{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T11:19:40Z","timestamp":1768994380597,"version":"3.49.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>To assess the dosimetric feasibility of a stereotactic body radiotherapy (SBRT) dose escalated protocol, with a simultaneous integrated boost (SIB) and a simultaneous integrated protection (SIP) approach, in patients with locally advanced pancreatic cancer (LAPC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>Twenty LAPC lesions, previously treated with SBRT at our Institution, were re-planned. The original prescribed and administered dose was 50\/30\/25 Gy in five fractions to PTV<jats:sub>sib<\/jats:sub> (tumor-vessel interface [TVI])\/PTV<jats:sub>t<\/jats:sub> (tumor volume)\/PTV<jats:sub>sip<\/jats:sub> (overlap area between PTV<jats:sub>t<\/jats:sub> and planning organs at risk volume [PRV<jats:sub>oars<\/jats:sub>]), respectively. At re-planning, the prescribed dose was escalated up to 60\/40\/33 Gy in five fractions to PTV<jats:sub>sib<\/jats:sub>\/PTV<jats:sub>t<\/jats:sub>\/PTV<jats:sub>sip<\/jats:sub>, respectively. All plans were performed using an inspiration breath hold (IBH) technique and generated with volumetric modulated arc therapy (VMAT). Well-established and accepted OAR dose constraints were used (D<jats:sub>0.5cc<\/jats:sub> &amp;lt; 33 Gy for luminal OARs and D<jats:sub>0.5cc<\/jats:sub> &amp;lt; 38 Gy for corresponding PRV<jats:sub>oars<\/jats:sub>). The primary end-point was to achieve a median dose equal to the prescription dose for the PTV<jats:sub>sib<\/jats:sub> with D<jats:sub>98<\/jats:sub>\u2265 95% (95% of prescription dose is the minimum dose), and a coverage for PTV<jats:sub>t<\/jats:sub> and PTV<jats:sub>sip<\/jats:sub> of D<jats:sub>95<\/jats:sub>\u226595%, with minor deviations in OAR dose constraints in &amp;lt; 10% of the plans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PTV<jats:sub>sib<\/jats:sub> median (\u00b1 SD) dose\/D<jats:sub>95<\/jats:sub>\/conformity index (CI) were 60.54 (\u00b1 0.85) Gy\/58.96 (\u00b1 0.86) Gy\/0.99 (\u00b1 0.01), respectively; whilst PTV<jats:sub>t<\/jats:sub> median (\u00b1 SD) dose\/D<jats:sub>95<\/jats:sub> were 44.51 (\u00b1 2.69) Gy\/38.44 (\u00b1 0.82) Gy, and PTV<jats:sub>sip<\/jats:sub> median (\u00b1 SD) dose\/D<jats:sub>95<\/jats:sub> were 35.18 (\u00b1 1.42) Gy\/33.01 (\u00b1 0.84) Gy, respectively. With regard to OARs, median (\u00b1 SD) maximum dose (D<jats:sub>0.5cc<\/jats:sub>) to duodenum\/stomach\/bowel was 29.31 (\u00b1 5.72) Gy\/25.29 (\u00b1 6.90) Gy\/27.03 (\u00b1 5.67) Gy, respectively. A minor acceptable deviation was found for a single plan (bowel and duodenum D<jats:sub>0.5cc<\/jats:sub>=34.8 Gy). V38 &amp;lt; 0.5 cc was achieved for all PRV luminal OARs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In LAPC patients SBRT, with a SIB\/SIP dose escalation approach up to 60\/40\/33 Gy in five fractions to PTV<jats:sub>sib<\/jats:sub>\/PTV<jats:sub>t<\/jats:sub>\/PTV<jats:sub>sip<\/jats:sub>, respectively, is dosimetrically feasible with adequate PTVs coverage and respect for OAR dose constraints.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2020.600940","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T12:19:03Z","timestamp":1608207543000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Dosimetric Feasibility Study of Dose Escalated Stereotactic Body Radiation Therapy (SBRT) in Locally Advanced Pancreatic Cancer (LAPC) Patients: It Is Time to Raise the Bar"],"prefix":"10.3389","volume":"10","author":[{"given":"Renzo","family":"Mazzarotto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Simoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Guariglia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renato","family":"Micera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"De Robertis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Pierelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuele","family":"Zivelonghi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Malleo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Paiella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Salvia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Cavedon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Milella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Bassi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.4324","article-title":"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","volume":"315","author":"Hammel","year":"2016","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/80.10.751","article-title":"Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone","volume":"80","year":"1988","journal-title":"J Natl Cancer Inst"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.34.8904","article-title":"Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial","volume":"29","author":"Loehrer","year":"2011","journal-title":"J Clin Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1985.3.3.373","article-title":"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\u2014an Eastern Cooperative Oncology Group study","volume":"3","author":"Klaassen","year":"1985","journal-title":"J Clin Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdn281","article-title":"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\u201301 FFCD\/SFRO study","volume":"19","author":"Chauffert","year":"2008","journal-title":"Ann Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.17.7188","article-title":"DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer","volume":"27","author":"Iacobuzio-Donahue","year":"2009","journal-title":"J Clin Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.33.8038","article-title":"Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression","volume":"29","author":"Crane","year":"2011","journal-title":"J Clin Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30856","article-title":"Stereotactic body radiotherapy for unresected pancreatic cancer: A nationwide review","volume":"123","author":"de Geus","year":"2017","journal-title":"Cancer"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30706","article-title":"Outcomes for patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiation therapy versus conventionally fractionated radiation","volume":"123","author":"Zhong","year":"2017","journal-title":"Cancer"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32756","article-title":"Conventionally fractionated radiation therapy versus stereotactic body radiation therapy for locally advanced pancreatic cancer\u00a0(CRiSP): An international systematic review and meta-analysis","volume":"126","author":"Tchelebi","year":"2020","journal-title":"Cancer"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.13975","article-title":"Higher Biologically Effective Dose Predicts Survival in SBRT of Pancreatic Cancer: A Multicentric Analysis (PAULA-1)","volume":"40","author":"Arcelli","year":"2020","journal-title":"Anticancer Res"},{"key":"B12","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1186\/1748-717X-8-254","article-title":"Pathologic response with neoadjuvant chemotherapy and stereotactic body radiotherapy for borderline resectable and locally-advanced pancreatic cancer","volume":"8","author":"Rajagopalan","year":"2013","journal-title":"Radiat Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-014-4274-5","article-title":"The Role of Stereotactic Body Radiation Therapy for Pancreatic Cancer: A Single-Institution Experience","volume":"22","author":"Moningi","year":"2015","journal-title":"Ann Surg Oncol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"100200","DOI":"10.1016\/j.eclinm.2019.10.013","article-title":"Efficacy and feasibility of stereotactic radiotherapy after folfirinox in patients with locally advanced pancreatic cancer (LAPC-1 trial)","volume":"19","author":"Suker","year":"2019","journal-title":"EClinicalMedicine"},{"key":"B15","first-page":"S0936","article-title":"Hypofractionated Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost and Simultaneous Integrated Protection in Pancreatic Ductal Adenocarcinoma","volume-title":"Clin Oncol (R Coll Radiol)","author":"Simoni","year":"2020"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.prro.2019.07.018","article-title":"Australasian Gastrointestinal Trials Group (AGITG) and Trans-Tasman Radiation Oncology Group (TROG) Guidelines for Pancreatic Stereotactic Body Radiation Therapy (SBRT)","volume":"10","author":"Oar","year":"2020","journal-title":"Pract Radiat Oncol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.adro.2018.07.008","article-title":"Dose escalation for locally advanced pancreatic cancer: How high can we go","volume":"3","author":"Colbert","year":"2018","journal-title":"Adv Radiat Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.prro.2019.06.016","article-title":"Radiation Therapy for Pancreatic Cancer: Executive Summary of an ASTRO Clinical Practice Guideline","volume":"9","author":"Palta","year":"2019","journal-title":"Pract Radiat Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.prro.2019.11.005","article-title":"Pancreas SBRT: Who, What, When, Where, and How\u2026","volume":"10","author":"Bernard","year":"2020","journal-title":"Pract Radiat Oncol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1001\/jamasurg.2019.2278","article-title":"Outcomes of Primary Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma","volume":"154","author":"Maggino","year":"2019","journal-title":"JAMA Surg"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.prro.2019.06.016","article-title":"The effectiveness of a pneumatic compression belt in reducing respiratory motion of abdominal tumors in patients undergoing stereotactic body radiation","volume":"13","author":"Lovelock","year":"2004","journal-title":"Technol Cancer Res Treat"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2017.05.013","article-title":"An evaluation of motion mitigation techniques for pancreatic SBRT","volume":"124","author":"Campbell","year":"2017","journal-title":"Radiother Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.prro.2019.10.012","article-title":"Setup Management for Stereotactic Body Radiation Therapy of Patients With Pancreatic Cancer Treated via the Breath-Hold Technique","volume":"10","author":"Forbang Teboh","year":"2020","journal-title":"Pract Radiat Oncol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1002\/acm2.12693","article-title":"Evaluation of the effects of motion mitigation strategies on respiration-induced motion in each pancreatic region using cine-magnetic resonance imaging","volume":"20","author":"Fujimoto","year":"2019","journal-title":"J Appl Clin Med Phys"},{"key":"B25","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.tipsro.2020.06.001","article-title":"On-line adaptive MR guided radiotherapy for locally advanced pancreatic cancer: Clinical and dosimetric considerations","volume":"15","author":"Placidi","year":"2020","journal-title":"Tech Innov Patient Support Radiat Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2013.02.022","article-title":"Stereotactic body radiation therapy for locally advanced and borderline resectable pancreatic cancer is effective and well tolerated","volume":"86","author":"Chuong","year":"2013","journal-title":"Int J Radiat Oncol Bio Phys"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3109\/0284186X.2015.1004367","article-title":"Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma","volume":"54","author":"Mellon","year":"2015","journal-title":"Acta Oncol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.ijrobp.2016.05.010","article-title":"A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458)","volume":"96","author":"Shaib","year":"2016","journal-title":"Int J Radiat Oncol Bio Phys"},{"key":"B29","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1186\/s12885-016-2765-4","article-title":"A phase-I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the \u2018SPARC\u2019 trial protocol","volume":"16","author":"Holyoake","year":"2016","journal-title":"BMC Cancer"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1097\/COC.0000000000000518","article-title":"Pattern of marginal local failure in a phase ii trial of neoadjuvant chemotherapy and stereotactic body radiation therapy for resectable and borderline resectable pancreas cancer","volume":"42","author":"Kharofa","year":"2019","journal-title":"Am J Clin Oncol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"S1879","DOI":"10.1016\/j.prro.2020.01.012","article-title":"Dose-Escalated Radiation Therapy for Pancreatic Cancer: A Simultaneous Integrated Boost Approach","volume":"13","author":"Koay","year":"2020","journal-title":"Pract Radiat Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1080\/0284186X.2018.1546899","article-title":"Magnetic resonance imaging (MRI) compared with computed tomography (CT) for interobserver agreement of gross tumor volume delineation in pancreatic cancer: a multi-institutional contouring study on behalf of the AIRO group for gastrointestinal cancers","volume":"58","author":"Caravatta","year":"2019","journal-title":"Acta Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2020.600940\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T12:19:06Z","timestamp":1608207546000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2020.600940\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,17]]},"references-count":32,"alternative-id":["10.3389\/fonc.2020.600940"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2020.600940","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,17]]},"article-number":"600940"}}