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Ablative radiation therapy for locally advanced pancreatic cancer: techniques and results.

ABSTRACT: Standard doses of conventionally fractionated radiation have had minimal to no impact on the survival duration of patients with locally advanced unresectable pancreatic cancer (LAPC). The use of low-dose stereotactic body radiation (SBRT) in 3- to 5-fractionshas thus far produced a modest improvement in median survival with minimal toxicity and shorter duration of treatment, but failed to produce a meaningful difference at 2 years and beyond. A much higher biologically effective dose (BED) is likely needed to achieve tumor ablation The challenge is the delivery of ablative doses near the very sensitive gastrointestinal tract. Advanced organ motion management, image guidance, and adaptive planning techniques enable delivery of ablative doses of radiation (> = 100Gy BED) when more protracted hypofractionated regimens or advanced image guidance and adaptive planning are used. This approach has resulted in encouraging improvements in survival in several studies. This review will summarize the evolution of the radiation technique over time from conventional to ablative and describe the practical aspects of delivering ablative doses near the GI tract using cone beam CT image (CBCT) guidance and online adaptive MRI guidance.

SUBMITTER: Reyngold M

PROVIDER: S-EPMC6555709 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Ablative radiation therapy for locally advanced pancreatic cancer: techniques and results.

Reyngold Marsha M Parikh Parag P Crane Christopher H CH

Radiation oncology (London, England) 20190606 1

Standard doses of conventionally fractionated radiation have had minimal to no impact on the survival duration of patients with locally advanced unresectable pancreatic cancer (LAPC). The use of low-dose stereotactic body radiation (SBRT) in 3- to 5-fractionshas thus far produced a modest improvement in median survival with minimal toxicity and shorter duration of treatment, but failed to produce a meaningful difference at 2 years and beyond. A much higher biologically effective dose (BED) is li ...[more]

PMID: 31171025

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Project description:PurposeStereotactic body radiation therapy (SBRT) is a promising treatment modality for locally advanced pancreatic cancer (LAPC). We evaluated the clinical outcomes of SBRT in patients with LAPC.Patients and methodsWe retrospectively analyzed the medical records of patients with LAPC who underwent SBRT at our institution between April 2011 and July 2016. Fiducial markers were implanted using endoscopic ultrasound guidance one week prior to 4-dimensional computed tomography (CT) simulation and daily cone beam CT was used for image guidance. Patients received volumetric modulated arc therapy or intensity modulated radiotherapy using respiratory gating technique. A median dose of 28 Gy (range, 24-36 Gy) was given over four consecutive fractions delivered within one week. Survival outcomes including freedom from local disease progression (FFLP), progression-free survival (PFS), and overall survival (OS) were analyzed. Acute and late toxicities related to SBRT were assessed.ResultsA total of 95 patients with LAPC were analyzed, 52 of which (54.7%) had pancreatic head cancers. Most (94.7%) had received gemcitabine-based chemotherapy. The 1-year FFLP rate was 80.1%. Median OS and PFS were 16.7 months and 10.2 months, respectively; the 1-year OS and PFS rates were 67.4% and 42.9%, respectively. Among 79 patients who experienced failure, the sites of first failures were isolated local progressions in 12 patients (15.2%), distant metastasis in 55 patients (69.6%), and both in 12 patients (15.2%). Seven patients (7.4%) were able to undergo surgical resection after SBRT and four had margin-negative resections. Three patients (3.2%) had grade 3 nausea/vomiting during SBRT, and late grade 3 toxicity was observed in another three patients.ConclusionsLAPC patients who received chemotherapy and SBRT had favorable FFLP and OS with minimal treatment-related toxicity. The most common pattern of failure was distant metastasis, which warrants further studies on the optimal scheme of chemotherapy and SBRT.

Project description:Background and objectiveTo assess the efficacy of a Risk-Adapted Ablative Radiotherapy (RAdAR) approach, after intensive induction chemotherapy, in patients with locally advanced pancreatic cancer (LAPC).Material and methodsPatients with LAPC who received RAdAR following induction chemotherapy from January 2017 to December 2019 were included in this observational study. The RAdAR approach consisted of an anatomy- and simultaneous integrated boost (SIB)-based dose prescription strategy. RAdAR was delivered with stereotactic ablative radiation therapy (SAbR), administering 30 Gy in 5 fractions to the tumor volume (PTVt) and 50 Gy SIB (BED10 100 Gy) to the vascular involvement, or with (hypo-)fractionated ablative radiotherapy (HART) prescribing 50.4 Gy in 28 fractions to the PTVt, with a vascular SIB of 78.4 Gy (BED10 100 Gy). Primary end points were freedom from local progression (FFLP), overall survival (OS), and progression-free survival (PFS).ResultsSixty-four LAPC patients were included. Induction chemotherapy consisted of gemcitabine/nab-paclitaxel in 60.9% and FOLFIRINOX in 39.1% of cases. SAbR was used in 52 (81.2%) patients, and HART in 12 (18.8%). After RAdAR, surgery was performed in 17 (26.6%) patients. Median follow-up was 16.1 months. Overall local control (LC) rate was 78.1%, with no difference between resected and non-resected patients (2-year FFLP 75.3% vs 56.4%; p = 0.112). Median OS and PFS were 29.7 months and 8.7 months, respectively, for the entire cohort. Resected patients had a better median OS (not reached versus 26.1 months; p = 0.0001) and PFS (19 versus 5.6 months; p < 0.0001) compared to non-resected patients. In non-resected patients, no significant difference was found between SAbR and HART for median FFLP (28.1 versus 18.5 months; p = 0.614), OS (27.4 versus 25.3 months; p = 0.624), and PFS (5.7 versus 4.3 months; p = 0.486). One patient (1.6%) experienced acute grade 4 gastro-intestinal bleeding. No other acute or late grade ≥ 3 toxicities were observed.ConclusionsThe RAdAR approach, following intensive induction chemotherapy, is an effective radiation treatment strategy for selected LAPC patients, representing a promising therapeutic option in a multimodality treatment regimen.

Project description:IntroductionFOLFIRINOX (the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) is the preferred systemic regimen for locally advanced pancreatic cancer (LAPC). Furthermore, stereotactic body radiation therapy (SBRT) is a promising treatment option for achieving local control in these patients. However, clinical outcomes in patients with LAPC treated using FOLFIRINOX followed by SBRT have not been clarified. Therefore, we aimed to evaluate clinical outcomes of induction FOLFIRINOX treatment followed by SBRT in patients with LAPC.MethodsTo this end, we retrospectively reviewed the medical records of patients with LAPC treated with induction FOLFIRINOX followed by SBRT in a single tertiary hospital. We evaluated overall survival (OS), progression-free survival (PFS), resection rate, SBRT-related adverse events, and prognostic factors affecting survival.ResultsFifty patients were treated with induction FOLFIRINOX for a median of 8 cycles (range: 3-28), which was followed by SBRT. The median OS and PFS were 26.4 (95% confidence interval [CI]: 22.4-30.3) and 16.7 months (95% CI: 13.0-20.3), respectively. Nine patients underwent conversion surgery (eight achieved R0) and showed better OS than those who did not (not reached vs. 24.1 months, p = 0.022). During a follow-up period of 23.6 months, three cases of grade 3 gastrointestinal bleeding at the pseudoaneurysm site were noted, which were managed successfully. Analysis of the factors affecting clinical outcomes revealed that a high radiation dose (≥ 35 Gy) resulted in a higher rate of conversion surgery (25% [8/32] vs. 5.6% [1/18], respectively) and was an independent favorable prognostic factor for OS in the adjusted analysis (hazard ratio: 2.024, 95% CI: 1.042-3.930, p = 0.037).ConclusionOur findings suggest that induction FOLFIRINOX followed by SBRT in patients with LAPC results in better survival with manageable toxicities. A high total SBRT dose was associated with a high rate of conversion surgery and could afford better survival.

Project description:ImportanceSurgical resection has been considered the only curative option for patients with pancreatic cancer. Nonoperative local treatment options that can provide a similar benefit are needed. Emerging radiation techniques that address organ motion have enabled curative radiation doses to be given in patients with inoperable disease.ObjectiveTo determine the association of hypofractionated ablative radiation therapy (A-RT) with survival for patients with locally advanced pancreatic cancer (LAPC) treated with a novel radiation planning and delivery technique.Design, setting, and participantsThis cohort study included 119 consecutive patients treated with A-RT between June 2016 and February 2019 and enrolled in a prospectively maintained database. Patients were treated with a standardized technique within a large academic cancer center regional network. All patients with localized, unresectable, or medically inoperable pancreatic cancer with tumors of any size and less than 5 cm luminal abutment with the primary tumor were eligible.InterventionsAblative RT (98 Gy biologically effective dose) was delivered using standard equipment. Respiratory gating, soft tissue image guidance, and selective adaptive planning were used to address organ motion and limit the dose to surrounding luminal organs.Main outcomes and measuresThe primary outcome was overall survival (OS). Secondary outcomes included incidence of local progression and progression-free survival.ResultsBetween 2016 and 2019, 119 patients (59 men, median age 67 years) received A-RT, including 99 with T3/T4 and 53 with node-positive disease, with a median carbohydrate antigen 19-9 (CA19-9) level greater than 167 U/mL. Most (116 [97.5%]) received induction chemotherapy for a median of 4 months (0.5-18.4). Median OS from diagnosis and A-RT were 26.8 and 18.4 months, respectively. Respective 12- and 24-month OS from A-RT were 74% (95% CI, 66%-83%) and 38% (95% CI, 27%-52%). Twelve- and 24-month cumulative incidence of locoregional failure were 17.6% (95% CI, 10.4%-24.9%) and 32.8% (95% CI, 21.6%-44.1%), respectively. Postinduction CA19-9 decline was associated with improved locoregional control and survival. Grade 3 upper gastrointestinal bleeding occurred in 10 patients (8%) with no grade 4 to 5 events.Conclusions and relevanceThis cohort study of patients with inoperable LAPC found that A-RT following multiagent induction therapy for LAPC was associated with durable locoregional tumor control and favorable survival. Prospective randomized trials in patients with LAPC are warranted.

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Ablative radiation therapy for locally advanced pancreatic cancer: techniques and results.

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Ablative radiation therapy for locally advanced pancreatic cancer: techniques and results.

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