tbuckley/cabot-search huggingface dataset:
A phase I study of the multikinase inhibitor cabozantinib (C) plus docetaxel (D) and prednisone (P) in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Fatima H. Karzai, Avani Atul Shah, Michelle A. Ojemuyiwa, Ravi Amrit Madan, Andrea Borghese Apolo, Nancy Ann Dawson, Philip M. Arlen, Marc Robert Theoret, John Joseph Wright, Clara Chen, Jane B. Trepel, Anna Couvillon, Guinevere Chun, Nancy Harold, Seth M. Steinberg, Douglas K. Price, James L. Gulley, William Douglas Figg, William L. Dahut
Journal: Journal of Clinical Oncology (2014)

108 Background: Cabozantinib (C) is a multikinase inhibitor of c-Met, vascular endothelial growth factor receptor two and RET. C has shown activity in metastatic castrate resistant prostate cancer (mCRPC), with resolution of bone lesions on bone scan (BS), regression of soft tissue/visceral disease (STD), reductions in circulating tumor cells and bone biomarkers. Combining docetaxel (D) with other agents, without overlapping toxicities, can target different cellular signaling pathways necessary for tumor survival. Methods: Patients (pts), with no prior D for CRPC, receive a fixed dose of D (75 mg/m2 IV day one of each 21 day cycle) and prednisone (P) (5 mg po q12 hours) with C at three escalating dose levels: 20 mg, 40 mg, or 60 mg (all po daily). Using a standard three-plus-three design, three to six pts are treated at each dose level until the maximum tolerated dose (MTD) has been defined. Results: Thirteen pts have been accrued; four on dose level one, six on dose level two, and three on dose level three. Median age 69 (45 to 84). Four pts have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of zero and nine pts have a PS of one. Median Gleason score is nine (7 to 10). Median on-study prostate-specific antigen (PSA) is 129.2 ng/mL (0.01-508.5 ng/mL). Median cycles is six (1 to 17). Grade 1 adverse events (AEs), possibly related to C; dysgeusia (4/12), oral mucositis (4/12), increased ALT (3/12), and epistaxis (3/12). Grade 2 AEs; nausea (2/12), hand/foot syndrome (2/12), fatigue (2/12), dysgeusia (2/12), oral mucositis (2/12), hypophosphatemia (2/12), and anemia (2/12). Grade 3 AE is hypophosphatemia (2/12). Grade 4 AE is neutropenia (1/12). MTD of C is 60 mg. Of nine evaluable pts, six have bone only disease. Of these six, three pts have PSA declines of less than 30% with improvement on BS (two pts) or stable BS (one pt). The other three pts have PSA declines of greater than 30% and bone scan improvement. Three pts have STD and bone disease; one patient had a PSA decline of greater than 30% with improvement on BS and SD by CT scan. One patient had an increase in PSA of less than 30% with improvement on BS and CT. The third pt had PD by CT and an increase in PSA equal to 30%. PFS probability at six months is 90.0% and is 67.5% at eight months and beyond. Conclusions: The addition of C to D and P, has an acceptable toxicity profile. CT scan and BS improvements did not correlate with PSA declines in all pts. An expansion cohort will combine D plus P with C at the MTD (60 mg) to determine clinical benefit. Clinical trial information: NCT01683994.
Do perceived barriers to lung cancer screening differ between attending physicians and residents?
Authors: Mikael Anne Greenwood-Hickman, Laura Jones, Katie Marsh, M. Patricia Rivera, Paul Molina, Dan Reuland, J. Michael Bowling, Katherine Birchard, Susan Maygarden, Louise Henderson
Journal: Journal of Clinical Oncology (2016)

192 Background: In February 2015, legislation went into effect requiring Medicare to cover lung cancer (LC) screening with low dose computed tomography (LDCT) for high risk patients. Despite this, much debate and uncertainty exist among physicians about LC screening best practices. We aim to compare perceived barriers to LC screening between resident and attending physicians in Family and Internal Medicine, two departments selected for their high likelihood of seeing patients eligible for LC screening. Methods: Between February and July of 2015, a 23 question Qualtrics survey was conducted among physicians and residents at a large academic hospital to assess knowledge and beliefs of LC screening. In the Family and Internal Medicine departments, we surveyed 100 residents (30% response rate) and 86 attendings (49% response rate). Responses from the two departments were combined and stratified by attending or resident status. Results: Most respondents were White and non-Hispanic. Attendings were older (mean age 47, range 32-64) and mostly male (54%), while residents were younger (mean age 30, range 28-35) and mostly female (63%). The majority of attendings (62%) and residents (78%) agreed that limited time during patient visits requires presenting problems take priority over LC screening. Other barriers cited by both groups included cost to patients (74% attendings and 83% residents), potential for complications (53% and 70%), and too many false positives (67% and 73%). Over half of both groups agreed that inconsistent recommendations make it difficult to decide whether or not to screen for LC. In addition, the majority of both groups indicated that they were undecided about the benefit of LC screening for patients (43% attendings and 55% residents). No statistically significant differences were found. Conclusions: Regardless of resident or attending status, respondents identified inconsistent recommendations, time restrictions during visits, cost to patients, potential complications, and a high false positive rate as barriers to LC screening. Both groups reported being undecided about the utility of LC screening. These findings suggest a need for alternative strategies for future LC screening implementation.
Is empathy associated with a derived sense of meaning among resident physicians working with patients nearing the end of life on a hematology-oncology ward?
Authors: Daniel Curtis McFarland, Jonathan Komisar
Journal: Journal of Clinical Oncology (2016)

28 Background: An association between empathy and physician-in-training based meaning derived from patient deaths has not been explored previously. If meaning is associated with empathy, an intervention to enhance meaning may counteract empathy decline and promote clinician resilience. This study sought to understand if empathy might be associated with the ability to find meaning in the clinical situations that residents face in oncology. Methods: Internal Medicine residents rotating on a Hematology/Oncology ward were asked “Do you derive a sense of meaning from working with dying patients? Yes or No.” The Interpersonal-Reactivity Index (IRI) was used to measure empathy and demographic information. Results: 64 responded (66.7% response rate). 43 (67.2%) derived a sense of meaning while 21 (32.8%) did not. The ‘meaning’ group empathy score (IRI) was 60.7 (SD 10.8) and the ‘no meaning’ group empathy score (IRI) was 51.7 (SD 11.5) (p &lt; .01). Empathy subscale differences were notable for decreased cognitive empathy via the Fantasy Score (14.0 versus 9.9) (p &lt; .01) and decreased affective empathy via the Empathic Concern scale (18.8 versus 15.9) (p &lt; .05). Conclusions: The majority of physicians-in-training derived a sense of meaning from working with patients at the end of life and had significantly higher levels of empathy. The ability to impart meaning-finding has been demonstrated in patients and could be taught to physicians-in-training and lead to higher empathy levels. [Table: see text]
Pregnancy and survival after primary breast carcinoma in young women: A meta-analysis of healthy mother effect studies.
Authors: D. Mauri, A. Valachis, L. Tsali, K. Tsalis, N. P. Polyzos, L. L. Pesce
Journal: Journal of Clinical Oncology (2010)

9122 Background: Due to a trend towards postponing childbearing in the western world and the increased rate of infertility among young couples, diagnosis of breast cancer in nulliparous women is expected to rise over the next decades. Thereafter an increased number of these women is expected willing to conceive after breast cancer. Based on literature, most physicians usually recommend pregnancy two years after diagnosis of breast cancer. Nonetheless, the prognostic significance of pregnancy following treatment of breast cancer is limited to trials with small patient cohorts. Furthermore, a healthy mother effects (HME) selection bias appears to be consistent in most of these studies, since women undergoing childbearing after treatment were healthier when compared to the control group. Aim: To perform a systematic review and meta-analysis of published trials corrected for HME bias in order to assess the effect of pregnancy (at least 10 months after diagnosis) vs. no pregnancy on overall survival of primary breast cancer patients aged <45. Methods: We searched MEDLINE and ISI (last search January 2010) for eligible studies. From each study we extracted relative Hazard Ratio (HR) or, if not provided, all the necessary data to impute it. In case period from diagnosis was not reported we extract relative data to estimate it. Results: Electronic searches strategy yielded 1606 hits pertaining to 20 potentially eligible studies involving 49370 premenopausal breast cancer patients. Ten studies (total screened 41415, pregnants 1157, matched-controls 13187) were eligible since considering HME potential bias in matching controls. Among these 9 studies (pregnants 1089, matched-controls 13051) presented data for analyses. Overall survival was statistically higher among patients getting pregnant compared to no pregnancy: fixed effect model estimated pooled-HR 0.51 (95% CI: 0.42-0.62). No study heterogeneity was observed: Q=10.4 p.=0.17; I∧2 = 48%. Conclusions: Pooled available evidence indicates thatin primary breast cancer patients younger than 45 years old, pregnancy (at least 10 months after the diagnosis) does not jeopardize prognosis and appears to provide significant survival benefits No significant financial relationships to disclose.
Electrochemotherapy for cutaneous metastases in breast cancer: Experience from a designated treatment centre.
Authors: Shramana Mitul Banerjee, Jackie Newby, Shahab Khan, Virginia Homfray, Diane Whittaker, Christopher Keefe, Mohammed R. Keshtgar
Journal: Journal of Clinical Oncology (2015)

48 Background: Electrochemotherapy (ECT) combines the administration of poorly permeable chemotherapeutic agents with electroporation. It has been shown to be effective when compared with other treatments. This study assessed how breast cancer patients were benefited and identified potential problems at a designated treatment centre. Methods: This was a single centre prospective study of patients with cutaneous metastases from breast cancer. Patients who fulfilled NICE UK (National Institute Of Clinical Excellence) and local guidelines were treated. Gabapentin was given prior to general anaesthesia. Intravenous Bleomycin 15,000IU/m2 was given as a bolus. Treatment was commenced 8 minutes later with Cliniporator. Electrical pulses were delivered via an electrode inserted through the skin surface. Treatment response, disease progression free duration, post-operative pain and length of in-patient stay (LOS) were recorded. Patients recorded a symptom diary post treatment. Results: 20 treatments were performed in 16 patients from 2011-2015 with 53 separate areas treated. 8 patients had diffuse lesions, 5 had discrete lesions and 3 had both diffuse and discrete areas. 16 patients were being treated with ECT for the first time and 4 patients required 2 treatments. Median LOS was 3 days. Median follow up was 6 months (range 3-12).12 patients had complete response (75%) and 4 patients partial response. There was no disease progression for 6 months or more in 9 patients (56%) and 2 further patients had disease stabilised for 3 months with systemic or cutaneous progression in the remaining patients in 3 months or less. There were no deaths or immediate adverse events from ECT. 5 Patients (31%) with extensive diffuse chest wall disease reported persistent discomfort post treatment requiring extended period of post treatment analgesia. Conclusions: Electrochemotherapy is safe and effective treatment for cutaneous metastases. Appropriate patient selection for treatment, pre-emptive analgesia, post treatment support and follow up is essential in order to maximise the benefits and minimise potential side-effects particularly in extensive chest wall disease.
New GMP-Grade, Xeno-Component Free Medium for the Activation and Expansion of T Cells
Authors: Mario Assenmacher, Nadine Mockel-Tenbrinck, Alexander Scheffold, Georg Rauser, Hermann Bohnenkamp, Jürgen Schmitz, Uwe Odenthal, Bergendahl Veit, Ulrike Kolrep, Melanie Fahrendorff
Journal: Blood (2011)
Molecular pathologic phenotypes and outcome in adenocarcinoma of the ampulla of Vater.
Authors: D. K. Chang, A. Johns, C. J. Scarlett, M. Pajic, A. Chou, C. Toon, J. S. Samra, R. Sutherland, A. J. Gill, A. V. Biankin
Journal: Journal of Clinical Oncology (2011)

196 Background: Individuals with adenocarcinoma of the ampulla of Vater demonstrate a broad range of outcomes, as they may arise from any of the three epithelia that converge at that location. This variation in outcomes poses specific challenges in clinical decision making concerning the aggressiveness of treatment, and the appropriateness and type of adjuvant therapy. Methods: We assessed the relationship between molecular pathologic phenotypes defined using a combination of histopathology and protein expression (CDX2 [caudal-type homeodomain transcription factor 2] and MUC1), and outcome in 72 patients who underwent operative resection for adenocarcinoma of the ampulla of Vater. Results: Patients with a pancreaticobiliary phenotype (CDX2 negative, MUC1 positive) compared to an intestinal phenotype carcinoma segregated into an independently poor prognostic group (HR = 3.40, 95% CI: 1.71 – 6.76, p = 0.0005). Stratification using lymph node (LN) status (the only other independent poor prognostic factor) (HR = 3.19, 95% CI: 1.54 – 6.58, p = 0.0017) defined three clinically relevant phenotypes: 1) those with a non-pancreaticobiliary (intestinal) phenotype without LN metastases who had an excellent outcome (5-year survival 88.4%, median survival 172.8 months); 2) those that had a pancreaticobiliary phenotype and lymph node metastases that had a poor outcome (5-year survival 20.0%, median survival 7.4 months); and 3) the remainder (intestinal/LN positive or pancreaticobiliary/LN negative) who had an intermediate outcome (5-year survival 46.9%, median survival 57.0 months). Conclusions: A combination of histopathologic and molecular criteria identified three distinct clinically relevant phenotypes of adenocarcinoma of the ampulla of Vater that have significantly different outcomes. This distinction, which requires validation, may be used to refine current therapeutic strategies by guiding aggressiveness of surgery and selection for adjuvant therapy, which would improve overall outcomes. No significant financial relationships to disclose.
Does “two is better than one” apply to surgeons? Comparing single-surgeon and cosurgeon bilateral mastectomy outcomes.
Authors: Suniti Nimbkar, Melissa Anne Mallory, Katya Losk, Kristen Camuso, Mehra Golshan
Journal: Journal of Clinical Oncology (2015)

35 Background: Bilateral mastectomies (BM) are generally performed by a single surgeon (SS). A two-attending ‘co-surgeon’ (CS) technique, in which each surgeon concurrently performs a unilateral mastectomy, offers an alternative operative approach. We sought to examine differences in general surgery time (GST), overall surgery time (OST), and patient outcomes for BM performed by CS and SS at our institution. Methods: Patients undergoing BM with tissue expander reconstruction (BMTR) between January 2010 and May 2014 at our institution were identified and divided into SS and CS cases. Operative records were used to calculate GST (incision to end of BM procedure), reconstruction time (plastic surgery start time to end of reconstruction) and OST (OST = GST + reconstructive time). Patient age, presence and stage of cancer, breast weight, axillary procedure [sentinel node biopsy (SNB) or axillary dissection (ALND)], and 30-day postoperative complications were extracted from medical charts. Differences in GST and OST between CS and SS performed cases were assessed using a t-test. A linear regression was performed to identify factors contributing to GST. Results: We identified 116 BMTR cases performed by 8 breast surgeons, [CS, n = 67 (57.8%); SS, n = 49 (42.2%)]. Demographic characteristics did not significantly differ between groups. In the bivariate analyses, GST and OST for CS cases were significantly shorter than for SS, 75.8 vs 116.8 minutes, p &lt; 0.0001, and 255.2 vs 278.3 minutes, p = 0.005, respectively. The linear regression demonstrated a significant decrease in GST when BMTR was performed by CS (β = -38.82, p &lt; 0.0001); total breast weight (β = 0.0093, p = 0.03) and axillary dissection (β = 28.69, p = 0.0003) were found to significantly impact GST. Conclusions: The GST of BMTR is significantly decreased using a CS-approach without impacting complication rates. However, the degree of GST and OST-reduction suggests the addition of a CS does not proportionally impact surgical time as would be expected. A CS-approach may be more beneficial for patients with large total breast weight or those requiring ALND. A larger study is warranted to better characterize time, cost, and outcomes of the CS-approach for BM.
Molecular and clinical prognostic factors in metastatic colorectal cancer (CRC) patients (pts): A retrospective study.
Authors: Luisa Foltran, Paola Ermacora, Nicoletta Pella, Giuseppe Aprile, Giovanna De Maglio, Elena Masiero, Manuela Giangreco, Stefania Eufemia Lutrino, Laura Ferrari, Mariaelena Casagrande, Stefano Pizzolitto, Gianpiero Fasola
Journal: Journal of Clinical Oncology (2014)

511 Background: Strong evidence is emerging about the usefulness of mutational profiling for CRC pts. This study aimed to evaluate the overall survival in three molecular groups, taking as reference the all-wild type category: (1) BRAF mutated; (2) KRAS mutated codons 12-13 only; (3) any of KRAS codons 61-146, PIK3CA exon 9-20 or NRAS cod 12-13-61 mutations. Also clinical variables were investigated as potential prognostic factors. Methods: Data of 194 consecutive pts treated for metastatic colorectal cancer (mCRC) at our University Hospital in Udine, Italy, between Jan 2004 and Jan 2013 were reviewed. Point mutations were detected by pyrosequencing platform PyroMark Q96 ID instrument for KRAS/NRAS codons 12, 13, 61, and 146, BRAF exon 15, and PIK3CA exons 9 and 20. Clinical and molecular prognostic factors were identified using the Cox proportional hazards model. Results: The all wild-type population consisted of 76 pts (39%). 62 cases (32%) harboured mutations in KRAS codons 12-13. BRAF V600E mutation was found in 10 (5.2%) samples. Mutations in KRAS 61-146, PIK3CA and NRAS codons were detected in 9 (4.6%), 32 (16.5%) and 6 (3.1%) pts, respectively. All factors significant in univariate analysis were subjected to multivariate analysis (see Table). The all-wild type category had the longest survival (27.7 months). Patients carrying BRAF mutations reported an overall survival of 7.6 months and those with KRAS 12-13 mutation 16.7 months. Conclusions: This study reinforces the prognostic value of a full mutational molecular profile and points out some prognostic clinical factors in CRC. The influence of clinical variables such as right colon cancer, primary tumour not resected, exposure to bevacizumab and lines of chemotherapy need further investigation. [Table: see text]
Health-related quality of life of of women with breast cancer undergoing chemotherapy in the northern region of Brazil.
Authors: Namie Okino Sawada, Mary Elizabeth de Santana, Helena Megumi Sonobe
Journal: Journal of Clinical Oncology (2015)

92 Background: In Brazil, the estimate for the year 2015 is approximately 576,000 new cases of cancer. Breast cancer is the most common in Brazilian women and the state of Pará is the first with the highest incidence of breast cancer in northern Brazil. The high incidence and changes caused by treatment and own illness as the disturbances in body image, functional, emotional and social changes cause fear in women, as well as disrupting daily activities and impact the health-Related Quality of Life (HRQOL). Improving HRQOL is an important goal so the evaluation of HRQoL of these patients is of interest to health professionals, as they provide information that help in planning treatment and rehabilitation. The objective is to evaluate the HRQoL of patients with breast cancer in chemotherapy treatment. Methods: It is a cross-sectional study with quantitative exploratory design. This place was a public hospital in the city of Belém do Pará, Women were included with breast cancer, over eighteen years old and excluded those with cognitive problems and metastases. The European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ C 30) and Questionnaire Breast Cancer Module (QLQ BR23) have been administrated. The project was approved by the Ethics Committee and were respected the resolution 466/2012 CNS / MS. Results: The sample consisted of 89 women with breast cancer undergoing chemotherapy, most in the age group over 40, mulatto, married, fundamental level of education, domestic load, Catholic religion, live in rural areas with incomes of one to two minimum salaries. The EORTC QLQ C 30 showed that the average QOL was 75.56, and the most impaired functions were physical (M = 65.62) and role performance (M = 58.61) and the most frequent symptoms were diarrhea, constipation, dyspnea, nausea and vomiting, fatigue, pain and loss of appetite. EORTC BR23 demonstrated functional scale (M = 49.95) and symptoms scale (M = 33.00). Conclusions: The results show that the side effects of chemotherapy affect the physical and functional function and consequently HRQoL of these patients.
Ablation for hepatocellular carcinoma: Validating the 3-cm breakpoint.
Authors: Ryan Thomas Groeschl, T. Clark Gamblin, Kiran Turaga
Journal: Journal of Clinical Oncology (2013)

277 Background: Although many previous studies on ablation outcomes for hepatocellular carcinoma (HCC) have dichotomized tumor size around a 3cm cutoff to determine prognostic significance, a growing number of reports describe excellent outcomes for larger tumors. To address the sensibility of this somewhat arbitrary 3-cm cutoff, we stratified patients by 1cm tumor size intervals and hypothesized that disease-specific survival (DSS) would not vary significantly between adjacent groups. Methods: Patients treated with local ablation for T1 HCC (≤8cm) were identified from the Surveillance, Epidemiology, and End Results database (2004-2008). Log-rank tests were used to compare DSS curves of adjacent study groups, and multivariable Cox proportional hazards models were used adjust for confounding variables. Results: There were 1,093 patients included in the study (26% female, median age: 62 years). The 3-year DSS was significantly lower in patients with 3-4cm tumors compared to 2-3cm tumors (58% vs 72%, p=0.002, Table). In adjusted models, DSS did not vary significantly between any size intervals up to 3cm. Patients with 3-4cm tumors, however, had a poorer prognosis compared to patients with 2-3cm tumors (hazard ratio: 1.60, 95% confidence interval: 1.18-2.18, p=0.002). DSS also fell significantly when tumor size increased from 5-6cm to 6-7cm (53% vs 21%, 0.006). Age and alpha-fetoprotein levels were also independently predictive of DSS in most multivariable models; however, the presence or absence of cirrhosis was not predictive in any models (smallest p=0.382). Conclusions: This study defends the use of a 3cm breakpoint when studying outcomes after ablation for HCC. Although some have advocated that ablation is more successful in cirrhotics, we found no evidence for this in our study. [Table: see text]