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Pancreatic Neoplasms: HELP
Articles by Dr. C Crane
Based on 52 articles published since 2009
(Why 52 articles?)
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Between 2009 and 2019, C. Crane wrote the following 52 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 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.

2 Editorial Is personalization of care coming to pancreatic oncology? 2013

Crane, Christopher H. · ·Ann Surg Oncol · Pubmed #23188544.

ABSTRACT: -- No abstract --

3 Editorial Keys to personalized care in pancreatic oncology. 2012

Crane, Christopher H / Iacobuzio-Donahue, Christine A. · ·J Clin Oncol · Pubmed #23045599.

ABSTRACT: -- No abstract --

4 Editorial Challenges in the study of adjuvant chemoradiation after pancreaticoduodenectomy. 2010

Crane, Christopher H / Varadhachary, Gauri R / Wolff, Robert A / Fleming, Jason B. · ·Ann Surg Oncol · Pubmed #20012500.

ABSTRACT: -- No abstract --

5 Editorial Is there a role for intraoperative radiation therapy in patients with resected pancreatic adenocarcinoma? 2009

Meyer, Jeffrey J / Crane, Christopher H. · ·Ann Surg Oncol · Pubmed #19526207.

ABSTRACT: -- No abstract --

6 Editorial Stereotactic radiotherapy for pancreatic cancer? 2009

Crane, Christopher H / Willett, Christopher G. · ·Cancer · Pubmed #19117338.

ABSTRACT: -- No abstract --

7 Review Ablative Radiotherapy Doses for Locally Advanced: Pancreatic Cancer (LAPC). 2017

Crane, Christopher H / O'Reilly, Eileen M. · ·Cancer J · Pubmed #29189331.

ABSTRACT: Standard palliative doses of radiation for locally advanced unresectable pancreatic cancer have had minimal to no impact on survival. Randomized trials evaluating these palliative doses have not shown a significant survival benefit with the use of radiation as consolidation after chemotherapy. Results from nonrandomized studies of 3- to 5-fraction low-dose stereotactic radiation (SBRT) have likewise had a minimal impact, but with less toxicity and a shorter treatment time. Doses of SBRT have been reduced to half the level that is necessary (biological equivalent dose, BED of 53 Gy) to achieve tumor ablation in the treatment of other solid tumors (100 Gy BED) to protect the gastrointestinal (GI) tract. The survival benefit of these palliative options is modest. In contrast, ablative doses of radiation (100 Gy BED) can be delivered using the same SBRT technique in 15 to 25 fractions. In addition to precision tumor targeting and solutions for respiratory motion as with SBRT, the delivery of ablative doses takes advantage of heterogeneous dosing, increased fractionation, which allows higher doses to be given, as well as adaptive planning to address day-to-day GI tract motion in selected cases. These higher doses have resulted in encouraging long-term survival results in multiple studies. In this review, we discuss the critical concepts and components of techniques that can be used to deliver ablative radiotherapy doses for patients with pancreatic tumors: fractionation, intentional dose heterogeneity, respiratory gating, image guidance, and adaptive planning.

8 Review Hypofractionated ablative radiotherapy for locally advanced pancreatic cancer. 2016

Crane, Christopher H. ·The University of Texas MD Anderson Cancer Centre, USA. ·J Radiat Res · Pubmed #27029741.

ABSTRACT: The role of radiation in locally advanced unresectable pancreatic cancer (LAPC) is controversial. Randomized trials evaluating standard doses of chemoradiation have not shown a significant benefit from the use of consolidative radiation. Results from non-randomized studies of 3-5-fraction stereotactic body radiotherapy (SBRT) have been similar to standard chemoradiation, but with less toxicity and a shorter treatment time. Doses of SBRT have been reduced to subablative levels for the sake of tolerability. The benefit of both options is unclear. In contrast, ablative doses can be delivered using an SBRT technique in 15-28 fractions. The keys to the delivery of ablative doses are computed tomography (CT) image guidance and respiratory gating. Higher doses have resulted in encouraging long-term survival results. In this review, we present a comprehensive solution to achieving ablative doses for selected patients with pancreatic tumors by using a combination of classical, modern and novel concepts of radiotherapy: fractionation, CT image guidance, respiratory gating, intentional dose heterogeneity, and simultaneous integrated protection.

9 Review Management of borderline resectable pancreatic cancer. 2014

Katz, Matthew H G / Crane, Christopher H / Varadhachary, Gauri. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: ccrane@mdanderson.org. · Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. ·Semin Radiat Oncol · Pubmed #24635867.

ABSTRACT: Borderline resectable pancreatic cancers are those that, although technically resectable, are at high risk for margin-positive resection following surgery de novo. Generally, such cancers are characterized by localized primary tumors that involve the mesenteric vasculature to a limited degree and that may require venous or hepatic arterial resection at pancreatectomy. In this article, we review diagnosis and staging algorithms, pretreatment strategies, and multidisciplinary treatment protocols for patients with this stage of disease. The rationale for and results following treatment with neoadjuvant chemotherapy and chemoradiation and subsequent surgical resection of the primary tumor are described in detail and existing data are reviewed.

10 Review The integration of chemoradiation in the care of patient with localized pancreatic cancer. 2009

Crane, C H / Varadhachary, G / Settle, S H / Fleming, J B / Evans, D B / Wolff, R A. ·Unit 97, Department of Radiation Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, 1515, Holcombe Boulevard, Houston, 77030 Texas, USA. ccrane@mdanderson.org ·Cancer Radiother · Pubmed #19167921.

ABSTRACT: The use of chemoradiation for patients with localized pancreatic cancer is controversial. Although some randomized trials have indicated that chemoradiation improves the median survival of patients with locally advanced as well as resected pancreatic cancer, other more recent trials have called into question the role of chemoradiation and have supported the use of chemotherapy. In the adjuvant setting, the high local tumor recurrence/persistence rate in all trials probably reflects the inclusion of patients with incompletely resected tumors, whose prognosis is similar to the prognosis of patients with locally advanced who do not undergo resection, making these trials difficult to interpret. More precise clinical staging and selection of patients appropriate for surgical resection is an important goal. The keys to the successful integration of radiotherapy in the care of patients with localized pancreatic cancer are selection, sequencing and smaller treatment volumes. A strategy of initial chemotherapy followed by consolidation with a well-tolerated chemoradiation regimen both in the adjuvant and locally advanced settings maximizes benefits of both treatment options, which are in fact complementary. Herein, we discuss the rationale for this approach as well as the ongoing investigation of novel radiation approaches designed to enhance outcome through the molecular and physical targeting of disease as well as the investigation of neoadjuvant chemoradiation in radiographically resectable and borderline resectable pancreatic cancer.

11 Clinical Trial Phase I Trial of Consolidative Radiotherapy with Concurrent Bevacizumab, Erlotinib and Capecitabine for Unresectable Pancreatic Cancer. 2016

Chadha, Awalpreet S / Skinner, Heath D / Gunther, Jillian R / Munsell, Mark F / Das, Prajnan / Minsky, Bruce D / Delclos, Marc E / Chatterjee, Deyali / Wang, Huamin / Clemons, Marilyn / George, Geena / Singh, Pankaj K / Katz, Matthew H / Fleming, Jason B / Javle, Milind M / Wolff, Robert A / Varadhachary, Gauri R / Crane, Christopher H / Krishnan, Sunil. ·Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. · Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. ·PLoS One · Pubmed #27336466.

ABSTRACT: PURPOSE: To determine the safety, tolerability and maximum tolerated dose (MTD) of addition of erlotinib to bevacizumab and capecitabine-based definitive chemoradiation (CRT) in unresectable pancreatic cancer. METHODS: Seventeen patients with CT-staged, biopsy-proven unresectable pancreatic cancer were enrolled between 3/2008 and 10/2010. Prior chemotherapy was permitted. Two patients each were enrolled at dose levels (DLs) 1-4 and 9 patients at DL 5. All patients received 50.4 Gy (GTV only) in 28 fractions with concurrent capecitabine, bevacizumab and erlotinib. Dose of each drug was escalated in 5 DLs using the continual reassessment method. Bevacizumab was escalated from 5mg/Kg q2weeks (DLs 1-4) to 10mg/Kg q2weeks (DL 5); daily erlotinib from 100mg/day (DLs 1-2) to 150 mg/Kg (DLs 3-5); and capecitabine from 400mg/m2 twice daily on days of radiation (DL 1) to 650mg/m2 (DLs 2-3) to 825 mg/m2 (DLs 4-5). Reassessment for potential resection was performed 6-8 weeks later. RESULTS: Sixteen patients received gemcitabine-based chemotherapy prior to CRT. With a median clinical follow-up of 10 months, no grade 3 toxicities were observed in DLs 1-4. Three (33%) patients at DL 5 developed a grade 3 acute toxicity (2 diarrhea, 1 rash). No grade 4 or 5 toxicities were seen. DL 4 was selected as the MTD; therefore, the recommended doses in combination with radiation are: bevacizumab, 5mg/Kg q2weeks; erlotinib, 150 mg/Kg daily; and capecitabine, 825mg/m2 BID. Median survival was 17.4 months. Of the five patients who underwent resection, 4 were originally deemed locally advanced and 1 was borderline resectable. Three patients had excellent pathological response (2 complete response and 20% viable tumor) at surgery, and the 2 patients with complete response are still alive at 61 and 67 months of follow up with no local or distant failures. CONCLUSIONS: This chemoradiation regimen at the recommended dose levels is safe and tolerable for patients with unresectable pancreatic cancer and merits further evaluation.

12 Clinical Trial RECQ1 A159C Polymorphism Is Associated With Overall Survival of Patients With Resected Pancreatic Cancer: A Replication Study in NRG Oncology Radiation Therapy Oncology Group 9704. 2016

Li, Donghui / Moughan, Jennifer / Crane, Christopher / Hoffman, John P / Regine, William F / Abrams, Ross A / Safran, Howard / Liu, Chang / Chang, Ping / Freedman, Gary M / Winter, Kathryn A / Guha, Chandan / Abbruzzese, James L. ·Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: dli@mdanderson.org. · NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. · Department of Radiation Oncology, University of Maryland, Baltimore, Maryland. · Rush University Medical Center, Chicago, Illinois. · Brown University Oncology Group, Providence, Rhode Island. · Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Radiation Oncology, Montefiore Medical Center, Bronx, New York. · Duke University Medical Center, Durham, North Carolina. ·Int J Radiat Oncol Biol Phys · Pubmed #26725729.

ABSTRACT: PURPOSE: To confirm whether a previously observed association between RECQ1 A159C variant and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population prospectively treated with postoperative chemoradiation. METHODS AND MATERIALS: Patients were selected, according to tissue availability, from eligible patients with resected pancreatic cancer who were enrolled on the NRG Oncology Radiation Therapy Oncology Group 9704 trial of 5-fluorouacil (5-FU)-based chemoradiation preceded and followed by 5-FU or gemcitabine. Deoxyribonucleic acid was extracted from paraffin-embedded tissue sections, and genotype was determined using the Taqman method. The correlation between genotype and overall survival was analyzed using a Kaplan-Meier plot, log-rank test, and multivariate Cox proportional hazards models. RESULTS: In the 154 of the study's 451 eligible patients with evaluable tissue, genotype distribution followed Hardy-Weinberg equilibrium (ie, 37% had genotype AA, 43% AC, and 20% CC). The RECQ1 variant AC/CC genotype carriers were associated with being node positive compared with the AA carrier (P=.03). The median survival times (95% confidence interval [CI]) for AA, AC, and CC carriers were 20.6 (16.3-26.1), 18.8 (14.2-21.6), and 14.2 (10.3-21.0) months, respectively. On multivariate analysis, patients with the AC/CC genotypes were associated with worse survival than patients with the AA genotype (hazard ratio [HR] 1.54, 95% CI 1.07-2.23, P=.022). This result seemed slightly stronger for patients on the 5-FU arm (n=82) (HR 1.64, 95% CI 0.99-2.70, P=.055) than for patients on the gemcitabine arm (n=72, HR 1.46, 95% CI 0.81-2.63, P=.21). CONCLUSIONS: Results of this study suggest that the RECQ1 A159C genotype may be a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant 5-FU before and after 5-FU-based chemoradiation. Further study is needed in patients treated with gemcitabine to determine whether an association exists.

13 Clinical Trial Neoadjuvant therapy is associated with a reduced lymph node ratio in patients with potentially resectable pancreatic cancer. 2015

Roland, Christina L / Yang, Anthony D / Katz, Matthew H G / Chatterjee, Deyali / Wang, Huamin / Lin, Heather / Vauthey, Jean N / Pisters, Peter W / Varadhachary, Gauri R / Wolff, Robert A / Crane, Christopher H / Lee, Jeffrey E / Fleming, Jason B. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. ·Ann Surg Oncol · Pubmed #25352267.

ABSTRACT: BACKGROUND: The use of neoadjuvant therapy (NAC) for the treatment of potentially resectable pancreatic cancer remains controversial. In this study, we sought to evaluate cancer-specific endpoints in patients undergoing a NAC versus a surgery-first (SF) approach with specific emphasis on lymph node metastases. METHODS: A total of 222 patients who underwent NAC and 85 patients who underwent SF were identified from 1990 to 2008 and compared for cancer-related endpoints. Peripancreatic lymph nodes from 135 neoadjuvant therapy patients were evaluated for histologic tumor regression. RESULTS: Patients who underwent NAC followed by surgery had improved overall survival and time to local recurrence compared with the SF approach. NAC patients were less likely to have lymph node metastases (p = 0.001), lymphovascular invasion (LVI), and had smaller tumors. On multivariate analysis, lymph node positivity was associated with SF, tumor size, and the presence of LVI. NAC patients with N0 disease had equivalent outcomes to patients with a low-LNR (0.01-0.15), whereas patients with a LNR >0.15 had reduced survival, and time to local and distant recurrence. Ten of 135 (7.4 %) NAC patients had evidence of tumor regression in at least one lymph node. CONCLUSIONS: Patients with potentially resectable PDAC selected to undergo NAC had improved survival and longer time to recurrence. Although some of these differences may be related to improvements in multimodality therapy completion rates, tumor regression in lymph node metastases exists and may demonstrate a biologic benefit of NAC compared with a SF approach.

14 Clinical Trial Transport properties of pancreatic cancer describe gemcitabine delivery and response. 2014

Koay, Eugene J / Truty, Mark J / Cristini, Vittorio / Thomas, Ryan M / Chen, Rong / Chatterjee, Deyali / Kang, Ya'an / Bhosale, Priya R / Tamm, Eric P / Crane, Christopher H / Javle, Milind / Katz, Matthew H / Gottumukkala, Vijaya N / Rozner, Marc A / Shen, Haifa / Lee, Jeffery E / Wang, Huamin / Chen, Yuling / Plunkett, William / Abbruzzese, James L / Wolff, Robert A / Varadhachary, Gauri R / Ferrari, Mauro / Fleming, Jason B. · ·J Clin Invest · Pubmed #24614108.

ABSTRACT: BACKGROUND: The therapeutic resistance of pancreatic ductal adenocarcinoma (PDAC) is partly ascribed to ineffective delivery of chemotherapy to cancer cells. We hypothesized that physical properties at vascular, extracellular, and cellular scales influence delivery of and response to gemcitabine-based therapy. METHODS: We developed a method to measure mass transport properties during routine contrast-enhanced CT scans of individual human PDAC tumors. Additionally, we evaluated gemcitabine infusion during PDAC resection in 12 patients, measuring gemcitabine incorporation into tumor DNA and correlating its uptake with human equilibrative nucleoside transporter (hENT1) levels, stromal reaction, and CT-derived mass transport properties. We also studied associations between CT-derived transport properties and clinical outcomes in patients who received preoperative gemcitabine-based chemoradiotherapy for resectable PDAC. RESULTS: Transport modeling of 176 CT scans illustrated striking differences in transport properties between normal pancreas and tumor, with a wide array of enhancement profiles. Reflecting the interpatient differences in contrast enhancement, resected tumors exhibited dramatic differences in gemcitabine DNA incorporation, despite similar intravascular pharmacokinetics. Gemcitabine incorporation into tumor DNA was inversely related to CT-derived transport parameters and PDAC stromal score, after accounting for hENT1 levels. Moreover, stromal score directly correlated with CT-derived parameters. Among 110 patients who received preoperative gemcitabine-based chemoradiotherapy, CT-derived parameters correlated with pathological response and survival. CONCLUSION: Gemcitabine incorporation into tumor DNA is highly variable and correlates with multiscale transport properties that can be derived from routine CT scans. Furthermore, pretherapy CT-derived properties correlate with clinically relevant endpoints. TRIAL REGISTRATION: Clinicaltrials.gov NCT01276613. FUNDING: Lustgarten Foundation (989161), Department of Defense (W81XWH-09-1-0212), NIH (U54CA151668, KCA088084).

15 Clinical Trial Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression. 2011

Crane, Christopher H / Varadhachary, Gauri R / Yordy, John S / Staerkel, Gregg A / Javle, Milind M / Safran, Howard / Haque, Waqar / Hobbs, Bridgett D / Krishnan, Sunil / Fleming, Jason B / Das, Prajnan / Lee, Jeffrey E / Abbruzzese, James L / Wolff, Robert A. ·Dept of Radiation Oncology, Unit 97, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX. ccrane@mdanderson.org ·J Clin Oncol · Pubmed #21709185.

ABSTRACT: PURPOSE: This phase II trial was designed to assess the efficacy and safety of cetuximab, gemcitabine, and oxaliplatin followed by cetuximab, capecitabine, and radiation therapy in locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Treatment-naive eligible patients (n = 69) received intravenous gemcitabine (1,000 mg/m(2)) and oxaliplatin (100 mg/m(2)) every 2 weeks for four doses, followed by radiation (50.4 Gy to the gross tumor only) with concurrent capecitabine (825 mg/m(2) twice daily on radiation treatment days). Cetuximab (500 mg/m(2)) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy. Diagnostic cytology specimens were immunostained for Smad4(Dpc4) expression. RESULTS: Median overall survival time was 19.2 months (95% CI, 14.2 to 24.2 months), and 1-year, 2-year, and 4-year actuarial overall survival rates were 66.0%, 25.02%, and 11.3%, respectively. Acneiform rash correlated with improved survival (P = .001), but initial CA19-9, borderline resectable initial stage, and surgical resection (n = 7) did not. The 1-year and 2-year radiographic local progression rates were 22.8% and 61.0%, respectively. The worst acute toxic effects were GI toxicity (32% and 10% for grades 2 and 3, respectively); fatigue (26% and 6% for grades 2 and 3, respectively); sensory neuropathy (9% and 1% for grades 2 and 3, respectively); and acneiform rash (54% and 3% for grades 2 and 3, respectively). Smad4(Dpc4) expression correlated with a local rather than a distant dominant pattern of disease progression (P = .016). CONCLUSION: This regimen appears effective and has acceptable toxicity. The primary end point (1-year overall survival rate > 45%) was met, with encouraging survival duration. Smad4(Dpc4) immunostaining correlated with the pattern of disease progression. Prospective validation of Smad4(Dpc4) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment strategies for patients with localized pancreatic cancer.

16 Clinical Trial Survival and quality of life of patients with resected pancreatic adenocarcinoma treated with adjuvant interferon-based chemoradiation: a phase II trial. 2011

Katz, Matthew H G / Wolff, Robert / Crane, Christopher H / Varadhachary, Gauri / Javle, Milind / Lin, E / Evans, Douglas B / Lee, Jeffrey E / Fleming, Jason B / Pisters, Peter W T. ·Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, USA. ·Ann Surg Oncol · Pubmed #21701927.

ABSTRACT: PURPOSE: We conducted a phase II trial to assess the survival duration and quality of life of patients who received adjuvant interferon-based chemoradiation for pancreatic adenocarcinoma after pancreaticoduodenectomy. METHODS: Patients with a performance status of 0 or 1 were enrolled to receive interferon-alfa-2b (3 million units MWF), cisplatin (30 mg/m(2), 6 doses) and 5-fluorouracil (5-FU; 175 mg/m(2)/day), concurrent with external-beam radiation (50.4 Gy) and followed by 2 courses of systemic 5-FU. The protocol was modified to include an optional 9 day break in the middle of chemoradiation. Quality of life was assessed by use of validated instruments. RESULTS: Twenty-eight patients were eligible for analysis. The operation of 15 (54%) patients was performed at other institutions. All patients had T3 tumors, 22 (79%) had positive lymph nodes and 4 (14%) had positive (R1) margins. 24 (86%) patients completed therapy. In all, 25 (89%) patients experienced grade 3 toxicity and 3 (11%) patients were hospitalized. The most common grade 3 events were leukopenia (15, 54%) and neutropenia (12, 43%). No grade 4 toxicity occurred. Overall quality of life decreased during chemoradiation but returned to baseline thereafter and was stable throughout surveillance. 19 patients have died; the median follow-up of the 9 survivors is 62 months. The median OS duration of treated patients was 42.3 (95% confidence interval 30.5-54.2) months. CONCLUSIONS: Adjuvant interferon-based chemoradiation can be delivered safely and tolerably-though with substantial reversible toxicity-to patients of good performance status at an experienced cancer center. Therapy may be associated with an improvement in overall survival.

17 Clinical Trial Phase II study of bevacizumab with concurrent capecitabine and radiation followed by maintenance gemcitabine and bevacizumab for locally advanced pancreatic cancer: Radiation Therapy Oncology Group RTOG 0411. 2009

Crane, Christopher H / Winter, Kathryn / Regine, William F / Safran, Howard / Rich, Tyvin A / Curran, Walter / Wolff, Robert A / Willett, Christopher G. ·Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. ccrane@mdanderson.org ·J Clin Oncol · Pubmed #19636002.

ABSTRACT: PURPOSE: The primary objective of this study was to assess the 1-year survival of patients with locally advanced, unresectable pancreatic cancer treated with the combination of bevacizumab, capecitabine, and radiation. Secondary end points were toxicity, progression-free survival (PFS), and response rate (RR). PATIENTS AND METHODS: Patients with locally advanced pancreatic cancer without duodenal invasion were treated with 50.4 Gy per 28 fractions to the gross tumor with concurrent capecitabine 825 mg/m(2) orally twice daily on days of radiation and bevacizumab 5 mg/kg on days 1, 15, and 29 followed by maintenance gemcitabine 1 g/m(2) weekly for 3 weeks and bevacizumab 5 mg/kg every 2 weeks, both in 4-week cycles until progression. Treatment plans were reviewed for quality assurance (QA). RESULTS: Between January 2005 and February 2006, 82 eligible patients were treated. The median and 1-year survival rates were 11.9 months (95% CI, 9.9 to 14.0 months) and 47% (95% CI, 36% to 57%). Median PFS was 8.6 months (95% CI, 6.9 to 10.5), and RR was 26%. Overall, 35.4% of patients had grade 3 or greater treatment-related gastrointestinal toxicity (22.0% during chemoradiotherapy, 13.4% during maintenance chemotherapy). Unacceptable radiotherapy protocol deviations (ie, inappropriately generous volume contoured) correlated with grade 3 or greater gastrointestinal toxicity during chemoradiotherapy (45% v 18%; adjusted odds ratio, 3.7; 95% CI, 0.98 to 14.1; P = .05). CONCLUSION: The addition of bevacizumab to chemoradiotherapy followed by bevacizumab and gemcitabine resulted in a similar median survival to previous Radiation Therapy Oncology Group studies in patients with locally advanced pancreatic cancer. Prospective QA may help limit toxicity in future trials.

18 Article Expression of the DNA repair gene MLH1 correlates with survival in patients who have resected pancreatic cancer and have received adjuvant chemoradiation: NRG Oncology RTOG Study 9704. 2018

Lawrence, Yaacov R / Moughan, Jennifer / Magliocco, Anthony M / Klimowicz, Alexander C / Regine, William F / Mowat, Rex B / DiPetrillo, Thomas A / Small, William / Simko, Jeffry P / Golan, Talia / Winter, Kathryn A / Guha, Chandan / Crane, Christopher H / Dicker, Adam P. ·Department of Oncology, Chaim Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel HaShomer, Israel. · Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania. · Statistics and Data Management Center, NRG Oncology, Philadelphia, Pennsylvania. · Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, Florida. · Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut. · University of Maryland School of Medicine, Baltimore, Maryland. · Toledo Clinic Cancer Centers, Toledo, Ohio. · Department of Radiation Oncology, Rhode Island Hospital/The Warren Alpert Medical School of Brown University, Providence, Rhode, Island. · Department of Radiation Oncology, Loyola University Medical Center, Chicago, Illinois. · Department of Pathology, University of California-San Francisco Medical Center, San Francisco, California. · Department of Radiation Oncology, Montefiore Medical Center, Bronx, New York. · Memorial Sloan Kettering Cancer Center, New York, New York. ·Cancer · Pubmed #29053185.

ABSTRACT: BACKGROUND: The majority of patients with pancreatic cancer who undergo curative resection experience rapid disease recurrence. In previous small studies, high expression of the mismatch-repair protein mutL protein homolog 1 (MLH1) in pancreatic cancers was associated with better outcomes. The objective of this study was to validate the association between MLH1 expression and survival in patients who underwent resection of pancreatic cancer and received adjuvant chemoradiation. METHODS: Samples were obtained from the NRG Oncology Radiation Therapy Oncology Group 9704 prospective, randomized trial (clinicaltrials.gov identifier NCT00003216), which compared 2 adjuvant protocols in patients with pancreatic cancer who underwent resection. Tissue microarrays were prepared from formalin-fixed, paraffin-embedded, resected tumor tissues. MLH1 expression was quantified using fluorescence immunohistochemistry and automated quantitative analysis, and expression was dichotomized above and below the median value. RESULTS: Immunohistochemical staining was successfully performed on 117 patients for MLH1 (60 and 57 patients from the 2 arms). The characteristics of the participants who had tissue samples available were similar to those of the trial population as a whole. At the time of analysis, 84% of participants had died, with a median survival of 17 months. Elevated MLH1 expression levels in tumor nuclei were significantly correlated with longer disease-free and overall survival in each arm individually and in both arms combined. Two-year overall survival was 16% in patients who had low MLH1 expression levels and 53% in those who had high MLH1 expression levels (P < .0001 for both arms combined). This association remained true on a multivariate analysis that allowed for lymph node status (hazard ratio, 0.41; 95% confidence interval, 0.27-0.63; P < .0001). CONCLUSIONS: In the current sample, MLH1 expression was correlated with long-term survival. Further studies should assess whether MLH1 expression predicts which patients with localized pancreatic cancer may benefit most from aggressive, multimodality treatment. Cancer 2018;124:491-8. © 2017 American Cancer Society.

19 Article Hypofractionated Radiation Therapy With BED >100 Gy May Rival Surgical Outcomes. 2017

Crane, Christopher H. ·Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York. ·Int J Radiat Oncol Biol Phys · Pubmed #28871978.

ABSTRACT: -- No abstract --

20 Article Stereotactic body radiation vs. intensity-modulated radiation for unresectable pancreatic cancer. 2017

Park, Joseph J / Hajj, Carla / Reyngold, Marsha / Shi, Weiji / Zhang, Zhigang / Cuaron, John J / Crane, Christopher H / O'Reilly, Eileen M / Lowery, Maeve A / Yu, Kenneth H / Goodman, Karyn A / Wu, Abraham J. ·a Department of Radiation Oncology , Memorial Sloan Kettering Cancer Center , New York , NY , USA. · b Department of Epidemiology and Biostatistics , Memorial Sloan Kettering Cancer Center , New York , NY , USA. · c Department of Gastrointestinal Oncology Service , Memorial Sloan Kettering Cancer Center , New York , NY , USA. · d Department of Radiation Oncology , University of Colorado Cancer Center , Aurora , CO , USA. ·Acta Oncol · Pubmed #28661823.

ABSTRACT: BACKGROUND: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for unresectable pancreatic cancer, and is postulated to be more effective and less toxic than conventionally fractionated intensity modulated radiation therapy (IMRT). MATERIAL AND METHODS: We retrospectively reviewed unresectable stage I-III pancreatic adenocarcinoma treated from 2008 to 2016 at our institution with SBRT (five fractions, 30-33 Gy) or IMRT (25-28 fractions, 45-56 Gy with concurrent chemotherapy). Groups were compared with respect to overall survival (OS), local and distant failure, and toxicity. Log-rank test and Cox proportional hazards regression model, and competing risks methods were used for univariate and multivariate analysis. RESULTS: SBRT patients (n = 44) were older than IMRT (n = 226) patients; otherwise there was no significant difference in baseline characteristics. There was no significant difference in OS or local or distant failure. There was no significant difference in rates of subsequent resection (IMRT =17%, SBRT =7%, p = .11). IMRT was associated with more acute grade 2+ gastrointestinal toxicity, grade 2+ fatigue, and grade 3+ hematologic toxicity (p = .008, p < .0001, p = .001, respectively). CONCLUSIONS: In this analysis, SBRT achieves similar disease control outcomes as IMRT, with less acute toxicity. This suggests SBRT is an attractive technique for pancreatic radiotherapy because of improved convenience and tolerability with equivalent efficacy. However, the lack of observed advantages in disease control with this moderate-dose SBRT regimen may suggest a role for increasing SBRT dose, if this can be accomplished without significant increase in toxicity.

21 Article Recommendations for MRI-based contouring of gross tumor volume and organs at risk for radiation therapy of pancreatic cancer. 2017

Heerkens, H D / Hall, W A / Li, X A / Knechtges, P / Dalah, E / Paulson, E S / van den Berg, C A T / Meijer, G J / Koay, E J / Crane, C H / Aitken, K / van Vulpen, M / Erickson, B A. ·Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin. · Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin; Medical Diagnostic Imaging Department, College of Health and Science, University of Sharjah, Sharjah, Dubai. · Department of Radiation Oncology, MD Anderson Hospital, Houston, Texas. · Department of Radiation Oncology, Royal Marsden Hospital London, England. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: berickson@mcw.edu. ·Pract Radiat Oncol · Pubmed #28089481.

ABSTRACT: PURPOSE: Local recurrence is a common and morbid event in patients with unresectable pancreatic adenocarcinoma. A more conformal and targeted radiation dose to the macroscopic tumor in nonmetastatic pancreatic cancer is likely to reduce acute toxicity and improve local control. Optimal soft tissue contrast is required to facilitate delineation of a target and creation of a planning target volume with margin reduction and motion management. Magnetic resonance imaging (MRI) offers considerable advantages in optimizing soft tissue delineation and is an ideal modality for imaging and delineating a gross tumor volume (GTV) within the pancreas, particularly as it relates to conformal radiation planning. Currently, no guidelines have been defined for the delineation of pancreatic tumors for radiation therapy treatment planning. Moreover, abdominal MRI sequences are complex and the anatomy relevant to the radiation oncologist can be challenging. The purpose of this study is to provide recommendations for delineation of GTV and organs at risk (OARs) using MRI and incorporating multiple MRI sequences. METHODS AND MATERIALS: Five patients with pancreatic cancer and 1 healthy subject were imaged with MRI scans either on 1.5T or on 3T magnets in 2 separate institutes. The GTV and OARs were contoured for all patients in a consensus meeting. RESULTS: An overview of MRI-based anatomy of the GTV and OARs is provided. Practical contouring instructions for the GTV and the OARs with the aid of MRI were developed and included in these recommendations. In addition, practical suggestions for implementation of MRI in pancreatic radiation treatment planning are provided. CONCLUSIONS: With this report, we attempt to provide recommendations for MRI-based contouring of pancreatic tumors and OARs. This could lead to better uniformity in defining the GTV and OARs for clinical trials and in radiation therapy treatment planning, with the ultimate goal of improving local control while minimizing morbidity.

22 Article Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy? 2017

Chadha, Awalpreet S / Liu, Guan / Chen, Hsiang-Chun / Das, Prajnan / Minsky, Bruce D / Mahmood, Usama / Delclos, Marc E / Suh, Yelin / Sawakuchi, Gabriel O / Beddar, Sam / Katz, Matthew H / Fleming, Jason B / Javle, Milind M / Varadhachary, Gauri R / Wolff, Robert A / Crane, Christopher H / Wang, Xuemei / Thames, Howard / Krishnan, Sunil. ·Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas; Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: skrishnan@mdanderson.org. ·Int J Radiat Oncol Biol Phys · Pubmed #28068240.

ABSTRACT: PURPOSE: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). METHODS: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gy (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC <0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors. RESULTS: The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P=.01) and multivariate analysis (hazard ratio = 1.66, P=.01). MSD (9.8 vs 6 Gy, P=.03), median V10 (32.6 vs 16%, P=.04), V15 (23.2 vs 9.5%, P=.03), and V20 (15.4 vs 4.6%, P=.02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P=.002; OR= 3.42) were independent predictors for the development of severe post-CRT lymphopenia. CONCLUSION: Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia.

23 Article Preoperative Therapy and Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: a 25-Year Single-Institution Experience. 2017

Cloyd, Jordan M / Katz, Matthew H G / Prakash, Laura / Varadhachary, Gauri R / Wolff, Robert A / Shroff, Rachna T / Javle, Milind / Fogelman, David / Overman, Michael / Crane, Christopher H / Koay, Eugene J / Das, Prajnan / Krishnan, Sunil / Minsky, Bruce D / Lee, Jeffrey H / Bhutani, Manoop S / Weston, Brian / Ross, William / Bhosale, Priya / Tamm, Eric P / Wang, Huamin / Maitra, Anirban / Kim, Michael P / Aloia, Thomas A / Vauthey, Jean-Nicholas / Fleming, Jason B / Abbruzzese, James L / Pisters, Peter W T / Evans, Douglas B / Lee, Jeffrey E. ·Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit 1484, Houston, TX, 77030, USA. · Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Gasteroenterology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Diagnostic Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Division of Medical Oncology, Department of Medicine, Duke University, Durham, NC, USA. · University Health Network, Toronto, ON, Canada. · Division of Surgical Oncology, Department of Surgery, The Medical College of Wisconsin, Milwaukee, WI, USA. · Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit 1484, Houston, TX, 77030, USA. jelee@mdanderson.org. ·J Gastrointest Surg · Pubmed #27778257.

ABSTRACT: BACKGROUND: The purpose of this study was to evaluate a single-institution experience with delivery of preoperative therapy to patients with pancreatic ductal adenocarcinoma (PDAC) prior to pancreatoduodenectomy (PD). METHODS: Consecutive patients (622) with PDAC who underwent PD following chemotherapy and/or chemoradiation between 1990 and 2014 were retrospectively reviewed. Preoperative treatment regimens, clinicopathologic characteristics, operative details, and long-term outcomes in four successive time periods (1990-1999, 2000-2004, 2005-2009, 2010-2014) were evaluated and compared. RESULTS: The average number of patients per year who underwent PD following preoperative therapy as well as the proportion of operations performed for borderline resectable and locally advanced (BR/LA) tumors increased over time. The use of induction systemic chemotherapy, as well as postoperative adjuvant chemotherapy, also increased over time. Throughout the study period, the mean EBL decreased while R0 margin rates and vascular resection rates increased overall. Despite the increase in BR/LA resections, locoregional recurrence (LR) rates remained similar over time, and overall survival (OS) improved significantly (median 24.1, 28.1, 37.3, 43.4 months, respectively, p < 0.0001). CONCLUSIONS: Despite increases in case complexity, relatively low rates of LR have been maintained while significant improvements in OS have been observed. Further improvements in patient outcomes will likely require disruptive advances in systemic therapy.

24 Article Preoperative Chemoradiation for Pancreatic Adenocarcinoma Does Not Increase 90-Day Postoperative Morbidity or Mortality. 2016

Denbo, Jason W / Bruno, Morgan L / Cloyd, Jordan M / Prakash, Laura / Lee, Jeffrey E / Kim, Michael / Crane, Christopher H / Koay, Eugene J / Krishnan, Sunil / Das, Prajnan / Minsky, Bruce D / Varadhachary, Gauri / Shroff, Rachna / Wolff, Robert / Javle, Milind / Overman, Michael J / Fogelman, David / Aloia, Thomas A / Vauthey, Jean-Nicolas / Fleming, Jason B / Katz, Matthew H G. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA. mhgkatz@mdanderson.org. ·J Gastrointest Surg · Pubmed #27730398.

ABSTRACT: BACKGROUND: The impact of preoperative chemoradiation on postoperative morbidity and mortality of patients with pancreatic adenocarcinoma remains controversial. METHODS: Consecutive pancreatectomies for adenocarcinoma performed between 2011 and 2015 were prospectively monitored for 90 days by using a previously reported surveillance system to determine the association between preoperative chemoradiation and adverse events, pancreatic fistulae, readmissions, and mortality. RESULTS: Among 209 consecutive patients who underwent pancreatectomy, 159 (76 %) experienced at least one adverse event within 90 postoperative days. Patients who received preoperative chemoradiation (n = 137, 66 %) were more likely to have borderline resectable/locally advanced tumors, to have received induction chemotherapy, and to require vascular resection at pancreatectomy than those who did not receive chemoradiation (all P < 0.05). Nonetheless, there were no significant differences in the rates of severe complications, readmission, or mortality between these groups (all P > 0.05). Among patients who underwent pancreatoduodenectomy, the rate of pancreatic fistula was similar between those who received chemoradiation and those who did not (P = 0.96). In contrast, those who received chemoradiation prior to distal pancreatectomy had a lower rate of pancreatic fistula (P < 0.01). CONCLUSION: Preoperative chemoradiation is not associated with an increase in 90-day morbidity or mortality, and it may reduce the rate of pancreatic fistula following distal pancreatectomy.

25 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.

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