tbuckley/cabot-search huggingface dataset:
Impact of clinical and molecular features on risk of recurrence following curative intent resection of metastases in metastatic colorectal cancer.
Authors: Matthew E. Burge, Belinda Lee, Margaret Lee, Rachel Wong, Phillip Parente, Jayesh Desai, Ben Tran, Louise M. Nott, Jeremy David Shapiro, Gary Edward Richardson, Allan Solomon Zimet, Peter Gibbs
Journal: Journal of Clinical Oncology (2017)

785 Background: Resection of metastases with curative intent is an integral component of mCRC management. However, relapse rates are high and identifying patients most likely to benefit from this approach is of considerable importance. Among patients with mCRC, mutations (mt) in RAS and BRAF genes portent a worse prognosis. Our hypothesis, therefore, is that patients harbouring these mutations may have a higher relapse rate after resection of metastases. We also wished to analyse clinical predictors of relapse, including site of metastases. Methods: We interrogated the TRACC database of patients undergoing resection with curative intent who had mutation status available. The frequency of RAS and BRAF mt was established and their association with clinical parameters determined. Relapse free (RFS) and overall survival (OS), from the date of resection, was estimated for the mt and wild type (wt) groups using the Kaplan Meier method. Multivariate analysis is planned to investigate factors associated with RFS, including stage of the primary tumour, synchronous metastases, site and number of metastases, CEA, peri-operative chemotherapy use, site of the primary (left v right) and RAS and BRAF mutation status. Results: 188 patients were identified. 89 were KRAS/BRAF wt, 92 KRAS mt and 7 BRAF mt. 40% had presented with metastatic disease and 27% had a right sided primary. 76%, 22% and 2% underwent resection of liver, lung or both metastases. Microscopic resection margin was involved in 6%. Resection was performed prior to any chemotherapy in 48%. No difference was seen in relapse free or overall survival between the mt and wt groups. Conclusions: We found no difference in relapse free or overall survival by mutation subgroup suggesting this should not influence suitability for curative intent resection, but analyses is planned on a much larger cohort once data is available. A multivariate analysis, adjusting for important prognostic variables, is planned.
Comparative effectiveness of biological therapies on improvements in quality of life in patients with psoriasis
Authors: I.Y.K. Iskandar, D.M. Ashcroft, R.B. Warren, M. Lunt, K. McElhone, C.H. Smith, N.J. Reynolds, C.E.M. Griffiths
Journal: British Journal of Dermatology (2017)

Evidence of the comparative effectiveness of biological therapies for psoriasis on health-related quality of life (HRQoL) in routine clinical practice is limited.To examine the comparative effectiveness of adalimumab, etanercept and ustekinumab on HRQoL in patients with psoriasis, and to identify potential predictors for improved HRQoL.This was a prospective cohort study in which changes in HRQoL were assessed using the Dermatology Life Quality Index (DLQI) and EuroQoL-5D (EQ-5D) at 6 and 12 months. Multivariable regression models were developed to identify factors associated with achieving a DLQI of 0/1 and improvements in the EQ-5D utility score.In total, 2152 patients with psoriasis were included, with 1239 patients on adalimumab, 517 on etanercept and 396 on ustekinumab; 81% were biologic naïve. For the entire cohort, the median (interquartile range) DLQI and EQ-5D improved from 18 (13-24) and 0·73 (0·69-0·80) at baseline to 2 (0-7) and 0·85 (0·69-1·00) at 6 months, respectively (P < 0·001). Similar improvements were achieved at 12 months. At 12 months, multivariable regression modelling showed that female sex, multiple comorbidities, smoking and a higher DLQI or a lower EQ-5D utility score at baseline predicted a lower likelihood of achieving a DLQI of 0/1 or improvement in the EQ-5D. Compared with adalimumab, patients receiving etanercept, but not ustekinumab, were less likely to achieve a DLQI of 0/1. There was no significant difference between the biological therapies in EQ-5D improvement.In routine clinical practice biological therapies produce marked improvement in HRQoL, which is influenced by the choice of biological therapy, baseline impairment in HRQoL, lifestyle characteristics and comorbidities. These findings should help inform selection of optimal biological therapy for patients related to improvements in HRQoL.
Case 9-2017
Authors: Amulya Nagarur, Lloyd Axelrod, Anand S. Dighe
Journal: New England Journal of Medicine (2017)

A 27-year-old woman presented with nausea, vomiting, and confusion. She was unable to answer questions and had a blood pressure of 73/54 mm Hg; laboratory testing revealed a blood sodium level of 104 mmol per liter. Diagnostic tests were performed.
Cell-free tumor DNA and <i>TERT</i> promoter mutations in bladder cancer.
Authors: Franklin W. Huang, Mikael L. Rinne, Kevin T. Lundgren, Stephanie Anne Mullane, Irene Moreno, Sarah Reed, Greg Gydush, Viktor Adalsteinsson, Jesse Novak, William C. Hahn, Sabina Signoretti, Toni K. Choueiri, Levi A. Garraway, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2017)

353 Background: Currently, there are no FDA-approved blood biomarkers for the prognosis or prediction of outcomes in urothelial carcinoma (UC). The telomerase reverse transcriptase ( TERT) promoter is recurrently mutated at high frequency in UC (50%). These mutations have been correlated with tumor recurrence and survival. Tumor cell-free DNA (cfDNA) with somatic genomic alterations can be found in the plasma of cancer patients and has the potential for use as a non-invasive cancer biomarker. Detection of TERT promoter mutations in cfDNA might be used as a prognostic tool to monitor disease outcome in UC patients. We set out to detect tumor cfDNA and TERT promoter mutations in cfDNA from patients with UC at different stages. Methods: UC patients receiving chemotherapy in the neoadjuvant, first or second-line metastatic setting had blood collected either before or during therapy. cfDNA was isolated from ~1ml plasma samples using the QIAmp (Qiagen) kit. Samples underwent ultra-low pass whole genome sequencing (ULP-WGS) to determine whether tumor cfDNA could be detected in these samples. TERT promoter mutations were detected using a sensitive qPCR assay. Results: 40 plasma samples from a total of 32 patients with urothelial carcinoma were analyzed. Sufficient amounts of plasma cfDNA were obtained for library construction and ULP-WGS in 11 patients. 6 of these 11 patients were determined to be positive for detectable tumor cfDNA and of these, all were metastatic and 50% (3/6) were positive for a TERT promoter mutation. In total, 8 out of 40 samples (20%) were positive for a TERT promoter mutation, including samples from two patients where total cfDNA yield was insufficient for library construction. A total of ~20% of patients with metastatic disease were positive for TERT promoter mutations in cfDNA. The low percentage of samples having sufficient cfDNA most likely reflects the low volume of plasma used. Conclusions: TERT promoter mutations were identified in cfDNA of UC patients. ULP-WGS showed tumor cfDNA in patients with a high tumor burden and metastatic disease. TERTpromoter mutations in cfDNA could potentially be used as a non-invasive method for detection of disease. These results have implications for the use of cfDNA in the evaluation of advanced UC.
Exon 19 deletion association with progression-free survival compared to L858R mutation at exon 21 in treatment with first-line EGFR-TKIs: A meta-analysis of subgroup data from eight phase III randomized controlled trials.
Authors: Wenhua Liang, Jin Sheng, Xuan Wu, Yaxiong Zhang, Shiyang Kang, Li Zhang
Journal: Journal of Clinical Oncology (2014)

8107 Background: The superior efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) compared with cytotoxic chemotherapy in patients harboring sensitive EGFR mutations has been extensively proved by a well-known series of eight phase III randomized controlled trials (RCT). However, the question of whether the efficacy of EGFR-TKIs differs between EGFR exon 19 deletions and exon 21 L858R mutations has not been statistically answered. Methods: Subgroup data on hazard ratio (HR) for progression free survival (PFS) in these RCTs were extracted and were synthesized based on random-effect model. Comparison of outcomes between specific mutations was estimated through indirect methods. All calculations were performed using STATA version 11.0. Results: A total of 7 randomized RCTs (IPASS, WJTOG3405, EUTRAC, OPTIMAL, LUXLUNG3, and LUXLUNG6, as well as NEJ002 being included in sensitivity analysis) involving 1489 patients with either 19 or 21 exon alteration receiving first-line EGFR-TKIs were included. First-SIGNAL study was not eligible without reporting PFS on specific mutations. The pooled HRTKI/chemotherapy for PFS were 0.276 (95% CI 0.200 to 0.382, P<0.001) in patients with 19 exon deletion and 0.470 (95% CI 0.346 to 0.637, P<0.001) in those with exon 21 L858R mutations. Indirect comparison revealed that patients with exon 19 deletions had more favorable outcome for PFS than those with exon 21 L858R mutations (HR19 exon deletion/exon 21 L858R mutations=0.587, 95% CI 0.376 to 0.917; P=0.02). Sensitivity analysis by incorporating direct comparison result from NEJ002 study did not affect the overall outcome. Conclusions: Exon 19 deletions might be associated with longer PFS compared with L858 mutation at exon 21.
Distress screening in patients with urogenital malignancies.
Authors: Pia Paffenholz, Maria Angerer-Shpilenya, Johannes Salem, David Pfister, Axel Heidenreich
Journal: Journal of Clinical Oncology (2017)

412 Background: Malignant tumors do not only have a somatic but also a psychological impact on patients. To date, only a few studies are available which evaluated the potential psychological burden of patients suffering from urogenital cancers. In this prospective, longitudinal study we examine the baseline psychological distress of patients treated for urogenital malignancies focussing on testicular cancer (TC) and prostate cancer (PCA). Methods: Psychological distress of 192 inpatients treated for urogenital malignancies was evaluated using the distress thermometer (DT), an established tool for the detection of distress, prior to any surgical or systemic therapy. The DT consists of a visual analogue scale ranging from 0 to 10 resulting in a low (0-3), moderate (4-6) or high (7-10) stress level. Furthermore, it contains a 36-item list of problems subdivided into 5 categories (practical, family, emotional, spiritual/religious, physical). Results: The mean DT score was 5 (interquartile range (IQR) 3-7) with the most common stressors being of emotional origin, namely fear (50%), worry (44%), nervousness (42%), sleep disorders (39%) and fatigue (32%). DT analysis did not reveal any difference between the tumor entities but 64% of all patients displayed a moderate to high stress level requiring psycho-oncological support. The comparison of PCA and TC demonstrated a higher distress level in PCA patients in the subgroups of metastatic disease (median 5.5, IQR 4-8 vs. median 4, IQR 2-6; p = 0.018), secondary therapy (median 6, IQR 5-8 vs. median 4.5, IQR 2.75-6; p = 0.023) and salvage treatment (median 7, IQR 4.5-9 vs. 5, IQR 2.75-6; p = 0.021). PCA patients receiving salvage treatment displayed significantly higher distress levels compared to non-salvage treated patients (median 7, IQR 4.5-9 vs. median 5, IQR 2-7; p 0.028). Conclusions: Our study shows that 64% of urological tumor patients should be offered psycho-oncological support. Especially patients suffering from advanced stage PCA seem to have a high stress level. Thus, physicians in the field of urologic oncology should be aware of their patients’ psychological distress in order to identify high-risk patients and provide them with an appropriate psycho-oncological support.
Relations of changes in serum carcinoembryonic antigen (CEA) levels before and after chemoradiotherapy (CRT) and after surgery to histological response and outcomes in patients with locally advanced rectal cancer (LARC).
Authors: Gota Saito, Sotaro Sadahiro, Hiroshi Miyakita, Kazutake Okada, Akira Tanaka, Toshiyuki Suzuki
Journal: Journal of Clinical Oncology (2017)

804 Background: Multidisciplinary treatment had been a standard of care for locally advanced rectal cancer. Serum CEA had been reported as one of the predictive factors to CRT, however, serum CEA levels may change after CRT and surgery. We examined the relations of serum CEA before CRT, after CRT, and after surgery to histological response and outcomes. Methods: The subjects were 149 patients with cStage II or III adenocarcinoma of the rectum who underwent surgery after CRT from 2005 through 2013. A total dose of 40 to 45 Gy with concurrent oral UFT or S-1 was delivered. Surgery was performed 6 to 8 weeks after CRT. A serum CEA &gt; 5 ng/mL was defined as positive. Patients with negative serum CEA before CRT were designated as group 1. Patients with positive serum CEA before CRT that became negative after CRT were designated as group 2. Patients with positive serum CEA after CRT that became negative after surgery were designated as group 3, and patients with positive serum CEA after CRT as well as after surgery were designated as group 4. The median follow-up period of the survivors was 60.4 months. Results: The numbers of patients in Groups 1, 2, 3, and 4 were 55 (37%), 41 (28%), 37 (25%), and 16 (11%), respectively. The incidences of pCR, T downstaging, and N downstaging did not differ significantly among the groups (p = 0.094, 0.060, and 0.346). Rates of marked regression (TRG Grade 1 or 2) were 55% in Group 1, 42% in Group 2, 16% in Group 3, 25% in group 4. The rates were significantly higher in groups 1 and 2 (p = 0.001).5y DFS was 76% in group 1, 75% in group 2, 77% in group 3, and 48% in group 4 and was significantly lower in group 4 (p = 0.024). 5y OS was 88% in group 1, 91% in group 2, 85% in group 3, and 68% in group 4 and was significantly lower in group 4 than that in groups 1 and 2 (p = 0.03, 0.019). Conclusions: In patients with rectal cancer who received CRT, changes in serum CEA levels before and after CRT and after surgery were intimately related to the histological response of the primary lesion. Patients who continued to have positive serum CEA levels after surgery had poor outcomes, strongly suggesting the presence of occult distant metastasis.
Effect of chemotherapy-induced peripheral neuropathy on postural control in cancer survivors.
Authors: Haley K. Herman, Scott M. Monfort, Xueliang Jeff Pan, Ajit M.W. Chaudhari, Maryam B. Lustberg
Journal: Journal of Clinical Oncology (2017)

128 Background: Advances in screening and treatment have significantly improved the survival of cancer patients. However, chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity of curative treatment; many patients either cannot complete planned course of treatment or have long standing effects on quality of life. CIPN has been shown to lead to pain, falls, and difficulty walking. Balance changes have been reported with other neuropathies but have not been investigated in depth in cancer patients. This study aims to improve our understanding of changes in postural control associated with CIPN. We hypothesize that patients who report more significant CIPN symptoms will perform more poorly on balance testing. Methods: Eleven cancer patients were enrolled (9 female/ 2 male; 9 breast cancer/ 2 GI cancer; 1.67 ± 0.05 m; 85.8 ± 19.3 kg; 56.5 ± 14.5 yrs). These patients included cases (n = 7), tested within 6 weeks of finishing taxane or oxaliplatin chemotherapy, and controls (n = 4) who did not receive chemotherapy. Patients’ sensory symptoms were assessed by EORTC QLQ-CIPN20. Standing on a balance plate, patients were instructed to close their eyes and remain still while their center of pressure (CoP) was recorded. Medial-lateral root mean squared CoP excursion (RMS) was calculated to provide a measure of postural stability, with higher values indicating poorer control of CoP position and being predictive of falls. Results: Groups were not statistically different in terms of height, mass, or age (p &gt; 0.1). Cases had an average of 3.8 mm (95% CI: 1.7 mm, 6.0 mm) increase in RMS over controls (p = 0.004). Furthermore, cases scored an average of 37.6 points (95% CI: 19.5 points, 55.7 points) lower on a normalized CIPN 20 scale, suggesting worse sensory symptoms (p = 0.002). Conclusions: Patients with CIPN symptoms displayed significantly poorer control of their CoP. This supports the hypothesis that CIPN symptoms associate with poorer balance. The balance deficits reported here are consistent with increased risk of falls and negative post-treatment sequelae. This further suggests a need for closer monitoring and even targeted balance-focused rehabilitation following chemotherapy.
Next-generation sequencing (NGS) in patients with advanced metastatic breast cancer: Identification of molecular alterations and analysis of associations with treatment on phase I studies at MD Anderson Cancer Center.
Authors: Jennifer J. Wheler, Roman Yelensky, Stacy L. Moulder, Apostolia Maria Tsimberidou, Gerald Steven Falchook, Filip Janku, Johnique T. Atkins, Ralph Zinner, Daniel D. Karp, David S. Hong, Phil Stephens, Robert A. Wolff, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2013)

1051 Background: Matching molecular alterations in patients with breast cancer to targeted therapy may increase response rates. Methods: We analyzed 22 sequential breast cancer patients with next generation sequencing (NGS) profiling of their tumors profiling (FoundationOne) treated on Phase I trials at the Clinical Center for Targeted Therapy at MD Anderson Cancer Center. Objectives included: (1) characterize molecular alterations including mutations, amplifications and deletions, (2) evaluate associations between molecular alterations and response to therapy. Results: Twenty-two breast cancer patients, all female with median age 56 years were included. Twenty-one of 22 of patients (95%) analyzed demonstrated at least one molecular alteration. Twenty-one of 22 patients were evaluable for response to therapy (1 patient had not yet reached restaging). Sixteen patients were treated on Phase I trials with targeted therapy that was either directly or indirectly associated with a molecular alteration. Seven of these 16 patients (44%) achieved stable disease (SD) ≥6 months/partial response (PR)/complete response (CR) including 3 patients with PR and 1 patient with CR. Examples of molecular alterations include: mutations in PIK3CA (8 patients), PIK3R1 (2 patients), PTEN (1 patient), cMET (1 patient), NF1 (one patient); amplifications in CCND1 (8 patients), FGFR1 (4 patients), MYC (3 patients), MCL1 (3 patients), IRS2 (2 patients) and CCNE1(1 patient). Conclusions: A majority of patients with advanced or metastatic breast cancer whose tumors underwent NGS profiling demonstrated molecular alterations. Of the 9 patients who had either SD≥6 months/PR/CR on Phase I treatment, 7 (78%) had molecular alterations, either directly or indirectly associated with therapy. Further investigation of larger cohorts of patients with NGS is ongoing.
A multicenter, open label, phase II study to assess the efficacy and safety of APO866 in the treatment of patients with refractory or relapsed cutaneous T-cell lymphoma.
Authors: Simone M. Goldinger, Sharon Gobbi, Michelle Ding, Anna Lisa Frauchiger, Regina Fink-Puches, Claus-Detlev Klemke, Brigitte Dréno, Martine Bagot, Chalid Assaf, Reinhard Dummer
Journal: Journal of Clinical Oncology (2015)

e20044 Background: Cutaneous T-cell lymphoma (CTCL) is characterized by the accumulation of clonal T-cells in the skin. Given the nature of the disease and the toxicities of treatments used, the intensity and duration of long-term therapy is limited. Current investigations focus on more sustainable and safe treatment for CTCL. APO866 is a drug that induces cell death by inhibiting the biosynthesis of NAD+ from niacinamide (vitamin B3). Here, we report the results of an open label, phase II study of APO866 in patients with relapsed and refractory CTCL. Methods: This multi-centre, open label, single-arm GCP-conducted phase II study aimed to determine efficacy, safety and tolerability of APO886 in patients with histologically confirmed relapsed or refractory Stage Ib to IVb CTCL (NCT00431912). APO866 was administered every 28 days for a total of 3 cycles by continuous intravenous infusion at 0.126 mg/m2/h during 96 h. The primary efficacy endpoint considering cutaneous and extra-cutaneous disease (measured by TBI and imaging) was assessed at week 16. A pre-specified interim efficacy analysis was planned after 11 patients. Descriptive statistics were used for safety. Results: The study was stopped due to lack of efficacy after recruitment of 14 patients (February 2007 – January 2011). Two patients withdrew their consent due to disease progression. The intention-to-treat set included 14 patients. At week 16 one patient had partial response (PR), 6 showed stable disease (SD) and 5 progressive disease (PD). No complete response (CR) was observed. The per-protocol set included 5 patients (1 PR and 4 SDs). The most frequently reported drug-related AE was diarrhea (43%), followed by vomiting, lymphopenia, and thrombocytopenia (21% each). Grade 4 AEs included lymphopenia and sepsis. Conclusions: APO866, a drug inhibiting nicotinamide phosphoribosyltransferase (NMPRTase), revealed a reasonable toxicity profile but was not powerful enough to demonstrate efficacy in CTCL. Due to its mode of action and its immunosuppression involving all lymphocytes this drug might play a role in the treatment of autoimmune diseases. Future research for this indication is needed. Clinical trial information: NCT00431912.