Dose escalation in locally advanced pancreatic cancer patients receiving chemoradiotherapy

Chung, Sung Pil; Chang, Jee Suk; Lee, Byung Min; Kim, Kyung Hwan; Lee, Kyong Joo; Seong, Jinsil

doi:10.1016/j.radonc.2017.04.010

Cited by 48 publications

(35 citation statements)

References 19 publications

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“…Regarding outcome after high-dose radiotherapy similar results were reported by Chung and colleagues: In a retrospective analysis of 152 patients receiving radiochemotherapy with 61 Gy or more the median overall survival time was 21.9 months [17]. In a phase-I/II dose escalation trial Ben-Josef and colleagues reported a median overall survival time of 14.8 months with most patients of the study receiving 55 Gy prescribed dose [18].…”

Section: Discussionsupporting

confidence: 65%

“…Obviously, the radiation dosage is still too low. Considering the described advantage of dose escalation [14,17] a further increase of dose might be required to warrant local control. Therefore, uncertainties causing geographical misses must be minimized to enable further dose escalation and improve dose coverage while adjacent OARs are still sufficiently spared.…”

Section: Discussionmentioning

confidence: 99%

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Dose-escalated radiotherapy for unresectable or locally recurrent pancreatic cancer: Dose volume analysis, toxicity and outcome of 28 consecutive patients

et al. 2017

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PurposeThe role of radiotherapy for unresectable pancreatic cancer is controversial. A benefit of additional radiotherapy is supported by some observations. A dose-effect relationship was recently found by dose escalation employing image guided and intensity modulated radiotherapy.MethodsWe retrospectively evaluated 28 consecutive patients, all with history of extensive prior therapies for unresectable locally advanced/ recurrent pancreatic cancer (LAPC/LRPC). Treatment was delivered by helical tomotherapy after daily position verification with computed tomography. Dose to the planned target volume (PTV) was 51 Gy, while the dose to the macroscopic tumor was escalated by a simultaneous integrated boost to a median cumulative dose of 66 Gy (60–66 Gy). Concomitant chemotherapy consisted mainly of capecitabine (n = 23).Results10 of 28 patients presented acute toxicities > grade 2, one patient succumbed to gastrointestinal bleeding after treatment. No correlations of toxicities and dose volume histograms (DVH) of retrospectively delineated small bowel loops were observed, although average small bowel volume receiving ≥ 20 Gy was 374 ml. DVH analyses revealed a correlation of splenic parameters and acute toxicity: Vomiting, anorexia, dehydration, hematologic toxicity, fatigue, combined gastro-intestinal toxicity wit R-values between 0.392 and 0.561 (all p-values > 0.05). Only one patient developed late toxicities > grade 2. With an average follow-up time in surviving patients of 14 months median overall survival time was 19 months and median time to local recurrence 13 months. In 8 patients with available imaging of local recurrence: 5 in field recurrences, 2 marginal recurrences and one lymph node recurrence outside the high dose radiation field were observed. In univariate analysis only ΔCA-19-9 during radiotherapy was associated with local control (p = 0.029) and overall survival (p = 0.049).ConclusionDose escalated normo-fractionated radiotherapy for LAPC/LRPC seems feasible and suitable to prolong local control and in consequence long-term survival. However, in-field local progression is still frequently observed and possibilities to increase the local effectiveness should be evaluated. Exposure of the spleen was predictive for acute toxicity and should be further investigated.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Dose-escalated radiotherapy for unresectable or locally recurrent pancreatic cancer: Dose volume analysis, toxicity and outcome of 28 consecutive patients

et al. 2017

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“… 41 , 42 The clinical benefits associated with IMRT are likely driven by the ability to provide higher RT doses, downstaging, and margin negative resections, which is consistent with the results of our study. 42 , 43 Treatment at an HVF or AC may be more likely to involve peer review of treatment plans, which can lead to improvements in clinical care. 44 Taken together, the increased subspecialized care likely to be received at an HVF and/or AC may help account for these clinical benefits.…”

Section: Discussionmentioning

confidence: 99%

Treatment strategies and clinical outcomes of locally advanced pancreatic cancer patients treated at high-volume facilities and academic centers

David

Kim

Placencio-Hickok

et al. 2019

Advances in Radiation Oncology

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Purpose Locally advanced pancreatic cancer (LAPC) treatment has varying practice patterns with poor outcomes. We investigated treatment using single-agent chemotherapy and multiagent chemotherapy (MAC) with or without radiation therapy (RT) at high-volume facilities (HVFs) and academic centers (ACs). Methods and Materials The National Cancer Database was used to obtain data on 10,139 patients with LAPC. HVF was defined as the top 5% of facilities per number of patients treated at each facility. Univariate and multivariable (MVA) analysis Cox regressions were performed to identify the impact of HVF, AC, MAC, and RT on overall survival (OS). Results The median age of patients was 66 years (range, 22-90); 50.1% were male and 49.9% female. Of the patients, 46.1% received MAC, 53.8% received single-agent chemotherapy, 45.7% received RT, 54.3% did not receive RT, and 5% underwent surgical resection. The median follow-up was 48.8 months. On MVA, treatment at HVFs and ACs remained significantly associated with improved OS, with a hazard ratio (HR) of 0.84 ( P < .001) and 0.94 ( P = .004), respectively. The median OS for HVF treatment compared with low-volume facilities was 14.3 versus 11.2 months, respectively ( P < .001). The median OS for AC treatment versus non-AC was 12.1 versus 10.8 months, respectively ( P < .001). Additionally, on MVA, receipt of RT and MAC remained significantly associated with improved OS (HR: 0.76; P < .001; and HR: 0.73; P < .001, respectively). MVA for receipt of surgery showed that MAC is a significant predictor for receiving surgery (odds ratio: 1.29; P = .009). Conclusions Our results build on a growing literature supporting RT and MAC in treating LAPC. Additionally, we believe that—in the absence of prospective data—this makes a strong case for considering MAC with RT at ACs and HVFs for treating LAPC.

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“…It has been reported that radiation dose escalation improves treatment outcome of RT for locally advanced pancreatic cancer [19][20][21][22]. It is desirable to escalate the dose to above 70 Gy in 2 Gy fractions [22,23].…”

Section: Discussionmentioning

confidence: 99%

A preferred patient decubitus positioning for magnetic resonance image guided online adaptive radiation therapy of pancreatic cancer

Chen

Hall

et al. 2019

Physics and Imaging in Radiation Oncology

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Background and purpose: In radiotherapy (RT) for pancreatic cancer, the dose to adjacent organs-at-risk (OAR) often limits the delivery of curative dose. This work aimed to find a body decubitus position that would lead to increased separation between the duodenum and pancreatic head. Materials and methods: Abdominal magnetic resonance images (MRI) of 11 healthy volunteers were acquired using a 1.5T MR-Linac for supine, left decubitus and right decubitus body positions. The geometry changes between different body positions were measured using Hausdorff Distance (HD) and overlap volume. RT plans were created on the MRIs. Commonly used dose-volume parameters (DVP), e.g., V 40Gy-volume received at least 40 Gy, for OARs were compared for the three body positions. Results: The average of maximum HD between the duodenum and pancreatic head for all the cases was 4.0 ± 3.1 mm for supine, 7.3 ± 4.4 mm for left and 3.3 ± 1.4 mm for right positions (P < 0.01). The DVPs of the duodenum (e.g., V 20Gy , V 45Gy) for the left position were lower than those for the supine and right positions (P < 0.01). The right decubitus led to the highest duodenum DVPs. On average, the highest dose escalation was increased from 69 ± 4 Gy to 74 ± 5 Gy (P = 0.002) if body position was changed from supine to left decubitus. Conclusion: The left decubitus increased the separation between duodenum and pancreas head, improving OAR sparing in RT for pancreatic cancer and allowing safer dose escalations to the tumor. The left decubitus positioning with proper immobilization could be adopted for MRI-guided adaptive RT.

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Dose escalation in locally advanced pancreatic cancer patients receiving chemoradiotherapy

Cited by 48 publications

References 19 publications

Dose-escalated radiotherapy for unresectable or locally recurrent pancreatic cancer: Dose volume analysis, toxicity and outcome of 28 consecutive patients

Dose-escalated radiotherapy for unresectable or locally recurrent pancreatic cancer: Dose volume analysis, toxicity and outcome of 28 consecutive patients

Treatment strategies and clinical outcomes of locally advanced pancreatic cancer patients treated at high-volume facilities and academic centers

A preferred patient decubitus positioning for magnetic resonance image guided online adaptive radiation therapy of pancreatic cancer

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