tbuckley/cabot-search huggingface dataset:
Breast Reconstruction With Postmastectomy Radiation: Choices and Tradeoffs
Authors: Matthew M. Poppe, Jayant P. Agarwal
Journal: Journal of Clinical Oncology (2017)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 45-year-old premenopausal woman presented with multifocal cancer in the right breast, with lesions at 1:00 and 4:00, the largest measuring approximately 3 cm on exam, and multiple palpable right axillary lymph nodes. A core biopsy confirmed invasive ductal carcinoma, grade 2 of 3, that was estrogen receptor positive, progesterone receptor positive, and HER2 negative. Fine needle aspiration of a right axillary node confirmed metastatic carcinoma. A positron emission tomography (PET)/ computed tomography done before starting chemotherapy demonstrated an absence of metastatic disease with expected avidity in two separate breast masses and multiple conglomerated 1-2 cm level I and II axillary lymph nodes. She received neoadjuvant chemotherapy with doxorubicin plus cyclophosphamide, followed by paclitaxel, and had a complete clinical response with resolution of the breast and axillary masses on exam. A repeat PET/computed tomography demonstrated reduced size of the breast and axillary disease, and no significant residual PET avidity. Her breast surgeon recommended a right mastectomy with axillary node dissection. As part of her multidisciplinary treatment plan, she consulted with two plastic surgeons to discuss reconstruction options. Plastic Surgeon A advised placement of an implant at the time of mastectomy while Surgeon B contrasted the pros and cons of an autologous transverse rectus abdominis muscle flap reconstruction with an implant based reconstruction. Surgeon B believed that autologous reconstruction would yield the best long-term cosmetic outcome. Before making her surgery decision, the patient consulted with a radiation oncologist to discuss the effect radiation may have on her reconstruction outcome.
Rapamycin and zoledronic acid synergistically repolarize tumour associated macrophages towards anti-HCC responses
Authors: M. Aslam, M. Ashfaq-Khan, M.A. Qureshi, L. Kaps, S.Y. Weng, Y.O. Kim, R. Surabattula, D. Schuppan
Journal: Journal of Hepatology (2017)
Tmbim1 is a multivesicular body regulator that protects against non-alcoholic fatty liver disease in mice and monkeys by targeting the lysosomal degradation of Tlr4
Authors: Guang-Nian Zhao, Peng Zhang, Jun Gong, Xiao-Jing Zhang, Pi-Xiao Wang, Miao Yin, Zhou Jiang, Li-Jun Shen, Yan-Xiao Ji, Jingjing Tong, Yutao Wang, Qiao-Fang Wei, Yong Wang, Xue-Yong Zhu, Xin Zhang, Jing Fang, Qingguo Xie, Zhi-Gang She, Zhihua Wang, Zan Huang, Hongliang Li
Journal: Nature Medicine (2017)
The prognosis of single large hepatocellular carcinoma was distinct from the BCLC stage A or B
Authors: P.-C. Lee, C.-W. Su, K.-C. Fang, C.-Y. Chang, Y.-H. Huang, T.-I. Huo, M.-C. Hou, H.-C. Lin, J.-C. Wu
Journal: Journal of Hepatology (2017)
Abstract B30: The RNA-binding protein LARP1 is a cancer therapeutic target
Authors: Essam A. Ghazaly, John Le Quesne, Dahai Jiang, Selanere L. Mangala, James Chettle, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Chathunissa Gnanaranjan, Manuela Mura, Chara Stavraka, Anil K. Sood, Sarah P. Blagden
Journal: Cancer Research (2017)

Abstract Ovarian cancer is the most lethal of gynecological cancers killing 60% of women diagnosed with the disease within 5 years. The major contributor to this high mortality is the emergence of chemotherapy resistance; the tumor is initially sensitive to chemotherapy (especially cisplatin, the mainstay of treatment) but recurs with increasingly resistant disease. Effective methods of overcoming treatment resistance are a major unmet medical need and would prolong survival and improve quality of life for women with this disease. We have shown previously that the RNA binding protein La-related protein 1 (LARP1) binds and post-transcriptionally regulates the stability of mRNAs encoding cell survival and stress response proteins including mTOR, BCL2 and BIK. In ovarian cancer tissue, elevated levels of LARP1 protein correlate with adverse survival outcome and chemotherapy resistance. In vivo inhibition of LARP1 using therapeutic RNA interference (packaged in DOPC nanoliposomes) restores cisplatin sensitivity in resistant ovarian cancer xenograft models. In concurrent studies, using a novel ultra-high performance liquid chromatography tandem mass spectrometry method, we have quantified LARP1 in the circulation of ovarian cancer patients and found that high levels correspond with poor prognosis. Circulating LARP1 has prognostic significance and may act as a companion biomarker to a LARP1 inhibitor. We conclude that LARP1, through its regulation of multiple mRNAs within critical pathophysiological pathways, is an important cancer therapeutic target and that RNA-based drugs designed to target LARP1 restore chemotherapy sensitivity in xenograft models. Citation Format: Essam A. Ghazaly, John Le Quesne, Dahai Jiang, Selanere L. Mangala, James Chettle, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Chathunissa Gnanaranjan, Manuela Mura, Chara Stavraka, Anil K. Sood, Sarah P. Blagden. The RNA-binding protein LARP1 is a cancer therapeutic target. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B30.
Modelling the impact of targeted interventions on the HCV epidemic in Pakistan: the road to HCV elimination
Authors: A.G. Lim, H. Qureshi, H. Mahmood, S. Hamid, C. Davies, A. Trickey, N. Glass, Q. Saeed, H. Fraser, J.G. Walker, C. Mukandavire, M. Hickman, N.K. Martin, M. May, F. Averhoff, P. Vickerman
Journal: Journal of Hepatology (2017)
A Phase 1 Study of Total Marrow Irradiation Combined with High-Dose Melphalan for Patients with Relapsed/ Refractory Multiple Myeloma
Authors: Pritesh R. Patel, Annie L. Oh, Matthew Koshy, Bulent Aydogan, Karen Sweiss, John G. Quigley, Santosh L. Saraf, Irum Khan, Eileen D. Hacker, Nadim Mahmud, David J. Peace, Howard Ozer, Jennifer Windhorst, Ralph R Weichselbaum, Damiano Rondelli
Journal: Blood (2016)
Long-term disease progression in chronic hepatitis B Chinese patients with comorbid nonalcoholic fatty liver disease
Authors: J.G. Fan, G.F. Chen, D. Ji, D.W. Ye, C. Wang, Q. Shao, F. Li, B. Li, V. Wu, A. Wong, Y.D. Wang, J. Chen, A. Sanyal, G. Lau
Journal: Journal of Hepatology (2017)
Molecular characterization of Hepatitis C virus resistance-associated substitutions after interferon-free treatment failure by massive parallel sequencing
Authors: Q. Chen, C. Perales, J. Crespo, M. Buti, J.L. Calleja, J. Gregori, F. Rodríguez-Frías, L. Nieto, J. Niubó, M. Rodríguez, I. Conde, M.L.G. Buey, I. Fernández, J. Torras, R. Morillas, M. Diago, F. Sáez-Royuela, M. Forné, J. Tunes, J.G. Samaniego, J.A. Carrión, J.I. Arenas, X. Forns, Z. Mariño, R. Andrade, S. Montoliu, M.Á. Simón, G.S. Antolín, J.J. Sánchez-Ruano, J.M. Pascasio, J.I. Esteban, J. Quer
Journal: Journal of Hepatology (2017)
CheckMate 227: A randomized, open-label phase 3 trial of nivolumab, nivolumab plus ipilimumab, or nivolumab plus chemotherapy versus chemotherapy in chemotherapy-naïve patients with advanced non-small cell lung cancer (NSCLC)
Authors: L. Paz-Ares, J. Brahmer, M.D. Hellmann, M. Reck, K. O'Byrne, H. Borghaei, W.J. Geese, H. Lu, F.E. Nathan, S. Ramalingam
Journal: Annals of Oncology (2017)
Immune response and adverse events to influenza vaccine in cancer patients undergoing PD-1 blockade
Authors: S.I. Rothschild, C. Balmelli, L. Kaufmann, M. Stanczak, M. Syedbasha, D. Vogt, O. Gautschi, A. Egli, A. Zippelius, H. Laeubli
Journal: Annals of Oncology (2017)
Association Between Medication Use for Attention-Deficit/Hyperactivity Disorder and Risk of Motor Vehicle Crashes
Authors: Zheng Chang, Patrick D. Quinn, Kwan Hur, Robert D. Gibbons, Arvid Sjölander, Henrik Larsson, Brian M. D’Onofrio
Journal: JAMA Psychiatry (2017)

Motor vehicle crashes (MVCs) are a major public health problem. Research has demonstrated that individuals with attention-deficit/hyperactivity disorder (ADHD) are more likely to experience MVCs, but the effect of ADHD medication treatment on the risk of MVCs remains unclear.To explore associations between ADHD medication use and risk of MVCs in a large cohort of patients with ADHD.For this study, a US national cohort of patients with ADHD (n = 2 319 450) was identified from commercial health insurance claims between January 1, 2005, and December 31, 2014, and followed up for emergency department visits for MVCs. The study used within-individual analyses to compare the risk of MVCs during months in which patients received ADHD medication with the risk of MVCs during months in which they did not receive ADHD medication.Dispensed prescription of ADHD medications.Emergency department visits for MVCs.Among 2 319 450 patients identified with ADHD, the mean (SD) age was 32.5 (12.8) years, and 51.7% were female. In the within-individual analyses, male patients with ADHD had a 38% (odds ratio, 0.62; 95% CI, 0.56-0.67) lower risk of MVCs in months when receiving ADHD medication compared with months when not receiving medication, and female patients had a 42% (odds ratio, 0.58; 95% CI, 0.53-0.62) lower risk of MVCs in months when receiving ADHD medication. Similar reductions were found across all age groups, across multiple sensitivity analyses, and when considering the long-term association between ADHD medication use and MVCs. Estimates of the population-attributable fraction suggested that up to 22.1% of the MVCs in patients with ADHD could have been avoided if they had received medication during the entire follow-up.Among patients with ADHD, rates of MVCs were lower during periods when they received ADHD medication. Considering the high prevalence of ADHD and its association with MVCs, these findings warrant attention to this prevalent and preventable cause of mortality and morbidity.
Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis
Authors: Bakhtawar K Mahmoodi, Kunihiro Matsushita, Mark Woodward, Peter J Blankestijn, Massimo Cirillo, Takayoshi Ohkubo, Peter Rossing, Mark J Sarnak, Bénédicte Stengel, Kazumasa Yamagishi, Kentaro Yamashita, Luxia Zhang, Josef Coresh, Paul E de Jong, Brad C Astor
Journal: The Lancet (2012)
Results of an Open, Non-Comparative, Phase I/II Investigator Initiated Trial (IIT) in Relapsed or Refractory Multiple Myeloma Patients Using Vorinostat, Bortezomib, Doxorubicin and Dexamethasone (VBDD)
Authors: Alexander Keller, Johannes M. Waldschmidt, Dagmar Wider, Dorothee Jakobs, Mandy Möller, Heike Reinhardt, Milena Pantic, Olga Grishina, Gabriele Ihorst, Annette M May, Anna Frey, Ulrike Kohlweyer, Justus Duyster, Manfred Jung, Monika Engelhardt, Ralph Wäsch
Journal: Blood (2015)
Midodrine and albumin for prevention of complications of cirrhosis in patients in the waiting list for liver transplantation. A randomized, multicenter, double-blind, placebo-controlled trial
Authors: E. Solà, C. Solé, M. Simón-Talero, M. Martín-Llahí, J. Castellote, R. Garcia-Martínez, R. Moreira, M. Torrens, P. Márquez, N. Fabrellas, G.D. Prada, P. Huelin, M. Ventura, M. Manríquez, A. Nazar, X. Ariza, P. Suñé, I. Graupera, E. Pose, J. Colmenero, M. Pavesi, M. Guevara, X. Xiol, J. Córdoba, V. Vargas, P. Ginès
Journal: Journal of Hepatology (2017)
Treatment with direct-acting antiviral agents is associated with improvement of renal function in a cohort of hepatitis C virus infected patients with chronic kidney disease
Authors: C. Masetti, F. De Leonardis, P. Rossi, A. Bosa, D. Di Paolo, M. Milana, F. Santopaolo, A. Pecchioli, S. Di Nardi, S. Francioso, I. Lenci, L. Baiocchi, A. Brega, F. Antenucci, T. Marianelli, M. Angelico
Journal: Journal of Hepatology (2017)
Uncontrolled glycaemia increases the risk of developing spontaneous bacterial peritonitis in patients with cirrhosis
Authors: A.I. Servin-Caamaño, A.E. Navarro-Estrada, J.L. Pérez-Hernández, V.L.-L. de Guevara, A. Cruz-Estrada, F.H. de La Tijera
Journal: Journal of Hepatology (2017)
Subject Index Vol. 77, 2008
Authors: C. Franco, A. Martínez-Aran, J. Sánchez-Moreno, M. Reinares, M. Salamero, C. Arango, J.L. Ayuso-Mateos, F. Kapczinski, E. Vieta, Laura Sirri, Silvana Grandi, Giovanni A. Fava, John S. Ogrodniczuk, Anthony S. Joyce, Larry D. Lynd, William E. Piper, Paul I. Steinberg, Kathryn Richardson, Dionyssios Leftheriotis, Ioannis Michopoulos, Panayota Flevari, Athanassios Douzenis, Christoforos Koborozos, Anna Kostopoulou, George N. Theodorakis, Lefteris Lykouras, Dimitrios T. Kremastinos, Franziska Geiser, Christian Meier, Ingo Wegener, Katrin Imbierowicz, Rupert Conrad, Reinhard Liedtke, Johannes Oldenburg, Ursula Harbrecht, Robert H. Howland, Pamela J. Schettler, Mark Hyman Rapaport, David Mischoulon, Trisha Schneider, Amy Fasiczka, Katia Delrahiem, Rachel Maddux, Michael Lightfoot, Andrew A. Nierenberg, A.R. Rosa, Eriko Nakatani, Akiko Nakagawa, Gerda van Aalst, Robert A. Schoevers, Jaap Peen, Ernesto Caffo, Carlotta Belaise, Barbara Forresi, Jouko K. Salminen, Hasse Karlsson, Jarmo Hietala, Jaana Kajander, Sargo Aalto, Juha Markkula, Helena Rasi-Hakala, Tuula Toikka, Henricus L. Van, Jack Dekker
Journal: Psychotherapy and Psychosomatics (2008)
Abstract 160: Tuberosis Sclerosis Complex 1 Mediated Neointima Formation and Arterial Thrombosis Following Vascular Injury
Authors: Eo Jin Kim, Yong-Joo Ahn, Maya Hwewon Kim, Hyung-Hwan Kim
Journal: Circulation Research (2014)

Objectives: Vascular injury and thrombosis are main leading causes of cardiovascular diseases. Tuberous sclerosis complex (TSC) is a genetic disorder caused by heterozygous mutations in either of two genes, TSC1 and TSC2. Although role of TSCs has been implicated in cardiovascular diseases, the tissue- and isoform-specific roles of TSCs in the vascular response to injury are not known. Methods and Results: To determine the role of TSC1 in arterial injury and thrombosis, we generated vascular smooth muscle cell-specific TSC1 conditional knockout mice (TSC1SM22-/-) by crossing vascular smooth muscle cell-specific Cre (SM22Cre) mice with TSC1flox/flox mice and performed carotid artery ligation in haploinsufficient TSC1 conditional knockout mice (TSC1SM22+/-) compared with that of WT or haploinsufficient TSC2 knockout mice (TSC2+/-). Acute carotid artery occlusion was investigated by 5% ferric chloride injury. Arterial thrombosis and neointima formation were measured at 14 days after arterial ligation. Expression of proteins was observed by immunoblot analysis. The neointima formation was significantly increased in TSC1SM22+/- mice (intimal thickness/medial thickness ratio; 1.14 ± 0.14, p&lt;0.001) compared with that of WT mice (0.13 ± 0.03). Two weeks after arterial injury, arterial thrombus area was increased in TSC1SM22+/- mice (thrombus area/luminal area ratio; 72.1 ± 4.4, p&lt;0.001) compared with that of WT mice (0.1 ± 0.0) but there are no significant effect in acute arterial thrombosis induced by ferric chloride. Loss of TSC1 and hyper-activation of mammalian target of rapamycin complex 1 including mTOR and S6 proteins were observed by immunoblot analysis of carotid artery tissue lysates of TSC1SM22+/- mice compared with that of WT. Conclusion: These findings suggest that regulation of TSC1 and mTOR might be useful for therapeutic intervention in vascular injury and thrombosis.
Treatment with sofosbuvir and ledipasvir without ribavirin for 12 weeks is highly effective for recurrent hepatitis C after living donor liver transplantation: a Japanese multicenter experience
Authors: Y. Ueda, T. Ikegami, N. Akamatsu, A. Soyama, M. Shinoda, R. Goto, H. Okajima, T. Yoshizumi, A. Taketomi, Y. Kitagawa, S. Eguchi, N. Kokudo, S. Uemoto, Y. Maehara
Journal: Journal of Hepatology (2017)
Impact of von Willebrand factor/ADAMTS-13 on the pro-coagulant imbalance detected in cirrhosis
Authors: V. La Mura, A. Tripodi, N. Bitto, G. Tosetti, V. Chantarangkul, L. Baronciani, C. Valsecchi, F. Peyvandi, F. Salerno, P. Lampertico, M. Colombo, M. Primignani
Journal: Journal of Hepatology (2017)
Topical Mercurials for the Treatment of Pediculosis
Authors: Justin D. Arnold
Journal: JAMA Dermatology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Quadriceps strengthening with and without blood flow restriction in the treatment of patellofemoral pain: a double-blind randomised trial
Authors: Lachlan Giles, Kate E Webster, Jodie McClelland, Jill L Cook
Journal: British Journal of Sports Medicine (2017)

Background Quadriceps strengthening exercises are part of the treatment of patellofemoral pain (PFP), but the heavy resistance exercises may aggravate knee pain. Blood flow restriction (BFR) training may provide a low-load quadriceps strengthening method to treat PFP. Methods Seventy-nine participants were randomly allocated to a standardised quadriceps strengthening (standard) or low-load BFR. Both groups performed 8 weeks of leg press and leg extension, the standard group at 70% of 1 repetition maximum (1RM) and the BFR group at 30% of 1RM. Interventions were compared using repeated-measures analysis of variance for Kujala Patellofemoral Score, Visual Analogue Scale for ‘worst pain’ and ‘pain with daily activity’, isometric knee extensor torque (Newton metre) and quadriceps muscle thickness (cm). Subgroup analyses were performed on those participants with painful resisted knee extension at 60°. Results Sixty-nine participants (87%) completed the study (standard, n=34; BFR, n=35). The BFR group had a 93% greater reduction in pain with activities of daily living (p=0.02) than the standard group. Participants with painful resisted knee extension (n=39) had greater increases in knee extensor torque with BFR than standard (p&lt;0.01). No between-group differences were found for change in Kujala Patellofemoral Score (p=0.31), worst pain (p=0.24), knee extensor torque (p=0.07) or quadriceps thickness (p=0.2). No difference was found between interventions at 6 months. Conclusion Compared with standard quadriceps strengthening, low load with BFR produced greater reduction in pain with daily living at 8 weeks in people with PFP. Improvements were similar between groups in worst pain and Kujala score. The subgroup with painful resisted knee extension had larger improvements in quadriceps strength from BFR. Trial registration number 12614001164684.
Role of FDG-PET/CT for Detection of Occult Bone Marrow Involvement in Patients from the Middle East and North Africa Region with Hodgkin Lymphoma
Authors: Moussab Damlaj, Giamal Edin Mohamed Gmati, Ghulam Syed, Mohsen Al Zahrani, Khadega Ahmed Abuelgasim, Mushtaq Rather, Salama Hend, Hejazi Ayman, Abdul-Rahman Jazieh, Ahmed Askar
Journal: Blood (2016)
A TIAM Double Hit to Oppose YAP/TAZ
Authors: Luca Azzolin, Stefano Piccolo
Journal: Cancer Cell (2017)

In this issue of Cancer Cell, Diamantopoulou et al. uncover dual mechanisms of inhibiting YAP/TAZ by TIAM1 that oppose invasiveness of colorectal cancer cells: TIAM1 interacts with TAZ in the cytoplasm to promote TAZ degradation by the destruction complex, whereas it antagonizes binding of TAZ/YAP to TEAD in the nucleus.
Transient elastography evolution in non treated patients with chronic hepatitis B (CHB) infection
Authors: M.L. González-Diéguez, M.A. de Jorge, C. Alvarez-Navascues, C. Rodríguez-Escaja, E. Rubio, A. Castaño, V. Cadahia, M. Varela, M. Rodriguez
Journal: Journal of Hepatology (2017)
The assessment of liver fibrosis stage by two-dimensional shear wave ultrasound and transient elastography in patients with chronic liver disease
Authors: S.G. Kim, B. Lee, J.J. Yoo, Y.S. Kim, S.W. Jeong, J. Youn Jang, S.H. Lee, Y.D. Kim, G.J. Cheon, H.S. Kim, B.S. Kim
Journal: Journal of Hepatology (2017)
Safety and tolerability of veliparib combined with capecitabine plus radiotherapy in patients with locally advanced rectal cancer (LARC): Final results of a phase Ib study.
Authors: Michael Michael, Mary Frances Mulcahy, Dustin A. Deming, Houman Vaghefi, Gayle S. Jameson, Angela DeLuca, Hao Xiong, Wijith Munasinghe, Matthew W. Dudley, Philip Komarnitsky, Kyle D. Holen, Brian G. Czito
Journal: Journal of Clinical Oncology (2015)

3517 Background: Standard treatment for patients (pts) with LARC consists of chemoradiation followed by surgery. To achieve higher response rates and reduce risk of recurrence, further optimization is needed. Veliparib (ABT-888), a potent orally bioavailable PARP1/2 inhibitor, has been shown to enhance antitumor activity of chemotherapy and radiotherapy (RT) in preclinical models. Herein, we present the final results from a phase Ib dose-escalation study (NCT01589419) of veliparib plus capecitabine (C) and RT (C/RT) in pts with LARC. Methods: Stage II/III rectal cancer pts ( ≥ 18 years) received C (p.o. 825 mg/m2 BID) and RT (1.8 Gy QD) for approx. 5.5 weeks (5 days/week). Veliparib (p.o. 20–400 mg BID) was administered from day 2 until 2 days after RT (7 days/week). Pts underwent surgery 5–10 weeks after RT. Primary objectives were to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of veliparib plus C/RT, using an exposure-adjusted continual reassessment method. Safety, pharmacokinetics (PK), and antitumor activity were also assessed. Results: As of 23 Nov 2014, 32 pts (81% male, median age 57 years) received study treatment (veliparib < 400 mg, n = 16; 400 mg, n = 16). Most common adverse events possibly or probably related to treatment were fatigue (41%), nausea (41%), diarrhea (25%), and vomiting (22%); grade 3/4 events were diarrhea (n = 2), anemia, lymphopenia, and pulmonary embolism (n = 1 each). Dose-limiting toxicities (grade 2) occurred in 2 pts: radiation skin injury, and nausea and vomiting, at 70 and 400 mg veliparib, respectively. The MTD was not reached. The RP2D for veliparib was 400 mg BID. Veliparib (20–70 mg BID) PK was dose proportional, with no clear impact on the PK of C. Postsurgery tumor downstaging was observed in 72% of 32 evaluable pts; 28% achieved a pathologic complete response. Sphincter-sparing surgery was performed in 70% of 30 evaluable pts. Conclusions: Veliparib plus C/RT had an acceptable safety profile in LARC pts and the RP2D is 400 mg BID. Veliparib showed a dose-proportional PK profile and no effect on the PK of C. The combination treatment showed promising preliminary antitumor activity. Clinical trial information: NCT01589419.