tbuckley/cabot-search huggingface dataset:
Molecular biomarkers as predictive factors of pCR for early triple-negative breast cancer.
Authors: Ismael Ghanem, Carlos Castañeda, Ana Perez-Campos, Oscar Toldos, Blanca Sancho Perez, Luis Manso, Jose Luis Rodriguez-Peralto, Mónica Calderón, Hernan Cortes-Funes, David Lora, Rosa Garcia-Martin, Eva Ciruelos
Journal: Journal of Clinical Oncology (2013)

1041 Background: Early triple-negative breast cancer (TNBC) patients (p) without pathologic complete response (pCR) after neoadjuvant chemotherapy (NCT) have unsuccessful prognosis. Predictive factors for pCR are necessary in order to improve the treatment choice. The aims of the study are to determine the expression of different biomarkers (BM) in the initial biopsy (IB) of TNBC, to analyze the relationship between the BM expression and pCR, and to determine the expression changes of BM after NCT. Methods: We reviewed retrospectively the medical records of 49 TNBC p treated with NCT between 2001 and 2011 at two institutions. Expression of 14 BM in the IB and after NCT was independently analyzed by inmunohistochemistry by two pathology specialists. Staining intensity 0-1 + was considered as negative expression, and 2-3-4 + as positive. Ki 67&gt;13% was interpreted as positive. Results: Forty-nine p with a median age of 47 years (27-79) were evaluated. Twenty-seven p (55%) had grade 3. Tumor stages were T1(2%), T2(26%), T3(39%), and T4(33%). 38p (77%) were node positive. Five p (10%) received anthracyclines and 42p (86%) anthracyclines plus taxanes. Fourteen p (29%) presented pCR, 27p (55%) partial response, 4p (8%) stable disease, 2p (4%) progressive disease, and 2p (4%) were not evaluable. The BM expression in the IB was: CD44 (88%), CK 5/6 (27%), EGFR ( 0%), Ki 67 (73%), Wt-1 (10%), p-Akt (24%), HER2 (19%), NY-ESO-1 (11%), MAGE A1 (0%), HER3 (14%), BRCA1 (84%), PTEN (12%), IGFR1 (12%) and AR (14%). Diferentially expressed BM in IB for p with and without pCR, respectively, were p-Akt 0/8(0%) vs 5/13(38%) p=0.11, CK 5/6: 4/9 (44%) vs 2/15 (13%) p=0.15 and Ki 67: 7/7(100%) vs 10/17(59%) p=0.06. The Table shows the BM expression before and after NCT for p without pCR. Conclusions: Tumor samples of TNBC show high expression of CD44, ki67, and BRCA1. Most of BM has a decrease in expression after NCT. CK 5/6, Ki 67, and p-Akt could be predictive factor for pCR, although larger prospective studies are needed. [Table: see text]
Randomized phase II trial of capecitabine and lapatinib with or without cixutumumab in patients with HER2+ breast cancer previously treated with trastuzumab and an anthracycline and/or a taxane: NCCTG N0733 (Alliance).
Authors: Paul Haluska, Albert M. Bernath, Karla V. Ballman, Amylou C. Dueck, Hannah M. Linden, Matthew P. Goetz, Donald W. Northfelt, Xiaonan Hou, Kathleen S. Tenner, Piyawan Tienchaiananda, Lynn M. Flickinger, Beiyun Chen, Helen X. Chen, Wilma L. Lingle, Christine M. Pellegrino, Robert W. Sponzo, Monica Madden Reinholz, Edith A. Perez
Journal: Journal of Clinical Oncology (2014)

632 Background: Crosstalk between the insulin-like growth factor (IGF) and HER2 pathways in multiple preclinical models suggest a mechanism of resistance to HER2-targeted therapy. Cixutumumab (CIX, IMC-A12), an anti-IGF-1 Receptor monoclonal antibody, was investigated in combination with capecitabine and lapatinib (cape/lap) to determine if the addition of an IGF target agent would improve PFS compared to cape/lap in unselected HER2+ metastatic breast cancer (mbc) patients (pts). IGF binding protein (IGFBP) levels may be important in predicting tumor dependence on IGF signaling and are potential biomarkers. Methods: Following an initial safety cohort, this open label phase II study randomized (2:1) pts to cape/lap with CIX (Arm B) or cape/lap (Arm A). Primary endpoint was progression-free survival (PFS) with 144 pts planned for a target hazard ratio of 0.56. PFS was estimated using Kaplan-Meier and compared using Cox regression. Secondary endpoints included assessing the overall survival and treatment tolerability. Correlative studies included assessments of IGFBPs 1-6 using a Luminex multiplex assay on pt serum. Results: 64 evaluable pts were accrued, including 8 to the safety cohort. The most common grade 3 events were diarrhea, fatigue and mucositis. Dose reductions in the safety cohort for 6 of 8 pts prompted a dose reduction of cape/lap in Arm B of the randomized portion. The randomized portion of the study was closed early at 56 pts due to slow accrual. Median PFS by in Arm A was 6.0 mo vs. 4.9 mo in Arm B (p= 0.89). Median overall survival (16.8 vs 14.7 mo, p=0.93), time to treatment failure (TTF) (4.6 vs 4.4 mo, p=0.66), and duration of response (4.8 vs 6.9 mo, p=0.26) were not different between arms. In Arm B, increase in IGFBP5 correlated with poor PFS (1.4 vs 9.9 mo, p= 0.02) and high IGFBP5 correlated with improved TTF (9.9 vs 3.9 mo, p= 0.03). Conclusions: CIX is reasonably tolerated in combination with cape/lap following a dose reduction, but does not improve PFS in unselected pts with HER2+ mbc. IGFBP5 may be an important determinant of benefit from IGF targeted therapy and warrants further investigation. Clinical trial information: NCT00684983.
A randomized phase II trial of upfront docetaxel and vinorelbine followed by either maintenance oral vinorelbine or observation in patients with HER2-negative locally advanced (LA) or metastatic (M) breast cancer (BC).
Authors: Fadi Sami Farhat, Marwan Ghosn, Nizar Bitar, Moussa Dehaini, Georges Y. Chahine, Cynthia Mourad, Ahmed Othman, Mayssam El-Mouhebb, Joseph Gergi Kattan
Journal: Journal of Clinical Oncology (2014)

TPS1136 Background: Vinorelbine (V) and docetaxel (D) are among the most active agents in the treatment of MBC and their combination has a proven efficacy in this setting. V and D both target the tubulin-microtubule system, pre-clinical studies suggest a potential synergy between the 2 drugs. Maintenance therapy has lately demonstrated significant outcome improvement nevertheless the high cost of treatment in developing countries remains an issue. The oral form of vinorelbine (oV) is a convenient and cost-effective treatment, its role as maintenance treatment has not yet been investigated in LA-MBC. The purpose of this study is to assess the efficacy and safety of V+D combination and whether oV used as maintenance therapy can delay cancer progression in patients with LA-MBC. Methods: This is a prospective, multicenter, randomized, phase II trial of Docetaxel (60mg/m2 D1) in combination with Vinorelbine (D1, 20mg/m2 I.V and D8, 60mg/m2 Oral), given every 3 weeks for a total of 6 cycles. Patients with objective response or stable disease after 6 cycles are randomized to the arm of maintenance therapy (Oral V 60mg/m2 D1 and D8 at first cycle increased at 2nd cycle to 80mg/m2D1 and D8) or to the observation arm. In the maintenance therapy arm cycles are repeated every 3 weeks until disease progression, unacceptable toxicity or patient refusal. Inclusion criteria were: Pre/post-menopausal women (≥ 18 years) with Her2 negative, LABC or MBC, PS ≤2, disease free survival ≥ 6 months, no symptom or sign of brain metastasis. The primary endpoint (EP) is time to progression (TTP). Secondary EPs include overall response rate (RECIST v1.1), clinical benefit rate, duration of response, 3 years overall survival, safety (CTCAE 4.03) and patient reported outcomes (FACT-B v.4). As of January 2014, 50 patients have been enrolled in the study and 32 randomized. Estimated enrolment is 126 pts. Recruitment is ongoing and planned for 36 months. This study will be the first one to evaluate the role of oral vinorelbine as maintenance treatment in first-line LA-MBC and will provide additional data on the efficacy and safety of D+V combination.
A phase I study of irinotecan and 5'-DFUR in patients with metastatic colorectal cancer: With consideration of gene polymorphism
Authors: S. Hazama, K. Matoba, A. Nagashima, K. Matsuoka, M. Oka
Journal: Journal of Clinical Oncology (2004)

3630 Background: 5-Fluorouracil plus irinotecan (CPT-11) is standard 1st-line therapy in patients (pts) with metastatic colorectal cancer (MCRC). 5'-DFUR is a tumor-activated oral fluoropyrimidine. We conduct a phase I trial of CPT-11 and 5'-DFUR to determine the maximum tolerated dose (MTD) and toxicities of this regimen. However, detoxification of SN-38 (active form of CPT-11) is depending on UGT1A1 polymorphism. Here we report the results from a phase I study to determine the significance of UGT1A1 polymorphism on toxicity in pts with MCRC. Patients and methods: Eligibility criteria were as follows; histologically proven CRC with unresectable metastatic lesions, PS 0–2, age<75, adequate organ functions, and written informed consent. 5'-DFUR was administered orally (level 1 and 2; 600 mg/body, level 2b and 3; 800 mg/body) on 5 consecutive days with 2 days' rest for 12 weeks, and CPT-11 was infused (level 1, 2, 2b, and 3: 50, 70, 70, 100 mg/m2, respectively) on days 1, 15, 29, 43, 57, and 71. Dose limiting toxicities were determined as grade 3 hematological and grade 3 non-hematological during 12 weeks. Genotypes were determined by analyzing the sequence of TATA box of UGT1A1 of genomic DNA from the pts. Results: Fifteen pts were registered (3 pts each in level 1 to 2b and 6 in level 3). No toxicity of grade 3 or over was observed at level 1 to 2b. At level 3, the planned therapy was discontinued in 3 pts because of grade 3 neutropenia and/or diarrhea, which settled the MTD on this level. Polymorphism of UGT1A1 is characterized by (TA)7, instead of (TA)6. The frequency of genotypes was as follows: 6/6–10/15(67%), 6/7–5/15(33%) and 7/7–0/15(0%). Three pts who had grade 3 toxicities on level 3 had abnormal allele (6/7). On the other hand, three pts who had normal allele (6/6) had no toxicity of grade 2 or over on level 3. Conclusions: The recommended doses are CPT-11 70 mg/m2 and 5' -DFUR 800 mg/body. However, pts who had normal allele (6/6) could tolerate on level 3, so MTD and RD for pts with normal allele should be settled by further examinations. The RD in the phase I study may be changed, when the gene polymorphism is taken into consideration. No significant financial relationships to disclose.
Barriers to care in two differing models of follow-up for long-term childhood cancer survivors.
Authors: Brooke Russell, Kathleen Reynolds, Maria Spavor, Janine Giese-Davis
Journal: Journal of Clinical Oncology (2017)

100 Background: Long-term childhood cancer survivors (CCSs) require lifetime medical follow-up to screen for and treat adverse health outcomes related to cancer and its treatment. In Alberta, primary-care providers (PCPs) are involved in this follow-up care, though differently so in Northern and Southern regions of the province. Our aim was to identify potential province-wide and region-specific preferences and care barriers that may impact medical and quality-of-life outcomes for patients. Methods: Forty-four PCPs following CCSs completed surveys about knowledge gaps, communication, and health-system barriers. Knowledge gaps were assessed using a hypothetical case vignette followed by three multiple-choice questions regarding appropriate follow-up, based on available guidelines. Communication barriers were measured using a 6-item 5-point scale. Health-system barriers were measured using a 12-item 5-point scale. Results: PCPs were 54.54% female, age 31-72 ( m=51.36) with 1-50 years of practice ( m=22.49). These preliminary results suggest PCPs across Alberta are experiencing moderate communication barriers (scale: 0-24, m=10.85, SD=6.59) but fewer health-system barriers (scale: 0-48, m=14.58, SD=5.11). Scores on the case vignette were markedly low province-wide (scale: 0-3, m=0.65, SD=0.65), indicating considerable knowledge gaps regarding long-term oncology-related care follow-up. No statistically significant differences were observed between regions. Conclusions: Albertan PCPs are experiencing barriers to care and knowledge gaps when following ASCCs. This is of primary concern for PCPs in Southern Alberta, currently tasked with the sole responsibility of providing oncology-related follow-up care. These data will be linked with data collected from their patients to explore the relationship between PCPs’ barriers and knowledge, and the symptoms, quality of life, and unmet needs of their patients.
Integrating cancer survivorship care into allogeneic BMT recovery.
Authors: Kelly Bugos, Sarah Stenger, Andrea Segura Smith, Laura Johnston, Morgan Gross, Gayla Knight, Suzanne Lambert, Lori S. Muffly
Journal: Journal of Clinical Oncology (2017)

39 Background: AlloBMT patients are at risk for chronic morbidity and late effects. Prior to 2015, the Stanford BMT program conducted group classes at three months post-transplant to prepare alloBMT patients and their families for the transition to survivorship, but no formal cancer survivorship program existed. Cancer survivorship care is required by the Foundation for the Accreditation of Cellular Therapy ( FACT). In order to fill this gap, we developed a standardized pathway to survivorship care for alloBMT survivors. Aim: To implement an initial cancer survivorship care consultation with comprehensive symptom assessment, late effects monitoring, and development of a survivorship care plan (SCP) three to six months after alloBMT. Methods: Standard work was implemented including patient introduction to survivorship by the BMT nurses and Advanced Practice Providers [APP] and during group ‘moving home’ class; responsibility for referral to survivorship; metric tracking, and administration of patient survey. The survivorship visit included an evaluation by the patient’s BMT social worker, introduction to post-BMT nurse coordinator and consult with cancer survivorship APP. Eligible patients were alloBMT recipients receiving care in the outpatient setting. Results: From July 28, 2015 to January 25, 2016, 90% (66/72) of eligible alloBMT patients were referred to cancer survivorship by day 100, 66% (42/66) of referred patient s were seen in survivorship clinic by day 180, 33% (22/66) deferred the visit or were unreachable, 1% (2/66) died. Of the 42 patients who received a cancer survivorship visit, 38% (13/42) responded to a post-visit survey. Responses indicated the patients believed their health goals and needs were addressed, and a SCP in the context of a comprehensive visit was valuable. Conclusions: Integrating standardized cancer survivorship care into the alloBMT recovery period is feasible, satisfactory to patients, and adds a structured approach for long-term effects monitoring and treatment. Early experience and patient surveys demonstrate value in an individual visits 3-6 months after alloBMT with a focus on returning to life and goal oriented post-transplant care.
Development of an adaptive, personalized, and scalable dementia care program: Early findings from the Care Ecosystem
Authors: Katherine L. Possin, Jennifer Merrilees, Stephen J. Bonasera, Alissa Bernstein, Winston Chiong, Kirby Lee, Leslie Wilson, Sarah M. Hooper, Sarah Dulaney, Tamara Braley, Sutep Laohavanich, Julie E. Feuer, Amy M. Clark, Michael W. Schaffer, A. Katrin Schenk, Julia Heunis, Paulina Ong, Kristen M. Cook, Angela D. Bowhay, Rosalie Gearhart, Anna Chodos, Georges Naasan, Andrew B. Bindman, Daniel Dohan, Christine Ritchie, Bruce L. Miller
Journal: PLoS Medicine (2017)

Our objective was to develop and test a scalable model of dementia specialty care that complements primary care with additional caregiver support and education, medication consultation, and support in planning for future medical, financial, and legal decisions consistent with patient values.Care is delivered via the phone and web by unlicensed Care Team Navigators (CTNs), who are trained and supervised by a dementia specialist nurse, social worker, and pharmacist.• This "Care Ecosystem" is being tested via a pragmatic randomized controlled trial.The care model was iteratively improved during the trial based on input from caregivers, primary care providers, and clinical team members.• Based on the inputs, the care model was revised to enhance caregiver support, to clarify triage protocols, to include more strategies for managing problematic patient behaviors, to personalize care protocols, to better inform caregivers and patients about the services available, to adjust recruitment efforts to target the underserved, and to address CTN stress and burnout.• The trial continues with the revised care model and ongoing evaluation of patient, caregiver, and health care cost outcomes.New implementation projects are adapting the care model to fit the priorities and workflows of three health care delivery organizations.
A study of triple-negative breast cancer patients tested with a 25-gene panel of hereditary cancer genes.
Authors: John F. Sandbach, Gayle Patel, Elisabeth King, Brent Evans, John Kidd, Lucy R. Langer, Krystal Brown, Richard J. Wenstrup, Jennifer Saam
Journal: Journal of Clinical Oncology (2015)

1067 Background: Although triple-negative breast cancer (TNBC) accounts for 15% to 20% of all breast cancers diagnosed in the US, its epidemiology is not well understood. Previous studies have shown a high incidence of BRCA1 and, more recently, BRCA2 mutations in patients with TNBC. As panel testing becomes more prevalent, these studies can be extended to other genes with a known breast cancer risk and improve understanding of the genetic origin of TNBC. Here we examined the gene distribution of mutations identified with a 25-gene hereditary cancer panel in patients with TNBC. Methods: We queried a commercial laboratory database for patients affected with breast cancer who were tested with a 25-gene panel of hereditary cancer genes from September 2013 through December 2014. Patients affected with TNBC were analyzed separately. All patient data was obtained by health care provider report on test requisition forms. Results: We identified 2,535 patients with a personal history of TNBC and 17,304 patients with a personal history of other breast cancers. Of the TNBC patients, 14.5% (367) were identified as having a pathogenic mutation, compared to only 8.8% (1,522) among patients with a personal history of other breast cancers. As previously reported, the TNBC mutation carriers were found to a have a higher occurrence of BRCA1 mutations than patients with other breast cancers (47.5% and 18.1%, respectively). In line with more recent studies, we also found that 19.7% (74) of mutations in TNBC patients were in BRCA2. Additionally, patients with TNBC showed a marked shift in the mutation distribution in several genes relative to patients with other breast cancers. This included an enrichment in RAD51C (3.5%) and PALB2 (10.9%) mutations, but a depletion in ATM (1.9%) and CHEK2 (1.1%) mutations. Conclusions: This data confirms previous findings that patients with TNBC have a high incidence of BRCA1 mutations. This study also shows that patients with TNBC have a different distribution of mutations compared to patients with other breast cancers. This data offers insight into the underlying genetic mutations that may drive the development of TNBC, which may allow affected patients to receive more appropriate medical management.
Building a healthy body after cancer: Results of a focus group with young adult survivors to inform an intervention for exercise after treatment.
Authors: Brittany Kimball, Gladys Asiedu, Carrie A. Thompson
Journal: Journal of Clinical Oncology (2017)

164 Background: Adolescent and young adult (AYA) cancer survivors have distinctive and often unmet needs, may lead long lives after treatment, and are a population for whom targeted health supports are limited. Exercise in particular has become increasingly recognized as a vital part of cancer survivors’ health needs, yet, little is known about what interventions would be most appropriate for this population. This ongoing study reports early data on barriers and facilitators to exercise in AYA lymphoma survivors. Methods: We conducted a focus group with five young adult lymphoma survivors. Participants completed questionnaires to assess quality of life, exercise habits, and knowledge about evidence for exercise after cancer treatment. Charts were abstracted for demographic and treatment-related details. The focus group was audio recorded and transcribed. Data is being analyzed thematically to generate applied findings and identify areas for action. Results: Participants were 24-35 years old, 60% male, and an average of 2.97 years from the time of diagnosis. All reported some form of physical activity, with 80% active and 20% moderately active. Preliminary analysis identified fatigue, weight gain, and lack of time as barriers to exercise. Participants identified fatigue particularly in the early survivorship period, and discussed the issue of non-cancer survivor peers not relating with or recognizing fatigue after treatment. 100% of participants reported that someone from their doctor’s office had talked with them about exercise, but indicated during the focus group that this recommendation did not motivate them to exercise. Other themes revolve around the relationship between healthy diet and physical activity. In terms of an intervention, survivors were interested in activity trackers and fitness apps, exercise variety, and fitness groups targeted specifically for AYA survivors. Conclusions: Fatigue, weight gain, and time are barriers to exercise for AYA survivors. Interventions that incorporate fitness tracking technology, provide variety, and/or include other AYA survivors may be successful in this unique population.
Clinical analysis of introduction chemotherapy for advanced germ cell tumors at Japanese high-volume center.
Authors: Terukazu Nakamura, Kazuya Mikami, Yasunori Kimura, Fumiya Hongo, Natsuki Takaha, Tsuneharu Miki
Journal: Journal of Clinical Oncology (2012)

e15099 Background: Recently, cure rate of advanced testicular cancer even with poor prognostic factors have much improved. Inadequate treatment, however, may lead the patients "difficult-to-treat" situation. The aim of this study is to assess the results of the induction therapy at the Japanese single high volume center. Methods: We assessed clinical outcomes about 82 cases of advanced germ cell tumors that had induction chemotherapy at our hospital from Jun, 1998 until Dec, 2010. Results: Median age was 58 year-old (range:17-34y.o.). Seminoma was found in 16 cases (19.5%) and non-seminoma in 66 cases (80.5%), regarding primary histology. Clinical stageII was 37 cases, stageIIIA, IIIB, IIIC was 8, 24, 13 cases, respectively. IGCCC showed good in 41 cases (50%), intermediate 25 (30.5%), poor 15 (19.5%). BEP therapy was done in 74 (90.3%), EP 5 (6.1%), VIP 2 (2.4%) and PVB 1 (1.2%). Median cycles of induction therapy was 4 (range 1~5). Complete response was observed in 14 cases (17.1%), partial response with marker normalization in 58.5%, partial response without marker normalization in 12.2%, progressive disease in 8.5% including 4 cases of growing teratoma. RPLND after induction therapy was performed in 55 patients. Necrosis was found in 56.4%, teratoma only in 27.3% and viable cancer in 16.3%. Patients with salvage chemotherapy were 22 (27.5%) cases. Five- and 10-year overall survival was 93.3% and 89.6%, respectively. Clinical outcomes at 63 months of median follow-up was as follows; no evidence of disease 73 cases (89.0%), alive with disease 1case (2.4%) and death 7 cases (8.6%). Stratified by IGCCC, 5-year overall survival was 97.6% in good prognosis, 96.0% in intermediate prognosis and 79.0% in poor prognosis. Causes of death were as follows; pancreatic juice leakage after RPLND in 1 case, cerebral infarction in 1 case, cerebral bleeding in 1 case, traffic accident in 1 case, and cancer death in 3 cases. Conclusions: Clinical outcomes at Japanese high volume center were good, especially in good and intermediate prognosis. It was very clear that improvement of poor prognosis, especially high tumor volume, was required.