tbuckley/cabot-search huggingface dataset:
Initiating a structured advance care planning (ACP) process within a telephonic disease management model.
Authors: Melissa Jameson, Mitra Abdullahpour, Cynthia Taniguchi, Marcus A. Neubauer, J. Russell Hoverman, Jad Hayes, Kathryn Eagye
Journal: Journal of Clinical Oncology (2014)

73 Background: Utilizing a telephonic disease management (DM) model for educating and assisting patients to self-manage treatment side effects is a known element of practice quality. Yet, disease management models frequently neglect important aspects of patient education regarding end of life care. A model is needed whereby structured ACP content and processes are included within the disease management scope of work and documented accordingly. Methods: Over a nine month period, a DM model with an ACP education component was applied in a community oncology setting. Practice DM services were provided through a centralized call center and delivered telephonically for patients receiving chemotherapy. DM staff was comprised of registered nurses with oncology credentialing and ACP training. The model included an introduction of ACP principles within the first telephonic outreach to the patient, highlighting the purpose of ACP and the importance of ongoing communication of patient values and goals for care throughout the treatment trajectory. On subsequent calls, with the patient’s permission, DM staff provided education regarding potential end of life treatments and advance directives. Patient education and learning outcomes were documented in the electronic health record (EHR). Results: A total of 154 patients participated in the DM program. An introduction to ACP was provided for 131 patients (85%). EHR inclusion of patient values and goals for care was achieved for 93 patients (60%). 93 patients (60%) agreed to receive subsequent education regarding potential end of life treatment interventions. During the nine-month period, 21 patients (14%) transitioned to hospice care. Conclusions: Telephonic DM offers a realistic and sustainable option for initiating the ACP process. A key learning is that patients are frequently open with discussing end of life care while in the comfort and safety of their home. EHR documentation of ACP content and patient preferences for care is a critical step for real-time sharing of information among the clinical team. Further study is needed to determine whether this intervention has an impact on appropriate hospice enrollment and other quality end points.
A Profound Biological Difference of Chronic and Blast Phase Chronic Myeloid Leukemia in Ex Vivo Drug Responses
Authors: Paavo Pietarinen, Tea Pemovska, Emma I Andersson, Perttu Koskenvesa, Mika Kontro, Swapnil Potdar, John Patrick Mpindi, Olli Kallioniemi, Krister Wennerberg, Caroline A Heckman, Satu Mustjoki, Kimmo Porkka
Journal: Blood (2014)
Importance of subset classification based on tumor size for patients with single hepatocellular carcinoma.
Authors: Jian-Hong Zhong, Bang-De Xiang, Liang Ma, Yan-Yan Wang, Ning-Fu Peng, Wen-Feng Gong, Shi-Dong Lu, Le-Qun Li
Journal: Journal of Clinical Oncology (2016)

373 Background: Single hepatocellular carcinoma (HCC) regardless of size that without vascular invasion is classified as stage A disease in the Barcelona Clinic Liver Cancer staging system. However, patients with different tumor size may have different overall survival after hepatectomy. This study compared the prognosis of patients with single HCC after hepatectomy among groups with different tumor size. Methods: Patients with newly diagnosed single HCC from January 1, 2004 to October 31, 2013 were classified according to tumor size: group 1, ≤ 5 cm; group 2, &gt; 5 cm and ≤ 8 cm; group 3, &gt; 8 cm and &lt; 10 cm; and group 4, ≥ 10 cm. Overall survival analysis was performed according to tumor size. Results: A total of 857 patients were enrolled. Among them, 814 (95.0%) were with Child-Pugh A class liver function. Blood loss was 367 ± 424 mL. Groups 1, 2, 3, and 4 consisted of 426 (49.7%), 229 (26.7%), 52 (6.1%), and 150 (17.5%) patients, respectively. The 5 years overall survival ranged from 35 to 63% in all four groups. The median survival time differed significantly according to tumor size (76, 49, 43, and 38 months in groups 1, 2, 3, and 4, respectively; P &lt; 0.001). Group 3 had overall similar survival to group 4. Multivariate analysis showed that group 3 and 4 had significantly worse overall survival compared to group 1 and 2. Conclusions: Patients in group 3 and 4 had significant worse prognosis than those in group 1 or group 2. Our results suggest that subset classification based on tumor size is warranted to patients’ prognosis.
Molecular Basis of Genomic Instability and Progression in Multiple Myeloma: Potential Role of Apurinic (Apyrimidinic) Endonuclease.
Authors: Masood A. Shammas, Hemanta Koley, Paola Neri, Pierfrancesco Tassone, Ramesh B. Batchu, Robert Bertheau, Robert J. Shmookler Reis, Nikhil C. Munshi
Journal: Blood (2005)
Preoperative breast MRI in early-stage breast cancer: A decision analysis.
Authors: P. Young, B. Kim, J. Malin
Journal: Journal of Clinical Oncology (2011)

6035 Background: Rapid uptake of new imaging technology is a major contributor to rising health care costs. Preoperative breast magnetic resonance imaging (MRI) for patients with early-stage breast cancer has dramatically increased in use without evidence of improved outcomes compared to standard triple assessment (clinical examination, imaging with mammography and/or ultrasonography, and needle biopsy) and is associated with higher rates of mastectomy. Methods: A decision analytic model was developed to evaluate the impact of adding breast MRI to the preoperative evaluation of women with early-stage breast cancer who were candidates for breast-conserving therapy (BCT) on patient outcome measures in quality-adjusted-life-years (QALYs). Model inputs including survival, recurrence rates, and health utilities were obtained from a comprehensive literature review. One-way sensitivity analyses were performed to estimate threshold values for key parameters at which adding MRI would become the optimal imaging strategy over standard triple assessment. Results: Preoperative breast MRI was associated with a decrease of 0.094 QALYs compared with no MRI, based on a 20-year life expectancy after diagnosis of early-stage breast cancer. In order for routine preoperative breast MRI to become the optimal strategy, the conversion rate to mastectomy after preoperative MRI would need to be <1% (vs. range of 3.6-54% reported in the literature) Across a wide range of local recurrence rates following BCT, MRI remained inferior to no MRI. Conclusions: Routine preoperative breast MRI appears to confer no advantage over standard diagnostic evaluations for early-stage breast cancer and may lead to worse outcomes.
Trastuzumab therapy in HER2-positive, metastatic breast cancer.
Authors: A. D. Smith, K. Guilbert, D. Lister, S. Streilein, V. C. Bourrier, B. Lozar, S. Navaratnam, G. A. Harding, M. W. Pitz
Journal: Journal of Clinical Oncology (2011)

e11018 Background: Breast cancer is the most common cancer diagnosis among women. Trastuzumab is a monoclonal antibody that targets breast cancer cells which overexpress the human epidermal growth factor receptor 2 (HER2). In this study, we set out to review patients with HER2 positive, metastatic breast cancer who were treated with trastuzumab in Manitoba, to document treatment practices, monitoring for toxicity, and clinical outcomes. Methods: Using the Manitoba Cancer Registry and the Provincial Oncology Drug Program database we selected all women who received trastuzumab in 2006 for HER2 positive, metastatic breast cancer. Data was collected using the electronic record. Supplemental data was retrieved from paper charts whenever possible. Women were followed from time of diagnosis of breast cancer until death, with administrative censoring at December 31, 2008. Results: In total, 65 women met the study criteria. The average age at diagnosis of breast cancer was 52.3 years, and 20% had de novo metastatic disease. Women were administered trastuzumab on either a weekly or three-weekly schedule for an average duration of 19.4 months. Patients received an average of 11,109 mg of trastuzumab, corresponding to a drug cost of $68,200. Trastuzumab was stopped in 7 women (11%) because of cardiac toxicity. Median progression free survival for this cohort was 10.7 months with a median overall survival of 20.5 months. Conclusions: In women with HER2 positive, metastatic breast cancer, trastuzumab is often used for a long period of time resulting in significant drug costs. Many women continued trastuzumab despite disease progression, which requires further study. Cardiac toxicity remains a common complication and guidelines for cardiac monitoring should be considered.
Dosimetric analyses of the thyroid gland in breast cancer patients who received regional lymphatic irradiation.
Authors: M. Akin, A. Ergen, A. Unal, N. S. Bese
Journal: Journal of Clinical Oncology (2011)

e11032 Background: Thyroid gland is one of the radiosensitive endocrine organs in the body. It has been shown that after direct irradiation of thyroid with total doses of 26-30Gy, functional abnormalities could be observed. In this study we assessed thyroid doses in breast cancer patients who received postoperative regional irradiation. Methods: Retrospective analyses of treatment plans from 122 breast cancer patients who were treated with 3 dimensional conformal planning was performed. Precise plan version release 2.16 was used for planning. All patients received irradiation to supraclavicular/level III lymph nodes in addition to chest-wall/breast or other lymph node areas with a total dose of 46Gy in 23 fractions. Thyroid gland was contoured manually on 2-5 mm thickness of computed tomography scans. Absolute thyroid volume, mean thyroid doses were assessed. Results: The mean thyroid volume of all patients was; 16.7 cc (min: 1.9 cc max: 41.6 cc). The mean number of the mean dose that thyroid gland received was 2208 cGy (32 cGy - 4651 cGy). 36 % (44) of the 122 patients received doses higher than 26Gy. Conclusions: Although the thyroid gland in majority of the breast cancer patients treated with conformal RT exposed considerable doses. Patients may require careful periodic clinical and laboratory evaluation to avoid excess morbidity. Dosimetric factors derived from the analysis of dose-volume histograms can also predict the occurrence of thyroid disorders, and help to adapt the prescribed dose and the ballistic of irradiation.
A phase II trial of PTK-787 (PTK/ZK) in recurrent or progressive meningiomas
Authors: R. DeBoer, S. A. Grimm, J. Chandler, L. Gallot, S. Kennedy, K. Burns, L. Rice, C. Cabreza, K. Muro, J. J. Raizer
Journal: Journal of Clinical Oncology (2008)

2060 Background: Treatment options are limited for patients (pts) with recurrent meningiomas. VEGF and PDGF promote angiogenesis and cellular proliferation. PTK-787 is an orally active inhibitor of VEGF and PDGF receptors. The primary endpoint of this trial was to determine the efficacy of PTK-787 in pts with recurrent or progressive meningiomas as noted by radiographic response. Main secondary endpoints were 6-month progression-free survival (PFS-6) and overall survival. Methods: Adult patients with histologically proven meningiomas (grade I, II, or III) or hemangiopericytomas were eligible. Pts must have a history of progressive disease, KPS ≥60, and not be on enzyme inducing anti-convulsants. No limit on number of prior therapies was placed. PTK-787 administration began at 250 mg BID and increased by 250 mg/day weekly to a dose of 500 mg BID. Exams were done after each 4-week treatment cycle; imaging was done every 8 weeks. Treatment continued for 12 months or until disease progression. Evaluation of VEGF, EGFR, PDGF, HER2, and ET 1 and 2 in tissue is planned. Results: 13 of planned 25 pts have enrolled: 6 grade II and 6 grade III meningiomas, 1 hemangiopericytoma (7 men; 6 women). Median age was 60 years (range 30–89). Median number of cycles to date is 4 (range 1.5–9.4) with 4 pts still on treatment. No grade 4 toxicity was observed. All pts experienced fatigue, which reached grade 3 in 3 pts. Other grade 3 toxicities: jaw pain, elevated transaminases, anorexia, rash, and hypertension. Due to intolerability, original dose escalation to 750 mg BID was reduced to 500 mg BID. Two pts were withdrawn due to rash prior to imaging and were not evaluable for response. Best response in the remaining 11 evaluable pts was partial response in 1 (8%), stable disease in 9 (69%), and progression in 1. Overall PFS-6 was 46% and median time to progression was 15.7 weeks (range 7.6–32) among the 7 evaluable pts who progressed. Conclusions: This is the first trial to use a combination VEGF/PDGF inhibitor in pts with recurrent or progressive meningiomas. PTK-787 is better tolerated at a total dose of 1,000 mg. Although data is accumulating, disease stabilization and minor responses were seen, suggesting this targeted approach may be useful in meningiomas. Updated data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis
Phase I and pharmacokinetic study of a subcutaneously administered human-engineered monoclonal antibody ING-1 in patients with advanced adenocarcinomas
Authors: B. Kiner-Strachan, S. Goel, G. Vanhove, R. J. Bauer, D. Verdier-Pinard, S. Karri, K. Desai, A. Bulgaru, M. Macapinlac, S. Mani
Journal: Journal of Clinical Oncology (2005)

2558 Background: ING-1 is a high-affinity, human-engineered monoclonal antibody that recognizes a 40 kD Epithelial Cell Adhesion Molecule (EpCAM) glycoprotein. EpCAM is expressed in high levels on most carcinomas and is an attractive target for immunotherapy. Methods: This was an open-label, multi-dose, phase I, dose-escalating study in patients (pt) with advanced adenocarcinomas to determine the MTD, bioavailability, safety, tolerability, immunogenicity and pharmacokinetics (PK) of weekly subcutaneous (SC) ING-1, administered for 6 weeks. PK samples were drawn during week 1 and 6 predose, at 6 hours and at days 2, 3, 5, 8, 15, 22, 29, 37, 38, 40, and 43. Results: Fourteen pt [lung (1 pt), ovarian (3 pt), colorectal (10 pt)] received a median of 6 (range: 1–9) doses of ING-1 between 0.1 and 2 mg/kg. No week-1 DLT was observed. However, at 1 mg/kg, a 62-year-old man with colon cancer developed grade 3 reversible pancreatitis after the 3rd dose. His plasma ING-1 levels were similar to the other 2 subjects receiving 1 mg/kg. The episode resolved with conservative management. Patients still receiving therapy at 1 and 2 mg/kg were subsequently dose reduced to 0.6 mg/kg. Across all doses, grade 2 or greater drug-related toxicities included nausea (1 pt), diarrhea (4 pt), abdominal pain (4 pt), leg pain (1 pt), pancreatitis (1 pt), and anemia (1 pt). Two patients, with ovarian and colon cancer experienced stable disease of 12 and 6 weeks respectively. Peak ING-1 levels after the first dose increased with dose from 0.122 0.054 ÿg/mL (mean SD, n=4) at 0.1 mg/kg to 6.77 1.55 ÿg/mL (n=3) at 1 mg/kg. Only one subject received 2 mg/kg ING-1, with a peak level of 3.57 ÿg/mL. Peak ING-1 levels after the last dose were higher than after the first dose, suggesting accumulation of ING-1. Low (< 90 neq/mL) human anti-human antibody (HAHA) responses were noted in 3 of the 13 (23%) subjects assessed and were directed towards a variable region of ING-1. Conclusions: ING-1 administered weekly SC had modest side effects with little observed clinical benefit in this refractory patient population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration XOMA US [LLC]
Health services utilization differences between patients with metastatic (M1) and nonmetastatic (M0) prostate cancer (PCa).
Authors: Candice Yong, Ebere Onukwugha, C. Daniel Mullins, Brian S. Seal, Arif Hussain
Journal: Journal of Clinical Oncology (2013)

203 Background: Metastatic (M1) disease is diagnosed in up to 5% of PCa patients, but there is limited information about the differences in health services utilization between stage IV M1 and stage IV M0 patients in the one year leading up to and following diagnosis. Methods: We analyzed patients aged 66 or older from the linked Surveillance, Epidemiology, and End Results &amp; Medicare (SEER-Medicare) database. Patients with incident stage IV PCa diagnosed between 2005 and 2007 were identified and followed until one year post-diagnosis. Health services utilization measures included skilled nursing facility (SNF) stay, hospice stay, hospitalization, use of walking aid, wheelchair, and oxygen. We calculated the proportion of M1 and M0 patients utilizing each health service in the year before and after diagnosis. Results: Application of inclusion criteria resulted in 3,379 patients, of which 671 (19.9%) had M0 and 2,708 (80.1%) had M1 disease. The mean (median) age of the sample was 78 (77) years. The increase in the percentage of patients with SNF stay from the year prior to diagnosis to the year post-diagnosis was much larger in the M1 population (M0: 2.1% to 8.7%; M1: 5.2% to 23.6%). The proportion of M1 patients with hospice stay increased from 0.1% in the year prior to diagnosis to 21.1% in the year post-diagnosis, compared to an increase from 0% to 5.1% in the M0 population. Compared to M0 patients, M1 patients also exhibited greater increases in oxygen use (M0: 5.3% to 6.6%; M1: 6.5% to 12.6%), walking aid use (M0: 3.4% to 4.3%; M1: 3.5% to 10.6%), and wheelchair use (M0: 1.8% to 4.5%; M1: 4.1% to 11.4%) in the year following diagnosis. However, the increase in hospitalization in the year following diagnosis was lower in the M1 population (M0: 17.9% to 76.9%; M1: 24.4% to 66.6%). Conclusions: Among stage IV PCa patients, health services utilization is generally higher for M1 patients than M0 patients in the one year following diagnosis. However, hospitalization is lower among M1 patients compared to M0 patients in the one year following diagnosis. The finding that more than 20% of M1 patients had SNF and hospice stays in the one year following diagnosis suggests that M1 PCa is associated with substantial disease burden.
Final results: A phase I study of sorafenib and palliative radiation in patients with malignancy in the thorax, abdomen, or pelvis.
Authors: A. M. Brade, S. W. Kim, C. Chung, J. F. Wan, B. Southwood, N. Chaudary, L. Wang, M. Milosevic, A. M. Oza
Journal: Journal of Clinical Oncology (2011)

e13602 Background: The combination of VEGF-directed therapy with radiotherapy (RT) has shown preclinical promise but data of potential toxicities are limited. We initiated a phase I study combining sorafenib (S) with palliative radiotherapy in patients with primary or metastatic malignancy in the thorax, abdomen or pelvis. Methods: Cohorts of 3-6 patients with measureable tumor lesions in the chest, abdomen or pelvis were treated with S (dose levels: 1 - 200 od; 2 - 200 mg bid; 3 - 400 mg bid) for 4 weeks and RT (30 Gy in 10 daily fractions) in weeks 2 and 3. Each anatomic cohort escalated S dose independently. Primary endpoint: maximum tolerated dose of S (MTD) - the dose level below that resulting in ≥ 2/6 patients with dose limiting, acute, in-field toxicities (≥Gr 3 and attributable to RT). Results: From May 2007 to Nov 2010, 34 patients were entered on study (thorax/abdomen/pelvis - 14/16/4). The thoracic, abdominal and pelvic cohorts reached dose levels 3, 3 and 1, respectively. Significant S dose modifications occurred in 6/10 patients on dose level 3 due to S systemic toxicities. DLTs were noted in each cohort: thorax dose level 2 – Gr 3 esophagitis; abdomen dose level 3: Gr 3 ALT elevation; pelvis dose level 1 – Gr 5 perforation of tumor-involved bowel. No other high grade, RT-related toxicities were observed. Grade 2 acute RT skin toxicity was observed in 7/8 patients who completed both 4 weeks of S on dose level 2 or 3, and had RT plans using only 2 or 3 beams implying a minimum drug/RT dose threshold for this phenomenon. Conclusions: MTD was not defined for any anatomic cohort. The trial was terminated as systemic toxicity of sorafenib resulted in dose reductions and discontinuations at 400 mg bid precluding efficient evaluation of RT-related toxicity combined with this dose of sorafenib. Gr 2 RT dermatitis was consistently seen in patients receiving 4 weeks of uninterrupted sorafenib 200 or 400 mg bid. The severity and prevalence of Gr 2 dermatitis was greater than expected for 30 Gy in 10 fraction RT. One patient developed Gr 3 esophagitis following esophageal RT. It is likely that sorafenib in conjunction with higher dose RT may require drug dose or schedule modification to mitigate acute cutaneous or mucosal reactions.
Expression of Protein Z (PZ) and Protein Z-Dependent Protease Inhibitor (ZPI) In Situ in Human Malignant Tissues.
Authors: Ewa Sierko, Marek Wojtukiewicz, Piotr Tokajuk, Lech Zimnoch, Rodryg Ramlau, Walter Kisiel, George J. Broze
Journal: Blood (2005)
Outcomes of resected stage 1 non-small cell lung cancer (NSCLC) in patients (Pts) aged 70 years and older
Authors: A. K. Viswanathan, B. Goodgame, W. T. Lim, F. Gao, K. Hennenfent, J. Subramanian, C. R. Miller, R. Battafarano, R. Govindan
Journal: Journal of Clinical Oncology (2005)

8027 Background: Nearly 30% of pts with lung cancer are 70 years or older at the time of diagnosis. Surgery is an option for fit elderly pts with early stage NSCLC. We studied the outcomes of 280 pts treated in our institution who were 70 years or older at the time of diagnosis of NSCLC. Methods: Stage I elderly pts ≥ 70 years and pts < 70 years were matched for sex, extent of surgery, histology, grade, pleural invasion, and T-stage. None of the pts received adjuvant chemotherapy. Univariate and multivariate conditional logistic regression models were used to compare the recurrence rates between elderly and young pts, as well as to adjust the potential effects of other unmatched characteristics. Results: Univariate analysis showed that pts age ≥ 70 were less likely to relapse (p<0.03). Multivariate analysis also showed that pts age ≥70 were less likely to recur (p=0.015, OR = 0.56), after adjusting the effects of lobectomy (p=0.005, OR = 0.2) and a tumor size of >3 cm (p=0.03, OR = 2.4) when compared with pts age <70 years at presentation. Conclusions: In this study, compared to matched pts< 70 years of age, pts ≥70 years have lower relapse rates, but also have lower 5 year survivals, indicating possible competing causes of mortality. Adjustment for cause-specific mortality to eliminate bias is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, AstraZeneca, Bristol-Myers Squibb, Genentech Lilly Oncology, Merck, Pfizer AstraZeneca, Aventis, Bristol-Myers Squibb, Ligand, Lilly Oncology, Pfizer