Medicine and Health Sciences Commons^™

An Atypical Presentation Of Lichen Planus-Like Reaction From Pembrolizumab., M. Lee, N. Seetharamu

Journal Articles

Introduction:With the advent of immunotherapy, a new subtype of side effects called IRAEs or immune related adverse effects have become more common. They may present in various organ systems as colitis, pneumonitis, hypophysitis, and thyroiditis and commonly as dermatological reactions. Case:This is a case report of a lung cancer patient that was started on Pembrolizumab and developed shortly after what appeared to be clinically at first pustular psoriasis but on biopsy was confirmed to be lichen planus. She was discontinued on the Pembrolizumab and treated with both systemic and topical steroids and improved. Conclusion:This case highlights a cutaneous reaction from …

Excellent Response To Nivolumab And Ipilimumab In Metastatic Gastroesophageal Junction Squamous Carcinoma., N. Sadagopan, C. Devoe

Journal Articles

Unresectable gastroesophageal junction (GEJ) cancers have a poor prognosis and limited treatment options. We report the case of a patient with a Siewert class III gastroesophageal junction squamous carcinoma with metastatic spread into the liver who had an exceptional response to a combination therapy of nivolumab and ipilimumab despite being programmed death-ligand 1 (PD-L1) negative, microsatellite stable (MSS), and having a low tumor mutational burden. He initially experienced disease progression on the chemotherapy regimens modified DCF and FOLFIRI resulting in limited functional status, esophageal stent placement, and feeding tube placement. After about 6 months on nivolumab and ipilimumab, he had …

Older-Patient-Specific Cancer Trials: A Pooled Analysis Of 2,277 Patients (A151715)., D. Dao, T. Zemla, A. Jatoi, R. A. Freedman, A. Hurria, H. Muss, H. J. Cohen, M. Citron, D. Budman, J. G. Le-Rademacher, +6 Additional Authors

Journal Articles

BACKGROUND: Less than 3% of older patients with cancer are enrolled in clinical trials. To reverse this underrepresentation, we compared older patients enrolled with older-patient-specific trials, defined as those designed for older patients with cancer, with those enrolled in age-unspecified trials.

MATERIALS AND METHODS: We focused on individual patient data from those ≥65 years (younger patients excluded) and included all Alliance phase III adjuvant breast cancer trials from 1985-2012.

RESULTS: Among 2,277 patients, 1,014 had been enrolled to older-patient-specific and 1,263 to age-unspecified trials. The median age (range) in the older-patient-specific trials was 72 (65-89) years compared with 68 (65-84) …

Merkel Cell Carcinoma Masquerading As Cellulitis: A Case Report And Review Of The Literature, F. Safa, M. Pant, C. Weerasinghe, R. Felix, T. Terjanian

Journal Articles

© 2018 Multimed Inc. Merkel cell carcinoma (MCC) is an uncommon malignancy of the skin arising from cells located in the deeper layers of the epidermis called Merkel cells. This malignancy rarely presents as a metastatic disease, and the field is therefore deficient in regards to management. We report the case of a 49-year-old woman who presented with a presumptive diagnosis of osteomyelitis of the left fifth digit that was resistant to treatment with antibiotics; she underwent debridement of the digit that revealed MCC and was later to have metastatic disease to her lungs, liver, and musculoskeletal system. The management …

Mutation Patterns Identify Adult Patients With De Novo Acute Myeloid Leukemia Aged 60 Years Or Older Who Respond Favorably To Standard Chemotherapy: An Analysis Of Alliance Studies, A. K. Eisfeld, J. Kohlschmidt, K. Mrózek, J. S. Blachly, C. J. Walker, D. Nicolet, S. Orwick, S. E. Maharry, J. E. Kolitz, C. D. Bloomfield, +6 Additional Authors

Journal Articles

© 2018 Macmillan Publishers Limited, part of Springer Nature. Thus far, only 5-15% of AML patients aged ≥60 years are cured with chemotherapy. Identification of patients who are less (more) likely to respond to standard chemotherapy might enable early risk stratification toward alternative treatment regimens. We used a next-generation sequencing panel of 80 cancer- and/or leukemia-associated genes to profile molecularly 423 older patients with de novo AML. Using variables identified in multivariable models and co-occurring mutations in NPM1-mutated AML, we classified the patients into good-, intermediate-, and poor-risk groups for complete remission (CR) attainment, disease-free (DFS), and overall survival (OS). …

Oral Curcumin For Radiation Dermatitis: A Urcc Ncorp Study Of 686 Breast Cancer Patients, J. R. Wolf, C. E. Heckler, J. J. Guido, A. R. Peoples, J. S. Gewandter, M. Ling, V. P. Vinciguerra, T. Anderson, L. Evans, G. R. Morrow, +2 Additional Authors

Journal Articles

No abstract provided.

Hybrid Capture–Based Genomic Profiling Of Circulating Tumor Dna From Patients With Advanced Cancers Of The Gastrointestinal Tract Or Anus, A. B. Schrock, D. Pavlick, S. J. Klempner, J. H. Chung, B. Forcier, A. Welsh, L. Young, B. Leyland-Jones, C. Devoe, V. A. Miller, +9 Additional Authors

Journal Articles

© 2018 American Association for Cancer Research. Purpose: Genomic profiling of tumor biopsies from advanced gastrointestinal and anal cancers is increasingly used to inform treatment. In some cases, tissue biopsy can be prohibitive, and we sought to investigate whether analysis of blood-derived circulating tumor DNA (ctDNA) may provide a minimally invasive alternative. Experimental Design: Hybrid capture–based genomic profiling of 62 genes was performed on blood-based ctDNA from 417 patients with gastrointestinal carcinomas to assess the presence of genomic alterations (GA) and compare with matched tissue samples. Results: Evidence of ctDNA was detected in 344 of 417 samples (82%), and of …

Nf1 Mutations Are Recurrent In Adult Acute Myeloid Leukemia And Confer Poor Outcome, A. K. Eisfeld, J. Kohlschmidt, K. Mrózek, A. Mims, C. J. Walker, J. S. Blachly, D. Nicolet, S. Orwick, J. E. Kolitz, C. D. Bloomfield, +7 Additional Authors

Journal Articles

© 2018 Macmillan Publishers Limited, part of Springer Nature Targeted mutation assessment of 81 genes in 1021 adults with de novo acute myeloid leukemia (AML) identified recurrent mutations in the neurofibromin 1 (NF1) gene in 52 (5.1%) patients, including 36 (5.2%) younger and 16 (4.8%) older patients, which suggests NF1 belongs to the 20 most frequently mutated genes in adult AML. NF1 mutations were found throughout the gene, and comprised missense, frameshift, and nonsense mutations. One mutation hotspot, at amino acid threonine 676 (Thr676), was found in 27% of AML patients with NF1 mutations. NF1-mutated patients belonged more often to …

Renal Involvement In Chronic Lymphocytic Leukemia., R. Wanchoo, C. Bernabe Ramirez, J. Barrientos, K. D. Jhaveri

Journal Articles

Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed adult leukemia in the USA and Western Europe. Kidney disease can present in patients with CLL as a manifestation of the disease process such as acute kidney injury with infiltration or with a paraneoplastic glomerular disease or as a manifestation of extra renal obstruction and tumor lysis syndrome. In the current era of novel targeted therapies, kidney disease can also present as a complication of treatment. Tumor lysis syndrome associated with novel agents such as the B-cell lymphoma 2 inhibitor venetoclax and the monoclonal antibody obinutuzumab are important nephrotoxicities associated with …

Chylothorax In Patients With Chronic Lymphocytic Leukemia: A Case Series., D. Sammartino, S. Khanijo, S. Koenig, J. F. Katsetos, A. Tufano, K. R. Rai, J. C. Barrientos

Journal Articles

Chylothorax, which is defined as the presence of chyle in the pleural space, is often caused by malignancy. However, chylothorax as a result of underlying CLL is exceedingly rare in the literature. Chyle contains fat soluble vitamins and lymphocytes, meaning that its collection into the pleural space may further exacerbate the immunosupressed state of an individual with CLL. Here, we report three cases of patients with CLL who developed chylothorax, and their management. Chylothorax, although rare with CLL, should be considered in the differential diagnosis when patients with CLL present with pleural effusions, especially if recurrent. Discovery of a chylothorax …

Bi-Specific And Tri-Specific Antibodies- The Next Big Thing In Solid Tumor Therapeutics, K. Runcie, D. R. Budman, V. John, N. Seetharamu

Journal Articles

No abstract provided.

Extended Follow-Up And Impact Of High-Risk Prognostic Factors From The Phase 3 Resonate Study In Patients With Previously Treated Cll/Sll, J. R. Brown, P. Hillmen, S. O'Brien, J. C. Barrientos, N. M. Reddy, S. E. Coutre, C. S. Tam, S. P. Mulligan, U. Jaeger, J. C. Byrd, +20 Additional Authors

Journal Articles

No abstract provided.

Cpx-351 (Cytarabine And Daunorubicin) Liposome For Injection Versus Conventional Cytarabine Plus Daunorubicin In Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia, J. E. Lancet, G. L. Uy, J. E. Cortes, L. F. Newell, T. L. Lin, E. K. Ritchie, R. K. Stuart, S. A. Strickland, J. E. Kolitz, B. C. Medeiros, +11 Additional Authors

Journal Articles

© 2018 by American Society of Clinical Oncology. Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of …

Genome-Wide Association Study Identifies An Acute Myeloid Leukemia Susceptibility Locus Near Bicra, C. J. Walker, C. C. Oakes, L. K. Genutis, B. Giacopelli, S. Liyanarachchi, D. Nicolet, A. K. Eisfeld, M. Scholz, J. E. Kolitz, C. D. Bloomfield, +12 Additional Authors

Journal Articles

No abstract provided.

Activity Of Pazopanib And Trabectedin In Advanced Alveolar Soft Part Sarcoma, S. Stacchiotti, O. Mir, A. Le Cesne, B. Vincenzi, A. Fedenko, R. G. Maki, N. Somaiah, S. Patel, M. Brahmi, A. Kawai, +13 Additional Authors

Journal Articles

No abstract provided.

Synchronous Presence Of Egfr, Alk Driver Mutations Along With Pd L1 Overexpression In A Resected Early Stage Non-Small Cell Lung Cancer: A Case Report And Review Of Literature., N. Thumallapally, S. Parylo, A. Vennepureddy, U. Ibrahim, A. Sokoloff

Journal Articles

Treatment of lung cancer has been revolutionized with development of drugs that target key driver mutations and immune checkpoints. Until recently, it was believed that these driver mutations are mutually exclusive. However, few reports have emerged citing the presence of both mutations either synchronously or metachronously. We describe a case report of lung adenocarcinoma harboring two driver mutations in the same tumor cells as well as exhibiting high PDL1 expression. We further discuss the possible association of these driver mutations with PDL1 expression.

Discovery And Functional Implications Of A Mir-29b-1/Mir-29a Cluster Polymorphism In Acute Myeloid Leukemia, A. Ngankeu, P. Ranganathan, V. Havelange, D. Nicolet, S. Volinia, B. L. Powell, J. E. Kolitz, G. L. Uy, R. M. Stone, R. Garzon, +4 Additional Authors

Journal Articles

© Ngankeu et al. We previously reported that microRNA (miR)-29b is down-regulated and has a tumor suppressor role in acute myeloid leukemia (AML). However, little is known about the mechanisms responsible for miR-29b expression downregulation in AML. In this work we screened for mutations that could affect miR-29b expression. Using Sanger sequencing, we identified a germline thymidine (T) base deletion within the miR-29b-1/miR-29a cluster precursor in 16% of AML patients. Remarkably we found a significant enrichment for the presence of the miR-29 polymorphism in core binding factor (CBF) newly diagnosed AML patients (n = 61/303; 20%) with respect to age, …

Repurposing Mebendazole As A Replacement For Vincristine For The Treatment Of Brain Tumors, M. De Witt, A. Gamble, D. Hanson, D. Markowitz, C. Powell, S. Al Dimassi, M. Atlas, J. Boockvar, R. Ruggieri, M. Symons

Journal Articles

No abstract provided.

Relationship Between Obesity And Clinical Outcome In Adults With Acute Myeloid Leukemia: A Pooled Analysis From Four Calgb (Alliance) Clinical Trials, J. J. Castillo, F. Mulkey, S. Geyer, J. E. Kolitz, W. Blum, B. L. Powell, S. L. George, R. A. Larson, R. M. Stone

Journal Articles

Obesity has been previously suggested as an adverse prognostic marker in patients with acute leukemia. To evaluate the relationship between obesity and clinical outcome, disease-free survival (DFS) and overall survival (OS), in patients with acute myelogenous leukemia (AML), including acute promyelocytic leukemia (APL), we performed a pooled analysis of four CALGB (Alliance) clinical trials. Our study included 446 patients with APL from CALGB 9710, and 1,648 patients between 18 and 60 years of age with non-APL AML from CALGB 9621, 10503, and 19808. Obesity was defined as BMI >/=30 kg/m(2) . Multivariate Cox proportional-hazard regression models were fitted for DFS …

Sotatercept (Ace-011) For The Treatment Of Chemotherapy-Induced Anemia In Patients With Metastatic Breast Cancer Or Advanced Or Metastatic Solid Tumors Treated With Platinum-Based Chemotherapeutic Regimens: Results From Two Phase 2 Studies, H. Raftopoulos, A. Laadem, P. J. Hesketh, J. Goldschmidt, N. Gabrail, C. Osborne, M. Ali, M. L. Sherman, D. Wang, J. Crawford, +3 Additional Authors

Journal Articles

PURPOSE: Sotatercept may represent a novel approach to the treatment of chemotherapy-induced anemia (CIA). We report the results from two phase 2 randomized studies examining the use of sotatercept for the treatment of CIA in patients with metastatic cancer. METHODS: In study A011-08, patients with metastatic breast cancer were randomized to 2:2:2:1 to receive sotatercept 0.1, 0.3, or 0.5 mg/kg, or placebo, respectively, every 28 days. In study ACE-011-NSCL-001, patients with solid tumors treated with platinum-based chemotherapy received sotatercept 15 or 30 mg every 42 days. The primary endpoint for both studies was hematopoietic response, defined as a hemoglobin (Hb) …

A Phase Ii Randomized Trial Comparing Standard And Low Dose Rituximab Combined With Alemtuzumab As Initial Treatment Of Progressive Chronic Lymphocytic Leukemia In Older Patients: A Trial Of The Ecog-Acrin Cancer Research Group (E1908), C. S. Zent, X. V. Wang, R. P. Ketterling, C. A. Hanson, E. N. Libby, J. C. Barrientos, T. G. Call, J. E. Chang, J. J. Liu, M. S. Tallman, +5 Additional Authors

Journal Articles

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients requiring initial therapy are often older and frailer and unsuitable candidates for standard chemoimmunotherapy regimens. Shorter duration combination monoclonal antibody (mAb) therapy using alemtuzumab and rituximab has been shown to be effective and tolerable treatment for CLL. Standard dose anti-CD20 mAb therapy causes loss of CD20 expression by surviving CLL cells, which can be minimized by decreasing the mAb dose. We report a randomized phase II clinical trial enrolling older (>/= 65 years) patients (median age 76 years, n=31) with treatment naive progressive CLL. Patients received 8-12 weeks of standard subcutaneous alemtuzumab …

Acalabrutinib (Acp-196) In Relapsed Chronic Lymphocytic Leukemia, J. C. Byrd, B. Harrington, S. O'Brien, J. A. Jones, A. Schuh, S. Devereux, J. Chaves, W. G. Wierda, J. C. Barrientos, R. R. Furman, +20 Additional Authors

Journal Articles

Background Irreversible inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromises its therapeutic index. Acalabrutinib (ACP-196) is a more selective, irreversible BTK inhibitor that is specifically designed to improve on the safety and efficacy of first-generation BTK inhibitors. Methods In this uncontrolled, phase 1-2, multicenter study, we administered oral acalabrutinib to 61 patients who had relapsed CLL to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of acalabrutinib. Patients were treated with acalabrutinib at a dose of 100 …

A Quantitative Proteomics-Based Signature Of Platinum Sensitivity In Ovarian Cancer Cell Lines, G. Fan, K. O. Wrzeszczynski, C. Fu, G. Su, D. J. Pappin, R. Lucito, N. K. Tonks

Journal Articles

Although DNA encodes the molecular instructions that underlie the control of cell function, it is the proteins that are primarily responsible for implementing those instructions. Therefore quantitative analyses of the proteome would be expected to yield insights into important candidates for the detection and treatment of disease. We present an iTRAQ (isobaric tag for relative and absolute quantification)-based proteomic analysis of ten ovarian cancer cell lines and two normal ovarian surface epithelial cell lines. We profiled the abundance of 2659 cellular proteins of which 1273 were common to all 12 cell lines. Of the 1273, 75 proteins exhibited elevated expression …

Reciprocal Interaction Of Wnt And Rxr-Alpha Pathways In Hepatocyte Development And Hepatocellular Carcinoma, J. Li, M. Chanrion, E. Sawey, T. Wang, E. Chow, A. Tward, Y. Su, W. Xue, R. Lucito, L. Zender, +3 Additional Authors

Journal Articles

Genomic analysis of human hepatocellular carcinoma (HCC) is potentially confounded by the differentiation state of the hepatic cell-of-origin. Here we integrated genomic analysis of mouse HCC (with defined cell-of-origin) along with normal development. We found a major shift in expression of Wnt and RXR-alpha pathway genes (up and down, respectively) coincident with the transition from hepatoblasts to hepatocytes. A combined Wnt and RXR-alpha gene signature categorized HCCs into two subtypes (high Wnt, low RXR-alpha and low Wnt, high RXR-alpha), which matched cell-of-origin in mouse models and the differentiation state of human HCC. Suppression of RXR-alpha levels in hepatocytes increased Wnt …

Quality Of Life And Symptom Assessment In Randomized Clinical Trials Of Bladder Cancer: A Systematic Review, M. A. Feuerstein, M. Jacobs, A. Piciocchi, B. Bochner, A. Pusic, P. Fayers, J. Blazeby, F. Efficace, Promotion Registry Patient-Reported Outcome Measurements Over Time In Oncology

Journal Articles

OBJECTIVES: Patient-reported outcomes (PRO) help patients, caretakers, clinicians, and policy makers make informed decisions regarding treatment effectiveness. Our objective was to assess the quality of PRO reporting and methodological strengths and weaknesses in randomized controlled trials (RCT) in bladder cancer.; METHODS: A systematic literature search of bladder cancer RCT published between January 2004 and March 2014 was performed. Relevant studies were evaluated using a predetermined extraction form that included trial demographics, clinical and PRO characteristics, and standards of PRO reporting based on recommendations of the International Society for Quality of Life Research.; RESULTS: In total, 9 RCTs enrolling 1,237 patients …

Humoral Immune Response Against Nontargeted Tumor Antigens After Treatment With Sipuleucel-T And Its Association With Improved Clinical Outcome, D. Guhathakurta, N. A. Sheikh, L. Q. Fan, H. Kandadi, T. C. Meagher, S. J. Hall, J. B. Whitmore, M. W. Frohlich, J. B. Trager, C. G. Drake, +7 Additional Authors

Journal Articles

PURPOSE: Antitumor activity of cancer immunotherapies may elicit immune responses to nontargeted (secondary) tumor antigens, or antigen spread. We evaluated humoral antigen spread after treatment with sipuleucel-T, an immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), designed to target prostatic acid phosphatase (PAP; primary antigen). EXPERIMENTAL DESIGN: Serum samples from patients with mCRPC enrolled in the placebo-controlled phase III IMPACT study (evaluable n = 142) were used to assess humoral antigen spread after treatment with sipuleucel-T. Immunoglobulin G (IgG) responses to self-antigens (including tumor antigens) were surveyed using protein microarrays and confirmed using Luminex xMAP. IgG responses …

Romidepsin In Peripheral And Cutaneous T-Cell Lymphoma: Mechanistic Implications From Clinical And Correlative Data, S. E. Bates, R. Eisch, A. Ling, D. Rosing, M. Turner, S. Pittaluga, H. M. Prince, M. H. Kirschbaum, S. L. Allen, R. L. Piekarz, +15 Additional Authors

Journal Articles

Romidepsin is an epigenetic agent approved for the treatment of patients with cutaneous or peripheral T-cell lymphoma (CTCL and PTCL). Here we report data in all patients treated on the National Cancer Institute 1312 trial, demonstrating long-term disease control and the ability to retreat patients relapsing off-therapy. In all, 84 patients with CTCL and 47 with PTCL were enrolled. Responses occurred early, were clinically meaningful and of very long duration in some cases. Notably, patients with PTCL receiving romidepsin as third-line therapy or later had a comparable response rate (32%) of similar duration as the total population (38%). Eight patients …

Therapeutic Potential Of New B Cell-Targeted Agents In The Treatment Of Elderly And Unfit Patients With Chronic Lymphocytic Leukemia, K. R. Rai

Journal Articles

Chronic lymphocytic leukemia (CLL), the most common adult leukemia in the Western world, is primarily a disease of the elderly, with most patients >= 65 years of age and having at least one major comorbidity. Aggressive chemoimmunotherapy regimens recommended to achieve remission and improve survival in young, fit patients are often poorly tolerated in elderly and/or less physiologically fit ("unfit") patients, necessitating alternative treatment options. Although patient age, fitness, and comorbidities are key considerations in the selection of a treatment regimen, historically, clinical trials have been limited to young, fit patients by virtue of the ethical concerns associated with potential …

Successful Pregnancy Outcome In Paroxysmal Nocturnal Hemoglobinuria (Pnh) Following Escalated Eculizumab Dosing To Control Breakthrough Hemolysis, R. Sharma, A. Keyzner, J. Liu, T. Bradley, S. L. Allen

Journal Articles

Pregnancy in women with paroxysmal nocturnal hemoglobinuria (PNH) is associated with increased maternal and fetal morbidity and mortality. There is limited published experience regarding therapy of PNH during pregnancy. We describe a case of a 30 year old female with hypoplastic myelodysplastic syndrome and PNH. After two years of treatment with eculizumab, she became pregnant. She developed breakthrough hemolysis at 20 weeks gestation. Pharmacokinetic and pharmacodynamic studies demonstrated a subtherapeutic eculizumab level with absence of complement blockade. Escalation of her eculizumab dose successfully controlled hemolysis and restored therapeutic eculizumab level and activity. She delivered a healthy baby at 36 weeks.

Tamibarotene In Patients With Acute Promyelocytic Leukaemia Relapsing After Treatment With All-Trans Retinoic Acid And Arsenic Trioxide, D. Sanford, F. Lo-Coco, M. A. Sanz, E. Di Bona, S. Coutre, J. K. Altman, M. Wetzler, S. L. Allen, F. Ravandi, H. Kantarjian, J. E. Cortes

Journal Articles

Treatment of acute promyelocytic leukaemia (APL) with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is highly effective first-line therapy, although approximately 5-10% of patients relapse. Tamibarotene is a synthetic retinoid with activity in APL patients who relapse after chemotherapy and ATRA, but has not been studied in relapse after treatment with ATO and ATRA. We report on a phase II study of tamibarotene in adult patients with relapsed or refractory APL after treatment with ATRA and ATO (n = 14). Participants were treated with tamibarotene (6 mg/m2 /d) during induction and for up to six cycles of consolidation. The …