28 results on '"Maria Diab"'
Search Results
2. Pancreatic adenocarcinoma: molecular drivers and the role of targeted therapy
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Maria Diab, Bayan Al-Share, and Nour Hammad
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Pancreatic ductal adenocarcinoma ,medicine.medical_treatment ,Disease ,Adenocarcinoma ,Germline ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Pancreatic cancer ,Internal medicine ,medicine ,Humans ,Molecular Targeted Therapy ,Chemotherapy ,business.industry ,Prognosis ,medicine.disease ,Tumor tissue ,Pancreatic Neoplasms ,030104 developmental biology ,030220 oncology & carcinogenesis ,business ,Carcinoma, Pancreatic Ductal - Abstract
Prognosis from pancreatic ductal adenocarcinoma (PDAC) continues to be poor despite the many efforts channeled to improve its management. Although the mainstay treatment is still traditional chemotherapy, recent advances highlighted a promising potential for targeted therapy in the management of this disease. Those advances emphasize the significance of timely genomic profiling of tumor tissue as well as germline testing of patients to identify potential markers of targeted therapy. While targeted therapy is reserved for a relatively small subset of patients with PDAC, ongoing research is uncovering additional markers, and targeted agents, that will hopefully translate to better outcomes for patients.
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- 2021
3. High-Risk Features Are Prognostic in dMMR/MSI-H Stage II Colon Cancer
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Glen G. Balch, Tyra M. Gaines, Christina Wu, Walid L. Shaib, Madhusmita Behera, Philip A. Philip, Maria Diab, Olatunji B. Alese, Amr Mohamed, Bassel F. El-Rayes, Mehmet Akce, and Renjian Jiang
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Oncology ,stage II ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Perineural invasion ,Disease ,high risk ,Carcinoembryonic antigen ,Internal medicine ,medicine ,cancer ,Survival analysis ,RC254-282 ,Original Research ,Chemotherapy ,biology ,colon ,Proportional hazards model ,business.industry ,Cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Bowel obstruction ,adjuvant chemotherapy ,biology.protein ,business - Abstract
BackgroundHigh-risk features, such as T4 disease, bowel obstruction, poorly/undifferentiated histology, lymphovascular, perineural invasion, and MethodsUnivariate (UVA) and multivariate (MVA) Cox proportional hazards (Cox-PH) models were built to assess the association between clinical and demographic characteristics and overall survival. Kaplan–Meier survival curves were generated with log-rank tests to evaluate the association between adjuvant chemotherapy in high-risk and low-risk cohorts separately.ResultsA total of 2,293 stage II CC patients have dMMR/MSI-H; of those, 29.5% (n = 676) had high-risk features. The high-risk dMMR/MSI-H patients had worse overall survival [5-year survival and 95%CI, 73.2% (67.3–78.1%) vs. 80.3% (76.7–83.5%), p = 0.0001]. In patients with stage II dMMR/MSI-H CC, the high-risk features were associated with shorter overall survival (OS) along with male sex, positive carcinoembryonic antigen, Charlson–Deyo score >1, and older age. Adjuvant chemotherapy administration was associated with better OS, regardless of the high-risk features in dMMR/MSI-H (log-rank test, p = 0.001) or not (p = 0.0006). When stratified by age, the benefit of chemotherapy was evident only in patients age ≥65 with high-risk features.ConclusionHigh-risk features are prognostic in the setting of dMMR/MSI-H stage II CC. Adjuvant chemotherapy may improve survival specifically in patients ≥65 years and with high-risk features.
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- 2021
4. Pharmacotherapeutic strategies for treating pancreatic cancer: advances and challenges
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Ramzi M. Mohammad, Maria Diab, Philip A. Philip, and Asfar S. Azmi
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Oncology ,medicine.medical_specialty ,Pancreatic ductal adenocarcinoma ,endocrine system diseases ,medicine.medical_treatment ,Drug resistance ,Adenocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Stroma ,Internal medicine ,Pancreatic cancer ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Pharmacology (medical) ,Pharmacology ,Chemotherapy ,business.industry ,General Medicine ,Immunotherapy ,Prognosis ,medicine.disease ,digestive system diseases ,Pancreatic Neoplasms ,Late diagnosis ,030220 oncology & carcinogenesis ,business ,030217 neurology & neurosurgery ,Carcinoma, Pancreatic Ductal - Abstract
Despite many efforts to improve the outcome of pancreatic ductal adenocarcinoma (PDAC), its prognosis remains poor, which is mostly related to late diagnosis and drug resistance. Improving systemic therapy is considered the major challenge in improving the outcome of this disease.This review covers novel chemotherapy and targeted agents in the treatment of PDAC, with a focus on advanced stage disease.Current frontline therapies used in the treatment of patients with PDAC with favorable performance status are gemcitabine (GEM) and nab-paclitaxel or 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX). PDAC has a number of genetic mutations that may explain its biological behavior, such as KRAS, p53 and CDK2NA, which occur in more than 90% of cases. Unfortunately, to this day, a specific targeting agent to any of those frequent gene mutations is lacking. Emerging areas of targeted therapies include the DNA repair, stroma, metabolism, and stem cells. Immunotherapy with either vaccines or immune checkpoint inhibitors has not produced any significant improvements in outcome of PDAC. Incorporating different approaches in therapy, including conventional, immunological, and others, is key in offering patients with the best possible care.
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- 2018
5. Gastric cancer: a comprehensive review of current and future treatment strategies
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Mohammed Najeeb Al Hallak, Maria Diab, Asfar S. Azmi, and Rachel E. Sexton
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Disease ,medicine.disease_cause ,Article ,Helicobacter Infections ,03 medical and health sciences ,0302 clinical medicine ,Clinical Trials, Phase II as Topic ,Stomach Neoplasms ,Internal medicine ,medicine ,Biomarkers, Tumor ,Animals ,Humans ,Molecular Targeted Therapy ,Stage (cooking) ,Survival rate ,Neoplasm Staging ,Randomized Controlled Trials as Topic ,biology ,Helicobacter pylori ,business.industry ,Cancer ,biology.organism_classification ,medicine.disease ,Epstein–Barr virus ,Combined Modality Therapy ,030104 developmental biology ,Clinical Trials, Phase III as Topic ,030220 oncology & carcinogenesis ,Treatment strategy ,Cancer development ,business - Abstract
Gastric cancer remains a major unmet clinical problem with over 1 million new cases in 2018 worldwide. It is the fourth most commonly occurring cancer in men and the seventh most commonly occurring cancer in women. A major fraction of gastric cancer has been linked to variety of pathogenic infections including but not limited to Helicobacter pylori (H. pylori) or Epstein Barr virus (EBV). Strategies are being pursued to prevent gastric cancer development such as H. pylori eradication, which has helped to prevent significant proportion of gastric cancer. Today, treatments have helped to manage this disease and the 5-year survival for stage IA and IB tumors treated with surgery are between 60% and 80%. However, patients with stage III tumors undergoing surgery have a dismal 5-year survival rate between 18% and 50% depending on the dataset. These figures indicate the need for more effective molecularly driven treatment strategies. This review discusses the molecular profile of gastric tumors, the success and challenges with available therapeutic targets along with newer biomarkers and emerging targets.
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- 2020
6. S1460 A Rare Case of Porto-Spleno-Mesenteric Venous Thrombosis (PSMVT) Secondary to Mild Acute Pancreatitis
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Saurabh Chawla, Shishir K. Maithel, Steven Keilin, Ahmed A. Messallam, Field F. Willingham, Vaishali Patel, Pretesh Patel, Maria Diab, and Ambreen A. Merchant
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Neuroendocrine neoplasia ,Pathology ,medicine.medical_specialty ,Hepatology ,Pancreatic neuroendocrine tumor ,business.industry ,Radiofrequency ablation ,law ,Gastroenterology ,Medicine ,business ,medicine.disease ,law.invention - Published
- 2021
7. Clinical features and outcomes of colloid carcinoma of pancreas compared to pancreatic ductal adenocarcinoma
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Renjian Jiang, Katerina Mary Zakka, Walid L. Shaib, Maria Diab, Madhusmita Behera, Olatunji B. Alese, Christina Wu, Lana Khalil, Michelle D. Reid, Mehmet Akce, Mckenna Penely, and Bassel F. El-Rayes
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Cancer Research ,Pathology ,medicine.medical_specialty ,medicine.anatomical_structure ,Pancreatic ductal adenocarcinoma ,Oncology ,business.industry ,medicine ,Carcinoma ,Ductal adenocarcinoma ,Pancreas ,medicine.disease ,business - Abstract
e16259 Background: Colloid carcinoma (CC) of the pancreas is a rare histopathological subtype of ductal adenocarcinoma (PDAC), with poorly defined prognostic factors and therapeutic outcomes. The aim of this study is to characterize the clinicopathological features and evaluate the overall survival (OS) and prognostic factors of patients with pancreatic CC using National Cancer Database (NCDB). Methods: Patients diagnosed with CC of the pancreas and PDAC between 2004 and 2016 were identified from the NCDB using ICD-O-3 morphology (8480/3 for CC and 8140/3 for PDAC) and topography codes (C25). Univariate and multivariable analyses were conducted and Kaplan-Meier analysis and Cox proportional hazards models were used to perform OS analysis. Results: A total of 56,846 patients met the inclusion criteria for the final analysis. Of the total population included, 2,430 patients (4.3%) had CC and 54,416 patients (95.7%) had PDAC. For both, CC and PDAC, there was a male preponderance (52.0%, 52.5%), Caucasians (85.1%, 84%), occurrence above the age of 70 (39.2%, 38.2%), and the most common primary site was the head of the pancreas (50.5%, 53%). For CC, the percentage of pathologic stage III colloid pancreas cancer appeared the lowest (3.5%, 85 patients), compared to stage I (16.7%), stage II (37.8%), and stage IV (42.1%). While in PDAC, the percentage of pathologic stage I (5.94%) and stage III (4.44%) patients was lower than stage II (37.21%) and IV (52.41%). CC and PDAC more frequently presented with < 5cm tumor, at academic or research cancer centers, and diagnosed between 2009 and 2013 compared to 2004–2008 ( p< 0.001). For both CC and PDAC, the majority underwent surgical resection (58%, 53%), systemic chemotherapy (57.8%, 63%) and did not receive radiotherapy (78.8%, 77.6%). A positive surgical margin on pathologic evaluation was associated with worse outcomes for CC and PDAC in both univariate and multivariate analysis (HR 1.61; 1.56–1.66; p< 0.001 and HR 1.43; 1.38–1.48, p< 0.001). CC had a better 1-year overall survival (OS) in all stages compared to PDAC (p < 0.001). In multivariate analysis, mucinous carcinoma histology, female sex, diagnosis between 2004 and 2009, well/moderately differentiated histology, chemotherapy, age at diagnosis less than 60, radiation therapy after surgery, and local surgical procedure of primary site and pancreatectomy (p < 0.001) were associated with better OS compared to PDAC. Colloid histology was associated with better 1-year overall survival (OS) in all stages compared to PDAC (p < 0.001). Conclusions: Colloid carcinoma of pancreas is associated with a better overall survival as compared to pancreatic ductal adenocarcinoma. This is the largest study to address the clinical features and outcomes of colloid carcinoma of pancreas.
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- 2021
8. Increased neutrophil infiltration and lower prevalence of tumor mutation burden and microsatellite instability are hallmarks of RAS mutant colorectal cancers
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Subbaya Subramanian, Anthony F. Shields, Emil Lou, Joanne Xiu, Richard M. Goldberg, Muhammad Shaalan Beg, Maria Diab, Yasmine Baca, Elisa Fontana, Philip A. Philip, Wolfgang Michael Korn, Heinz-Josef Lenz, Ritu Pandey, Weijing Sun, Andrew C. Nelson, Wafik S. El-Deiry, Mohamed E. Salem, and Tobias Arkenau
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Cancer Research ,Mutation ,Tumor microenvironment ,business.industry ,Mutant ,Microsatellite instability ,medicine.disease_cause ,medicine.disease ,digestive system diseases ,Oncology ,Immune infiltration ,Lower prevalence ,medicine ,Cancer research ,KRAS ,business ,Infiltration (medical) - Abstract
3563 Background: The tumor microenvironment (TME) of colorectal cancers (CRC) is modulated by oncogenic drivers such as KRAS. The TME comprises a broad landscape of immune infiltration. How tumor genomics associates with the immune cell landscape is less known. We aim to characterize immune cell types in RAS wild-type (WT) and mutant (MT) CRC, and to examine the prevalence of immuno-oncologic (IO) biomarkers (e.g. tumor mutation burden (TMB), PD-L1, MSI-H/dMMR) in these tumors. We performed genomic and transcriptomic analysis to confirm associations of mutant RAS with immune infiltration of the TME conducive to metastasis vs. potential response to immunotherapies. Methods: A total of 7,801 CRC were analyzed using next-generation sequencing on DNA (NextSeq, 592 Genes and WES, NovaSEQ), RNA (NovaSeq, whole transcriptome equencing) and IHC (Caris Life Sciences, Phoenix, AZ). MSI/MMR was tested by FA, IHC and NGS. TMB-H was based on a cut-off of > 10 mutations per MB). Immune cell fraction was calculated by QuantiSeq (Finotello 2019, Genome Medicine). Significance was determined by X2 and Fisher-Exact and p adjusted for multiple comparisons (q) was = than 50 yrs. In MSS tumors, there was a significantly higher neutrophil infiltration in KRAS MT (median cell fraction 6.6% vs. 5.9%) and NRAS MT (6.9%) overall and also when individual codons were studied. B cells, M2 macrophages, CD8+ T cells, dendritic cells and fibroblasts were lower in KRAS mutant tumors; B cells and M1 macrophages are lower in NRAS (q
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- 2021
9. Treatment outcomes for stage T1b-2 esophagogastric adenocarcinomas
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Walid L. Shaib, Christina Wu, Bassel F. El-Rayes, Maria Diab, Subir Goyal, Mehmet Akce, Lana Khalil, Olatunji B. Alese, and Jeffrey M. Switchenko
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Cancer Research ,Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Treatment outcome ,medicine.disease ,Gastroesophageal Junction ,Gastroenterology ,Oncology ,Internal medicine ,medicine ,Stage (cooking) ,Stomach cancer ,business ,Neoadjuvant therapy - Abstract
e16085 Background: Treatment of localized esophageal, gastroesophageal junction (GEJ), and stomach cancer is neoadjuvant therapy with either chemoradiation or chemotherapy followed by surgery. Treatment for T1b-2 stage disease is not well evaluated and this stage is underrepresented in prospective studies. The aim of this study is to evaluate survival outcomes among the three treatment modalities (neoadjuvant chemotherapy (NACT), neoadjuvant chemoradiation (NACRT), and upfront surgery (US)) in this population using the National Cancer Database (NCDB). Methods: Patients (pts) with clinical stage T1b-2N0 and any pathological stage (excluding metastatic) adenocarcinoma of the esophagus, GEJ, and stomach treated with neoadjuvant therapy or upfront surgery, with or without adjuvant chemotherapy (AC), were identified between 2004 and 2015 in the NCDB. Univariate and multivariable analyses were conducted, and Kaplan-Meier analysis and Cox proportional hazard models were used to identify the association between the three treatment modalities and overall survival (OS). Results: A total of 2260 pts were analyzed. The median follow-up was 66.6 months. The median age was 67 years. Most pts were White (86%) and male (77%). 1018 (45%) had moderately-differentiated grade, while 946 (42%) had poorly-differentiated/undifferentiated grade. The most common site of disease was the lower third of esophagus (34.1%). 161 pts (7%) received NACT, of whom 45 pts received AC; 537 pts (24%) received NACRT, of whom 40 pts received AC. 1562 pts (69%) underwent US, of whom 146 pts received AC. US with AC was associated with the best survival, followed by NACT with AC; median OS was 90.1 and 86.8 months for surgery with AC and NACT with AC, respectively. NACRT was associated with the worst survival (39.5 and 40.2 months with and without AC, respectively). The 5-year OS rates were 59.8%, 58.5%, 52.1%, 44.9%, 37.3%, and 37.8%, for US, NACT, and NACRT, with and without AC, respectively. The rate of tumor upstaging was highest in the NACT group, followed by the NACRT group, and lowest in the US group. Postsurgically, 62 (39%) and 48 (30%) pts in the NACT group and 198 (37%) and 161 (30%) pts in the NACRT group had upstaging in their T and N stages, respectively, compared to 214 (13%) and 326 (21%) pts in the US group. For the 1107 pts who also had pathological T1b-2N0 stage disease following US, no difference in survival was observed with or without AC. Conclusions: Upfront surgery with adjuvant chemotherapy and perioperative chemotherapy are associated with the best survival compared to preoperative radiotherapy. This is the largest study to address the best approach for the treatment of T1b-2 stage disease.
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- 2021
10. Gallbladder Cancer: Current and Emerging Therapies
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Maria Diab and Philip A. Philip
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Oncology ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Gallstones ,Disease ,medicine.disease ,Gemcitabine ,Targeted therapy ,Internal medicine ,medicine ,Adjuvant therapy ,Adenocarcinoma ,Gallbladder cancer ,business ,medicine.drug - Abstract
Despite its rare prevalence, gallbladder cancer (GBC) is associated with a poor prognosis. Patients typically experience vague symptoms and present with advanced stages of disease. Gallstones are the most prevalent risk factors. Tumors that are associated with gallstones have a different pathogenesis compared to those originating from anomalous pancreaticobiliary duct junction or on a background of adenomatous polyps. Approximately 10–30% of patients will qualify for surgical resection, which is the only potentially curable treatment. Patients with resected, node- or margin-positive disease are candidates for adjuvant therapy. Options include fluoropyrimidine-based chemoradiation with or without chemotherapy, as well as fluoropyrimidine- or gemcitabine-based chemotherapy alone. For patients with advanced disease, prognosis is poor despite treatment, which includes fluoropyrimidine- or gemcitabine-based chemotherapy, with or without fluoropyrimidine chemoradiation. Targeted biologic therapy, such as inhibitors of VEGF, EGFR, and HER2, as well as pathways with aberrant expression, have been evaluated in the setting of advanced disease. Unfortunately, the trials are underpowered. Further studies are in dire need.
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- 2019
11. Novel Targeted Treatment Approaches in Pancreatic Cancer
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Philip A. Philip, Muhammad Saad Hamid, Maria Diab, Asfar S. Azmi, and Ramzi M. Mohammad
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Oncology ,medicine.medical_specialty ,endocrine system diseases ,Performance status ,business.industry ,FOLFIRINOX ,Cancer ,medicine.disease ,digestive system diseases ,Gemcitabine ,Oxaliplatin ,Irinotecan ,Clinical trial ,Internal medicine ,Pancreatic cancer ,Medicine ,business ,medicine.drug - Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains the fourth leading cause of cancer-related death in the United States. Since the hallmark clinical trial in 1997 that showed superiority of gemcitabine over 5-fluorouracil, gemcitabine has been the mainstay of treatment of PDAC, either as single agent or in combination with other treatments. FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin) was also recently introduced for the treatment of patients with a good performance status. However, despite large cancer sequencing initiatives in the past decade that have allowed for a better understanding of the molecular biology of PDAC, highly efficacious therapies, especially in the setting of locally advanced and metastatic disease, are still lacking. Although several target agents have been investigated in PDAC, almost all have failed to demonstrate a survival benefit in late-phase clinical trials. In this chapter, we will review novel target agents that were evaluated in clinical trials for the treatment of PDAC, focusing on small-molecule therapies.
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- 2019
12. Cetuximab and methotrexate in recurrent or metastatic head and neck squamous cell carcinoma-A single institution analysis of 54 patients
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Misako Nagasaka, Seongho Kim, Ammar Sukari, Maria Diab, Jailan A. Elayoubi, Khaled Al Sibai, Omer Kucuk, and Bassel Atassi
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Adult ,Male ,Michigan ,medicine.drug_class ,medicine.medical_treatment ,Cetuximab ,Antimetabolite ,Article ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Carcinoma ,medicine ,Humans ,Epidermal growth factor receptor ,030223 otorhinolaryngology ,Aged ,Retrospective Studies ,Chemotherapy ,Performance status ,biology ,business.industry ,Middle Aged ,medicine.disease ,Head and neck squamous-cell carcinoma ,Survival Rate ,stomatognathic diseases ,Methotrexate ,Otorhinolaryngology ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Carcinoma, Squamous Cell ,Female ,Neoplasm Recurrence, Local ,business ,medicine.drug - Abstract
Platinum-based chemotherapy is the standard of care treatment for patients with non-resectable, recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).1 However, the toxicides of platinum must not be ignored. In reality, many patients with non-resectable R/M HNSCC cannot tolerate platinum-based chemotherapy due to their performance status (PS) and/or comorbidities. Methotrexate (MTX), a folate antimetabolite that inhibits DNA synthesis, repair and cellular replication, has shown a modest response rate (RR) of 10% while RR was 32% for ciplatin/5-FU in R/M HNSCC, although this was in exchange with significantly increased toxicides with dsplatin/5-FU compared to MTX (P = 0.001).2 Cetuximab (CTX) is a chimeric monoclonal antibody directed against the extracellular portion of the epidermal growth factor receptor (EGFR). CTX monotherapy has shown RR of 13% in R/M HNSCC post-platinum-failure.3 Both CTX and MTX have shown single-agent activity in non-resectable R/M HNSCC with favourable toxicity profiles. However, data on combination CTX/MTX are limited. The purpose of this study is to provide outcomes data on combination CTX/MTX in non-resectable R/M HNSCC patients.
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- 2018
13. Impact of primary tumor size/horizontal extent on survival in colorectal cancer
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Katerina Mary Zakka, Renjian Jiang, Christina Wu, Wei Zhou, Maria Diab, Mehmet Akce, Olatunji B. Alese, Walid L. Shaib, and Bassel F. El-Rayes
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Colorectal cancer ,Internal medicine ,Pathologic staging ,Medicine ,In patient ,Primary tumor size ,business ,medicine.disease - Abstract
125 Background: Pathologic staging in colorectal cancer (CRC) is crucial in patient management. Data regarding the impact of size/horizontal tumor extent is limited, contradictory and currently excluded from the American Joint Committee on Cancer (AJCC) staging model. However, a previously published SEER analysis showed that AJCC stages I and IIIA have similar 2- and 5- year survival rates, and worse rates for stage II. Using the largest cohort to date, we report the impact of primary tumor size on CRC survival. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2010 and 2015. Univariate and multivariate analyses were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor/patient characteristics and overall survival (OS). Results: A total of 61,145 patients were identified with a similar gender distribution (M/F:50.9%/49.1%). The mean age was 62.7years (SD+/-14.1) and 82% were non-Hispanic Whites. Majority had colon primary (82.7%) and 82.4% had microsatellite stable (MSS) disease. Distribution across stages I-IV was 20.1%, 32.1%, 34.7% and 13.2% respectively. Among the total study population, AJCC stage correlated closely with OS on multivariate analysis (HR 1.49, 2.29, 8.38 for stages II to IV compared to stage I), while the distinguishing power for tumor size was relatively mild (HR 1.19 and 1.33 for 5-10 cm and >5cm compared to 10cm were associated with worse survival compared to those 10cm (HR 1.57; 1.37-1.80; p
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- 2021
14. Phase II trial of nivolumab and metformin in patients with treatment refractory microsatellite stable metastatic colorectal cancer
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Walid L. Shaib, Gregory B. Lesinski, Olatunji B. Alese, Maria Diab, Manali Rupji, Mehmet Akce, Jeffrey M. Switchenko, Bassel F. El-Rayes, and Christina Wu
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Cancer Research ,business.industry ,Tumor-infiltrating lymphocytes ,Colorectal cancer ,medicine.disease ,Blockade ,Metformin ,Immune system ,Oncology ,Microsatellite Stable ,Cancer research ,Medicine ,In patient ,Nivolumab ,business ,medicine.drug - Abstract
95 Background: Preclinical data suggests metformin can improve immune exhaustion of tumor infiltrating lymphocytes and potentiate the effects of PD-1 blockade. By normalizing the hypoxic TME, metformin was shown to improve cytotoxic T cell function and efficacy of anti-PD-1 antibody in highly aggressive B16 melanoma and MC38 colon adenocarcinoma tumor models. Based on this preclinical rationale we conducted a phase II study with nivolumab and metformin combination in treatment refractory MSS metastatic colorectal cancer (mCRC). Methods: Nivolumab 480 mg IV every 4 weeks and Metformin 1000 mg po twice daily was administered in 28-day cycles following a 14-day metformin only lead-in phase.Eligible patients included stage IV metastatic treatment refractory MSS mCRC (patients must have received oxaliplatin, irinotecan, and fluoropyrimidine), age ≥18 years, ECOG PS 0-1, adequate organ function, no prior anti PD-1 agent. The primary endpoint was overall response rate (ORR). Secondary endpoints included overall survival (OS) and progression free survival (PFS). Simon’s two-stage Minimax design was employed (H0: ORR =4%; H1: ORR=15%; alpha = 0.1; power =80%). If ≥1 objective response was observed in the first evaluable 18 patients, 10 additional patients would be included in the cohort. ≥3 objective responders in 28 patients would be required to be considered positive study. Pre-treatment and on-treatment research biopsies and correlative peripheral blood specimens were collected. Results: A total of 24 patients were enrolled, 6 patients were replaced per protocol, and 18 patients had evaluable disease. Of the 18 evaluable patients 11/18 (61%) were female, median age 58 [IQR 50-67]. 2 patients had prolonged stable disease (4 and 10 cycles). No patients had objective response based on RECIST 1.1. Median OS and PFS was 5.1 months [95% CI (2-11.7)] and 2.3 months [95% CI (1.7-2.4)], respectively. Most common grade 3 and 4 toxicities were anemia (n=2) and diarrhea (n=2). Conclusions: In treatment refractory MSS mCRCnivolumab and metformin combination was well tolerated. Two patients achieved stable disease, but no objective response was seen; therefore, the study did not proceed with the second stage of enrollment. Immunologic correlative analysis of this study is ongoing. Clinical trial information: NCT03800602.
- Published
- 2021
15. Tyrosine kinase inhibitors as a first-line treatment in patients with newly diagnosed chronic myeloid leukemia in chronic phase: A mixed-treatment comparison
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Shahzad Raza, Rim Hasan, Belal Firwana, Ibrahim Yousef, Aref Al-Kali, Ahmad Zarzour, Mohamad Bassam Sonbol, Donald C. Doll, Maria Diab, Archana Garipalli, and M. Hassan Murad
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.drug_class ,Pharmacology ,Tyrosine-kinase inhibitor ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,medicine ,business.industry ,Myeloid leukemia ,Imatinib ,medicine.disease ,Dasatinib ,030104 developmental biology ,Nilotinib ,030220 oncology & carcinogenesis ,Molecular Response ,business ,Tyrosine kinase ,Chronic myelogenous leukemia ,medicine.drug - Abstract
Tyrosine kinase inhibitors (TKI) are the initial treatment for majority of newly diagnosed patients with chronic myelogenous leukemia (CML) in chronic phase (CP) and are associated with marked improvement in hematological, cytogenetic, molecular response and survival rates compared with other therapies. In this review, we summarize the evidence of TKI efficacy for patients with newly diagnosed CP-CML. Six trials at low risk of bias evaluating TKIs as an initial treatment in adults with newly diagnosed CP-CML and enrolling 2,456 patients were included. Follow-up times ranged from a median of 3 months to 5 years. Direct comparison showed statistically higher rates of major molecular response (MMR ≤ 0.1%(IS)) achievement with second-generation TKIs at 12 months which was sustained throughout treatment period. Bayesian mixed-treatment comparison (MTC) analysis demonstrated superiority of both nilotinib and dasatinib over imatinib in terms of efficacy. Nilotinib was associated with higher deeper molecular responses (MR(4.5) ≤ 0.0032%(IS)) at 60 months than dasatinib but no difference in MMR. The differences between nilotinib and dasatinib are likely clinically trivial. Among TKIs, nilotinib was found to have the best survival profile. Both nilotinib and dasatinib are associated with significantly better MMR compared to imatinib that is sustained over 60 months. This analysis shows that new-generation TKIs are not only showing faster response but also maintaining a more potent one through longer follow-up period. It is important to note out that MTC is not a substitute for well-conducted RCTs investigating direct comparisons.
- Published
- 2015
16. Calcium Release-Activated Calcium (CRAC) Channel Inhibition Suppresses Pancreatic Ductal Adenocarcinoma Cell Proliferation and Patient-Derived Tumor Growth
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Mark Szlaczky, Maria Diab, Mohammed Najeeb Al-Hallak, Gabriel Mpilla, Srikant Viswanadha, Amro Aboukameel, Asfar S. Azmi, Steve Kim, Anteneh Tesfaye, Mandana Kamgar, Rachel E. Sexton, Philip A. Philip, Kumar V. Penmetsa, Husain Yar Khan, and Ramzi M. Mohammad
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0301 basic medicine ,Cancer Research ,endocrine system diseases ,stim ,pancreatic cancer ,chemistry.chemical_element ,Calcium ,lcsh:RC254-282 ,Article ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,novel therapy ,Pancreatic cancer ,medicine ,orai1 ,Cell growth ,Chemistry ,ORAI1 ,crac channel ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,digestive system diseases ,Gemcitabine ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Signal transduction ,medicine.drug - Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains an unmet clinical problem in urgent need of newer molecularly driven treatment modalities. Calcium signals, particularly those associated with calcium release-activated calcium (CRAC) channels, are known to influence the development, growth, and metastasis of many cancers. This is the first study investigating the impact of CRAC channel inhibition on PDAC cell lines and patient-derived tumor models. PDAC cell lines were exposed to a novel CRAC channel inhibitor, RP4010, in the presence or absence of standard of care drugs such as gemcitabine and nab-paclitaxel. The in vivo efficacy of RP4010 was evaluated in a hyaluronan-positive PDAC patient-derived xenograft (PDx) in the presence or absence of chemotherapeutic agents. Treatment of PDAC cell lines with single-agent RP4010 decreased cell growth, while the combination with gemcitabine/nab-paclitaxel exhibited synergy at certain dose combinations. Molecular analysis showed that RP4010 modulated the levels of markers associated with CRAC channel signaling pathways. Further, the combination treatment was observed to accentuate the effect of RP4010 on molecular markers of CRAC signaling. Anti-tumor activity of RP4010 was enhanced in the presence of gemcitabine/nab-paclitaxel in a PDAC PDx model. Our study indicates that targeting CRAC channel could be a viable therapeutic option in PDAC that warrants further clinical evaluation.
- Published
- 2020
17. Gastric Cancer Heterogeneity and Clinical Outcomes
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Mohammed Najeeb Al Hallak, Maria Diab, Hafiz Uddin, Rachel E. Sexton, and Asfar S. Azmi
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Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Review ,Aggressive disease ,Disease ,lcsh:RC254-282 ,Genetic Heterogeneity ,03 medical and health sciences ,Gastric adenocarcinoma ,Sex Factors ,0302 clinical medicine ,Downregulation and upregulation ,Stomach Neoplasms ,Internal medicine ,Databases, Genetic ,microRNA ,Biomarkers, Tumor ,medicine ,Humans ,Gene Regulatory Networks ,differential gene expression ,030304 developmental biology ,0303 health sciences ,business.industry ,gastric cancer ,Gene Expression Profiling ,oncomine ,Computational Biology ,Cancer ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Pathway analysis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,classification ,Late diagnosis ,030220 oncology & carcinogenesis ,Female ,Neoplasm Grading ,Transcriptome ,business - Abstract
Gastric adenocarcinoma is a highly aggressive disease with poor overall survival. The aggressive nature of this disease is in part due to the high intra and inter tumoral heterogeneity and also due to the late diagnosis at presentation. Once progression occurs, treatment is more difficult due to the adaptation of tumors, which acquires resistance to commonly used chemotherapeutics. In this report, using publicly available data sets and pathway analysis, we highlight the vast heterogeneity of gastric cancer by investigating genes found to be significantly perturbed. We found several upregulated genes in the diffuse gastric cancer subtypes share similarity to gastric cancer as a whole which can be explained by the increase in this subtype of gastric cancer throughout the world. We report significant downregulation of genes that are underrepresented within the literature, such as ADH7, GCNT2, and LIF1, while other genes have not been explored within gastric cancer to the best of our knowledge such as METTL7A, MAL, CWD43, and SLC2A12. We identified gender to be another heterogeneous component of this disease and suggested targeted treatment strategies specific to this heterogeneity. In this study, we provide an in-depth exploration of the molecular landscape of gastric cancer in order to shed light onto novel areas of gastric cancer research and explore potential new therapeutic targets.
- Published
- 2020
18. Current and Emerging Therapies in Pancreatic Cancer
- Author
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Maria Diab and Philip A. Philip
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Oncology ,medicine.medical_specialty ,business.industry ,Disease ,medicine.disease ,medicine.disease_cause ,Circulating tumor cell ,Treatment plan ,Pancreatic cancer ,Internal medicine ,microRNA ,Medicine ,Biomarker (medicine) ,CA19-9 ,KRAS ,business - Abstract
Pancreatic cancer (PC) continues to be the fourth leading cause of cancer-related mortality despite decades of attempts to eradicate this disease. To this day, an effective tool for the screening and early diagnosis of pancreatic cancer is missing. A number of biomarkers was evaluated in the diagnostic, therapeutic, and prognostic settings of pancreatic cancer. KRAS, which is mutated in >90% of cases, is considered a rational target in treating pancreatic cancer. Unfortunately, therapy targeting KRAS is still lacking. MicroRNAs represent an attractive biomarker due to their abundance and feasibility of analysis. Multiple panels of microRNAs can differentiate pancreatic cancer from healthy and nonmalignant tissues. Biomarkers, such as hENT1 and SPARC, may assist in predicting benefit from specific therapeutic agents and be a tool to provide patients with an “individualized” treatment plan. Furthermore, “liquid biopsies” may allow monitoring circulating tumor DNA and circulating tumor cells during therapy. However, to this date, CA 19-9 remains the only FDA-approved biomarker for use in the clinic.
- Published
- 2017
19. Uncommon Cancers of the Pancreas
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Philip A. Philip and Maria Diab
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medicine.medical_specialty ,Pathology ,business.industry ,General surgery ,Pancreatoblastoma ,Acinar cell carcinoma ,medicine.disease ,Malignancy ,medicine.anatomical_structure ,Pancreatic cancer ,medicine ,Cyst ,Pancreas ,Cystadenocarcinoma ,business ,Intraductal Papillary Neoplasm - Published
- 2017
20. The Role of microRNAs in the Diagnosis and Treatment of Pancreatic Adenocarcinoma
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Asfar S. Azmi, Maria Diab, Philip A. Philip, Irfana Muqbil, and Ramzi M. Mohammad
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Pancreatic ductal adenocarcinoma ,endocrine system diseases ,diagnosis ,lcsh:Medicine ,pancreatic ductal adenocarcinoma ,Disease ,Review ,Malignancy ,03 medical and health sciences ,Internal medicine ,microRNA ,medicine ,Cytotoxic T cell ,In patient ,Treatment resistance ,therapy ,business.industry ,biology ,lcsh:R ,micro-RNA ,General Medicine ,medicine.disease ,digestive system diseases ,3. Good health ,030104 developmental biology ,Adenocarcinoma ,prognosis ,business - Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a very challenging malignancy. Disease is diagnosed in an advanced stage in the vast majority of patients, and PDAC cells are often resistant to conventional cytotoxic drugs. Targeted therapies have made no progress in the management of this disease, unlike other cancers. microRNAs (miRs) are small non-coding RNAs that regulate the expression of multitude number of genes by targeting their 3′-UTR mRNA region. Aberrant expression of miRNAs has been linked to the development of various malignancies, including PDAC. In PDAC, a series of miRs have been defined as holding promise for early diagnostics, as indicators of therapy resistance, and even as markers for therapeutic response in patients. In this mini-review, we present an update on the various different miRs that have been defined in PDAC biology.
- Published
- 2016
21. Comprehensive molecular profiling of patients with pancreatic adenocarcinoma: A single institution’s experience
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Gregory Dyson, Mandana Kamgar, Maria Diab, Philip A. Philip, Anteneh Tesfaye, Anthony F. Shields, and W. Michael Korn
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Treatment options ,medicine.disease ,Internal medicine ,medicine ,Adenocarcinoma ,Profiling (information science) ,In patient ,Single institution ,business - Abstract
e16236Background: Limited treatment options in patients with pancreatic adenocarcinoma (PDA) necessitate the search for new therapeutic targets. One area of major interest is the exploitation of DN...
- Published
- 2018
22. Impact of adjuvant chemotherapy in higher risk stage II colon cancer with a deficient mismatch repair (dMMR)/ microsatellite instability-high (MSI-H) profile
- Author
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Christina Wu, Philip A. Philip, Renjian Jiang, Mehmet Akce, Amr Mohamed, Maria Diab, Madhusmita Behera, and Bassel F. El-Rayes
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Phase iii trials ,business.industry ,Adjuvant chemotherapy ,Microsatellite instability ,Stage ii ,medicine.disease ,digestive system diseases ,Internal medicine ,medicine ,DNA mismatch repair ,business ,Stage ii colon cancer - Abstract
3604Background: Randomized phase III trials have shown that patients with dMMR/ MSI-H stage II colon cancer (CC) do not benefit from adjuvant chemotherapy. However, a subgroup of stage II patients ...
- Published
- 2018
23. The Effect of a Neutropenic Diet on Infection and Mortality Rates in Cancer Patients: A Meta-Analysis
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Belal Firwana, Thomas E. Witzig, Maria Diab, Mohamad Bassam Sonbol, and Ahmad Zarzour
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Cancer Research ,medicine.medical_specialty ,Neutropenia ,Neutrophils ,Medicine (miscellaneous) ,Infections ,law.invention ,Leukocyte Count ,Randomized controlled trial ,law ,Risk Factors ,Internal medicine ,Neoplasms ,medicine ,Humans ,Intensive care medicine ,Randomized Controlled Trials as Topic ,Infection Control ,Nutrition and Dietetics ,business.industry ,Mortality rate ,Hazard ratio ,Cancer ,medicine.disease ,Confidence interval ,Diet ,Oncology ,Meta-analysis ,Relative risk ,business - Abstract
Neutropenic diets (ND) are often prescribed to cancer patients aiming to reduce infection risk. The goal of this meta-analysis was to determine if ND indeed reduced the risk of infection and death in cancer patients compared to regular diets (RD). We identified studies in cancer patients that compared the effect of ND vs. RD on the risk of infections and mortality of any cause. The overall effect was calculated by use of a random effects model. Four studies were identified encompassing 918 patients. There was no difference in major infection or mortality rates between ND and RD groups. When analyzing for the overall composite outcome of any infection or fever, the hazard ratio was significantly higher in the ND arm (relative risk = 1.18, confidence interval: 1.05 to 1.34, P= 0.007). When the analysis was restricted to only the randomized trials, both groups had a comparable composite outcome. This meta-analysis shows no superiority with respect to mortality or infection of using a neutropenic diet in cancer patients. Larger studies are needed that study a broader range of nutritional issues, including the microbiome, in this patient population. Until then, it may be time to relax the restrictions of ND.
- Published
- 2015
24. Musculoskeletal symptoms in chronic myeloid leukemia patients after stopping tyrosine kinase inhibitors
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Maria Diab, Charles A. Schiffer, and Ghayathri Jeyakumar
- Subjects
musculoskeletal diseases ,Oncology ,Cancer Research ,medicine.medical_specialty ,Pregnancy ,Shoulders ,business.industry ,Myeloid leukemia ,Imatinib ,macromolecular substances ,medicine.disease ,Cervical spine ,Response to treatment ,respiratory tract diseases ,Dasatinib ,Internal medicine ,Medicine ,business ,Tyrosine kinase ,medicine.drug - Abstract
e18547 Background: TKIs have revolutionized outcomes for CML patients (pts) but are not without cost or side effects. For pts with a prolonged response to treatment, discontinuing (d/c) treatment is appealing and has been investigated in a number of trials. In pts in whom treatment was stopped, musculoskeletal (MSK) symptoms were reported that were shown in some cases to resolve with resuming TKIs. Methods: Records of pts with chronic phase CML who stopped TKIs were reviewed. Results: We report 8 pts with chronic phase CML whose TKI was stopped following a prolonged molecular remission. 5 pts were receiving imatinib and 3 dasatinib. 5 pts were experiencing intolerable side effects of TKIs and agreed to a trial of d/c; 2 pts requested d/c; a third pt was planning for pregnancy. The median duration of therapy with TKI before d/c was 10 years. 6/8 pts developed MSK complaints with arthralgias and joint stiffness after cessation. Involved joints included the cervical spine, shoulders, elbows, small joints of the hand, hips and knees. Arthralgia was Grade 1 in 3 pts, and Grades 2 and 3 in 1 and 2 pts, respectively. Joints were not swollen, erythematous or tender to touch. The median time from cessation of TKIs to the onset of symptoms was 2.25 mos (range: < 1-6 months). 3 pts with symptoms underwent rheumatologic work up that was nonrevealing. 5/8 pts remain in molecular remission. Of the 3 with molecular relapse, 2 had arthralgias that improved with resuming TKIs; the third remained asymptomatic. Of those who did not relapse, 1 remains symptom-free and 2 had resolution of their MSK symptoms. 1 had little benefit with corticosteroid therapy and imatinib was resumed. However, this retreatment was d/c due to side effects and she continues to experience mild arthralgias. 1 pt did not benefit from resuming TKIs, which was therefore d/c. Conclusions: The etiology of the so-called TKI “withdrawal syndrome” remains unclear. The incidence of this syndrome has not been fully elucidated, and it seems to be underappreciated and perhaps under-reported by patients. Although most symptoms are relatively mild and self-limited, this should be discussed with patients considering stopping TKIs.
- Published
- 2017
25. Evaluating the effect of neutropenic diet on infection and mortality rate in cancer patients: A meta-analysis
- Author
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Belal Firwana, Thomas E. Witzig, Maria Diab, and Mohamad Bassam Sonbol
- Subjects
Cancer Research ,medicine.medical_specialty ,Chemotherapy ,business.industry ,Mortality rate ,Risk of infection ,medicine.medical_treatment ,Cancer ,medicine.disease ,Oncology ,Meta-analysis ,Internal medicine ,medicine ,business - Abstract
9619 Background: Dietary manipulation for patients undergoing chemotherapy has been proposed as a method to reduce the risk of infection. These diets, referred to as “neutropenic diets (ND)” usuall...
- Published
- 2015
26. Long Term Outcomes of First Line Tyrosine Kinase Inhibitors for Chronic Phase Chronic Myeloid Leukemia: A Mixed-Treatment Comparison
- Author
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Rim Hasan, Shahzad Raza, Mohamad Bassam Sonbol, Ibraheem Yousef, Donald C. Doll, Aref Al-Kali, Maria Diab, Archana Garipalli, and Belal Firwana
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,Pharmacology ,medicine.disease ,Biochemistry ,Discontinuation ,Transplantation ,Dasatinib ,Imatinib mesylate ,Nilotinib ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Progression-free survival ,business ,Adverse effect ,medicine.drug ,Chronic myelogenous leukemia - Abstract
Background: Tyrosine kinase inhibitors (TKI) are associated with marked improvements in molecular response and survival compared with previous therapies for patients with chronic myelogenous leukemia (CML) in chronic phase (CP). We previously reported efficacy and safety of TKI at 12-month follow-up (Firwana et. al.JCO. 2014; 32(15_suppl): 7054). Here, we summarize the evidence of TKI efficacy and safety of TKI, comparing them directly and in-directly, in the mature follow-up for patients with newly diagnosed CP-CML. Methods: We included randomized controlled trials (RCTs) evaluating TKI in adults with newly diagnosed CP-CML. TKI (imatinib, dasatinib and nilotinib) were included if used as an initial treatment. Studies on bosutinib were excluded as it is only approved in the US for the treatment of CP-CML after failure of initial therapy. Studies that included patients with accelerated- or blast-phase CML, intolerant or resistant patients to first-line treatment, those on IFN-α, older agents or stem cell transplantation were excluded. Main outcomes are efficacy, represented by major molecular response (MMR, ≤ 0.1% BCR-ABLIS) and deeper molecular responses (MR4.5, ≤ 0.0032%IS), survival, represented by overall survival (OS) and progression free survival (PFS), and safety represented by medication discontinuation rate due to adverse events. Latest period of reporting outcome data were considered. As available trials provides direct comparison with imatinib, with no head-to-head trials to compare other TKI, we conducted a mixed treatment comparison (MTC) analysis which pools evidence from direct and indirect comparisons to facilitate simultaneous inference regarding all treatments. Bayesian mixed-treatment comparison method was used to rank TKI in terms of effectiveness. Results: Four landmark trials reported in 15 published articles and conference abstracts were identified involving 1647 patients with CP-CML. Follow-up times ranged from 3 months to 6 years. Table-1 depicts the results of MTC for imatinib, dasatinib and nilotinib. MTC analysis demonstrated superiority of both nilotinib and dasatinib over imatinib in terms of efficacy and safety. Nilotinib ranked first in efficacy with better improvement in MMR and MR4.5 at 48-month follow-up despite its different regimens, followed by dasatinib. Dasatinib has the highest medication discontinuation rate due to adverse events or drug-related toxicity. Among TKI, nilotinib was found to have the best survival profile; however, it was statistically nonsignificant. Conclusion: Both nilotinib and dasatinib are associated with significantly better efficacy and safety profiles compared to imatinib. At 48-month follow-up period, nilotinib ranked first to achieve MMR and MR4.5, with lower discontinuation rate due to adverse events. This analysis shows that new generation TKI are not only showing faster response, but also maintaining a more potent one through longer follow up period. It is important to note out that MTC is not a substitute for well conducted RCTs investigating direct comparisons. Table-1: Results of mixed treatment comparison for imatinib, dasatinib and nilotinib using fixed-effect Bayesian method. Comparison Mean risk difference (95% CrI) compared to from reference standard (Imatinib) Rank* MMR MR 4.5 PFS OS Discontinuation due to adverse events 48 months 48 months 36 months 48 months 48 months Imatinib Reference Reference Reference Reference Reference 4 Dasatinib 0.62 (0.26 to 1.01) 0.32 (-0.05 to 0.69) 0.21 (-0.43 to 0.85) 0.17 (-0.49 to 0.83) 0.59 (-0.05 to 1.25) 3 Nilotinib 300 0.92 (0.56 to 1.28) 0.81 (0.45 to 1.18) 1.02 (0.24 to 1.86) 0.19 (-0.51 to 0.89) -0.11 (-0.66 to 0.43) 1 Nilotinib 400 0.76 (0.41 to 1.12) 0.68 (0.31 to 1.05) 0.05 (-0.57 to 0.65) 0.81 (0.01 to 1.67) 0.30 (-0.20 to 0.81) 2 *Reported rank is valid for all outcomes, except for PFS and OS, where Nilotinib 400 ranks #1 and Nilotinib 300 ranks #2. Also, for rate of medication discontinuation due to adverse events, Dasatinib has the highest rate for discontinuation, followed by Nilotinib, both doses. Abbreviations: CrI, credible intervals; MMR, major molecular response, BCR-ABLIS ≤ 0.1%; MR4, deeper molecular responses, BCR-ABLIS ≤ 0.0032%; PFS, progression free survival; OS, overall survival. Disclosures No relevant conflicts of interest to declare.
- Published
- 2014
27. Malignant acrospiroma: a case report in the era of next generation sequencing
- Author
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Maria Diab, Muaiad Kittaneh, and Ali Gabali
- Subjects
Male ,medicine.medical_specialty ,Pathology ,Cancer Research ,Acral ,medicine.medical_treatment ,Sweat Gland Neoplasm ,Case Report ,lcsh:RC254-282 ,DNA sequencing ,Targeted therapy ,Acrospiroma ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Surgical oncology ,medicine ,Genetics ,Humans ,Next generation ,Neoplasm Metastasis ,Aged ,Malignant ,Adjuvant radiotherapy ,Genome, Human ,business.industry ,High-Throughput Nucleotide Sequencing ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Sweat Gland Neoplasms ,Oncology ,030220 oncology & carcinogenesis ,Malignant acrospiroma ,Personalized medicine ,Radiology ,business - Abstract
Background Malignant acrospiroma is a rare tumor of the eccrine sweat glands accounting for around 6% of all malignant eccrine tumors. Typically, it presents as large ulcerated nodules, and diagnosis can be challenging as it has great overlap with its benign counterpart. Case presentation We herein report a case of acral malignant acrospiroma, initially treated with surgical excision and adjuvant radiotherapy. After metastatic disease was confirmed, subject received multiple lines of chemo- as well as targeted therapy. Genomic testing was also done using next generation sequencing. Conclusion To the best of our knowledge, this is the first case of acral malignant acrospiroma with reported next generation sequencing results.
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28. Outcomes of Autologous Stem Cell Transplant (ASCT) in African-American (AA) Patients with Multiple Myeloma (MM)
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Voravit Ratanatharathorn, Tania Jain, Muneer H. Abidi, Lois Ayash, Abhinav Deol, Maria Diab, Divaya Bhutani, Joseph P. Uberti, and Reda A. Awali
- Subjects
Cart ,Oncology ,Transplantation ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Retrospective cohort study ,Hematology ,medicine.disease ,Lymphoma ,immune system diseases ,Concomitant ,Internal medicine ,hemic and lymphatic diseases ,Medicine ,Primary effusion lymphoma ,business ,Plasmablastic lymphoma ,Multiple myeloma - Abstract
s / Biol Blood Marrow Transplant 21 (2015) S127eS146 S139 The aim of our study was to review toxicities related to the continuation of cART during chemotherapy in HIV-infected patients undergoing autologous stem cell transplants (ASCT) for haematological malignancies. This was a retrospective study, which included HIVinfected patients who were on cART and underwent ASCT for a haematological malignancy from January 1st 2003 to December 31st 2013 at a single institution. We reviewed adverse effects related to the use cART during conditioning chemotherapy. A total of 11 patients were included, n1⁄41 acute myeloid leukemia (AML), n1⁄44 multiple myeloma (MM), n1⁄44 Burkitt lymphoma, n1⁄41 plasmablastic lymphoma, n1⁄41 primary effusion lymphoma and n1⁄41 Hodgkin lymphoma. Of the 11 patients, 6 (54%) were on non-Protease inhibitor (PI) and 5 (56%) were on PI based cART during their transplant. NoTRM were observed; all patients continued cART during conditioning chemotherapy. 6 Patients relapsed, 2 were salvaged by allogeneic HSCT, and 2 MM patients were given salvage treatment. There were 5 non-treatment related deaths, n1⁄41 developed secondary malignancy, n1⁄41 relapsed AML, n1⁄42 relapsed MM and one patient died due to zidovudine induced lactic acidosis 10 months post ASCT. Overall survival from ranged from 1-8 yrs. This case series demonstrated that concomitant use of cART during conditioning chemotherapy for patients undergoing ASCT does not adversely affect treatment outcomes. Therefore, we recommend continuing cART during ASCT. However, we recommend avoiding zidovudine during conditioning chemotherapy due to high risk of myelosuppression. Figure 1. Progression free in survival among Caucasian patients compared to African American patients during the 24-month follow-up period (Log Rank1⁄4
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