tbuckley/cabot-search huggingface dataset:
Annual Hazard Rates of Recurrence for Breast Cancer During 24 Years of Follow-Up: Results From the International Breast Cancer Study Group Trials I to V
Authors: Marco Colleoni, Zhuoxin Sun, Karen N. Price, Per Karlsson, John F. Forbes, Beat Thürlimann, Lorenzo Gianni, Monica Castiglione, Richard D. Gelber, Alan S. Coates, Aron Goldhirsch
Journal: Journal of Clinical Oncology (2016)

Predicting the pattern of recurrence can aid in the development of targeted surveillance and treatment strategies. We identified patient populations that remain at risk for an event at a median follow-up of 24 years from the diagnosis of operable breast cancer.International Breast Cancer Study Group clinical trials I to V randomly assigned 4,105 patients between 1978 and 1985. Annualized hazards were estimated for breast cancer-free interval (primary end point), disease-free survival, and overall survival.For the entire group, the annualized hazard of recurrence was highest during the first 5 years (10.4%), with a peak between years 1 and 2 (15.2%). During the first 5 years, patients with estrogen receptor (ER)--positive disease had a lower annualized hazard compared with those with ER-negative disease (9.9% v 11.5%; P = .01). However, beyond 5 years, patients with ER-positive disease had higher hazards (5 to 10 years: 5.4% v 3.3%; 10 to 15 years: 2.9% v 1.3%; 15 to 20 years: 2.8% v 1.2%; and 20 to 25 years: 1.3% v 1.4%; P < .001). Among patients with ER-positive disease, annualized hazards of recurrence remained elevated and fairly stable beyond 10 years, even for those with no axillary involvement (2.0%, 2.1%, and 1.1% for years 10 to 15, 15 to 20, and 20 to 25, respectively) and for those with one to three positive nodes (3.0%, 3.5%, and 1.5%, respectively).Patients with ER-positive breast cancer maintain a significant recurrence rate during extended follow up. Strategies for follow up and treatments to prevent recurrences may be most efficiently applied and studied in patients with ER-positive disease followed for a long period of time.
New recurring cytogenetic abnormalities and association of blast cell karyotypes with prognosis in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group report of 343 cases
Authors: Nancy R. Schneider, Andrew J. Carroll, Jonathan J. Shuster, D. Jeanette Pullen, Michael P. Link, Michael J. Borowitz, Bruce M. Camitta, Julie A. Katz, Michael D. Amylon
Journal: Blood (2000)
Testing procedures and reasons why HER2-positive breast cancer patients did not receive trastuzumab in the adjuvant setting.
Authors: A. C. Houts, L. Benn, D. Lalla, P. G. Solari, M. S. Walker, E. J. Stepanski, L. S. Schwartzberg
Journal: Journal of Clinical Oncology (2010)

e11072 Background: Use of trastuzumab in the adjuvant and metastatic setting has been shown to improve outcomes (DFS and OS) in HER2+ patients. An earlier study found that 13% of HER2+ patients with stage II-III breast cancer did not receive trastuzumab. This study examined reasons HER2+ patients receiving adjuvant treatment did not get trastuzumab and examined HER2 testing patterns. Methods: Data and text fields of 12 community site EMRs were searched to identify patients believed to be HER2+ but with no record of trastuzumab treatment. Records from 1142 cases yielded 74 patients with invasive HER2+ disease but who were not treated with trastuzumab. For comparison, a random sample of 76 patients who did receive trastuzumab was identified. Chart extraction by experienced oncology nurses documented details of testing and reasons for non use of trastuzumab. Results: 95% of patients had documentation of IHC 3+ or FISH > 2.0. Treated patients were younger (53 vs. 66 yrs old), with later stage disease, larger tumor size, and a greater number of positive lymph nodes. The most common medical reasons for withholding trastuzumab were: small tumor size, negative nodes and early stage of disease (30%); advanced age (11%); and unspecified heart disease (5%). Patient reasons for declining trastuzumab included: declined systemic therapy or wanted hormonal treatment only (22%); perceived risk (11%); perceived lack of efficacy (8%); and cost (3%). There were no significant differences between patients who did or did not have documentation for non use (47%). Conclusions: In contrast to reports of inadequate HER2 testing based on administrative claims data, this detailed medical record review showed 95% correct testing. Oncologists treating patients for early-stage cancer appeared to follow testing and treatment guidelines. Although HER2+ implies high risk, older patients and those with smaller tumors and node negative disease were most likely to not receive trastuzumab. Documentation of medical reasons for not using trastuzumab was poor, but when provided was consistent with guidelines. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech Genentech
Experimental Studies on the Genetics of Spontaneous Leukemia in Mice
Authors: R. K. Cole, J. Furth
Journal: Cancer Research (1941)

The genetic constitution of an individual largely governs its morphological development and its response to both internal and external stimuli. The inherited character may be expressed regardless of the non- genetic or environmental influences; or the nongenetic influences may completely suppress the genetic tenden- cies. Neither, in a large majority of the cases, is com- pletely suppressed by the other. For a satisfactory study of one, it is desirable that the other be kept constant. But biological material is never constant and environmental changes are always present although they may not be readily determined. Changes in genetic constitution also occur universally and, while progeny may resemble their parents to all outward appearances, special breeding tests will show the ex- istence of certain minor variations and such variations can be accentuated through suitable breeding pro- cedures. The extensive investigations herein reported were designed to evaluate the importance of genetic consti- tution in the development of spontaneous leukemia in mice.
Characterizing the specialty palliative care workforce in the United States: Results of a national survey.
Authors: Arif Kamal, Janet Bull, Ursula A. Rogers, Keith Mark Swetz, Dio Kavalieratos, Amy Pickar Abernethy
Journal: Journal of Clinical Oncology (2014)

90 Background: Increasingly, oncology teams and specialty palliative care (PC) clinicians are collaborating in the care of patients with serious or advanced cancer. Because of such partnerships, PC services have grown tremendously, with teams now available in most US cancer centers. Despite increased penetrance of services, little is known about the workforce that delivers this care, including their demographics, training, and future plans. Methods: Members of the American Academy of Hospice and Palliative Medicine (e.g. advanced practice provider (APP), registered nurses, chaplains) completed a workforce characteristics survey through electronic invitation in the second half of 2013; respondents were recruited via e-mail, blog and Facebook posts, and Twitter tweets. Descriptive statistics were calculated. Results: 1,241 clinicians responded, representing approximately a third of those who received the survey; 68% were physicians and 14% were APPs. Most (56%) were older than 50 years of age; 65% were female. Of physicians, 58% were board-certified through the experiential track, while 22% had completed fellowship training. Of clinical responsibilities, about half (48%) split time between consultative PC and hospice; 30% performed PC consultations only. Regarding organization size, 35% work with 1-3 other colleagues; 8% work alone. Regarding tenure, 34% have worked in PC for &lt;5 years; 22% for &gt;10 years. 82% reported they would become a PC clinician again, if asked to revisit their career choice. Of motivations for joining clinical PC, leading reasons were “opportunity for personal growth” and “influential experience during practicing another specialty”. About half (47%) intend to leave the field within 10 years. Of reasons to leave, 49% will retire; 24% may leave due to burnout; and 20% reported dissatisfaction with practice. Conclusions: The specialty PC workforce is diverse and faces sustainability challenges due to advancing physician age, impending retirements, evolving burnout, and dissatisfaction with the profession. If patients are going to have adequate access to services, research and approaches are needed to develop solutions that sustain and grow specialty PC.
Predicting chemotherapy toxicity in older adults with cancer: A prospective 500 patient multicenter study.
Authors: A. Hurria, K. Togawa, S. G. Mohile, C. Owusu, H. D. Klepin, C. Gross, S. M. Lichtman, V. Katheria, S. Klapper, W. P. Tew
Journal: Journal of Clinical Oncology (2010)

9001 Background: Older adults are vulnerable to chemotherapy (chemo) toxicity (tox); however, there is limited data to identify those at risk. The goals of this study are to: 1) identify risk factors for grade 3-5 chemo tox in older adults and 2) develop a risk-stratification schema for grade 3-5 tox based on the number of risk factors. Methods: Patients age ≥ 65 with cancer from 7 institutions completed a pre- chemo assessment capturing: 1) sociodemographics, 2) tumor/treatment variables, 3) labs, 4) Karnofsky performance status, and 5) geriatric assessment [functional, psychological, and nutritional status, comorbidity, cognition, and social activity/support (Hurria et al, Cancer 2005)]. Patients were followed through the chemo course to capture grade 3-5 tox. Multivariate logistic regression was used to identify independent risk factors for grade 3-5 tox. Results: 500 patients [mean age 73 (range 65-91)] with cancer [lung (29%), breast/gyn (28%), GI (27%), GU (10%), or other (6%)] participated (61% had stage IV disease, 71% received 1st-line chemo). Grade 3-5 tox occurred in 53% (50% grade 3, 12% grade 4, 2% grade 5). Grade 3-5 hematological (heme) and non-heme tox occurred in 26% and 43% respectively. Risk factors for grade 3-5 tox included: 1) age ≥ 73, 2) cancer type (GI or GU), 3) standard dose, 4) poly-chemo, 5) falls in last 6 months, 6) assistance with instrumental activities (IADL), and 7) decreased social activity. A risk stratification schema (number of risk factors: % incidence of grade 3-5 tox) was developed - 1: 23%; 2: 36%; 3: 50%; 4: 60%; 5: 83%; 6: 90%; 7: 100%. Conclusions: This study identified risk factors for grade 3-5 chemo tox in older adults. A risk stratification schema based on the number of risk factors was developed. Risk factors for grade 3-5 toxicity OR (95% CI) P value Age <73 1.0 ≥73 2.1 (1.4-3.2) <0.01 Cancer type Gyn 1.0 Lung 1.1 (0.6-2.0) 0.71 Breast 1.6 (0.8-3.2) 0.22 Other 1.8 (0.7-4.7) 0.23 GU 2.4 (1.1-5.1) 0.02 GI 3.4 (1.9-6.1) <0.01 Dose upfront Reduced 1.0 Standard 1.7 (1.1-2.8) 0.03 No. of chemo agents 1 1.0 >1 1.7 (1.1-2.7) 0.01 Falls in last 6 mos None 1.0 ≥1 1.9 (1.2-3.3) 0.01 IADL No assistance 1.0 Assistance 1.6 (1.0-2.4) 0.03 Social activity (Medical Outcomes Study) ≥50 1.0 <50 1.6 (1.1-2.6) 0.03 No significant financial relationships to disclose.
Lipoarabinomannan-Responsive Polycytotoxic T Cells Are Associated with Protection in Human Tuberculosis
Authors: Martin Busch, Christian Herzmann, Stephanie Kallert, Andreas Zimmermann, Christoph Höfer, Daniel Mayer, Sebastian F. Zenk, Rainer Muche, Christoph Lange, Barry R. Bloom, Robert L. Modlin, Steffen Stenger
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

The development of host-targeted, prophylactic, and therapeutic interventions against tuberculosis requires a better understanding of the immune mechanisms that determine the outcome of infection with Mycobacterium tuberculosis.To identify T-cell-dependent mechanisms that are protective in tuberculosis.Multicolor flow cytometry, cell sorting and growth inhibition assays were employed to compare the frequency, phenotype and function of T lymphocytes from bronchoalveolar lavage or the peripheral blood.At two independent study sites, bronchoalveolar lavage cells from donors with latent tuberculosis infection limited the growth of virulent Mycobacterium tuberculosis more efficiently than those in patients who developed disease. Unconventional, glycolipid-responsive T cells contributed to reduced mycobacterial growth because antibodies to CD1b inhibited this effect by 55%. Lipoarabinomannan was the most potent mycobacterial lipid antigen (activation of 1.3% T lymphocytes) and activated CD1b-restricted T cells that limited bacterial growth. A subset of IFN-γ-producing lipoarabinomannan-responsive T cells coexpressed the cytotoxic molecules perforin, granulysin, and granzyme B, which we termed polycytotoxic T cells. Taking advantage of two well-defined cohorts of subjects latently infected with Mycobacterium tuberculosis or patients who developed active disease after infection, we found a correlation between the frequency of polycytotoxic T cells and the ability to control infection (latent tuberculosis infection, 62%; posttuberculosis patients, 26%).Our data define an unconventional CD8(+) T-cell subset (polycytotoxic T cells) that is based on antigen recognition and function. The results link clinical and mechanistic evidence that glycolipid-responsive, polycytotoxic T cells contribute to protection against tuberculosis.
Abstract 19806: Enhanced Intracellular Ca2+ Buffering Capacity Causes Failure of Intracellular Ca2+ Wave Propagation in Tachycardia-induced Atrial Remodeling
Authors: Maura Greiser, Benoit-Gilles Kerfant, Niels Voigt, Sander Verheule, Ursula Ravens, Dobromir Dobrev, Ulrich Schotten
Journal: Circulation (2010)
Is performance status related to functional capacity in patients with non small cell lung cancer (NSCLC)?
Authors: M.-A. Dalzell, H. Kreisman, D. Small, N. MacDonald
Journal: Journal of Clinical Oncology (2004)

7224 BackgroundPerformance status (PS) is a key factor in determining patient eligibility for clinical trials, predicting treatment toxicity and prognosis. Despite the importance of this clinical measurement tool, PS is subjective and interobserver variability high. The objective of this study was to evaluate functional capacity in ambulatory patients (PS 0–3) with NSCLC and compare results with physician assigned ECOG values. MethodsA series of sixty-one (61) patients with NSCLC (Stage III A, B and IV)referred to CNRP, age 42 to 89, were evaluated with standardized clinical tests including cardiopulmonary exercise capacity, hand grip strength (Jamar Dynamometer), and lower limb endurance capacity(Chair Rise Test) .Individual test results were compared to age and sex matched population data and weighted (0–3), according to severity of functional limitation ( mild, moderate, severe). Global scores (0–9) were calculated and correlated with physician assigned ECOG values. ResultsSixty percent (60%) of patients with PS 0–1 and 76% of those with PS 2–3 recorded significant cardiopulmonary limitations including high resting heart rate (>100), low HR reserve, low exercise capacity and poor recovery following exercise testing. All patients scored below the 50th percentile for hand grip strength and endurance capacity. Median upper and lower limb scores were at the 25th percentile in PS 0–1 and below the 10th percentile in PS 2–3 compared to age and sex matched populations. Global functional scores ranged from 0–9, with a median score of 4 in PS 0–1 and 8 in PS 2–3. There was a statistically significant difference (Wilcoxon Signed Rank Test) between ECOG performance status and objective measurement of functional capacity (P<.001).ConclusionsPatients traditionally scored to have good PS may in fact perform poorly on tests of functional capacity. The majority of our patients would have had difficulty with simple activities of daily living. Further studies are required to determine whether these tests more accurately risk stratify patients than tools such as the ECOG PS. No significant financial relationships to disclose.
Response to: ‘Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women’ by Gao <i>et al</i>
Authors: S Kluzek, M T Sanchez-Santos, K M Leyland, A Judge, J Newton, N K Arden
Journal: Annals of the Rheumatic Diseases (2016)

Response to: 'Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women' by Gao et al.We would like to thank Gao et al for their interest in our paper 'Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women'.(1) Gao et al highlighted a number of issues related to a discordance between pain and radiographic changes and sensitivity of the pain assessment.Although a single definition of knee osteoarthritis (KOA) remains elusive, the presence of knee pain is the main symptom of knee osteoarthritis(OA)(2-4) and there is still a strong relationship between pain and ROA.(5, 6) Notwithstanding this, a substantial number of patients with radiographic knee osteoarthritis (ROA) are asymptomatic.Although OA is the most common 'source' of knee pain in ROA, it is true, as pointed out by Gao et al. that many other diagnoses may be judged to account for a patient's symptoms including bursitis,
A phase I trial of combination therapy of tumor lysate-pulsed dendritic cells and adoptive transfer of anti-CD3 activated T cells (TP-DC/CAT) in patients with advanced gastrointestinal (GI) cancers
Authors: K. Shimizu, K. Tanigawa, N. Takeshita, A. Aruga, J. J. Mulé, K. Takasaki
Journal: Journal of Clinical Oncology (2004)

2585 Background: We have previously shown that tumor lysate-pulsed DC vaccination (TP-DC) elicited therapeutic rejection of established tumor in animal models. Administration of activated T cells was also shown to inhibit tumor relapse in patients (pts) with hepatocellular carcinoma (HCC) after curative operation. In addition, combination of TP-DC with administration of activated T cells elicited more significant therapeutic rejection of established tumor than the single therapy alone in animal models. We therefore sought to examine the therapeutic potency of TP-DC with administration of anti-CD3 activated T cells (CAT) against GI cancers: 3 pts were diagnosed with pancreatic cancer, 7 pts with HCC, 3 pts with intrahepatic cholangiocarcinoma, 2 pts with esophageal sarcoma, 12 pts with colorectal cancer. Methods: Monocyte-derived DC was generated in serum-free medium containing GM-CSF (100 ng/ml) and IL-4 (50 ng/ml). Pts received TP-DC intradermally (i.d.) 4 times every 3 weeks with 1 x 109 CAT activated with interleukin-2 and antibody to CD3: 4 pts received 1 x 106 DC, 7 received 2 x 107, 16 received 1 x 108. The safety as well as the biological and the clinical effects of TP-DC were studied. Twenty seven pts were included. Ten of these pts had evaluable unresected tumor resistant to conventional chemotherapy. Results: TP-DC/CAT was well tolerated; the major adverse events being fever and skin erythema of low grade (grade 1 and grade 2). No grade 3 and 4 adverse events was noted. Two of 10 pts with evaluable unresected tumor achieved partial remission (6 months); 4 pts achieved stable disease (4 months). 13 of 16 pts receiving 1 x 108 DC developed a strong positive skin reaction to tumor lysates. In 6 pts, a positive skin reaction to tumor lysates was shown to be maintained in 12 months after the development of the positive skin reaction to tumor lysates. Conclusion: The results of this Phase I trial appear promising for further development in pts with advanced GI cancers. No significant financial relationships to disclose.
Depletion of human regulatory T cells (Treg) and antigen-specific immune responses to cancer vaccines
Authors: T. M. Clay, A. Hobeika, T. Osada, D. Serra, D. Niedzwiecki, H. K. Lyerly, M. A. Morse
Journal: Journal of Clinical Oncology (2008)

3010 Background: CD4+CD25+FoxP3+ regulatory T cells (Treg) limit antigen-specific immune responses and are a cause of suppressed anticancer immunity. Conversely, depletion of Treg leads to immune enhancement. The immunotoxin denileukin diftitox which selectively targets lymphocytes expressing CD25 may deplete FoxP3+ Treg. Methods: We evaluated the proliferative potential of PBMC to various antigens in vitro following exposure to denileukin diftitox. We then performed a pilot study in which patients with advanced CEA expressing malignancies, being immunized with autologous dendritic cells modified with a fowlpox vector encoding CEA (rF-CEA(6D)-TRICOM), received denileukin diftitox 18 mcg/kg, once, 4 days before the immunizations began, or 9 mcg/kg prior to each of the 4 immunizations. ELISPOT, cytokine flow cytometry, and ELISA were used to measure the T cell and antibody response. Results: In vitro, escalating doses of denileukin diftitox depleted FoxP3+ Treg, decreased Treg function in vitro, and enhanced antigen-specific T cell responses. In the pilot study (n=15), denileukin diftitox was associated with a 74 ± 6% decrease in Treg in those receiving multiple doses, but not in those receiving a single dose. An earlier peak in the vaccine-induced CEA-specific T cell responses, and significant levels (>0.5%) of circulating CD8+ and CD4+ CEA-specific T cells were also seen in the multiple dose group. Conversely, a single dose of denileukin diftitox enhanced anti-CEA, but not antifowlpox vector, antibody responses. Multiple doses abolished the anti-CEA antibody response. Conclusions: These results indicate the potential for combining Treg depletion with anticancer vaccines to enhance tumor antigen specific immune responses. No significant financial relationships to disclose.
Ultrasound findings predict progression to inflammatory arthritis in anti-CCP antibody-positive patients without clinical synovitis
Authors: Jackie L Nam, Elizabeth M A Hensor, Laura Hunt, Philip G Conaghan, Richard J Wakefield, Paul Emery
Journal: Annals of the Rheumatic Diseases (2016)

To determine whether ultrasound can identify anti-cyclic citrullinated peptide (anti-CCP) antibody-positive patients without clinical synovitis (CS) who progress to inflammatory arthritis (IA).In a prospective study, anti-CCP-positive patients without CS underwent ultrasound imaging of 32 joints (wrists, metacarpophalangeal joints, proximal interphalangeal joints and metatarsophalangeal joints (MTPs)) and were monitored for the development of IA. Associations between baseline ultrasound findings (grey scale (GS), power Doppler (PD) and erosions) and (1) progression to IA and (2) development of CS within an individual joint were measured.Consecutive anti-CCP-positive patients (n=136; mean age 51 years, 100 women) were followed up for median of 18.3 months (range 0.1-79.6). At baseline 96% had GS, 30% had PD and 21% had one or more erosions. IA developed in 57 patients (42%) after median of 8.6 months (range 0.1-52.4). Ultrasound abnormalities (GS ≥2, PD ≥1 or erosion ≥1) were found in 86% at baseline compared with 67% of non-progressors (χ2=6.3, p=0.012). Progression to IA was significantly higher in those with ultrasound findings in any joint (excluding MTPs for GS) (GS ≥2: 55% vs 24%, HR (95% CI) 2.3 (1.0 to 4.9), p=0.038; PD ≥2: 75% vs 32%, 3.7 (2.0 to 6.9), p<0.001 and erosion ≥1: 71% vs 34%, 2.9 (1.7 to 5.1), p<0.001). Furthermore, progression occurred earlier with PD ≥2 (median 7.1 vs 52.4 months) and erosion ≥1 (15.4 vs 46.5). At the individual joint level, the trend for progression to CS was more significant for GS and PD (GS ≥2: 26% vs 3%, 9.4 (5.1 to 17.5), p<0.001; PD ≥2: 55% vs 4%, 31.3 (15.6 to 62.9), p<0.001).Ultrasound features of joint inflammation may be detected in anti-CCP-positive patients without CS. Ultrasound findings predict progression (and rate of progression) to IA, with the risk of progression highest in those with PD signal.NCT02012764; Results.