Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC trial): study protocol for a multicentre randomized controlled trial

Versteijne, Eva; Eijck, Casper H.J. van; Punt, Cornelis J.A.; Suker, Mustafa; Zwinderman, Aeilko H.; Dohmen, Miriam A. C.; Groothuis, Karin; Busch, O.; Besselink, Marc G.; Hingh, Ignace H. J. T. de; Tije, Albert J. ten; Patijn, Gijs A.; Bonsing, Bert A.; Vos‐Geelen, Judith de; Klaase, Joost M.; Festen, Sebastiaan; Boerma, Djamila; Erdmann, Joris I.; Molenaar, I.; Harst, Erwin van der; Kolk, Marion van der; Rasch, Coen R. N.; Tienhoven, Geertjan van

doi:10.1186/s13063-016-1262-z

Cited by 138 publications

(136 citation statements)

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“…These reports may indicate we should perform combination of preoperative therapy and postoperative early adjuvant therapy for RPC cases with CA19-9 ≥ 529. RCT trial (PREOPANC trial) as to preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer is conducted at the moment; the results will lead our studies to further directions [37]. …”

Section: Discussionmentioning

confidence: 99%

Preoperative predictors for early recurrence of resectable pancreatic cancer

et al. 2017

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BackgroundThe first-line treatment for resectable pancreatic cancer (RPC) is surgical resection. However, our patients have often experienced early recurrence after curative resection for RPC, with desperately poor prognosis. Some reports indicated that minimally distant metastasis not detected at operation might cause early recurrence. The present study aimed to identify preoperative clinicopathological features of early recurrence after curative resection of RPC.MethodsNinety RPC patients who underwent curative resection between 2000 and 2014 at our institution were retrospectively analyzed.ResultsOf the 90 patients, 32 had recurrence within 1 year. Univariate analysis demonstrated that preoperative serum carbohydrate antigen (CA19-9) ≥529 U/mL (P = 0.0011), preoperative serum s-pancreas-1 antigen (SPan-1) ≥37 U/mL (P = 0.0038), and histological grades G2–G4 (P = 0.0158) were significantly associated with recurrence within 1 year after curative resection. Multivariate analysis demonstrated that preoperative serum CA19-9 ≥ 529 U/mL (P = 0.0477) and histological grade G2–G4 (P = 0.0129) were independent predictors of recurrence within 1 year. Recurrent cases within 1 year postoperatively had significantly more distant metastasis than cases with no recurrence within 1 year (P < 0.001).ConclusionsPreoperative serum CA19-9 ≥ 529 U/mL and histological grades G2–G4 were independent predictive factors for recurrence within 1 year after pancreatectomy for RPC. Furthermore, recurrent cases within 1 year had more frequent distant metastasis than cases with no recurrence within 1 year. These results suggest that RPC patients with preoperative serum CA19-9 ≥ 529 U/mL should receive preoperative therapy rather than surgery.

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Section: Discussionmentioning

confidence: 99%

Preoperative predictors for early recurrence of resectable pancreatic cancer

et al. 2017

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“…This margin is used clinically for the fiducial marker‐based daily online position verification, but may also be used for bony anatomy‐based position verification 15. Ideally, the applied margin is determined based on calculations incorporating quantified uncertainties determined specifically for the patient population and applied treatment technique.…”

Section: Discussionmentioning

confidence: 99%

“…Patients were treated between July 2013 and October 2014 with a planned therapy scheme of 13 × 3.0 Gy (patient 7) or 15 × 2.4 Gy (all others; these patients participated in the PREOPANC trial15). The daily CBCT scans were obtained in free breathing prior to irradiation (Synergy system; Elekta Oncology Systems, Crawley, UK); a total of 132 daily CBCTs (13–15 per patient) were available.…”

Section: Methodsmentioning

confidence: 99%

Dosimetric effects of anatomical changes during fractionated photon radiation therapy in pancreatic cancer patients

Horst

Houweling

Tienhoven

et al. 2017

J Applied Clin Med Phys

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Pancreatic tumors show large interfractional position variation. In addition, changes in gastrointestinal gas volumes and body contour take place over the course of radiation therapy. We aimed to quantify the effect of these anatomical changes on target dose coverage, for the clinically used fiducial marker‐based patient position verification and, for comparison, also for simulated bony anatomy‐based position verification. Nine consecutive patients were included in this retrospective study. To enable fraction dose calculations on cone‐beam CT (CBCT), the planning CT was deformably registered to each CBCT (13–15 per patient); gas volumes visible on CBCT were copied to the deformed CT. Fraction doses were calculated for the clinically used 10 MV VMAT treatment plan (with for the planning target volume (PTV): D98% = 95%), according to fiducial marker‐based and bony anatomy‐based image registrations. Dose distributions were rigidly summed to yield the accumulated dose. To evaluate target dose coverage, we defined an iCTV +5 mm volume, i.e., the internal clinical target volume (iCTV) expanded with a 5 mm margin to account for remaining uncertainties including delineation uncertainties. We analyzed D98%, Dmean, and D2% for iCTV +5 mm and PTV (i.e., iCTV plus 10 mm margin). We found that for fiducial marker‐based registration, differences between fraction doses and planned dose were minimal. For bony anatomy‐based registration, fraction doses differed considerably, resulting in large differences between planned and accumulated dose for some patients, up to a decrease in D98% of the iCTV +5 mm from 95.9% to 85.8%. Our study shows that fractionated photon irradiation of pancreatic tumors is robust against variations in body contour and gastrointestinal gas, with dose coverage only mildly affected. However, as a result of interfractional tumor position variations, target dose coverage can severely decline when using bony anatomy for patient position verification. Therefore, the use of intratumoral fiducial marker‐based daily position verification is essential in pancreatic cancer patients.

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“…All patients gave written informed consent for both the PREOPANC trial (EudraCT number 2012-003181-40) and MIPA (NCT01989000) study and were the first four patients that randomized for preoperative radiochemotherapy at the Academic Medical Center (AMC) within the PREOPANC trial [17]. Both studies were approved by the local medical ethics committee (PREOPANC: Erasmus Medical Center, Rotterdam; MIPA: AMC, Amsterdam) [17]. Preoperative radiochemotherapy consisted of 15 fractions of 2.4 Gy combined with gemcitabine 1000 mg/m 2 once a week for three weeks, preceded and followed by a modified course of gemcitabine 1000 mg/m 2 , once a week for two weeks.…”

Section: Methodsmentioning

confidence: 99%

Considerable interobserver variation in delineation of pancreatic cancer on 3DCT and 4DCT: a multi-institutional study

et al. 2017

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BackgroundThe delineation of pancreatic tumors on CT is challenging. In this study, we quantified the interobserver variation for pancreatic tumor delineation on 3DCT as well as on 4DCT.MethodsEight observers (radiation oncologists) from six institutions delineated pancreatic tumors of four patients with (borderline) resectable pancreatic cancer. The study consisted of two stages. In the 3DCT-stage, the gross tumor volume (GTV) was delineated on a contrast-enhanced scan. In the 4DCT-stage, the internal GTV (iGTV) was delineated, accounting for the respiratory motion. We calculated the volumes of the (i)GTV, the overlap of the delineated volumes (expressed as generalized conformity index: CIgen), the local observer variation (local standard deviation: SD) and the overall observer variation (overall SD). We compared these results between GTVs and iGTVs. Additionally, observers were asked to fill out a questionnaire concerning the difficulty of the delineation and their experience in delineating pancreatic tumors.ResultsThe ratios of the largest to the smallest delineated GTV and iGTV within the same patient were 6.8 and 16.5, respectively. As the iGTV incorporates the GTV during all respiratory phases, the mean volumes of the iGTV (40.07 cm3) were larger than those of the GTV (29.91 cm3). For all patients, CIgen was larger for the iGTV than for the GTV. The mean overall observer variation (root-mean-square of all local SDs over four patients) was 0.63 cm and 0.80 cm for GTV and iGTV, respectively. The largest local observer variations were seen close to biliary stents and suspicious pathological enlarged lymph nodes, as some observers included them and some did not. This variation was more pronounced for the iGTV than for the GTV. The observers rated the 3DCT-stage and 4DCT-stage equally difficult and treated on average three to four pancreatic cancer patients per year.ConclusionsA considerable interobserver variation in delineation of pancreatic tumors was observed. This variation was larger for 4D than for 3D delineation. The largest local observer variation was found around biliary stents and suspicious pathological enlarged lymph nodes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-017-0777-0) contains supplementary material, which is available to authorized users.

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Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC trial): study protocol for a multicentre randomized controlled trial

Cited by 138 publications

References 41 publications

Preoperative predictors for early recurrence of resectable pancreatic cancer

Preoperative predictors for early recurrence of resectable pancreatic cancer

Dosimetric effects of anatomical changes during fractionated photon radiation therapy in pancreatic cancer patients

Considerable interobserver variation in delineation of pancreatic cancer on 3DCT and 4DCT: a multi-institutional study

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