tbuckley/cabot-search huggingface dataset:
Feasibility of utilizing a novel mhealth platform to deliver an evidence-based exercise intervention among testicular cancer survivors (TCS).
Authors: Chunkit Fung, Jennifer Peckham, Michelle Porto, Po Lin Lin, Deepak M. Sahasrabudhe, Elizabeth A. Guancial, Bonnie Ky, Eugene Storozynsky, Michelle Christine Janelsins, Charles E. Heckler, Eva Culakova, Lauren B. Bruckner, Supriya Gupta Mohile, Karen Michelle Mustian
Journal: Journal of Clinical Oncology (2017)

e21608 Background: Cardiovascular disease results in significant morbidity among TCS. Exercise for Cancer Patients (EXCAP) is a self-directed, individually tailored intervention that improves cardiovascular fitness in cancer patients, yet this has not been tested in TCS. We conducted a randomized phase II feasibility study of a novel exercise intervention using a mHealth delivery platform for EXCAP. Methods: We developed mHealth-EXCAP, which integrates data from a wearable digital activity tracker (DAT) into a patient’s electronic medical record (EMR), allowing providers to monitor and adjust EXCAP prescriptions via a patient-centered virtual portal. We randomized TCS ( &lt; 69 yr at diagnosis, any treatments, not in active or maintenance stage of exercise behavior) into 3 study arms: Arm 1 (mHealth-EXCAP), Arm 2 (EXCAP) and Arm 3 (usual care). TCS in both Arm 1 and 2 completed a 12 week EXCAP program with the goal of 12,000 daily steps and daily resistance exercises but Arm 1 used the mHealth platform. Arm 3 used a TCS care plan that promotes exercises. Results: 74 TCS were screened (32 ineligible; 23 declined), 19 consented and 14 (74%) completed study (3 withdrew; 2 lost to follow up) as of 1/31/17. Median age (yr) was 35 (Arm 1; n = 6), 48 (Arm 2; n = 4), and 48 (Arm 3; n = 4). In Arm 1, 83% TCS wore DAT and synced daily step data to EMR &gt; 90% of days. EXCAP prescriptions were adjusted via EMR portal on average 5 times over 12 weeks for each TCS and their weekly daily step goals were met 73% of the time. The number of daily steps recorded by DAT and those synced from DAT to EMR differed by a mean of 1.5% steps (±1.8). Median baseline number of daily steps were 5,525 (Arm 1), 6,795 (Arm 2), and 5,904 (Arm 3) and increased by 5,236, 1,160, and 1,544 respective steps at 12 weeks, with only Arm 1 (50% TCS) achieving &gt; 12,000 daily steps. At 3 months after intervention, 33% TCS in Arm 1 maintained &gt; 12,000 daily steps. On average, TCS in Arm 1 performed resistance exercises 26 minutes a day/5 times a week vs. 28 minutes a day/4 times a week in Arm 2. Conclusions: mHealth-EXCAP is feasible to implement among TCS and may decrease sedentary behavior. Ongoing research will examine its effects on cardiovascular fitness and risk factors.
Phase Ib study of cabozantinib plus panitumumab in KRAS wild-type (WT) metastatic colorectal cancer (mCRC).
Authors: John H. Strickler, Christel N. Rushing, Hope Elizabeth Uronis, Michael Morse, Gerard C. Blobe, Yousuf Zafar, Shiaowen David Hsu, Christy Arrowood, Sherri Haley, Evan Dropkin, Donna Niedzwiecki, Herbert Hurwitz
Journal: Journal of Clinical Oncology (2016)

3548 Background: Anti-EGFR therapy improves survival for patients (pts) with RAS WT mCRC, but nearly all pts develop therapeutic resistance. MET amplification (amp) is a well-described driver of acquired resistance to anti-EGFR therapy. Cabozantinib (C) is an oral inhibitor of multiple tyrosine kinases, including VEGFR1-3 and MET. Panitumumab (P) is an anti-EGFR monoclonal antibody. We designed a phase Ib study of C+P to target MET amp and enhance the activity of anti-EGFR therapy. Methods: Eligible pts with chemotherapy refractory KRAS WT mCRC were enrolled in a 3+3 dose finding cohort (Dose Find) to identify the recommended phase II dose (RPTD). Prior anti-EGFR therapy was permitted. Cycle length was 28 days. Pts were then enrolled in a single-arm expansion cohort (EXP) and treated at the RPTD. The EXP cohort included a 2-week C monotherapy lead-in. The objectives of the EXP cohort were to better describe the safety, tolerability, and efficacy of C+P. Response assessment occurred every 2 months (mos) using RECIST version 1.1. Peripheral blood was sequenced for > 54 gene mutations and focal amps, including MET (Guardant Health, Inc.). Results: As of 11/24/2015, 16 pts were evaluable for toxicity (6 Dose Find; 10 EXP), and 14 pts were evaluable for response (6 Dose Find; 8 EXP). 13 pts had received prior anti-EGFR therapy. There were no dose limiting toxicity events in the Dose Find cohort (0/6). The RPTD was C 60mg PO daily and P 6 mg/kg IV Q2 weeks. In the Dose Find and EXP cohorts, there were no grade 4 or 5 treatment related adverse events (TRAEs). The most frequently reported (all grades > 30%) TRAEs were (n, %) acneiform rash (10, 63%), oral mucositis (9, 56%), diarrhea (8, 50%), increased AST (7, 44%), paronychia (6, 38%), increased ALT (5, 31%), and fatigue (5, 31%). Median PFS was 3.7 mos (95% C.I., 2.3–7.4 mos). Median OS was 7.5 mos (95% C.I., 6.4–12.1 mos). 2 pts (14%) had a confirmed partial response, and 5 pts had PFS > 6 months. Conclusions: In this heavily pre-treated patient population, the combination of C+P demonstrated an acceptable safety profile and encouraging clinical activity at the RPTD. Recruitment for the EXP cohort is now complete. Blood biomarker analysis will be presented. Clinical trial information: NCT02008383.
Clinical significance of preoperative chemoradiotherapy for advanced esophageal cancer patients using propensity score matching.
Authors: Yoshinori Fujiwara, Shuichi Fukuda, Masanori Tsujie, Kotaro Kitani, Masao Yukawa, Hiroshi Takeyama, Masatoshi Inoue
Journal: Journal of Clinical Oncology (2016)

e15532 Background: We introduced preoperative chemoradiotherapy(CRT) for advanced esophageal cancer in 1995 and have been reported it’s results. Although there were some reports compared preoperative CRT and surgery alone in Japan, it is known to be inferior to RCT. We evaluated the clinical significance of the preoperative CRT compared to surgery alone by calculating propensity score (PS) which make a pseudo-randomization. Methods: 112 resectable esophageal squamous cell carcinoma patients(StageII-IVA, preoperative CRT group 55, surgery alone group 57). We calculated PS by statistics software and make a matching by preoperative clinical factors of both groups. Additionally, we performed the matching between two groups using IPSW(Inverse Propensity Sore Matching). We analyzed a survival rate (Overall survival,OS ) and prognostic factors in Cox proportion hazard model. Results: 1,41 patients were selected by PS matching in each groups. OS of CRT group was better than that of surgery alone group (five years OS, 59.8% vs35.2%, p < 0.05). 2, For forest plot, it thought to be a benefit of the CRT for StageII, cT2,T3 disease. 3,379 patients were evaluated by IPSW in both groups. OS of CRT group was better than that of surgery alone group (five years OS, 68.2% vs34.7%, p < 0.05). For forest plot, it thought to be a benefit of the CRT for both StageII and III disease. 4,In preoperative CRT group, sex, effects of CRT were prognostic factors for OS in univariate analysis ,and clinical effects and a pathological effect of CRT were independent prognostic factors for OS in multivariate analysis. Conclusions: As a result of having let a background factor make matching by PS and IPSW,preoperative CRT might be become the candidate the treatment for resectable esophageal cancer patients.
C6-ceramide to induce sensitivity to cetuximab (Cet) in KRAS mutant colorectal cancer (CRC).
Authors: Alvaro G. Menendez, Harold J. Wanebo, Daniel J. Curzake, LuGuang Luo
Journal: Journal of Clinical Oncology (2016)

e14068 Background: Based on in vitro studies, C6-ceramide has proven synergistic activity with chemotherapeutic drugs in several different types of cancer. The aim forthis study was to compare growth inhibition percentage of cytostatics 5-fluoruracil (5-FU),oxaliplatin (Ox) and cetuximab (Cet) with or without C6-ceramide in KRAS wild type (KRAS WT)and KRAS mutant (KRAS Mut) colorectal cancer (CRC) cell lines (SW48 and SW480,respectively). Through this experiment, the potential benefits of combination therapy with chemotherapy and C6-ceramide could be determined. Methods: A series of human CRC cell lines were incubated with IC50 concentrations of test drugs, which were established in the early stages ofour study. Concentrations of 0.8μM for 5-FU, 0.04μM for oxaliplatin, 12.5 and 25 μg/mL for Cet,and various concentrations of C6-ceramide ranging from 5 to 10 μm were applied to both celllines. The cell survival was assessed using the Tryptan Blue stain at 0.4% following 72 hours of incubation with experimental substances. Results: C6-ceramide was capable of individually inhibiting the growth of both cell lines, with a predominance in KRAS-Mut CRC cell line (SW-480). Moreover, it was noted that the addition of C6-ceramide to a combination of Ox, Cet and 5-FU increased inhibitory percentages in both cell lines, with an especially significant effect on KRAS-mutated cells. The greatest effect was seen when 10μM of C6-ceramide was added to the IC50 concentrations of chemotherapeutic agents (using the 25μg/mL concentration of Cet),where inhibitory percentage increased from 32.5% to 92.5%. Conclusions: C6-Ceramide appearsto have direct inhibitory properties, especially on KRAS mutant cells. Also when added to Ox, 5-FU and Cet, C6-ceramide potentiated their cytostatic properties in KRAS WT and reverted the apparent insensitivity of KRAS Mut to those substances.
The impact of concomitant use of tyrosine kinase inhibitors and proton pump inhibitors on survival in older adults with cancer.
Authors: Manvi Sharma, Holly Michelle Holmes, Hemalkumar B Mehta, Hua Chen, Rajender R Aparasu, Sharon Hermes Giordano, Ya-Chen T. Shih, Michael L Johnson
Journal: Journal of Clinical Oncology (2018)

e18732 Background: The concomitant use of tyrosine-kinase-inhibitors(TKI) and proton-pump-inhibitors(PPI) is a concern due to potential drug-drug interaction that reduces TKI absorption, thus potentially reducing effectiveness of TKI. This study evaluated the impact of concomitant use of TKI-PPI on risk of death in older adults with cancer. Methods: This was a retrospective study using SEER-Medicare data for the years 2007-2012. We included 9,366 patients with lung, renal cell, chronic myeloid leukemia, liver or pancreatic cancer with Medicare part D claims for any one of the following TKIs: erlotinib, sunitinib, imatinib, sorafenib, nilotinib, dasatinib and lapatinib. The primary outcome was overall survival in 90 days and one year following the first 90 days of starting a TKI (exposure period). Descriptive analyses were used to examine the concomitant use of TKI and PPI defined as at least 30 days of overlap of TKI and PPI claim during the exposure period. Cox proportional hazards regression adjusted with inverse probability of treatment weighting was used to determine the risk-adjusted association with survival. Results: There were 2,258 (24.1%) patients with concomitant use of TKI-PPI. Polypharmacy (use of 5 or more medicines) (aOR = 3.94, 95% CI:2.65-5.86), prior PPI use (aOR = 3.85, 95% CI:3.35-4.42), non-steroidal anti-inflammatory use (aOR = 1.43, 95% CI:1.29-1.60), diagnosis of gastroesophageal reflux disease and gastric ulcers (aOR = 2.82, 95% CI:2.52-3.14; aOR = 1.38, 95%CI:1.10-1.74 respectively), prior chemotherapy (aOR = 1.39, 95% CI:1.16-1.66) and higher Charlson’s comorbidity score (aOR for 3 and higher = 1.38, 95% CI: 1.20-1.60) were associated with increased likelihood of concomitant use of TKI and PPI. The concomitant use of TKI-PPI was found to be associated with an increased risk of death in 90 days (aHR = 1.16, 95% CI:1.05-1.28) and increased risk of death in 1 year (aHR = 1.10, 95% CI:1.04-1.18). Conclusions: Nearly one in four older cancer patients taking TKI used PPI concomitantly, and concomitant use was associated with an increased risk of death. Concerted medication therapy management efforts are needed to identify and reduce PPI use when TKIs are initiated.
Loss-of-function mutations in caspase recruitment domain-containing protein 14 (CARD14) are associated with a severe variant of atopic dermatitis
Authors: Alon Peled, Ofer Sarig, Guangping Sun, Liat Samuelov, Chi A. Ma, Yuan Zhang, Tom Dimaggio, Celeste G. Nelson, Kelly D. Stone, Alexandra F. Freeman, Liron Malki, Lucia Seminario Vidal, Latha M. Chamarthy, Valeria Briskin, Janan Mohamad, Mor Pavlovsky, Jolan E. Walter, Joshua D. Milner, Eli Sprecher
Journal: Journal of Allergy and Clinical Immunology (2018)
Impact of bilateral mastectomy with or without immediate reconstruction on time to subsequent therapy in breast cancer in a community oncology clinic.
Authors: Rajshekhar Chakraborty, Ronald Regal, Brian Johnson, Jennifer Benedict, Bret Edward Buckley Friday
Journal: Journal of Clinical Oncology (2017)

e18154 Background: Due to an increase in the elective decision to pursue contralateral prophylactic mastectomy (CPM), the incidence of bilateral mastectomy (BM) with/without postmastectomy reconstruction (R) [BM+/-R] has increased in the last decade. While prior studies at academic centers have investigated concerns regarding its impact on subsequent cancer therapy, we hypothesized that BM+/-R is associated with a delay in initiation of adjuvant therapy (AT) in a community oncology clinic. Methods: This study involved chart review of all patients who underwent mastectomy as definitive surgery for stage I-III breast cancer between 2007 and 2012 and were subsequently followed at Essentia Health Cancer Center. The primary endpoint of the study was the proportion of patients receiving subsequent AT within 6 weeks of surgery (TST6) when compared between different surgical groups. Results: A total of 478 patients were included in the study, with a median age of 63 years. Patients were divided into 4 groups, BM-R (n = 133), BM+R (n = 73), unilateral mastectomy (UM) –R (n = 244) and UM+R (n = 28). Significant demographic differences were identified between the groups including age ( p&lt; 0.001), medical comorbidities ( p&lt; 0.001), and BMI ( p&lt; 0.001). The incidence of any major post-operative complication (including flap/implant failure, infection and wound necrosis/dehiscence) or additional surgeries within 6 weeks of surgery was higher in patients undergoing reconstruction, [BM+R (19%) and UM+R (18%)] compared to those who did not [BM-R (6%) and UM-R (4%)] ( p&lt; 0.001). Patients having major complications or needing additional surgeries within 6 weeks had a lower adjusted likelihood of achieving TST6 compared to those who did not (OR = 0.35; p= 0.009). However, there was no significant difference in TST6 between the surgical groups ( p= 0.31). Conclusions: Immediate post-mastectomy reconstruction is associated with a significantly increased risk of postoperative complications or need for additional surgeries within 6 weeks. In an appropriately selected patient population, CPM and reconstruction do not significantly delay subsequent AT in a community oncology clinic.
Characteristics and outcomes of myelodysplastic syndrome (MDS) with chromosome (chr)3q abnormalities.
Authors: Mansour Alfayez, Rita Elias Assi, Hagop M. Kantarjian, Elias Jabbour, Farhad Ravandi, Courtney Denton Dinardo, Gautam Borthakur, Koichi Takahashi, Jorge E. Cortes, Guillermo Garcia-Manero, Tapan M. Kadia
Journal: Journal of Clinical Oncology (2018)

7069 Background: Balanced and unbalanced chr 3q21;q26.2 abnormalities result in aberrant expression of the oncogene ecotropic viral integration site 1 implicated in leukemogenesis, and correlate with poor outcomes in acute myeloid leukemia (AML). These abnormalities occur in < 1% of MDS. Methods: We retrospectively reviewed the baseline characteristics of MDS patients (pts) with inv(3)(q21q26)/t(3;3)(q21;q26)/unbalanced abnormalities, diagnosed between 2000 and 2017, and assessed its impact on treatment response, overall survival (OS) and transformation to AML. Results: 56 patients [53% male; median age 66.5 yrs (29-85)] were included. 21 (38%) had therapy-related MDS and 51 (91%) were High/Very High risk by IPSS-R. Isolated Chr 3q21-26 abnormalities were seen in 18 (32%) pts; 38 (68%) had additional abnormalities the most common being chr 7 (24 pts (63%)). The median number of additional chr alterations per pt was 2 (1–25). Common molecular markers were TP53 (8/19; 42%), ASXL1 (2/6; 33%), RAS (5/44; 11%), RUNX1 (3/6; 50%) and PTPN11 (3/9; 33%). Of 34 pts received HMA-based therapy, 29% achieved CR/CRi/CRp compared to 40 % (4/10) in non-HMA group (8 pts received high intensity chemotherapy, including 2 pts with SCT) (p = 0.7); the median duration of response was 5.5 months (mos) in HMA-treated pts vs 19.25 mos in non-HMA group (p = 0.057). The median OS was 13.2 mos in the HMA-treated group vs 7.5 mos in non-HMA based therapy, showing a trend of higher early mortality in the latter (p = 0.042; HR 1.3, 95% CI 0.6-3.0). Stratified by IPSS-R, OS was 11.2 mos, 13.8 mos and 21.1 mos in Very High, High and Intermediate risk group; respectively (p = 0.03). Of the 48 pts with available follow-up, AML transformation was seen in 27 pts (56%): 23/35 (66%) in HMA-treated and 4/13 (31%) in non-HMA group (median time to transformation: 5.5 mos vs 4.75 mos, respectively; p = 0.4). Conclusions: MDS with chr 3q21;26.2 abnormalities is an aggressive disease with high risk of transformation to AML. Additional cytogenetic abnormalities are common including –7/7q, and relationship with specific molecular abnormalities is unclear. Treatment with HMA does not seem to affect survival or transformation to AML and novel therapeutic approaches are needed.
Treatment and outcomes from a large, prospective, national longitudinal cohort study of screen detected ductal carcinoma in situ (DCIS).
Authors: Alastair Mark Thompson, Graham Ball, Karen Clements, Matthew Wallis, Jeremy Thomas, Anthony Maxwell, Gill Lawrence, Adele Francis, Andrew Hanby, Maggie Wilcox, Elinor Sawyer, Hilary Dobson, Ian Tomlinson, Andrew Evans, Valerie Speirs, Mark Sibbering, Stewart Nicholson, Olive Kearins, Sarah Pinder, David John Dodwell
Journal: Journal of Clinical Oncology (2016)

1570 Background: The degree of over-diagnosis and over-treatment for ductal carcinoma in situ (DCIS) remains contentious. Hypotheses from retrospective data were tested in a prospective, population-based study. Methods: A prospective longitudinal cohort of 12,838 women diagnosed through a population-based national breast screening program accrued 2003-2012 with proforma for imaging, surgery, pathology and adjuvant therapy. Follow-up was linked to national databases and case note review to analyse patterns of care, recurrence and mortality. Results: Data was complete for 9,972/12,838 (78%) women (mean age 60 years; range 46-87) with median follow up 62 months (range 6-116). Breast conservation (BCS) was definitive surgery for 7,028 (70.5%) women; use increased with older age (CHI2 380, 6 df p < 0.001). Mastectomy (Mx; n = 2,944) was associated with higher grade DCIS (CHI2 19.31, 2 df P < 0.001), larger size (CHI2 203.9, 5 df P < 0.001) and comedo necrosis (CHI2 9.1, 1 df P = 0.003). For patients undergoing BCS, use of radiotherapy was associated with high grade (CHI2 199.9, 2 df P < 0.001), comedo necrosis (CHI2 62.3, 1 df P = 0.001), larger size (CHI2 57.5, 5 df P < 0.001), microinvasion (CHI2 49.9, 1 df P = < 0.001), and use of endocrine therapy (CHI2 16.47, 3 df P < 0.001), but not close ( < 1mm) or involved margin(s). In women who underwent BCS, ipsilateral in-breast recurrence (n = 368; CHI2 27.14, 5 df P < 0.001) and ipsilateral invasive cancer (n = 182; CHI2 32.62, 5 df P < 0.001) were significantly reduced by radiotherapy, independent of margins. Endocrine therapy reduced local recurrence by 1.52%, independent of radiotherapy. Among 324 deaths (3.3% of the cohort), 47 were from invasive breast cancer. There was no difference in overall mortality by type of surgery (3.16% BCS vs 3.5% Mx; CHI2 0.017, 3 1f, P = 0.90), use of radiotherapy (2.48% or not 3.84%; CHI2 0.30, 1 df, P = 0.59) or endocrine therapy (3.88% or not 3.14%; CHI2 0.077, 1 df, P = 0.78). Conclusions: This prospective cohort of contemporary, screen-detected DCIS demonstrates ipsilateral recurrence, but not mortality, is reduced by radiotherapy and endocrine therapy. Death due to breast cancer was rare, outnumbered 5:1 by death from other causes.
Retrospective study of patients with malignant pleural mesothelioma treated and followed at Instituto Oncológico Henry Moore (IOHM).
Authors: Mariana Abal, Ernesto Gil Deza, Claudia Lorena Acuna, Edgardo G. J. Rivarola, Carlos Fernando Garcia Gerardi, Gabriela Malcervelli, Dario Niewiadomski, Flavio Tognelli, Eduardo L. Morgenfeld, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2016)

e20085 Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm with a high mortality rate. The only recommended treatment is a platinum doublet with an antifolate based on phase III trials against cisplatin alone. Methods: we reviewed the clinical records of Pt with MPM treated with chemotherapy between 01/01/2002 and 31/12/2015. A survival analysis (Kaplan Meier - KM) comparing first line treatments with or without Pemetrexed and with or without Cisplatin was made. Results: Fifty eight Pt with advanced MPM were studied. Median age was 63 years old (range 37-85). Sex: male 28 Pt (48%) / female 30 Pt (52%). Stage: I = 9 Pt, II = 10 Pt, III = 19 Pt and IV = 20 Pt. PS: 0-1: 50 Pt (86%) , 2 : 6 Pt (10%), 3-4: 2Pt (4%). The most frequent histologic subtype was Epithelioid in 47 Pt (81%). The first line of chemotherapy was a platinum doublet in 55 Pt (95%): CDDP-PEM = 22 Pt; Carbo-Pem = 15 Pt; CDDP-Doxo = 9 Pt; Carbo-Gemcitabine = 3 Pt; CDDP + Gem or VNR or Vp16 1 Pt each; Carbo + Doxo or Mitoxantrone or Paclitaxel one Pt each. Fifty two Pt were evaluable for treatment response: PR = 15 Pt; SD = 21 Pt y Prog = 16 Pt. Nineteen Pt received a second line (Most were monodrugs: Doxo –VNR- Gem o Paclitaxel) with no response and seven Pt received a third line with monodrugs, also with no response. Median overall survival for this cohort was 12,2 months (range 1-91 m). The comparison between first line treatments with Cisplatinum (n = 34) or Carboplatinum (n = 21) did not show differences in overall survival (Log rank p = 0.107). Similarly, the comparison between treatments with Pemetrexed (n = 37) or without it (n = 18) did not show differences (log Rank p = 0.353). Conclusions: 1) The IOHM in Buenos Aires, Argentina, registered 33,074 new Pt between 1/1/2002 and 31/12/2015, therefore MPM accounts for only 0.18% of all cases. 2) We found no differences between first lines using carboplatinum or cisplatinum, nor did we find any differences when it came to using Premetrexed or other agents. 3) It appears that second and third line treatments are not useful. 4) Median overall survival has not changed for advanced MPM Pt in fourteen years. 5) New studies and/or new drugs are mandatory for this disease category.