tbuckley/cabot-search huggingface dataset:
Quality of life (QOL) among patients (pts) with HER2+ breast cancer (bc) treated with adjuvant lapatinib and/or trastuzumab in the ALTTO study (BIG 2-06, Alliance N063D).
Authors: Amylou C. Dueck, David W. Hillman, Lisa A. Kottschade, Michele Y. Halyard, Jeff A. Sloan, Lynn M. Flickinger, Antonio C. Wolff, Lyndsay Harris, Julie Gralow, Kathleen I. Pritchard, Susan Ellard, Nguyet Le-Lindqwister, Frances M. Boyle, Evandro De Azambuja, Worta J. McCaskill-Stevens, Jo Anne Zujewski, Martine J. Piccart-Gebhart, Edith A. Perez
Journal: Journal of Clinical Oncology (2014)

647 Background: The Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO; NCT00490139) study was an international randomized open-label phase III study of 2 targeted therapies for HER2+ bc. Efficacy results will be reported in a separate abstract. Methods: Pts were randomized to 1 of 4 arms with sequential or concurrent chemotherapy: (A) trastuzumab (T) for 52 weeks (w); (B) oral lapatinib (L) for 52w; (C) T for 12w followed by 6w washout followed by L for 34w; or (D) T+L for 52w. Functional Assessment of Cancer Therapy-Breast (FACT-B) and Linear Analogue Self-Assessment (LASA) items measuring overall and 5 QOL domains, fatigue, rash, and diarrhea were administered on paper at baseline, w12, w52, year 3, and year 5 in pts enrolled in ALTTO through the US NCI CTSU. Mean scores were compared using analysis of covariance and paired t-tests. Results: Among 777 pts, 607, 521, and 492 completed booklets at baseline, w12, and w52. At w12, worsening of LASA domains (overall QOL, mental, physical, social wellbeing), FACT-B Trial Outcome Index (TOI), fatigue, rash and diarrhea reached statistical significance within all arms (all p<0.05 except FACT-B TOI for arm C p=0.21). Worsening was similar across arms for these LASA domains and fatigue. Diarrhea worsening was more severe in upfront L-containing (B & D) arms compared to upfront T alone (A & C) arms (B vs A, B vs C, D vs A, D vs C p<0.001). Rash worsening was most severe in B (vs C p=0.02, vs D p=0.007, vs A p=0.10). At w52, LASA domains, fatigue, and FACT-B TOI returned to baseline levels with changes similar across arms (all p>0.05). Rash (C vs A, D vs A p<0.05) and diarrhea (B vs A, C vs A, D vs A, C vs B, D vs B p<0.05) exhibited statistically significant worsening from baseline in L-containing arms relative to A. Conclusions: While L had a larger negative impact than T on diarrhea and rash, QOL did not appear to differ across arms. Patient QOL was negatively impacted similarly across arms at w12 but returned to baseline by the end of the treatment period at w52. These data enhance the understanding of QOL impact of anti-HER2 therapy in pts with early stage bc. Long term QOL collection is ongoing. Clinical trial information: NCT00490139.
Diversity and heterogeneity in molecular analysis of advanced sarcomas: The clinical, regulatory, and financial challenge for drug development and precision medicine.
Authors: Vivek Subbiah, Rishi Agarwal, Filip Janku, Apostolia Maria Tsimberidou, Shreyaskumar Patel, Robert S. Benjamin, Joseph A. Ludwig, Peter Meade Anderson, Dejka M. Araujo, Vinod Ravi, Anthony Paul Conley, Neeta Somaiah, Wei-Lien Wang, Aung Naing, Ralph Zinner, David S. Hong, Funda Meric-Bernstam
Journal: Journal of Clinical Oncology (2014)

10595 Background: Therapeutic options are limited for advanced sarcomas. Search for molecular alterations could lead to identification of novel therapies for refractory sarcoma patients. Rarity poses an extreme challenge in drug development. Methods: We reviewed the charts of patients with advanced sarcoma patients who were referred to the phase 1 clinic at MD Anderson Cancer center and had molecular profiling done by commercially available CLIA certified labs. We analyzed the preliminary responses to matched therapy in these patients. Results: Among the 57 pts analyzed, median age =48 years (M: F=25:32), median ECOG PS=1, median no. of prior therapies=3. Most common subtypes were leiomyosarcoma (n=13; 22%), rhabdomyosarcoma (n=8; 14 %), liposarcoma (n=7; 12 %), osteosarcoma (n=7; 12 %), clear cell sarcoma (n=3), and synovial sarcoma (n=3). Forty-five/57 (78%) patients had > 1 genomic aberration. Each pt’s aberration profile was distinct. For instance, in osteosarcoma no 2 ps had the same profile. In other soft tissue sarcomas, aberrations involved CDKN2A/B loss or mutation (n=10; 22 %), TP53 alterations (n=15; 33%), CDK4 amplification (n=8; 17%), MDM2 amplification (n=7; 15%), and RB1 loss/mutation (n=6; 13%). In addition, novel aberrations: KIAA1549-BRAF fusion protein in a spindle cell sarcoma, CD30 + in osteosarcoma, and PTPRD mutation in Ewing’s sarcoma were identified. Molecularly matched therapy are ongoing (Table ). Conclusions: Based on the uniqueness and distinct biology of sarcoma, we conclude that the established model for drug development in sarcoma of “one size fits all approach” does not fit the reality of sarcoma biology. New creative models for precision medicine with regulatory approval, establishment of levels of evidence, modification of reimbursement policies by health care payers and innovative dynamic ways to collect N of 1 clinical data in real time with open access are warranted. Diagnosis Aberration Matched therapy Response RMS PIK3CA PI3K inhibitor SD(18 weeks) Spindle cell sarcoma KIAA1549-BRAF PTEN loss RAF+mTOR SD(26% decrease)(16 weeks) LMS PTEN loss VEGF +mTOR SD(16 weeks) LMS PIK3R1 mTOR+HDAC SD(15 weeks)
Enobosarm and lean body mass in patients with non-small cell lung cancer.
Authors: Jeffrey Crawford, Mary Ann Johnston, Ryan P. Taylor, James T. Dalton, Mitchell S. Steiner
Journal: Journal of Clinical Oncology (2014)

9618 Background: Cancer induced muscle wasting is a selective and progressive cancer related symptom that begins early in the course of malignancy. Greater than 50% of NSCLC patients have muscle wasting at diagnosis, increasing to >80% prior to death. Historically, interventions targeting muscle wasting and cachexia focused on weight, ignoring the importance of lean body mass (LBM).Enobosarm is a first-in-class, non-steroidal, oral, selective androgen receptor modulator (SARM). We report results for 2 Phase 3 clinical trials of enobosarm, POWER 1 (P1) and POWER 2 (P2), for the prevention and treatment of muscle wasting in patients with advanced NSCLC. Methods: Patients (pts) with Stage III or IV NSCLC were randomized at initiation of first-line chemotherapy based upon the planned chemotherapy regimen; platinum + taxane (P1, n=321) or platinum + non-taxane (P2, n=320). Pts (males and postmenopausal females ≥30y with ECOG ≤1) received either enobosarm 3mg or placebo (pbo) for 5 months. LBM was measured by Dexa and body weight (BW) by scale weight, w/hospital gown & w/o shoes, at baseline day (d)84 and 147. Results: In P1 and P2, decreases in BW were observed from baseline in both enobosarm and pbo groups. In P1, enobosarm treated pts had a lower rate of decline in BW as compared to pbo through d84 (p=0.053) and 147 (p=0.038). Despite declining BW, increases in LBM were still observed in enobosarm pts (+0.41 kg) compared to pbo (-0.92 kg) by continuous variable analysis at d84 (p=0.0002) and 147 (p<0.0001). In P2, there was no difference in loss of BW between groups; however, enobosarm pts demonstrated significant increases in LBM (+0.47 kg) compared to pbo (-0.37 kg) at d84 (p=0.0111) and 147 (p=0.0028). Additionally, a larger proportion of pts receiving enobosarm maintained or increased LBM at d84 and 147 in both trials (P1: p=0.036 and 0.026; P2: p=0.113 and 0.013; by responder analysis) as compared to pbo. The incidence of adverse events was similar between enobosarm and pbo in both trials. Conclusions: Overall, enobosarm was safe and well tolerated. Enobosarm had a clinically significant effect on muscle, despite decreases in BW, which may translate into improvement in physical function. Impact on survival will be evaluated. Clinical trial information: NCT01355497, NCT01355484.
Impact of novel therapies on multiple myeloma survival in the US: Current and future outcomes.
Authors: Amar Drawid, Satyin Kaura, Daniel Kiely, Mohamad A. Hussein, Malik Kaman, Nisha Gilra, Brian G. Durie
Journal: Journal of Clinical Oncology (2015)

e19536 Background: Multiple myeloma (MM) survival improved dramatically with the introduction of new therapies in the mid-late 2000s. These therapies essentially transformed MM from an acute condition to a potentially manageable chronic disease. The impact of further advances in MM therapy is uncertain, but can be projected by analyzing historical data and expected future clinical trial outcomes. This study uses a novel approach to estimate current and future patient outcomes in MM. Methods: For the historical perspective (1980-2008), we calculated overall survival for patients diagnosed in a given year (cohort OS) by analyzing data from Surveillance, Epidemiology & End Results (SEER). For the predictive analysis, we calculated cohort OS using a patient flow model by integrating data from clinical trials, cancer registries and demographics as well as assumptions from key opinion leaders. We simulated progression of each cohort based on treatment rates and time spent in each line of therapy. The resulting OS curves were calibrated to 19 years of historical data. Results: The median cohort OS in the US remained relatively static from 1980–2001 at ~30 months, but increased by ~43% to 43 months in 2008. The median cohort OS is expected to continue rising to ~72 months in 2022, which represents ~67% improvement from 2008 and ~140% improvement from 2001 (TABLE 1). The life expectancy of patients diagnosed with MM in 2022 would thus be ~75 years, but will still be shorter than the ~86 year life expectancy of the general population at the median diagnosis age of ~69 years. Conclusions: This analysis highlights the dramatic improvements in MM survival since 2000 and the expected improvement in the future, demonstrating the transformative impact and value of novel therapies. Over the next few years, with better scientific understanding of MM and the use of novel drug regimens, we expect to see additional improvement of ~67% in OS for MM patients. Nevertheless, there is opportunity to further bridge the life expectancy gap between the general population and MM patients. Comparison of historical and predicted overall survival (OS). 1994 2001 2008 2015 2022 Historical OS (months) 28 30 43 Predicted OS (months) 57 72
Association of 25-OH vitamin D deficiency with worse outcome for elderly patients with aggressive B-cell lymphomas treated with CHOP plus rituximab (R): An analysis of the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL).
Authors: Joerg Thomas Bittenbring, Marina Achenbach, Bettina Altmann, Marita Ziepert, Joerg Reichrath, Juergen Geisel, Evi Regitz, Niels Murawski, Carsten Zwick, Gerhard Held, Michael Pfreundschuh
Journal: Journal of Clinical Oncology (2013)

8569 Background: Vitamin D deficiency was shown to be is associated with a worse outcome in patients with non-Hodgkin's lymphoma (Drake et al., 2010) To study whether this observation could be confirmed in patients with aggressive B-cell lymphomas treated uniformly within a prospective trial, we analyzed 25-OH vitamin D serum levels in patients treated within the RICOVER-60 trial of the DSHNHL. Methods: 25-OH Vitamin D serum levels were determined with a commercial chemoluminescence immunoassay in the serum from elderly patients of the RICOVER-60 trial which compared 6 or 8 cycles of CHOP, both with and without rituximab. Results: 193 of 359 pts (53.8%) had vitamin D deficiency (&lt;10 ng/ml) and 165/359 patients (46.0%) had vitamin D insufficiency (10-30 ng/ml) according to current definitions. When treated with R-CHOP, patients with vitamin D levels ≤8 ng/ml had a 3-year EFS of 59% compared to 79% of patients with vitamin D serum levels &gt;8 ng/ml; the respective figures for 3-year overall survival were 70% and 82%, respectively. In R-CHOP pts these differences were significant in a multivariable analysis adjusting for IPI risk factors with a hazard ratio (HR) of 2.1 (p=0.008) for EFS and a HR of 1.9 (p=0.040) for OS. In pts treated without R effects of vitamin D deficiency were significant only for OS (HR 1.8; p=0.025), but not with respect to EFS (HR 1.2; p=0.388). These results were confirmed in an independent validation set of 63 patients treated within the prospective RICOVER-noRx study. Conclusions: Vitamin D deficiency is a significant risk factor for patients with aggressive B-cell lymphomas treated with R-CHOP. The stronger adverse effect of vitamin D deficiency in patients receiving rituximab suggests that vitamin D deficiency interferes with the R mechanisms of this antibody. A prospective study evaluating the effects of vitamin D substitution on outcome of patients receiving R-CHOP is warranted. Supported by Deutsche Krebshilfe.
Second primary lung cancer in the United States: 1992–2008.
Authors: Nicholas Donin, Lorna Kwan, Andrew T. Lenis, Drakaki Alexandra, Mark S. Litwin, Karim Chamie
Journal: Journal of Clinical Oncology (2017)

309 Background: Tobacco smoke is a known risk factor for both bladder and lung cancer. We hypothesized that bladder cancer survivors are at high risk for second primary lung cancers (SPLC), and sought to describe the incidence and mortality attributable to SPLC among survivors of bladder cancer as well as other common cancers in the United States. Methods: We identified adult patients diagnosed with a localized primary malignancy from 8 of the most common non-pulmonary cancer sites in Surveillance, Epidemiology, and End Results (SEER) data from 1992–2008. We explored factors associated with the incidence and mortality from SPLC using bivariable and multivariable models. Finally, we compared standardized incidence rates (SIRs) for SPLC in our cohort with the control arm of the National Lung Screening Trial (NLST), a large lung cancer screening trial in patients at high risk for lung cancer. Results: We identified 1,431,809 survivors of common non-pulmonary cancers, of whom 24,477 (1.7%) developed SPLC at a mean (SD) follow-up of 5.7 (3.6) years. Bladder cancer survivors developed SPLC at twice the rate of other cancer survivors, with 10% developing SPLC in the 20 years following their bladder cancer diagnosis. Increasing age and male gender were independent risk factors for SPLC, irrespective of the primary cancer type. Of patients who developed SPLC, 19,059 (78%) died during follow-up. Lung cancer was responsible for 73% of these deaths, such that over half (57%) of the cancer survivors who develop SPLC ultimately died of lung cancer. Bladder cancer survivors demonstrated a SIR of 512 cases/100,000 person-years, which approaches the rate (572 cases/100,000 person-years) seen in the control arm of the NLST. Conclusions: Over half of patients who develop SPLC died of their disease. Almost 10% of bladder cancer survivors develop SPLC in the 20-years following their diagnosis. This rate approaches that seen in the control arm of the NLST, suggesting that the incidence in bladder cancer survivors could justify lung cancer screening in this population. Further efforts to better define the potential risks and benefits of lung cancer screening in bladder cancer survivors is warranted.
A screening tool to identify FIT geriatric oncology patients.
Authors: Ashwin Reddy Sama, Benjamin E Leiby, Kristine Swartz, Joshua Schoppe, Amy R. MacKenzie, Walter K Kraft, Andrew E. Chapman
Journal: Journal of Clinical Oncology (2015)

e20532 Background: A Vulnerable Elders Survey (VES 13) score of ≥ 3 has been validated to predict vulnerability for community elders but not geriatric oncology patients. A test to accurately identify fit patients who can receive standard therapy is needed. The objective of this study is to evaluate VES 13 as a tool to identify fit patients as determined by a comprehensive geriatric assessment (CGA). We proposed to find a score at which an acceptable number of fit patients could be identified, and to find a rule to identify patients who would not need a full CGA. Methods: Jefferson Senior Adult Oncology Center is a multi-disciplinary clinic in which patients are seen by a medical oncologist, geriatrician, pharmacist, social worker and dietician. Patients complete a self-administered VES 13 prior to the visit. Patients undergo a CGA and are classified by the group as “FIT”, “VULNERABLE” or “FRAIL”. Chart review of 211 patients was performed. A receiver operative curve was constructed to determine the best VES 13 cut off point for patients to be classified as fit. Recursive partitioning was used to identify an optimal rule based on VES 13, Timed Up and Go (TUG), ADL, IADL, and ECOG score for determining fitness. Results: The final sample of 103 patients had complete data including: multi-disciplinary assessment of vulnerability, VES 13, TUG, ADL, IADL, and ECOG score. 28 patients were fit by CGA and 75 were either vulnerable or frail. The mean VES 13 score of the fit patients was 2.1 and for “not FIT” patients was 6. A VES 13 score of < / = 4 was recommended as the optimal cutoff to identify fit patients with a sensitivity of 82% and specificity 77%. No VES 13 score could identify all fit patients. A rule of “FIT = VES < 3 and TUG < = 8” for fitness classified all CGA-defined Frail or Vulnerable subjects as “NOT FIT” and had a 100% PPV for predicting fitness. The increase in PPV decreased the sensitivity; some fit patients will undergo a CGA, but no patients who need a CGA will be missed. Conclusions: The use of VES 13 as a sole screening tool could lead to misdiagnosing many vulnerable or frail patients as fit. This is the first report of an algorithm and the first step in developing a tool that could identify fit geriatric oncology patients. This could possibly obviate the need for a full CGA in some patients.
Recurrent MYB rearrangement in blastic plasmacytoid dendritic cell neoplasm
Authors: K Suzuki, Y Suzuki, A Hama, H Muramatsu, M Nakatochi, M Gunji, D Ichikawa, M Hamada, R Taniguchi, S Kataoka, N Murakami, D Kojima, Y Sekiya, E Nishikawa, N Kawashima, A Narita, N Nishio, Y Nakazawa, H Iwafuchi, K-i Watanabe, Y Takahashi, M Ito, S Kojima, S Kato, Y Okuno
Journal: Leukemia (2017)
Efficacy and safety of atezolizumab (atezo) and bevacizumab (bev) in a phase Ib study of microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC).
Authors: Howard S. Hochster, Johanna C. Bendell, James M. Cleary, Paul Foster, Wei Zhang, Xian He, Genevive Hernandez, Koho Iizuka, S. Gail Eckhardt
Journal: Journal of Clinical Oncology (2017)

673 Background: Blockade of the PD-L1/PD-1 axis is a proven immunologic approach for treatment of many cancers; however, not all pts respond to monotherapy. Bev, an anti–VEGF-A antibody, has demonstrated clinical efficacy in mCRC and enhanced T-cell infiltration in tumors in preclinical studies. Thus, we postulated that combining atezo (anti-PD-L1) with bev would augment anti-tumor immune responses, resulting in improved and more durable clinical benefit. We report results from the first study of an anti-PD-L1 agent + VEGF-A blockade in MSI-high mCRC. Methods: A Ph Ib study (NCT01633970) investigated atezo + various chemotherapeutic/biologic regimens (eg, bev) in pts with advanced solid tumors, including mCRC. Pts received atezo 1200 mg q3w plus bev 15 mg/kg q3w (data cutoff, May 20, 2016). The primary objective was to evaluate the safety of atezo + bev. Secondary objectives included anti-tumor activity per RECIST v1.1. MSI status was tested locally. Results: Ten MSI-high mCRC pts were enrolled. Three pts had received 1 prior chemotherapy and 7 pts had received ≥ 2. Median age was 52.5 y. The minimum (range) of safety follow-up was 2.6 (2.6-20.3) mo. Median (range) treatment duration with atezo + bev was 10.1 (2-20) and 9.0 (2-19) mo, respectively. Efficacy results are shown below; the confirmed ORR per RECIST v1.1 was 30% (95% CI, 6.7%-65.3%). Median OS had not been reached with a median follow-up of 11.1 mo. Treatment-related all-grade AEs occurred in 80% of pts; 40% of pts had a related G3/4 AE. The most common related AE was proteinuria (40%; n = 3 G2 and n = 1 G3). No G5 events occurred. One AE led to discontinuation of atezo and 3 AEs led to discontinuation of bev. Biomarker data will be presented. Conclusions: Initial clinical activity was observed in heavily pretreated pts with MSI-high mCRC receiving atezo + bev; the disease control rate was 90%. This combination was well tolerated without unexpected toxicities. Further follow-up is ongoing. Clinical trial information: NCT01633970. [Table: see text]
Twelve-month prevalence of mental disorders in cancer patients across major tumor entities.
Authors: Anja Mehnert, Susanne Kuhnt, Elmar Brähler, Hermann Faller, Martin Härter, Monika Keller, Holger Schulz, Karl Wegscheider, Joachim Weis, Hans-Ulrich Wittchen, Uwe Koch
Journal: Journal of Clinical Oncology (2015)

9552 Background: Many studies have shown high levels of emotional and psychosocial distress in cancer patients. However, it is not well known yet to what extent psychological problems meet the criteria of a mental disorder according to clinical diagnosis classification systems (ICD-10, DSM-IV/V). We investigated the 12-month prevalence of mental disorders in a representative sample of cancer patients treated in different care settings in order to provide epidemiological data for evidence-based psycho-oncological service care planning. Methods: We interviewed a representative sample of patients with different tumour entities (N = 2,141) in outpatient, inpatient and rehabilitation settings using the standardized computer-assisted Composite International Diagnostic Interview for mental disorders adapted for cancer patients (CIDI-O). Results: The overall 12-month prevalence for any mental disorder was 39.4% (95%CI: 37.3-41.5%). The following prevalence rates were diagnosed: 15.8% (95%CI: 14.3-17.4%) for anxiety disorders, 12.6% (95%CI: 11.2-13.9%) for mood disorders, 9.5% (95%CI: 8.3-10.8%) for somatoform disorders, 7.3% (95%CI: 6.2-8.4%) for nicotine abuse, 3.7% (95%CI: 3.0-4.5%) for disorders resulting from a general medical condition, 1.1% (95%CI: 0.6-1.5%) alcohol abuse or dependence and 0% eating disorders. Highest prevalence of mental disorders was found in patients with head and neck cancer, breast cancer, malignant melanoma and kidney/urinary tract cancers. Conclusions: Mental disorders are highly prevalent in cancer patients. Having shown differences regarding type and amount of mental disorders across different tumour entities, our results emphasize a different need for psycho-oncological and psychotherapeutic support leading to an appropriate allocation of direct personnel and others resources.