tbuckley/cabot-search huggingface dataset:
Real-world analysis of eribulin in metastatic breast cancer (MBC): An assessment of time to treatment failure (TTF) in a community oncology setting.
Authors: George Dranitsaris, Debu Tripathy, Nancy L. Beegle, Traci L. Kalberer, John David Cox, Claudio Faria
Journal: Journal of Clinical Oncology (2013)

174 Background: There have been important advances in the treatment of patients with MBC. However, certain patient subgroups such as whose who are triple negative remain a therapeutic challenge. Eribulin is the newest cytotoxic to gain regulatory approval for MBC in the Unites States. In this analysis, the safety and efficacy of eribulin in TNBC patients and those with prior anthracycline exposure were assessed in an early cohort treated in a U.S. community oncology setting. Methods: Ninety patients treated in eight community oncology clinics across the U.S. were identified. Patients were followed from the first cycle of eribulin until disease progression, discontinuation due to toxicity, or death. Data collection included baseline patient and disease characteristics, prior and subsequent anticancer therapy, use of supportive care drugs, number and type of dose limiting toxicity, delivered dose intensity, duration of eribulin therapy and time to treatment failure (TTF). Results: Eribulin was administered after a median of three prior lines of chemotherapy (range 0 to 15). The drug was delivered as a single agent in 79 of 90 patients (88%) at the clinically approved dosage of 1.4 mg/m 2 on days 1 and 8 of a 21 day cycle. Patients received a median of 4 cycles (1 to 16) for an overall mean duration of 2.9 months (0 to 14.2 months). Approximately 17 of 90 patients (18.9%) were identified as triple negative and 57 of 90 (63.3%) had received prior anthracycline treatment. The median TTF (inter quartile range) was 4 mon (2.3 to 5.6) in all patients. There were no significant differences in TTF by triple negative status (HR=0.1.22, p = 0.49) and prior exposure to anthracyclines (HR=0.78, p = 0.15). In all patients, the most common dose limiting toxicities were neutropenia (32%), anemia (31%), neuropathy (21%) and febrile neutropenia (8.9%). These events led to the premature discontinuation of eribulin in 8 of 90 patients (8.9%). Conclusions: TTF with eribulin was comparable regardless of triple negative status and prior exposure to anthracyclines. These findings are consistent with results from previous clinical studies and warrant further real-world analyses in a larger population.
Clinical validity of circulating tumor cell (CTC) enumeration in 841 subjects with metastatic breast cancer (MBC).
Authors: M. C. Liu, M. Mego, S. Nakamura, F. Nole, J. Pierga, M. Toi, E. Munzone, H. Yagata, M. T. Sandri, F. Bidard, H. Wang, D. F. Hayes, M. Cristofanilli
Journal: Journal of Clinical Oncology (2011)

10592 Background: CTCs are associated with poor clinical outcomes in MBC. Multiple technologies have been evaluated for CTC capture, enumeration, and characterization, but only one (CellSearch; Veridex) has been evaluated independently by different investigators with serial assessments and longitudinal follow-up in a defined prospective clinical trial. We combined these datasets to further validate the prognostic and predictive significance of this biomarker in MBC. Methods: Six studies were identified in the peer-reviewed published literature; all used the same CTC decision point (>=5 CTC/7.5 mL blood) and clinical endpoints (PFS, OS) in patients with progressive MBC. CTC enumeration was performed with the FDA cleared immunomagnetic/immunofluorescence assay (CellSearch). Study teams contributed blinded data to create a dataset of 841 subjects with CTC results linked to clinicopathologic variables and survival. Analyses were defined prior to data collection and conducted in subsets where pertinent data were available. Results: >=5 CTCs predicted for worse PFS at baseline (HR 1.32; CI 1.13, 1.55) and 2-5 (HR 2.16; CI 1.67, 2.78), 6-8 (HR 2.75; CI 2.05, 3.70), 9-12 (HR 2.71; CI 2.08, 3.52), 13-20 (HR 2.64; CI 2.03, 3.42), and >=21 wks (HR 1.88; CI 1.45, 2.42) from initiating new therapy (tx). OS results were also significant. The predictive value of CTC level was not affected by type (chemotx, endocrine tx, biologic tx) or line (first, second, >=third) of tx, presence/absence of bone metastases, or presence/absence of disease limited to bone. Multivariate Cox regression analysis was performed with the baseline CTC level adjusting for clinicopathologic variables to predict PFS and OS; some factors maintained an association, but CTC level was the strongest predictor of outcomes. Conclusions: This analysis substantiates the prognostic and predictive utility of CTCs assessed before and during tx for MBC. Persistently elevated CTC levels are highly associated with treatment failure irrespective of clinicopathologic variables, disease subtype, and type or line or tx. Serial CTC assessments should be used as a surrogate marker for patient outcomes to assist in selecting appropriate treatment regimens in MBC.
FIS impact upon <i>BRCA</i> testing uptake and prophylactic oophorectomy/mastectomy among HBOC attendees
Authors: H. T. Lynch, C. Snyder, J. F. Lynch, S. Ghate, S. A. Narod, G. Gong
Journal: Journal of Clinical Oncology (2008)

1533 Background: A family information service (FIS) is an informal, family centered cancer control educational program designed to provide individuals at high risk for hereditary cancers with information about genetic testing, surveillance and management options. Methods: We evaluated the effectiveness of FIS to reinforce participation in genetic testing and surveillance and management recommendations, inclusive of prophylactic mastectomy and oophorectomy option among members of 116 families with BRCA mutations. We studied 7857 members who were at 25% or higher pedigree risk, > 18 years of age, and alive a year after the availability of BRCA testing. All subjects were informed of their putative cancer risk and offered genetic testing. A subset of subjects was invited to attend an FIS. Chi-square test, logistic regression and Kaplan-Meier survival analysis were performed to compare the rate or time-course of BRCA mutation testing and prophylactic mastectomy and/or oophorectomy between FIS attendees and non-attendees. Results: The rate of BRCA mutation testing uptake was significantly higher among FIS attendees (419/566, 74%) than non-attendees (1038/7291, 14%) (P < 0.0001). After mutation result disclosure, the proportion of mutation-positive females who underwent prophylactic mastectomy was significantly higher in FIS attendees (27/104, 26%) than in non-attendees (38/228, 17%) (p<0.05), while the percentage of mutation/positive females without cancer who underwent prophylactic oophorectomy was significantly higher in FIS attendees (21/43, 49%) than in non-attendees (31/113, 27%) (P = 0.011). Conclusions: FIS significantly influenced attendees’ cancer control behavior in terms of BRCA mutation testing uptake and prophylactic surgeries among HBOC members. No significant financial relationships to disclose.
Denosumab or zoledronic acid (ZA) therapy on pain interference and cancer-specific quality of life (CSQoL) in patients with castrate-resistant prostate cancer (CRPC) and bone metastases (BM).
Authors: Donald Patrick, Charles S. Cleeland, Lesley Fallowfield, Matthew Raymond Smith, Laurence Klotz, Stephane Oudard, Gavin M. Marx, Rachel Wei, Katarina Ohrling, Yi Qian
Journal: Journal of Clinical Oncology (2014)

12 Background: Patients with castration-resistant prostate cancer (CRPC) and bone metastases (BM) may experience debilitating pain that impacts daily functioning and diminishes the quality of life. Previous results from a phase III trial demonstrated superiority of denosumab to ZA in delaying or preventing skeletal-related events (pathological fracture, radiation or surgery to the bone, spinal cord compression) in CRPC patients with BM. In this ad-hoc analysis, we present the results of denosumab or ZA therapy on pain interference (PI) and cancer specific quality of life (CSQoL), focusing on the subgroup of CRPC patients with no/mild pain at baseline. Methods: Men with CRPC and BM (no prior IV bisphosphonate use) were randomized to receive either SC denosumab 120 mg+IV placebo or SC placebo+IV ZA 4mg (adjusted for creatinine clearance) every four weeks. Patients were instructed to take calcium and vitamin D supplements. The Brief Pain Inventory–Short Form (BPI-SF) was used to assess PI. The pre-specified clinically meaningful time of a greater than or equal to two point increase from baseline in PI score (overall, physical, and emotional subdomains) was determined for CRPC patients receiving denosumab or ZA therapy. Patients also completed the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at baseline and each monthly visit to determine CSQoL scores. Declining FACT-G scores points to worsening CSQoL, where a greater than or equal to five point decrease is clinically meaningful. Results: Of the 1,901 patients enrolled (n=950, denosumab; n=951, ZA), 1,045 (55%) had no/mild pain at baseline. Compared with ZA, denosumab therapy delayed the time to a greater than or equal to two point increase from baseline in PI for the overall score (HR=0.83 [0.71, 0.98]; P=0.023), physical (HR=0.87 [0.75, 1.02]; P=0.077) and emotional (HR=0.83 [0.71, 0.97]; P=0.020) subdomains. Over a period of 18 months, more ZA-treated patients than denosumab-treated patients experienced a greater than or equal to five point decrease in FACT-G total scores (average relative difference=6.8%, range -9.4 to 14.6%) or worsening of CSQoL. Conclusions: Denosumab therapy significantly delayed the time to worsening of pain interference and maintained a higher overall CSQoL (FACT-G) compared to ZA in CRPC patients with BM. Clinical trial information: NCT00321620.
Impact of yoga on quality of life for young adult noncurative cancer patients: A pilot study.
Authors: Melanie Keats, Hillary Woodside, S. Nicole Culos-Reed
Journal: Journal of Clinical Oncology (2016)

249 Background: A growing body of evidence is emerging to suggest that the practice of yoga can improve disease and treatment-related side effects in the non-curative cancer patient by addressing their physical, psychological, and spiritual needs. Regrettably, the literature regarding the positive benefits of yoga for the young adult (YA) non-curative cancer patient is limited. Accordingly, the purpose of this ongoing exploratory study is to examine the feasibility and safety of a 7-week home/hospice based instructive Hatha yoga intervention (Yoga Thrive - available on DVD) in non-curative, YA cancer patients. Secondary outcomes include the examination of the efficacy of yoga in mitigating cancer and treatment-related side effects through ratings of self-reported quality of life (QOL). Methods: A single-arm, non-randomized, pre and post-test, pilot investigation of a 7-week instructive home/hospice-based Hatha yoga program is currently ongoing. Pre/post program data include measures of QOL, specific to palliative disease and spiritual domains as well as open-ended measures of perceived program value. Feasibility data (e.g., recruitment, adherence, safety) are also collected. Results: To date, four YA non-curative cancer patients have participated in the 7-week yoga program. Preliminary data show a significant difference in both functional well-being (p= .047, η p 2 = 0.78) and spirituality (FACIT-Sp) scores (p= 0.04, η p 2 = 0.77). Although not statistically significant, a large effect in physical well-being (η p 2 = 0.38); general cancer outcomes (FACT-G) (η p 2 = 0.42); and palliative specific scores (η p 2 = 0.62) have also emerged. Early responses to the post-program exit questions suggest that participants find the program as an opportunity for self-care, separate from traditional cancer therapies. Subjective improvements in flexibility and mindfulness (e.g., body awareness, relaxation, and calmness) have also been reported. Additionally, participants have complemented the program for its ease and flexibility of use. Conclusions: Early findings of this study provide support for the feasibility and efficacy of a home/hospice-based yoga program for YA non-curative cancer patients.
The impact of very early referral on the effectiveness of specialty cancer care management services for oncology patients in active treatment.
Authors: Eric J. Gratias, Melissa Lindholm, Arthur H. Rossof, Richard B. Weininger, Margaret Rausa, Pamela Schumacker, Steven Hartley, Diane Richards, David Spangler, Debra Stern, J. Scott Reid
Journal: Journal of Clinical Oncology (2016)

157 Background: Many patients receiving treatment for cancer experience high levels of morbidity and reduction in quality of life. Proactive specialty cancer care management programs can be offered to patients experiencing these challenges. These patients are most often self-identified, referred by a physician, or identified by claims from a commercial or government insurer or vendor. While earlier intervention of case management or palliative care services has been shown to improve outcomes for cancer patients, a variety of logistic challenges frequently interfere with early referral. Methods: All oncology patients obtaining regimen-based chemotherapy prior authorizations were referred for specialty cancer care management via the prior authorization process. Additionally, all oncology patients in active treatment or with active disease whose benefits included care management were eligible through standard referral mechanisms. Patient satisfaction scores were measured every 3 months for all patients enrolled in the program. The medical cost savings value of referral to the specialty cancer care management program was evaluated by comparing patients referred to the program within 30 days of diagnosis (very early referrals) against patients found between 30 and 120 days from the time of diagnosis. Results: Compared with patients referred through standard methods, patients referred to the specialty cancer care management team at the time of chemotherapy authorization resulted in a high percentage of very early referrals. Patients enrolled in specialty cancer case management within 30 days of diagnosis saved an average of $16,000 per surviving participant, or 30% more than patients referred between 30 and 120 days from diagnosis. Overall, patients engaged in specialty cancer case management are highly satisfied. Overall satisfaction with the nurse/case manager was 98%. Conclusions: Early referral of high risk oncology patients to patient-centered care management programs improves the overall patient experience while simultaneously reducing health care costs, and should be strongly considered for all oncology patients with high morbidity or mortality risk.
CpG island methylation in PTEN, MGMT, and E/H cadherin promoters, mutations of K-ras and B-raf may indicate how progression in the colorectal adenocarcinoma sequence occurs.
Authors: B. Metzger, M. Dicato, G. Mahon
Journal: Journal of Clinical Oncology (2011)

3608 Background: The colorectal adenocarcinoma sequence summarizes the epigenetic and genetic modifications, which arise during cancer progression. These modifications have effect on the methylation status of different gene promoters and mutations in the K-ras and B-raf genes. Included in the sequence during cancer progression may be, as we have previously shown (ESMO 2010, abstr.:646P): methylation of the gene promoters of H-cadherin then of MGMT deregulating removal toxic methyl adducts on guanine bases and inducing the activation of K-ras through G to A point mutations, activation of B-raf gene by a V600E mutation and finally methylation of E-cadherin, linked to emergence of metastasis. Methods: DNA extraction was obtained by standard methods from resected tumour samples. In order to add PTEN methylation status in this sequence, shown to co-occur with K-ras and B-raf mutations in colorectal cancer (CRC), we screened for PTEN inactivation by promoter hypermethylation over 200 CRC patients from which MGMT, E- and H-cadherin methylation, K-ras and B-raf status we determined. PTEN methylation was analyzed by methylation-specific PCR, gel electrophoresis after Sybr green staining and UV-photography. From each individual patient we examined germline DNA from white blood cells as described above. Results: Of the 95 out of 222 tumors (43%) with a PTEN hypermethylation, 77 (81%) were also methylated in CDH13, 52 (55%) were MGMT methylated, 35 (37%) had a K-ras gene mutation and were B-raf wild type as expected, their mutations being mutually exclusive. We are analysing the 127 non PTEN hypermethylated patients especially in regards to B-raf mutations, Smad and others. All results were tumor specific as all the sequenced blood controls were unmethylated respectively wild type. Conclusions: PTEN methylation occurs after CDH13 and MGMT methylation and induces mutations in K-ras or B-raf genes. These results further add on and sustain the colorectal adenocarcinoma sequence.
CANES family health team EMR optimization pilot.
Authors: Zabin Dhanji, Nicki Cunningham, Dafna Carr
Journal: Journal of Clinical Oncology (2014)

129 Background: While Electronic Medical Records (EMRs) have been widely adopted within primary care, practices are at various stages of maturity in their use. Cancer Care Ontario (CCO) has embarked on an EMR Optimization initiative, in collaboration with primary care providers (PCPs) and OntarioMD. The project is intended to support PCPs in leveraging the functionality in their EMR systems in order to support cancer screening through the development of training guides and tools. Working with the CANES Family Health Team (FHT), CCO is piloting the usefulness and effectiveness of these tools in meeting these objectives and using the results to inform how to support provincial pilots. Methods: The EMR Optimization guides and tools provide practices with training on five key areas: practice workflows, data discipline, searches, reminders and preventative care summary reports. Working with a multi-disciplinary team at the CANES FHT, CCO provided the team with the EMR Optimization tools and training on these five key areas. The training was supplemented with exercises on topics such as data discipline and practice workflow. The practice team then had opportunities to work with the guides and tools and integrate them into their daily workflow. Results: Preliminary results of an EMR maturity survey show that even after a short period of time, the team has developed an awareness of and a focus on improving data quality through standardization. In addition, they have learned how to leverage the functionality of their EMR system for preventative care purposes. Participant feedback indicates that they found the EMR guide and tip-sheets easy to understand and follow. Conclusions: The CANES pilot has resulted in practice staff moving up the EMR maturity curve and has taught the team how to leverage their EMR to support cancer screening. In addition, the pilot has helped inform CCO’s training strategy and refine the guides and tools. The next steps are to develop self-directed training tools and resources that will support a broader scale pilot to be implemented throughout 14 regions in Ontario.
The positive effect of the psychostimulant modafinil on fatigue from cancer that persists after treatment is completed
Authors: G. R. Morrow, L. J. Gillies, J. T. Hickok, J. A. Roscoe, D. Padmanaban, J. J. Griggs
Journal: Journal of Clinical Oncology (2005)

8012 Background: Fatigue is the most common adverse effect reported by patients undergoing cancer treatment. Several large studies have shown up to 90% may experience fatigue sometime during treatment. Approximately a quarter report that their fatigue persists for months or even years beyond cancer treatment. Control of this debilitating side effect remains inadequate. Methods: 51 Women (mean age=54.5 yrs) who completed breast cancer treatment an average of 23.5 months previously and who were reporting persistent fatigue were enrolled in a one month open label trial of modafinil (Provigil 200 mg with breakfast). Four patients did not complete the trial: 3 dropped out within a week complaining of 'agitation' (all were very slight with weights under 110#), 1 patient found she was unexpectedly pregnant and was withdrawn from the study. All patients completed psychometrically sound measures of fatigue and other side effects before and after treatment. Results: The mean fatigue severity level at baseline for the 51 enrollees was 6.9 on a scale where 0 = 'not present' and 10 = 'as bad as you can imagine'. After treatment, mean fatigue severity had fallen to 3.7 (p<.01). Forty-four of the 51 (86%) reported at least a one point improvement over the course of the one month study. Patient-reported global effectiveness measured after treatment supported the finding that modafinil was an effective treatment for fatigue; the mean rating was 5.0 (s.d.=2.0: with 1 = 'no benefit' and 7 = 'great improvement'). Fifty one percent reported improvement in sleep and 51% reported less drowsiness. Additional improvements were reported by a majority of patients in general activity (64%), mood (63%), walking ability (63%), normal work ability (66%), relations with other people (66%) and enjoyment of life (61%). Conclusions: Patients with fatigue that persisted an average of almost two years following cancer treatment experienced a benefit from modafinil in an open label trial. If these findings are confirmed by a randomized clinical trial currently underway, modafinil could provide clinical benefit for the unfortunately common side effect of cancer-related fatigue. Supported by Cephalon Pharmaceuticals and NCI PHS grant U10 CA37420 No significant financial relationships to disclose.