{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:09:27Z","timestamp":1792696167828,"version":"4.5.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010441","name":"Medizinischen Fakult\u00e4t Heidelberg, Universit\u00e4t Heidelberg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010441","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Effective treatment strategies for unresectable locally advanced pancreatic cancer (LAPC) patients are eagerly warranted. Recently, convincing oncological outcomes were demonstrated by carbon ion radiotherapy. Nevertheless, there is a lack of evidence for this modern radiation technique due to the limited number of carbon ion facilities worldwide. Here, we analyze feasibility and efficacy of carbon ion radiotherapy in the management of LAPC at Heidelberg Ion Beam Therapy Center (HIT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Between 2015 and 2020, 21 LAPC patients were irradiated with carbon ions with a total dose of 48 Gy (RBE) in single doses of 4 Gy (RBE). Three patients (14%) were treated with concomitant chemotherapy with gemcitabine 300 mg\/m<jats:sup>2<\/jats:sup> body surface weekly. Toxicity rates were extracted from the charts. Overall survival, progression free survival, local control, and locoregional control were evaluated using Kaplan\u2013Meier estimates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One patient developed ascites CTCAE grade III during radiotherapy, which was related to a later histologically confirmed metachronous peritoneal carcinomatosis. No further higher-graded toxicity could be observed. The most common symptoms were nausea and abdominal pain. After a median estimated follow-up time of 19.1 months, the median progression free survival was 3.7 months, and the median overall survival was 11.9 months. The estimated 1-year local control and locoregional control rates were 89 and 84%, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Carbon ion radiotherapy of LAPC patients is safely feasible. Local tumor control rates were high. Nevertheless, compared to historical data, an overall survival improvement could not be observed. This could be explained by the poor prognosis of the selected underlying patients that mostly did not respond to prior chemotherapy as well as the early and frequent emergence of distant metastases that demonstrate the necessity of additional chemotherapy in further studies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2021.708884","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T11:12:58Z","timestamp":1626261178000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Effectiveness of Carbon Ion Radiation in Locally Advanced Pancreatic Cancer"],"prefix":"10.3389","volume":"11","author":[{"given":"Jakob","family":"Liermann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Naumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Weykamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Hoegen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Debus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Herfarth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.14740\/wjon1166","article-title":"Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors","volume":"10","author":"Rawla","year":"2019","journal-title":"World J Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00595-007-3745-8","article-title":"Surgery Versus Radiochemotherapy for Resectable Locally Invasive Pancreatic Cancer: Final Results of a Randomized Multi-Institutional Trial","volume":"38","author":"Doi","year":"2008","journal-title":"Surg Today"},{"key":"B3","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":"B4","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":"B5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.07.5663","article-title":"Impact of Chemoradiotherapy After Disease Control With Chemotherapy in Locally Advanced Pancreatic Adenocarcinoma in GERCOR Phase II and III Studies","volume":"25","author":"Huguet","year":"2007","journal-title":"J Clin Oncol"},{"key":"B6","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":"B7","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. Gastrointestinal Tumor Study Group","volume":"80","year":"1988","journal-title":"J Natl Cancer Inst"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)00172-8","article-title":"FOLFIRINOX for Locally Advanced Pancreatic Cancer: a Systematic Review and Patient-Level Meta-Analysis","volume":"17","author":"Suker","year":"2016","journal-title":"Lancet Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2009.05.071","article-title":"Radiation Dose-Volume Effects in the Stomach and Small Bowel","volume":"76","author":"Kavanagh","year":"2010","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2009.07.1754","article-title":"Use of Normal Tissue Complication Probability Models in the Clinic","volume":"76","author":"Marks","year":"2010","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2005.07.002","article-title":"Phase II Study to Assess the Efficacy of Conventionally Fractionated Radiotherapy Followed by a Stereotactic Radiosurgery Boost in Patients With Locally Advanced Pancreatic Cancer","volume":"63","author":"Koong","year":"2005","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2020.05.012","article-title":"Carbon Ion Radiotherapy in Pancreatic Cancer: A Review of Clinical Data","volume":"147","author":"Liermann","year":"2020","journal-title":"Radiother Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.21037\/jgo.2019.03.02","article-title":"Proton Beam Radiotherapy for Pancreas Cancer","volume":"11","author":"Rutenberg","year":"2020","journal-title":"J Gastrointest Oncol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2018.05.048","article-title":"MR-Guided Gated Stereotactic Radiation Therapy Delivery for Lung, Adrenal, and Pancreatic Tumors: a Geometric Analysis","volume":"102","author":"van Sornsen de Koste","year":"2018","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B15","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.ijrobp.2015.12.362","article-title":"Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer","volume":"95","author":"Shinoto","year":"2016","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2004.09.008","article-title":"The Centenary of the Discovery of the Bragg Peak","volume":"73","author":"Brown","year":"2004","journal-title":"Radiother Oncol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.radonc.2010.01.015","article-title":"Proton vs Carbon Ion Beams in the Definitive Radiation Treatment of Cancer Patients","volume":"95","author":"Suit","year":"2010","journal-title":"Radiother Oncol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/1748-717X-9-88","article-title":"Bringing the Heavy: Carbon Ion Therapy in the Radiobiological and Clinical Context","volume":"9","author":"Schlaff","year":"2014","journal-title":"Radiat Oncol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"01TR02","DOI":"10.1088\/1361-6560\/aa9102","article-title":"RBE and Related Modeling in Carbon-Ion Therapy","volume":"63","author":"Karger","year":"2017","journal-title":"Phys Med Biol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2012.01.038","article-title":"Mapping of RBE-Weighted Doses Between HIMAC- and LEM-Based Treatment Planning Systems for Carbon Ion Therapy","volume":"84","author":"Steinstrater","year":"2012","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B21","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1186\/s12885-020-07434-8","article-title":"Carbon Ion Radiotherapy as Definitive Treatment in non-Metastasized Pancreatic Cancer: Study Protocol of the Prospective Phase II PACK-Study","volume":"20","author":"Liermann","year":"2020","journal-title":"BMC Cancer"},{"key":"B22","doi-asserted-by":"publisher","first-page":"796","DOI":"10.3390\/cancers13040796","article-title":"Impact of FAPI-PET\/CT on Target Volume Definition in Radiation Therapy of Locally Recurrent Pancreatic Cancer","volume":"13","author":"Liermann","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1991.9.1.191","article-title":"Median Follow-Up in Clinical Trials","volume":"9","author":"Shuster","year":"1991","journal-title":"J Clin Oncol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2018.08.026","article-title":"A Single Institutional Experience of Combined Carbon-Ion Radiotherapy and Chemotherapy for Unresectable Locally Advanced Pancreatic Cancer","volume":"129","author":"Shinoto","year":"2018","journal-title":"Radiother Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2018.04.057","article-title":"Multi-Institutional Study of Carbon-Ion Radiotherapy for Locally Advanced Pancreatic Cancer: Japan Carbon-Ion Radiation Oncology Study Group (J-CROS) Study 1403 Pancreas","volume":"101","author":"Kawashiro","year":"2018","journal-title":"Int J Radiat Oncol Biol Phys"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.708884\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T11:13:00Z","timestamp":1626261180000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.708884\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,14]]},"references-count":25,"alternative-id":["10.3389\/fonc.2021.708884"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2021.708884","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,14]]},"article-number":"708884"}}