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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sudarshana Datta, MD [2]
In patients with pancreatic cancer, surgery is the primary modality of treatment.
Extrapancreatic disease requires palliative therapy and curative resection is not performed in such patients.Patients with unresectable disease are treated with chemotherapy and/or radiation therapy as a part of adjuvant or neoadjuvant therapy.
Curative resection is not contraindicated in all patients with vascular invasion.[1][2][3][4][5]
Involvement of the portal or superior mesenteric vein can be resected and reconstructed with the help of splenic, saphenous or internal jugular veins.[6][7][8][9] However, the involvement of arteries such as the hepatic, celiac or superior mesenteric are contraindications to resection.[10]
Various methods of surgical resection may be employed and each of these has its own sets of risks and perioperative complications. The facts are discussed by the patient and surgical team before arriving at a well-informed decision.
The method of surgical resection depends on the following features:[11]
- Locally invasive characteristics of the neoplasm
- Size
- Location
Methods of curative resection options include:
- Distal Pancreatectomy
- Total pancreatectomy
- Pancreaticoduodenectomy, where pylorus may or may not be spared on an individual basis
The National Comprehensive Cancer Network (NCCN) has recommended certain guidelines on resectability of pancreatic neoplasms based on a statement passed by the American pancreatic association:[12][13][14][15][16]
- Patient selection is based on:
- Resection margins
- High probability of cure
- Patient's age
- Comorbidities
European Society for Medical Oncology (ESMO) has certain guidelines on the treatment of metastatic pancreatic cancer:[17][18][19][18][18][18]
- Chemotherapy not preferred
- Gemcitabine is preferred over 5 FU
- Treatment is symptomatic with bypass surgery or stent placement for gastric outlet obstruction or obstructive jaundice
In case of locally advanced disease which is unresectable, the following methods of treatment are preferred:[20][20] Microwave ablation Photodynamic therapy Irreversible electroporation Photodynamic therapy High-intensity focused ultrasound (HIFU) Iodine-125–cryosurgery Iodine-125 Stereotactic body radiation therapy (SBRT) Radiofrequency ablation (RFA)
CHEMOTHERAPY
Metastatic disease/ Advanced pancreatic cancer which is unresectable:[21][22][23][24][25][26][27] The National Comprehensive Cancer Network (NCCN) has recommended guidelines for treatment in patients based on their performance status. In order to predict survival of patients in various stages of pancreatic cancer, the performance status of a patient is a major prognostic factor. Patients with poor prognostic factors have poor performance status. This includes-[28] Metastatic disease Large tumor Severe weight loss Therapy proposed for patients based on the resectability of disease and performance status is as follows:[29][30][31][32][33][34] In patients with locally advanced unresectable or metastatic disease with good performance status Preferred treatment: FOLFIRINOX[35][36][37][38][39][40][41][42][43][43][39][43] In patients with locally advanced unresectable or metastatic disease with good performance status with intolerance to FOLFIRINOX Preferred treatment:Paclitaxel protein bound+ Gemcitabine In patients with locally advanced unresectable or metastatic disease with poor performance status Preferred treatment: Gemcitabine monotherapy[44][45][46][47] In patients with locally advanced unresectable or metastatic disease with poor performance status refractory to Gemcitabine: Preferred treatment: Capecitabine or capecitabine+erlotinib[48] One year survival of FOLFIRINOX (leucovorin+5-lfuorouracil [LV5-FU]+oxaliplatin+irinotecan)>Gemcitabine[49][50][51][36][52][53][54] One year survival of Gemcitabine+ Erlotinib> Gemcitabine[55][56][26][26] One year survival of Gemcitabine+ Capecitabine≥Gemcitabine [57][58][59][30][60] One year survival of Gemcitabine+ nanoparticle albumin-bound (nab)-paclitaxel> Gemcitabine[61][62]
NEW TREATMENTS
Irinotecan in an encapsulated form inside a nanoliposome is being used in advanced pancreatic cancer patients who have been earlier been treated using gemcitabine-based chemotherapy. [63]
Liposomal Irinotecan is used along with leucovorin and fluorouracil.[64]
ADJUVANT THERAPY
The use of gemcitabine as adjuvant therapy is considered a standard form of therapy following surgical resection in pancreatic cancer patients.[65][66][67][68][69][70][71][72]
NEOADJUVANT THERAPY
Neoadjuvant therapy may be used as a form of therapy due to the following reasons:[73][74][75][76][23][39][77][59][32][78][79][80][81][82][39][23]
Toxic effects of chemotherapy can be tolerated more easily before surgery as compared to after resection
Shrinkage of tumor with neoadjuvant therapy makes resection easier and improves patient prognosis
Systemic treatment for cancer involving various systems improves prognosis
No therapy is considered as first line therapy under this category.Decisions for treatment are made on an individual basis.
SURGERY There are different surgical techniques that may be used for resectable pancreatic cancer and their prognosis has been extensively studied: [83][84][85][86][14][14][11][87][88][89][90][91][15] Pancreaticoduodenectomy (Whipple Procedure)[17][14][92] It is mainly performed for tumors located in: Periampullary region Duodenum Bile duct (Cholangiocarcinoma) Pancreatic duct Head of pancreas Whipple procedure involves removal of the following components due to common blood supply: Stomach antrum Gallbladder Duodenum Head of pancreas After removal of the above structures, the biliary and distal pancreatic ducts are anastomosed to the jejunum to facilitate surgical drainage. Biliary drainage may also be performed preoperatively.[93][93]
This procedure is associated with several morbidities:[94][95][96][97]
Postoperative abcess Wound infection[98] Anastomotic leak Delay in gastric emptying[99]
Pylorus sparing Whipple procedure: The pylorus may be spared as a modification of Whipple procedure to decrease gastric emptying due to antrectomy. This significantly reduces the incidence of nutritional deficiencies arising from this surgery.
The European Society for Medical Oncology states that the only curative therapy is surgical resection.
Ten percent is the five year survival of patients with pancreatic cancer.
Patients with node-positive tumors have very poor long term survival.
Distal Pancreatectomy [94] This procedure has a limited use in curative resection of pancreatic cancer. It is mainly performed for tumors located in: Body of pancreas Tail of pancreas This form of surgery has fewer morbidities than the Whipple procedure.
Distal Pancreatectomy involves the following components:
Separation of the distal pancreas bearing the tumor from the normal tissue Resection of the affected portion
Oversewing of the distal pancreatic duct
This procedure is associated with several morbidities:[100][101][102][103]
Pancreatic endocrine insufficiency Bleeding Leakage of pancreatic stump
It is the least preferred due to high mortality rate.
It is mainly performed for tumors located in:
Neck of the pancreas.
Due to involvement of neck, patients develop insulin dependent DM.
Lymphadnectomy
Removal of positive nodes is preferrable, but some surgeons advocate extended lymphadnectomy.
CA 19-9 level
Elevated levels of CA 19-9 can help in the following ways:[105]
Predicts the likelihood of complete resection
Prognosis of patients with resectable disease
Predicts the presence of occult metastases
However, CA 19-9 levels are not used to dictate the initial strategy for treatment of pancreatic cancer.
PALLIATIVE THERAPY
Pain There are various techniques for pain management as palliative therapy in patients:
Narcotic analgesics Narcotic analgesics+ tricyclic antidepressants/ antiemetics Endoscopic decompression with stent placement in patients with biliary or pancreatic duct obstruction Radiation therapy Neurolysis of the celiac ganglia by many approaches Intraoperative Transgastric Transthoracic Transabdominal
Jaundice Obstructive jaundice can present with features of cholangitis: Fever and chills Nausea, vomiting Clay-colored stools Dark urine Yellowish discoloration of skin Pruritus Right upper quadrant pain Anorexia Preferred treatment in patients: Endoscopic decompression with stent placement in patients with biliary obstruction Techniques of biliary decompression: Cholecystojejunostomy Choledochojejunostomy
Types of stents: Metal- costly, longer lifespan Plastic- cheaper, need replacement every three months
Duodenal obstruction Preferred treatment: Endoscopic stenting of duodenal obstruction Gastrojejunostomy
- ↑ Al-Haddad M, Martin JK, Nguyen J, Pungpapong S, Raimondo M, Woodward T, Kim G, Noh K, Wallace MB (2007). "Vascular resection and reconstruction for pancreatic malignancy: a single center survival study". J. Gastrointest. Surg. 11 (9): 1168–74. doi:10.1007/s11605-007-0216-x. PMID 17632763.
- ↑ Donahue TR, Isacoff WH, Hines OJ, Tomlinson JS, Farrell JJ, Bhat YM, Garon E, Clerkin B, Reber HA (2011). "Downstaging chemotherapy and alteration in the classic computed tomography/magnetic resonance imaging signs of vascular involvement in patients with pancreaticobiliary malignant tumors: influence on patient selection for surgery". Arch Surg. 146 (7): 836–43. doi:10.1001/archsurg.2011.152. PMID 21768431.
- ↑ Tseng JF, Raut CP, Lee JE, Pisters PW, Vauthey JN, Abdalla EK, Gomez HF, Sun CC, Crane CH, Wolff RA, Evans DB (2004). "Pancreaticoduodenectomy with vascular resection: margin status and survival duration". J. Gastrointest. Surg. 8 (8): 935–49, discussion 949–50. doi:10.1016/j.gassur.2004.09.046. PMID 15585381.
- ↑ Martin RC, Scoggins CR, Egnatashvili V, Staley CA, McMasters KM, Kooby DA (2009). "Arterial and venous resection for pancreatic adenocarcinoma: operative and long-term outcomes". Arch Surg. 144 (2): 154–9. doi:10.1001/archsurg.2008.547. PMID 19221327.
- ↑ Castleberry AW, White RR, De La Fuente SG, Clary BM, Blazer DG, McCann RL, Pappas TN, Tyler DS, Scarborough JE (2012). "The impact of vascular resection on early postoperative outcomes after pancreaticoduodenectomy: an analysis of the American College of Surgeons National Surgical Quality Improvement Program database". Ann. Surg. Oncol. 19 (13): 4068–77. doi:10.1245/s10434-012-2585-y. PMID 22932857.
- ↑ Leach SD, Lee JE, Charnsangavej C, Cleary KR, Lowy AM, Fenoglio CJ, Pisters PW, Evans DB (1998). "Survival following pancreaticoduodenectomy with resection of the superior mesenteric-portal vein confluence for adenocarcinoma of the pancreatic head". Br J Surg. 85 (5): 611–7. doi:10.1046/j.1365-2168.1998.00641.x. PMID 9635805.
- ↑ Fuhrman GM, Leach SD, Staley CA, Cusack JC, Charnsangavej C, Cleary KR, El-Naggar AK, Fenoglio CJ, Lee JE, Evans DB (1996). "Rationale for en bloc vein resection in the treatment of pancreatic adenocarcinoma adherent to the superior mesenteric-portal vein confluence. Pancreatic Tumor Study Group". Ann. Surg. 223 (2): 154–62. PMC 1235091. PMID 8597509.
- ↑ Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N, Nakagawa N, Sueda T (2013). "Benefit of portal or superior mesenteric vein resection with adjuvant chemotherapy for patients with pancreatic head carcinoma". J Surg Oncol. 107 (4): 414–21. doi:10.1002/jso.23229. PMID 22886567.
- ↑ Ramacciato G, Mercantini P, Petrucciani N, Giaccaglia V, Nigri G, Ravaioli M, Cescon M, Cucchetti A, Del Gaudio M (2009). "Does portal-superior mesenteric vein invasion still indicate irresectability for pancreatic carcinoma?". Ann. Surg. Oncol. 16 (4): 817–25. doi:10.1245/s10434-008-0281-8. PMID 19156463.
- ↑ Mollberg N, Rahbari NN, Koch M, Hartwig W, Hoeger Y, Büchler MW, Weitz J (2011). "Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis". Ann. Surg. 254 (6): 882–93. doi:10.1097/SLA.0b013e31823ac299. PMID 22064622.
- ↑ 11.0 11.1 Ryan DP, Hong TS, Bardeesy N (2014). "Pancreatic adenocarcinoma". N. Engl. J. Med. 371 (11): 1039–49. doi:10.1056/NEJMra1404198. PMID 25207767.
- ↑ Fonseca AL, Fleming JB (2017). "Surgery for pancreatic cancer: critical radiologic findings for clinical decision making". Abdom Radiol (NY). doi:10.1007/s00261-017-1332-z. PMID 28948329.
- ↑ Al-Hawary MM, Francis IR, Chari ST, Fishman EK, Hough DM, Lu DS, Macari M, Megibow AJ, Miller FH, Mortele KJ, Merchant NB, Minter RM, Tamm EP, Sahani DV, Simeone DM (2014). "Pancreatic ductal adenocarcinoma radiology reporting template: consensus statement of the Society of Abdominal Radiology and the American Pancreatic Association". Radiology. 270 (1): 248–60. doi:10.1148/radiol.13131184. PMID 24354378.
- ↑ 14.0 14.1 14.2 14.3 Khorana AA, Mangu PB, Berlin J, Engebretson A, Hong TS, Maitra A, Mohile SG, Mumber M, Schulick R, Shapiro M, Urba S, Zeh HJ, Katz MH (2016). "Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline". J. Clin. Oncol. 34 (21): 2541–56. doi:10.1200/JCO.2016.67.5553. PMID 27247221.
- ↑ 15.0 15.1 Yamada S, Fujii T, Sugimoto H, Nomoto S, Takeda S, Kodera Y, Nakao A (2013). "Aggressive surgery for borderline resectable pancreatic cancer: evaluation of National Comprehensive Cancer Network guidelines". Pancreas. 42 (6): 1004–10. doi:10.1097/MPA.0b013e31827b2d7c. PMID 23532000.
- ↑ Balaban EP, Mangu PB, Khorana AA, Shah MA, Mukherjee S, Crane CH, Javle MM, Eads JR, Allen P, Ko AH, Engebretson A, Herman JM, Strickler JH, Benson AB, Urba S, Yee NS (2016). "Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline". J. Clin. Oncol. 34 (22): 2654–68. doi:10.1200/JCO.2016.67.5561. PMID 27247216.
- ↑ 17.0 17.1 Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goéré D, Seufferlein T, Haustermans K, Van Laethem JL, Conroy T, Arnold D (2015). "Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up". Ann. Oncol. 26 Suppl 5: v56–68. doi:10.1093/annonc/mdv295. PMID 26314780.
- ↑ 18.0 18.1 18.2 18.3 Seufferlein T, Bachet JB, Van Cutsem E, Rougier P (2012). "Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up". Ann. Oncol. 23 Suppl 7: vii33–40. doi:10.1093/annonc/mds224. PMID 22997452.
- ↑ Evans DB, George B, Tsai S (2015). "Non-metastatic Pancreatic Cancer: Resectable, Borderline Resectable, and Locally Advanced-Definitions of Increasing Importance for the Optimal Delivery of Multimodality Therapy". Ann. Surg. Oncol. 22 (11): 3409–13. doi:10.1245/s10434-015-4649-2. PMID 26122369.
- ↑ 20.0 20.1 Rombouts SJ, Vogel JA, van Santvoort HC, van Lienden KP, van Hillegersberg R, Busch OR, Besselink MG, Molenaar IQ (2015). "Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer". Br J Surg. 102 (3): 182–93. doi:10.1002/bjs.9716. PMID 25524417.
- ↑ Irigoyen A, Gallego J, Guillén Ponce C, Vera R, Iranzo V, Ales I, Arévalo S, Pisa A, Martín M, Salud A, Falcó E, Sáenz A, Manzano Mozo JL, Pulido G, Martínez Galán J, Pazo-Cid R, Rivera F, García García T, Serra O, Fernández Parra EM, Hurtado A, Gómez Reina MJ, López Gomez LJ, Martínez Ortega E, Benavides M, Aranda E (2017). "Gemcitabine-erlotinib versus gemcitabine-erlotinib-capecitabine in the first-line treatment of patients with metastatic pancreatic cancer: Efficacy and safety results of a phase IIb randomised study from the Spanish TTD Collaborative Group". Eur. J. Cancer. 75: 73–82. doi:10.1016/j.ejca.2016.12.032. PMID 28222309.
- ↑ Middleton G, Palmer DH, Greenhalf W, Ghaneh P, Jackson R, Cox T, Evans A, Shaw VE, Wadsley J, Valle JW, Propper D, Wasan H, Falk S, Cunningham D, Coxon F, Ross P, Madhusudan S, Wadd N, Corrie P, Hickish T, Costello E, Campbell F, Rawcliffe C, Neoptolemos JP (2017). "Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial". Lancet Oncol. 18 (4): 486–499. doi:10.1016/S1470-2045(17)30084-0. PMID 28259610.
- ↑ 23.0 23.1 23.2 Xia BT, Fu B, Wang J, Kim Y, Ahmad SA, Dhar VK, Levinsky NC, Hanseman DJ, Habib DA, Wilson GC, Smith M, Olowokure OO, Kharofa J, Al Humaidi AH, Choe KA, Abbott DE, Ahmad SA (2017). "Does radiologic response correlate to pathologic response in patients undergoing neoadjuvant therapy for borderline resectable pancreatic malignancy?". J Surg Oncol. 115 (4): 376–383. doi:10.1002/jso.24538. PMID 28105634.
- ↑ Choi SJ, Kim HJ, Kim JS, Bak YT, Kim JS (2016). "Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report". BMC Cancer. 16: 588. doi:10.1186/s12885-016-2616-3. PMC 4971692. PMID 27484349.
- ↑ Wang Y, Hu GF, Zhang QQ, Tang N, Guo J, Liu LY, Han X, Wang X, Wang ZH (2016). "Efficacy and safety of gemcitabine plus erlotinib for locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis". Drug Des Devel Ther. 10: 1961–72. doi:10.2147/DDDT.S105442. PMC 4912328. PMID 27358556.
- ↑ 26.0 26.1 26.2 Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C (2016). "Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial". JAMA. 315 (17): 1844–53. doi:10.1001/jama.2016.4324. PMID 27139057.
- ↑ Chen J, Kaley K, Garcon MC, Rodriguez T, Saif MW (2016). "A novel schedule of erlotinib/capecitabine (7/7) as salvage therapy in previously treated advanced pancreatic adenocarcinoma: a case series". Therap Adv Gastroenterol. 9 (2): 162–8. doi:10.1177/1756283X15622779. PMC 4749861. PMID 26929778.
- ↑ Tas F, Sen F, Odabas H, Kılıc L, Keskın S, Yıldız I (2013). "Performance status of patients is the major prognostic factor at all stages of pancreatic cancer". Int. J. Clin. Oncol. 18 (5): 839–46. doi:10.1007/s10147-012-0474-9. PMID 22996141.
- ↑ Brasiūniene B, Juozaityte E (2007). "The effect of combined treatment methods on survival and toxicity in patients with pancreatic cancer". Medicina (Kaunas). 43 (9): 716–25. PMID 17986845.
- ↑ 30.0 30.1 Mukherjee S, Hurt CN, Bridgewater J, Falk S, Cummins S, Wasan H, Crosby T, Jephcott C, Roy R, Radhakrishna G, McDonald A, Ray R, Joseph G, Staffurth J, Abrams RA, Griffiths G, Maughan T (2013). "Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial". Lancet Oncol. 14 (4): 317–26. doi:10.1016/S1470-2045(13)70021-4. PMC 3620899. PMID 23474363.
- ↑ Hurt CN, Falk S, Crosby T, McDonald A, Ray R, Joseph G, Staffurth J, Abrams RA, Griffiths G, Maughan T, Mukherjee S (2017). "Long-term results and recurrence patterns from SCALOP: a phase II randomised trial of gemcitabine- or capecitabine-based chemoradiation for locally advanced pancreatic cancer". Br. J. Cancer. 116 (10): 1264–1270. doi:10.1038/bjc.2017.95. PMC 5482737. PMID 28376080.
- ↑ 32.0 32.1 Huguet F, Girard N, Guerche CS, Hennequin C, Mornex F, Azria D (2009). "Chemoradiotherapy in the management of locally advanced pancreatic carcinoma: a qualitative systematic review". J. Clin. Oncol. 27 (13): 2269–77. doi:10.1200/JCO.2008.19.7921. PMID 19307501.
- ↑ Hazel JJ, Thirlwell MP, Huggins M, Maksymiuk A, MacFarlane JK (1981). "Multi-drug chemotherapy with and without radiation for carcinoma of the stomach and pancreas: a prospective randomized trial". J Can Assoc Radiol. 32 (3): 164–5. PMID 7028759.
- ↑ Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouché O, Bosset JF, Aparicio T, Mineur L, Azzedine A, Hammel P, Butel J, Stremsdoerfer N, Maingon P, Bedenne L (2008). "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. 19 (9): 1592–9. doi:10.1093/annonc/mdn281. PMID 18467316.
- ↑ Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa-Akouz F, Péré-Vergé D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M (2011). "FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer". N. Engl. J. Med. 364 (19): 1817–25. doi:10.1056/NEJMoa1011923. PMID 21561347.
- ↑ 36.0 36.1 Peddi PF, Lubner S, McWilliams R, Tan BR, Picus J, Sorscher SM, Suresh R, Lockhart AC, Wang J, Menias C, Gao F, Linehan D, Wang-Gillam A (2012). "Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma". JOP. 13 (5): 497–501. PMID 22964956.
- ↑ Marthey L, Sa-Cunha A, Blanc JF, Gauthier M, Cueff A, Francois E, Trouilloud I, Malka D, Bachet JB, Coriat R, Terrebonne E, De La Fouchardière C, Manfredi S, Solub D, Lécaille C, Thirot Bidault A, Carbonnel F, Taieb J (2015). "FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicenter prospective observational cohort". Ann. Surg. Oncol. 22 (1): 295–301. doi:10.1245/s10434-014-3898-9. PMID 25037971.
- ↑ Blazer M, Wu C, Goldberg RM, Phillips G, Schmidt C, Muscarella P, Wuthrick E, Williams TM, Reardon J, Ellison EC, Bloomston M, Bekaii-Saab T (2015). "Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas". Ann. Surg. Oncol. 22 (4): 1153–9. doi:10.1245/s10434-014-4225-1. PMC 4373613. PMID 25358667.
- ↑ 39.0 39.1 39.2 39.3 Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, Sabbatino F, Santos DD, Allen JN, Blaszkowsky LS, Clark JW, Faris JE, Goyal L, Kwak EL, Murphy JE, Ting DT, Wo JY, Zhu AX, Warshaw AL, Lillemoe KD, Fernández-del Castillo C (2015). "Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer". Ann. Surg. 261 (1): 12–7. doi:10.1097/SLA.0000000000000867. PMC 4349683. PMID 25599322.
- ↑ Mellon EA, Hoffe SE, Springett GM, Frakes JM, Strom TJ, Hodul PJ, Malafa MP, Chuong MD, Shridhar R (2015). "Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma". Acta Oncol. 54 (7): 979–85. doi:10.3109/0284186X.2015.1004367. PMID 25734581.
- ↑ Sadot E, Doussot A, O'Reilly EM, Lowery MA, Goodman KA, Do RK, Tang LH, Gönen M, D'Angelica MI, DeMatteo RP, Kingham TP, Jarnagin WR, Allen PJ (2015). "FOLFIRINOX Induction Therapy for Stage 3 Pancreatic Adenocarcinoma". Ann. Surg. Oncol. 22 (11): 3512–21. doi:10.1245/s10434-015-4647-4. PMC 4849545. PMID 26065868.
- ↑ Stein SM, James ES, Deng Y, Cong X, Kortmansky JS, Li J, Staugaard C, Indukala D, Boustani AM, Patel V, Cha CH, Salem RR, Chang B, Hochster HS, Lacy J (2016). "Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer". Br. J. Cancer. 114 (7): 737–43. doi:10.1038/bjc.2016.45. PMC 4984865. PMID 27022826.
- ↑ 43.0 43.1 43.2 Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, El-Rayes BF, Wang-Gillam A, Lacy J, Hosein PJ, Moorcraft SY, Conroy T, Hohla F, Allen P, Taieb J, Hong TS, Shridhar R, Chau I, van Eijck CH, Koerkamp BG (2016). "FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis". Lancet Oncol. 17 (6): 801–810. doi:10.1016/S1470-2045(16)00172-8. PMC 5527756. PMID 27160474.
- ↑ Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A (2005). "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. 23 (15): 3509–16. doi:10.1200/JCO.2005.06.023. PMID 15908661.
- ↑ Van Cutsem E, van de Velde H, Karasek P, Oettle H, Vervenne WL, Szawlowski A, Schoffski P, Post S, Verslype C, Neumann H, Safran H, Humblet Y, Perez Ruixo J, Ma Y, Von Hoff D (2004). "Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer". J. Clin. Oncol. 22 (8): 1430–8. doi:10.1200/JCO.2004.10.112. PMID 15084616.
- ↑ Rocha Lima CM, Green MR, Rotche R, Miller WH, Jeffrey GM, Cisar LA, Morganti A, Orlando N, Gruia G, Miller LL (2004). "Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate". J. Clin. Oncol. 22 (18): 3776–83. doi:10.1200/JCO.2004.12.082. PMID 15365074.
- ↑ Ishii H, Furuse J, Boku N, Okusaka T, Ikeda M, Ohkawa S, Fukutomi A, Hamamoto Y, Nakamura K, Fukuda H (2010). "Phase II study of gemcitabine chemotherapy alone for locally advanced pancreatic carcinoma: JCOG0506". Jpn. J. Clin. Oncol. 40 (6): 573–9. doi:10.1093/jjco/hyq011. PMID 20185458.
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