Dose Escalation in Stereotactic Body Radiation Therapy for Pancreatic Cancer

Zaorsky, Nicholas G.; Lehrer, Eric J.; Handorf, Elizabeth; Meyer, Joshua E.

doi:10.1097/coc.0000000000000472

Cited by 33 publications

(37 citation statements)

References 39 publications

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“…10,11,14 The median OS and 2-year OS rates in our study were in line with the ones in Krishnan et al 14 (median OS: 20.3 months versus 17.8 months, 2-year OS rate: 36.8% versus 36.0%, 3-year OS rate: 18.7% versus 31.0%). However, there were controversial results from the meta-analysis; 34 the median OS of two studies with the most weight employing BED 10 >70 Gy was 12.5 months and 10.3 months, which was inferior to our study. In contrast, the median OS with the most weight employing a BED 10 of 60-70 Gy from two studies were found to be 13.9 months and 15.0 months, respectively.…”

Section: Discussioncontrasting

confidence: 95%

Failure patterns and outcomes of dose escalation of stereotactic body radiotherapy for locally advanced pancreatic cancer: a multicenter cohort study

Zhu

Cao

et al. 2020

Ther Adv Med Oncol

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Objective: This study aims to compare recurrence patterns and outcomes of biologically effective dose (BED10, α/β = 10) of 60–70 Gy with those of a BED10 >70 Gy for locally advanced pancreatic cancer (LAPC). Methods: Patients from three centers with a biopsy and a radiographically proven LAPC were retrospectively included and data were prospectively collected from June 2012 to June 2019. Radiotherapy was delivered by stereotactic body radiation therapy. Recurrences were categorized as in-field, marginal, and outside-the-field recurrence. Patients in two groups were required to receive abdominal enhanced contrast CT or MRI every 2–3 months and CA19-9 examinations every month during follow-up. Treatment-related toxicities were evaluated every month. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Results: After propensity score matching, there were 486 patients in each group. The median prescription dose of the two groups was 37 Gy/5–8 f (range: 36–40.8 Gy/5–8 f) and 42 Gy/5–8 f (range: 40–49.6 Gy/5–8 f), respectively. The median OS of patients with a BED10 >70 Gy and a BED10 60–70 Gy was 20.3 months (95% CI: 19.1–21.5 months) and 18.2 months (95% CI: 17.8–18.6 months) respectively ( p < 0.001). The median PFS of the two cohorts was 15.4 months (95% CI: 14.2–16.6 months) and 13.3 months (95% CI: 12.9–13.7 months) respectively ( p < 0.001). A higher incidence of in-field and marginal recurrence was found in patients with BED10 of 60–70 Gy (in-field: 97/486 versus 72/486, p = 0.034; marginal: 109/486 versus 84/486, p = 0.044). However, more patients with BED10 >70 Gy had grade 2 or 3 acute (87/486 versus 64/486, p = 0.042) and late gastrointestinal toxicities (77/486 versus 55/486, p = 0.039) than those with BED10 of 60–70 Gy. Conclusion: BED10 >70 Gy was found to have the best survival benefits along with a higher incidence of acute and late gastrointestinal toxicities. Therefore, a higher dose may be required in the case of patients’ good tolerance.

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Section: Discussioncontrasting

confidence: 95%

Failure patterns and outcomes of dose escalation of stereotactic body radiotherapy for locally advanced pancreatic cancer: a multicenter cohort study

Zhu

Cao

et al. 2020

Ther Adv Med Oncol

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“…In the abovementioned systematic review, the authors report that total SBRT dose and a higher number of fractions were significantly associated with local control at one year, but further details were lacking [8]. Another meta-analysis dedicated to the topic of radiation dose-escalation for pancreatic cancer by Zaorsky et al has recently been published [9]. This review included the results of SBRT for non-metastatic pancreatic cancer in 508 patients within a total of 15 studies.…”

Section: Biological Dose Escalation For Pancreatic Cancermentioning

confidence: 99%

The role of biological dose-escalation for pancreatic cancer

Bruynzeel

Lagerwaard

2019

Clinical and Translational Radiation Oncology

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The role of chemo-radiotherapy for treatment of locally advanced pancreatic cancer (LAPC) has been discussed for many years, and the absence of an overall survival benefit compared to gemcitabine chemotherapy alone in the recent LAP07 study seems to have increased the controversy. However, even in this study, chemo-radiotherapy resulted in decreased local progression (p = 0.03). In combination with increased efficacy of novel systemic therapy consisting of oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX), radiation dose-escalation may show to be beneficial in LAPC. Stereotactic body radiation therapy (SBRT) can be expected to be the most suitable approach to perform local radiation doseescalation, and has been shown to be both effective and tolerable at doses of 25-35 Gy in 3-5 fractions. Whether further dose-escalation for LAPC will be both feasible and useful is debatable, because of dose restrictions to adjacent critical organs at risk, and the observation that thus far a benefit of delivering BED 10 in excess of 70 Gy has not shown to improve local control significantly. If an attempt to further dose-escalate is performed, stereotactic MR-guided adaptive radiation therapy (SMART) theoretically has the highest potential. In addition to superior soft-tissue setup without the need for implanted fiducial markers and online MR-guidance during delivery with minimal safety margins, daily plan adaptation directed at avoiding undue high doses to critical organs such as the duodenum, stomach and bowel are advantages of this technique over current SBRT. This paper aims to illustrate the SMART technique, which has been delivered in 300 fractions for LAPC or locally recurrent pancreatic cancer at Amsterdam UMC since early 2016.

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“…The median OS and 2-year OS rates of patients with BED 10 > 70Gy in our center (data not published) were consistent with the ones in Krishnan et al [27] (median OS: 20.3 months vs. 17.8 months, 2-year OS rate: 36.8% vs. 36.0%, 3-year OS rate: 18.7% vs. 31.0%). However, there were controversial results from the meta-analysis [28]. The median OS of two included studies with the most weight employing BED 10 > 70Gy was 12.5 months and 10.3 months, while the median OS with the most weight employing a BED 10 of 60-70Gy from another two studies were found to be 13.9 months and 15.0 months, respectively.…”

Section: Discussionmentioning

confidence: 97%

Development and Validation of Multicenter Predictive Nomograms for Locally Advanced Pancreatic Cancer after Chemoradiotherapy

Zhu

Liu

Cao

et al. 2020

Preprint

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Background: Due to common practice of hypofractionated radiotherapy in pancreatic cancer and heterogeneous chemotherapy regimens in previous studies, modified nomograms are required. Therefore, we aim to develop and validate prognostic nomograms for locally advanced pancreatic cancer (LAPC) after stereotactic body radiation therapy (SBRT) and chemotherapy.Methods: The development cohort comprised 925 patients with LAPC receiving SBRT and gemcitabine-based chemotherapy in our center, while 297 patients from another two centers formed the validation cohort. Nomograms were created from COX models and internally validated by bootstrap. Model discriminations were evaluated by calibration plots and concordance index (C-index). A decision curve analysis (DCA) was performed to evaluate clinical benefits of nomograms. Additionally, recursive partitioning analysis (RPA) was used for stratifications of survival probability based on the total score of each patient calculated by nomograms.Results: Weight loss, tumor diameter, radiation dose, CA19-9 kinetics after treatment and surgical resection were included in the nomogram for overall survival (OS), while the five factors plus performance status formed the nomogram for progression free survival (PFS). The corrected C-indexes for estimated 1-year and 2-year OS of the development cohort were 0.88 (95% CI: 0.85-0.91) and 0.86 (95% CI: 0.83-0.90). For those of the validation cohort, it was 0.88 (95% CI: 0.82-0.94) and 0.83 (95% CI: 0.74-0.91). Additionally, the corrected C-index for predicted 1-year PFS in the development and validation cohort was 0.83 (95% CI: 0.81-0.86) and 0.82 (95% CI: 0.78-0.87), respectively. The calibration plots showed good agreement of 1- and 2-year OS and 1-year PFS between the estimations and actual observations. Potential clinical benefits were demonstrated with DCA. Additionally, for 1- and 2-year OS and 1-year PFS, patients were stratified into four groups with different survival probability by RPA.Conclusion: The validated nomograms provided useful predictions of OS and PFS for LAPC with chemoradiotherapy.

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Dose Escalation in Stereotactic Body Radiation Therapy for Pancreatic Cancer

Cited by 33 publications

References 39 publications

Failure patterns and outcomes of dose escalation of stereotactic body radiotherapy for locally advanced pancreatic cancer: a multicenter cohort study

Failure patterns and outcomes of dose escalation of stereotactic body radiotherapy for locally advanced pancreatic cancer: a multicenter cohort study

The role of biological dose-escalation for pancreatic cancer

Development and Validation of Multicenter Predictive Nomograms for Locally Advanced Pancreatic Cancer after Chemoradiotherapy

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