Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Theodore S. Hong
Based on 34 articles published since 2009
(Why 34 articles?)
||||

Between 2009 and 2019, Theodore Hong wrote the following 34 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 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.

2 Review FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. 2016

Suker, Mustafa / Beumer, Berend R / Sadot, Eran / Marthey, Lysiane / Faris, Jason E / Mellon, Eric A / El-Rayes, Bassel F / Wang-Gillam, Andrea / Lacy, Jill / Hosein, Peter J / Moorcraft, Sing Yu / Conroy, Thierry / Hohla, Florian / Allen, Peter / Taieb, Julien / Hong, Theodore S / Shridhar, Ravi / Chau, Ian / van Eijck, Casper H / Koerkamp, Bas Groot. ·Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Hepatogastroenterology, Antoine Beclère Hospital, Assistance publique-Hôpitaux de Paris, Paris Sud University, Clamart, France. · Department of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, USA. · Department of Radiation Oncology, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA. · Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA. · Department of Medicine, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. · Department of Medicine, Division of Medical Oncology, University of Kentucky-Markey Cancer Center, Lexington, KY, USA. · Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London and Surrey, UK. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, Vandoeuvre-lès-Nancy, France. · Department of Hematology, Medical Oncology, Hemostasis, Rheumatology and Infectious Diseases, Paracelsus Medical University of Salzburg, Salzburg, Austria. · Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, Assistance publique-Hôpitaux de Paris, Sorbonne Paris Cité, Paris Descartes University, Cancer Research Personalized Medicine (CARPEM), Paris, France. · Department of Radiation Oncology, Florida Hospital Cancer Institute, Orlando, FL, USA. · Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. Electronic address: b.grootkoerkamp@erasmusmc.nl. ·Lancet Oncol · Pubmed #27160474.

ABSTRACT: BACKGROUND: 35% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) in patients with locally advanced pancreatic cancer. We aimed to assess the effectiveness of FOLFIRINOX as first-line treatment in this patient population. METHODS: We systematically searched Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar from July 1, 1994, to July 2, 2015, for studies of treatment-naive patients of any age who received FOLFIRINOX as first-line treatment of locally advanced pancreatic cancer. Our primary outcome was overall survival. Secondary outcomes were progression-free survival; rates of grade 3 or 4 adverse events; and the proportion of patients who underwent radiotherapy or chemoradiotherapy, surgical resection after FOLFIRINOX, and R0 resection. We evaluated survival outcomes with the Kaplan-Meier method with patient-level data. Grade 3 or 4 adverse events, and the proportion of patients who underwent subsequent radiotherapy or chemoradiotherapy or resection, were pooled in a random-effects model. FINDINGS: We included 13 studies comprising 689 patients, of whom 355 (52%) patients had locally advanced pancreatic cancer. 11 studies, comprising 315 patients with locally advanced disease, reported survival outcomes and were eligible for patient-level meta-analysis. Median overall survival from the start of FOLFIRINOX ranged from 10·0 months (95% CI 4·0-16·0) to 32·7 months (23·1-42·3) across studies with a pooled patient-level median overall survival of 24·2 months (95% CI 21·7-26·8). Median progression-free survival ranged from 3·0 months (95% CI not calculable) to 20·4 months (6·5-34·3) across studies with a patient-level median progression-free survival of 15·0 months (95% 13·8-16·2). In ten studies comprising 490 patients, 296 grade 3 or 4 adverse events were reported (60·4 events per 100 patients). No deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent radiotherapy or chemoradiotherapy ranged from 31% to 100% across studies. In eight studies, 154 (57%) of 271 patients received radiotherapy or chemoradiotherapy after FOLFIRINOX. The pooled proportion of patients who received any radiotherapy treatment was 63·5% (95% CI 43·3-81·6, I(2) 90%). The proportion of patients who underwent surgical resection for locally advanced pancreatic cancer ranged from 0% to 43%. The proportion of patients who had R0 resection of those who underwent resection ranged from 50% to 100% across studies. In 12 studies, 91 (28%) of 325 patients underwent resection after FOLFIRINOX. The pooled proportion of patients who had resection was 25·9% (95% CI 20·2-31·9, I(2) 24%). R0 resection was reported in 60 (74%) of 81 patients. The pooled proportion of patients who had R0 resection was 78·4% (95% CI 60·2-92·2, I(2) 64%). INTERPRETATION: Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months-longer than that reported with gemcitabine (6-13 months). Future research should assess these promising results in a randomised controlled trial, and should establish which patients might benefit from radiotherapy or chemoradiotherapy or resection after FOLFIRINOX. FUNDING: None.

3 Review Pancreatic adenocarcinoma. 2014

Ryan, David P / Hong, Theodore S / Bardeesy, Nabeel. ·From the Division of Hematology-Oncology, Department of Medicine (D.P.R., N.B.), and the Department of Radiation Oncology (T.S.H.), Massachusetts General Hospital, Boston. ·N Engl J Med · Pubmed #25207767.

ABSTRACT: -- No abstract --

4 Review Intraductal papillary mucinous neoplasm: clinical surveillance and management decisions. 2014

Chin, Joanna Y / Pitman, Martha B / Hong, Theodore S. ·Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. Electronic address: tshong1@partners.org. ·Semin Radiat Oncol · Pubmed #24635864.

ABSTRACT: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a relatively rare cystic neoplasm. Although most IPMNs appear to be benign and may be managed by surveillance, all IPMNs are considered premalignant lesions with malignant potential. As such, current efforts are focused on identifying those neoplasms that are at high risk for malignancy to optimize treatment strategy and outcome. IPMNs with invasive carcinoma have clinical outcomes that approach those of conventional pancreatic ductal adenocarcinoma. Management guidelines recommend surgical resection for IPMNs with high-risk imaging or cytologic features. The role of adjuvant therapy is unclear, and we review the evidence for chemoradiation here. Some studies suggest adjuvant chemoradiation may have the greatest impact in malignant IPMNs with adverse histologic features, that is, lymph node metastasis at the time of diagnosis or positive surgical margins. As more IPMNs are recognized and treated, more evidence will accumulate to guide clinicians regarding appropriate use of radiotherapy in the management of IPMN.

5 Review Chemoradiation therapy: localized esophageal, gastric, and pancreatic cancer. 2013

Pretz, Jennifer L / Wo, Jennifer Y / Mamon, Harvey J / Kachnic, Lisa A / Hong, Theodore S. ·Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA, USA. ·Surg Oncol Clin N Am · Pubmed #23622077.

ABSTRACT: Chemoradiation plays an important role in management of locally advanced gastrointestinal tumors. This article reviews data regarding chemoradiation for tumors of the upper gastrointestinal tract. For esophageal and gastroesophageal junction cancers, chemoradiation is standard of care in the preoperative setting. In gastric cancer, 2 standards have emerged: definitively treating with perioperative chemotherapy alone and using chemoradiation postoperatively. For pancreatic cancer, the benefit of radiation is less well defined. The future of treatment sites lies in trials evaluating new chemotherapy regimens, alternative systemic therapies, and different radiation fractionation schema. Because care of these patients is complex, multimodality team evaluation before treatment is encouraged.

6 Clinical Trial Elective nodal irradiation with simultaneous integrated boost stereotactic body radiotherapy for pancreatic cancer: Analyses of planning feasibility and geometrically driven DVH prediction model. 2019

Nakamura, Akira / Prichard, Hugh A / Wo, Jennifer Y / Wolfgang, John A / Hong, Theodore S. ·Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ·J Appl Clin Med Phys · Pubmed #30636367.

ABSTRACT: PURPOSE: We evaluate the feasibility of the elective nodal irradiation strategy in stereotactic body radiotherapy (SBRT) for pancreatic cancer. METHODS: Three simultaneous integrated boost (SIB)-SBRT plans (Boost1, Boost2, and Boost3) were retrospectively generated for each of 20 different patients. Boost1 delivered 33 and 25 Gy to PTV1 and PTV2, respectively. Boost2 delivered 40, 33, and 25 Gy to boostCTV, PTV1, and PTV2, respectively. Boost3 delivered 33 and 25 Gy to PTV1 and PTV3, respectively. PTV1 covered the initial standard SBRT plan (InitPlan) gross tumor volume (GTV). PTV2 covered CTVgeom which was created by a 10-mm expansion (15 mm posterior) of GTV. PTV3 covered CTVprop which included elective nodal regions. The boostCTV included GTV as well as involved vasculature. The planning feasibility in each scenario and dose-volume histograms (DVHs) were analyzed and compared with the InitPlan (delivered 33 Gy only to PTV1) by paired t-test. Next, a novel DVH prediction model was developed and its performance was evaluated according to the prediction accuracy (AC) of planning violations. Then, the model was used to simulate the impacts of GTV-to-organs at risk (OAR) distance and gastrointestinal (GI) OAR volume variations on planning feasibility. RESULTS: Significant dose increases were observed in GI-OARs in SIB-SBRT plans when compared with InitPlan. All dose constraints were met in 63% of cases in InitPlan, Boost1, and Boost2, whereas Boost3 developed DVH violations in all cases. Utilizing previous patient anatomy, the novel DVH prediction model achieved a high AC in the prediction of violations for GI-OARs; the positive predictive value, negative predictive value, and AC were 66%, 90%, and 84%, respectively. Experiments with the model demonstrated that the larger proximity volume of GI-OAR at the shorter distance substantially impacted on planning violations. CONCLUSIONS: SIB-SBRT plan with geometrically defined prophylactic areas can be dosimetrically feasible, but including all nodal areas with 25 Gy in five fractions appears to be unrealistic.

7 Clinical Trial A phase 1/2 and biomarker study of preoperative short course chemoradiation with proton beam therapy and capecitabine followed by early surgery for resectable pancreatic ductal adenocarcinoma. 2014

Hong, Theodore S / Ryan, David P / Borger, Darrell R / Blaszkowsky, Lawrence S / Yeap, Beow Y / Ancukiewicz, Marek / Deshpande, Vikram / Shinagare, Shweta / Wo, Jennifer Y / Boucher, Yves / Wadlow, Raymond C / Kwak, Eunice L / Allen, Jill N / Clark, Jeffrey W / Zhu, Andrew X / Ferrone, Cristina R / Mamon, Harvey J / Adams, Judith / Winrich, Barbara / Grillo, Tarin / Jain, Rakesh K / DeLaney, Thomas F / Fernandez-del Castillo, Carlos / Duda, Dan G. ·Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: tshong1@partners.org. · Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts. ·Int J Radiat Oncol Biol Phys · Pubmed #24867540.

ABSTRACT: PURPOSE: To evaluate the safety, efficacy and biomarkers of short-course proton beam radiation and capecitabine, followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS AND MATERIALS: Patients with radiographically resectable, biopsy-proven PDAC were treated with neoadjuvant short-course (2-week) proton-based radiation with capecitabine, followed by surgery and adjuvant gemcitabine. The primary objective was to demonstrate a rate of toxicity grade ≥ 3 of <20%. Exploratory biomarker studies were performed using surgical specimen tissues and peripheral blood. RESULTS: The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty patients were enrolled, of whom 35 patients were treated in the phase 2 portion. There were no grade 4 or 5 toxicities, and only 2 of 35 patients (4.1%) experienced a grade 3 toxicity event (chest wall pain grade 1, colitis grade 1). Of 48 patients eligible for analysis, 37 underwent pancreaticoduodenectomy. Thirty of 37 (81%) had positive nodes. Locoregional failure occurred in 6 of 37 resected patients (16.2%), and distant recurrence occurred in 35 of 48 patients (72.9%). With median follow-up of 38 months, the median progression-free survival for the entire group was 10 months, and overall survival was 17 months. Biomarker studies showed significant associations between worse survival outcomes and the KRAS point mutation change from glycine to aspartic acid at position 12, stromal CXCR7 expression, and circulating biomarkers CEA, CA19-9, and HGF (all, P<.05). CONCLUSIONS: This study met the primary endpoint by showing a rate of 4.1% grade 3 toxicity for neoadjuvant short-course proton-based chemoradiation. Treatment was associated with favorable local control. In exploratory analyses, KRAS(G12D) status and high CXCR7 expression and circulating CEA, CA19-9, and HGF levels were associated with poor survival.

8 Clinical Trial Phase I study of neoadjuvant accelerated short course radiation therapy with photons and capecitabine for resectable pancreatic cancer. 2014

Wo, Jennifer Y / Mamon, Harvey J / Ferrone, Cristina R / Ryan, David P / Blaszkowsky, Lawrence S / Kwak, Eunice L / Tseng, Yolanda D / Napolitano, Brian N / Ancukiewicz, Marek / Swanson, Richard S / Lillemoe, Keith D / Fernandez-del Castillo, Carlos / Hong, Theodore S. ·Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, United States. Electronic address: jwo@partners.org. · Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, United States. · Department of General Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, United States. · Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, United States. · Harvard Radiation Oncology Program, Boston, United States. · Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, United States. · Department of General Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, United States. ·Radiother Oncol · Pubmed #24231241.

ABSTRACT: PURPOSE: In this phase I study, we sought to determine the feasibility and tolerability of neoadjuvant short course radiotherapy (SC-CRT) delivered with photon RT with concurrent capecitabine for resectable pancreatic adenocarcinoma. MATERIALS AND METHODS: Ten patients with localized, resectable pancreatic adenocarcinoma were enrolled from December 2009 to August 2011. In dose level I, patients received 3 Gy × 10. In dose level 2, patients received 5 Gy × 5 (every other day). In dose level 3, patients received 5 Gy × 5 (consecutive days). Capecitabine was given during weeks 1 and 2. Surgery was performed 1-3 weeks after completion of chemotherapy. RESULTS: With an intended accrual of 12 patients, the study was closed early due to unexpected intraoperative complications. Compared to the companion phase I proton study, patients treated with photons had increased intraoperative RT fibrosis reported by surgeons (27% vs. 63%). Among those undergoing a Whipple resection, increased RT fibrosis translated to an increased mean OR time of 69 min. Dosimetric comparison revealed significantly increased low dose exposure to organs at risk for patients treated with photon RT. CONCLUSIONS: This phase I experience evaluating the tolerability of neoadjuvant SC-CRT with photon RT closed early due to unexpected intraoperative complications.

9 Clinical Trial Phase I study of preoperative short-course chemoradiation with proton beam therapy and capecitabine for resectable pancreatic ductal adenocarcinoma of the head. 2011

Hong, Theodore S / Ryan, David P / Blaszkowsky, Lawrence S / Mamon, Harvey J / Kwak, Eunice L / Mino-Kenudson, Mari / Adams, Judith / Yeap, Beow / Winrich, Barbara / DeLaney, Thomas F / Fernandez-Del Castillo, Carlos. ·Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. tshong1@partners.org ·Int J Radiat Oncol Biol Phys · Pubmed #20421151.

ABSTRACT: PURPOSE: To evaluate the safety of 1 week of chemoradiation with proton beam therapy and capecitabine followed by early surgery. METHODS AND MATERIALS: Fifteen patients with localized resectable, pancreatic adenocarcinoma of the head were enrolled from May 2006 to September 2008. Patients received radiation with proton beam. In dose level 1, patients received 3 GyE × 10 (Week 1, Monday-Friday; Week 2, Monday-Friday). Patients in Dose Levels 2 to 4 received 5 GyE × 5 in progressively shortened schedules: level 2 (Week 1, Monday, Wednesday, and Friday; Week 2, Tuesday and Thursday), Level 3 (Week 1, Monday, Tuesday, Thursday, and Friday; Week 2, Monday), Level 4 (Week 1, Monday through Friday). Capecitabine was given as 825 mg/m(2) b.i.d. Weeks 1 and 2 Monday through Friday for a total of 10 days in all dose levels. Surgery was performed 4 to 6 weeks after completion of chemotherapy for Dose Levels 1 to 3 and then after 1 to 3 weeks for Dose Level 4. RESULTS: Three patients were treated at Dose Levels 1 to 3 and 6 patients at Dose Level 4, which was selected as the MTD. No dose limiting toxicities were observed. Grade 3 toxicity was noted in 4 patients (pain in 1; stent obstruction or infection in 3). Eleven patients underwent resection. Reasons for no resection were metastatic disease (3 patients) and unresectable tumor (1 patient). Mean postsurgical length of stay was 6 days (range, 5-10 days). No unexpected 30-day postoperative complications, including leak or obstruction, were found. CONCLUSIONS: Preoperative chemoradiation with 1 week of proton beam therapy and capecitabine followed by early surgery is feasible. A Phase II study is underway.

10 Article Association Between Very Small Tumor Size and Decreased Overall Survival in Node-Positive Pancreatic Cancer. 2018

Muralidhar, Vinayak / Nipp, Ryan D / Mamon, Harvey J / Punglia, Rinaa S / Hong, Theodore S / Ferrone, Cristina / Fernandez-Del Castillo, Carlos / Parikh, Aparna / Nguyen, Paul L / Wo, Jennifer Y. ·Harvard Radiation Oncology Program, Boston, MA, USA. · Department of Medical Oncology, Massachusetts General Hospital, Boston, MA, USA. · Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA, USA. · Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA. · Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. · Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA. jwo@mgh.harvard.edu. ·Ann Surg Oncol · Pubmed #30298331.

ABSTRACT: BACKGROUND: In pancreatic adenocarcinoma (PDAC), increasing tumor size usually correlates with a worse prognosis. However, patients with a very small primary tumor who experience lymph node involvement may have a different disease biology. This study sought to determine the interaction between tumor size and lymph node involvement in terms of overall survival (OS). METHODS: The study identified 17,073 patients with a diagnosis of M0 resected PDAC between 1983 and 2013 using the Surveillance, Epidemiology, and End Results database. The patients were stratified by lymph node involvement (N0 vs N+) and T stage (T1a-T1b vs T1c vs T2 vs T3 vs T4). The Kaplan-Meier method was used to estimate OS, and Cox regression analysis was used to compare survival between subgroups after adjustment for patient-specific factors. RESULTS: Lymph node involvement and T stage significantly interacted (p < 0.001). Among the patients with node-negative disease, 5-year OS decreased monotonically with increasing T stage (59.1%, 30.6%, 22.9%, 16.6%, and 8.0%, respectively; p < 0.001). In contrast, among the patients with node-positive disease, those with T1a-T1b tumors (< 10 mm) had worse 5-year OS than those with T1c tumors (7.4% vs 17.6%; adjusted hazard ratio, 0.70; 95% confidence interval, 0.50-0.97; p = 0.034) and similar survival compared with those who had T2, T3, or T4 tumors (9.7%, 8.2%, and 4.8%, respectively; p > 0.2 in all cases). CONCLUSIONS: Among patients with lymph node-positive PDAC, very small primary tumors are associated with decreased OS. This finding raises the possibility that small tumors capable of lymph node metastasis might represent more biologically aggressive cancers.

11 Article Are Staging Computed Tomography (CT) Scans of the Chest Necessary in Pancreatic Adenocarcinoma? 2018

Mehtsun, Winta T / Chipidza, Fallon E / Fernández-Del Castillo, Carlos / Hemingway, Katherine / Fong, Zhi Ven / Chang, David C / Pandharipande, Pari / Clark, Jeffrey W / Allen, Jill / Hong, Theodore S / Wo, Jennifer Y / Warshaw, Andrew L / Lillemoe, Keith D / Ferrone, Cristina R. ·Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. · Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA. · Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA. · Department of Radiology, Massachusetts General Hospital, Boston, MA, USA. · Department of Medical Oncology, Massachusetts General Hospital, Boston, MA, USA. · Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. cferrone@partners.org. ·Ann Surg Oncol · Pubmed #30276641.

ABSTRACT: BACKGROUND: There is no consensus on the use of chest imaging in pancreatic ductal adenocarcinoma (PDAC) patients. Among PDAC patients, we examined the use of chest computed tomography (CT) over time and determined whether the use of chest CT led to a survival difference or change in management via identification of indeterminate lung nodules (ILNs). METHODS: Retrospective clinical data was collected for patients diagnosed with PDAC from 1998 to 2014. We examined the proportion of patients undergoing staging chest CT scan and those who had ILN, defined as ≥ 1 well-defined, noncalcified lung nodule(s) ≤ 1 cm in diameter. We determined time to overall survival (OS) using multivariate Cox regression. We also assessed changes in management of PDAC patients who later developed lung metastasis only. RESULTS: Of the 2710 patients diagnosed with PDAC, 632 (23%) had greater than one chest CT. Of those patients, 451 (71%) patients had ILNs, whereas 181 (29%) had no ILNs. There was no difference in median overall survival in patients without ILNs (16.4 [13.6, 19.0] months) versus those with ILN (14.8 [13.6, 15.8] months, P = 0.18). Examining patients who developed isolated lung metastases (3.3%), we found that staging chest CTs did not lead to changes in management of the primary abdominal tumor. CONCLUSIONS: Survival did not differ for PDAC patients with ILNs identified on staging chest CTs compared with those without ILNs. Furthermore, ILN identification did not lead to changes in management of the primary abdominal tumor, questioning the utility of staging chest CTs for PDAC patients.

12 Article Pilot study on the impact of F18-labeled thymidine PET/CT on gross tumor volume identification and definition for pancreatic cancer. 2018

Pretz, Jennifer L / Blake, Michael A / Killoran, Joseph H / Mamon, Harvey J / Wo, Jennifer Y / Zhu, Andrew X / Hong, Theodore S. ·Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: jpretz@partners.org. · Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. ·Pract Radiat Oncol · Pubmed #29042120.

ABSTRACT: PURPOSE: Accurate target definition for radiation therapy planning in localized pancreatic cancer is critical, particularly when using strategies that omit elective coverage. Standard imaging modalities such as computed tomography (CT), magnetic resonance imaging, and endoscopic ultrasound have limited concordance with pathologic evaluation. Biologic imaging with [F18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) can also be difficult to interpret because increased activity is indicative of increased glucose metabolism, rather than cellular proliferation. [F18]-3'-deoxy-3'-fluorothymidine labeled thymidine (FLT) is a proliferative marker which exploits the expression of pyrimidine-metabolizing enzymes. We evaluate the impact of FLT-PET on pancreatic target definition for radiation planning. METHODS AND MATERIALS: Patients with biopsy-proven, newly diagnosed, untreated pancreatic adenocarcinoma were enrolled on an institutional review board-approved prospective study. Patients were injected with FLT and scanned 20 to 30 minutes later. Two physicians (referred to as observer 1 and observer 2) independently contoured the gross tumor volume (GTV) and involved nodes on CT scan only and then again with the assistance of coregistered FLT-PET. Conformality index (CI), the ratio of the volumes of intersection and union, was used as the metric for volume comparison (where CI = 0 represents no overlap and CI = 1 represents perfect overlap). RESULTS: Nine patients were enrolled in this study. FLT-avidity was discerned in 8 of 9 patients. Average CT-GTV volume for observers 1 and 2 was 38.1 and 26.5 mL, respectively. Average FLT-GTV volume for observers 1 and 2 was 39.1 and 25.0 mL, respectively. For the 8 patients with FLT-avid tumors, addition of FLT data improved concordance of GTV definition between physicians in 6 of 8 tumors. Average CI for interobserver CT-GTV was 0.325. Addition of FLT-PET information improved the average CI to 0.400. CONCLUSIONS: FLT-PET improves interobserver concordance in GTV definition. Further studies will focus on verification of these findings, pathologic verification of the FLT-PET signal, and optimization of the FLT-PET signal threshold for autosegmentation.

13 Article Tolerability and Long-term Outcomes of Dose-Painted Neoadjuvant Chemoradiation to Regions of Vessel Involvement in Borderline or Locally Advanced Pancreatic Cancer. 2018

Wo, Jennifer Y / Niemierko, Andrzej / Ryan, David P / Blaszkowsky, Lawrence S / Clark, Jeffrey W / Kwak, Eunice L / Lillemoe, Keith D / Drapek, Lorraine N / Zhu, Andrew X / Allen, Jill N / Faris, Jason E / Murphy, Janet E / Nipp, Ryan / Fernandez-Del Castillo, Carlos / Ferrone, Cristina R / Hong, Theodore S. ·Departments of Radiation Oncology. · Medical Oncology. · General Surgery, Massachusetts General Hospital, Boston, MA. ·Am J Clin Oncol · Pubmed #28134673.

ABSTRACT: PURPOSE: We reviewed our experience involving patients with borderline resectable or locally advanced pancreatic cancer, treated with the dose-painted (DP) boost technique to regions of vessel involvement which preclude upfront surgical resection. We evaluated patient outcomes with respect to tolerability and treatment outcomes. MATERIALS AND METHODS: We retrospectively reviewed 99 patients with borderline resectable (n=25) or locally advanced pancreatic cancer (n=74) treated with DP-neoadjuvant chemoradiation from 2010 to 2015. Tumor and regional lymph nodes were prescribed 50.4 Gy and the region around the involved blood vessel was boosted to 58.8 Gy in 28 fractions. The primary outcome was acute toxicity and late duodenal toxicity. Secondary outcomes included conversion to surgical resectability, local failure, disease-free survival, and overall survival (OS). Cox proportional hazards models were performed to evaluate for predictors of survival. RESULTS: All but 1 patient completed chemoradiation. The rates of grade 2+ and 3+ nausea were 40% and 12%, respectively. With regards to late toxicity, 5 patients developed potential RT-related grade 3+ duodenal complications including duodenal ulceration/bleeding (n=3) and duodenal stricture (n=2). With a median follow-up of 15 months, the median OS was 18.1 months. Among 99 patients in our study, 37 patients underwent surgical resection. For patients who underwent surgical resection (n=37), the median OS was 30.9 months. On multivariate analysis, only normalization of CA 19-9 post-RT was associated with improved OS. CONCLUSIONS: We found that DP-neoadjuvant chemoradiation to regions of vessel involvement is both feasible and well tolerated. In addition, we demonstrated that over one third of patients with initially deemed unresectable disease were able to undergo surgical resection after receiving neoadjuvant therapy including DP-chemoradiation.

14 Article Intraoperative Radiotherapy in the Era of Intensive Neoadjuvant Chemotherapy and Chemoradiotherapy for Pancreatic Adenocarcinoma. 2018

Keane, Florence K / Wo, Jennifer Y / Ferrone, Cristina R / Clark, Jeffrey W / Blaszkowsky, Lawrence S / Allen, Jill N / Kwak, Eunice L / Ryan, David P / Lillemoe, Keith D / Fernandez-Del Castillo, Carlos / Hong, Theodore S. ·Harvard Radiation Oncology Program, Harvard Medical School. · Departments of Radiation Oncology. · Surgery. · Medicine, Division of Medical Oncology, Massachusetts General Hospital, Boston, MA. ·Am J Clin Oncol · Pubmed #27740973.

ABSTRACT: OBJECTIVES: Improved outcomes with FOLFIRINOX or gemcitabine with nab-paclitaxel in the treatment of metastatic pancreatic adenocarcinoma (PDAC) have prompted incorporation of these regimens into neoadjuvant treatment of locally advanced unresectable PDAC. Whereas some patients remain unresectable on surgical exploration, others are able to undergo resection after intensive neoadjuvant treatment. We evaluated outcomes and toxicity associated with use of intensive neoadjuvant treatment followed by intraoperative radiotherapy (IORT) in combination with resection or exploratory laparotomy. METHODS: We retrospectively analyzed patients with locally advanced unresectable or borderline-resectable PDAC who received intensive neoadjuvant treatment with induction chemotherapy and chemoradiotherapy followed by exploratory laparotomy in an IORT-equipped operating suite between 2010 and 2015. Surgical outcomes and overall survival (OS) were compared. RESULTS: Of 68 patients, 41 (60.3%) underwent resection, 18 (26.5%) had unresectable disease, and 9 (13.2%) had distant metastases. Of 41 resectable patients, 22 received IORT for close/positive resection margins on intraoperative frozen section. There was no significant difference in operative times or morbidity with addition of IORT to resection. Median OS was 26.6 months for all patients who underwent resection, 35.1 months for patients who underwent resection and IORT, and 24.5 months for patients who underwent resection alone (P=NS). Of 18 patients with unresectable disease, all but 1 received IORT, with median OS of 24.8 months. IORT was associated with increased hospital stay (4 vs. 3.5 d), but no significant difference in operative times or morbidity. CONCLUSIONS: IORT in addition to intensive neoadjuvant chemotherapy and chemoradiotherapy was not associated with increased toxicity when used with resection or exploratory laparotomy, and was associated with encouraging survival rates in patients with close/positive margins and patients with unresectable disease.

15 Article A novel chemoradiation targeting stem and nonstem pancreatic cancer cells by repurposing disulfiram. 2017

Cong, Juan / Wang, Yangyang / Zhang, Xiao / Zhang, Nan / Liu, Ling / Soukup, Klara / Michelakos, Theodoros / Hong, Theodore / DeLeo, Albert / Cai, Lei / Sabbatino, Francesco / Ferrone, Soldano / Lee, Hang / Levina, Vera / Fuchs, Bryan / Tanabe, Kenneth / Lillemoe, Keith / Ferrone, Cristina / Wang, Xinhui. ·Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. · Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. · University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA. · Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. · Department of Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. · University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA. · Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. · Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: xwang30@mgh.harvard.edu. ·Cancer Lett · Pubmed #28864067.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) has a 5-year relative survival rate of 8% and is projected to be the second leading cause of cancer death by 2030, underscoring the urgency to develop new strategies to improve current therapeutic modalities for PDAC. Targeting pancreatic cancer stem cells (PCSCs), which are resistant to radiation and chemotherapy, is a promising strategy. A novel approach which can be readily clinically translated is to repurpose disulfiram (DSF), a drug for treating alcoholism, to target PCSCs. Chemoradiation or the combination of chemotherapy agents FOLFIRINOX, currently standard care for PDAC, can increase stemness in some established or primary PDAC cell lines. However, DSF in the presence of exogenously or endogenously supplied copper (Cu), when combined with chemotherapy or chemoradiation, targets both PCSCs and nonstem PDAC cells. Previously, we demonstrated that DSF/Cu effectively targets breast cancer stem cells in the context of fractionated radiation (FIR) by inhibiting the NF-κB-stemness gene pathway. Therefore, the hypothesis that PCSCs can be effectively targeted by incorporating DSF/Cu into the standard chemoradiation regimen consisting of 5-FU and FIR was investigated and found to be effective in vitro in targeting PCSCs, identified as either ALDH

16 Article Use of Angiotensin System Inhibitors Is Associated with Immune Activation and Longer Survival in Nonmetastatic Pancreatic Ductal Adenocarcinoma. 2017

Liu, Hao / Naxerova, Kamila / Pinter, Matthias / Incio, Joao / Lee, Hang / Shigeta, Kohei / Ho, William W / Crain, Jonathan A / Jacobson, Alex / Michelakos, Theodoros / Dias-Santos, Daniella / Zanconato, Andrea / Hong, Theodore S / Clark, Jeffrey W / Murphy, Janet E / Ryan, David P / Deshpande, Vikram / Lillemoe, Keith D / Fernandez-Del Castillo, Carlos / Downes, Michael / Evans, Ronald M / Michaelson, James / Ferrone, Cristina R / Boucher, Yves / Jain, Rakesh K. ·Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Leder Human Biology and Translational Medicine, Biology and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts. · Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts. · Laboratory for Quantitative Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Gene Expression Laboratory, Salk Institute for Biological Studies in La Jolla, La Jolla, California. · Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. yves@steele.mgh.harvard.edu jain@steele.mgh.harvard.edu. ·Clin Cancer Res · Pubmed #28600474.

ABSTRACT:

17 Article Predictors of Early Mortality After Surgical Resection of Pancreatic Adenocarcinoma in the Era of Neoadjuvant Treatment. 2017

Nipp, Ryan D / Zanconato, Andrea / Zheng, Hui / Ferrone, Cristina R / Lillemoe, Keith D / Wo, Jennifer Y / Hong, Theodore S / Clark, Jeffrey W / Ryan, David P / Fernández-Del Castillo, Carlos. ·From the Departments of *Medical Oncology, †Surgery, ‡Biostatistics Center, and §Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. ·Pancreas · Pubmed #27846142.

ABSTRACT: OBJECTIVES: Neoadjuvant treatments are increasingly used for patients with pancreatic ductal adenocarcinoma (PDAC), yet some experience early mortality after resection. We sought to identify predictors of early mortality after PDAC resection and determine their interaction with neoadjuvant therapy. METHODS: We performed a retrospective study of patients with PDAC resection from March 2011 to March 2014. We compared those who died within one year after surgery to those living beyond 1 year, and those who received neoadjuvant therapy to those taken directly to surgery. We used logistic regression to identify predictors of early mortality and determine their interaction with neoadjuvant therapy. RESULTS: Of 191 patients who underwent resection, 59 (30.9%) died within 1 year and 79 (41.4%) received neoadjuvant therapy. Early mortality patients were older, with higher comorbidity, and more likely to have lymph node positivity. Patients receiving neoadjuvant therapy were younger, with lower comorbidity, and more likely to have upfront unresectable disease. Predictors of early mortality included: higher comorbidity, poorly differentiated tumor grade, and lymph node positivity. We found that neoadjuvant therapy moderated the effects of comorbidity and lymph node positivity on early mortality risk. CONCLUSIONS: We identified predictors of early mortality after PDAC resection and determined their interaction with neoadjuvant therapy.

18 Article Understanding the Paradigm Shift in Pancreatic Cancer. 2016

Ryan, David P / Hong, Theodore S. ·Massachusetts General Hospital and Harvard Medical School, Boston, MA. ·J Oncol Pract · Pubmed #27858558.

ABSTRACT: -- No abstract --

19 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.

20 Article Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. 2015

Ferrone, Cristina R / Marchegiani, Giovanni / Hong, Theodore S / Ryan, David P / Deshpande, Vikram / McDonnell, Erin I / Sabbatino, Francesco / Santos, Daniela Dias / Allen, Jill N / Blaszkowsky, Lawrence S / Clark, Jeffrey W / Faris, Jason E / Goyal, Lipika / Kwak, Eunice L / Murphy, Janet E / Ting, David T / Wo, Jennifer Y / Zhu, Andrew X / Warshaw, Andrew L / Lillemoe, Keith D / Fernández-del Castillo, Carlos. ·*Department of Surgery †Department of Radiation Oncology; and ‡Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. ·Ann Surg · Pubmed #25599322.

ABSTRACT: PURPOSE: On the basis of the ACCORD trial, FOLFIRINOX is effective in metastatic pancreatic adenocarcinoma (PDAC), making it a rational choice for locally advanced PDAC (LA). Aims of this study are to evaluate the accuracy of imaging in determining the resectability of PDAC and to determine the surgical and clinicopathologic outcomes of pancreatic resections after neoadjuvant FOLFIRINOX therapy. PATIENTS AND METHODS: Clinicopathologic data were retrospectively collected for surgical PDAC patients receiving neoadjuvant FOLFIRINOX or no neoadjuvant therapy between April 2011 and February 2014. Americas Hepato-Pancreato-Biliary Association/Society of Surgical Oncology/Society for Surgery of the Alimentary Tract consensus guidelines defined LA and borderline. Imaging was reviewed by a blinded senior pancreatic surgeon. RESULTS: Of 188 patients undergoing resection for PDAC, 40 LA/borderline received FOLFIRINOX and 87 received no neoadjuvant therapy. FOLFIRINOX resulted in a significant decrease in tumor size, yet 19 patients were still classified as LA and 9 as borderline. Despite post-FOLFIRINOX imaging suggesting continued unresectability, 92% had an R0 resection. When compared with no neoadjuvant therapy, FOLFIRINOX resulted in significantly longer operative times (393 vs 300 minutes) and blood loss (600 vs 400 mL), but significantly lower operative morbidity (36% vs 63%) and no postoperative pancreatic fistulas. Length of stay (6 vs 7 days), readmissions (20% vs 30%), and mortality were equivalent (1% vs 0%). On final pathology, the FOLFIRINOX group had a significant decrease in lymph node positivity (35% vs 79%) and perineural invasion (72% vs 95%). Median follow-up was 11 months with a significant increase in overall survival with FOLFIRINOX. CONCLUSIONS: After neoadjuvant FOLFIRINOX imaging no longer predicts unresectability. Traditional pathologic predictors of survival are improved, and morbidity is decreased in comparison to patients with clearly resectable cancers at the time of presentation.

21 Article Delaying chemoradiation until after completion of adjuvant chemotherapy for pancreatic cancer may not impact local control. 2014

Wo, Jennifer Y / Childs, Stephanie K / Szymonifka, Jackie / Mamon, Harvey J / Ryan, David P / Blaszkowsky, Lawrence S / Kwak, Eunice L / Ferrone, Cristina R / Allen, Jill N / Zhu, Andrew X / Wolpin, Brian M / Chan, Jennifer A / Abrams, Thomas A / McCleary, Nadine J / Fernandez-Del Castillo, Carlos / Hong, Theodore S. ·Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: jwo@partners.org. · Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. · Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. · Department of General Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. · Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. ·Pract Radiat Oncol · Pubmed #24890357.

ABSTRACT: BACKGROUND: Timing of administration of adjuvant chemoradiation (CRT) for pancreatic cancer has varied across studies. To date, the impact of timing of adjuvant CRT on long-term outcomes has not been evaluated. This study evaluates the effect of timing of adjuvant CRT on locoregional control (LRC) and overall survival (OS). METHODS AND MATERIALS: We performed a review of 159 patients with resected pancreatic adenocarcinoma who received adjuvant CRT between 1998 and 2010. Median dose of CRT was 50.4 Gy. The primary study variable was timing of CRT, dichotomized as immediate CRT versus delayed CRT. Consistent with Radiation Therapy Oncology Group (RTOG) 9704, immediate chemoradiation was defined as after ≤1 cycle of chemotherapy, whereas delayed CRT was defined as after >1 cycle. Cox multivariate analysis (MVA) was performed. RESULTS: Median follow-up was 55 months. Seventy-four percent of patients received immediate CRT, and 26% patients received delayed CRT. Patients treated with delayed CRT were more likely to receive adjuvant gemcitabine (100% vs 53%; P < .001). Timing of adjuvant CRT was not associated with LRC or OS on univariate or MVA. Preoperative carcinoembryonic antigen ≥1.3 ng/mL (hazard ratio, 3.18; P = .017) and positive margins (hazard ratio, 5.35; P < .001) were associated with lower rates LRC on MVA. Higher lymph node positivity ratio and not receiving adjuvant gemcitabine were independently associated with worse OS. CONCLUSIONS: Timing of adjuvant CRT for resectable pancreatic cancer may not significantly affect LRC or OS. These findings support the ongoing RTOG 0848 trial design, and provide reassurance that delaying CRT until completion of chemotherapy should not significantly impact LRC.

22 Article Updated long-term outcomes and prognostic factors for patients with unresectable locally advanced pancreatic cancer treated with intraoperative radiotherapy at the Massachusetts General Hospital, 1978 to 2010. 2013

Cai, Sophie / Hong, Theodore S / Goldberg, Saveli I / Fernandez-del Castillo, Carlos / Thayer, Sarah P / Ferrone, Cristina R / Ryan, David P / Blaszkowsky, Lawrence S / Kwak, Eunice L / Willett, Christopher G / Lillemoe, Keith D / Warshaw, Andrew L / Wo, Jennifer Y. ·Harvard Medical School, Boston, Massachusetts. ·Cancer · Pubmed #24006012.

ABSTRACT: BACKGROUND: In the current study, the authors evaluated long-term outcomes, intraoperative radiotherapy (IORT)-related toxicity, and prognostic factors for overall survival (OS) among patients with unresectable locally advanced pancreatic cancer (LAPC) who received IORT as part of their treatment at the Massachusetts General Hospital (MGH). METHODS: Medical records were reviewed for 194 consecutive patients with unresectable LAPC who were treated with IORT at MGH between 1978 and 2010. OS was calculated using the Kaplan-Meier method. Prognostic factors were evaluated at the univariate level by the log-rank test and at the multivariate level by the Cox proportional hazards model. Rates of disease progression and treatment toxicity were calculated. RESULTS: The 1-year, 2-year, and 3-year survival rates were 49%, 16%, and 6%, respectively. Six patients (3%) survived for > 5 years. The median OS was 12.0 months. Among 183 patients with known post-IORT disease status, the 2-year local progression-free survival and distant metastasis-free survival rates were 41% and 28%, respectively. On multivariate analysis, an IORT applicator diameter ≤ 8 cm (hazards ratio [HR], 0.51; 95% confidence interval [95% CI], 0.30-0.84 [P = .009]), a Charlson age-comorbidity index ≤ 3 (HR, 0.47; 95% CI, 0.31-0.73 [P = .001]), and receipt of chemotherapy (HR, 0.46; 95% CI, 0.33-0.66 [P < .001]) predicted improved OS. The median OS for patients with all 3 positive prognostic factors was 21.2 months. CONCLUSIONS: Well-selected patients with LAPC with small tumors and low Charlson age-comorbidity indices can achieve good long-term survival outcomes with a treatment regimen that incorporates chemotherapy and IORT.

23 Article FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience. 2013

Faris, Jason E / Blaszkowsky, Lawrence S / McDermott, Shaunagh / Guimaraes, Alexander R / Szymonifka, Jackie / Huynh, Mai Anh / Ferrone, Cristina R / Wargo, Jennifer A / Allen, Jill N / Dias, Lauren E / Kwak, Eunice L / Lillemoe, Keith D / Thayer, Sarah P / Murphy, Janet E / Zhu, Andrew X / Sahani, Dushyant V / Wo, Jennifer Y / Clark, Jeffrey W / Fernandez-del Castillo, Carlos / Ryan, David P / Hong, Theodore S. ·Department of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. jfaris@partners.org ·Oncologist · Pubmed #23657686.

ABSTRACT: The objective of our retrospective institutional experience is to report the overall response rate, R0 resection rate, progression-free survival, and safety/toxicity of neoadjuvant FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and chemoradiation in patients with locally advanced pancreatic cancer (LAPC). Patients with LAPC treated with FOLFIRINOX were identified via the Massachusetts General Hospital Cancer Center pharmacy database. Demographic information, clinical characteristics, and safety/tolerability data were compiled. Formal radiographic review was performed to determine overall response rates (ORRs). Twenty-two patients with LAPC began treatment with FOLFIRINOX between July 2010 and February 2012. The ORR was 27.3%, and the median progression-free survival was 11.7 months. Five of 22 patients were able to undergo R0 resections following neoadjuvant FOLFIRINOX and chemoradiation. Three of the five patients have experienced distant recurrence within 5 months. Thirty-two percent of patients required at least one emergency department visit or hospitalization while being treated with FOLFIRINOX. FOLFIRINOX possesses substantial activity in patients with LAPC. The use of FOLFIRINOX was associated with conversion to resectability in >20% of patients. However, the recurrences following R0 resection in three of five patients and the toxicities observed with the use of this regimen raise important questions about how to best treat patients with LAPC.

24 Article Pancreatic ductal adenocarcinoma: is there a survival difference for R1 resections versus locally advanced unresectable tumors? What is a "true" R0 resection? 2013

Konstantinidis, Ioannis T / Warshaw, Andrew L / Allen, Jill N / Blaszkowsky, Lawrence S / Castillo, Carlos Fernandez-Del / Deshpande, Vikram / Hong, Theodore S / Kwak, Eunice L / Lauwers, Gregory Y / Ryan, David P / Wargo, Jennifer A / Lillemoe, Keith D / Ferrone, Cristina R. ·Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA. ·Ann Surg · Pubmed #22968073.

ABSTRACT: OBJECTIVE: Patients who undergo an R0 resection of their pancreatic ductal adenocarcinoma (PDAC) have an improved survival compared with patients who undergo an R1 resection. It is unclear whether an R1 resection confers a survival benefit over locally advanced (LA) unresectable tumors. Our aim was to compare the survival of patients undergoing an R1 resection with those having LA tumors and to explore the prognostic significance of a 1-mm surgical margin. METHODS: Clinicopathologic data from a pancreatic cancer database between January 1993 and July 2008 were reviewed. Locally advanced tumors had no evidence of metastatic disease at exploration. RESULTS: A total of 1705 patients were evaluated for PDAC in the Department of Surgery. Of the 1084 (64%) patients who were surgically explored, 530 (49%) were considered unresectable (286 locally unresectable, 244 with distant metastasis). One hundred fifty-seven (28%) of the resected PDACs had an R1 resection. Patients undergoing an R1 resection had a slightly longer survival compared with those who had locally advanced unresectable cancers (14 vs 11 months; P < 0.001). Patients with R0 resections had a favorable survival compared with those with R1 resections (23 vs 14 months; P < 0.001), but survival after resections with 1-mm margin or less (R0-close) were similar to R1 resections: both groups had a significantly shorter median survival than patients with a margin of greater than 1 mm (R0-wide) (16 vs 14 vs 35 months, respectively; P < 0.001). CONCLUSIONS: Patients undergoing an R1 resection still have an improved survival compared with patients with locally advanced unresectable pancreatic adenocarcinoma. R0 resections have an improved survival compared with R1 resections, but this survival benefit is lost when the tumor is within 1 mm of the resection margin.

25 Article Pancreatic neuroendocrine tumors with involved surgical margins: prognostic factors and the role of adjuvant radiotherapy. 2012

Arvold, Nils D / Willett, Christopher G / Fernandez-del Castillo, Carlos / Ryan, David P / Ferrone, Cristina R / Clark, Jeffrey W / Blaszkowsky, Lawrence S / Deshpande, Vikram / Niemierko, Andrzej / Allen, Jill N / Kwak, Eunice L / Wadlow, Raymond C / Zhu, Andrew X / Warshaw, Andrew L / Hong, Theodore S. ·Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA, USA. ·Int J Radiat Oncol Biol Phys · Pubmed #22414286.

ABSTRACT: PURPOSE: Pancreatic neuroendocrine tumors (pNET) are rare neoplasms associated with poor outcomes without resection, and involved surgical margins are associated with a worse prognosis. The role of adjuvant radiotherapy (RT) in these patients has not been characterized. METHODS AND MATERIALS: We retrospectively evaluated 46 consecutive patients with positive or close (<1 mm) margins after pNET resection, treated from 1983 to 2010, 16 of whom received adjuvant RT. Median RT dose was 50.4 Gy in 1.8-Gy fractions; half the patients received concurrent chemotherapy with 5-fluorouracil or capecitabine. No patients received adjuvant chemotherapy. Cox multivariate analysis (MVA) was used to analyze factors associated with overall survival (OS). RESULTS: Median age at diagnosis was 56 years, and 52% of patients were female. Median tumor size was 38 mm, 57% of patients were node-positive, and 11% had a resected solitary liver metastasis. Patients who received RT were more likely to have larger tumors (median, 54 mm vs. 30 mm, respectively, p = 0.002) and node positivity (81% vs. 33%, respectively, p = 0.002) than those not receiving RT. Median follow-up was 39 months. Actuarial 5-year OS was 62% (95% confidence interval [CI], 41%-77%). In the group that did not receive RT, 3 patients (10%) experienced local recurrence (LR) and 5 patients (18%) developed new distant metastases, while in the RT group, 1 patient (6%) experienced LR and 5 patients (38%) developed distant metastases. Of all recurrences, 29% were LR. On MVA, male gender (adjusted hazard ratio [AHR] = 3.81; 95% CI, 1.21-11.92; p = 0.02) and increasing tumor size (AHR = 1.02; 95% CI, 1.01-1.04; p = 0.007) were associated with decreased OS. CONCLUSIONS: Long-term survival is common among patients with involved-margin pNET. Despite significantly worse pathologic features among patients receiving adjuvant RT, rates of LR between groups were similar, suggesting that RT might aid local control, and merits further evaluation.

Next