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Stereotactic Body Radiation Therapy for Locally Progressive and Recurrent Pancreatic Cancer after Prior Radiation.

ABSTRACT: Introduction:Pancreatic adenocarcinoma is an aggressive malignancy that has consistently demonstrated poor outcomes despite aggressive treatments. Despite multimodal treatment, local disease progression and local recurrence are common. Management of recurrent or progressive pancreatic carcinomas proves a further challenge. In patients previously treated with radiation therapy, stereotactic body radiation therapy (SBRT) is a promising modality capable of delivering high dose to the tumor while limiting dose to critical structures. We aimed to determine the feasibility and tolerability of SBRT for recurrent or local pancreatic cancer in patients previously treated with external beam radiation therapy (EBRT). Materials and methods:Patients treated with EBRT who developed recurrent or local pancreatic ductal adenocarcinoma treated with SBRT reirradiation at our institution, from 2004 to 2014 were reviewed. Our primary endpoints included overall survival (OS), local control, regional control, and late grade 3+ radiation toxicity. Endpoints were analyzed with the Kaplan-Meier method. The association of these survival endpoints with risk factors was studied with univariate Cox proportional hazards models. Results:We identified 38 patients with recurrent/progressive pancreatic cancer treated with SBRT following prior radiation therapy. Prior radiation was delivered to a median dose of 50.4?Gy in 28 fractions. SBRT was delivered to a median dose of 24.5?Gy in 1-3 fractions. Surgical resection was performed on 55.3% of all patients. Within a median follow-up of 24.4?months (inter-quartile range, 14.9-32.7?months), the median OS from diagnosis for the entire cohort was 26.6?months (95% CI: 20.3-29.8) with 2-year OS of 53.0%. Median survival from SBRT was 9.7?months (95% CI, 5.5-13.8). The 2-year freedom from local progression and regional progression was 58 and 82%, respectively. For the entire cohort, 18.4 and 10.5% experienced late grade 2+ and grade 3+ toxicity, respectively. Conclusion:This single institution retrospective review identified SBRT reirradiation to be a feasible and tolerable treatment strategy for patients with previous locally progressive or recurrent pancreatic adenocarcinoma.

SUBMITTER: Sutera P

PROVIDER: S-EPMC5845878 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Stereotactic Body Radiation Therapy for Locally Progressive and Recurrent Pancreatic Cancer after Prior Radiation.

Sutera Philip P Bernard Mark E ME Wang Hong H Bahary Nathan N Burton Steven S Zeh Herbert H Heron Dwight E DE

Frontiers in oncology 20180307

<h4>Introduction</h4>Pancreatic adenocarcinoma is an aggressive malignancy that has consistently demonstrated poor outcomes despite aggressive treatments. Despite multimodal treatment, local disease progression and local recurrence are common. Management of recurrent or progressive pancreatic carcinomas proves a further challenge. In patients previously treated with radiation therapy, stereotactic body radiation therapy (SBRT) is a promising modality capable of delivering high dose to the tumor ...[more]

PMID: 29564223

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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:PurposeStereotactic body radiation therapy (SBRT) has emerged as a potential therapeutic option for locally recurrent rectal cancer (LRRC) but contemporaneous clinical data are limited. We aimed to evaluate the local control, toxicity, and survival outcomes in a cohort of patients previously treated with neoadjuvant pelvic radiation therapy for nonmetastatic locally recurrent rectal cancer, now treated with SBRT.Methods and materialsInoperable rectal cancer patients with ≤3 sites of pelvic recurrence and >6 months since prior pelvic radiation therapy were identified from a prospective registry over 4 years. SBRT dose was 30 Gy in 5 fractions, daily or alternate days, using cumulative organ at risk dose constraints. Primary outcome was local control (LC). Secondary outcomes were progression free survival, overall survival, toxicity, and patient reported quality of life scores using the EQ visual analog scale (EQ-VAS) tool.ResultsThirty patients (35 targets) were included. Median gross tumor volume size was 14.3 cm3. In addition, 27 of 30 (90%) previously received 45 to 50.4 Gy in 25 of 28 fractions, with 10% receiving an alternative prescription. All patients received the planned reirradiation SBRT dose. The median follow-up was 24.5 months (interquartile range, 17.8-28.8). The 1-year LC was 84.9% (95% confidence interval [CI], 70.6-99) and a 2-year LC was 69% (95% CI, 51.8-91.9). The median progression free survival was 12.1 months (95% CI, 8.6-17.66), and median overall survival was 28.3 months (95% CI, 17.88-39.5 months). No patient experienced >G2 acute toxicity and only 1 patient experienced late G3 toxicity. Patient-reported QoL outcomes were improved at 3 months after SBRT (Δ EQ-VAS, +10 points, Wilcoxon signed-rank, P = .009).ConclusionsOur study demonstrates that, for small volume pelvic disease relapses from rectal cancer, reirradiation with 30 Gy in 5 fractions is well tolerated and achieves an excellent balance between high local control rates with limited toxicity.

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:We previously reported clinical outcomes and physician-reported toxicity of gemcitabine and hypofractionated stereotactic body radiation therapy (SBRT) in locally advanced pancreatic cancer (LAPC). Here we prospectively investigate the impact of gemcitabine and SBRT on patient-reported quality of life (QoL).Forty-nine LAPC patients received 33 Gy SBRT (6.6 Gy daily fractions) upfront or after ≤3 doses of gemcitabine (1000 mg/m2) followed by gemcitabine until progression. European Organization for Research and Treatment of Cancer QoL core cancer (QLQ-C30) and pancreatic cancer-specific (European Organization for Research and Treatment of Cancer QLQ-PAN26) questionnaires were administered to patients pre-SBRT and at 4 to 6 weeks (first follow-up [1FUP]) and 4 months (2FUP) post-SBRT. Changes in QoL scores were deemed clinically relevant if median changes were at least 5 points in magnitude.Forty-three (88%) patients completed pre-SBRT questionnaires. Of these, 88% and 51% completed questionnaires at 1FUP and 2FUP, respectively. There was no change in global QoL from pre-SBRT to 1FUP (P = .17) or 2FUP (P > .99). Statistical and clinical improvements in pancreatic pain (P = .001) and body image (P = .007) were observed from pre-SBRT to 1FUP. Patients with 1FUP and 2FUP questionnaires reported statistically and clinically improved body image (P = .016) by 4 months. Although pancreatic pain initially demonstrated statistical and clinical improvement (P = .020), scores returned to enrollment levels by 2FUP (P = .486). A statistical and clinical decline in role functioning (P = .002) was observed in patients at 2FUP.Global QoL scores are not reduced with gemcitabine and SBRT. In this exploratory analysis, patients experience clinically relevant short-term improvements in pancreatic cancer-specific symptoms. Previously demonstrated acceptable clinical outcomes combined with these favorable QoL data indicate that SBRT can be easily integrated with other systemic therapies and may be a potential standard of care option in patients with LAPC.

Dataset Information

Stereotactic Body Radiation Therapy for Locally Progressive and Recurrent Pancreatic Cancer after Prior Radiation.

Publications

Stereotactic Body Radiation Therapy for Locally Progressive and Recurrent Pancreatic Cancer after Prior Radiation.

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