Publications by authors named "Nagla Abdel Karim"

32 Publications

The Unusual Presentation of a Single Case of Synchronous Metastatic Clear Cell Renal Cell Carcinoma to the Gallbladder: A Case Report and Literature Review.

Curr Health Sci J 2021 Jul-Sep;47(3):457-461. Epub 2021 Sep 30.

Department of Medicine: Hematology and Oncology, Augusta University, Augusta, GA, USA.

Clear cell renal cell carcinoma, accounts for approximately 70% of all adult renal tumors. This disease is well known for its high metastatic potential, with estimates of 25-50% of patients reporting metastasis to distant structures. However, there have only been several reported cases in medical literature describing hematogenous spread to the gallbladder, with the majority occurring metachronously, in males, and with multiple metastases. This case report follows an extremely unique presentation in a 60-year-old female. Although the patient did not exhibit the usual signs and symptoms or meet the typical demographics seen with metastatic renal cell carcinoma, it should find a place on the differential diagnosis list when a gallbladder lesion is detected on imaging during the initial staging and/or restaging in patients with renal-cell carcinoma.
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http://dx.doi.org/10.12865/CHSJ.47.03.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8679144PMC
September 2021

Characterization of KRAS Mutation Subtypes in Non-small Cell Lung Cancer.

Mol Cancer Ther 2021 Dec 13;20(12):2577-2584. Epub 2021 Sep 13.

Department of Hematology-Oncology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania.

is the most commonly mutated oncogene in NSCLC and development of direct KRAS inhibitors has renewed interest in this molecular variant. Different mutations may represent a unique biologic context with different prognostic and therapeutic impact. We sought to characterize genomic landscapes of advanced, -mutated non-small cell lung cancer (NSCLC) in a large national cohort to help guide future therapeutic development.Molecular profiles of 17,095 NSCLC specimens were obtained using DNA next-generation sequencing of 592 genes (Caris Life Sciences) and classified on the basis of presence and subtype of mutations. Co-occurring genomic alterations, tumor mutational burden (TMB), and PD-L1 expression [22C3, tumor proportion score (TPS) score] were analyzed by mutation type.Across the cohort, 4,706 (27.5%) samples harbored a mutation. The most common subtype was G12C (40%), followed by G12V (19%) and G12D (15%). The prevalence of mutations was 37.2% among adenocarcinomas and 4.4% in squamous cell carcinomas. Rates of high TMB (≥10 mutations/Mb) and PD-L1 expression varied across mutation subtypes. G12C was the most likely to be PD-L1 positive (65.5% TPS ≥ 1%) and PD-L1 high (41.3% TPS ≥ 50%). was mutated in 8.6% of wild-type NSCLC but more frequent in -mutant NSCLC, with the highest rate in G13 (36.2%). mutations were more frequent in wild-type NSCLC (73.6%). mutation subtypes have different co-occurring mutations and a distinct genomic landscape. The clinical relevance of these differences in the context of specific therapeutic interventions warrants investigation.
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http://dx.doi.org/10.1158/1535-7163.MCT-21-0201DOI Listing
December 2021

Diagnosis and management of cold agglutinin disease associated with low-grade B-cell lymphoma in a patient receiving pembrolizumab for lung cancer.

BMJ Case Rep 2021 Aug 16;14(8). Epub 2021 Aug 16.

Hematology Oncology, Augusta University, Augusta, Georgia, USA.

A 65-year-old with non-small cell lung cancer developed autoimmune haemolytic anaemia while receiving pembrolizumab containing chemoimmunotherapy. Initially thought to be due to pembrolizumab induced haemolysis, he was treated with steroids, and pembrolizumab was held. Haemolysis was refractory to steroids and blood was observed to agglutinate in cold room temperatures. Cold agglutinins in high titre and monoclonal serum IgM kappa protein were detected. Bone marrow biopsy showed marginal zone lymphoma confirming low grade B-cell lymphoma causing cold agglutinin disease. B-cell depletion by rituximab stopped haemolysis, and pembrolizumab was safely continued for lung cancer.
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http://dx.doi.org/10.1136/bcr-2021-243751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370555PMC
August 2021

Role of indoleamine 2,3-dioxygenase in acute myeloid leukemia.

Future Oncol 2020 Dec 25;16(36):3085-3094. Epub 2020 Sep 25.

Medical Oncology, Augusta University, Augusta, GA 30912, USA.

Indoleamine 2,3 dioxygenase (IDO), first discovered in the 1960s, is an enzyme that has become a highly investigated metabolic target in cancer research. IDO is the rate-limiting step in tryptophan metabolism catabolism into its byproducts - kynurenines. Both IDO and kynurenines have been implicated in altering the tumor microenvironment, allowing for a tolerogenesis by affecting T-cell maturation and proliferation, and more specifically by inducing differentiation into T regulatory cells. Two mechanisms have been suspected in creating this environment: tryptophan starvation and metabolite toxicity. IDO has been shown to be expressed not only in cancer cells but also in antigen-presenting cells. The exact mechanisms underlying the two different sites of expression have not been fully elucidated. To date, most literature has focused on the role of IDO in solid tumors; we provide a review of IDO and its impact on hematological malignancies - more specifically, acute myeloid leukemia. The pathophysiology of IDO will be discussed, including a summarization of the literature to date on how IDO expression effects prognosis and disease progression in acute myeloid leukemia, along with current IDO-specific therapeutics with future considerations.
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http://dx.doi.org/10.2217/fon-2019-0642DOI Listing
December 2020

Anti-PDL1 effect in squamous non-small cell lung cancer.

Transl Lung Cancer Res 2020 Apr;9(2):406-409

Cardiothoracic Surgery Department, Weill Cornell Medicine/New York Presbyterian Hospital, New York, NY, USA.

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http://dx.doi.org/10.21037/tlcr.2020.02.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225162PMC
April 2020

Stenting in Non-Small Cell Lung Cancer: How Does It Affect the Outcomes?

Asian Pac J Cancer Prev 2020 Jan 1;21(1):175-178. Epub 2020 Jan 1.

Hematology-Oncology Department, Vontz Center, University of Cincinnati, Ohio, U S A.

Objective: Approximately 30% of lung cancer patients develop central airway obstruction (CAO) that remarkably shortens survival. There is little data about the benefits of stenting within this heterogeneous patient group. Our objective was to review their overall survival (OS) and their risk of hospitalization versus patients who did not have lesions requiring stent placement.

Methods: We retrospectively reviewed charts of 171 non-small cell lung cancer (NSCLC) patients who underwent bronchoscopy in the University of Cincinnati Cancer Center from the year 2011 to 2013. Twenty-five patients with advanced lung cancer were evaluated by interventional pulmonology service for endobronchial stent placement for CAO. Eight patients did not require placement of a stent and 17 had obstructive lesions that required stenting by interventional pulmonology.

Results: Demographical parameters such as age and gender did not have a significant impact on the risk of hospitalization or OS of both groups of patients, however, those whose lesions did not mandate stent placement had significantly lower odds of hospitalization compared to patients with CAO requiring a stent (OR: 15.913, 95% CI: 1.211-209.068, P = 0.0352). Patients with advanced NSCLC and CAO that required stent placement had an OS of 13.9 m [3.9-19.9 m] compared to an OS of 23.9 m for patients with CAO not requiring a stent. We found out that patients with less severe CAO have lower odds of hospitalization and better OS compared to patients with CAO mandating stent placement.

Conclusion: CAO patients with interventional pulmonology (IP) evaluation and management in addition, may have improved OS suggesting that IP consultation might offer both improvement in quality of life and overall survival to patients with advanced NSCLC and CAO. 
.
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http://dx.doi.org/10.31557/APJCP.2020.21.1.175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294028PMC
January 2020

Exosomes as a Surrogate Marker for Autophagy in Peripheral Blood, Correlative Data from Phase I Study of Chloroquine in Combination with Carboplatin/Gemcitabine in Advanced Solid Tumors.

Asian Pac J Cancer Prev 2019 12 1;20(12):3789-3796. Epub 2019 Dec 1.

Department of Hematology -Oncology, University of Cincinnati, U S A.

Background: Autophagy is a catabolic process, utilized constitutionally by body cells to recycle nutrients and to remove unwanted/damaged intracellular constituents. It is enhanced during periods of stress, such as starvation and hypoxia, aiding in cell survival and it is linked to major cellular processes, such as apoptosis and antigen expression. The process has been extensively studied in vitro models or tumor tissue samples with rare application on human subjects.

Methods: Plasma samples from 24 advanced solid tumor patients were collected at different time points before and after chemotherapy. Their exosomes were isolate and blotted for microtubule-associated protein-1 light chain-3 (LC-3B) protein as a marker for autophagy. All the subjects received a standard chemotherapy regimen of carboplatin- gemcitabine with chloroquine (CQ)/ hydroxychloroquine (HCQ) in chronic doses throughout their treatment period as an autophagy modulator. CQ/HCQ was given in 50 mg increments as guided by their tolerability to treatment.

Results: A total of 267 plasma samples were obtained for the 24 patients and processed. Each sample corresponds to a single time point. The first group included 6 patients, all received 50 mg of CQ with chemotherapy. LC-3B I was detected in their isolated exosomes, while LC3-BII was not detected in their samples. The second cohort of patients included 3 subjects who re-ceived 100mg of HCQ. They demonstrated both LC3-BI and II on day 15 after chemotherapy in one patient, and on third cycle after 24 hours in the second patient. The third cohort included 3 subjects who received 150 mg of HCQ. All cases demonstrated LC3-BI and II on first cycle of treatment after less than 24 hours. The last cohort included 8 subjects, who received a fixed dose of 100 mg of HCQ with treatment. In this cohort, we were able to detect both LC3-B isoforms on advanced time points of second and third cycles.

Conclusion: Detection of autophagy protein LC3-B in exosomes serves as a dynamic method to monitor autophagy. It can be utilized to study the effects of anti-neoplastic agents on autophagy and mechanisms of drug resistance, however, to standardize our results a larger specimen of patients should be included.
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http://dx.doi.org/10.31557/APJCP.2019.20.12.3789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173380PMC
December 2019

Corrigendum to "Nivolumab and Ipilimumab in the Treatment of Metastatic Uveal Melanoma: A Single-Center Experience".

Case Rep Oncol Med 2019;2019:3868790. Epub 2019 Oct 28.

Department of Internal Medicine, Division of Hematology/Oncology, Medical College of Georgia-Augusta University, Augusta, GA, USA.

[This corrects the article DOI: 10.1155/2019/3560640.].
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http://dx.doi.org/10.1155/2019/3868790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854979PMC
October 2019

Papillary renal cell carcinoma: what is missing in research? A case report and a review of literature.

SAGE Open Med Case Rep 2019 28;7:2050313X19869475. Epub 2019 Aug 28.

Division of Hematology/Oncology, Stem Cell Transplantation, University of Cincinnati, Cincinnati, OH, USA.

The incidence of renal cell carcinomas in adults ranges has been increasing over the past decades in both men and women. Once the incidence was 2.9%, now is reported to have increased to 3%-5% with male predominance according to the most recent reports of cancer statistics. The disease typically describes a group of different histopathological subtypes; the most common is clear cell carcinoma which accounts for 70%-80% of the diagnosed cases, while papillary renal cell carcinoma and chromophobe types represent 20% and 5%, respectively. In 1996, the renal cell carcinomas Heidelberg classification was introduced by Delahunt et al. It divides renal cell tumors into benign and malignant parenchymal neoplasms, excluding Wilm's tumor and secondary metastases and limiting each subcategory to the most commonly documented genetic abnormalities, if applicable. In this report, we discuss a case of metastatic type I papillary renal cell carcinoma treated with the anti-vascular endothelial growth factor receptor sunitinib and showing marked long-term clinical response. Through this case, we highlight the importance of re-classifying papillary renal cell carcinoma subtypes to prioritize the clinical management of these cases.
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http://dx.doi.org/10.1177/2050313X19869475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713961PMC
August 2019

Retrospective Study of the Effect of Statins on the Outcome of Lung Cancer Patients, University of Cincinnati Experience.

Asian Pac J Cancer Prev 2019 08 1;20(8):2391-2396. Epub 2019 Aug 1.

Department of Hematology-Oncology, Division of Internal Medicine, Vontz Center for Molecular Studies, University of Cincinnati, 3125 Eden Ave, Cincinnati OH 45267, United States. Email:

Objectives: Numerous studies addressed the effect of statin on cancer patients. The aim of this study is to define the effect of statin administration with chemotherapy on the patients’ outcomes. Methods: We retrospectively researched the database of the University of Cincinnati cancer to identify lung cancer patients who received statins (S+, n=41) during their treatment in our institute. We also, retrieved data for contemporaneously treated patients who did not receive statins (S-, n=159) as a control arm. Clinico-demographical data and overall survival (OS) were analyzed using Pearson’s Chi-square (χ2) test and Kaplan-Meier survival curves with Log-rank test. Adjustment using Cox proportional hazard ratios (HR) were done based on (age, gender, race and stage) to identify effect of statins on their outcomes. Results: The median age for S+ was 64y (IQR; 55-69) and 71.2% of the patients were white. Histopathology was 55.4% and 31.7% for adenocarcinoma and squamous cell carcinoma, respectively. Fifty-six percent were stage IV in each study arm and the median OS was14.9 m. Median OS was insignificantly lower in S–ve arm (13.7 vs 15.6 months; P=0.652, HR=0.91, 95%CI 0.52-1.57). Our results show that after different types of adjustments, S+ did not show survival advantage (P>0.05) compared to the control arm. Conclusion: While showing an increase in overall survival in patients with advanced lung cancer, the results of this study did not reach statistical significance. This could be due for the small sample size of this retrospective study.
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http://dx.doi.org/10.31557/APJCP.2019.20.8.2391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852798PMC
August 2019

Nivolumab and Ipilimumab in the Treatment of Metastatic Uveal Melanoma: A Single-Center Experience.

Case Rep Oncol Med 2019 17;2019:3560640. Epub 2019 Apr 17.

Department of Internal Medicine, Division of Hematology/Oncology, Medical College of Georgia-Augusta University, Augusta, GA, USA.

Background: Metastatic uveal melanoma (MUM) is associated with a poor prognosis, with a median overall survival (OS) of 4-15 months. Despite new insights into the genetic and molecular background of MUM, satisfactory systemic treatment approaches are currently lacking. The study results of innovative treatment strategies are urgently needed.

Patients And Methods: This was a retrospective case series of 8 patients with MUM managed at the University of Cincinnati between January 2015 and January 2018. The immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 1.1 criteria were used for patient evaluation, and magnetic resonance imaging was used for evaluation at treatment checkpoints.

Objective: To assess the clinical outcome of patients with MUM treated with a combination of checkpoint inhibitors.

Results: The series included eight patients, six men and two women, with MUM. Their median age at MUM diagnosis was 69 (range, 55-77) years. All patients were treated with ipilimumab and nivolumab combination along with transarterial chemoembolization (TACE), followed by nivolumab maintenance and monthly TACE procedures. The majority of patients had a partial response or stable disease. Two of the patients had partial response, while four others had stable disease. Two other patients experienced disease progression.

Conclusion: We report the outcomes of eight patients with MUM treated with the combination of ipilimumab and nivolumab. We report the clinical outcome and toxicity associated with this treatment approach. Further studies are warranted to explore immunotherapy in MUM. These findings support the consideration of immunotherapy in MUM.
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http://dx.doi.org/10.1155/2019/3560640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501230PMC
April 2019

Cardiotoxicity with immune system targeting drugs: a meta-analysis of anti-PD/PD-L1 immunotherapy randomized clinical trials.

Immunotherapy 2019 06;11(8):725-735

Cardiothoracic Surgery Departments, Weill Cornell Medicine, New York, NY 14853, USA.

With antiprogrammed death receptor-1 (anti-PD-L1) therapy, a recent meta-analysis reported higher incidence of cutaneous, endocrine and gastrointestinal complications especially with dual anti-PD-L1 immunotherapy (IMM). Our primary outcome was assessment of all cardiotoxicity grades in IMM compared with different treatments, thus a systemic review and a meta-analysis on randomized clinical trials (RCTs) were done. We included 11 RCTs with 6574 patients (3234 patients in IMM arm vs 3340 patients in the other arm). Three non-small-cell lung cancer RCTs, seven melanoma RCTs and only one prostatic cancer RCT met the inclusion criteria. There were five RCTs that compared monoimmunotherapy to chemotherapy "(n = 2631 patients)". No difference exists in all cardiotoxicity grades or high-grade cardiotoxicity (p > 0.05). Lung cancer exhibited a higher response rate and lower mortality in IMM. There was no reported statistically significant cardiotoxicity associated with anti-PD/PD-L1 use. Lung cancer subgroups showed better response and survival rates.
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http://dx.doi.org/10.2217/imt-2018-0118DOI Listing
June 2019

Role of Targeted Therapy and Immune Checkpoint Blockers in Advanced Non-Small Cell Lung Cancer: A Review.

Oncologist 2019 09 26;24(9):1270-1284. Epub 2019 Mar 26.

University of California Davis Comprehensive Cancer Center, Sacramento, California, USA.

Advanced non-small cell lung cancer (NSCLC) is a complex disease comprising molecularly distinct tumor types, each with a unique biology that is becoming increasingly better characterized. The aim of this review is to present an optimized treatment schema and the accompanying diagnostic testing approach for patients with advanced NSCLC. There are a number of therapies currently approved for patients with advanced NSCLC, including agents that target particular oncogenic drivers, as well as immune checkpoint blockers (ICBs) that elicit an antitumor response. Identification of genetic alterations (e.g., epidermal growth factor receptor, anaplastic lymphoma kinase, reactive oxygen species proto-oncogene 1, B-Raf proto-oncogene) or programmed cell death ligand-1 expression levels in NSCLC requires diligent molecular testing at initial diagnosis and, in some cases, at disease progression to ensure the most efficacious treatment is delivered. Accurate molecular diagnostic testing, along with the careful selection of currently approved targeted agents, ICBs, or systemic chemotherapy, provides therapy that is personalized according to patients' needs to achieve the best possible outcome. Enrollment in clinical trials that further the development of tailored therapies is highly recommended at all stages of treatment. IMPLICATIONS FOR PRACTICE: Targeted therapies and immune checkpoint blockers provide effective and tailored options for patients with non-small cell lung cancer. Careful molecular analysis of tumor samples is necessary to identify the genetic alterations that are present, to ensure that each patient receives the most efficacious treatment for their specific tumor type. Personalized therapy provides each patient with the best probability for prolonged survival. Enrolling patients in clinical trials should be the first consideration before making each treatment decision.
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http://dx.doi.org/10.1634/theoncologist.2018-0112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738296PMC
September 2019

Myeloid Sarcoma.

Oncol Res Treat 2019 6;42(4):224-229. Epub 2019 Mar 6.

Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.

Hematological malignancies can manifest as extramedullary soft tissue masses in relatively rare cases. The rarity of it causes a diagnostic and therapeutic challenge. One of the rarest manifestations is myeloid sarcoma (MS). MS develops as part of acute myeloid leukemia, myeloproliferative neoplasm, or myelodysplastic syndrome or at relapse, especially following allogeneic hematopoietic stem cell transplant. The tumor displays high myeloperoxidase expression, hence the color green, and is called chloroma. It most commonly appears in lymph nodes, skin and soft tissues, bone, testes, gastrointestinal tract, and peritoneum. Immunohistochemistry shows CD68-KP1 as the most commonly expressed marker, then myeloperoxidase, CD117, CD99, CD68/PG-M1, lysozyme, CD34, terminal deoxynucleotidyl transferase, CD56, CD61, CD30, glycophorin A, and CD4. Different chromosomal abnormalities including MLL rearrangement, t(8; 21), monosomy 7, trisomy 8, trisomy 11, trisomy 4, inversion (16), monosomy 16,16q deletion, 5q deletion, and 20q deletion were reported. Most of the literature about MS are case reports and small retrospective studies, thus there is limited clinical knowledge of the cases and their presentation and management plans. Here, we provide a review of what has been reported in the literature about MS in the light of our experiences.
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http://dx.doi.org/10.1159/000497210DOI Listing
September 2019

Small or Non-Small Cell Lung Cancer Based Therapy for Treatment of Large Cell Neuroendocrine Cancer of The Lung? University of Cincinnati Experience.

J Oncol 2018 1;2018:9761826. Epub 2018 Nov 1.

Department of Hematology-Oncology, Vontz Center for Molecular Studies, University of Cincinnati, 3125 Eden Ave, Cincinnati, OH 45267, USA.

Large cell neuroendocrine cancer (LCNEC) of the lung exhibits morphological and immunohistochemical characteristics of both neuroendocrine and large cell carcinomas. No defined optimal therapy has been described for this subset of patients and the question of whether these patients should be treated with non-small cell lung cancer (NSCLC) treatment protocols, according to the National Comprehensive Cancer Network (NCCN) guidelines, or with small cell lung cancer (SCLC) due to histological and clinical similarities is still uncertain. We conducted a retrospective review of patients identified with diagnosis of LCNEC of the lung at the University of Cincinnati Cancer Center from the year 2002 to 2012 to determine which treatment approach resulted in improved outcomes in this rare category of disease. Patients who received chemotherapy whether NSCLC (group A) or SCLC (group B) protocols did not show significant changes in OS (P=0.911). Meanwhile, patients who underwent surgery (group C) had better OS compared to groups A and B (P= 0.027 and 0.024, respectively). This analysis reveals that outcomes for SCLC or NSCLC treatment strategies in LCNEC patients did not result in survival advantages and future research should be addressing it as a separate entity.
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http://dx.doi.org/10.1155/2018/9761826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236557PMC
November 2018

Clinical Presentation and Treatment Options for Clear Cell Lung Cancer: University of Cincinnati A Case Series and Literature Review of Clear Cell Lung Cancer

Asian Pac J Cancer Prev 2018 Sep 26;19(9):2373-2376. Epub 2018 Sep 26.

Department of Hematology- Oncology, Vontz Center for molecular studies, University of Cincinnati, OH,USA. Email:

Clear cell carcinomas are common finding in renal, ovarian and uterine carcinomas. However, clear cell lung cancer (CCLC), first described by Liebow and Castleman in 1963, is considered an extremely rare variant of lung tumors. The 2011 WHO classification of lung tumors considered CCLC as a rare cytologic feature of squamous cell or adenocarcinomas. It is no longer recognized as a formal subtype, albeit it can be referred to in the pathological diagnosis as “with clear cell features” even with marginal fractions of the tumor cells. Such recognition is needed since the variation in clinical features and outcome in this subset of patients. The disease has a clinically vague natural history, is characterized by slight female predominance and is often seen in the elderly. As frequently encountered with rare diseases, its clinical course and treatment options have many questions still yet to be answered. In this paper, we review both the natural history and treatment options mentioned in literature, in the light of our experience by reporting a case series of four patients diagnosed with CCLC and highlight their aspects.
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http://dx.doi.org/10.22034/APJCP.2018.19.9.2373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249457PMC
September 2018

-Paclitaxel-Based Therapy in Underserved Patient Populations: The ABOUND.PS2 Study in Patients With NSCLC and a Performance Status of 2.

Front Oncol 2018 24;8:253. Epub 2018 Jul 24.

Department of Internal Medicine, Medical Oncology, Sarah Cannon Research Institute, Nashville, TN, United States.

Introduction: The phase II ABOUND.PS2 study (NCT02289456) assessed safety/tolerability of a first-line modified -paclitaxel/carboplatin regimen for patients with advanced non-small cell lung cancer (NSCLC) and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2.

Methods: Chemotherapy-naive patients with stage IIIB/IV NSCLC and ECOG PS 2 received four cycles of -paclitaxel 100 mg/m days 1 and 8 plus carboplatin area under the curve 5 day 1 q3w (induction). Patients without progression received -paclitaxel monotherapy (100 mg/m days 1 and 8 q3w) until progression/unacceptable toxicity. Primary endpoint: percentage of patients discontinuing induction due to treatment-emergent adverse events (TEAEs).

Results: 11/40 treated patients (27.5%; 95% CI, 14.60-43.89) discontinued chemotherapy induction due to TEAEs; 16/40 (40.0%) continued -paclitaxel monotherapy. Median progression-free and overall survival were 4.4 (95% CI, 2.99-7.00) and 7.7 (95% CI, 4.93-13.17) months. Grade 3/4 TEAEs during induction included neutropenia (22.5%), anemia (17.5%), thrombocytopenia (5.0%), and peripheral neuropathy (2.5%).

Conclusion: This -paclitaxel-based regimen was tolerable in patients with advanced NSCLC and ECOG PS 2, with efficacy comparable to historical chemotherapy data.
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http://dx.doi.org/10.3389/fonc.2018.00253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066533PMC
July 2018

Mutation in Metastatic Uveal Melanoma and Treatment Outcome.

Case Rep Oncol Med 2018 4;2018:4256365. Epub 2018 Apr 4.

Department of Ophthalmology, University of Cincinnati, Cincinnati, OH, USA.

Metastatic prognosis in uveal melanoma is assessed by gene expression profiling (GEP) testing of the tumor cells, usually obtained by fine needle aspiration (FNA). GEP has demonstrated high accuracy in distinguishing class I and II tumors, both having different metastatic potential. Transcriptomic studies identified distinct mutations including somatic mutations in and , detected in more than 80%, and contribute to the upregulation of the mitogen-activated protein kinase (MAPK) pathway and the development of uveal melanoma (UM). The role of these mutations in treatment selection and possible benefit from targeted therapy are somewhat unclear. However, until the discovery of novel agents, local versus systemic therapies remain options for treatment that can still be considered for disease control in certain cases. We report a series of patients with metastatic UM with distinct mutational profiles. One had significant liver metastases with proven mutation on tissue biopsy while peripheral blood molecular profiling did not show these mutations. The other three cases had no mutation. All cases received nab-paclitaxel (Abraxane) as a treatment drug, and we record their responses to treatment and their molecular-profiling results.
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http://dx.doi.org/10.1155/2018/4256365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904798PMC
April 2018

Pulmonary sarcomatoid carcinoma: University of Cincinnati experience.

Oncotarget 2018 Jan 18;9(3):4102-4108. Epub 2017 Dec 18.

Vontz Center for Molecular Studies, University of Cincinnati, Cincinnati, OH 45219, USA.

Objectives: To review the outcomes of treatment in patients with pulmonary sarcomatoid carcinoma (PSC) treated at the University of Cincinnati Medical Center (UCMC).

Results: There was no significant difference in survival of patients treated with chemotherapy alone (median, 256 days) compared to patients not undergoing treatment (median, 205.5 days). Patients who underwent surgery and adjuvant chemotherapy showed a trend in improvement of survival (median, 457.6 days). Patients requiring only surgery had the longest OS of 713.5 days.

Conclusions: Systemic chemotherapy alone did not improve survival in patients with PSC. Surgery provides the greatest overall survival benefit and adjuvant chemotherapy may also improve survival.

Methods: From 2000 to 2014, twenty-five patients with pathologically confirmed PSC were treated at UCMC. The outcomes were retrospectively analyzed by treatment with overall survival (OS) as the endpoint.
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http://dx.doi.org/10.18632/oncotarget.23468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790524PMC
January 2018

A Phase Ib Study of the Dual PI3K/mTOR Inhibitor Dactolisib (BEZ235) Combined with Everolimus in Patients with Advanced Solid Malignancies.

Target Oncol 2017 06;12(3):323-332

Division of Hematology-Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, 45267, USA.

Background: The combination of everolimus and the imidazoquinoline derivative, BEZ235 (dactolisib), a dual PI3K/mTOR inhibitor, demonstrated synergy in a preclinical model.

Objective: To establish clinical feasibility, a phase Ib dose-escalation trial investigating safety and pharmacokinetics of this combination in patients with advanced tumors was performed.

Patients And Methods: BEZ235 was orally administered daily in escalating doses of 200, 400, and 800 mg along with everolimus at 2.5 mg daily in 28-day cycles. Nineteen patients were enrolled. Adverse events and tumor responses were evaluated using CTCAE v4.0 and RECIST 1.1, respectively. Pharmacokinetic analyses were performed.

Results: Common toxicities observed included fatigue, diarrhea, nausea, mucositis, and elevated liver enzymes. No confirmed responses were observed. BEZ235 pharmacokinetics exhibited dose-proportional increases in C and AUC over the three doses, with high inter-individual variability. Non-compartmental and population pharmacokinetic-based simulations indicated significant increases in everolimus C and AUC on day 28 and decreased clearance to 13.41 L/hr.

Conclusions: The combination of BEZ235 and everolimus demonstrated limited efficacy and tolerance. BEZ235 systemic exposure increased in a dose-proportional manner while oral bioavailability was quite low, which may be related to gastrointestinal-specific toxicity. The changes in steady-state pharmacokinetics of everolimus with BEZ235 highlight potential drug-drug interactions when these two drugs are administered together. Clinicaltrials.gov: NCT01508104.
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http://dx.doi.org/10.1007/s11523-017-0482-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447332PMC
June 2017

Pulmonary Sarcomatoid Carcinomas Commonly Harbor Either Potentially Targetable Genomic Alterations or High Tumor Mutational Burden as Observed by Comprehensive Genomic Profiling.

J Thorac Oncol 2017 06 16;12(6):932-942. Epub 2017 Mar 16.

Illinois CancerCare, Peoria, Illinois.

Introduction: Pulmonary sarcomatoid carcinoma (PSC) is a high-grade NSCLC characterized by poor prognosis and resistance to chemotherapy. Development of targeted therapeutic strategies for PSC has been hampered because of limited and inconsistent molecular characterization.

Methods: Hybrid capture-based comprehensive genomic profiling was performed on DNA from formalin-fixed paraffin-embedded sections of 15,867 NSCLCs, including 125 PSCs (0.8%). Tumor mutational burden (TMB) was calculated from 1.11 megabases (Mb) of sequenced DNA.

Results: The median age of the patients with PSC was 67 years (range 32-87), 58% were male, and 78% had stage IV disease. Tumor protein p53 gene (TP53) genomic alterations (GAs) were identified in 74% of cases, which had genomics distinct from TP53 wild-type cases, and 62% featured a GA in KRAS (34%) or one of seven genes currently recommended for testing in the National Comprehensive Cancer Network NSCLC guidelines, including the following: hepatocyte growth factor receptor gene (MET) (13.6%), EGFR (8.8%), BRAF (7.2%), erb-b2 receptor tyrosine kinase 2 gene (HER2) (1.6%), and ret proto-oncogene (RET) (0.8%). MET exon 14 alterations were enriched in PSC (12%) compared with non-PSC NSCLCs (∼3%) (p < 0.0001) and were more prevalent in PSC cases with an adenocarcinoma component. The fraction of PSC with a high TMB (>20 mutations per Mb) was notably higher than in non-PSC NSCLC (20% versus 14%, p = 0.056). Of nine patients with PSC treated with targeted or immunotherapies, three had partial responses and three had stable disease.

Conclusion: Potentially targetable GAs in National Comprehensive Cancer Network NSCLC genes (30%) or intermediate or high TMB (43%, >10 mutations per Mb) were identified in most of the PSC cases. Thus, the use of comprehensive genomic profiling in clinical care may provide important treatment options for a historically poorly characterized and difficult to treat disease.
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http://dx.doi.org/10.1016/j.jtho.2017.03.005DOI Listing
June 2017

Diabetes Insipidus: An Unusual Presentation of Adenocarcinoma of the Lung in a Patient with no Identifiable Lung Mass.

N Am J Med Sci 2015 Oct;7(10):476-9

Division of Hematology/Oncology, University of Cincinnati, Cincinnati, Ohio, United States.

Context: Lung cancers are known to metastasize to unusual sites. Despite this knowledge often times the diagnosis of a primary lung cancer gets delayed especially when the patient presents without respiratory symptoms.

Case Report: The patient discussed in our review is a 47-year-old female, smoker who had presented to several hospitals with months of headache, nausea and intermittent episodes of vomiting. She was noted to have hypernatremia due to diabetes insipidus and a pituitary lesion on her magnetic resonance images. The pituitary mass on biopsy was found to represent a metastatic focus from a primary lung adenocarcinoma.

Conclusion: Clinicians should be aware of malignancies that are well known to metastasize to the posterior pituitary. Conversely, since not every patient presents with symptoms of metastasis, there is a need to recognize the clinical syndromes (e. g., diabetes insipidus-like symptoms or more subtle symptoms like cranial nerve palsies) associated with potential metastasis to the pituitary.
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http://dx.doi.org/10.4103/1947-2714.168677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677473PMC
October 2015

Systemic Chemotherapy for Progression of Brain Metastases in Extensive-Stage Small Cell Lung Cancer.

Case Rep Oncol Med 2015 26;2015:620582. Epub 2015 Aug 26.

Department of Neurology and Rehabilitation Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45219, USA.

Lung cancer is the most common cause of cancer related mortality in men and women. Approximately 15% of lung cancers are small cell type. Chemotherapy and radiation are the mainstay treatments. Currently, the standard chemotherapy regimen includes platinum/etoposide. For extensive small cell lung cancer, irinotecan and cisplatin have also been used. Patients with relapsed small cell lung cancer have a very poor prognosis, and the morbidity increases with brain metastases. Approximately 10%-14% of small cell lung cancer patients exhibit brain metastases at the time of diagnosis, which increases to 50%-80% as the disease progresses. Mean survival with brain metastases is reported to be less than six months, thus calling for improved regimens. Here we present a case series of patients treated with irinotecan for progressive brain metastases in small cell lung cancer, which serves as a reminder of the role of systemic chemotherapy in this setting.
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http://dx.doi.org/10.1155/2015/620582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563064PMC
September 2015

Phase II Clinical Trial of Gefitinib for the Treatment of Chemonaïve Patients with Advanced Non-small Cell Lung Cancer with Poor Performance Status.

Clin Med Insights Oncol 2014 25;8:121-8. Epub 2014 Nov 25.

King Saud bin Abdul-Aziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia.

Background: Patients with advanced non-small cell lung cancer (NSCLC) have no curative treatment options; therefore, improving their quality of life (QOL) is an important goal. Gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, is a safe oral agent that may be of benefit to a specific population of NSCLC.

Patients And Methods: A Phase II clinical trial included chemonaïve patients with advanced NSCLC and poor performance status (PS). Response rate, progression-free survival, overall survival, QOL using the Functional Assessment of Cancer Therapy - Lung (FACT-L) questionnaire, and Trial Outcome Index (TOI) were evaluated.

Results: Twelve out of 19 enrolled patients were evaluable. The median age for the evaluable patients was 68.8 years (59.7-74.6). Out of all the patients, 7 (58.3%) had adenocarcinoma and 5 (41.7%) had squamous cell carcinoma. The median duration of treatment was 62.5 days (26.5-115.0) in the evaluable patients. Grade 3/4 toxicities included fatigue, rash, diarrhea, and nausea. One patient had partial response, eight patients had stable disease (SD), and three patients progressed. The median overall survival for the evaluable population was 4.9 months (2.3-16). The median progression-free survival was 3.7 months (1.9-6.6). TOI was marginally associated with the overall survival, with a hazard ratio of 0.92 (95% confidence interval: 0.84, 1.0) (P = 0.061). FACT-L score and the TOI were highly correlated (r = 0.96, P < 0.0001). TOI scores were higher in African Americans compared to Caucasians and increased with age.

Conclusion: Our results suggest that gefitinib use in patients with NSCLC and poor PS may improve the QOL of older patients and African American patients.
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http://dx.doi.org/10.4137/CMO.S15172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245085PMC
December 2014

Male pelvic squamous cell carcinoma of unknown primary origin.

Case Rep Oncol Med 2014 13;2014:953698. Epub 2014 Nov 13.

The Vontz Center for Molecular Studies, 3125 Eden Avenue, RM 1312, ML 0562, Cincinnati, OH 45267, USA.

Pelvic squamous cell carcinoma of unknown primary origin has been described in several case reports of female patients. However, there have been no published reports describing male patients with pelvic squamous cell cancer of unknown primary origin. Our case describes a 52-year-old man who presented with right buttock pain, rectal urgency, and constipation. His physical examination demonstrated tenderness to palpation around his gluteal folds. Computed tomography scan of his abdomen and pelvis demonstrated a large mass in his retroperitoneum. The mass was determined to be squamous cell carcinoma of unknown primary origin. Additionally, the patient had small nodules in his right lower lung lobe and right hepatic lobe. The patient was treated with concomitant chemoradiation, including cisplatin and intensity-modulated radiation therapy, followed by carboplatin and paclitaxel. The patient achieved partial remission, in which he remained one year after his presentation. Our case is consistent with the literature which suggests that squamous cell carcinoma of unknown primary origin occurring outside of the head and neck region may have a more favorable prognosis than other carcinomas of unknown primary origin. Further studies are necessary to determine the most appropriate work-up, diagnosis, and optimal treatment strategies.
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http://dx.doi.org/10.1155/2014/953698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4247932PMC
December 2014

Bilateral choroidal metastasis from non-small cell lung cancer.

Case Rep Oncol Med 2014 14;2014:858265. Epub 2014 Sep 14.

Division of Hematology/Oncology, Department of Medicine, University of Cincinnati, OH 45069, USA.

Breast and lung cancers are the most common primary neoplasms to manifest with choroidal metastases. The incidence of choroidal metastases from metastatic lung cancer was reported to be 2-6.7%. We report a case of bilateral choroidal metastasis from non-small cell lung cancer. A 59-year-old Caucasian female patient, never a smoker, was diagnosed with stage IV lung adenocarcinoma metastatic to the pleura, bones, and the brain. Her initial scan of the chest showed innumerable soft tissue nodules and mediastinal adenopathy compatible with metastatic disease. Her initial brain MRI showed numerous small enhancing lesions consistent with extensive disease. Unfortunately, during her follow-up visits, she presented with bulge on her left eye. Simultaneously, her follow-up chest scan showed increase in the size of the lung nodules. She continued to have a reasonable performance status at that time, except for mild increase in her dyspnea. The choroidal metastases require a multidisciplinary care and should be among the differential patients with malignancy who present with ocular symptoms.
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http://dx.doi.org/10.1155/2014/858265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180387PMC
October 2014

Hepatic epithelioid hemangioendothelioma in a patient with hemochromatosis.

J Natl Compr Canc Netw 2014 Sep;12(9):1203-7

From the Department of Internal Medicine, University of Cincinnati College of Medicine; Division of Hematology Oncology, UC Department of Pediatrics, Cincinnati Children's Hospital; and the Divisions of Pathology and Hematology and Oncology, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare hepatic vascular tumor that represents a diagnostic challenge. The rarity of this neoplasm precludes establishment of a standard-of-care treatment. Risk factors for HEHE are not well-known. Liver transplant remains the most common therapeutic modality for nonmetastatic disease. This article describes a patient who presented with abdominal pain, fatigue, poor appetite, and weight loss. Genetic testing showed that the patient was homozygous for C282Y consistent with hereditary hemochromatosis, and liver biopsy was consistent with malignant epithelioid hemangioendothelioma. The patient was referred for a liver transplant but was deemed inappropriate for transplant secondary to peritoneal studding, with frozen-section analysis showing metastatic disease at the time of surgery.
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http://dx.doi.org/10.6004/jnccn.2014.0119DOI Listing
September 2014

Influenza vaccination in cancer patients undergoing systemic therapy.

Clin Med Insights Oncol 2014 1;8:57-64. Epub 2014 May 1.

Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.

Background: Cancer patients often experience preventable infections, including influenza A and B. These infections can be a cause of significant morbidity and mortality. The increased risk of infection may be because of either cancer itself or treatment-induced immunosuppression.1 Influenza immunization has been shown to decrease the risk of influenza infection in patients with intact immunity.2 In cancer patients, active immunization has been shown to confer protective immunity against several infections at similar rates to healthy individuals, which has translated into decreased duration and severity of infection and potentially improved morbidity and mortality.3.

Objectives: To assess the efficacy of influenza vaccination in stimulating immunological response in patients with cancer during chemotherapy compared to control groups.To assess the efficacy of influenza vaccination in preventing confirmed influenza and influenza-like illness and/or stimulating immunological response in children with cancer treated with chemotherapy, compared to placebo, no intervention, or different dosage schedules.To determine the adverse effects associated with influenza vaccination in patients with cancer.

Search Methods: We searched MEDLINE/PubMed database for articles published from 1964 to 2013 using the search terms "cancer," "adult," "influenza vaccination," and "chemotherapy."

Selection Criteria: We included studies based on systematic sampling with defined clinical criteria irrespective of the vaccination status of cancer patients. Studies measure the serological response or clinical response to compare between the study group and the control group. Studies assessed the inactivated influenza vaccines and live attenuated influenza vaccine (LAIV) protective serological reaction and the clinical outcomes after vaccination.

Data Collection And Analysis: Two independent authors assessed the methodological quality of included studies and extracted data.

Main Results: We included 16 studies (total number of participants = 1,076). None of the included studies reported clinical outcomes. All included studies reported on influenza immunity and adverse reaction on vaccination. We included 6 solid tumor studies and 10 hematological studies. In 12 studies, the serological response to influenza vaccine was compared in patients receiving chemotherapy (n = 425) versus those not receiving chemotherapy (n = 376). In three studies, the serological responses to influenza vaccination in patients receiving chemotherapy are compared to that in healthy adult. Measures used to assess the serological responses included a four-fold rise increase in antibody titer development of hemagglutination inhibition (HI) titer >40, and pre- and post-vaccination geometric mean titers (GMTs). Immune responses in patients receiving chemotherapy were consistently weaker (four-fold rise of 17-52%) than in those who had completed chemotherapy (50-83%) and healthy patients (67-100%). Concerning adverse effects, oncology patients received influenza vaccine, and the side effects described were mild local reactions and low-grade fever. No life-threatening or persistent adverse effects were reported. AUTHORS’

Conclusion: Patients with solid and some of hematological tumors are able to mount a serological response to influenza vaccine, but it remains unclear how much this response protects them from influenza infection or its complications. Meanwhile, influenza vaccine appears to be safe in these patients. While waiting results of randomized controlled trials to give us more details about the clinical benefits of the influenza vaccination, the clinicians should consider the currently proved benefits of influenza vaccination on management of the cancer patients undergoing systematic chemotherapy such as decrease in the duration and severity of the of the disease, and significant decrease in influenza-associated morbidity and mortality in these high-risk patients.3.
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http://dx.doi.org/10.4137/CMO.S13774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011725PMC
June 2014

Benign metastasizing leiomyoma: a rare type of lung metastases-two case reports and review of the literature.

Case Rep Oncol Med 2014 12;2014:842801. Epub 2014 Feb 12.

Department of Medicine, Division of Hematology/Oncology, University of Cincinnati, Cincinnati, OH 45219, USA.

Benign metastasizing leiomyoma (BML) is a rare disease that usually occurs in women of reproductive age. They typically have history of uterine leiomyoma treated with hysterectomy. BML can metastasize to distant organs, with the lung being the most common organ. We report two patients who presented with benign metastasizing leiomyoma to the lung. Our first case was a fifty-two-year-old female who presented with multiple lung masses, with a past medical history of uterine leiomyoma who underwent hysterectomy 17 years ago. A CT-guided biopsy showed benign appearing spindle cells and pathology confirmed her diagnosis with additional positive estrogen/progesterone receptor stains. Our second case was a fifty-six-year-old female who presented with multiple cavitary pulmonary nodules. She subsequently underwent a video-assisted thoracoscopic surgery (VATS) with wedge resection of one of the nodules. Pathology confirmed the diagnosis based on morphology and immunohistochemical staining strongly positive for estrogen/progesterone receptors. Benign metastasizing leiomyoma is a rare condition which may affect women of reproductive age. This should be considered in the differential in patients who present with multiple pulmonary nodules, especially with a history of uterine leiomyoma. Additional stains, such as estrogen/progesterone receptors, may need to be done to confirm the diagnosis.
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http://dx.doi.org/10.1155/2014/842801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970365PMC
April 2014
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