Upper gastrointestinal complications associated with gemcitabine-concurrent proton radiotherapy for inoperable pancreatic cancer

Takatori, Kento; Terashima, Kazuki; Yoshida, Rihito; Horai, Aya; Satake, Shinya; Ose, Takayuki; Kitajima, Naoto; Kinoshita, Yoshikazu; Demizu, Yusuke; Fuwa, Nobukazu

doi:10.1007/s00535-013-0857-3

Cited by 48 publications

(27 citation statements)

References 20 publications

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“…In contrast to the current series demonstrating negligible toxicity for patients with locally advanced pancreas cancer treated with protons, Takatori et al [17] reported an analysis of the upper gastrointestinal complications associated with gemcitabine concurrent proton radiation therapy for patients with inoperable pancreatic cancer. The study demonstrated a 49.4% rate of gastric/duodenal ulceration in the treated patients.…”

Section: Discussionmentioning

confidence: 71%

Proton Therapy and Concomitant Capecitabine for Non-Metastatic Unresectable Pancreatic Adenocarcinoma

Sachsman¹,

Nichols²,

Morris³

et al. 2014

International Journal of Particle Therapy

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Purpose: To review early outcomes for patients enrolled on our institution's protocol (PC01) for patients with unresectable pancreatic cancer, and to test whether the serious adverse event rate could be reduced from 15% (expected) to ,5%. Patients and Methods: Twelve patients were enrolled, but only 11 patients are reported in this analysis. Pathology on all patients was reviewed at University of Florida Health Medical Center in Jacksonville to confirm the diagnosis of pancreatic adenocarcinoma. Unresectability was defined by radiographic evidence of encasement of the celiac axis and/or superior mesenteric artery or by occlusion of the superior mesenteric vein, portal vein, or both confluences. Patients received proton therapy to a planning target volume dose of 59.4 Gy (relative biological effective) at 1.8 Gy (relative biological effective) per fraction over 7 weeks with concomitant oral capecitabine (1000 mg orally twice-daily, 5 days/week on radiation treatment days only). Only gross disease was targeted. Results: Median follow-up for all patients was 14 months (range, 5 to 25 months). Median follow-up for surviving patients was 23 months (range, 8 to 25 months). Median age was 68 years (range, 51 to 86 years). One-and 2-year overall survival, progression-free survival, distant metastasis-free survival, and freedom from local progression rates were 61% and 31% (median, 18.4 months), 55% and 14%, 68% and 27%, and 86% and 69%, respectively. No patient experienced a grade 3 or greater toxicity during treatment or follow-up. Grade 2 toxicity was limited to a single patient experiencing grade 2 fatigue. Median weight loss over the course of treatment was 1.7 kg (range, loss of 5.7 to gain of 4.9 kg). Four patients had an adequate radiographic response to radiation therapy to justify surgical exploration. Conclusion: Proton therapy with concomitant capecitabine as delivered on the PC01 protocol was well-tolerated with no grade 2 or greater gastrointestinal toxicities. The

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Section: Discussionmentioning

confidence: 71%

Proton Therapy and Concomitant Capecitabine for Non-Metastatic Unresectable Pancreatic Adenocarcinoma

Sachsman¹,

Nichols²,

Morris³

et al. 2014

International Journal of Particle Therapy

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“…First attempts at dose escalation performed by Terashima, et al [52] and Takatori, et al [53] observed a particularly high incidence (50%) of GI radiation-induced ulcers of 50 and 126 enrolled patients, respectively. The two studies from Hyogo Ion Beam Medical Center employed a significantly a higher prescription of 2.5 to 2.7 GyE per fraction compared to other PT studies in Table 3.…”

Section: Summary Of Pt Clinical Studies Inmentioning

confidence: 99%

Clinical Limitations of Photon, Proton and Carbon Ion Therapy for Pancreatic Cancer

Dell’Oro

Short

Wilson

et al. 2020

Cancers

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Introduction: Despite improvements in radiation therapy, chemotherapy and surgical procedures over the last 30 years, pancreatic cancer 5-year survival rate remains at 9%. Reduced stroma permeability and heterogeneous blood supply to the tumour prevent chemoradiation from making a meaningful impact on overall survival. Hypoxia-activated prodrugs are the latest strategy to reintroduce oxygenation to radioresistant cells harbouring in pancreatic cancer. This paper reviews the current status of photon and particle radiation therapy for pancreatic cancer in combination with systemic therapies and hypoxia activators. Methods: The current effectiveness of management of pancreatic cancer was systematically evaluated from MEDLINE® database search in April 2019. Results: Limited published data suggest pancreatic cancer patients undergoing carbon ion therapy and proton therapy achieve a comparable median survival time (25.1 months and 25.6 months, respectively) and 1-year overall survival rate (84% and 77.8%). Inconsistencies in methodology, recording parameters and protocols have prevented the safety and technical aspects of particle therapy to be fully defined yet. Conclusion: There is an increasing requirement to tackle unmet clinical demands of pancreatic cancer, particularly the lack of synergistic therapies in the advancing space of radiation oncology.

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“…Most of the patients received a dose of 67.5 Gy (RBE) in 25 fractions. The initial report suggested tolerability of this regimen [15] ; however, a subsequent publication in the gastroenterology literature reported a high rate of upper gastrointestinal complications [16] . Post-treatment endoscopic examinations in 45 of 91 patients revealed radiation-induced ulcers in the stomach and duodenum.…”

Section: Clinical Studiesmentioning

confidence: 99%

Proton therapy for pancreatic cancer

Nichols

Huh

et al. 2015

WJGO

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tissue sparing. Because of this, protons appear to represent a superior modality for radiotherapy delivery to patients with unresectable tumors and those receiving postoperative radiotherapy. A particularly exciting opportunity for protons also exists for patients with resectable and marginally resectable disease. In this paper, we review the current literature on proton therapy for pancreatic cancer and discuss scenarios wherein the improvement in the therapeutic index with protons may have the potential to change the management paradigm for this malignancy. Core tip: Radiotherapy is commonly offered to patients with pancreatic malignancies although its ultimate utility is compromised since the pancreas is surrounded by exquisitely radiosensitive normal tissues, such as the duodenum, stomach, jejunum, liver, and kidneys. Proton radiotherapy can be used to create dose distributions that conform to tumor targets with significant normal tissue sparing. Because of this, protons appear to represent a superior modality for radiotherapy delivery to patients with unresectable tumors and those recei ving postoperative radiotherapy. A particularly exciting opportunity for protons also exists for patients with resectable and marginally resectable disease. AbstractRadiotherapy is commonly offered to patients with pancreatic malignancies although its ultimate utility is compromised since the pancreas is surrounded by exquisitely radiosensitive normal tissues, such as the duodenum, stomach, jejunum, liver, and kidneys. Proton radiotherapy can be used to create dose distributions that conform to tumor targets with significant normal MINIREVIEWSSeptember 15, 2015|Volume 7|Issue 9|

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Upper gastrointestinal complications associated with gemcitabine-concurrent proton radiotherapy for inoperable pancreatic cancer

Abstract: Approximately half of the patients treated with GPT for inoperable pancreatic cancer exhibited radiation-induced ulcers in the stomach and duodenum.

Cited by 48 publications

References 20 publications

Proton Therapy and Concomitant Capecitabine for Non-Metastatic Unresectable Pancreatic Adenocarcinoma

Proton Therapy and Concomitant Capecitabine for Non-Metastatic Unresectable Pancreatic Adenocarcinoma

Clinical Limitations of Photon, Proton and Carbon Ion Therapy for Pancreatic Cancer

Proton therapy for pancreatic cancer

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