tbuckley/cabot-search huggingface dataset:
Clinical utilization of targetable molecular results in pancreatic cancer: Longer-term outcomes from the Individualized Molecular Pancreatic Cancer Therapy (IMPACT) trial.
Authors: Lorraine A. Chantrill, Adnan Nagrial, Amber Johns, Skye McKay, Anthony J. Gill, Nick Pavlakis, Peter S. Grimison, Gholamreza Asghari, Nicola Waddell, Angela Chou, Venessa T. Chin, Lucille T Sebastian, Jaclyn Verghis, Sonia Yip, Katrin Marie Sjoquist, John Simes, Andrew Biankin
Journal: Journal of Clinical Oncology (2017)

314 Background: The IMPaCT trial screened patients with advanced pancreas cancer for molecular targets and aimed to test molecularly guided therapy in a pilot randomized study, but closed in December 2015 having delivered personalized treatment to only 1 patient. A follow up analysis of the screened cohort provides insight into the clinical utilisation of targetable molecular results in pancreas cancer. Methods: IMPaCT screened for 3 genetic phenotypes matched to precision treatment: Her2 amplification (trastuzamab + gemcitabine), KRAS wildtype (erlotinib + gemcitabine) and DNA damage repair pathway defects (platinum-based). Previously recruited primary resected APGI participants known to be alive were also screened for these targets. The initial pilot protocol included randomisation, but after amendment in early 2015, became a single-arm study allowing one cycle of gemcitabine + nab-paclitaxel during screening. Results: A total of 101 potential patients were screened. This was enriched for patients with known targets where sequence data was available from primary pancreatectomy. 23 had one of the 3 molecular targets in this enriched population (4 Her2 amplified, 16 KRAS wt, 2 BRCA2, 1 ATM). The prospectively recruited de novo metastatic cohort (n = 63) had an actionable mutation detection rate of 14.3%. Of the 23 patients identified, 3 received personalised treatment off study, 1 on study, 3 are currently alive without recurrence, 1 is monitored for suspected recurrence, 2 developed second primary malignancies, 10 died or progressed prior to result and 3 decided not to use personalised treatment. The identification of a molecular target did not significantly affect overall survival. Conclusions: Although actionable molecular targets were detected, recruitment rates on the IMPaCT trial were low (1%). Follow up illustrates that these molecular results were incorporated into clinical care off trial or still have the potential to be utilised in another 6.9% of the cohort. Further follow up is planned for long term outcomes. Clinical trial information: ACTRN12612000777897.
Off-label capecitabine, eribulin, or ixabepilone use in metastatic breast cancer (MBC).
Authors: Laura Rose Bobolts, Akhil Kumar, Marc L. Fishman, William S. Shimp, James Edward Krook, Val Fishman, Sharon Davis, Carol Anthony, Robert Walton, Dinah Huff, William John Michael Hrushesky
Journal: Journal of Clinical Oncology (2013)

e12034 Background: Anthracyclines and taxanes have proven to be the most effective treatments for MBC. The FDA indications for capecitabine, eribulin, and ixabepilone recommend prior anthracycline and taxane therapy, unless contraindicated. The proportion of patients who receive these drugs after having received an anthracycline and/or taxane is unknown. We retrospectively reviewed capecitabine, eribulin, and ixabepilone treatment requests to examine the utilization patterns, specifically in relation to prior anthracycline and/or taxane therapy. Methods: All capecitabine, eribulin, or ixabepilone requests for MBC from 2009 through January 2013 were reviewed. The proportion of requests for these agents with and without FDA stipulated prior therapies were contrasted, using Chi squared analyses. Results: 36 MBC requests were identified for capecitabine, eribulin, or ixabepilone. The majority (67%) of these occurred among patients who had no documentation of prior anthracycline therapy. 36% of all requests were not preceded by any documented taxane therapy. Anthracyclines were avoided more frequently than taxanes (p=0.011). All requests without documentation of prior taxane use (36%; 13/36) were also made without prior anthracycline use. Oncologists were more likely to initiate capecitabine without prior anthracycline and taxane, as compared to eribulin or ixabepilone (64% v 18% v 18%, respectively; p=0.042). Conclusions: In our sample, more than two thirds of MBC treatment requests for eribulin, capecitabine, or ixabepilone occurred prior to a request for an anthracycline, and more than a third prior to receiving a taxane. Since, in general, it is considered standard of care to use the most active drugs early in the course of disease, this trend could have negative effects upon the optimal control of MBC. [Table: see text]
Phase I study of weekly albumin-bound paclitaxel (ab-P) plus weekly cetuximab (Cet) plus intensity-modulated radiation therapy (IMRT) in patients with stage III/IVb head and neck squamous cell carcinoma (HNSCC).
Authors: Matthew G. Fury, Eric Jeffrey Sherman, Shyam S. Rao, Suzanne L. Wolden, Stephanie Smith-Marrone, Kenneth K. Ng, Boris Mueller, Daphna Y. Gelblum, Pinaki R. Dutta, James Lee, Ronglai Shen, Sarah Kurz, Nora Katabi, Sofia Haque, Nancy Y. Lee, David G. Pfister
Journal: Journal of Clinical Oncology (2013)

6034 Background: There is a clinical need to improve the efficacy of standard Cet + concurrent RT for pts with stage III/IVB HNSCC. Taxanes have potent activity against HNSCC, and ab-P may offer therapeutic advantages in comparison with other drugs of this class. Methods: This was a single institution phase I study with a modified 3 + 3 design. 4 dose levels (DLs) of weekly ab-P were explored (30, 45, 60, and 80 mg/m 2 ) during IMRT. Standard Cet (450 mg/m 2 loading dose followed by 250 mg/m 2 weekly) concurrent with IMRT (total dose, 70 Gy) was prescribed for all pts. The maximum-tolerated dose (MTD) would be exceeded if &gt;2/6 pts experienced DLTs at a given dose level. NCI CTCAE v.3 was used, and DLT monitoring extended until 2 wks after IMRT. Results: 25 eligible pts (20M, 5F) enrolled, with median age 58 years (range, 46-84) and median KPS 90 (range 80-100). Primary tumor sites were oropharynx, 20 (10 HPV pos, 5 HPV neg, 5 not done); neck node with unknown primary, 2; and larynx, oral cavity, and maxillary sinus, 1 each. Two pts never received ab-P and were deemed inevaluable. At DL 1 (ab-P, 30 mg/m 2 ), there was one DLT (g.4 pneumonia) among 6 pts. At DL2 (ab-P, 45 mg/m 2 ), there were 2 DLTs (g.4 cerebrovascular accident; g.3 decrease in L. ventricle ejection fraction/CHF exacerbation) among 6 pts. At DL3 (ab-P, 60 mg/m 2 ), there was 1 DLT (g.3 supraventricular tachycardia) among 6 pts. MTD was exceeded at DL4 (ab-P, 80 mg/m 2 ) with 3 DLTS (g.3 neuropathy, g.3 dehydration, g.3 anemia) among 5 evaluable pts. For the entire study population, most common ≥ g3 AEs were: lymphopenia 100%, functional mucositis, 56%, and pain in throat/oral cavity, 52%. There were no treatment-related deaths. Among 23 evaluable pts at a median follow up of 29 months, 2y PFS rate is 64% (95% CI: 41-80%) and 2y OS rate is 90% (95% CI: 66-97). Conclusions: The recommended phase II dose is ab-P 60 mg/m 2 weekly when given concurrently with IMRT and standard weekly Cet. This regimen merits further study as an alternative to IMRT + Cet alone for pts who require a non-platinum regimen. This study was approved and funded by the NCCN from general research support provided by Celgene, Inc. Clinical trial information: NCT00736619.
Independent validation of effect of <i>HSD3B1</i> genotype on response to androgen deprivation therapy (ADT) in hormone-sensitive prostate cancer (HSPC).
Authors: Andrew W. Hahn, David Michael Gill, Austin Poole, James M. Farnham, Lisa A Cannon-Albright, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2017)

172 Background: A germline inherited polymorphic variant (1245A→C) in the HSD3B1 gene was recently reported to correlate with shorter duration of response to ADT in men with HSPC (Hearn JW, Lancet Oncology, 2016). HSD3B1 gene encodes the enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which catalyzes adrenal androgen precursors into dihydrotestosterone, the most potent androgen. Presence of one or more variant alleles was associated with shorter response to ADT compared to those with no variant alleles of this gene. Objective of this study was to validate these results in an independent cohort. Methods: Clinical data and samples were from a prospectively maintained prostate cancer registry at the University of Utah (Salt Lake City, UT). Genotyping was performed as described by Hearn at al. Primary endpoint was progression-free survival on ADT, i.e time to onset of castration resistance. We performed pre-specified multivariate analyses to assess the independent predictive value of HSD3B1 genotype on PFS on ADT (Table). Results: 102 men with new mHSPC met eligibility and included in the analysis. The allelic frequency of the HSD3B1 (1245C) variant in our cohort was 31%, i.e. similar to that reported by Hearn et al. In multivariate analysis, those men in the homozygous variant group had significantly shorter PFS in comparison to those in the homozygous wild type group; no significant difference in PFS was observed in those men in the heterozygous group compared to those in the homozygous wild type group (Table). Conclusions: HSD3B1(1245C) predicted inferior response to ADT in our independent cohort of men with mHSPC. We also confirm that this polymorphism is quite common in this population. [Table: see text]
Overexpression of fatty acid binding protein 5 and tumorigenesis in hepatocellular carcinoma.
Authors: Takanori Ohata, Hideki Yokoo, Toshiya Kamiyama, Kenji Wakayama, Tatsuya Orimo, Tatsuhiko Kakisaka, Yousuke Tsuruga, Hirofumi Kamachi, Akinobu Taketomi
Journal: Journal of Clinical Oncology (2014)

e15110 Background: Hepatocellular carcinoma (HCC) is one of the cancer types with poor prognosis. At present, the serum level of Alphafetoprotein (AFP), Prothrombin Induced by Vitamin K Absence II (PIVKA II) or Alphafetoprotein Lens culinaris agglutiin 3 (AFP-L3%) are used for tumor markers of HCC, but they are not adequate to predict survival or recurrence after curative hepatectomy. Fatty Acid Binding Protein 5 (FABP5) has been reported in several cancers such as pancreatic cancer, breast cancer, also involved with tumor growth or invasiveness by using several cancer cell lines. However, there are few reports mentioned about HCC. We have previously reported that FABP5 expression was closely related with poor prognosis and recurrence by Immunohistochemical Staining Method and showed positive correlation of AFP, AFP-L3%, PIVKA II, tumor size, intrahepatic metastasis, and micro/macro vascular invasion from univariate and multivariate analysis (AASLD Liver Meeting 2013). Purpose: To analyze the correlation between the expression of FABP5 and malignant behavior of HCC using human HCC cell lines (HLF, HLF, HepG2). Methods: Protein expression of FABP5 in HCC cell lines was assessed by Western blot. We evaluated the invasiveness and proliferation of the higher FABP5 expression cell lines with or without knockdown of FABP5 by short hairpin RNA. Invasiveness was estimated by the Matrigel Invasion Assay, and proliferation by MTS Assay. PCR arrays were used to examine genes involved in cancer progression and invasiveness following FABP5 inhibition. Results: Western blot showed that expression of FABP5 about HLE, HLF were high and that of HepG2 was low. HLE and HLF were highly invasive and proliferative cell lines. Moreover, the knockdown of FABP5 inhibited cell proliferation and invasiveness of high expression cell lines. PCR arrays confirmed the downregulation of the epithelial–mesenchymal transition (EMT) genes following FABP5 inhibition. Conclusions: FABP5 behaves as a significant prognostic and recurrence factor for HCC patients because FABP5 promotes invasiveness and proliferation through activation of EMT pathway. Therefore, FABP5 may serve as a new molecular target for the development of HCC therapies.
Immune-reconstitution after combined haploidentical and umbilical cord blood transplantation.
Authors: Koen van Besien, Nitin Jain, Viviane Schouten, Hongtao Liu, Jodie Ulaszek, Amittha Wickrema, Andrew S. Artz
Journal: Journal of Clinical Oncology (2012)

6535^ Background: Umbilical cord blood (UCB) stem cells are frequently employed for allogeneic stem cell transplantation. However, delayed myeloid and lymphoid immune-reconstitution with UCB transplantation leads to increased risk of infections. We recently reported a pilot study combining UCB with a HLA haploidentical donor (Liu et al. Blood. 2011). Here, we report the immune reconstitution after the haploidentical-cord blood transplantation. Methods: Pts received reduced-intensity conditioning with fludarabine/melphalan/rATG and were assessed for lymphocyte subsets, serological response to pneumococcal vaccination, Cylex Immuknow assay which measures amount of ATP secreted by CD4 lymphocytes on stimulation by PHA, and T-cell spectratyping. Results: 45 pts, enrolled between 01/2007 and 04/2011, are included in this analysis. The median absolute lymphocyte subset counts at serial time-points are shown in the Table. The median absolute values of CD3, CD4 and CD8 counts remained below the normal range throughout the 1st year post-transplant. The NK-cells and B-cells reached normal range by day 30 and day 100, respectively. Serological response to pneumococcal vaccination was seen in 7/17 (defined as seroconversion or &gt;3 fold rise in titers of serotype 14, 19F and 23F) evaluable pts at a median 74 days after vaccination. Immuknow assay showed that 6/6 pts tested within first 30 days of transplant had low values whereas 5/8 tested &gt;1yr had normal/high values. Of the 9 pts who were assessed for T-cell receptor repertoire by T-cell spectratyping, 7 had a polyclonal, complex T cell repertoire similar to healthy controls. CMV viremia requiring treatment occurred in 14 patients. EBV reactivation occurred in 18 pts and 5 developed PTLD 68 to 314 days after transplant. Conclusions: Haploidentical cord blood transplantation leads to rapid myeloid recovery and recovery of B-cell and NK cell numbers. T-cell recovery is more delayed, but at 1-year most pts have a polyclonal T cell repertoire and robust T-cell responses. [Table: see text]
Psychosocial distress in lymphoma survivors at 3 years’ follow-up.
Authors: Allison Claire Rosenthal, Matthew John Maurer, Cristine Allmer, Stephen Maxted Ansell, Umar Farooq, Thomas Matthew Habermann, Brian K. Link, Thomas E. Witzig, Kathleen J. Yost, James Robert Cerhan, Carrie A. Thompson
Journal: Journal of Clinical Oncology (2017)

193 Background: National standards recommend distress screening as part of cancer care. While many patients report improved quality of life after cancer treatment concludes there remains a population who experience ongoing anxiety and depressive symptoms. We sought to describe psychosocial distress in lymphoma survivors and frequency of visits to mental health providers (MHP). Methods: Lymphoma patients were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource and systematically followed. Brief Profile of Mood States (POMS) and State Trait Anxiety Inventory (STAI) were administered 3 yrs after diagnosis. Lower scores on POMS indicated more distress. A higher score on STAI indicated more anxiety, and a score ≥ 40 was considered clinically significant. Pts were asked if they ever saw a MHP due to their lymphoma. Results: Between 2002-2012, 2465 lymphoma pts age 18-91 (10% 18-40, 54% 41-65, and 36% &gt; 65) were enrolled, met survivor definition, and completed 3-yr POMS and STAI questionnaires. 57% were male. 40% had aggressive and 60% had indolent lymphoma. The median score on STAI 1 (state) was 32 (range 20-76) and on STAI 2 (trait) was 31 (range 20-77). Median POMS total mood disturbance (TMD) score was 88 (range 1-100). 8% of pts reported seeing a MHP. 609 pts (25%) had clinically significant anxiety by STAI 1, 73 (12%) of whom saw a MHP. Those who reported clinically significant anxiety on STAI were more likely to be younger, unemployed, unmarried, and less likely to have seen a MHP. Anxiety levels were similar between those with aggressive lymphoma and indolent lymphoma regardless of treatment. Higher distress levels, measured by TMD, were more often reported by those who were unemployed or over age 65 while there was no association with lymphoma subtype, marital status, or choice of therapy. Conclusions: Clinically significant anxiety was reported in 25% of 3-yr survivors of lymphoma and was associated with younger age, unmarried status, and unemployment. Higher distress levels were associated with older age, and unemployment. However, only 8% of our cohort was seen by a MHP. Identifying distress and appropriately referring to a MHP is important for the optimal care of lymphoma survivors.
Comparison of clinical primary tumor site (PTS) response to induction chemotherapy (IC) with APF (<i>nab-</i>paclitaxel, cisplatin, and 5-FU) or APF plus cetuximab (APF+Cetux) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).
Authors: Jessica C. Ley, Brian Nussenbaum, Jason Diaz, Jason Rich, Randal Paniello, Ravi Uppaluri, Wade L. Thorstad, Hiram Alberto Gay, Toni Rachocki, Jaisy Varges, Tanya Marya Wildes, Loren S. Michel, Douglas Adkins
Journal: Journal of Clinical Oncology (2014)

6013 Background: Achievement of a favorable (> PR) response (particularly CR) at the PTS to IC predicts a higher likelihood of long-term disease control after definitive chemoradiotherapy (CRT) in SCCHN. Low T classification and p16 + oropharynx [OP]SCCHN associate with favorable PTS response to IC. Based on improved tumor response rate with cetuximab added to chemotherapy in the EXTREME trial, we hypothesized a higher PTS CR rate with the addition of cetuximab to APF given as IC before CRT. Methods: Two consecutive prospective phase II trials (APF and APF+Cetux) were performed with the primary objective to determine the response rates (CR, PR, <PR) at the PTS. 30 patients were treated with APF (weekly nab-paclitaxel 100 mg/m2 and every 3 week cisplatin 75 mg/m2 and 5-FU 750 mg/m2/dayx3) and 30 patients were treated with APF+Cetux (APF + weekly cetuximab 250 mg/m2). After two cycles of IC, PTS response assessment by clinical exam was performed by experienced oncologic otolaryngologists. Patients were then scheduled for a third cycle of IC followed by definitive CRT (with cisplatin). Results: After two cycles of APF or APF+Cetux, CR rates at the PTS were 76.7% (23 patients) and 53% (16 patients), respectively. PR and <PR rates at the PTS after two cycles of APF were 16.7% (5 patients) and 6.7% (2 patients) and after APF+Cetux were 47% (14 patients) and 0%, respectively. CR rates at the PTS were consistently higher with APF compared to APF+Cetux when stratified for T classification and p16 status (Table). Conclusions: Unexpectedly, the addition of cetuximab to APF did not increase the CR rate at the PTS even when stratified for T classification and p16 status. This observation is consistent with our historical experience of TPF+Cetux (Adkins et al ASCO 2011 #5560). Validation of these findings in a randomized trial is indicated. Clinical trial information: NCT01566435 AND NCT00736944. Characteristic APF (n=30) APF+Cetux (n=30) No. % No. % T2 # 8 - 8 - CR 8 100 4 50 PR 0 0 4 50 T3 # 13 - 11 - CR 9 69 6 55 PR 4 31 5 45 T4 # 9 - 11 - CR 6 67 6 55 PR 1 11 5 45 <PR 2 22 0 0 P16+ OPSCC* # 17 - 17 - CR 13 76 11 65 PR 3 18 6 35 <PR 1 6 0 0 P16- SCCHN # 13 - 12 - CR 10 77 4 33 PR 2 15 8 67 <PR 1 8 0 0 * p16 not performed in 1.
Focal Pegylated Liposomal Doxorubicin–Induced Urticarialike Reaction at Cutaneous Transformed Sézary Lesions
Authors: Roger Haber, Caroline Ram-Wolff, Pauline Laly, Martine Bagot
Journal: JAMA Dermatology (2017)

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Higher volumetric breast density to predict risk for aggressive breast cancer subtype in postmenopausal Korean women.
Authors: In Hae Park, Kyungran Ko, Ji Soo Choi, So-youn Jung, Seeyoun Lee, Seok Won Kim, Youngmee Kwon, Kyung Hwan Shin, Han Sung Kang, Eun Sook Lee, Keun-Seok Lee, Jungsil Ro
Journal: Journal of Clinical Oncology (2013)

e11584 Background: In Asian population, the peak incidence of breast cancer is women in their late forties. We investigated the association between volumetric breast density and breast cancer risk according to menstruation status and breast cancer subtypes in Korean women. Methods: We prospectively enrolled 509 newly diagnosed breast cancer patients and 1336 healthy control subjects who performed mammography at the National Cancer Center in Korea between Sep 2011 and Nov 2012. Breast density was estimated using volumetric breast composition measurement (Volpara TM ). We collected clinical data including menstruation status, parity, BMI and use of postmenopausal hormones. For cancer patient, we additionally acquired following pathologic data: histologic type, tumor size and grade, receptor status, Ki-67, and nodal status. Results: Of a total of subjects, 1064 (57.7%) women were postmenopausal status. The risk of breast cancer increased progressively with increase in volumetric breast density (P trend &lt;0.001) in all subjects. In addition, breast cancer risk increased in women &lt; 60 years old (odds radio (OR) = 1.81), higher body mass index (BMI) (&lt; 25kg/m 2 vs. ≥ 25kg/m 2 ) (OR = 2.41), and fewer childbirth (0/1 vs. ≥ 2) (OR=2.38). In postmenopausal women, higher breast density (category 4) showed a 3.00-fold (OR = 3.00, 95% confidence interval (CI) = 1.75-5.16, P&lt;0.001) increased risk of breast cancer compared with lower breast density (category 1-2). In contrast, there was no such association in premenopausal women. The associations of volumetric breast density were stronger for HER2 positivity (P trend &lt;0.019), and high Ki-67 (P trend &lt;0.006) in postmenopausal breast cancer patients. There was a statistically significant association between lower breast density and hormone receptor (HR) positive/HER2 negative breast cancer (P trend &lt;0.019). Conclusions: High volumetric breast density is associated with the risk of breast cancer having more aggressive tumor characteristics in postmenopausal women.