tbuckley/cabot-search huggingface dataset:
Improving clinical prognostic categories beyond performance status: Enhancing accuracy in survival prediction with a three-item patient-reported outcome (PRO) index from the LCSS in lung cancer and mesothelioma.
Authors: Richard J. Gralla, Patricia J Hollen, James Thomas Symanowski, Pavlos Msaouel, Nina Kohn, Martin Lesser
Journal: Journal of Clinical Oncology (2014)

8065 Background: Accurate prediction of survival of patient groups is required for appropriate trial design. Performance status (PS) is often used both for trial eligibility and for stratification. Three global PRO items (quality of life, activity level, symptom distress) from the LCSS (Lung Cancer Symptom Scale) apply to all patients. We tested whether an index of the 3 items would predict survival in patients with lung cancer or mesothelioma, and if major differences were found within the same PS groups (with either ECOG or KPS). Methods: This study analyzed data from the prospective mesothelioma EMPHACIS study comparing pemetrexed + cisplatin (DDP) with DDP in 444 patients, and from the prospective AP-QL trial of 622 patients treated with docetaxel + DDP or carboplatin. Each of the 3 global items at baseline in NSCLC predicted improved survival if the value was above the median (positive factor) compared with below (negative factor) (p < 0.003). An index was created using the number of negative factors, 0 to 3. The LCSS can be completed in < 3 minutes. Results: As seen in the table, survival varied significantly for those with 0 vs 3 negative factors and for 1 or 2 vs 3 factors, at baseline in both NSCLC and mesothelioma. When we tested only for the subgroup of patients with ECOG PS =1 in NSCLC, or for KPS 80-90 (similar to ECOG 1) in mesothelioma, major survival differences were still identified by the PRO index. Conclusions: This analysis demonstrates that large survival differences exist within the same PS groups for both ECOG 1 and KPS 80-90. The 3-item PRO index can be rapidly and inexpensively obtained and can assist in more accurate stratification of patients in randomized trials in thoracic malignancies. # of negative PRO factors Med survival: months – all patients Median survival: months KPS 80-90 Survival: 1 year Survival: 1 year Mesothelioma (N = 444) (n = 368) All patients KPS 80- 90 0 14.6 ** 12.9 ** 61% 59% 1,2 10.8 * 10.1 * 45% 42% 3 7.4 7.6 26% 30% NSCLC (N = 622) ECOG 1 (n = 413) All patients ECOG 1 0 16 ** 15.4 ** 64% 62% 1,2 13 * 11.5 54% 48% 3 9 9.4 38% 36% Reference group is 3 negative PRO factors. ** p < 0.001 by log-rank; * p < 0.05 by log rank.
Gemcitabine plus nab-paclitaxel use in metastatic pancreatic cancer: A study of 40 patients.
Authors: Ivan Barrera, Sabin Dragos Filimon, Jassy Meng, Tomas Kavan, Young soo Rho, Gerald Batist, Petr Kavan
Journal: Journal of Clinical Oncology (2017)

498 Background: Metastatic pancreatic adenocarcinoma (mPDAC) carries a dismal prognosis, with often a poor response to treatment (Tx). Although gemcitabine with nab-paclitaxel (GnP) is now a standard 1st-line (1L) Tx in mPDAC, provincial policies limit its use. To understand the implications of the restriction, this real-life study was conducted. Methods: A historical prospective data was compiled using the local electronic medical record (Endovault Oncology v3.0, NY) at the Jewish General Hospital-McGill. All patients (pts) diagnosed with mPDAC that received GnP from 2013-2016 were identified. Demographics and Tx data was obtained. Primary objective was to evaluate tolerability in all lines of Tx [grade &gt;2 CTCAE v4.03, mean Tx delay (mTxd)]. Secondary objectives were Tx attrition and outcomes [RECIST 1.1, complete response (CR), stable disease (SD) and progression disease (PD)]. Results: Of the 40 pts (female 60%, median age 64.3), 25 (62.5%) had primary at the head of the pancreas and 30 (75%) liver metastasis. 1L Tx: GnP 24 (60%), FOLFIRINOX 10 (FFX, 25%), Gemcitabine 5 (Gc, 12.5%) and FOLFOX 1 (2.5%). 70% of both FFX and Gc pts had grade 2 peripheral neuropathy (PN), neutropenia (NEUT) and fatigue. Half GnP pts had grade 2 NEUT and fatigue. mTxd in GnP, FFX and Gc were 7, 14 and 7 days. All FFX and Gc pts had PD. GnP cohort had 1 CR and 7 SD. 2L Tx was in 22 (55%): GnP 13 (59.5%), FFX 3 (13.5%), Capecitabine 2 (9%), FOLFOX 2 (9%) and Gc (9%). FFX pts 66.6% had grade 3 fatigue. GnP pts had grade 2 NEUT, PN and fatigue in 53.8%, 15.3% and 46.2%. mTxd were GnP 14 days and FFX 14 days. Except 1 SD, all FFX pts had PD. GnP pts had 1 CR, 6 SD, and 6 PD. All pts on Capecitabine, FOLFOX and Gc had PD. 3L Tx was in 6 (15%): 3 GnP (50%) and 3 on clinical trials (50%). All pts had PD and &lt; 3 cycles. In 1L FFX pts, 7/10 and 3/6 went on to receive GnP in 2L and 3L. All 1L Gc pts had 2L GnP. Only 3 pts and 1 pt from 1L GnP pts went on to receive 2L and 3L Tx. Conclusions: Due to access limitations to GnP, its use was likely reserved for poor performance status pts. Instead, 1L FFX was used when possible. 1L FFX pts received more Tx lines due to initial pt selection. Further studies are needed in broader populations to evaluate optimal 1L Tx selection accounting for expected attrition and overall survival.
Genetic variants associated with toxicity-related discontinuation of adjuvant aromatase inhibitor (AI) therapy.
Authors: Norah Lynn Henry, Todd C. Skaar, Jessica Dantzer, Lang Li, Anne T Nguyen, James M. Rae, Zeruesenay Desta, Steffi Oesterreich, Santosh Philips, Janet S Carpenter, Anna Maria Storniolo, Vered Stearns, Daniel F. Hayes, David A. Flockhart
Journal: Journal of Clinical Oncology (2012)

525 Background: Discontinuation of adjuvant AI therapy due to intolerable symptoms occurs in up to 30% of patients. Predictors of which patients will be unable to tolerate these medications have not been defined. We hypothesized that inherited variants in candidate genes are associated with treatment discontinuation because of AI-associated toxicity. Methods: We prospectively evaluated reasons for treatment discontinuation in women with hormone receptor positive breast cancer initiating adjuvant AI through a multicenter, prospective, randomized clinical trial of exemestane (exe) versus letrozole (let). Using multiple genetic models, we evaluated potential associations between 136 single nucleotide polymorphisms (SNP) in 24 candidate genes, selected a priori, primarily with roles in estrogen metabolism and signaling, and discontinuation of AI therapy because of toxicity. To account for multiple comparisons, statistical significance was defined as p&lt;0.0003. Results: Of the 467 enrolled patients who had available germ line DNA, 152 (33%) discontinued AI therapy because of toxicity. After adjusting for multiple covariates, multivariable analyses revealed that two inherited genetic variants in ESR1, which encodes estrogen receptor (ER) alpha, and one in CYP19A1 were associated with increased risk of discontinuation of AI therapy because of toxicity (Table). A variant in NCOR1 (ER co-repressor) was associated with decreased risk of discontinuation of letrozole because of toxicity. Conclusions: Variants in genes involved in estrogen metabolism and signaling may be associated with toxicity of AI therapy. [Table: see text]
Next-generation sequencing to identify mutations that may predict outcome after allogeneic stem cell transplantation for AML.
Authors: Marlise Rachael Luskin, Martin Carroll, Jennifer J. Morrissette, Robert D Daber, Noelle V. Frey, Alison W. Loren, Elizabeth O. Hexner, James K. Mangan, Alexander E. Perl, Caroline E Sloan, Edward Allen Stadtmauer, Adam Bagg, Selina M. Luger, David L. Porter, Ran Reshef
Journal: Journal of Clinical Oncology (2014)

7043 Background: Relapse is the most common reason for failure of allogeneic stem cell transplant (SCT). Identifying patients at increased relapse risk is crucial for improving outcomes. Prognostic somatic mutations have been identified in AML but their prognostic value after SCT is unknown. We hypothesize that next generation sequencing (NGS) can predict SCT outcome in AML. Methods: We performed NGS for 33 hematologic malignancy associated genes in 62 adult patients treated with SCT for de novo AML (2003-2013). Relapse free survival (RFS) was compared by Cox regression with adjustment for cytogenetic risk, conditioning intensity, donor type and graft source. Results: At least 1 mutation was identified in 56 (90%) patients (median 2, range 0-6) including 35 of 36 (97%) patients with intermediate cytogenetics (median 3, range 0-6). Among patients with intermediate cytogenetics transplanted in CR, poor prognostic mutations were found in 9 of 15 FLT3ITD negative patients (2 DNMT3A; 3 DNMT3A + IDH; 1 DNMT3A + TET2 + IDH2; 1 TET2; 1 TET2 + PHF6; 1 ASXL1); among FLT3ITD positive patients, 4 of 9 were additionally DNMT3A mutant which may confer added risk. Among patients with favorable cytogenetics transplanted in CR2, 2 of 8 patients had kit mutations; there were no mutations in DNMT3A, IDH, ASXL1, TET2, or PHF6. Among patients with unfavorable cytogenetics, 4 of 13 had additional poor prognostic mutations (1 FLT3ITD +TET2, 1 TET2, 2 TP53). In FLT3ITD negative patients with any cytogenetic risk, DNMT3A mutant status significantly worsened RFS (adjusted HR=4.76 [95% CI 1.34-16.9]; p=0.016). Conclusions: NGS identifies a high frequency of potentially prognostic mutations in SCT patients. Mutant DNMT3A may negatively impact prognosis in FLT3ITD negative AML post SCT. NGS testing of a larger cohort is warranted and underway. Identifying patients at high risk for relapse by molecular profiling may allow early intervention. Gene Total (VUS) FLT3-ITD 19 (0) DNMT3A 17 (1) NPM1 19 (0) ATM1 10 (7) ASXL1 7 (4) TET2 8 (2) RUNX1 8 (3) IDH1 5 (0) IDH2 7 (1) KIT 6 (1) NRAS 6 (0) WT1 4 (0) PHF6 1 (0) TP53 2 (0) FLT3-TKD 2 (0) PTPN1 5 (0) Abbreviations: VUS, variant of uncertain significance.
A phase III trial of ganitumab (GAN, AMG 479) with gemcitabine (G) as first-line treatment (tx) in patients (pts) with metastatic pancreatic cancer (MPC): An analysis of safety from the GAMMA trial (GEM and AMG 479 in Metastatic Adenocarcinoma of the Pancreas).
Authors: Charles S. Fuchs, Masafumi Ikeda, Gyorgy Bodoky, Takuji Okusaka, Shinichi Ohkawa, Nobumasa Mizuno, Anna Swieboda-Sadlej, Alberto F. Sobrero, Vincent Haddad, Jesse S. McGreivy
Journal: Journal of Clinical Oncology (2012)

4042 Background: GAN is an investigational, fully human, monoclonal antibody inhibitor of IGF1R. GAMMA is assessing the safety and efficacy of GAN plus G as first-line tx in MPC pts (ClinicalTrials.gov ID: NCT01231347). Methods: This is an ongoing, global, phase III, double-blind study. Pts are randomized 2:2:1 to receive placebo, GAN 12 mg/kg, or GAN 20 mg/kg (IV; days 1 and 15 Q28D) with G 1000 mg/m 2 (IV; days 1, 8, and 15 Q28D). The planned sample size is 825. Primary endpoint: overall survival. Key secondary endpoints: progression-free survival, 1-year survival rate, patient-reported outcomes, and safety. This study includes multiple planned safety analyses conducted by an independent Data Monitoring Committee (DMC). The current predefined safety analyses occurred when 150pts received ≥ 1 cycle of tx. Results: As of Sep 16, 2011, 207 pts are included in this aggregate analysis: 50% male; median age, 63 yrs (range 36-83); ECOG PS 0/1, 50%/50%. Of the 207 pts, 204 pts received study tx, and 61 pts ended study tx. Most frequent adverse events (AE) are shown (table). Ten pts (5%) died during or within 30 days of the end of tx. Seven events were attributed to or associated with disease progression. One event of cardiac failure was reported to be possibly tx related. Pulmonary embolism was suspected but not confirmed. Conclusions: The GAMMA study continues per protocol. The only grade 3/4 AE occurring in more than 5% of patients to date is neutropenia. [Table: see text]
Preliminary experience on treating advanced nasopharyngeal carcinoma (NPC) affecting/abutting neurological structures with induction chemotherapy followed by concurrent chemo-radiation with accelerated fractionation
Authors: W. M. Sze, A. W. M. Lee, M. Tong, C. Ng, I. Soong, K. Chan, R. Yeung, T. K. Yau
Journal: Journal of Clinical Oncology (2004)

5525 Background: To study the possibility of improving treatment tolerance and outcome for NPC with extensive infiltration affecting/ abutting neurological structures by induction chemotherapy followed by concurrent chemo-radiation with accelerated fractionation. Methods: During April 2001 to Feb 2003, 33 NPC patients with such ominous infiltration were treated with this strategy. Ninty-four percent of patients had UICC (5th edition) Stage IVA-B and 6% had Stage III disease. Thirty-two patients (97%) had undifferentiated carcinoma and only 1 patient had well differentiated squamous cell carcinoma. The chemotherapy plan included 3 cycles of Cisplatin (80 mg/m2 ) and Gemcitabine (1250 mg/m2 D1,8) for induction phase, and 2 cycles of Cisplatin (100 mg/m2 D1) for the concurrent phase. All patients were irradiated to a total dose of 70 Gy using 3-D conformal techniques and accelerated fractionation at 2 Gy per fraction, 6 daily fractions per week, throughout the whole course. Results: All patients completed the intended radiotherapy dose and the median overall treatment time was 41 days (range: 39–53). Grade ≥3 mucositis and skin reaction were observed in 82% and 21% patients, respectively. The mean weight loss during the whole course of treatment was 11% of the initial body weight. The chemotherapy toxicities and compliance are shown in table 1. With a median follow-up of 1.5 years (range: 0.6–2.3), the 2-year local failure-free, distant failure-free, progression-free and overall survival rates were 97%,76%, 73% and 76% respectively. Conclusions: The early treatment results achieved for this very poor prognostic group was very encouraging, but late toxicity has yet to be fully assessed and confirmation of therapeutic gain by prospective randomized trial is warranted. No significant financial relationships to disclose.
Erratum: Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia
Authors: Virginie J M Verhoeven, Pirro G Hysi, Robert Wojciechowski, Qiao Fan, Jeremy A Guggenheim, René Höhn, Stuart MacGregor, Alex W Hewitt, Abhishek Nag, Ching-Yu Cheng, Ekaterina Yonova-Doing, Xin Zhou, M Kamran Ikram, Gabriëlle H S Buitendijk, George McMahon, John P Kemp, Beate St Pourcain, Claire L Simpson, Kari-Matti Mäkelä, Terho Lehtimäki, Mika Kähönen, Andrew D Paterson, S Mohsen Hosseini, Hoi Suen Wong, Liang Xu, Jost B Jonas, Olavi Pärssinen, Juho Wedenoja, Shea Ping Yip, Daniel W H Ho, Chi Pui Pang, Li Jia Chen, Kathryn P Burdon, Jamie E Craig, Barbara E K Klein, Ronald Klein, Toomas Haller, Andres Metspalu, Chiea-Chuen Khor, E-Shyong Tai, Tin Aung, Eranga Vithana, Wan-Ting Tay, Veluchamy A Barathi, Peng Chen, Ruoying Li, Jiemin Liao, Yingfeng Zheng, Rick T Ong, Angela Döring, David M Evans, Nicholas J Timpson, Annemieke J M H Verkerk, Thomas Meitinger, Olli Raitakari, Felicia Hawthorne, Tim D Spector, Lennart C Karssen, Mario Pirastu, Federico Murgia, Wei Ang, Aniket Mishra, Grant W Montgomery, Craig E Pennell, Phillippa M Cumberland, Ioana Cotlarciuc, Paul Mitchell, Jie Jin Wang, Maria Schache, Sarayut Janmahasatian, Robert P Igo Jr, Jonathan H Lass, Emily Chew, Sudha K Iyengar, Theo G M F Gorgels, Igor Rudan, Caroline Hayward, Alan F Wright, Ozren Polasek, Zoran Vatavuk, James F Wilson, Brian Fleck, Tanja Zeller, Alireza Mirshahi, Christian Müller, André G Uitterlinden, Fernando Rivadeneira, Johannes R Vingerling, Albert Hofman, Ben A Oostra, Najaf Amin, Arthur A B Bergen, Yik-Ying Teo, Jugnoo S Rahi, Veronique Vitart, Cathy Williams, Paul N Baird, Tien-Yin Wong, Konrad Oexle, Norbert Pfeiffer, David A Mackey, Terri L Young, Cornelia M van Duijn, Seang-Mei Saw, Joan E Bailey-Wilson, Dwight Stambolian, Caroline C Klaver, Christopher J Hammond
Journal: Nature Genetics (2013)
Effects of exercise on cancer-related biomarkers in breast cancer survivors: An updated systematic review and meta-analysis of randomized controlled trials.
Authors: Dongwoo Kang, Ji Young Kim, Junga Lee, Justin Y Jeon
Journal: Journal of Clinical Oncology (2014)

e20691 Background: Physical activity and exercise has been identified as a curative intervention to improve physical and mental health, and even cancer prognosis, in breast cancer survivors. Though there have been many randomized clinical trials (RCTs) that attempted to prove the effect of exercise on cancer-related biomarkers, including fasting insulin level and inflammatory markers, in breast cancer survivors, the results has not been consistent. Thus, this systematic review and meta-analysis aimed to update and synthesize the biomarker outcomes from RCTs evaluating effects of structured exercise training in breast cancer survivors. Methods: MEDLINE, Cochrane-CENTRAL, EMBASE, and SPORTDiscus databases were searched until December 2013. We included RCTs that investigated whether exercise intervention can change cancer-related biomarkers in blood compared with a control group in breast cancer survivors. The primary outcome was fasting insulin level, and the secondary outcomes were fasting glucose level, insulin resistance, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), and interleukin 6 (IL-6). Pooled standard mean differences (SMD) in each outcome between intervention and control groups were calculated using a random-effects model. Results: Of 1,256 articles retrieved, 17 articles (674 participants, 14 RCTs) were included in the analysis. Overall, insulin levels significantly reduced after exercise intervention in the exercise group (SMD -0.80; 95% confidence interval [CI] −1.56 to −0.04; p=0.041) compared with the control participants. Fasting glucose level, insulin resistance, IGF-1, IGFBP-1, IGFBP-3, and IL-6 were not different between exercise and control groups after intervention. Conclusions: This meta-analysis proved that exercise can significantly reduce fasting insulin level in breast cancer survivors, which may positively affect breast cancer prognosis. Acknowledgments This research was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education(2013R1A1A2005986).
Osteonecrosis of the jaw: Long-term follow-up shows variable rate of healing
Authors: M. I. Hu, A. O. Hoff, B. B. Toth, K. Altundag, V. Guarneri, J. Cui, G. N. Hortobagyi, R. F. Gagel
Journal: Journal of Clinical Oncology (2007)

9061 Background: Osteonecrosis of the jaw (ONJ) is a rare but clinically significant disorder recently reviewed in a large retrospective study (Hoff et al, 42nd ASCO Annual Meeting 2006, Abstract #8528). A subset of the ONJ patients from that study with breast cancer or multiple myeloma (MM) was followed at the University of Texas M.D. Anderson Cancer Center (UTMDACC) dental clinic. This analysis describes the natural history of ONJ in this subset. Methods: Thirteen of 29 ONJ patients treated with intravenous bisphosphonates (IVBP) at UTMDACC and 1 treated elsewhere were evaluated in the dental clinic for &gt; 6 months (MM, n=7; breast cancer, n=7). The maximum length of exposed bone was measured at each visit. Patients received a standard regimen of conservative dental care with debridement when indicated. Results: All 14 patients received zoledronic acid (median cumulative dose 72 mg; range 24–152) and 10 also received pamidronate (median cumulative dose 1,710 mg; range 90–2,700). They were followed for a median duration of 17.1 months (range: 7.1–67.3). The mean length of exposed bone at initial evaluation was 11 mm (SD: 8.4). Each patient demonstrated fluctuating clinical courses. The lesion from baseline to the last visit progressed in 7 patients (median increase of 13 mm), remained stable in 2, regressed in 2 and resolved in 3. Persistent ONJ was seen if IVBP was stopped (n=8), decreased in frequency (n=1) or continued at the same dose/frequency (n=2). Complete resolution occurred in 3 MM patients, where IVBP was discontinued, decreased in frequency or replaced by weekly oral alendronate. Conclusions: Our experience shows that ONJ resolved in 21% but persisted in the majority of patients with a duration of up to 5 years with conservative dental care. Further studies are needed to evaluate the pathogenesis and healing process of ONJ. No significant financial relationships to disclose.
A randomised phase III trial of thalidomide plus dexamethasone versus dexamethasone in newly diagnosed multiple myeloma (E1A00): A trial coordinated by the Eastern Cooperative Oncology Group
Authors: S. V. Rajkumar, E. Blood, D. H. Vesole, R. Shepard, P. R. Greipp
Journal: Journal of Clinical Oncology (2004)

6508 Background: A phase III trial comparing thalidomide plus dexamethasone (Thal/Dex) versus dexamethasone alone (Dex) as first line therapy in newly diagnosed multiple myeloma (MM). Methods: Pts with newly diagnosed, untreated, symptomatic MM were eligible. Pts in the Thal/Dex arm (Arm A) received Thal 200 mg/day PO with Dex 40 mg on days 1–4, 9–12, and 17–20 PO. Pts in the Dex arm (Arm B) received Dex alone, at the same dose as Arm A. Therapy was repeated monthly. The primary endpoint was best response at 4 months on intention to treat basis. At 4 months pts could go off study for stem cell transplant or elect to continue therapy. Response was defined as a decrease in serum and urine monoclonal (M) protein by 50% or higher. If the serum M protein was unmeasurable, a 90% or higher decrease in urine M protein was required. Results: 207 pts were enrolled as planned: 103 randomized to Thal/Dex and 104 to Dex alone. Median age was 65 yrs. At this planned analysis, response data were available on 109 pts. Response rate with Thal/Dex was significantly higher than with Dex: 80% versus 53%, respectively, (p=0.0023; one-sided Fisher's exact test). Toxicity data is available on 192 pts. As a planned analysis, incidence rates of grade 3 or higher deep vein thrombosis (DVT), rash, bradycardia, and neuropathy and any grade 4–5 toxicity in the first 4 months were compared (Table). In this period, 14 pts died, 6 in arm A and 8 in Arm B. Grade 3 or higher cardiac ischemia occurred in 3 pts in Arm A and 2 pts in Arm B. Conclusions: Thal/Dex demonstrates superior response rates in newly diagnosed MM compared to Dex, comparable to historical results with complex intravenous regimens like VAD. Thal/Dex has higher toxicity compared to Dex, especially DVT. The use of Thal/Dex must be weighed in each pt given the higher toxicities compared to Dex alone. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene
Prognostic importance of left ventricular mechanical dyssynchrony in heart failure with preserved ejection fraction
Authors: Tor Biering‐Sørensen, Sanjiv J. Shah, Inder Anand, Nancy Sweitzer, Brian Claggett, Li Liu, Bertram Pitt, Marc A. Pfeffer, Scott D. Solomon, Amil M. Shah
Journal: European Journal of Heart Failure (2017)
Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial
Authors: Vanita R Aroda, Stephen C Bain, Bertrand Cariou, Milivoj Piletič, Ludger Rose, Mads Axelsen, Everton Rowe, J Hans DeVries
Journal: The Lancet Diabetes & Endocrinology (2017)