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Pancreatic Neoplasms: HELP
Articles by Ravi Shridhar
Based on 18 articles published since 2010
(Why 18 articles?)
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Between 2010 and 2020, Ravi Shridhar wrote the following 18 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 Review Neoadjuvant vs adjuvant therapy for resectable pancreatic cancer: the evolving role of radiation. 2014

Hoffe, Sarah / Rao, Nikhil / Shridhar, Ravi. ·Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL. Electronic address: Sarah.hoffe@moffitt.org. · Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL. ·Semin Radiat Oncol · Pubmed #24635868.

ABSTRACT: A major challenge with pancreatic cancer management is in the discrimination of clearly resectable tumors from those that would likely be accompanied by a positive resection margin if upfront surgery was attempted. The standard of care for clearly resectable pancreatic cancer remains surgery followed by adjuvant therapy, but there is considerable controversy over whether such therapeutic adjuvant strategies should include radiotherapy. Furthermore, in a malignancy with such high rates of distant metastasis, investigators are now exploring the feasibility and outcomes of delivering therapy in the neoadjuvant setting, both for clearly resectable as well as borderline resectable tumors. In this review, we explore the current standard of care of upfront surgery for clearly resectable cancers followed by adjuvant therapy, focusing on the role of radiotherapy. We highlight the difficulties in interpreting a literature fraught with inconsistencies in how resectable vs borderline resectable cancers are defined and treated. Finally, we explore the role of neoadjuvant strategies in the modern era.

3 Article Neoadjuvant therapy and pancreatic cancer: a national cancer database analysis. 2019

Shridhar, Ravi / Takahashi, Caitlin / Huston, Jamie / Meredith, Kenneth L. ·Department of Radiation Oncology, Florida Hospital Cancer Institute, Orlando, FL, USA. · US Naval Academy, Annapolis, MD, USA. · Department of Surgical Oncology, Sarasota Memorial Hospital, Sarasota, FL, USA. ·J Gastrointest Oncol · Pubmed #31392047.

ABSTRACT: Background: We sought to examine the impact of neoadjuvant chemotherapy (NCT), single agent or multiagent chemotherapy, and neoadjuvant chemoradiation (NCRT) on survival in pancreatic cancer. Methods: Utilizing the National Cancer Database, we identified patients who underwent pancreatic resection for adenocarcinoma (2006 to 2013). Overall survival (OS) analysis was performed using the Kaplan-Meier method. Multivariable cox proportional hazard models (MVA) and propensity score matching (PSM) were developed to identify predictors of survival. For upfront surgery (UFS), OS was limited to receipt of adjuvant treatment. Results: We identified 26,563 patients who underwent pancreatic resection: UFS =23,877, NCRT =1,482, and NCT =1,204. Multiagent chemotherapy was utilized in 77% of NCT and 42% of NCRT. There was improved R0 resections associated with neoadjuvant therapy compared to UFS, however, there was no difference between NCT and NCRT. In addition, the was improved R0 with MA-NCT (P<0.001) but not for single agent NCT (P=0.26). After PSM, the median OS for UFS, SA-NCT, MA-NCT, SA-NCRT, and MA-NCRT was 21.9, 21.5, 29.8, 25.3, and 25.8 months in all patients (P=0.001), and 23.6, 23.9, 31.6, 25.9, and 26.6 months in R0 patients (P=0.03), respectively. There was no difference in OS in patients with R1/2 resection. MVA after PSM demonstrated that only MA-NCT was associated with decreased mortality while increasing age, higher Charlson-Deyo index, N1, higher grade, tumor size, and positive margins were associated with higher mortality. Conclusions: There was improved OS associated with MA-NCT in pancreatic cancer patients compared to UFS with adjuvant therapy.

4 Article Correlation of tumor size and survival in pancreatic cancer. 2018

Takahashi, Caitlin / Shridhar, Ravi / Huston, Jamie / Meredith, Kenneth. ·Department of Surgery, Naval Medical Center Portsmouth, Portsmouth, VA, USA. · Department of Radiation Oncology, Florida Hospital Cancer Institute, Orlando, FL, USA. · Department of Gastrointestinal Oncology, Sarasota Memorial Healthcare System, Sarasota, FL, USA. · Department of Gastrointestinal Oncology, Florida State University College of Medicine, Tallahassee, FL, USA. ·J Gastrointest Oncol · Pubmed #30505594.

ABSTRACT: Background: Neoadjuvant therapy (NT) for resectable pancreatic adenocarcinoma (PAC) continues to be debated. We sought to establish the relationship between pancreatic tumor size, neoadjuvant chemotherapy (NCT), neoadjuvant chemoradiation (NCRT), and definitive surgery (DS) on survival. Methods: Utilizing the National Cancer Database we identified patients with PAC who underwent NT and DS. Patient characteristics and survival were compared with Mann-Whitney U, Pearson's Chi-square, and the Kaplan-Meier method. Multivariable analysis (MVA) was developed to identify predictors of survival. All tests were two-sided and α <0.05 was significant. Results: We identified 11,707 patients: 9,722 patients with tumors >2 cm and 1,985 with tumors ≤2 cm. There were 523 patients treated with NCT, 559 treated with NCRT, and 10,625 DS. Patients with tumors >2 cm were more likely to have higher T-stage, P<0.001, positive lymph nodes, P<0.001, poor histologic grade, P<0.001, and R1 resections, P<0.001. The median survival for patients with tumors ≤2 cm was 30.6 months compared to 20.5 months for those whose tumors were >2 cm, P<0.001. In the >2 cm groups the median survival for NCT, NCRT, and DS was 22.9, 25.8 and 21.3 months, P=0.01. MVA revealed that age, Charlson/Deyo score, N-stage, grade, tumor size >2 cm, R0 resection, and NT were predictors of survival. Ninety-day mortality was worse in both the NCT and NCRT compared to DS, P<0.001. Conclusions: The size of pancreatic cancer correlates to pathologic stage and overall survival. Tumors >2 and <2 cm benefited from a NT. However, the 90-operative mortality was significantly worse in those patients receiving NT.

5 Article Adjuvant radiation provides survival benefit for resected pancreatic adenocarcinomas of the tail. 2018

Jin, William H / Hoffe, Sarah E / Shridhar, Ravi / Strom, Tobin / Venkat, Puja / Springett, Gregory M / Hodul, Pamela J / Pimiento, Jose M / Meredith, Kenneth L / Malafa, Mokenge P / Frakes, Jessica M. ·University of South Florida Morsani College of Medicine, Tampa, FL, USA. · Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA. ·J Gastrointest Oncol · Pubmed #29998014.

ABSTRACT: Background: The appropriate adjuvant treatment for resected pancreatic cancer remains a controversy. We sought to determine the effect of adjuvant treatment on overall survival (OS) in patients with pancreatic tail adenocarcinoma. Methods: Retrospective review of patients with upfront surgically resected pancreatic tail cancer treated at our institution between 2000-2012 was performed to determine outcomes of patients treated with and without adjuvant radiation therapy (RT). Survival curves were calculated according to the Kaplan-Meier method. Univariate analysis (UVA) and multivariate analysis (MVA) were performed using the Cox proportional hazards model. Results: Thirty-four patients met inclusion criteria. 79% received adjuvant chemotherapy, either concurrent with RT or alone. The groups were well matched, with the only significant difference being patient sex. On both UVA and MVA there was significantly worse survival in patients with a post-op CA19-9 >90 [hazard ratio (HR) 5.55; 95% confidence interval (CI): 1.20-25.7, P=0.03] and improved survival in patients treated with adjuvant RT (HR 0.15; 95% CI: 0.04-0.58, P=0.006). The median and 2-year OS were 21.6 months and 47% for patients treated with adjuvant RT compared with 11.3 months and 21% for those treated without RT. Conclusions: Although few in patient numbers, this data suggests integration of adjuvant RT in resected pancreatic tail adenocarcinoma may improve OS.

6 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.

7 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.

8 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.

9 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.

10 Article Outcomes of a Clinical Pathway for Borderline Resectable Pancreatic Cancer. 2016

Rashid, Omar M / Pimiento, Jose M / Gamenthaler, Andrew W / Nguyen, Phuong / Ha, Tin T / Hutchinson, Tai / Springett, Gregory / Hoffe, Sarah / Shridhar, Ravi / Hodul, Pamela J / Johnson, Brad L / Illig, Karl / Armstrong, Paul A / Centeno, Barbara A / Fulp, William J / Chen, Dung-Tsa / Malafa, Mokenge P. ·Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · University of South Florida, Tampa, FL, USA. · Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. mokenge.malafa@moffitt.org. ·Ann Surg Oncol · Pubmed #26661409.

ABSTRACT: BACKGROUND: Without prospective data establishing a consensus multimodality approach to borderline resectable pancreatic adenocarcinoma, institutional treatment regimens vary. This study investigated the outcomes of the clinical pathway at the author's institution, which consists of neoadjuvant gemcitabine, docetaxel, capecitabine, and stereotactic radiotherapy followed by surgery. METHODS: The study reviewed all cases that met the National Comprehensive Cancer Network (NCCN) diagnostic criteria for borderline resectable pancreatic adenocarcinoma from 1 January 2006, to 31 December 2013. Pancreatectomy rates, margin status, pathologic response, disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) were retrospectively examined. Standard statistical methods and Kaplan-Meier survival analysis were used for statistical comparisons. RESULTS: Of 121 patients who met criteria, 101 entered the clinical pathway, and 94 (93.1 %) completed neoadjuvant chemotherapy and radiation therapy. Of the 101 patients, 55 (54.5 %) underwent pancreatectomy, with 53 patients (96.4 %) having microscopically negative margins (R0) and 2 patients (3.6 %) having microscopically positive margins (R1). Vascular resection was required for 22 patients (40 %), with rates of 95.5 % for R0 (n = 21) and 4.5 % for R1 (n = 1). A pathologic response to treatment was demonstrated by 45 patients (81.8 %) and a complete response by 10 patients (14.5 %). Pancreatectomy resulted in a median DFS of 23 months (95 % conflidence interval [CI] 14.5-31.5), a median DSS of 43 months (95 % CI, 25.7-60.3), and a median OS of 33 months (95 % CI, 25.0-41.0) versus a median DSS and OS of 14 months (95 % CI, 10.9-17.1) for patients without pancreatectomy (DSS: P = 3.5 × 10(-13); OS: P = 4.7 × 10(-10)). CONCLUSIONS: The study demonstrated high rates for neoajduvant therapy completion (93.1 %) and pancreatectomy (54.5 %). After pancreatectomy, DSS was significantly improved (43 months), with a pathologic response demonstrated by 81.8 % and a complete response by 14.5 % of the patients. The results support further study of this borderline resectable pancreatic adenocarcinoma clinical pathway.

11 Article Outcomes of resected pancreatic cancer in patients age ≥70. 2015

Hayman, Thomas J / Strom, Tobin / Springett, Gregory M / Balducci, Lodovico / Hoffe, Sarah E / Meredith, Kenneth L / Hodul, Pamela / Malafa, Mokenge / Shridhar, Ravi. ·1 University of South Florida Morsani College of Medicine, Tampa, FL, USA ; 2 Department of Radiation Oncology, 3 Gastrointestinal Tumor Program, 4 Senior Adult Oncology Program, Moffitt Cancer Center, Tampa, FL, USA ; 5 Gastrointestinal Oncology, Sarasota Memorial Hospital, Sarasota, FL, USA. ·J Gastrointest Oncol · Pubmed #26487943.

ABSTRACT: OBJECTIVE: To determine outcomes of patients ≥70 years with resected pancreatic cancer. METHODS: A study was conducted to identify pancreatic cancer patients ≥70 years who underwent surgery for pancreatic carcinoma from 2000 to 2012. Patients were excluded if they had neoadjuvant therapy. The primary endpoint was overall survival (OS). RESULTS: We identified 112 patients with a median follow-up of surviving patients of 36 months. The median patient age was 77 years. The median and 5 year OS was 20.5 months and 19%, respectively. Univariate analysis (UVA) showed a significant correlation for increased mortality with N1 (P=0.03) as well as post-op CA19-9 >90 (P<0.001), with a trend towards decreased mortality with adjuvant chemoradiation (P=0.08). Multivariate analysis (MVA) showed a statistically significant increased mortality associated with N1 (P=0.008), post-op CA19-9 >90 (P=0.002), while adjuvant chemoradiation (P=0.04) was associated with decreased mortality. CONCLUSIONS: These data show that in patients ≥70, nodal status, post-op CA19-9, and adjuvant chemoradiation, were associated with OS. The data suggests that outcomes of patients ≥70 years who undergo upfront surgical resection are not inferior to younger patients.

12 Article Radiosensitivity index predicts for survival with adjuvant radiation in resectable pancreatic cancer. 2015

Strom, Tobin / Hoffe, Sarah E / Fulp, William / Frakes, Jessica / Coppola, Domenico / Springett, Gregory M / Malafa, Mokenge P / Harris, Cynthia L / Eschrich, Steven A / Torres-Roca, Javier F / Shridhar, Ravi. ·Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. · Department of Biomedical Informatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. · Gastrointestinal Tumor Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. · Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. Electronic address: Javier.TorresRoca@moffitt.org. · Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. Electronic address: Ravi.Shridhar@moffitt.org. ·Radiother Oncol · Pubmed #26235848.

ABSTRACT: BACKGROUND AND PURPOSE: Adjuvant radiation therapy for resectable pancreatic cancer remains controversial. Sub-populations of radiosensitive tumors might exist given the genetic heterogeneity of pancreatic cancers. We evaluated whether RSI is predictive of survival in pancreatic cancer treated with radiation. MATERIALS AND METHODS: We identified 73 genomically-profiled pancreas cancer patients treated with upfront surgery between 2000 and 2011 (48 radiation, 25 no radiation). Briefly, RSI score is derived from the expression of 10 specific genes and a linear regression algorithm modeled on SF2 of 48 cancer cells. The primary endpoint was to assess the association of RSI with overall survival. RESULTS: Median follow-up was 67months for surviving patients. On multivariate analysis, patients with radioresistant tumors had a trend toward worse survival (Hazard ratio [HR] 2.1 [95% CI 1.0-4.3], p=0.054). Among high-risk, irradiated patients (positive margins, positive lymph nodes, or a post-operative CA19-9 >90; n=31), radiosensitive patients had significantly improved survival compared with radioresistant patients (median 31.2 vs. 13.2months; HR 0.42 [0.19, 0.94], p=0.04). Among irradiated patients (n=48), low-risk patients lived longer than both high-risk patients with radiosensitive tumors and radioresistant tumors (HR 2.7 [1.0, 7.2], p=0.04 and HR 6.3 [2.3, 17.0], p<0.001, respectively). CONCLUSIONS: Integrating RSI with standard high-risk variables has the potential to refine the classification of high-risk resected pancreatic cancer patients treated with radiation therapy.

13 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.

14 Article Comparative long-term outcomes of upfront resected pancreatic cancer after preoperative biliary drainage. 2015

Strom, Tobin J / Klapman, Jason B / Springett, Gregory M / Meredith, Kenneth L / Hoffe, Sarah E / Choi, Junsung / Hodul, Pamela / Malafa, Mokenge P / Shridhar, Ravi. ·Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA. tobin.strom@moffitt.org. · Gastrointestinal Tumor Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Department of Surgery, University of Wisconsin Hospital and Clinic-Madison, Madison, WI, USA. · Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA. · Department of Interventional Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA. Ravi0421@yahoo.com. ·Surg Endosc · Pubmed #25631110.

ABSTRACT: BACKGROUND: We evaluated whether preoperative biliary drainage was predictive of recurrence and survival among patients with resectable pancreatic cancer. METHODS: Patients with pancreatic cancer who were treated with upfront surgery between 2000 and 2012 were identified and stratified by preoperative percutaneous transhepatic cholangiogram-guided drainage (PTBD), placement of endoscopic stents (ERCP), or no biliary drainage (NBD). The primary endpoint was overall survival. RESULTS: We identified 193 patients with resectable pancreatic head cancer (33 PTBD; 96 ERCP; and 64 NBD). Key differences between the three groups were more patients who underwent >1 preoperative biliary procedures (p = 0.004) in the PTBD cohort. PTBD patients had a significant increase in hepatic recurrence rate compared with patients who did not undergo PTBD (44.8 vs. 23.3 %, p = 0.02). PTBD patients also had worse overall survival. Median and 5-year survival for PTBD, ERCP, and NBD patients were 17.5 months and 3 %, 22.4 months and 24 %, and 28.9 months and 32 %, respectively (p = 0.002). MVA revealed that percutaneous drainage was an independent predictor of worse overall survival [HR 1.76, 95 % CI (1.05-2.99), p = 0.03]. CONCLUSIONS: Patients with resectable pancreatic cancer who receive PTBD have more advanced disease, higher hepatic recurrence, and worse survival.

15 Article Resected pancreatic cancer outcomes in the elderly. 2015

Frakes, Jessica M / Strom, Tobin / Springett, Gregory M / Hoffe, Sarah E / Balducci, Lodovico / Hodul, Pamela / Malafa, Mokenge P / Shridhar, Ravi. ·Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA. · Gastrointestinal Tumor Program, Moffitt Cancer Center, Tampa, FL, USA. · Senior Adult Oncology, Moffitt Cancer Center, Tampa, FL, USA. · Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA. Electronic address: ravi0421@yahoo.com. ·J Geriatr Oncol · Pubmed #25555451.

ABSTRACT: OBJECTIVE: To determine if age affects outcome in patients with resected pancreatic head cancer. MATERIALS AND METHODS: An IRB-approved pancreatic cancer database was queried for patients with upfront resected pancreatic head cancer treated at our institution between 2000 and 2012. Overall survival (OS) curves were calculated according to the Kaplan-Meier method and log-rank analysis. Multivariate analysis was performed using the Cox proportional hazard model. RESULTS: We identified 193 patients. Patients ≥70 years were less likely to receive adjuvant treatment (p = 0.002); however there were no other significant differences between age groups. There was a trend towards increased pancreatic leaks in the elderly group (p = 0.06), but no difference in post-operative complications or mortality. There was no difference in overall survival based on age. Median and 5-year OS were 23 months and 26.7% in patients <70 years, 23.4 months and 23% in those 70-75, 16.1 months and 0% in those 76-80, and 18.7 months and 15.4% in those >80 years (p = 0.62). On univariate analysis, there was increased OS in patients with lower T stage, N0 status, post-operative CA19-9 level <90, and use of chemoradiotherapy (p< 0.05). Multivariate analysis revealed that lower tumor stage, N0, post-operative CA19-9 level <90, and use of any adjuvant therapy predicted decreased mortality (p < 0.05). Age, gender, tumor site, tumor grade, and positive margins were not prognostic on multivariate analysis. CONCLUSIONS: There is no difference in outcomes when comparing elderly patients with resected pancreatic cancer to those patients <70 years of age.

16 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.

17 Article Adjuvant radiotherapy and lymph node status for pancreatic cancer: results of a study from the Surveillance, Epidemiology, and End Results (SEER) Registry Data. 2014

Opfermann, Krisha J / Wahlquist, Amy E / Garrett-Mayer, Elizabeth / Shridhar, Ravi / Cannick, Leander / Marshall, David T. ·Departments of *Radiation Oncology †Medicine, Division of Biostatistics and Epidemiology, Medical University of South Carolina, Charleston, SC ‡Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL. ·Am J Clin Oncol · Pubmed #23211221.

ABSTRACT: OBJECTIVES: This study explores the relationship of lymph node ratio (LNR) and radiotherapy (RT) to overall survival (OS) for patients with resected pancreatic cancer. The impact of adjuvant RT, number of lymph nodes (LN) resected, positive LN resected, and disease extension was also evaluated. METHODS: The SEER database from 1998 to 2006 was reviewed, and 3314 patients with nonmetastatic carcinoma of the pancreas, surgical resection, examination of the regional LN, and a survival of >2 months were identified. Of these, 1597 patients received RT. Cox proportional hazards regression models and the logrank test were used to determine whether specific variables were related to OS. RESULTS: Median OS for patients having surgery alone was 14 months (1-y survival 58.1%, 2-y survival 33.6%) and for patients having adjuvant RT was 19 months (1-y survival 73.5%, 2-y survival 41.4%), P<0.001. For patients with LNR of 0%, OS was better compared with patients with any LN involvement, regardless of treatment group. Multivariable analysis found OS significantly related to LNR, total LN resected, positive resected LN, year of diagnosis, and regional extent of disease in patients without adjuvant RT. In patients who received adjuvant RT, OS significance was only persistent for LNR, the total LN resected, and positive resected LN. CONCLUSIONS: A higher LNR was indicative of worse OS in all patients. A strong association with improvement in OS was seen in patients having received adjuvant RT.

18 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.