scholarly journals Dosimetric Feasibility Study of Dose Escalated Stereotactic Body Radiation Therapy (SBRT) in Locally Advanced Pancreatic Cancer (LAPC) Patients: It Is Time to Raise the Bar

2020 ◽  
Vol 10 ◽  
Author(s):  
Renzo Mazzarotto ◽  
Nicola Simoni ◽  
Stefania Guariglia ◽  
Gabriella Rossi ◽  
Renato Micera ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Organs At Risk ◽  
Locally Advanced ◽  
Volumetric Modulated Arc Therapy ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Conformity Index ◽  
Breath Hold ◽  
Prescription Dose ◽  
Dose Constraints

Background and ObjectiveTo assess the dosimetric feasibility of a stereotactic body radiotherapy (SBRT) dose escalated protocol, with a simultaneous integrated boost (SIB) and a simultaneous integrated protection (SIP) approach, in patients with locally advanced pancreatic cancer (LAPC).Material and MethodsTwenty LAPC lesions, previously treated with SBRT at our Institution, were re-planned. The original prescribed and administered dose was 50/30/25 Gy in five fractions to PTVsib (tumor-vessel interface [TVI])/PTVt (tumor volume)/PTVsip (overlap area between PTVt and planning organs at risk volume [PRVoars]), respectively. At re-planning, the prescribed dose was escalated up to 60/40/33 Gy in five fractions to PTVsib/PTVt/PTVsip, respectively. All plans were performed using an inspiration breath hold (IBH) technique and generated with volumetric modulated arc therapy (VMAT). Well-established and accepted OAR dose constraints were used (D0.5cc < 33 Gy for luminal OARs and D0.5cc < 38 Gy for corresponding PRVoars). The primary end-point was to achieve a median dose equal to the prescription dose for the PTVsib with D98≥ 95% (95% of prescription dose is the minimum dose), and a coverage for PTVt and PTVsip of D95≥95%, with minor deviations in OAR dose constraints in < 10% of the plans.ResultsPTVsib median (± SD) dose/D95/conformity index (CI) were 60.54 (± 0.85) Gy/58.96 (± 0.86) Gy/0.99 (± 0.01), respectively; whilst PTVt median (± SD) dose/D95 were 44.51 (± 2.69) Gy/38.44 (± 0.82) Gy, and PTVsip median (± SD) dose/D95 were 35.18 (± 1.42) Gy/33.01 (± 0.84) Gy, respectively. With regard to OARs, median (± SD) maximum dose (D0.5cc) to duodenum/stomach/bowel was 29.31 (± 5.72) Gy/25.29 (± 6.90) Gy/27.03 (± 5.67) Gy, respectively. A minor acceptable deviation was found for a single plan (bowel and duodenum D0.5cc=34.8 Gy). V38 < 0.5 cc was achieved for all PRV luminal OARs.ConclusionsIn LAPC patients SBRT, with a SIB/SIP dose escalation approach up to 60/40/33 Gy in five fractions to PTVsib/PTVt/PTVsip, respectively, is dosimetrically feasible with adequate PTVs coverage and respect for OAR dose constraints.

scholarly journals Evaluating Dosimetric Constraints for Carbon Ion Radiotherapy in the Treatment of Locally Advanced Pancreatic Cancer

2020 ◽  
Author(s):  
Lien-Chun Lin ◽  
Guo-Liang Jiang ◽  
Nitin Ohri ◽  
Zheng Wang ◽  
Jiade Lu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
At Risk ◽  
Organs At Risk ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Dose Schedule ◽  
Locally Advanced Pancreatic Cancer ◽  
Carbon Ion Radiotherapy ◽  
Carbon Ion ◽  
Dose Constraints

Abstract Objective: To identify a safe carbon ion radiotherapy (CIRT) regimen for patients with locally advanced pancreatic cancer (LAPC). Methods: We generated treatment plans for 13 consecutive, unselected patients who were treated for LAPC with CIRT at our center using three dose and fractionation schedules: 4.6 GyRBE x 12, 4.0 GyRBE x 14, and 3.0 GyRBE x 17. We tested the ability to meet published dose constraints for the duodenum, stomach, and small bowel as a function of dose schedule and distance between the tumor and organs at risk. Results: Using 4.6 GyRBE x 12 and 4.0 GyRBE x 14, critical (high-dose) constraints could only reliably be achieved when target volumes were not immediately adjacent to organs at risk. Critical constraints could be met in all cases using 3.0 GyRBE x 17. Low-dose constraints could not uniformly be achieved using any dose schedule. Conclusion: While selected patients with LAPC may be treated safely with a CIRT regimen of 4.6 GyRBE x 12, our dosimetric analyses indicate that a more conservative schedule of 3.0 GyRBE x 17 may be required to safely treat a broader population of LAPC patients, including those with large tumors and tumors that approach gastrointestinal organs at risk. The result of this work was used to guide an ongoing clinical trial.

scholarly journals Evaluating Dosimetric Constraints for Carbon Ion Radiotherapy in the Treatment of Locally Advanced Pancreatic Cancer

2020 ◽  
Author(s):  
Lien-Chun Lin ◽  
Guo-Liang Jiang ◽  
Nitin Ohri ◽  
Zheng Wang ◽  
Jiade Lu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
At Risk ◽  
Organs At Risk ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Dose Schedule ◽  
Locally Advanced Pancreatic Cancer ◽  
Carbon Ion Radiotherapy ◽  
Carbon Ion ◽  
Dose Constraints

Abstract ObjectiveTo identify a safe carbon ion radiotherapy (CIRT) regimen for patients with locally advanced pancreatic cancer (LAPC).MethodsWe generated treatment plans for 13 consecutive, unselected patients who were treated for LAPC with CIRT at our center using three dose and fractionation schedules: 4.6 GyRBE x 12, 4.0 GyRBE x 14, and 3.0 GyRBE x 17. We tested the ability to meet published dose constraints for the duodenum, stomach, and small bowel as a function of dose schedule and distance between the tumor and organs at risk.ResultsUsing 4.6 GyRBE x 12 and 4.0 GyRBE x 14, critical (high-dose) constraints could only reliably be achieved when target volumes were not immediately adjacent to organs at risk. Critical constraints could be met in all cases using 3.0 GyRBE x 17. Low-dose constraints could not uniformly be achieved using any dose schedule.ConclusionWhile selected patients with LAPC may be treated safely with a CIRT regimen of 4.6 GyRBE x 12, our dosimetric analyses indicate that a more conservative schedule of 3.0 GyRBE x 17 may be required to safely treat a broader population of LAPC patients, including those with large tumors and tumors that approach gastrointestinal organs at risk. The result of this work was used to guide an ongoing clinical trial.

scholarly journals Evaluating Dosimetric Constraints for Carbon Ion Radiotherapy in the Treatment of Locally Advanced Pancreatic Cancer

2020 ◽  
Author(s):  
Lien-Chun Lin ◽  
Guo-Liang Jiang ◽  
Nitin Ohri ◽  
Zheng Wang ◽  
Jiade Lu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
At Risk ◽  
Organs At Risk ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Dose Schedule ◽  
Locally Advanced Pancreatic Cancer ◽  
Carbon Ion Radiotherapy ◽  
Carbon Ion ◽  
Dose Constraints

Abstract Objective: To identify a safe carbon ion radiotherapy (CIRT) regimen for patients with locally advanced pancreatic cancer (LAPC).Methods: We generated treatment plans for 13 consecutive, unselected patients who were treated for LAPC with CIRT at our center using three dose and fractionation schedules: 4.6 GyRBE x 12, 4.0 GyRBE x 14, and 3.0 GyRBE x 17. We tested the ability to meet published dose constraints for the duodenum, stomach, and small bowel as a function of dose schedule and distance between the tumor and organs at risk.Results: Using 4.6 GyRBE x 12 and 4.0 GyRBE x 14, critical (high-dose) constraints could only reliably be achieved when target volumes were not immediately adjacent to organs at risk. Critical constraints could be met in all cases using 3.0 GyRBE x 17. Low-dose constraints could not uniformly be achieved using any dose schedule.Conclusion: While selected patients with LAPC may be treated safely with a CIRT regimen of 4.6 GyRBE x 12, our dosimetric analyses indicate that a more conservative schedule of 3.0 GyRBE x 17 may be required to safely treat a broader population of LAPC patients, including those with large tumors and tumors that approach gastrointestinal organs at risk. The result of this work was used to guide an ongoing clinical trial.

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

2020 ◽  
Vol 12 ◽  
pp. 175883592097715
Author(s):  
Xiaofei Zhu ◽  
Yangsen Cao ◽  
Tingshi Su ◽  
Xixu Zhu ◽  
Xiaoping Ju ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Multicenter Cohort Study ◽  
Failure Patterns ◽  
Kaplan Meier ◽  
Prescription Dose ◽  
Contrast Ct

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.

Dose escalation in locally advanced pancreatic cancer patients receiving chemoradiotherapy.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 372-372
Author(s):  
Seung Yeun Chung ◽  
Jee Suk Chang ◽  
Byung Min Lee ◽  
Kyong Joo Lee ◽  
Si Young Song ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Dose Escalation ◽  
Organs At Risk ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Severe Toxicity ◽  
Grade 3 ◽  
Free Rate

372 Background: In locally advanced pancreatic cancer, radiotherapy (RT) is an effective treatment modality, but challenged by conflicting results. Now, in the era of intensity-modulated radiation therapy (IMRT), dose escalation is possible without increasing the dose to organs-at-risk. We investigated whether RT dose escalation would improve treatment outcomes without increasing severe toxicity. Methods: From 2005 to 2015, a total of 497 locally advanced - including both borderline resectable and unresectable - pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy were included. A total of 281 (56.5%) patients received 3D conformal RT and 216 (43.5%) patients received IMRT. Most common dose scheme for IMRT was 58.42 Gy in 23 fractions (EQD2 61.05 Gy). Patients were divided into two groups; < 61 Gy group (n = 345) and ≥ 61 Gy group (n = 152). Overall survival (OS), progression-free survival (PFS), local failure-free rate (LFFR), distant failure-free rate (DFFR) and toxicity rates were assessed. Results: At a median follow-up time of 14.1 months (range, 2.3-128.5 months), OS, PFS, LFFR, and DFFR rates were significantly higher in ≥ 61 Gy group. The 1-year OS rates were 74.7% and 60.6% (p = 0.001) and 1-year PFS rates were 46.2% and 30.9% (p < 0.001), for ≥ 61 Gy and < 61 Gy group, respectively. The 1-year LFFR was 86.9% and 70.9% (p = 0.001) and 1-year DFFR was 56.4% and 45.8% (p = 0.007), respectively. After multivariate analysis, ≥ 61 Gy group remained a favorable significant factor for OS (p = 0.019), PFS (p = 0.001), LFFR (p = 0.004), and DFFR (p = 0.008). When 152 patients in each group were matched by propensity score matching, ≥ 61 Gy group still showed higher OS (p = 0.011), PFS (p = 0.016), and LFFR (p = 0.002), but not DFFR (p = 0.205). There was no acute gastrointestinal toxicity higher than Grade 3 in both groups. Late toxicity rates were also similar, with RT-related duodenal and gastric hemorrhage ( ≥ Grade 3) in 19 patients (5.5%) in < 61 Gy group and 7 patients (4.6%) in ≥ 61 Gy group. Conclusions: Patients who received higher RT dose showed not only improved PFS and LFFR but improved OS without an increase in severe toxicity. Dose escalation via IMRT is recommended for RT in locally advanced pancreatic cancer patients.

A Critical Overview of Systematic Reviews of Chemotherapy for Advanced and Locally Advanced Pancreatic Cancer using both AMSTAR2 and ROBIS as Quality Assessment Tools

2020 ◽  
Vol 15 ◽  
Author(s):  
Amit Dang ◽  
Surendar Chidirala ◽  
Prashanth Veeranki ◽  
BN Vallish
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Systematic Reviews ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Risk Of Bias ◽  
Low Risk ◽  
Locally Advanced Pancreatic Cancer ◽  
Grade 3 ◽  
Critical Overview

Background: We performed a critical overview of published systematic reviews (SRs) of chemotherapy for advanced and locally advanced pancreatic cancer, and evaluated their quality using AMSTAR2 and ROBIS tools. Materials and Methods: PubMed and Cochrane Central Library were searched for SRs on 13th June 2020. SRs with metaanalysis which included only randomized controlled trials and that had assessed chemotherapy as one of the treatment arms were included. The outcome measures, which were looked into, were progression-free survival (PFS), overall survival (OS), and adverse events (AEs) of grade 3 or above. Two reviewers independently assessed all the SRs with both ROBIS and AMSTAR2. Results: Out of the 1,879 identified records, 26 SRs were included for the overview. Most SRs had concluded that gemcitabine-based combination regimes, prolonged OS and PFS, but increased the incidence of grade 3-4 toxicities, when compared to gemcitabine monotherapy, but survival benefits were not consistent when gemcitabine was combined with molecular targeted agents. As per ROBIS, 24/26 SRs had high risk of bias, with only 1/26 SR having low risk of bias. As per AMSTAR2, 25/26 SRs had critically low, and 1/26 SR had low, confidence in the results. The study which scored ‘low’ risk of bias in ROBIS scored ‘low confidence in results’ in AMSTAR2. The inter-rater reliability for scoring the overall confidence in the SRs with AMSTAR2 and the overall domain in ROBIS was substantial; ROBIS: kappa=0.785, SEM=0.207, p<0.001; AMSTAR2: kappa=0.649, SEM=0.323, p<0.001. Conclusion: Gemcitabine-based combination regimens can prolong OS and PFS but also worsen AEs when compared to gemcitabine monotherapy. The included SRs have an overall low methodological quality and high risk of bias as per AMSTAR2 and ROBIS respectively.

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