Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Alok A. Khorana
Based on 17 articles published since 2008
||||

Between 2008 and 2019, A. Khorana wrote the following 17 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Guideline Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update Summary. 2017

Khorana, Alok A / Mangu, Pamela B / Katz, Matthew H G. ·Cleveland Clinic, Cleveland, OH; American Society of Clinical Oncology, Alexandria, VA; and MD Anderson Cancer Center, Houston, TX. ·J Oncol Pract · Pubmed #28406730.

ABSTRACT: -- No abstract --

2 Guideline Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. 2017

Khorana, Alok A / Mangu, Pamela B / Berlin, Jordan / Engebretson, Anitra / Hong, Theodore S / Maitra, Anirban / Mohile, Supriya G / Mumber, Matthew / Schulick, Richard / Shapiro, Marc / Urba, Susan / Zeh, Herbert J / Katz, Matthew H G. ·Alok A. Khorana and Marc Shapiro, Cleveland Clinic, Cleveland, OH · Pamela B. Mangu, American Society of Clinical Oncology, Alexandria, VA · Jordan Berlin, Vanderbilt University, Nashville, TN · Anitra Engebretson, Pancreatic Cancer Action Network, Manhattan Beach, CA · Theodore S. Hong, Massachusetts General Hospital, Boston, MA · Anirban Maitra and Matthew H.G. Katz, The University of Texas MD Anderson Cancer Center, Houston, TX · Supriya G. Mohile, University of Rochester, Rochester, NY · Matthew Mumber, Harbin Clinic, Rome, GA · Richard Schulick, University of Colorado at Denver, Denver, CO · Susan Urba, University of Michigan, Ann Arbor, MI · and Herbert J. Zeh, University of Pittsburgh, Pittsburgh, PA. ·J Clin Oncol · Pubmed #28398845.

ABSTRACT: Purpose To update the Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline published on May 31, 2016. The October 2016 update focuses solely on new evidence that pertains to clinical question 4 of the guideline: What is the appropriate adjuvant regimen for patients with pancreatic cancer who have undergone an R0 or R1 resection of their primary tumor? Methods The recently published results of a randomized phase III study prompted an update of this guideline. The high quality of the reported evidence and the potential for its clinical impact prompted the Expert Panel to revise one of the guideline recommendations. Results The ESPAC-4 study, a multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy compared gemcitabine and capecitabine with gemcitabine monotherapy in 730 evaluable patients with resected pancreatic ductal adenocarcinoma. Median overall survival was improved in the doublet arm to 28.0 months (95% CI, 23.5 to 31.5 months) versus 25.5 months (95% CI, 22.7 to 27.9 months) for gemcitabine alone (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P = .032). Grade 3 and 4 adverse events were similar in both arms, although higher rates of hand-foot syndrome and diarrhea occurred in patients randomly assigned to the doublet arm. Recommendations All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of medical or surgical contraindications. The doublet regimen of gemcitabine and capecitabine is preferred in the absence of concerns for toxicity or tolerance; alternatively, monotherapy with gemcitabine or fluorouracil plus folinic acid can be offered. Adjuvant treatment should be initiated within 8 weeks of surgical resection, assuming complete recovery. The remaining recommendations from the original 2016 ASCO guideline are unchanged.

3 Guideline Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. 2016

Sohal, Davendra P S / Mangu, Pamela B / Khorana, Alok A / Shah, Manish A / Philip, Philip A / O'Reilly, Eileen M / Uronis, Hope E / Ramanathan, Ramesh K / Crane, Christopher H / Engebretson, Anitra / Ruggiero, Joseph T / Copur, Mehmet S / Lau, Michelle / Urba, Susan / Laheru, Daniel. ·Davendra P.S. Sohal and Alok A. Khorana, Cleveland Clinic, Cleveland, OH · Pamela B. Mangu, American Society of Clinical Oncology, Alexandria, VA · Manish A. Shah, The Weill Cornell Medical Center · Philip A. Philip, Karmanos Cancer Institute, Detroit · Susan Urba, University of Michigan Cancer Center, Ann Arbor, MI · Eileen M. O'Reilly, Memorial Sloan Kettering Cancer Center · Joseph T. Ruggiero, Weill Cornell Medical College, New York, NY · Hope E. Uronis, Duke University, Durham, NC · Ramesh K. Ramanathan, Mayo Clinic, Scottsdale · Michelle Lau, Community Hospital Based Cancer Center, Tempe, AZ · Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX · Anitra Engebretson, Patient Representative, Portland, OR · Mehmet S. Copur, St Francis Medical Center, Grand Island, NE · and Daniel Laheru, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD. ·J Clin Oncol · Pubmed #27247222.

ABSTRACT: PURPOSE: To provide evidence-based recommendations to oncologists and others for the treatment of patients with metastatic pancreatic cancer. METHODS: American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts to conduct a systematic review of the literature from April 2004 to June 2015. Outcomes were overall survival, disease-free survival, progression-free survival, and adverse events. RESULTS: Twenty-four randomized controlled trials met the systematic review criteria. RECOMMENDATIONS: A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. Goals of care, patient preferences, treatment response, psychological status, support systems, and symptom burden should guide decisions for treatments. A palliative care referral should occur at first visit. FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin; favorable comorbidity profile) or gemcitabine plus nanoparticle albumin-bound (NAB) -paclitaxel (adequate comorbidity profile) should be offered to patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1 based on patient preference and support system available. Gemcitabine alone is recommended for patients with ECOG PS 2 or with a comorbidity profile that precludes other regimens; the addition of capecitabine or erlotinib may be offered. Patients with an ECOG PS ≥ 3 and poorly controlled comorbid conditions should be offered cancer-directed therapy only on a case-by-case basis; supportive care should be emphasized. For second-line therapy, gemcitabine plus NAB-paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX, an ECOG PS 0 to 1, and a favorable comorbidity profile; fluorouracil plus oxaliplatin, irinotecan, or nanoliposomal irinotecan should be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, ECOG PS 0 to 1, and favorable comorbidity profile, and gemcitabine or fluorouracil should be offered to patients with either an ECOG PS 2 or a comorbidity profile that precludes other regimens. Additional information is available at www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki.

4 Review Pancreatic adenocarcinoma: treating a systemic disease with systemic therapy. 2014

Sohal, Davendra P S / Walsh, R Matthew / Ramanathan, Ramesh K / Khorana, Alok A. ·Affiliations of authors: Taussig Cancer Institute and Lerner College of Medicine (DPSS, AAK) and Digestive Disease Institute and Lerner College of Medicine (RMW), Cleveland Clinic, Cleveland, OH · Virgina G. Piper Cancer Center, Translational Genomics Research Institute, Scottsdale, AZ (RKR). ·J Natl Cancer Inst · Pubmed #24563516.

ABSTRACT: Pancreatic adenocarcinoma, even when resectable, remains highly lethal. Although surgical outcomes have improved considerably, median overall survival after surgery and adjuvant therapy such as single-agent gemcitabine remains less than 2 years. We discuss preclinical and clinical data supporting the contention that even early-stage pancreatic cancer is a systemic disease. Autopsy series reveal that 70% to 85% of patients die of systemic recurrence, rather than local disease, after pancreatic cancer resection. Preclinical studies using genomics and mouse models reveal evidence of metastatic spread even before histopathologic evidence of a pancreatic tumor. Analogous to breast cancer, we propose that the Halstedian approach of treating pancreatic cancer as a local, surgical problem should be replaced by Fisher's alternative hypothesis of cancer as a systemic disease. Newer multiagent chemotherapy regimens have shown meaningful response rates and improvement in overall survival in the metastatic setting and, for the first time, offer investigators an opportunity to use effective systemic therapy. We emphasize that a surgery-first approach is not resonant with our current understanding of pancreatic adenocarcinoma biology and that an upfront systemic approach for even resectable pancreatic cancer warrants testing in clinical trials.

5 Clinical Trial A Phase 2 Study of PCI-27483, a Factor VIIa Inhibitor in Combination with Gemcitabine for Advanced Pancreatic Cancer. 2019

Ramanathan, Ramesh K / Thomas, Gary W / Khorana, Alok A / Shah, Satish / Zhou, Cathy / Wong, Sofia / Cole, George / James, Danelle / Gabrail, Nashat Y. ·Honor Health Research Institute/Translational Genomics Research Institute, Scottsdale, Arizona, USA. · South Carolina Cancer Specialists, Hilton Head Island, South Carolina, USA. · University of Rochester, Rochester, New York, USA. · Gettysburg Cancer Center, Gettysburg, Pennsylvania, USA. · Pharmacyclics LLC, an AbbVie Company, Sunnyvale, California, USA. · Pharmacyclics LLC, an AbbVie Company, Sunnyvale, California, USA, gecole@pcyc.com. · Gabrail Cancer Center, Canton, Ohio, USA. ·Oncology · Pubmed #30844808.

ABSTRACT: OBJECTIVES: Tissue factor overexpression is associated with tumor progression, venous thromboembolism, and worsened survival in patients with cancer. Tissue factor and activated factor VII (FVIIa) complex may contribute to tumor invasiveness by promoting cell migration and angiogenesis. The study objective was to evaluate safety, pharmacokinetics, and efficacy of PCI-27483, a selective FVIIa inhibitor. METHODS: This was an open-label, multicenter phase 2 trial of patients with advanced pancreatic cancer. Part A of the study was an intrapatient dose escalation lead-in portion in patients concurrently receiving gemcitabine, and in part B, patients were randomized 1: 1 to the recommended phase 2 dose combination PCI-27483-gemcitabine versus gemcitabine alone. RESULTS: Target international normalized ratio (between 2.0-3.0) was achieved following PCI-27483 treatment. Overall safety of PCI-27483-gemcitabine (n = 26) was similar to gemcitabine alone (n = 16), with a higher incidence of mostly low-grade bleeding events (65% vs. 19%). Progression-free survival (PFS) and overall survival (OS) were not significantly different between patients treated with PCI-27483-gemcitabine (PFS: 3.7 months, OS: 5.7 months) and those treated with gemcitabine alone (PFS: 1.9 months, OS: 5.6 months). CONCLUSIONS: Targeted inhibition of the coagulation cascade was achieved by administering PCI-27483. PCI-27483-gemcitabine was well tolerated, but superiority to single agent gemcitabine was not demonstrated.

6 Clinical Trial Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. 2010

Philip, Philip A / Benedetti, Jacqueline / Corless, Christopher L / Wong, Ralph / O'Reilly, Eileen M / Flynn, Patrick J / Rowland, Kendrith M / Atkins, James N / Mirtsching, Barry C / Rivkin, Saul E / Khorana, Alok A / Goldman, Bryan / Fenoglio-Preiser, Cecilia M / Abbruzzese, James L / Blanke, Charles D. ·Wayne State University, Karmanos Cancer Institute, GI Oncology, Detroit, MI 48201, USA. philipp@karmanos.org ·J Clin Oncol · Pubmed #20606093.

ABSTRACT: PURPOSE: Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies. Preclinical and early clinical evidence has supported targeting the epidermal growth factor receptor (EGFR) signaling pathway in patients with pancreas cancer. This trial was conducted to evaluate the contribution of an EGFR-targeted agent to standard gemcitabine therapy. Cetuximab is a monoclonal antibody against the ligand-binding domain of the receptor. PATIENTS AND METHODS: Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine alone or gemcitabine plus cetuximab. The primary end point was overall survival. Secondary end points included progression-free survival, time to treatment failure, objective response, and toxicity. RESULTS: A total of 745 eligible patients were accrued. No significant difference was seen between the two arms of the study with respect to the median survival time (6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm; hazard ratio = 1.06; 95% CI, 0.91 to 1.23; P = .23, one-sided). Objective responses and progression-free survival were similar in both arms of the study. Although time to treatment failure was longer in patients on gemcitabine plus cetuximab (P = .006), the difference in length of treatment was only 2 weeks longer in the combination arm. Among patients who were studied for tumoral EGFR expression, 90% were positive, with no treatment benefit detected in this patient subset. CONCLUSION: In patients with advanced pancreas cancer, the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone. Alternate targets other than EGFR should be evaluated for new drug development.

7 Article Do patients with pancreatic body or tail cancer benefit from adjuvant therapy?A cohort study. 2018

Sohal, Davendra P S / Tullio, Katherine / Khorana, Alok A. ·Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Avenue, R35, Cleveland, OH 44195, United States. Electronic address: sohald@ccf.org. · Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Avenue, R35, Cleveland, OH 44195, United States. ·Surg Oncol · Pubmed #29937178.

ABSTRACT: INTRODUCTION: Evidence supporting adjuvant therapy for resected pancreatic cancer is limited primarily to head tumors. We analyzed data from the National Cancer Database (NCDB) to evaluate the relationship of tumor site with benefit from adjunctive (adjuvant, neoadjuvant, perioperative) therapy (Rx). METHODS: All NCDB patients with clinical stage I and II pancreatic cancer, diagnosed from 2003 to 2013, who underwent surgical resection and had data on site of primary were included. Overall survival (OS) analyses with hazard ratios (HR), 95% confidence intervals (CI), and two-sided p-values are presented. RESULTS: A total of 27,930 patients met inclusion criteria; median age 66 years, 51% males, 86% white. Primary site was coded as head (74.4%), body (9.3%), or tail (16.3%). Pathologic stage was predominantly stage II (77%); 81% had negative margins. Perioperative Rx was used in 4%, neoadjuvant in 8%, adjuvant in 48%. Median OS for the cohort was 24 months; for head, body and tail tumors, it was 21.6, 34.5, and 42.5 months, respectively. In univariable analyses, adjunctive Rx was associated with improved OS in head tumors (HR, any Rx vs. no Rx: 0.87; 95% CI 0.84-0.91; p < 0.0001) but not in body (1.82; 1.59-2.08; <0.0001) and tail (2.28; 2.05-2.53; <0.0001) tumors; multivariable models including statistically significant predictors (Charlson-Deyo comorbidity score, tumor grade and stage, positive resection margin) confirmed these results. CONCLUSIONS: Our study suggests that the benefit of adjunctive Rx is restricted to pancreatic head tumors; body and tail tumors have a much better prognosis. These results warrant further evaluation in prospective studies.

8 Article Neoadjuvant chemoradiation for non-metastatic pancreatic cancer increases margin-negative and node-negative rates at resection. 2017

Berriochoa, Camille A / Abdel-Wahab, May / Leyrer, Charles M / Khorana, Alok / Matthew Walsh, R / Kumar, Aryavarta M S. ·Department of Radiation Oncology, Cleveland Clinic, Taussig Cancer Institute, Cleveland, Ohio, USA. · Department of Medical Oncology, Cleveland Clinic, Taussig Cancer Institute, Cleveland, Ohio, USA. · Department of General Surgery, Cleveland Clinic, Cleveland, Ohio, USA. · Department of Radiation Oncology, Cleveland Medical Center, University Hospitals Seidman Cancer Center, Cleveland, Ohio, USA. ·J Dig Dis · Pubmed #29055078.

ABSTRACT: OBJECTIVE: To compare neoadjuvant to adjuvant chemoradiation in non-metastatic pancreatic cancer patients. METHODS: Single-institution data were obtained for patients with non-metastatic pancreatic cancer treated with concurrent chemoradiation from 2011 to 2014. Univariate analyses were performed to evaluate clinical and pathological outcomes. RESULTS: Fifty-two well-matched patients were enrolled (21 underwent neoadjuvant chemoradiation, 11 with adjuvant chemoradiation and 20 in the definitive group). Median tumor size was 2.6 cm pretreatment and 2.5 cm after neoadjuvant chemoradiation but 3.2 cm on pathology, with a treatment effect in 95.2% of specimens. Clinical node positivity at diagnosis for neoadjuvant and adjuvant chemoradiation groups was similar (28.6% vs 27.3%, P = 0.12). Of the 36 neoadjuvant patients, 21 (58.3%) underwent complete resection. In the neoadjuvant vs adjuvant chemoradiation groups, positive margins were decreased (4.8% vs 63.6%, P < 0.001), as was pathological nodal positivity (23.8% vs 90.9%, P < 0.001). After a median follow-up of 13.3 months, locoregional control for neoadjuvant and adjuvant chemoradiation was 7.7 and 7.2 months, respectively (P = 0.12) and the definitive group was 1.2 months (P = 0.014 compared with the surgical cohort). One-year overall survival was better with neoadjuvant than with adjuvant chemoradiation but this was not significant (94% vs 82%, P = 0.20); 1-year survival for the definitive group was 59% (P = 0.03 compared with the surgical cohort). CONCLUSIONS: Neoadjuvant chemoradiation remains a promising approach for non-metastatic pancreatic cancer for improving resectability and pathological and clinical findings. Computed tomography may not fully demonstrate the effectiveness of neoadjuvant treatment.

9 Article Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. 2016

Khorana, Alok A / Mangu, Pamela B / Berlin, Jordan / Engebretson, Anitra / Hong, Theodore S / Maitra, Anirban / Mohile, Supriya G / Mumber, Matthew / Schulick, Richard / Shapiro, Marc / Urba, Susan / Zeh, Herbert J / Katz, Matthew H G. ·Alok A. Khorana and Marc Shapiro, Cleveland Clinic, Cleveland, OH · Pamela B. Mangu, American Society of Clinical Oncology, Alexandria, VA · Jordan Berlin, Vanderbilt University, Nashville, TN · Anitra Engebretson, Patient Representative, Portland, OR · Theodore S. Hong, Massachusetts General Hospital, Boston, MA · Anirban Maitra and Matthew H.G. Katz, The University of Texas MD Anderson Cancer Center, Houston, TX · Supriya G. Mohile, University of Rochester, Rochester, NY · Matthew Mumber, Harbin Clinic, Rome, GA · Richard Schulick, University of Colorado at Denver, Denver, CO · Susan Urba, University of Michigan, Ann Arbor, MI · and Herbert J. Zeh, University of Pittsburgh, Pittsburgh, PA. ·J Clin Oncol · Pubmed #27247221.

ABSTRACT: PURPOSE: To provide evidence-based recommendations to oncologists and others on potentially curative therapy for patients with localized pancreatic cancer. METHODS: ASCO convened a panel of medical oncology, radiation oncology, surgical oncology, palliative care, and advocacy experts and conducted a systematic review of literature from January 2002 to June 2015. Outcomes included overall survival, disease-free survival, progression-free survival, and adverse events. RESULTS: Nine randomized controlled trials met the systematic review criteria. RECOMMENDATIONS: A multiphase computed tomography scan of the abdomen and pelvis or magnetic resonance imaging should be performed for all patients to assess the anatomic relationships of the primary tumor and for the presence of intra-abdominal metastases. Baseline performance status, comorbidity profile, and goals of care should be evaluated and established. Primary surgical resection is recommended for all patients who have no metastases, appropriate performance and comorbidity profiles, and no radiographic interface between primary tumor and mesenteric vasculature. Preoperative therapy is recommended for patients who meet specific characteristics. All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of contraindications. Adjuvant chemoradiation may be offered to patients who did not receive preoperative therapy with microscopically positive margins (R1) after resection and/or who had node-positive disease after completion of 4 to 6 months of systemic adjuvant chemotherapy. Patients should have a full assessment of symptoms, psychological status, and social supports and should receive palliative care early. Patients who have completed treatment and have no evidence of disease should be monitored. Additional information is available at www.asco.org/guidelines/PCPC and www.asco.org/guidelineswiki.

10 Article Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. 2016

Balaban, Edward P / Mangu, Pamela B / Khorana, Alok A / Shah, Manish A / Mukherjee, Somnath / Crane, Christopher H / Javle, Milind M / Eads, Jennifer R / Allen, Peter / Ko, Andrew H / Engebretson, Anitra / Herman, Joseph M / Strickler, John H / Benson, Al B / Urba, Susan / Yee, Nelson S. ·Edward P. Balaban, Cancer Care Partnership, State College · Edward P. Balaban and Nelson S. Yee, Penn State Hershey Cancer Institute, Hershey, PA · Pamela B. Mangu, American Society of Clinical Oncology, Alexandria, VA · Alok A. Khorana, Cleveland Clinic · Jennifer R. Eads, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH · Manish A. Shah, The Weill Cornell Medical Center · Peter Allen, Memorial Sloan Kettering Cancer Center, New York, NY · Somnath Mukherjee, University of Oxford, Oxford, United Kingdom · Christopher H. Crane and Milind M. Javle, The University of Texas MD Anderson Cancer Center, Houston, TX · Andrew H. Ko, University of California San Francisco Comprehensive Cancer Center, San Francisco, CA · Anitra Engebretson, Patient Representative, Portland, OR · Joseph M. Herman, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD · John H. Strickler, Duke University Medical Center, Durham, NC · Al B. Benson III, Lurie Comprehensive Cancer Center of Northwestern, Chicago, IL · and Susan Urba, University of Michigan Cancer Center, Ann Arbor, MI. ·J Clin Oncol · Pubmed #27247216.

ABSTRACT: PURPOSE: To provide evidence-based recommendations to oncologists and others for treatment of patients with locally advanced, unresectable pancreatic cancer. METHODS: American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts and conducted a systematic review of the literature from January 2002 to June 2015. Outcomes included overall survival, disease-free survival, progression-free survival, and adverse events. RESULTS: Twenty-six randomized controlled trials met the systematic review criteria. RECOMMENDATIONS: A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. The goals of care, patient preferences, psychological status, support systems, and symptoms should guide decisions for treatments. A palliative care referral should occur at first visit. Initial systemic chemotherapy (6 months) with a combination regimen is recommended for most patients (for some patients radiation therapy may be offered up front) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile. There is no clear evidence to support one regimen over another. The gemcitabine-based combinations and treatments recommended in the metastatic setting (eg, fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound paclitaxel) have not been evaluated in randomized controlled trials involving locally advanced, unresectable pancreatic cancer. If there is local disease progression after induction chemotherapy, without metastasis, then radiation therapy or stereotactic body radiotherapy may be offered also with an Eastern Cooperative Oncology Group performance status ≤ 2 and an adequate comorbidity profile. If there is stable disease after 6 months of induction chemotherapy but unacceptable toxicities, radiation therapy may be offered as an alternative. Patients with disease progression should be offered treatment per the ASCO Metastatic Pancreatic Cancer Treatment Guideline. Follow-up visits every 3 to 4 months are recommended. Additional information is available at www.asco.org/guidelines/LAPC and www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki.

11 Article Prospective Clinical Study of Precision Oncology in Solid Tumors. 2015

Sohal, Davendra P S / Rini, Brian I / Khorana, Alok A / Dreicer, Robert / Abraham, Jame / Procop, Gary W / Saunthararajah, Yogen / Pennell, Nathan A / Stevenson, James P / Pelley, Robert / Estfan, Bassam / Shepard, Dale / Funchain, Pauline / Elson, Paul / Adelstein, David J / Bolwell, Brian J. ·Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (DPSS, BIR, AAK, RD, JA, GWP, YS, NAP, JPS, RP, BE, DS, PF, PE, DJA, BJB) · University of Virginia School of Medicine, Charlottesville, VA (RD). ·J Natl Cancer Inst · Pubmed #26553780.

ABSTRACT: Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent. Tumors were sequenced using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board. Outcomes included feasibility and clinical impact. Colorectal (25%), breast (18%), lung (13%), and pancreatobiliary (13%) cancers were the most common diagnoses. Median time from consent to result was 25 days (range = 3-140). Of 223 evaluable samples, 49% (n = 109) of patients were recommended a specific therapy, but only 11% (n = 24) received such therapy: 12 on clinical trials, nine off-label, three on-label. Lack of clinical trial access (n = 49) and clinical deterioration (n = 29) were the most common reasons for nonrecommendation/nonreceipt of genomics-driven therapy.

12 Article Predicting early mortality in resectable pancreatic adenocarcinoma: A cohort study. 2015

Sohal, Davendra P S / Shrotriya, Shiva / Glass, Kate Tullio / Pelley, Robert J / McNamara, Michael J / Estfan, Bassam / Shapiro, Marc / Wey, Jane / Chalikonda, Sricharan / Morris-Stiff, Gareth / Walsh, R Matthew / Khorana, Alok A. ·Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio. · Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio. ·Cancer · Pubmed #25676016.

ABSTRACT: BACKGROUND: Survival after surgical resection for pancreatic cancer remains poor. A subgroup of patients die early (<6 months), and understanding factors associated with early mortality may help to identify high-risk patients. The Khorana score has been shown to be associated with early mortality for patients with solid tumors. In the current study, the authors evaluated the role of this score and other prognostic variables in this setting. METHODS: The current study was a cohort study of patients who underwent surgical resection for pancreatic cancer from January 2006 through June 2013. Baseline (diagnosis ±30 days) parameters were used to define patients as high risk (Khorana score ≥3). Statistically significant univariable associations and a priori prognostic variables were tested in multivariable models; adjusted hazard ratios (HR) were calculated. RESULTS: The study population comprised 334 patients. The median age was 67 years, 50% of the study population was female, and 86% of the patients were white. The pancreatic head was the primary tumor site for 73% of patients; 67% of tumors were T3 and 63% were N1. The median Khorana score was 2; 152 patients (47%) were determined to be high risk. Adjunctive treatment included chemotherapy (70%) and radiotherapy (40%). The postoperative (30-day) mortality rate was 0.9%. The 6-month mortality rate for the entire cohort was 9.4%, with significantly higher rates observed for high-risk patients (13.4% vs 5.6%; P = .02). On multivariable analyses (examining a total of 326 patients), the Khorana score (HR for high risk, 2.31; P = .039) and elevated blood urea nitrogen (HR, 4.34; P<.001) were associated with early mortality. CONCLUSIONS: Patients at high risk of early mortality after surgical resection of pancreatic adenocarcinoma can be identified using simple baseline clinical and laboratory parameters. Future studies should address preoperative interventions in these patients at high risk of early mortality.

13 Article Circulating microparticle tissue factor, thromboembolism and survival in pancreaticobiliary cancers. 2013

Bharthuar, Anubha / Khorana, Alok A / Hutson, Alan / Wang, Jian-Guo / Key, Nigel S / Mackman, Nigel / Iyer, Renuka V. ·Departments of Medicine and Biostatistics, Roswell Park Cancer Institute, Buffalo, N.Y. USA. ·Thromb Res · Pubmed #23856554.

ABSTRACT: BACKGROUND: Tissue factor (TF), the physiologic initiator of coagulation, is over-expressed in pancreatic cancer, and is associated with a pro-coagulant and pro-angiogenic state. We hypothesized that in patients with pancreaticobiliary cancers (PBC), elevated circulating microparticle-associated TF (MP-TF) activity would be associated with thrombosis and worsened survival. PATIENTS AND METHODS: Clinical data and plasma were obtained for consecutive patients with PBC seen at Roswell Park Cancer Institute from 2005-08. MP-TF activity levels were measured using a TF-dependent FXa generation assay. RESULTS: The study population comprised 117 patients, including pancreatic (n=80), biliary (n=34) or unknown primary histologically consistent with PBC (n=3). Of these, 52 patients (44.5%) experienced thromboembolism, including pulmonary embolism (n=15), deep venous thrombosis (n=21) and other arterial or venous events (n=32). Mean TF was 2.15 (range 0.17- 31.01) pg/mL. Median survival was 98.5 days for MP-TF activity ≥ 2.5 pg/mL versus 231 days for MP-TF activity<2.5 pg/mL (p<0.0001). In multivariate analysis, elevated MP-TF activity was associated with both VTE (OR 1.4, 95% CI 1.1-1.6) and mortality (HR 2.5, 95% CI 1.4-4.5). CONCLUSIONS: Elevated circulating MP-TF activity is associated with thrombosis and worsened survival in patients with PBC. MP-TF activity as a prognostic biomarker warrants further prospective evaluation.

14 Article Symptomatic and incidental thromboembolism are both associated with mortality in pancreatic cancer. 2011

Menapace, Laurel A / Peterson, Derick R / Berry, Andrea / Sousou, Tarek / Khorana, Alok A. ·James P. Wilmot Cancer Center, and Department of Medicine, University of Rochester, Rochester, New York, USA. ·Thromb Haemost · Pubmed #21713322.

ABSTRACT: Pancreatic cancer is known to be associated with VTE, but contemporary rates of incidental and symptomatic VTE events and their association with mortality are incompletely understood. We conducted a retrospective cohort study of consecutive pancreatic adenocarcinoma patients at the University of Rochester from 2006-2009. Data were analysed using a Cox model with time-dependent covariates. A total of 1,151 radiologic exams of 135 patients were included. Forty-seven patients (34.8%) experienced VTE including 12 pulmonary emboli (PE), 28 deep-vein thromboses (DVTs) and 47 visceral vein events. Incidental events comprised 33.3% of PEs, 21.4% of DVTs and 100% of visceral VTE. Median (95% CI) conditional survival beyond three months was 233 (162-322) more days for those without VTE, which was significantly greater than 12 (3-60) days for those with DVT as first event (p<0.0001) and 87 (14-322) days with visceral first events (p=0.022). In multivariate analysis, DVT (HR 25, 95% CI 10-63, p <0.0001), PE (HR 8.9, 95% CI 2.5-31.7, p = 0.007) and incidental visceral events (HR 2.6, 95% CI 1.6-4.2, p =0.0001) were all associated with mortality, though anticoagulants reduced these risks by 70% (26-88%, p = 0.009). In conclusion, VTE occurs in over one-third of contemporary pancreatic cancer patients and, whether symptomatic or incidental, is strongly associated with worsened mortality. The role of anticoagulation in treating incidental or visceral VTE warrants further study.

15 Minor Adjuvant Treatment in Potentially Curable Pancreatic Cancer: Need to Include Tumor Location in the Equation? 2018

Mukhija, Dhruvika / Sohal, Davendra P S / Khorana, Alok A. ·Department of Internal Medicine Taussig Cancer Center Cleveland Clinic Cleveland, OH Department of Hematology and Oncology Taussig Cancer Center Cleveland Clinic Cleveland, OH khorana@ccf.org. ·Pancreas · Pubmed #30113430.

ABSTRACT: -- No abstract --

16 Minor Reply to A. Wang-Gillam et al. 2017

Sohal, Davendra P S / Mangu, Pamela B / Laheru, Daniel / Khorana, Alok A. ·Davendra P.S. Sohal, Cleveland Clinic, Cleveland, OH · Pamela B. Mangu, American Society of Clinical Oncology, Alexandria, VA · Daniel Laheru, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD · and Alok A. Khorana, Cleveland Clinic, Cleveland, OH. ·J Clin Oncol · Pubmed #27918714.

ABSTRACT: -- No abstract --

17 Minor Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancer. 2008

Khorana, A A / Francis, C W / Menzies, K E / Wang, J-G / Hyrien, O / Hathcock, J / Mackman, N / Taubman, M B. · ·J Thromb Haemost · Pubmed #18795992.

ABSTRACT: -- No abstract --