 1 pt. due to a severe adverse event (SAE). At 8 weeks 11 pts. with stable disease (SD) were observed (disease control rate: 36% ITT) with a median PFS of 3.75 months (95% CI: 3,6-3,9 months). The median PFS in the ITT population was 2.0 months (95% CI: 1.9–2.1 months). Median OS had not been reached at the time of evaluation. Local reactions at the injection site were the main toxicities. Two severe adverse events with fatal outcome (1 pt. with cardiac arrhythmia, 1 pt. with stroke) could not clearly be related to the study medication. Conclusions: CY-503 showed a modest clinical activity in pts. with advanced melanoma. Side effects were mostly limited to local reactions at injection site. Given this heavily pretreated population, further investigations on the use of CY-503 in the treatment of malignant melanoma might be warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cytavis Biopharm GmbH Cytavis Biopharm GmbH Cytavis Biopharm GmbH Cytavis Biopharm GmbH
Clinical outcome of patients with leptomeningeal metastasis from non-small cell lung cancer: Okayama Lung Cancer Study Group.
Authors: S. Umemura, K. Kiura, K. Tsubouchi, N. Takigawa, K. Fujiwara, N. Horita, Y. Segawa, N. Hamada, I. Takata, M. Tanimoto
Journal: Journal of Clinical Oncology (2011)

7544 Background: Although the clinical outcomes in non-small cell lung cancer (NSCLC) patients have been improving recently, little is known about recent trend in prognosis of patients with leptomeningeal metastasis (LM) from NSCLC. The purpose of this study is to identify this issue and the association between epidermal growth factor receptor (EGFR) mutation status and prognosis of patients with LM who were treated with EGFR-tyrosine kinase inhibitors (TKIs). Methods: We retrospectively analyzed a series of 91 consecutive NSCLC patients with LM between 2001 and 2010. Survival time was defined as the duration from initial diagnosis of LM. Results: Demographics of the patients were as follows: Male/Female: 47/44, Adeno/Squamous/others: 83/2/6, Performance Status (PS) 0-1/2-4: 20/71, and non-smoker/smoker/unknown: 42/48/1. Median survival time (MST) of all patients was 3.6 months. A multivariate analysis revealed EGFR-mutant tumors and adenocarcinoma associated with a better prognosis. Among all 91 cases, 51 were received EGFR-TKIs (gefitinib/erlotinib: 33/18), and we next focused on the prognosis of these patients. Median progression free survial (PFS) time was not different between patients treated by gefitinib and by erlotinib. Of these, EGFR mutation status was assessed in 30 (3 from spinal fluid, 20 from primary site or others, and 7 from both), which showed 7 (23%) without any mutations (Group 1), 10 (33%) with exon 21 mutation (Group 2) and 13 (43%) with exon 19 deletion (Group 3). 1 patient in Group 2 harbored T790M. Interestingly, PS was significantly improved in groups 2 and 3 but not in group 1. MST of these subgroups was 1.4, 7.1 and 11.0 months for groups 1, 2, and 3 respectively (p<0.001). Median PFS time was 0.9, 2.0, and 7.8 months for groups 1, 2, and 3 respectively (p<0.001). A multivariate analysis showed that EGFR-mutant tumors were associated with better prognosis, but type of TKIs was not affected the outcome. Conclusions: The prognosis of patients with LM from NSCLC was still poor. EGFR-TKIs would be beneficial for those with EGFR mutations, especially exon 19 mutations rather than exon 21 mutations, for both improvement of PS and survival, irrespective of type of EGFR-TKIs.
Determining the optimal timing for radical cystectomy after neoadjuvant chemotherapy.
Authors: Chinedu O. Mmeje, Cooper Benson, Graciela M. Nogueras-Gonzalez, Isuru Sampath Jayaratna, Neema Navai, Jianjun Gao, Arlene O. Siefker-Radtke, Ashish M. Kamat, Colin P. N. Dinney, Jay Bakul Shah
Journal: Journal of Clinical Oncology (2015)

339 Background: We present the largest series reviewing complications and pathologic outcomes following neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), to determine whether the interval between chemotherapy and surgery (ICS) affects 90-day post-operative morbidity and lymph node metastasis. Methods: We analyzed 338 patients treated with NAC followed by RC from January 1995 through December 2013. The association of ICS with 90-day surgical morbidity, incidence of major complication, 90-day readmission, and lymph node metastasis was determined. Generalized linear models were used to determine potential predictors of each endpoint. Patients were stratified into four groups by ICS days (18 – 42; 43 – 64; 64 – 85; &gt; 85). Complications were classified using the Clavien system. Results: The overall morbidity of the cohort was 59%, with 66% being minor, and 34% being major complications. The median ICS was 46 days (18 – 199 days). There was no difference in the overall morbidity, readmission, or major complication rates among the four groups. Patients with an ICT &gt; 85 days had the highest incidence of lymph node metastasis (40%), though this was not found to be significant (p = 0.1). On multivariate analysis including predictors of perioperative morbidity, extravesical (pT 3 – 4 ) disease (OR = 1.97; p = 0.01) was an independent predictor of overall morbidity, while age at cystectomy (OR = 1.05; p = 0.004), and surgical time ≥ 7 hrs (OR = 2.87; p = 0.001) were independent predictors of major complications. Only surgical time ≥ 7 hrs (OR = 2.24; p = 0.006) was found to be a predictor of readmission. In a separate multivariate analysis that included risk factors for pathological node positivity, the predictors for lymph node metastasis included variant histology (OR = 2.06; p = 0.026) and extravesical disease (OR = 2.76; p = 0.002). Patients with an ICT &gt; 85 days had a higher risk of node metastasis though this was not significant. Conclusions: Patients can undergo RC anytime between 2.5 – 12 weeks after NAC with no difference in risk of surgical complications or nodal metastasis.
Prostate cancer burden at the Uganda Cancer Institute (UCI).
Authors: Fred Machyo Okuku, Jackson Orem, George Holoya, Christopher J De Boer, Matthew M. Cooney
Journal: Journal of Clinical Oncology (2015)

246 Background: In Uganda prostate cancer is the most common cancer and the incidence is increasing 5.2% annually. This burden is seen without screening programs in a country with limited access to cancer care. Data describing patient presentation and outcomes are lacking. Methods: Retrospective chart review for men with histologically-confirmed prostate cancer at the UCI from January 1 to December 17, 2012. Patient characteristics, treatments, and survival data were obtained. Results: There were 181 men with confirmed prostate cancer [C1] . Mean age was 69.5 (SD 9.0) with a median age of 70 (IQR: 64-75). Men presented with symptoms of lower urinary tract symptoms 73% (n=131), bone pain in 18% (n=32), elevated PSA 3% (n=5) and other causes 6% (n=11). Median baseline PSA was 91.3 ng/ml (IQR: 19.5-311.3 ng/ml) and upon presentation 51.1% (n=92) had a PSA value over 100 ng/ml. Gleason Score was 9 or 10 in 66.7% (n=120), Gleason Score 7 to 8 in 23.4% (n=44), and Gleason six or lower in 10% (n=18). Ninety percent (n=136) of patients had stage IV disease, 6.5% (n=11) were stage III, 11.9% were (n= 20) stage II, and 1 individual (0.6%) had stage I. Common sites of metastases included bone 73% (n=102), visceral metastases 21% (n=29), and lymph node involvement 4% (n=5). Spinal cord compression occurred in 30.9% (n=55) and 5.6% (n=10) experienced a fracture. A total of 14.9% (n=27) patients underwent radical prostatectomy and 17.7% (n=32) received radiotherapy. GNRH agonist was given to 45.3% (n=82) of patients, 29.2% (n=53) of men received diethylstilbestrol, and 26% (n=47) underwent bilateral orchiectomy. Chemotherapy was administered to 21.6% (n=39) and 52.5% (n=95) received bisphosphonates. During the 12 months of study 23.8% (n=43) of men experienced death and 54.4% (n=98) were lost to follow up. Conclusions: UCI patients present with significant symptoms, high PSA, and aggressive Gleason Scores. 90% present with stage IV disease and almost 33% develop spinal cord compression. Prostatectomy and radiotherapy are infrequently given and the primary treatments are hormonal manipulation and chemotherapy. Almost 25% of patients succumb within a year of presentation and there is a high rate of patients lost to follow up.
Clinical trial enrollment expansion to the community.
Authors: Judith Kostka, Jessica A. Zerillo, Andrea Kruse, Natalie Faye Sinclair, Maureen Patrick, Lauren McGovern, Frances Fuller, Kelly O'Neil, Nicole Hixon, Kristie Weeks, Bruce E. Johnson, Ian E. Krop, Jen Savoie, Farah Daftary, Michael Constantine, Mona S. Kaddis, Humberto A. Rossi, Naeem Tahir, Andrew David Norden
Journal: Journal of Clinical Oncology (2016)

112 Background: Oncology patients at community cancer practices generally do not access clinical trials to the same degree as patients at academic medical centers. Collaborations between research and clinical teams across academic hospitals and their affiliated community sites may help to improve this disparity. Methods: To improve clinical trial enrollment, a multidisciplinary team of research and clinical staff from the Dana-Farber Cancer Institute main campus and a community-based satellite site implemented a program to enhance identification of breast cancer patients eligible for clinical trials. The team constructed a process map, cause and effect diagram and collected diagnostic data, which was displayed with a Pareto chart. Process control charts were used to track data over time. Interventions included: (1) a web-based tool to pre-screen patients for community and main campus trials, (2) a training session for clinicians on trial communication skills, (3) designated clinician visits for follow-up trial discussions, and (4) research nurse telephone calls after the initial consultation. Results: Before the program (7/14-10/14), research staff screened 83% of new breast cancer patients for clinical trials, which increased to 97% after the program (11/14-9/15) (p &lt; 0.001). There was not a significant change in trials presented to eligible patients or enrollment in trials. Conclusions: The proportion of patients identified for clinical trials increased and there was numeric improvement in the proportion of eligible patients presented trials. There was an increase in clinical trial enrollment that did not reach statistical significance, possibly due to the low sample size. These results suggest that the interventions would benefit from further modification and use. The project demonstrates the challenges and opportunities inherent in growing successful clinical trial programs in community-based satellite sites. [Table: see text]
Do more lines of chemotherapy make you live longer? Treatment for ovarian cancer comparing cohorts of patients 1989–90 with 1995–6 in multivariate analysis of survival
Authors: M. K. Findley, H. Lee, M. V. Seiden, M. A. Shah, A. F. Fuller, A. Goodman, R. T. Penson
Journal: Journal of Clinical Oncology (2005)

5062 Background: Recurrent epithelial ovarian cancer (EOC) has come to be considered a chronic cancer frequently treated with multiple lines of chemotherapy. It remains unclear whether response to sequential treatment improves survival or simply reflects the biology of the disease. Methods: We reviewed 154 patients with EOC presenting in 1989–90 (n=72) and 1995–6 (n=82). The prognostic relevance of disease and treatment characteristics were examined in multivariate survival analysis. Results: Median overall survival (OS) was similar in the early (22.9) and late (22.3 months) cohorts (p=0.29). Median progression free survival (PFS) was apparently longer in the later cohort (9.4 (95%CI 7.1–13.1) vs. 14.9 (95%CI 11.8–20.7)) but did not reach statistical significance (p=0.88) Nearly twice as many patients received >3 lines of chemotherapy (22 vs. 12) for recurrent disease in the later cohort. Univariate and multivariate analysis showed that two parameters were associated with a longer survival time: early stage (p=0.013) and the use of paclitaxel (p=0.032). Patients treated with ≥ 3 lines of chemotherapy for recurrent disease lived for >3x as long as those with 2 or less (15.3 (95% CI 11.6–20.5) vs. 50.1 (95% CI 46.1–59.2) months, p=0.0009). Conclusions: Over the study period there has been little improvement in OS and although more treatment was given to patients in the later cohort, the combination of new agents in first line therapy, rather than the serial use of chemotherapy for recurrent disease, appears to have a greater impact on PFS. The dramatic difference in apparently better survival with multiple lines of therapy may reflect favorable tumor biology, more than the effect of treatment. No significant financial relationships to disclose.
Quality of life in patients with dermatologic toxicities: Experience from the SERIES clinic.
Authors: J. Gordon, Y. Balagula, S. W. Dusza, D. Chen, S. Berg, D. P. West, M. E. Lacouture
Journal: Journal of Clinical Oncology (2011)

9104 Background: Anti-cancer therapies such as radiation, cytotoxic chemotherapy, and novel targeted agents may cause a range of dermatologic toxicities (dTs). At present, there are limited data regarding the impact of dTs on dermatologic quality of life (dQoL). We systematically investigated their impact on dQoL in patients seen at the SERIES clinic, a referral center for management of dTs stemming from anti-cancer therapies. Methods: Medical records of patients seen in the dermatology referral clinic for cancer patients at Northwestern University between 9/2007 and 9/2008 were searched for completion of Skindex-16, a dermatology-specific QoL questionnaire. Skindex scores range from 0 (best QoL) to 96 (worst QoL) and measure 3 domains: symptoms, emotions and function. The impact of dTs on the total Skindex score and the scores of each domain were analyzed. Descriptive statistics (means, medians, range) were used to describe scores. Differences in mean scores were evaluated by linear regression. Results: A total of 425 patients were analyzed. EGFRI-associated papulopustular (ppr) rash, HFS/HFSR, nail toxicities, xerosis, fissures, pruritus and alopecia were observed in 26.7%, 12.5%, 9.2%, 31.1%, 5.0%, 18.1%, and 9.4% of patients, respectively. The presence of ppr rash was associated with a greater impact on the mean total, symptoms, emotions, and function domain scores as compared to patients without ppr rash (45.1 vs. 30.4; 11.6 vs. 8.4; 23.4 vs. 16.5; 10.1 vs. 5.6, p<0.001). Similarly, the presence of pruritus was associated with a greater impact on the mean total and all three domains scores (46.5 vs.31.6; 13.5 vs. 8.3; 23.2 vs. 17.2; 9.8 vs. 6.2, p<0.001, =0.003, =0.0008, respectively). Patients (n=32) with ≥ 3 dTs (ppr rash, nail toxicities, xerosis, fissures, and pruritus) had a significantly higher mean total as well as symptoms, emotions and function scores as compared to patients with fewer dTs (47.6, 14.4, 23.4, 9.8, respectively, p<0.001). Conclusions: dTs are associated with diminished dQoL; ppr rash and pruritus appear to have the greatest negative impact. Future emphasis should be placed on developing effective management strategies for dTs in order to minimize the likelihood of reduced dQoL.
Multidisciplinary tumor board for improvement of oncology collaboration in advanced cancer patients.
Authors: Sanders Chang, Amish Doshi, Cardinale B. Smith, Bethann Scarborough, Stelian Serban, Jeffrey Ciccone, Kavita Vyas Dharmarajan
Journal: Journal of Clinical Oncology (2016)

175 Background: The Palliative and Supportive Oncology Tumor Board was developed in 2015 to provide an interdisciplinary forum for discussion and management of patients with complex or refractory symptoms from advanced cancer. The board meets monthly and consists of medical, surgical, and radiation oncologists, interventional radiologists, pain management, palliative care specialists, residents, and fellows. Here, we assess the impact of the tumor board on the care of these patients. Methods: Electronic records of advanced cancer patients discussed at the tumor board from January 2015 to December 2015 were analyzed. We extracted data regarding sociodemographics, primary cancer site, pain interventions delivered, palliative care services utilized, and readmissions. Results: Thirty-two patients were presented at the tumor board over twelve months. The median age was 60 years (range 26-89); 47% were male. Primary cancer site included multiple myeloma (n = 11), gastrointestinal (n = 9), genitourinary (n = 5), breast (n = 2), lung (n = 2), skin (n = 1), and unknown origin (n = 2). At the time of discussion, 16 patients were hospitalized and 18 were in the ambulatory setting. Recommendations from the tumor board included altering medication regimen (n = 4), discussing eligibility to receive an anesthetic block (n = 7), undergoing vertebroplasty (n = 9), and planning palliative radiation treatment (n = 19). Patients were seen by specialists from pain (n = 21), interventional radiology (n = 14), neurosurgery (n = 9), palliative care (n = 20), radiation oncology (n = 21), or medical oncology (n= 32) within one day of their case presentation at the tumor board. Seven patients were transferred to the inpatient palliative care unit within a day of their tumor board discussion. Five patients were readmitted to the hospital within 30 days due to uncontrolled pain or other symptoms. Conclusions: The palliative and supportive oncology tumor board was well received by clinicians overall. It fostered interdisciplinary collaboration and supported comprehensive management of pain and other symptoms, as evidenced by the mix of cases discussed and the short time within which patients were seen after presentation by the participating specialists.