tbuckley/cabot-search huggingface dataset:
The impact of disease labels on disease experience in patients with prolonged incurable cancer.
Authors: Hilde Buiting, Veerle Busink, An K.L Reyners, Egbert F. Smit, Donald van Tol, Vincent K.Y. Ho
Journal: Journal of Clinical Oncology (2018)

e22011 Background: Advances in oncology have resulted in prolonged disease trajectories in patients with incurable cancer inducing discussions about the ‘right’ medical terminology. The impact of choosing a disease label on well-being can be high. We examined the impact of disease labels on well-being in patients with prolonged incurable cancer. Methods: Qualitative study based on 33 conversations covering a period of 2 years (2015-2017) at the day-care unit of a comprehensive cancer center in the Netherlands. 19 patients with incurable breast cancer (at least one year after diagnosis) and 11 patients with incurable lung cancer (at least 6 months after diagnosis) with cancer remission were included. Patients had received at least a second line of systemic treatment. Conversations were openly framed by questioning how patients felt in this stage. Questions about disease-labeling were asked explicitly and implicitly. Results: Patients ascribed different disease labels to themselves, either on purpose or not. They varied in their preference regarding specific disease labels (e.g. ‘chronic’, ‘palliative’, ‘patient’) in their communication about their disease. Patients with a more positive mood were often more comfortable with the label ‘chronic’, whereas patients with a less positive mood felt they could become trapped in a definition until the end of their life. Some patients preferred not to label their disease at all, as they felt it would make them ‘less human’. Some labels used by healthcare professionals distressed patients, especially when they heard different disease-labels from different healthcare professionals. Some patients however explicated to stick to their own disease label. Patients who were more willing to perceive themselves as a ‘patient’ tended to receive more support. Conclusions: Patients’ use of disease labels are part of their coping strategy, that is particularly associated with maintaining hope of a longer life. This emphasizes the importance to include appropriate disease labels by healthcare professionals. More research is warranted to explore which disease labels suit different patients best and to explore other outcomes than well-being such as (the frequency) of treatment decisions.
Timed sequential therapy with high-dose cytarabine and mitoxantrone as an effective and safe induction regimen for acute myeloid leukemia.
Authors: Melissa L. Larson, Sakina Burhani, Kirstin Gallas, Deborah Ann Katz, Maura Hoyt, Parameswaran Venugopal
Journal: Journal of Clinical Oncology (2018)

7055 Background: Traditionally, patients eligible for induction chemotherapy for AML are treated with the “7+3” regimen, which includes standard doses of infusional cytarabine and an anthracycline, with historical CR rates of 50-60%. We conducted a retrospective analysis of an alternate induction regimen. Based on timed sequential therapy, it consists of a 2-day treatment with high dose cytarabine, which improves remission rates when used in induction, and dose intensified anthracycline therapy, which improves outcomes in younger patients. We present the analysis of the regimen and the response rates of patients based on risk stratification, history of prior MDS and age. Methods: 382 patients were treated from 1998-2015. The treatment consisted of 2 doses of cytarabine 2gm/m2 (1.5 gm/m2 for patients aged greater than 70 years) IVPB over 3 hours given 12 hours apart followed by one dose of mitoxantrone 30 mg/m2 IVPB over 1 hour on days 1 and 5. Data regarding cytogenetics and MDS history was collected for each patient. IWG remission criteria were used to determine remission status. Results: Median age of the patients was 58 years (range 17-85). 205 were male; 177 were female. 25 patients had favorable risk; 200 had intermediate risk; 157 had unfavorable risk. A history of MDS was noted in 83 patients. 212 patients were under the age of 60 years; 170 were aged 60 years or older. The overall CR rate (CRR: CR+CRi+CRp) for all patients was 68.5%. The complete remission rates based on risk karyotypes were favorable 96%, intermediate 77%, and unfavorable 53%. Patients with no prior MDS had a CRR of 72.6% compared to 53% for patients with a history of MDS. Patients younger than 60 years had a CRR of 72.2% compared to 63.5% for aged 60 years or older. The 30 day induction death rate was 2.4%. Conclusions: This two-day induction regimen is a safe and effective treatment for de novo AML. There is a high response rate, particularly in patients with favorable and intermediate risk karyotypes, with a low rate of early mortality. The high response rates and tolerability noted with this regimen provides a platform for further clinical trials to enhance outcome by combining with novel targeted therapies for AML.
A clinically applicable molecular-based classification for endometrial cancers.
Authors: Jessica N. McAlpine, Melissa McConechy, Lien Hoang, Samuel Leung, Quentin Nakonechny, Amy Lum, Winnie Yang, Cyril Blake Gilks, David Huntsman, Aline Talhouk
Journal: Journal of Clinical Oncology (2016)

5518 Background: Classification of endometrial carcinomas (ECs) by morphologic features is inconsistent, and yields limited prognostic and predictive information. A new system for classification based on the molecular categories identified in The Cancer Genome Atlas (TCGA) is validated. Methods: We used a previously characterized molecular classification tool that recapitulates the TCGA prognostic subgroups but could be achieved through pragmatic assays, and on formalin-fixed paraffin-embedded samples. MMR immunohistochemistry (IHC), mutation status of the POLE exonuclease domain, and p53 IHC were sequentially evaluated on a cohort of 456 EC hysterectomy specimens and an additional 56 matched pre-operative biopsy and post-operative hysterectomy ECs. Molecular subgroups were tested for association with OS, DSS, and PFS. Prognostic value of our molecular-based classifier was compared to current clinicopathological based systems. The ability of the classifier to discriminate outcomes with the addition of other parameters (e.g. age, additional IHC) was evaluated with Harrell’s C-index and calibrated (Poisson regression) with observed outcomes. Results: OS, DSS, and PFS for the four molecular subgroups are distinct. The POLE group consistently has the best prognosis while the p53 abn has the poorest. Unlike TCGA we were able to distinguish between the two intermediate outcome survival curves with the MMR abn subgroup exhibiting worse outcomes than p53 wt. Prognostic ability was further improved if the molecular classifier is combined with select clinicopathologic parameters. Molecular classification in pre-and post-operative samples are concordant (kappa 0.80, accuracy 0.86). Conclusions: Molecular classification of ECs can be achieved using clinically applicable methods and provides independent prognostic information beyond established risk factors. This pragmatic molecular classification tool can be used from time of first diagnosis and will: provide consistent categorization of tumors, improve risk stratification, identify women who may have Lynch syndrome, stratify clinical trials, and we believe ultimately improve outcomes for women with EC.
Comparison of triple negative (TN) and HER2 positive (HER2+) invasive lobular carcinomas (ILCs) to a matched cohort of invasive ductal carcinomas.
Authors: Dan Le, Caroline Speers, Lovedeep Gondara, Alan Nichol, Caroline A. Lohrisch
Journal: Journal of Clinical Oncology (2018)

e13088 Background: Most ILCs are estrogen receptor (ER) positive and tend to relapse at different sites than IDCs, suggesting distinct biology. We explored prognosis for TN and HER2+ ILCs and IDCs. Methods: From the prospective British Columbia (BC) Cancer Outcomes Unit database, we identified TN and HER2+ ILCs diagnosed 01/2003 to 12/2013 referred to BC Cancer. Exclusions: stage IV, mixed ILC/IDC, unknown HER2, and prior / subsequent breast cancer. ILCs were propensity-score matched (1:2) to IDCs for age, T/N stage, biomarkers, grade, chemotherapy (CT), and nodal radiation (RT). Kaplan-Meier method was used to estimate relapse-free survival (RFS) and overall survival (OS). Results: Of 2925 ILCs diagnosed, 2587 were referred, and 143 were TN or HER2+. By comparison, there were 5526 TN and HER2+ IDCs. After exclusions, 127 TN and HER2+ cases (23% TN; 77% HER2+) were matched as shown in Table 1. Five-year RFS was ILCs 81% (95% confidence interval [CI], 73-87%) and IDCs 84% (95% CI, 79-88%). Five-year OS was ILCs 79% (95% CI, 71-85%) and IDCs 83% (95% CI, 78-87%). Conclusions: Fewer than 5% of ILCs are TN or HER2+. Low CT use may explain the similar low RFS in both ILCs and IDCs. For the ILC subgroup, therapy should mirror standard of care, which includes CT (plus anti-HER2 therapy for HER2+) for most T/N stages. Table 1: ILCs and matched IDCs ILC (n = 127) IDC (n = 254) Stage T1 51 (40.2%) 101 (39.8%) T2 51 (40.2%) 104 (40.9%) T3 15 (11.8%) 27 (10.6%) N0 60 (47.2%) 115 (45.3%) N1 31 (24.4%) 67 (26.4%) N2 13 (10.2%) 17 (6.7%) N3 10 (7.9%) 24 (9.5%) Grade 1 12 (9.5%) 22 (8.7%) 2 72 (56.7%) 143 (56.3%) 3 41 (32.3%) 88 (34.7%) CT1 87 (68.5%) 162 (63.8%) Hormone therapy2 77 (60.6%) 168 (66.1%) Nodal RT 53 (41.7%) 99 (39.0%) ER positive 93 (73.2%) 186 (73.2%) PR positive 55 (43.3%) 106 (41.7%) HER2 positive 98 (77.2%) 193 (76.0%) 1 p-value = 0.36 2not matched, p-value = 0.29
Unmet spiritual needs and its correlation with fatigue in early and advanced stage cancer patients in Indonesia.
Authors: Diah Martina, Rudi Putranto, Andhika Rachman, Hamzah Shatri
Journal: Journal of Clinical Oncology (2017)

e21709 Background: Spirituality is a powerful coping mechanism during life-threatening illness trajectories. The unmet spiritual needs have been associated with increasing pain, depression, and anxiety. However, its relation to fatigue as one of the most prevalent and distressing symptoms in cancer patients has remained understudied in either early or advanced stage. Methods: This study was a cross-sectional study with consecutive sampling in the national referral hospital of Indonesia, between September 2015 and January 2016. This study interviewed adult cancer patients undergoing treatment in outpatient and inpatient settings and excluded those with cognitive and/or affective disorders and weak general condition which did not allow the filling of questionnaire. We used validated Problems and Needs in Palliative Care (PNPC)-short version questionnaire (Bahasa version) to assess unmet spiritual and fatigue needs. In addition to finding both prevalences, this study applied Mann-Whitney tests to analyze the relationship between unmet spiritual and fatigue needs in the early and late stage. Results: By the end of the study 329 (97.6%) subjects completed the questionnaire, 45.3% of which was among advanced stage. The prevalences of spiritual problem and fatigue were 39% and 63% while the unmet needs of both aspects, respectively, were up to 78% and 42%. Experiencing unmet needs on one or more of spiritual aspects was significantly related to the emergence of unmet fatigue needs, particularly in the advanced stage of cancer (p = 0.024). In the early stage, unmet needs of fatigue were prominent among those who remained to experience difficulties to be engaged usefully (p = 0.006). In advance stage, the unmet needs of fatigue were significantly correlated with difficulties concerning the meaning of death (p = 0.038). Conclusions: Most cancer patients remained to suffer from unmet spiritual needs, and it was significantly correlated with the occurrence of fatigue. Although it escalated in the latest stage of cancer, both were also found and related at the earliest stage. It underlined the importance of addressing spiritual needs and fatigue adequately since the diagnosis of cancer was made.
Life expactation and intensity of cancer in brief: Family histories of the patients with myeloproliferative neoplasms.
Authors: Ali Zahit Bolaman, Mustafa Unubol, Gurhan Kadikoylu, Irfan Yavasoglu
Journal: Journal of Clinical Oncology (2017)

e18564 Background: Thrombosis and bleeding are the most important prognostic factors in myeloproliferative neoplasm (MPN). But there is not a prognostic factor for predicting survival at diagnosis. The determination of the intensity of the cancer incidence in brief- and family histories of patients may help to make a comment on the nature of the MPN. We investigated the effects of the concomitant diseases on survival and cancer intensity in brief- and family histories of the patients with MPN. Methods: Thirty-five (19 female, mean age 59 ±11 years) patients with MPN were enrolled to the study. The diagnosis of the patients were essential thrombocythemia in 19, polycythemia vera in six and primary myelofibrosis in six, and chronic myelocytic leukemia in four. By using Charlson’s concomitant disease index, concomitant disease weight incidence, concomitant state-age relationship, and probability of 10 years survey were investigated. Results: In brief history of the patients, only one (3%) patient had skin cancer. However there were some cancers in family history of 9 patients (26%). These were hematological malignancies in four patients (2 acute myelocytic leukemia and 2 non-Hodgkin’s lymphoma) and solid tumors in five patients (2 breast, 2 colon cancer, one skin and lung cancers). Mean Charlson’s concomitant disease weight index was 1.4±1.5 (0-6), concomitant state-age relationship was 3.2±2 (0-8), and probability of 10 years survey was 63±35% (0-98%). Conclusions: Although our study group is small, Charlson’s concomitant disease index may be used for the determining of life expectancy in MPN. Moreover cancer cluster in family history of these patients was notable.
Trends and correlates of secondhand smoke exposure among non-smoking cancer survivors in the United States: 1999-2012.
Authors: Oladimeji Akinboro, Bernard Bernhardt, Ian Robert Hantman, Daniel Pomerantz, Prasanta Basak, Rasim A. Gucalp, Stephen Jesmajian, Elizabeth Phillips
Journal: Journal of Clinical Oncology (2016)

10105 Background: Secondhand smoke exposure (SHSe) adversely affects outcomes in certain cancers and also increases the risk of non-cancer related deaths among cancer survivors. We sought to estimate and trend the prevalence of SHSe as well as the proportion of SHSe due to indoor household tobacco exposure among non-smoking adult cancer survivors in the United States (US). Methods: Data were obtained from the National Health and Nutrition Examination Survey for 3,482 adults aged at least 20 years with a self-reported history of cancer who were examined in 2 year cross-sectional cycles from 1999-2012. SHSe was defined with serum cotinine levels 0.05-10ng/ml among non-smokers. We calculated and trended the prevalence of SHSe as well as the geometric means of serum cotinine among non-smoking adult cancer survivors with SHSe. Independent associations of the following with SHSe were examined with multivariable logistic regression: age, gender, race, education, income, smoking history, cancer site, time since cancer diagnosis, and survey cycle. Survey weights were applied in estimating the population-based prevalence and 95% confidence intervals (CI). Results: The prevalence of SHSe among non-smoking US adult cancer survivors declined from 31.9% (CI 22.6-44.1%) to 14.1% (CI 9.1-19.1%) in 1999/2000 and 2011/2012, respectively (P-value for trend < 0.01). The geometric means of serum cotinine also declined from 1.8ng/ml (CI 1.3-2.6ng/ml) to 1.3ng/ml (CI 1.2-1.4ng/ml) (P-value for trend < 0.01). Among those with SHSe, exposure from indoor household smoking declined from 23.4% (CI 13.7-33.4%) in 2001/2002 to 8.8% (CI 0.2-17.3%) in 2011/2012 (P-value for trend < 0.01). Increasing age and being female were protective against SHSe while blacks, former smokers, poor, and less educated survivors had higher odds of SHSe. Conclusions: SHSe among non-smoking cancer survivors in the US is on the decline. However, SHSe is increasingly being mediated by tobacco exposure in settings outside the home. These findings suggest the need for a paradigm shift by healthcare professionals who address SHSe among non-smoking cancer survivors to encouraging their vigilance and avoidance of SHSe in settings outside the home.
Intensive chemotherapy (IC) versus hypomethylating agents (HMA) for the treatment of younger patients with myelodysplastic syndrome (MDS) and elevated bone marrow blasts.
Authors: Paolo Strati, Guillermo Garcia-Manero, Tapan M. Kadia, Gautam Borthakur, Marina Konopleva, Naval Guastad Daver, Courtney Denton Dinardo, Nicholas James Short, Musa Yilmaz, Kiran Naqvi, Sherry Pierce, Jorge E. Cortes, Hagop M. Kantarjian, Farhad Ravandi
Journal: Journal of Clinical Oncology (2018)

7064 Background: The AZA-001 trial has shown a survival advantage for patients with high-risk MDS treated with HMA as compared to IC. However, this study was conducted mainly in an older population. Methods: We retrospectively analyzed the characteristics and outcomes of patients with MDS, younger than 60 years of age, with ≥ 10% bone marrow blasts who received frontline treatment with HMA or anthracycline-cytarabine-based IC at our institution between 10/1993 and 12/2017. Results: One-hundred and six patients were included in the study, 57 treated with HMA and 49 with IC. Use of IC was associated with shorter time to response (1 vs 2 months; p < 0.001) and higher overall response rate (ORR; 82% vs 60%, p = 0.02). On univariate analysis (UA) age younger than 50 (p = 0.03) and use of IC (p = 0.02) were associated with ORR, but on multivariate analysis (MVA) only use of IC maintained its association (OR 4.3, 95% CI 2-9.1; p < 0.001). Rates of treatment discontinuation secondary to early death or toxicity were comparable; 31% of patients on HMA and 33% on IC proceeded to stem cell transplant (SCT). After a median follow-up of 15 months (range, 1-178 months), 38 (51%) out of 74 patients lost their response, and median response duration (RD) was 19 months (range, 1-166 months). Factors associated with longer RD on UA were lack of unfavorable cytogenetics (p = 0.04), consolidation with SCT in first remission (p = 0.009) and use of IC (p = 0.03); on MVA, use of IC maintained its association (HR 2.9, 95% CI 1.4-5.8, p = 0.03). Eight (8%) patients transformed to acute myeloid leukemia during frontline treatment, 7 (12%) on HMA and 1 (2%) on IC (p = 0.07). At most recent follow-up, 65 (61%) patients died, median overall survival was 21 months (range, 1-178 months) and was significantly longer for patients treated with IC (43 vs 15 months; p = 0.05). Conclusions: IC is more effective than HMA for younger patients with MDS and bone marrow blasts ≥ 10%, irrespective of other baseline characteristics. Strategies combining targeted agents with either HMA or IC should be investigated, to determine whether this advantage will be maintained.
Outcomes in patients with marginal zone lymphomas undergoing transformation to high-grade lymphomas.
Authors: Juan Pablo Alderuccio, Amrita Desai, Nicolas Gallastegui Crestani, Jeremy Ramdial, Erik Lesley Kimble, Macarena Ines De La Fuente, Jennifer Chapman, Francisco Vega, Wei Zhao, Isildinha M. Reis, Izidore S. Lossos
Journal: Journal of Clinical Oncology (2018)

7559 Background: Marginal zone lymphomas (MZLs) are characterized by a long overall survival (OS). High-grade transformation (HGT) to aggressive lymphoma negatively impacts OS. Thus, identifying patients predisposed to HGT is of utmost clinical importance. Given the paucity of data on HGT in MZL patients, we undertook a retrospective study of the largest cohort to date of MZL patients to identify risk factors for HGT and death, thought analyses of transformation-free survival (TFS) and OS. Methods: In the Florida Cancer Registry, we identified 564 biopsy proven MZL patients seen at our institution between 1/1990-12/2016. In 453 patients, diagnostic biopsies were reviewed and MZL diagnosis confirmed based on the WHO Lymphoma classification and these were studied. Results: Median follow-up of our cohort was 4.8 years (range 0.02-22.1yrs). The cases were classified as MALT (85.9%), splenic (7.7%) and nodal (6.4%) MZLs. 34 (7.5%) patients had biopsy proven HGT to diffuse large B cell lymphoma (DLBCL). The percentages of HGT was 17.2% in nodal, 11.4% in splenic, and 6.4% in MALT (p= 0.05). Among 34 HGT cases, the median time to HGT was 21 months (range: 0-135 months); HGT was present at the time of initial MZL diagnosis in 7(21%) patients. On multivariate analysis of TFS, patients with elevated LDH (HR 4.09,95%CI:1.91-8.76) and failure to achieve CR to initial therapy (HR 3.91,95%CI:1.80-8.48) had significantly higher risk for HGT. In separated models, IPI > 2 (HR = 2.19,95%CI:1.01-4.74), and FLIPI > 2 (HR = 2.52,95%CI:1.12-5.65) were significant predictors of higher risk for HGT. In the 34 patients with HGT, median OS from diagnosis was 129.6 months (95%LL = 55.2) and from HGT 87.6 months (95%LL = 14.4). Patients presenting with HGT within 12 months from MZL diagnosis had shorter OS compared to patients with late HGT [5-year OS rate 0.50 (95%CI:0.19-0.75) vs. 0.75 (95%CI:0.49-0.89), HR = 3.36, (p= 0.0192)]. Conclusions: In this largest single-institution study, HGT occurred in 7.5% of patients with higher proportion in nodal MZL (17.2%). Elevated LDH, FLIPI/IPI > 2 and failure to achieve CR to initial therapy were identified as major risk factors for HGT. Patients transforming within 12 months from MZL diagnosis had worst survival.
Towards a safer CD19 CART therapy with reduced risk of cytokine release syndrome (CRS).
Authors: Lucas H. Horan, Cheng Liu
Journal: Journal of Clinical Oncology (2016)

3049 Background: Despite remarkable clinical success, adoptive T-cell therapy (ACT) with anti-CD19 chimeric antigen rector (CAR) T cells is hindered by both pro-inflammatory and immuno-suppressive adverse events. Hyper-activation of CD19 CARs can trigger life-threatening cytokine release syndrome (CRS), while xenogeneic sequences in existing constructs can lead to diminished CAR T cell efficacy due to immunogenecity. Methods: To ameliorate these problems we developed a novel chimeric T-cell therapy platform, ARTEMIS, that functionally matches the potency of CAR T cells, but dramatically reduces the release of cytokines upon killing of target-positive tumors. To minimize the immunogenicity, we created a panel of fully-human CD19 antibodies using a human antibody library against cells expressing endogenous CD19. The CD19 antibodies were expressed as either ARTEMIS T cells or 2nd generation CD28z CAR T cells and tested for efficacy and safety both in vitro and in vivo. Results: In the Raji-lymphoma model with NSG mice, CD28z CART cells caused lethality within 24 hrs of T-cell injection into immunodeficient mice and led to pathologies resembling a pre-clinical CRS model. Strikingly, ARTEMIS T cells armed with the same anti-CD19 antibody showed no signs of toxicity and had potent anti-tumor effects. Both ARTEMIS and CAR T-cells engineered with our CD19 antibodies killed CD19+ cell lines with high specificity and potency. Compared to CAR, ARTEMIS T-cells have similar degranulation activity, intracellular cytokine production, and in vitro killing efficiencies. However, ARTEMIS T-cells release up to 1000-fold less cytokines and accumulate less exhaustion markers during in vitro killing assays. Conclusions: The therapeutic potential of CD19 CAR T cell therapy can be expanded with a better safety profile. The fully-human anti-CD19 antibody would reduce the risk of immunogenicity as compared with the mouse anti-CD19 antibody currently used in CAR T therapy. The ARTEMIS T-cell signaling platform was designed to be a safer ACT by relying on endogenous T-cell signaling factors. We show evidence that ARTEMIS begins to disentangle efficacy from CRS and holds the potential to be a clinically safer therapy by preventing ACT-triggered CRS.