tbuckley/cabot-search huggingface dataset:
Effects of adjuvant exemestane versus anastrozole on bone mineral density: Two-year results of the NCIC CTG MA.27 bone companion study.
Authors: D. L. Hershman, A. M. Cheung, J. W. Chapman, J. N. Ingle, F. Ahmed, H. Hu, J. Scher, S. Leeson, C. Elliott, A. Le Maitre, L. E. Shepherd, P. E. Goss
Journal: Journal of Clinical Oncology (2011)

518 Background: In MA.27 [Exemestane (EX) vs Anastrozole (AN) for 5 years], we hypothesized EX, an irreversible steroidal aromatase inhibitor (SAI), would affect bone turnover and risk of OP less than the non-SAI AN. Methods: MA.27 B recruited 497 patients (pts) from the main study into 2 cohorts: pts without OP (n=300; Group A) and pts with OP (n=197; Group B). Both groups received 800 IU Vit. D and 1000mg Calcium daily and Group B had additional bisphosphonate. Total hip and L1-L4 (postero-anterior) spine BMD were measured yearly for 5 years, with censoring of Group A if OP developed. Where possible, centrally reviewed BMD, and left hip data were used. Lunar data in g/cm2was converted to hologic equivalent. The co-primary objectives for Groups A and B were to determine differences in hip and spine BMD at 2 years. Two-sided Bonferroni adjusted Mann-Whitney tests were used to examine per person + change in BMD from baseline to 2 years (below, p<=0.025 for 5+ significance) and -t-tests, for treatment arm 6 and 12 month differences from baseline in serum P1NP and N-telopeptide. Results: Group A (n=287 eligible pts) and Group B (n=184 eligible pts) had the following results (shown in the table). There were no significant changes in bone turnover markers at 6 and 12 months. For women without OP, the group mean spine BMD change was 0.79+ on EX compared to −3.72+ on AN (p=0.05). Conclusions: In women without OP and not on bisphosphonate therapy, there is less early bone loss at the hip with adjuvant EX than with AN at year 1. For women with OP, bisphosphonate, calcium and vitamin D increased BMD despite AI therapy at one and two years. Percent change in patient BMD g/cm2. Exemestane Anastrozole N Mean % (95% CI) N Mean % (95% CI) P value At 1 year Hip Group A 99 -0.62 (-1.48; 0.23) 114 -1.66 (-2.73; -0.54) 0.007 Group B 64 0.61 (-1.81; 3.04) 66 0.83 (-0.16; 1.82) 0.23 L spine Group A 102 -0.59 (-1.73; 0.54) 116 -1.88 (-3.06; -0.7) 0.32 Group B 69 3.75 (2.13; 5.36) 66 2.6 (1.24; 3.96) 0.67 At 2 years Hip Group A 83 -1.93 (-2.93; -0.93) 79 -2.47 (-4.02; -0.92) 0.13 Group B 61 2.09 (-1.45; 5.63) 54 0.09 (-3.64; 3.82) 0.35 L spine Group A 87 -0.92 (-2.35; 0.5) 77 -2.39 (-3.77; -1.01) 0.08 Group B 63 2.11 (-0.84; 5.06) 57 3.72 (1.54; 5.89) 0.26
A phase II randomized trial of lapatinib with either vinorelbine or capecitabine as first- and second-line therapy for HER2 overexpressing metastatic breast cancer (MBC).
Authors: Christos A. Papadimitriou, Tomasz Sarosiek, Joanna Pikiel, Boguslawa Karaszewska, Christoph Salat, Christian Caglevic, Piotr Potemski, Etienne Brain, Kathryn Jane Briggs, Michelle DeSilvio, Luca Marini, Wolfgang Janni
Journal: Journal of Clinical Oncology (2013)

516 Background: Lapatinib (L) is approved for the treatment of human epidermal growth factor receptor 2 (HER2) positive MBC in combination with capecitabine (C) following progression after trastuzumab, anthracyclines and taxanes. Vinorelbine (V) is an important chemotherapy option in MBC. This randomized, open-label, multicenter phase II study (NCT01013740) evaluated the efficacy and safety of L with either V or C in women with HER2+ MBC. The analysis of progression-free survival (PFS) and safety showed comparable rates of efficacy and tolerability between the 2 arms (Janni et al, SABCS 2012). Here we report the results of the overall survival (OS) and crossover analyses. Methods: Patients with MBC who had received ≤1 chemotherapy regimen in the metastatic setting were randomized 2:1 to either L 1250 mg orally once daily (QD) continuously + V 20 mg/m 2 intravenously on days 1 and 8, every 3 weeks, or L 1250 mg orally QD continuously + C 2000 mg/m 2 /day orally in 2 doses, 12 hours apart on days 1-14 every 3 weeks. Patients were stratified by prior receipt of therapy for MBC and site of metastatic disease. The primary endpoint was PFS. Other endpoints included OS, overall response rate and safety. Patients progressing on one treatment arm were given the option of crossover to the other arm. All analyses were conducted with a descriptive intent only. The control arm of L+C was included in the study design to validate the patient population and lend support to the activity of L+V. Results: 112 patients were randomized in the study; 37 to the L+C arm and 75 to the L+V arm. The median OS in the L+C arm was 19.4 months [95% CI: 16.4-27.2] and 24.3 months [95% CI: 16.4-NE] in the L+V arm. At the time of analysis 42 patients had crossed over; 29 patients to L+C and 13 to L+V. Median PFS after crossover was 4 months [95% CI: 2.1-5.8] in the L+C arm and 3.2 months [95% CI: 1.7-5.1] in the L+V arm. Conclusions: L+V has shown consistent median OS with that reported in the pivotal study of L+C. The exploratory analysis of patients retreated with L after progression on L supports the biological rationale for maintaining HER2 suppression in HER2+ patients with progression on prior lines of anti-HER2 agents. Clinical trial information: NCT01013740.
Myeloma (MM) after autologous transplant (AutoHCT): Biochemical versus clinical progression.
Authors: R. F. Cornell, V. Singh, S. Devata, A. A. Saad, J. M. Palmer, P. Hari
Journal: Journal of Clinical Oncology (2011)

e18575 Background: Maintenance therapy after AutoHCT improves progression free but not overall survival in MM. Close monitoring and preemptive treatment at biochemical progression may delay clinical relapse of MM while reducing overall drug exposure. However the interval from biochemical to clinical progression is not generally studied, and limits the feasibility of such a preemptive strategy. Methods: In order to analyze patterns of relapse after AutoHCT, we studied biochemical and clinical relapse in 97 AutoHCT recipients with MM. Patients (pts) were monitored with q 3mo serum free light chain, protein electrophoresis and annual bone studies interpreted by standard IMWG criteria. Results: Median age was 60 (47-77), 61% male and 20% with light chain myeloma. Characteristics of the upfront transplant cohort (69%) at diagnosis: International Staging System (ISS) Stage III in 41%, median values of beta2-microglobin (b2m) 3.26, albumin 3.8, high-risk cytogenetics in 35%. Recipients of salvage AutoHCT ( 31%) had the following characteristics at diagnosis: median b2m 3.94, albumin 3.7, high-risk cytogenetics in 38% and ISS stage III in 40%. Thirty patients relapsed after AutoHCT at a median of 18 months. Of the 24 patients with intact immunoglobulin MM, 62% had early biochemical progression preceding clinical relapse by a median of 9.5 mo. Biochemical progression was light chain only in 8 (33%), electrophoretic (M-spike) only in 5 (21%) and simultaneous light chain and M spike in 2 (8%). Six patients (25%) clinically relapsed at the same time as biochemical progression. Three patients relapsed or experienced mortality at the first 3mo evaluation. Median time from biochemical to clinical relapse was 9mo for light chain only group, 10 mo for the M-spike and 9.5 mo for simultaneous group. In 6 relapsed pts with light chain MM, 3 had light chain progression preceding clinical. Conclusions: Majority of intact Ig MM patients experience biochemical progression 9-10 mo prior to clinically active disease. This time point is an opportunity for intervention with preemptive anti-MM therapy aimed at preventing clinical relapse and prolonging time to retreatment. Such approaches should be compared with routine maintenance.
The level of soluble programmed death ligand-1 in lung cancer: An exploratory biomarker study.
Authors: Rui Geng, Li Pan, Sutang Guo, Jiexian Jing, Xu Dong Zhang, Xia Song
Journal: Journal of Clinical Oncology (2016)

249 Background: A new approach to immunotherapy based on programmed death 1 (PD-1) and programmed death ligand-1 (PD-L1) pathway represents a remarkable innovation in lung cancer treatment. There is growing evidence that lung cancer cells exploit the PD-L1 to cause local immune-suppression. The aim of this prospective study was to investigate the prevalence and prognostic roles of soluble PD-L1 (sPD-L1) protein in the blood of patients with lung cancer. Methods: A total of 159 patients with lung cancer who were diagnosed by histopathology or cytopathology between July 2013 and October 2015 were enrolled. Blood samples plasma were collected at the time of diagnosis. 85 samples of healthy subjects matching in sex and age from the Health care Center of the hospital were also studied as control. The level of sPD-L1 protein in the blood was measured using an enzyme-linked immunosorbent assay (ELISA). 64 cases of patients with lung cancer who were treated with platinum based chemotherapy for 4-6 cycles were followed up. The median follow-up duration since the time of diagnosis was 18.6 months (range, 4-26.6 months). The associations between the level of sPD-L1 expression and clinicopathologic features and prognosis were statistically analyzed. Results: Expression of sPD-L1 in patients with lung cancer was significantly up-regulated compared with health people (P &lt; 0.001). A cut-off value of 2.37ng/ml was distinguished in patients according to Receiver operating characteristic curve (ROC). The expression of sPD-L1 was associated with abdominal organ metastasis (P = 0.015). A high sPD-L1 expression had a worse prognosis than a low expression in patients (13.4 months vs 19.8 months, P = 0.001). Conclusions: Our results indicated that plasma sPD-L1 protein was elevated in patients with lung cancer and was associated with a poor prognosis. Plasma sPD-L1 protein is a potent predicting biomarker in lung cancer and may play a pivotal role in tumor immune evasion.
Clinical outcomes of three-dimensional versus two-dimensional laparoscopic surgery for gastric cancer: A single center, prospective, randomized trial—An interim report.
Authors: Jian-Xian Lin, Changming Huang, Chaohui Zheng, Ping Li, Jianwei Xie, Jiabin Wang, Jun Lu, Qiyue Chen, Longlong Cao, Mi Lin
Journal: Journal of Clinical Oncology (2016)

53 Background: Laparoscopic surgery is more challenging compared with open surgery, in part because surgeons must operate in three-dimensional (3D) space through a two-dimensional (2D) projection on a monitor, which results in loss of depth perception. To counter this problem, 3D imaging for laparoscopic was developed. However, there is limited evidence regarding its efficacy and safety. We therefore conducted a phase III, single center, prospective, randomized study to validate the efficacy and safety of 3D laparoscopic gastrectomy for gastric cancer compared with 2D laparoscopic surgery. Methods: The eligible criteria were pathologically-proven adenocarcinoma, 18 to 75 years of age, no history of other malignant tumor, chemotherapy, or radiotherapy, and clinical stage T1-4aN0-3M0 with R0 resection. The primary end point was to determine whether there is a difference in operation time between the two groups. The morbidity and mortality were compared to evaluate the safety of this trial. Results: A total of 196 patients were randomized (97 cases in 3D Group; 99 cases in 2D Group) between January 1, 2015 and August 31, 2015. There were no significant differences between the two groups in clinicopathological characteristics. The mean number of retrieved lymph nodes was similar in the 3D and 2D groups (35.6±14.1 vs. 36.1±13.5 per case). The operation time was similar in 3D and 2D groups (183.6±34.1 vs. 180.0±37.2 min). The blood loss in 3D Group was 59.6±45.6 ml, which was less than that in 2D Group (69.9±62.4 ml) without statistically different. There were no significant differences in times to resumption of activities, first flatus, resumption of soft diet, and post-operative stay between the two groups (P &gt; 0.05, respectively). The morbidity of the 3D and 2D groups were 21.6% (21/97) and 17.1% (17/99), respectively (P = 0.428). There was no patient died during the postoperative stay in both groups. Conclusions: 3D laparoscopic gastrectomy is a safe and feasible procedure for gastric cancer. However, compared with 2D group, there was no so much benefit from 3D laparoscopic gastrectomy for gastric cancer. Clinical trial information: NCT02327481.
Patient-reported sexual and urinary function after open and robotic radical prostatectomy.
Authors: Joseph C. Klink, Jianbo Li, Eric A. Klein, Jihad Kaouk, J. Stephen Jones, Andrew J. Stephenson
Journal: Journal of Clinical Oncology (2013)

120 Background: Urinary continence (UC) and sexual function (SF) may be impacted differently after robotic-assisted laparoscopic (RALRP) versus open (ORP) radical prostatectomy. We compared UC and SF among patients treated by RALRP and ORP at a high-volume hospital who were enrolled in a prospective, longitudinal quality-of-life (QOL) protocol. Methods: Between 2007 and 2012, 516 patients treated by active surveillance, brachytherapy, cryotherapy, RALRP, and ORP were enrolled in a QOL protocol at our institution. The focus of this study is 361 patients who were treated by RALRP (N=190) and ORP (N=171). Functional outcomes were assessed at baseline and at 1, 3, 6, 12, and 24 months using a validated QOL instrument (Giesler RB et al. Qual Life Res 2000). SF was assessed by adding the scores from questions on the quality and frequency of erections. UC was assessed by adding the scores from three questions about the frequency and quantity of incontinence and pad usage. Wilcoxon rank sum test and linear regression multivariable analysis were used to assess SF and UC at each time point. Results: Treatment groups were similar in age, PSA, clinical stage, Gleason grade, BMI, baseline UC and SF scores and baseline PDE-5 inhibitor use (all P &gt; 0.05), but the RALRP patients were slightly older (60 vs 61 years, p=0.04) and had larger prostates (38 vs 44 grams, p=0.001). On multivariate analysis, UC was worse in the RALRP cohort at 1 month (12.0 vs 10.9, P = 0.02), 3 months (9.9 vs 8.5, P = 0.01), and 6 months (8.1 vs 6.8, P=0.01) but was similar at 12 and 24 months (all P &gt; 0.2). SF was similar between both RALRP and ORP at all time points (all P &gt; 0.3). At 24 months, UC for RALRP and ORP was 7.1 vs. 6.4, respectively which was not significant in multivariable analysis (P = 0.5). Likewise, SF for RALRP and ORP was 5.3 vs. 6.2 (multivariable P = 0.9). On repeated measures analysis there was no difference between the groups in UC or SF (P=0.4 and 0.5, respectively). Conclusions: Prospectively collected, patient reported QOL endpoints for SF are similar after RALRP and ORP at all time points in a high-volume hospital. Final UC is similar between both techniques, although RALRP patients may experience a slightly slower return to continence.
Subgroup analysis of patients enrolled in the United States in the CORRECT phase 3 trial of the multikinase inhibitor regorafenib (REG) in metastatic colorectal cancer (mCRC).
Authors: George P. Kim, Eric Van Cutsem, Heinz-Josef Lenz, Udit N. Verma, Marc Saltzman, Jyotsna Fuloria, Ali Khojasteh, Martin Wiesenfeld, Frank Cihon, Andrea Wagner, Axel Grothey
Journal: Journal of Clinical Oncology (2015)

e14649 Background: The CORRECT trial (NCT01103323) showed that REG improves overall survival (OS) vs placebo (PBO) in patients with mCRC who failed approved therapies (OS HR 0.77; 1-sided p = 0.0052; Grothey 2013). A total of 760 patients were randomized to REG (n = 505) or PBO (n = 255) in more than 100 centers across North America, Europe, Asia, and Australia. We conducted a post-hoc exploratory subgroup analysis of the 83 (11%) patients from 18 US centers. Methods: Eligible patients had an ECOG PS ≤ 1 and had received approved therapies, including a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab, and if KRAS wild-type cetuximab and/or panitumumab. Data from the overall cohort, including US patients, are provided for perspective. Descriptive statistics are shown. Results: Of the 83 US patients, 36 (43%) were randomized to PBO and 47 (57%) to REG. Baseline characteristics of the US group were consistent with the overall cohort: median age in the US was 58 yr (range, 34 – 85) vs 61 (22 – 85) overall, 49% of US patients were ECOG PS1 (vs 46%), and 46% received ≤ 3 treatments for mCRC (vs 52%). KRAS status mutant/wild-type was 57%/34% in the US vs 57%/39% overall. All patients in the trial had prior bevacizumab and 57% of US patients also had prior cetuximab and/or panitumumab (vs 51% overall). However, higher proportion of patients in the US were Black (11% vs 2%), KRAS status unknown (10% vs 4%), and had colon as the primary disease site (82% vs 65%). Mean percentages of planned REG dose were similar (76% US vs 79% overall) and mean REG treatment duration was 3.1 mos in US vs 2.8 mos overall. Rates of dose modifications REG/PBO were 87%/47% in the US vs 76%/38% overall and grade ≥ 3 adverse events REG/PBO were 74%/64% vs 78%/49%, respectively. Based on 44 total death events, the HR for OS in the US subgroup was 0.46 (95%CI 0.25 – 0.84) favoring REG; median OS was 4.7 mos for PBO, but could not be estimated for REG due to censored data. However, this analysis was based on a relatively small sample size and event count. Conclusions: Patients treated in the CORRECT study in the US appear similar to the overall cohort and results are generally consistent with the overall findings of the trial. Clinical trial information: NCT01103323.
EGFR tyrosine kinase inhibitors in the treatment of advanced non-small cell lung cancer
Authors: D. M. Kowalski, M. Krzakowski, P. Jaskiewicz, A. Janowicz-Zebrowska, M. Glogowski
Journal: Journal of Clinical Oncology (2008)

19117 Background: Treatment of patients with advanced and inoperable non-small cell lung cancer (NSCLC) in advanced inoperable stage aims to improve their quality of life and to prolong their life. The current first-line treatment for these patients includes palliative chemotherapy, radiotherapy, intensive symptomatic care and recently, molecular-targeted therapy. Methods: Our study aimed to evaluate clinical outcome of patients with advanced NSCLC treated with erlotinib. Between September 2005 and April 2007, 53 patients were enrolled. Patients with inoperable NSCLC confirmed pathologically, aged higher than 18 years, failure of platinum-based chemotherapy, Karnosfsky score 70–100 and normal hematological and biochemical tests were included. Retrospective analysis was performed on 53 patients (F/M 23/30) with mean age 56.9 (range 33–74). Karnofsky scores of 70, 80, 90 and 100 were found in 3 (5.7%), 11 (20.8%), 18 (33.9%) and 21 (39.6%), respectively. Smoking history was found in 24 (45%) patients. Clinical stages of NSCLC were as follows: II - 2 (3.8%), III - 18 (33.9%) and IV - 33 (62.3%). Second - line chemotherapy was used in 23 (43%) patients and in 37 (69.8%) patients received radiotherapy. Results: All patients were treated orally with 150 mg/d erlotinib with modifications as recomended. Average treatment time using erlotinib was 2.7 months (1–16). Improvement in physical activity was observed in 11 (20.8%) patients. Median time to progression was 2.9 months (1–16). Complete response was shown in 2 (3.8%) patients, stable disease were noted in 14 (26.4%) patients, progression was found in 30 (56.6%) during the treatment (response was not evaluated in 7 patients). No partial response was noted. Skin rash are most common adverse effect grade: 0, I, II and III was found in 25 (47.2%), 18 (33.9%), 9 (17%) and 1 (1.9%) of patients, respectively. In 7 (13.2%) of patients this side-effect required local treatment. Additionally, in 3 (5.7%) patients diarrhea was also observed. Conclusions: Treatment with erlotinib was generally well tolerated and based on our findings it may be of benefit in patients with advanced NSCLC after prior platinum-based chemotherapy. However, putative factors related to prediction of clinical response to treatment should be more extensively studied. No significant financial relationships to disclose.
Age-related variations: A retrospective analysis of 851 prospectively collected patient samples to determine the benefit of combining combinatorial protein biomarker assay for risk assessment in women with dense breast.
Authors: David Emery Reese, Michael Silver, Meredith C. Henderson, Sherri Borman, Christa Corn, Rao Mulpuri, Kasey Benson
Journal: Journal of Clinical Oncology (2015)

27 Background: Clinicians often experience difficulty in differentiating benign lesions from invasive breast cancers in patients designated as dense breast. A major limitation of radiological breast cancer screening methods involves a decrease in sensitivity and specificity in women with dense breast. Thus, we sought to test whether Klarify Breast, a combinatorial protein-based biomarker panel could improve early detection of significant breast lesions in a controlled fashion. Clearly, a diagnostic assay that would provide biochemical evidence in the patient’s clinical course is greatly needed. Methods: We have conducted two independent, multi-center, prospective clinical trials to establish the clinical validity of Klarify Breast – an assay that uses multiple Serum Protein Biomarkers (SPBs), Tumor-Associated Autoantibodies (TAAbs), patient specific clinical data and develop a score to differentiate patients with benign breast disease from those with invasive breast cancer. Independent panels of biomarkers and associated algorithms were developed using prospectively collected samples from women under age 50 (n = 351) and from women ages 25-75 (n = 500). Here, we present the benefit of integrating the results of Klarify Breast test with patient imaging to best assess risk in women with dense breast. Results: While performance of the assay was somewhat age dependent (women under the age of 50 demonstrated a higher sensitivity and specificity than women over the age of 50). Here we present data that both groups of women clearly benefit from the addition of a biomarker assay combined with standard of care imaging in identifying invasive breast lesions. Conclusions: Clearly, in women with dense breast, where radiologic studies alone do not permit full assessment in women with a dense breast finding. The biomarker test here, comprised of TAAbs and SPBs, offers a clear advantage in terms of NPV, PPV, Sensitivity and specificity. The results argue strongly for the use of appropriate biomarkers to augment imaging based breast cancer screening in women with dense breast or those who are at high risk. Clinical trial information: NCT01839045, NCT02078570.