Study Type
Study Type
Study Objective(Purpose of Study)
Study Objective(Purpose of Study)
Study Results
Study Results
Study Quality
Study Quality
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5-29. Review/Other-Tx N/A To provide the expected numbers of new cancer cases and deaths in 2015 nationally and for each state, as well as a comprehensive overview of cancer incidence, mortality, and survival rates and trends using the most current population-based data. The article also estimates the total number of deaths averted nationally during the past 2 decades and by state in 2011 as a result of the continual decline in cancer death rates and present actual number of deaths reported in 2011 by age for the 10 leading causes of death and for the 5 leading causes of cancer death. Cancer death rates have been continuously declining for the past 2 decades. Overall, the risk of dying from cancer decreased by 22% between 1991 and 2011. Regionally, progress has been most rapid for residents of the Northeast, among whom death rates have declined by 25% to 30%, and slowest in the South, where rates declined by about 15%. Further reductions in cancer death rates can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those in the lowest socioeconomic bracket and other disadvantaged populations. 4
2. Wolfgang CL, Herman JM, Laheru DA, et al. Recent progress in pancreatic cancer. CA Cancer J Clin. 2013;63(5):318-348. Review/Other-Tx N/A To review recent progress in pancreatic cancer, with emphasis on genetic advances and the multidisciplinary team approach to patient care. No results stated in abstract. 4
3. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825. Experimental-Tx 342 patients To further explore FOLFIRINOX as compared with single agent gemcitabine as first-line treatment in patients with metastatic pancreatic cancer. The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (hazard ratio for disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001). More adverse events were noted in the FOLFIRINOX group; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (hazard ratio, 0.47; 95% CI, 0.30 to 0.70; P<0.001). 1
4. Pawlik TM, Laheru D, Hruban RH, et al. Evaluating the impact of a single-day multidisciplinary clinic on the management of pancreatic cancer. Ann Surg Oncol. 2008;15(8):2081-2088. Observational-Tx 203 patients To evaluate the impact of a multidisciplinary clinic on the clinical care recommendations of patients with pancreatic cancer compared with the recommendations the patients received prior to review by the multidisciplinary tumor board. On presentation, the outside computed tomography (CT) report described locally advanced/unresectable disease (34.9%), metastatic disease (17.7%), and locally advanced disease with metastasis (1.1%). On review of submitted imaging and imaging performed at Hopkins, 38 out of 203 (18.7%) patients had a change in the status of their clinical stage. Review of the histological slides by dedicated pancreatic pathologists resulted in changes in the interpretation for 7 of 203 patients (3.4%). Overall, 48 out of 203 (23.6%) patients had a change in their recommended management based on clinical review of their case by the multidisciplinary tumor board. Enrollment into the National Familial Pancreas Tumor Registry increased from 52 out of 106 (49.2%) patients in 2005 to 158 out of 203 (77.8%) with initiation of the multidisciplinary clinic. 2
5. Fong Y, Gonen M, Rubin D, Radzyner M, Brennan MF. Long-term survival is superior after resection for cancer in high-volume centers. Ann Surg. 2005;242(4):540-544; discussion 544-547. Observational-Tx 2592 pancreatectomies and 3734 hepatectomies To examine the relationship between hospital volume with long-term survival in patients with cancer subjected to pancreatectomy or hepatectomy using a national database. In the study period, there were 2592 pancreatectomies and 3734 hepatectomies performed at 1101 and 1284 institutions, respectively. High-volume center was defined as >25 cases/y. By this definition, there were 10 high-volume centers for pancreatectomy and 12 centers for hepatectomy performing 11% (n = 291) of the pancreatectomies and 12% (n = 474) of the hepatectomies in this study period. Comparison by log-rank demonstrated superior survival for patients resected at high-volume centers (pancreatectomy: P = 0.001; hepatectomy: P = 0.02). This was confirmed by multivariate analysis. All analyses included an adjustment for within-center correlation. 2
6. Katz MH, Marsh R, Herman JM, et al. Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol. 2013;20(8):2787-2795. Review/Other-Tx N/A To review limitations of studies of borderline resectable PDAC reported to date, highlight important controversies related to this disease stage, emphasize the research infrastructure necessary for its future study, and present a recently-approved Intergroup pilot study (Alliance A021101) that will provide a foundation upon which subsequent well-designed clinical trials can be performed. We identified twenty-three studies published since 2001 which report outcomes of patients with tumors labeled as borderline resectable and who were treated with neoadjuvant therapy prior to planned pancreatectomy. These studies were heterogeneous in terms of the populations studied, the metrics used to characterize therapeutic response, and the indications used to select patients for surgery. Mechanisms used to standardize these and other issues that are incorporated into Alliance A021101 are reviewed. 4
7. Tummala P, Junaidi O, Agarwal B. Imaging of pancreatic cancer: An overview. J Gastrointest Oncol. 2011;2(3):168-174. Review/Other-Dx N/A To review the relative advantages and shortcomings of imaging modalities available for evaluation of patients with suspected pancreatic cancer and for preoperative determination of resectability. No results stated in abstract. 4
8. Schima W, Ba-Ssalamah A, Goetzinger P, Scharitzer M, Koelblinger C. State-of-the-art magnetic resonance imaging of pancreatic cancer. Top Magn Reson Imaging. 2007;18(6):421-429. Review/Other-Dx N/A To review the relative advantages and shortcomings of imaging modalities available for evaluation of patients with suspected pancreatic cancer and for preoperative determination of resectability. No results stated in abstract. 4
9. Vachiranubhap B, Kim YH, Balci NC, Semelka RC. Magnetic resonance imaging of adenocarcinoma of the pancreas. Top Magn Reson Imaging. 2009;20(1):3-9. Review/Other-Dx N/A To describe the attribute of MRI for evaluating pancreatic cancer. No results stated in abstract. 4
10. NCCN Clinical Practice Guidelines in Oncology. Pancreatic Adenocarcinoma. Version 2.2016. 2016; Available at: Review/Other-Tx N/A To provide NCCN practice guidelines on pancreatic carcinoma. No abstract available. 4
11. Iacobuzio-Donahue CA, Fu B, Yachida S, et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol. 2009;27(11):1806-1813. Observational-Tx 76 patients To present the clinical and pathologic features at autopsy of the first 76 patients with pancreatic cancer who participated in this program with particular reference to the histopathologic findings and genetic status in relation to patterns of failure. At autopsy, 30% of patients died with locally destructive pancreatic cancer, and 70% died with widespread metastatic disease. These divergent patterns of failure found at autopsy (locally destructive v metastatic) were unrelated to clinical stage at initial presentation, treatment history, or histopathologic features. However, Dpc4 immunolabeling status of carcinoma tissues harvested at autopsy, a sensitive marker of DPC4 genetic status, was highly correlated with the presence of widespread metastasis but not with locally destructive tumors (P = .007). 2
12. Moertel CG, Frytak S, Hahn RG, et al. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer. 1981;48(8):1705-1710. Experimental-Tx 194 patients To evaluate the effectiveness of split course radiation therapy to 6000 rads by controlled study attempts to confirm the value of combined radiation = 5-FU therapy demonstrated in the earlier Mayo Clinic study. Median survival with radiation alone was only 51/2 months from date of diagnosis. Both 5-FU-containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Forty percent of patients treated with the combined regimens were still living at one year compared with 10% of patients treated with radiation only. Survival differences between 4000 rads plus 5-FU and 6000 rads plus 5-FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level. 1
13. Cohen SJ, Dobelbower R, Jr., Lipsitz S, et al. A randomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern Cooperative Oncology Group study E8282. Int J Radiat Oncol Biol Phys. 2005;62(5):1345-1350. Experimental-Tx 104 patients To determine whether the addition of 5-fluorouracil (5-FU) and mitomycin-C (MMC) to radiation therapy improves outcome in this patient population. One hundred four patients were evaluable for efficacy. Hematologic and nonhematologic toxicities were more common in the combination arm. The response rates were 6% in the radiation therapy arm and 9% in the combination arm. There were no differences in median disease-free survival time (DFS) or overall survival time (OS) between the combination and radiation therapy alone arms: 5.1 vs. 5.0 months, respectively, for DFS (p = 0.19) and 8.4 vs. 7.1 months, respectively, for OS (p = 0.16). 1
14. Moertel CG, Childs DS, Jr., Reitemeier RJ, Colby MY, Jr., Holbrook MA. Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet. 1969;2(7626):865-867. Experimental-Tx 187 patients To determine the dosage of 5-F.u. that would produce definite but clinically tolerable toxicity when used in combination with radiation therapy applied to the abdomen or pelvis. A prospective, controlled double-blind study involving a substantial number of patients suggests that 5-fluorouracil (5-F.U.) significantly augments the effectiveness of radiation therapy for locally unresectable carcinoma of the stomach, pancreas, and large bowel. It is also possible that rarely this therapy may be curative. This approach should not be advocated as routine treatment since the vast majority of these patients still die of their cancer; and, if the present results are not spurious, the method offers only a few extra months of life. These results should, however, serve as stimulus and foundation for continued study of augmented radiation therapy. in 1
15. Radiation therapy combined with Adriamycin or 5-fluorouracil for the treatment of locally unresectable pancreatic carcinoma. Gastrointestinal Tumor Study Group. Cancer. 1985;56(11):2563-2568. Experimental-Tx 143 patients To compare, in patients with localized but unresectable pancreatic adenocarcinoma, programs of treatment of (1) 6000 rad of radiotherapy administered as a double-split course and complemented by 5-FU (as administered in its previous study), with (2) 4000 rad delivered as a continuous course and complemented by Adriamycin administration. A total of 138 of 143 analyzable patients have died, and no differences in the relative survival impact of the treatments have been observed (P greater than 0.8). Toxicity on the Adriamycin arm was more substantial (P less than 0.05) and primarily attributable to Adriamycin chemotherapy after the completion of radiotherapy. 1
16. Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. Gastrointestinal Tumor Study Group. J Natl Cancer Inst. 1988;80(10):751-755. Experimental-Tx 43 patients To compare the survival of patients treated with multidrug chemotherapy [streptozocin, mitomycin, and 5-fluorouracil (SMF)] versus radiation combined with 5-fluorouracil followed by the same three-drug SMF combination. In 43 patients randomly allocated between these two arms, an improved median survival for the combined-modality therapy (42 weeks) compared with chemotherapy alone (32 weeks) was demonstrated. Overall survival following this combined-modality treatment program (41% at 1 year) was significantly superior to that following SMF chemotherapy alone (19% at 1 year), by a two-tailed log rank test (P less than .02). 1
17. Klaassen DJ, MacIntyre JM, Catton GE, Engstrom PF, Moertel CG. Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil--an Eastern Cooperative Oncology Group study. J Clin Oncol. 1985;3(3):373-378. Experimental-Tx 148 patients To compare 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil. The median survival time was similar for both treatment programs and for both types of primary carcinoma, and was as follows: gastric primary carcinoma, 5-FU, 9.3 months; 5-FU plus radiotherapy, 8.2 months; pancreatic primary carcinoma, 5-FU, 8.2 months; 5-FU plus radiotherapy, 8.3 months. Substantially more toxicity was experienced by patients treated with the combined modality arm than by those patients receiving 5-FU alone. Severe or worse toxicity experienced by patients with gastric primary carcinoma treated by 5-FU was 19%, and the combined modality arm was 31%. The toxicity experienced by patients with pancreatic primary carcinoma treated with 5-FU was 27%, and the combined modality arm was 51%. Significant prognostic variables included: weight loss in stomach-cancer patients; and performance status, degree of anaplasia, and reduced appetite in pancreas-cancer patients. 1
18. Boz G, De Paoli A, Innocente R, et al. Radiotherapy and continuous infusion 5-fluorouracil in patients with nonresectable pancreatic carcinoma. Int J Radiat Oncol Biol Phys. 2001;51(3):736-740. Experimental-Tx 42 patients To report on our experience with the combination of RT and continuous infusion 5-FU in a group of patients with locally nonresectable pancreatic carcinoma. All patients completed the RT as planned, and 33 (78%) completed the full regimen of chemotherapy. Ten patients (23%) had a partial response, and 32 (77%) had stable disease. Subjective response, defined as the disappearance of symptoms observed at diagnosis, was also evaluated. Two patients (6%) had a complete, and 24 (75%) a partial, remission of symptoms. The median time to progression was 6.2 months, and the median survival time was 9.1 months. 2
19. Whittington R, Neuberg D, Tester WJ, Benson AB, 3rd, Haller DG. Protracted intravenous fluorouracil infusion with radiation therapy in the management of localized pancreaticobiliary carcinoma: a phase I Eastern Cooperative Oncology Group Trial. J Clin Oncol. 1995;13(1):227-232. Experimental-Tx 25 patients To determine the maximum-tolerated dose (MTD) of fluorouracil (5-FU) administered as a protracted intravenous (IV) infusion with concurrent radiation in patients with pancreaticobiliary carcinoma. The MTD of 5-FU was 250 mg/m2/d. The dose-limiting toxicity was oral mucositis. The median survival duration of all patients treated was 11.9 months and the 2-year survival rate was 19%. Eleven of 25 patients remain free of local progression and four patients are without evidence of progression at 18+, 18+, 34+, and 44+ months following treatment. 2
20. Loehrer PJ, Sr., Feng Y, Cardenes H, et al. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011;29(31):4105-4112. Experimental-Tx 71 patients To evaluate the role of radiation therapy with concurrent gemcitabine (GEM) compared with GEM alone in patients with localized unresectable pancreatic cancer. Of 74 patients entered on trial and randomly assigned to receive GEM alone (arm A; n = 37) or GEM plus radiation (arm B; n = 34), patients in arm B had greater incidence of grades 4 and 5 toxicities (41% v 9%), but grades 3 and 4 toxicities combined were similar (77% in A v 79% in B). No statistical differences were seen in quality of life measurements at 6, 15 to 16, and 36 weeks. The primary end point was survival, which was 9.2 months (95% CI, 7.9 to 11.4 months) and 11.1 months (95% CI, 7.6 to 15.5 months) for arms A and B, respectively (one-sided P = .017 by stratified log-rank test). 1
21. Chauffert B, Mornex F, Bonnetain F, et al. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol. 2008;19(9):1592-1599. Experimental-Tx 119 patients To compare an intensified induction phase with CHRT combining infusion FU and cisplatin, followed by maintenance gemcitabine with gemcitabine alone in histologically or cytologically proven LAPC. Overall survival was shorter in the CHRT than in GEM arm [median survival 8.6 (99% confidence interval 7.1-11.4) and 13 months (8.7-18.1), P = 0.03]. One-year survival was, respectively, 32% and 53%. These results were confirmed in a per-protocol analysis for patients who received 75% or more of the planned dose of radiotherapy. More overall grades 3-4 toxic effects were recorded in the CHRT arm, both during induction (36 versus 22%) and maintenance (32 versus 18%). 1
22. Sultana A, Tudur Smith C, Cunningham D, et al. Systematic review, including meta-analyses, on the management of locally advanced pancreatic cancer using radiation/combined modality therapy. Br J Cancer. 2007;96(8):1183-1190. Meta-analysis 11 trials; 794 patients To review systematically the published and unpublished literature, comparing the following therapies: 1. Chemoradiotherapy, followed by chemotherapy vs best supportive care; 2. Radiotherapy vs chemoradiotherapy; 3. Radiotherapy vs chemoradiotherapy, followed by chemotherapy; 4. Chemotherapy vs chemoradiotherapy, followed by chemotherapy (combined modality therapy); 5. 5FU-based chemoradiotherapy followed by chemotherapy vs another agent-based chemoradiotherapy, followed by chemotherapy. Length of survival with chemoradiation was increased compared with radiotherapy alone (two trials, 168 patients, HR 0.69; 95% confidence interval (CI) 0.51-0.94), but chemoradiation followed by chemotherapy did not lead to a survival advantage over chemotherapy alone (two trials, 134 patients, HR 0.79; CI 0.32-1.95). Meta-analyses could not be performed for the other comparisons. A survival benefit was demonstrated for chemoradiation over radiotherapy alone. Chemoradiation followed by chemotherapy did not demonstrate any survival advantage over chemotherapy alone, but important clinical differences cannot be ruled out due to the wide CI. M
23. Hammel P, Huguet F, Van Laethem J-L, et al. Comparison of chemoradiotherapy (CRT) and chemotherapy (CT) in patients with a locally advanced pancreatic cancer (LAPC) controlled after 4 months of gemcitabine with or without erlotinib: Final results of the international phase III LAP 07 study. ASCO Meeting Abstracts. 2013;31(15_suppl):LBA4003. Experimental-Tx 269 patients To define the role of 1) CRT after disease control with gemcitabine, 2) erlotinib in LAPC. From 442 pts included for R1, 269 pts reached R2 (arm1:136; arm 2:133). Main baseline characteristics in arms 1/2: female 44%/56%, mean age 63/62, head tumor 65%/62%, PS 0 56%/48%. After a median follow-up of 36 m, 221 deaths had occurred allowing the planned interim analysis (information fraction 56.4%). OS in R2 pts was 16.5 m [15.5-18.5] and 15.3 m [13.9–17.3] in arms 1 and 2, respectively (HR=1.03 [0.79-1.34], p=0.83). IDMC has confirmed that the futility boundary for the hypothesis of CRT superiority was crossed and considered this as the final analysis of the study. 1
24. Huguet F, Hammel P, Vernerey D, et al. Impact of chemoradiotherapy (CRT) on local control and time without treatment in patients with locally advanced pancreatic cancer (LAPC) included in the international phase III LAP 07 study. J Clin Oncol. 2014;32(5s):(suppl; abstr 4001^). Experimental-Tx 442 patients To study giving gemcitabine together with or without capecitabine and/or radiation therapy to see how well it works compared with giving gemcitabine together with or without erlotinib in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery. Among the 442 included patients, 269 patients had tumor control after 4 months of induction CT and were randomized to either the CRT arm (n=133) or the CT arm (n=136). The OS was not significantly different between the two arms (15.2 vs 16.5 months, p=0.8). At the time of analysis, 238 patients had a tumor progression, which was locoregional in 96 patients (50.5%) and metastatic in 97 patients (49.5%). In the CRT arm, patients had significantly less local tumor progression compared to the CT arm (34% vs 65%, p<0.0001). Median time without treatment (i.e. reintroduction of chemotherapy) was longer in the CRT arm compared to the CT arm (159 vs 96 days, respectively, p=0.05). 1
25. Mohiuddin M, Regine WF, Stevens J, et al. Combined intraoperative radiation and perioperative chemotherapy for unresectable cancers of the pancreas. J Clin Oncol. 1995;13(11):2764-2768. Experimental-Tx 49 patients To evaluate the effectiveness of combined intraoperative radiation therapy (IORT) and perioperative chemotherapy in the management of unresectable pancreatic cancer. The incidence of perioperative mortality was 0%. Early postsurgical morbidity (grade 3/4) was observed in seven of 49 patients (14%) and late treatment-related morbidity (grade 3/4) in eight of 43 patients (19%) alive beyond 6 months. Morbidity was primarily gastrointestinal (GI), with no hematologic toxicities observed. The median survival time in the total group of patients is 16 months, with a 2-year survival rate of 22% and a 4-year survival rate of 7%. Freedom from local progression of disease was achieved in 71% of patients. 2
26. Willett CG, Del Castillo CF, Shih HA, et al. Long-term results of intraoperative electron beam irradiation (IOERT) for patients with unresectable pancreatic cancer. Ann Surg. 2005;241(2):295-299. Observational-Tx 150 patients To analyze the effects of a treatment program of intraoperative electron beam radiation therapy (IOERT) and external beam radiation therapy and chemotherapy on the outcome of patients with unresectable or locally advanced pancreatic cancer. The 1-, 2-, and 3-year actuarial survival rates of all 150 patients were 54%, 15%, and 7%, respectively. Median and mean survival rates were 13 and 17 months, respectively. Long-term survival has been observed in 8 patients. Five patients have survived beyond 5 years and 3 more between 3 and 4 years. There was a statistically significant correlation of survival to the diameter of treatment applicator (a surrogate for tumor size) used during IOERT. For 26 patients treated with a small-diameter applicator (5 cm or 6 cm), the 2- and 3-year actuarial survival rates were 27% and 17%, respectively. In contrast, none of the 11 patients treated with a 9-cm-diameter applicator survived beyond 18 months. Intermediate survival rates were seen for patients treated with a 7- or 8-cm-diameter applicator. Operative mortality was 0.6%, and postoperative and late complications were 20% and 15%, respectively. 2
27. Kim EJ, Ben-Josef E, Herman JM, et al. A multi-institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer. Cancer. 2013;119(15):2692-2700. Experimental-Tx 68 patients To evaluate preoperative treatment with full-dose gemcitabine, oxaliplatin, and radiation therapy (RT) in patients with localized pancreatic cancer. Sixty-eight evaluable patients received treatment at 4 centers. By central radiology review, 23 patients had resectable disease, 39 patients had borderline resectable disease, and 6 patients had unresectable disease. Sixty-six patients (97%) completed cycle 1 with RT, and 61 patients (90%) completed cycle 2. Grade >/=3 adverse events during preoperative therapy included neutropenia (32%), thrombocytopenia (25%), and biliary obstruction/cholangitis (14%). Forty-three patients underwent resection (63%), and complete (R0) resection was achieved in 36 of those 43 patients (84%). The median overall survival was 18.2 months (95% confidence interval, 13-26.9 months) for all patients, 27.1 months (95% confidence interval, 21.2-47.1 months) for those who underwent resection, and 10.9 months (95% confidence interval, 6.1-12.6 months) for those who did not undergo resection. A decrease in CA 19-9 level after neoadjuvant therapy was associated with R0 resection (P = .02), which resulted in a median survival of 34.6 months (95% confidence interval, 20.3-47.1 months). Fourteen patients (21%) are alive and disease free at a median follow-up of 31.4 months (range, 24-47.6 months). 1
28. Small W, Jr., Berlin J, Freedman GM, et al. Full-dose gemcitabine with concurrent radiation therapy in patients with nonmetastatic pancreatic cancer: a multicenter phase II trial. J Clin Oncol. 2008;26(6):942-947. Experimental-Tx 39 patients To assess safety and efficacy of full-dose gemcitabine administered before and during concurrent three-dimensional conformal radiation (3D-CRT) in patients with nonmetastatic pancreatic cancer. Forty-one patients enrolled at six institutions between April 2002 and October 2003. Among the 39 treated patients, the most common toxicities were grade 3 neutropenia (12.8%), grade 3 nausea (10.3%), and grade 3 vomiting (10.3%). The response rate was 5.1% and disease control rate was 84.6%. Mean post-treatment CA 19-9 levels (228 +/- 347 U/mL) were significantly (P = .006) reduced compared with pretreatment levels (1,241 +/- 2,124 U/mL). Thirteen (81%) of 16 patients initially judged resectable, three (33%) of nine borderline-resectable patients, and one (7%) of 14 unresectable patients underwent resection after therapy. One-year survival rates were 73% for all patients, 94% for resectable patients, 76% for borderline-resectable patients, and 47% for unresectable patients. 1
29. Small W, Jr., Mulcahy MF, Rademaker A, et al. Phase II trial of full-dose gemcitabine and bevacizumab in combination with attenuated three-dimensional conformal radiotherapy in patients with localized pancreatic cancer. Int J Radiat Oncol Biol Phys. 2011;80(2):476-482. Experimental-Tx 28 patients To evaluate response rate, survival, and toxicity in patients with nonmetastatic pancreatic cancer treated with gemcitabine, bevacizumab, and radiotherapy. Twenty-eight of the 32 enrolled patients completed all three cycles. The median follow-up was 11.07 months. Most grade 3 or 4 toxicities occurred in the initial treatment phase; the most frequent toxicities were leukopenia (21%), neutropenia (17%), and nausea (17%). At week 10, 1 patient (4%) had a complete response, 2 patients (7%) had partial responses, 21 patients (75%) had stable disease, and 4 patients (14%) had progressive disease. The median pretreatment and posttreatment CA 19-9 levels (25 patients) were 184.3 and 57.9 U/ml, respectively (p = 0.0006). One of 10 patients proceeding to surgery experienced a major complication. Two of 6 patients undergoing resection had complete pathologic responses. The median progression-free and overall survival durations were 9.9 months and 11.8 months, respectively. 1
30. Ben-Josef E, Schipper M, Francis IR, et al. A phase I/II trial of intensity modulated radiation (IMRT) dose escalation with concurrent fixed-dose rate gemcitabine (FDR-G) in patients with unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys. 2012;84(5):1166-1171. Experimental-Tx 50 patients To determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. 2
31. Hong TS, Ryan DP, Blaszkowsky LS, et al. Phase I/II study of Proton-based Short Course Chemoradiation and Early Surgery for Adenocarcinoma of the Pancreas. International Journal of Radiation Oncology*Biology*Physics. 2010;78(3, Supplement):S99-S100. Experimental-Tx 27 patients To explore the safety and efficacy of a one-week course of pre-op CRT with proton beam therapy (PBT) and cape followed by early pancreaticoduodenectomy (PD). Thirty-one pts were enrolled on study. Twenty-seven patients are eligible for this analysis. Three pts were treated at each of dose levels 1-3. Six pts were at dose level 4, which was selected as MTD. No dose limiting toxicities were observed. Gr 3 toxicity was noted in 4 pts (pain-1, GI-1, stent obstruction/infxn- 2). An additional 16 patients were treated at the MTD for the phase II portion. Twenty-one pts underwent resection. Reasons for no resections were: metastatic disease-4, unresectable tumor-1, and unrelated to disease/therapy-1. Mean time from last therapy to surgery was 22 d (10-47). Mean post-PD length of stay was 8 days (range, 5-47). There was one unexpected SAE, g3 post-operative gastroparesis; no other unexpected 30-d post-op complications noted in comparison to historical controls. Four of 21 resected pts had positive margins. Seventeen of 21 had positive nodes. Median follow-up is 10 months. There have been 2 local failures/progression in ALL patients, both with synchronous metastatic disease (at 10 mos and 17 mos). Metastatic failure has occurred in 15 out of 27 patients (56%). 2
32. Hong TS, Ryan DP, Borger DR, et al. 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. Int J Radiat Oncol Biol Phys. 2014;89(4):830-838. Experimental-Tx 50 patients 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. 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). 2
33. Kozak KR, Kachnic LA, Adams J, et al. Dosimetric feasibility of hypofractionated proton radiotherapy for neoadjuvant pancreatic cancer treatment. Int J Radiat Oncol Biol Phys. 2007;68(5):1557-1566. Observational-Tx 9 patients To evaluate tumor and normal tissue dosimetry of a 5 cobalt gray equivalent (CGE) x 5 fraction proton radiotherapy schedule, before initiating a clinical trial of neoadjuvant, short-course proton radiotherapy for pancreatic adenocarcinoma. Hypofractionated proton and conventionally fractionated intensity-modulated radiotherapy plans both provided acceptable target volume coverage and dose homogeneity. Improved dose conformality provided by the hypofractionated proton regimen resulted in significant sparing of kidneys, liver, and small bowel, evidenced by significant reductions in the mean doses, expressed as percentage prescribed dose, to these structures. Kidney and liver sparing was most evident in low-dose regions (< or =20% prescribed dose for both kidneys and < or =60% prescribed dose for liver). Improvements in small-bowel dosimetry were observed in high- and low-dose regions. Mean stomach and duodenum doses, expressed as percentage prescribed dose, were similar for the two techniques. 2
34. Schellenberg D, Kim J, Christman-Skieller C. et al. Single-fraction stereotactic body radiation therapy and sequential gemcitabine for the treatment of locally advanced pancreas cancer. Int J Radiat Oncol Biol Phys. 2011;81(1):181-188. Experimental-Tx 20 patients To evaluate the toxicity, local control, and overall survival in patients treated with sequential gemcitabine and linear accelerator-based single-fraction stereotactic body radiotherapy (SBRT). All patients completed SBRT and a median of five cycles of chemotherapy. Follow-up for the 2 remaining alive patients was 25.1 and 36.4 months. No acute Grade 3 or greater nonhematologic toxicity was observed. Late Grade 3 or greater toxicities occurred in 1 patient (5%) and consisted of a duodenal perforation (G4). Three patients (15%) developed ulcers (G2) that were medically managed. Overall, median survival was 11.8 months, with 1-year survival of 50% and 2-year survival of 20%. Using serial computed tomography, the freedom from local progression was 94% at 1 year. 2
35. Herman JM, Chang DT, Goodman KA, et al. Phase 2 multi-insitutional trial evaluating gemcitabine and sterotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer. 2015;121(7):1128-37. Experimental-Tx 49 patients To determine whether gemcitabine (GEM) with fractionated stereotactic body radiotherapy (SBRT) results in acceptable late grade 2 to 4 gastrointestinal toxicity when compared with a prior trial of GEM with single-fraction SBRT in patients with locally advanced pancreatic cancer (LAPC). The median follow-up was 13.9 months (range, 3.9-45.2 months). The median age of the patients was 67 years and 84% had tumors of the pancreatic head. Rates of acute and late (primary endpoint) grade >/= 2 gastritis, fistula, enteritis, or ulcer toxicities were 2% and 11%, respectively. QLQ-C30 global quality of life scores remained stable from baseline to after SBRT (67 at baseline, median change of 0 at both follow-ups; P>.05 for both). Patients reported a significant improvement in pancreatic pain (P = .001) 4 weeks after SBRT on the QLQ-PAN26 questionnaire. The median plasma carbohydrate antigen 19-9 (CA 19-9) level was reduced after SBRT (median time after SBRT, 4.2 weeks; 220 U/mL vs 62 U/mL [P<.001]). The median overall survival was 13.9 months (95% confidence interval, 10.2 months-16.7 months). Freedom from local disease progression at 1 year was 78%. Four patients (8%) underwent margin-negative and lymph node-negative surgical resections. 1
36. Mellon EA, Hoffe SE, Springett GM, et al. Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma. Acta Oncol. 2015;54(7):979-985. Observational-Tx 159 patients To update the outcomes and toxicity using induction chemotherapy and SBRT for BRPC and LAPC in our institutional experience of 159 patients. 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%. 2
37. Moningi S, Dholakia AS, Raman SP, et al. The Role of Stereotactic Body Radiation Therapy for Pancreatic Cancer: A Single-Institution Experience. Ann Surg Oncol. 2015;22(7):2352-2358. Observational-Tx 88 patients To review our institutional experience of SBRT in the treatment of locally advanced (LAPC) and borderline resectable (BRPC) PCA. A total of 88 patients were included in the analysis, 74 with LAPC and 14 with BRPC. The median age at diagnosis was 67.2 years, and median follow-up from date of diagnosis for LAPC and BRPC patients was 14.5 and 10.3 months, respectively. Median OS from date of diagnosis was 18.4 months (LAPC, 18.4 mo; BRPC, 14.4 mo) and median PFS was 9.8 months (95 % CI 8.0-12.3). Acute toxicity was minimal with only three patients (3.4 %) experiencing acute grade >/=3 toxicity. Late grade >/=2 gastrointestinal toxicity was seen in five patients (5.7 %). Of the 19 patients (21.6 %) who underwent surgery, 79 % were LAPC patients and 84 % had margin-negative resections. 2
38. Bilimoria KY, Bentrem DJ, Ko CY, Stewart AK, Winchester DP, Talamonti MS. National failure to operate on early stage pancreatic cancer. Ann Surg. 2007;246(2):173-180. Observational-Tx 9,559 patients To evaluate utilization of surgery in early stage disease and identify factors predicting failure to undergo surgery. Of clinical Stage I patients 71.4% (6823/9559) did not undergo surgery; 6.4% (616/9559) were excluded due to comorbidities; 4.2% (403/9559) refused surgery; 9.1% (869/9559) were excluded due to age; and 38.2% (3,644/9559) with potentially resectable cancers were classified as "not offered surgery." Of the 28.6% (2736/9559) of patients who underwent surgery, 96.0% (2630/2736) underwent pancreatectomy, and 4.0% (458/2736) had unresectable tumors. Patients were less likely to undergo surgery if they were older than 65 years, were black, were on Medicare or Medicaid, had pancreatic head lesions, earned lower annual incomes, or had less education (P < 0.0001). Patients were less likely to receive surgery at low-volume and community centers. Patients underwent surgery more frequently at National Cancer Institute/National Comprehensive Cancer Network-designated cancer centers (P < 0.0001). Patients who were not offered surgery had significantly better survival than those with Stage III or IV disease but worse survival than patients who underwent pancreatectomy for Stage I disease (P < 0.0001). 2
39. Ishikawa O, Ohigashi H, Imaoka S, et al. Is the long-term survival rate improved by preoperative irradiation prior to Whipple's procedure for adenocarcinoma of the pancreatic head? Arch Surg. 1994;129(10):1075-1080. Observational-Tx 54 patients To determine whether or not both regional control and long-term survival rate were improved by preoperative irradiation prior to curative pancreatectomy for adenocarcinoma of the pancreatic head. At laparotomy, curative pancreatectomy was possible in 17 patients (74%) in group A and 19 (61%) in group B (not significant). In patients undergoing resection, the 1-year survival rate was 75% in group A and 43% in group B (P < .05). However, 3- and 5-year survival rates were almost the same in both groups (28% vs 32% and 22% vs 26%, respectively). With regard to the cause of death after pancreatectomy, group A had a significantly lower incidence of deaths due to regional recurrence within 1.5 postoperative years compared with group B, whereas deaths due to hepatic metastasis were markedly higher after 1 postoperative year in group A compared with group B. 2
40. Evans DB, Rich TA, Byrd DR, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992;127(11):1335-1339. Review/Other-Tx 28 patients To determine the morbidity and mortality of preoperative chemoradiation followed by pancreaticoduodenectomy in patients with adenocarcinoma of the pancreas and to document the radiologic and pathologic response to preoperative chemoradiation. Hospital admission because of gastrointestinal toxic effects was required in nine patients, yet no patient experienced a delay in operation. Restaging was performed 4 to 5 weeks after completion of chemoradiation, and five patients were found to have metastatic disease; the 23 patients without evidence of progressive disease underwent laparotomy. At laparotomy, three patients were found to have unsuspected metastatic disease, three patients had unresectable locally advanced disease, and 17 patients were able to undergo pancreaticoduodenectomy. One perioperative death resulted from myocardial infarction, and perioperative complications occurred in three patients. Histologic evidence of tumor cell injury was present in all resected specimens. 4
41. Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3496-3502. Experimental-Tx 86 patients To assess the outcomes of patients who received preoperative gemcitabine-based chemoradiation and pancreaticoduodenectomy (PD) for stage I/II pancreatic adenocarcinoma. The study enrolled 86 patients. At the time of restaging, disease progression or a decline in performance status precluded 13 patients from surgery. Seventy-three (85%) of 86 patients were taken to surgery, extrapancreatic disease was found in nine, and 64 (74%) of 86 underwent a successful PD. Median overall survival (86 patients) was 22.7 months with a 27% 5-year survival. Median survival was 34 months for the 64 patients who underwent PD and 7 months for the 22 unresected patients (P < .001). The 5-year survival for those who did and did not undergo PD was 36% and 0%, respectively. 2
42. Pisters PW, Abbruzzese JL, Janjan NA, et al. Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol. 1998;16(12):3843-3850. Experimental-Tx 35 patients To evaluate the toxicities, radiographic and pathologic responses, and event-free outcomes with combined modality treatment that involves preoperative rapid-fractionation chemoradiation, pancreaticoduodenectomy, and electron-beam intraoperative radiation therapy (EB-IORT) for patients with resectable pancreatic adenocarcinoma. Thirty-five patients were entered onto the study and completed chemoradiation, 34 (97%) as outpatients. Three patients (9%) experienced grade 3 nausea and vomiting; no other grade 3 or 4 toxicities were observed. Of the 27 patients taken to surgery, 20 patients (74%) underwent pancreaticoduodenectomy with EB-IORT. All patients had a less than grade III pathologic response to preoperative chemoradiation. At a median follow-up of 37 months, the 3-year survival rate in patients who underwent combined modality therapy was 23%. 2
43. Pisters PW, Wolff RA, Janjan NA, et al. Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome. J Clin Oncol. 2002;20(10):2537-2544. Experimental-Tx 35 patients To evaluate the toxicity of a preoperative regimen of paclitaxel and concurrent external-beam radiation therapy, pancreaticoduodenectomy, and electron-beam intraoperative radiation therapy (EB-IORT) for patients with resectable pancreatic adenocarcinoma. Thirty-five patients completed chemoradiation; 16 (46%) experienced grade 3 toxicity. Four patients (11%) required hospitalization for dehydration due to grade 3 nausea and vomiting. Twenty (80%) of 25 patients who underwent surgery underwent pancreatectomy; EB-IORT was used in 13 patients. There were no histologic complete responses to preoperative therapy; 21% of specimens demonstrated more than 50% nonviable cells (grade 2b treatment effect). With a median follow-up period of 46 months, the 3-year overall survival rate with chemoradiation and pancreatectomy was 28%. 2
44. Talamonti MS, Small W, Jr., Mulcahy MF, et al. A multi-institutional phase II trial of preoperative full-dose gemcitabine and concurrent radiation for patients with potentially resectable pancreatic carcinoma. Ann Surg Oncol. 2006;13(2):150-158. Experimental-Tx 20 patients To evaluate the toxicity associated with this neoadjuvant regimen in a multi-institutional setting; to determine radiographic, tumor marker, and pathologic responses to treatment; to evaluate morbidity and mortality among patients who undergo resection after completion of therapy; and to estimate overall survival in patients treated with this approach. There were 10 men and 10 women, with a median age of 58 years (range, 50-80 years). Nineteen patients (95%) completed therapy without interruption, and one experienced grade 3 gastrointestinal toxicity. The mean weight loss after therapy was 4.0%. Of 20 patients taken to surgery, 17 (85%) underwent resections (16 pancreaticoduodenectomies and 1 distal pancreatectomy). The complication rate was 24%, with an average length of stay of 13.5 days. There were no operative deaths. Pathologic analysis revealed clear margins in 16 (94%) of 17 and uninvolved lymph nodes in 11 (65%) of 17 specimens. One specimen contained no residual tumor, and three specimens revealed only microscopic foci of residual disease. With a median follow-up of 18 months, 7 (41%) of the 17 patients with resected disease are alive with no recurrence, 3 (18%) are alive with distant metastases, and 7 (41%) have died. 1
45. Varadhachary GR, Wolff RA, Crane CH, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3487-3495. Experimental-Tx 90 patients To report the results of a phase II trial of preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation (Gem-Cis- XRT) in stage I/II adenocarcinoma of the pancreatic head. The study enrolled 90 patients; 79 patients (88%) completed chemo-chemoradiation. Sixty-two (78%) of 79 patients were taken to surgery and 52 (66%) of 79 underwent PD. The median overall survival of all 90 patients was 17.4 months. Median survival for the 79 patients who completed chemo-chemoradiation was 18.7 months, with a median survival of 31 months for the 52 patients who underwent PD and 10.5 months for the 27 patients who did not undergo surgical resection of their primary tumor (P < .001). 1
46. White RR, Tyler DS. Neoadjuvant therapy for pancreatic cancer: the Duke experience. Surg Oncol Clin N Am. 2004;13(4):675-684, ix-x. Review/Other-Tx N/A To summarize the authors’ experience with neoadjuvant CRT over the past 10 years and how it has affected the management of patients with pancreatic cancer at Duke University Medical Center. No results stated in abstract. 4
47. Gillen S, Schuster T, Meyer Zum Buschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7(4):e1000267. Meta-analysis 111 studies; 4,394 patients To systematically review studies concerning the effects of neoadjuvant therapy on tumor response, toxicity, resection, and survival percentages in pancreatic cancer. A total of 111 studies (n = 4,394) including 56 phase I-II trials were analyzed. A median of 31 (interquartile range [IQR] 19-46) patients per study were included. Studies were subdivided into surveys considering initially resectable tumors (group 1) and initially non-resectable (borderline resectable/unresectable) tumors (group 2). Neoadjuvant chemotherapy was given in 96.4% of the studies with the main agents gemcitabine, 5-FU (and oral analogues), mitomycin C, and platinum compounds. Neoadjuvant radiotherapy was applied in 93.7% of the studies with doses ranging from 24 to 63 Gy. Averaged complete/partial response probabilities were 3.6% (95% CI 2%-5.5%)/30.6% (95% CI 20.7%-41.4%) and 4.8% (95% CI 3.5%-6.4%)/30.2% (95% CI 24.5%-36.3%) for groups 1 and 2, respectively; whereas progressive disease fraction was estimated to 20.9% (95% CI 16.9%-25.3%) and 20.8% (95% CI 14.5%-27.8%). In group 1, resectability was estimated to 73.6% (95% CI 65.9%-80.6%) compared to 33.2% (95% CI 25.8%-41.1%) in group 2. Higher resection-associated morbidity and mortality rates were observed in group 2 versus group 1 (26.7%, 95% CI 20.7%-33.3% versus 39.1%, 95% CI 29.5%-49.1%; and 3.9%, 95% CI 2.2%-6% versus 7.1%, 95% CI 5.1%-9.5%). Combination chemotherapies resulted in higher estimated response and resection probabilities for patients with initially non-resectable tumors ("non-resectable tumor patients") compared to monotherapy. Estimated median survival following resection was 23.3 (range 12-54) mo for group 1 and 20.5 (range 9-62) mo for group 2 patients. M
48. Hong TS, Ryan DP, Blaszkowsky LS, et al. Phase I study of preoperative short-course chemoradiation with proton beam therapy and capecitabine for resectable pancreatic ductal adenocarcinoma of the head. Int J Radiat Oncol Biol Phys. 2011;79(1):151-157. Experimental-Tx 15 patients To evaluate the safety of 1 week of chemoradiation with proton beam therapy and capecitabine followed by early surgery. 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. 2
49. Huguet F, Andre T, Hammel P, et al. Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. J Clin Oncol. 2007;25(3):326-331. Observational-Tx 181 patients To to assess whether initial CT effectively identified patients with rapidly progressing disease who were unlikely to benefit from radiotherapy and to evaluate the potential benefit of administering CRT after initial CT in patients whose disease had not progressed and who had an Eastern Cooperative Oncology Group performance status (PS) of less than 2. Median progression-free survival (PFS) and overall survival (OS) times for the 181 patients were 6.3 and 11.4 months, respectively. Fifty-three patients (29.3%) had metastatic disease after 3 months of CT and were not eligible for CRT. Among the 128 remaining patients (70.3%) who had no disease progression and who were, therefore, eligible for CRT, 72 (56%) received CRT (group A), whereas 56 (44%) continued with CT (group B). The two groups were balanced for initial characteristics (performance status, sex, age, and type of CT), as well as for induction CT results. In groups A and B, the median PFS times were 10.8 and 7.4 months, respectively (P = .005), and the median OS times were 15.0 and 11.7 months, respectively (P = .0009). 2
50. Krishnan S, Rana V, Janjan NA, et al. Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy. Cancer. 2007;110(1):47-55. Observational-Tx 323 patients To determine whether there were differences in outcome for patients with unresectable locally advanced pancreatic cancer (LAPC) who received treatment with chemoradiation therapy (CR) versus induction chemotherapy followed by CR (CCR). The median follow-up was 5.5 months (range, 1-63 months). For all patients, the median overall survival (OS) and progression-free survival (PFS) were 9 months and 5 months, respectively, and the 2-year estimated OS and PFS rates were 9% and 5%, respectively. The median OS and PFS were 8.5 months and 4.2 months, respectively, in the CR group and 11.9 months and 6.4 months, respectively, in the CCR group (both P < .001). The median times to local and distant progression were 6.0 months and 5.6 months, respectively, in the CR group and 8.9 and 9.5 months, respectively, in the CCR group (P = .003 and P = .007, respectively). There was no significant difference in the patterns of failure with the use of induction chemotherapy. 2
51. Louvet C, Labianca R, Hammel P, et al. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005;23(15):3509-3516. Experimental-Tx 313 patients To further explore the GemOx combination regimen and compare it to the standard Gem treatment in a phase III trial. Three hundred twenty-six patients were enrolled; 313 were eligible, and 157 and 156 were allocated to the GemOx and Gem arms, respectively. GemOx was superior to Gem in terms of response rate (26.8% v 17.3%, respectively; P = .04), progression-free survival (5.8 v 3.7 months, respectively; P = .04), and clinical benefit (38.2% v 26.9%, respectively; P = .03). Median overall survival (OS) for GemOx and Gem was 9.0 and 7.1 months, respectively (P = .13). GemOx was well tolerated overall, although a higher incidence of National Cancer Institute Common Toxicity Criteria grade 3 and 4 toxicity per patient was observed for platelets (14.0% for GemOx v 3.2% for Gem), vomiting (8.9% for GemOx v 3.2% for Gem), and neurosensory symptoms (19.1% for GemOx v 0% for Gem). 1
52. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691-1703. Experimental-Tx 861 patients To investigate the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer. A total of 861 patients were randomly assigned to nab-paclitaxel plus gemcitabine (431 patients) or gemcitabine (430). The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P<0.001). The survival rate was 35% in the nab-paclitaxel-gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4% at 2 years. The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group, as compared with 3.7 months in the gemcitabine group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.58 to 0.82; P<0.001); the response rate according to independent review was 23% versus 7% in the two groups (P<0.001). The most common adverse events of grade 3 or higher were neutropenia (38% in the nab-paclitaxel-gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%). Febrile neutropenia occurred in 3% versus 1% of the patients in the two groups. In the nab-paclitaxel-gemcitabine group, neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days. 1
53. Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261(1):12-17. Observational-Tx 188 patients 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. 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. 2