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Pancreatic Neoplasms: HELP
Articles by Eric A. Mellon
Based on 14 articles published since 2010
(Why 14 articles?)
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Between 2010 and 2020, Eric Mellon wrote the following 14 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 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.

2 Article Using adaptive magnetic resonance image-guided radiation therapy for treatment of inoperable pancreatic cancer. 2019

Rudra, Soumon / Jiang, Naomi / Rosenberg, Stephen A / Olsen, Jeffrey R / Roach, Michael C / Wan, Leping / Portelance, Lorraine / Mellon, Eric A / Bruynzeel, Anna / Lagerwaard, Frank / Bassetti, Michael F / Parikh, Parag J / Lee, Percy P. ·Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri. · Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California. · Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Carbone Cancer Center, Madison, Wisconsin. · Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida. · Department of Radiation Oncology, VU University Medical Center, Amsterdam, Netherlands. ·Cancer Med · Pubmed #30932367.

ABSTRACT: BACKGROUND: Adaptive magnetic resonance imaging-guided radiation therapy (MRgRT) can escalate dose to tumors while minimizing dose to normal tissue. We evaluated outcomes of inoperable pancreatic cancer patients treated using MRgRT with and without dose escalation. METHODS: We reviewed 44 patients with inoperable pancreatic cancer treated with MRgRT. Treatments included conventional fractionation, hypofractionation, and stereotactic body radiation therapy. Patients were stratified into high-dose (biologically effective dose [BED RESULTS: Median follow-up was 17 months. High-dose patients (n = 24, 55%) had statistically significant improvement in 2-year OS (49% vs 30%, P = 0.03) and trended towards significance for 2-year FFLF (77% vs 57%, P = 0.15) compared to standard-dose patients (n = 20, 45%). FFDF at 18 months in high-dose vs standard-dose groups was 24% vs 48%, respectively (P = 0.92). High-dose radiation (HR: 0.44; 95% confidence interval [CI]: 0.21-0.94; P = 0.03) and duration of induction chemotherapy (HR: 0.84; 95% CI: 0.72-0.98; P = 0.03) were significantly correlated with OS on univariate analysis but neither factor was independently predictive on multivariate analysis. Grade 3+ GI toxicity occurred in three patients in the standard-dose group and did not occur in the high-dose group. CONCLUSIONS: Patients treated with dose-escalated MRgRT demonstrated improved OS. Prospective evaluation of high-dose RT regimens with standardized treatment parameters in inoperable pancreatic cancer patients is warranted.

3 Article Dosimetric Benefits and Practical Pitfalls of Daily Online Adaptive MRI-Guided Stereotactic Radiation Therapy for Pancreatic Cancer. 2019

El-Bared, Nancy / Portelance, Lorraine / Spieler, Benjamin O / Kwon, Deukwoo / Padgett, Kyle R / Brown, Karen M / Mellon, Eric A. ·Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, Miller School of Medicine, Miami, Florida. · Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, Miller School of Medicine, Miami, Florida. Electronic address: eric.mellon@med.miami.edu. ·Pract Radiat Oncol · Pubmed #30149192.

ABSTRACT: PURPOSE: Magnetic resonance imaging guided (MRI-g) radiation therapy provides visualization of the target and organs at risk (OARs), allowing for daily online adaptive radiation therapy (OART). We hypothesized that MRI-g OART would improve OAR sparing and target coverage in patients with pancreatic cancer treated with stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Ten patients received pancreas SBRT to a dose of 33 to 40 Gy in 5 fractions. The dose was prescribed to 90% coverage of the planning target volume at 100% isodose (PTV100). After each fraction's setup magnetic resonance imaging scan, the target position was aligned by 3-dimensional shifts, the normal anatomy was recontoured, and the original radiation therapy plan was recalculated to create a nonadaptive plan. A reoptimized (adaptive) plan was then generated for each fraction and renormalized to 90% coverage of PTV100. Target and OAR doses between nonadaptive and adaptive plans were compared to assess the dosimetric impact of daily adaptation. RESULTS: The PTV100 mean for adaptive and nonadaptive techniques was 90% and 80.4% (range, 46%-97%), respectively (P = .0008). Point maximum (Dmax) 38 Gy duodenum objectives were met in 43 adaptive fractions compared with 32 nonadaptive fractions (P = .022). Both PTV100 ≥90% and all OAR objectives were achieved in 28 adaptive fractions compared with only 3 nonadaptive fractions. For nonadaptive plans, interfraction increases in stomach volume correlated with higher stomach V33 (P = .004), stomach Dmax (P = .009), duodenum V33 (P = .021), and duodenum Dmax (P = .105). No correlation was observed between stomach volume and OAR doses for adaptive plans. OART plans with Dmax violations of the spinal cord (20 Gy) in 4 fractions and large bowel (38 Gy) in 5 fractions were identified (although not delivered). CONCLUSIONS: MRI-g OART improves target coverage and OAR sparing for pancreas SBRT. This benefit partially results from mitigation of interfraction variability in stomach volume. Caution must be exercised to evaluate all OARs near the treatment area.

4 Article Dosimetric analysis of stereotactic body radiation therapy for pancreatic cancer using MR-guided Tri- 2018

Ramey, Stephen James / Padgett, Kyle R / Lamichhane, Narottam / Neboori, Hanmath J / Kwon, Deukwoo / Mellon, Eric A / Brown, Karen / Duffy, Melissa / Victoria, James / Dogan, Nesrin / Portelance, Lorraine. ·Department of Radiation Oncology, University of Miami, Miami, Florida. · Department of Radiation Oncology, University of Miami, Miami, Florida; Department of Radiology, University of Miami, Miami, Florida. · Department of Radiation Oncology, University of Maryland, Baltimore, Maryland. · Department of Epidemiology, University of Miami, Miami, Florida. · ViewRay Incorporated, Cleveland, Ohio. · Department of Radiation Oncology, University of Miami, Miami, Florida. Electronic address: lportelance@med.miami.edu. ·Pract Radiat Oncol · Pubmed #29703704.

ABSTRACT: -- No abstract --

5 Article Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy. 2018

Jin, William H / Mellon, Eric A / Frakes, Jessica M / Murimwa, Gilbert Z / Hodul, Pamela J / Pimiento, Jose M / Malafa, Mokenge P / Hoffe, Sarah E. ·University of South Florida Morsani College of Medicine, Tampa, FL, USA. · Moffitt Cancer Center, Tampa, FL, USA. ·J Gastrointest Oncol · Pubmed #29564168.

ABSTRACT: Background: Total psoas area (TPA), a marker of sarcopenia, has been used as an independent predictor of clinical outcomes in gastrointestinal (GI) cancers as a proxy for frailty and nutritional status. Our study aimed to evaluate whether TPA, in contrast to traditional measurements of nutrition like body mass index (BMI) and body surface area (BSA), was predictive of outcomes in borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) patients receiving stereotactic body radiation therapy (SBRT). Methods: Retrospective analysis of an institutional review board approved database of 222 BRPC and LAPC treated with SBRT from 2009-2016 yielded 183 patients that met our selection criteria of pre-SBRT computed tomography (CT) imaging with an identifiable L4 vertebra. Once the L4 vertebral level was identified, the bilateral psoas muscles were manually contoured. This area was normalized by patient height, with units described in mm Results: Low TPA (OR =1.903, P=0.036) was predictive of acute toxicities, and only TPA was predictive of Grade 3 or higher acute toxicities (OR =10.24, P=0.007). Both findings were independent of tumor resectability. Pain (P=0.003), fatigue (P=0.040), and nausea (P=0.039) were significantly associated with low TPA. No association was identified between any measurement of nutritional status and the development of late toxicities, overall survival, local progression or local recurrence. However, BRPC patients survived longer (median =21.98 months) than their LAPC (median =16.2 months) counterparts (P=0.002), independent of nutritional status. Conclusions: TPA measurement is readily available and more specific than BMI or BSA as a predictor of acute radiotoxic complications following SBRT in BRPC/LAPC patients. A TPA of <500 mm

6 Article Automated inverse optimization facilitates lower doses to normal tissue in pancreatic stereotactic body radiotherapy. 2018

Mihaylov, Ivaylo B / Mellon, Eric A / Yechieli, Raphael / Portelance, Lorraine. ·Department of Radiation Oncology, University of Miami,Miami, FL, United States of America. ·PLoS One · Pubmed #29351303.

ABSTRACT: PURPOSE: Inverse planning is trial-and-error iterative process. This work introduces a fully automated inverse optimization approach, where the treatment plan is closely tailored to the unique patient anatomy. The auto-optimization is applied to pancreatic stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: The automation is based on stepwise reduction of dose-volume histograms (DVHs). Five uniformly spaced points, from 1% to 70% of the organ at risk (OAR) volumes, are used. Doses to those DVH points are iteratively decreased through multiple optimization runs. With each optimization run the doses to the OARs are decreased, while the dose homogeneity over the target is increased. The iterative process is terminated when a pre-specified dose heterogeneity over the target is reached. Twelve pancreatic cases were retrospectively studied. Doses to the target, maximum doses to duodenum, bowel, stomach, and spinal cord were evaluated. In addition, mean doses to liver and kidneys were tallied. The auto-optimized plans were compared to the actual treatment plans, which are based on national protocols. RESULTS: The prescription dose to 95% of the planning target volume (PTV) is the same for the treatment and the auto-optimized plans. The average difference for maximum doses to duodenum, bowel, stomach, and spinal cord are -4.6 Gy, -1.8 Gy, -1.6 Gy, and -2.4 Gy respectively. The negative sign indicates lower doses with the auto-optimization. The average differences in the mean doses to liver and kidneys are -0.6 Gy, and -1.1 Gy to -1.5 Gy respectively. CONCLUSIONS: Automated inverse optimization holds great potential for personalization and tailoring of radiotherapy to particular patient anatomies. It can be utilized for normal tissue sparing or for an isotoxic dose escalation.

7 Article Outcomes of adjuvant radiotherapy and lymph node resection in elderly patients with pancreatic cancer treated with surgery and chemotherapy. 2017

Frakes, Jessica / Mellon, Eric A / Springett, Gregory M / Hodul, Pamela / Malafa, Mokenge P / Fulp, William J / Zhao, Xiuhua / Hoffe, Sarah E / Shridhar, Ravi / Meredith, Kenneth L. ·Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA. · Gastrointestinal Tumor Program, Moffitt Cancer Center, Tampa, FL, USA. · Biostatistics Core, Moffitt Cancer Center, Tampa, FL, USA. · University of Central Florida, Orlando, FL, USA. · Surgical Oncology, Sarasota Memorial Health Care System, Florida State University College of Medicine, Sarasota, FL, USA. ·J Gastrointest Oncol · Pubmed #29184679.

ABSTRACT: Background: We sought to determine the effects of post-operative radiation therapy (PORT) and lymph node resection (LNR) on survival in patients ≥70 years with pancreatic cancer treated with surgery and chemotherapy. Methods: An analysis of patients ≥70 years with surgically resected pancreatic cancer who received chemotherapy from the SEER database between 2004-2008 was performed to determine association of PORT and LNR on survival. Results: We identified 961 patients who met inclusion criteria. There was a trend towards increased survival associated with PORT in all patients (P=0.052) and N1 patients (P=0.060) but no benefit in N0 patients (P=0.161). There was no difference in OS based on number of lymph nodes removed in all (P=0.741), N0 (P=0.588), and N1 (P=0.070) patients. MVA for all patients revealed that higher T stage, N1, and high grade tumors were prognostic for increased mortality, while there was decreased mortality with PORT and mild benefit with increased lymph nodes resected (P=0.084). Conclusions: PORT demonstrated no benefit in survival of pancreatic cancer patients ≥70 who are resected and treated with adjuvant chemotherapy. Future investigation will need to address age as a stratification factor for pancreatic cancer in the adjuvant setting.

8 Article A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. 2017

Scott, Jacob G / Berglund, Anders / Schell, Michael J / Mihaylov, Ivaylo / Fulp, William J / Yue, Binglin / Welsh, Eric / Caudell, Jimmy J / Ahmed, Kamran / Strom, Tobin S / Mellon, Eric / Venkat, Puja / Johnstone, Peter / Foekens, John / Lee, Jae / Moros, Eduardo / Dalton, William S / Eschrich, Steven A / McLeod, Howard / Harrison, Louis B / Torres-Roca, Javier F. ·Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Department of Integrated Bioinformatics and Biostatistics, Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Department of Radiation Oncology, University of Miami, Miami, FL, USA. · Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Department of Medical Oncology and Cancer Genomics, Erasmus Medical Center, Rotterdam, Netherlands. · DeBartolo Family Personalized Medicine Institute, Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Chemical Biology and Molecular Medicine, Moffitt Cancer Center and Research Institute, Tampa, FL, USA. Electronic address: javier.torresroca@moffitt.org. ·Lancet Oncol · Pubmed #27993569.

ABSTRACT: BACKGROUND: Despite its common use in cancer treatment, radiotherapy has not yet entered the era of precision medicine, and there have been no approaches to adjust dose based on biological differences between or within tumours. We aimed to assess whether a patient-specific molecular signature of radiation sensitivity could be used to identify the optimum radiotherapy dose. METHODS: We used the gene-expression-based radiation-sensitivity index and the linear quadratic model to derive the genomic-adjusted radiation dose (GARD). A high GARD value predicts for high therapeutic effect for radiotherapy; which we postulate would relate to clinical outcome. Using data from the prospective, observational Total Cancer Care (TCC) protocol, we calculated GARD for primary tumours from 20 disease sites treated using standard radiotherapy doses for each disease type. We also used multivariable Cox modelling to assess whether GARD was independently associated with clinical outcome in five clinical cohorts: Erasmus Breast Cancer Cohort (n=263); Karolinska Breast Cancer Cohort (n=77); Moffitt Lung Cancer Cohort (n=60); Moffitt Pancreas Cancer Cohort (n=40); and The Cancer Genome Atlas Glioblastoma Patient Cohort (n=98). FINDINGS: We calculated GARD for 8271 tissue samples from the TCC cohort. There was a wide range of GARD values (range 1·66-172·4) across the TCC cohort despite assignment of uniform radiotherapy doses within disease types. Median GARD values were lowest for gliomas and sarcomas and highest for cervical cancer and oropharyngeal head and neck cancer. There was a wide range of GARD values within tumour type groups. GARD independently predicted clinical outcome in breast cancer, lung cancer, glioblastoma, and pancreatic cancer. In the Erasmus Breast Cancer Cohort, 5-year distant-metastasis-free survival was longer in patients with high GARD values than in those with low GARD values (hazard ratio 2·11, 95% 1·13-3·94, p=0·018). INTERPRETATION: A GARD-based clinical model could allow the individualisation of radiotherapy dose to tumour radiosensitivity and could provide a framework to design genomically-guided clinical trials in radiation oncology. FUNDING: None.

9 Article Predictors and survival for pathologic tumor response grade in borderline resectable and locally advanced pancreatic cancer treated with induction chemotherapy and neoadjuvant stereotactic body radiotherapy. 2017

Mellon, Eric A / Jin, William H / Frakes, Jessica M / Centeno, Barbara A / Strom, Tobin J / Springett, Gregory M / Malafa, Mokenge P / Shridhar, Ravi / Hodul, Pamela J / Hoffe, Sarah E. ·a Department of Radiation Oncology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA. · b Department of Radiation Oncology , University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center , Miami , Florida , USA. · c Department of Pathology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA. · d Gastrointestinal Tumor Program , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA. · e Department of Radiation Oncology , Florida Hospital Cancer Institute , Orlando , Florida , USA. ·Acta Oncol · Pubmed #27885876.

ABSTRACT: BACKGROUND: Neoadjuvant therapy response correlates with survival in multiple gastrointestinal malignancies. To potentially augment neoadjuvant response for pancreas adenocarcinoma, we intensified treatment with stereotactic body radiotherapy (SBRT) following multi-agent chemotherapy. Using this regimen, we analyzed whether the College of American Pathology (CAP) tumor regression grade (TRG) at pancreatectomy correlated with established response biomarkers and survival. MATERIALS AND METHODS: We identified borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer patients treated according to our institutional clinical pathway who underwent surgical resection with reported TRG (n = 81, median follow-up after surgery 24.2 months). Patients had baseline CA19-9, computed tomography (CT), endoscopic ultrasound, and FDG positron emission tomography (PET)/CT then underwent multi-agent chemotherapy (79% with three cycles of gemcitabine, docetaxel and capecitabine) followed by 5-fraction SBRT. They then underwent restaging CT, PET/CT and CA19-9. Overall (OS) and progression-free (PFS) survival were estimated and compared by Kaplan-Meier and log-rank methods. Univariate ordinal logistic regression correlated TRG with baseline, restaging and change in CA19-9 and the PET maximum standardized uptake value (SUVmax). RESULTS: Restaging level and decrease in CA19-9 correlated with improved TRG (p = .02 for both) as did restaging SUVmax (p < .01), yet there was no TRG correlation with decrease in SUVmax (p = .10) or CT response (p = .30). The TRG groups had similar OS and PFS except the TRG 0 (complete response) group. Compared to partial response levels (TRG 1-3, median OS 33.9 months, median PFS 13.0 months), the six (7%) patients with TRG 0 had no deaths (p = .05) and only one progression (p = .03). A group of 10 (12%) TRG 1 patients with only residual isolated tumor cells had similar outcomes to the other TRG 1-3 patients. CONCLUSION: Pre-operative PET-CT and CA19-9 response correlate with histopathologic tumor regression. Patients with complete pathologic response have superior outcomes, suggesting a rationale for intensification and personalization of neoadjuvant therapy in BRPC and LAPC.

10 Article Favorable perioperative outcomes after resection of borderline resectable pancreatic cancer treated with neoadjuvant stereotactic radiation and chemotherapy compared with upfront pancreatectomy for resectable cancer. 2016

Mellon, Eric A / Strom, Tobin J / Hoffe, Sarah E / Frakes, Jessica M / Springett, Gregory M / Hodul, Pamela J / Malafa, Mokenge P / Chuong, Michael D / Shridhar, Ravi. ·Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA ; · Gastrointestinal Tumor Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA ; · Department of Radiation Oncology, University of Maryland, Baltimore, MD, USA ; · Florida Hospital Cancer Institute, Orlando, FL, USA. ·J Gastrointest Oncol · Pubmed #27563444.

ABSTRACT: BACKGROUND: Neoadjuvant multi-agent chemotherapy and stereotactic body radiation therapy (SBRT) are utilized to increase margin negative (R0) resection rates in borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) patients. Concerns persist that these neoadjuvant therapies may worsen perioperative morbidities and mortality. METHODS: Upfront resection patients (n=241) underwent resection without neoadjuvant treatment for resectable disease. They were compared to BRPC or LAPC patients (n=61) who underwent resection after chemotherapy and 5 fraction SBRT. Group comparisons were performed by Mann-Whitney U or Fisher's exact test. Overall Survival (OS) was estimated by Kaplan-Meier and compared by log-rank methods. RESULTS: In the neoadjuvant therapy group, there was significantly higher T classification, N classification, and vascular resection/repair rate. Surgical positive margin rate was lower after neoadjuvant therapy (3.3% vs. 16.2%, P=0.006). Post-operative morbidities (39.3% vs. 31.1%, P=0.226) and 90-day mortality (2% vs. 4%, P=0.693) were similar between the groups. Median OS was 33.5 months in the neoadjuvant therapy group compared to 23.1 months in upfront resection patients who received adjuvant treatment (P=0.057). CONCLUSIONS: Patients with BRPC or LAPC and sufficient response to neoadjuvant multi-agent chemotherapy and SBRT have similar or improved peri-operative and long-term survival outcomes compared to upfront resection patients.

11 Article Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer. 2016

Chuong, Michael D / Frakes, Jessica M / Figura, Nicholas / Hoffe, Sarah E / Shridhar, Ravi / Mellon, Eric A / Hodul, Pamela J / Malafa, Mokenge P / Springett, Gregory M / Centeno, Barbara A. ·1 University of Maryland Medical Center, Baltimore, MD 21201, USA ; 2 H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA ; 3 University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA ; 4 Florida Hospital Cancer Institute, Florida Hospital Orlando, Orlando, FL 32804, USA. ·J Gastrointest Oncol · Pubmed #27034789.

ABSTRACT: BACKGROUND: While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described. METHODS: This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score. RESULTS: We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS. CONCLUSIONS: These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients.

12 Article Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma. 2015

Mellon, Eric A / Hoffe, Sarah E / Springett, Gregory M / Frakes, Jessica M / Strom, Tobin J / Hodul, Pamela J / Malafa, Mokenge P / Chuong, Michael D / Shridhar, Ravi. ·Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute , Tampa, Florida , USA. ·Acta Oncol · Pubmed #25734581.

ABSTRACT: PURPOSE: Limited data are available to guide neoadjuvant treatment of borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer. MATERIAL AND METHODS: We updated our institutional outcomes with a neoadjuvant chemotherapy and stereotactic body radiotherapy (SBRT) approach. An IRB-approved analysis was performed of all BRPC and LAPC patients treated with our departmental treatment protocol. After staging, medically fit patients underwent chemotherapy for 2-3 months, with regimen at the discretion of the treating medical oncologist. Patients then received SBRT delivered in five consecutive daily fractions with median total radiation doses of 30 Gy to tumor and 40 Gy dose painted to tumor-vessel interfaces. This was followed by restaging imaging for possible resection. Overall survival (OS), event free survival (EFS), and locoregional control (LRC) rates were estimated and compared by Kaplan-Meier and log-rank methods. RESULTS: We identified 159 patients, 110 BRPC and 49 LAPC, with 14.0 months median overall follow-up. The resection and margin negative (R0) rate for BRPC patients who completed neoadjuvant therapy was 51% and 96%, respectively. Estimated median OS was 19.2 months for BRPC patients and 15.0 months for LAPC patients (p = 0.402). Median OS was 34.2 months for surgically resected patients versus 14.0 months for unresected patients (p < 0.001). Five of 21 (24%) LAPC patients receiving FOLFIRINOX chemotherapy underwent R0 resection. In LAPC, FOLFIRINOX recipients underwent R0 resection more often than other chemotherapy recipients (5 of 21 vs. 0 of 28, p = 0.011). There was a trend for improved survival in those resected LAPC patients (p = 0.09). For those not undergoing resection, one year LRC was 78%. Any grade ≥ 3 potentially radiation-related toxicity rate was 7%. CONCLUSIONS: These data underscore the feasibility, safety, and effectiveness of neoadjuvant SBRT and chemotherapy for BRPC and LAPC.

13 Article Adjuvant radiotherapy and lymph node dissection in pancreatic cancer treated with surgery and chemotherapy. 2014

Mellon, Eric A / Springett, Gregory M / Hoffe, Sarah E / Hodul, Pamela / Malafa, Mokenge P / Meredith, Kenneth L / Fulp, William J / Zhao, Xiuhua / Shridhar, Ravi. ·Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida. ·Cancer · Pubmed #24390779.

ABSTRACT: BACKGROUND: The objective of this study was to determine the effects of postoperative radiation therapy (PORT) and lymph node dissection (LND) on survival in patients with pancreatic cancer. METHODS: The 2004 to 2008 Surveillance, Epidemiology, and End Results (SEER) database was analyzed to identify patients with pancreatic cancer who underwent surgery and received chemotherapy and to evaluate the correlation between overall survival (OS), PORT, and LND. RESULTS: In total, 2966 patients were identified who underwent pancreatic resection (1842 PORT, 1124 no PORT). Median survival, 1-year OS, and 3-year OS were 21 months, 77%, and 28%, respectively, with PORT versus 20 months, 70%, and 25%, respectively, without PORT (P = .02). Subset analysis revealed that the benefit of PORT was limited to lymph node-positive (N1) patients. Median survival, 1-year OS, and 3-year OS for patients with N1 disease were 19 months, 73%, and 25%, respectively, for those who received PORT versus 18 months, 67%, and 20%, respectively, for those who did not receive PORT (P < .01). An increasing lymph node count was associated with increased survival on multivariate analysis in all patients and in patients with N1 disease (both P < .001). Significant cutoff points for OS based on LND in patients with N1 disease were identified for those who had ≥8, ≥10, ≥12, ≥15, and ≥20 lymph nodes resected. Multivariate analysis for OS revealed that increasing age, T3 and T4 tumors, N1 stage, and moderately and poorly differentiated grade were prognostic for increased mortality, while female gender, PORT, and LND were prognostic for decreased mortality. In patients with N1 disease, other than patient age, all of these factors remained significant. In patients with N0 disease, only T1 and T2 tumor classification and having a tumor that was less than high grade were associated with survival benefit. CONCLUSIONS: This SEER analysis demonstrated an associated survival benefit of PORT and LND in patients with N1, surgically resected pancreatic cancer who received chemotherapy.

14 Article Stereotactic body radiation therapy for locally advanced and borderline resectable pancreatic cancer is effective and well tolerated. 2013

Chuong, Michael D / Springett, Gregory M / Freilich, Jessica M / Park, Catherine K / Weber, Jill M / Mellon, Eric A / Hodul, Pamela J / Malafa, Mokenge P / Meredith, Kenneth L / Hoffe, Sarah E / Shridhar, Ravi. ·Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA. ·Int J Radiat Oncol Biol Phys · Pubmed #23562768.

ABSTRACT: PURPOSE: Stereotactic body radiation therapy (SBRT) provides high rates of local control (LC) and margin-negative (R0) resections for locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC), respectively, with minimal toxicity. METHODS AND MATERIALS: A single-institution retrospective review was performed for patients with nonmetastatic pancreatic cancer treated with induction chemotherapy followed by SBRT. SBRT was delivered over 5 consecutive fractions using a dose painting technique including 7-10 Gy/fraction to the region of vessel abutment or encasement and 5-6 Gy/fraction to the remainder of the tumor. Restaging scans were performed at 4 weeks, and resectable patients were considered for resection. The primary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: Seventy-three patients were evaluated, with a median follow-up time of 10.5 months. Median doses of 35 Gy and 25 Gy were delivered to the region of vessel involvement and the remainder of the tumor, respectively. Thirty-two BRPC patients (56.1%) underwent surgery, with 31 undergoing an R0 resection (96.9%). The median OS, 1-year OS, median PFS, and 1-year PFS for BRPC versus LAPC patients was 16.4 months versus 15 months, 72.2% versus 68.1%, 9.7 versus 9.8 months, and 42.8% versus 41%, respectively (all P>.10). BRPC patients who underwent R0 resection had improved median OS (19.3 vs 12.3 months; P=.03), 1-year OS (84.2% vs 58.3%; P=.03), and 1-year PFS (56.5% vs 25.0%; P<.0001), respectively, compared with all nonsurgical patients. The 1-year LC in nonsurgical patients was 81%. We did not observe acute grade ≥3 toxicity, and late grade ≥3 toxicity was minimal (5.3%). CONCLUSIONS: SBRT safely facilitates margin-negative resection in patients with BRPC pancreatic cancer while maintaining a high rate of LC in unresectable patients. These data support the expanded implementation of SBRT for pancreatic cancer.