The Evolving Field of Stereotactic Body Radiation Therapy in Pancreatic Cancer.
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ABSTRACT:
SUBMITTER: Ghaly M
PROVIDER: S-EPMC6954104 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Publications
The Evolving Field of Stereotactic Body Radiation Therapy in Pancreatic Cancer.
Ghaly Maged M Gogineni Emile E Saif Muhammad W MW
Pancreas (Fairfax, Va.) 20191106 1
Pancreatic cancer remains a devastating disease with dismal outcomes despite the development of novel chemotherapeutic regimens and radiation techniques. Stereotactic body radiation therapy (SBRT) offers an advantage both in image guidance and radiation dose delivery to direct ablative doses to tumors with acceptable toxicity compared to conventional techniques. Recent literature is clustered with data pertaining to SBRT in patients with resectable, borderline resectable and locally advanced pan ...[more]
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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.
| S-EPMC6461258 | biostudies-literature
Project description:Pancreatic cancer is a formidable malignancy with poor outcomes. The majority of patients are unable to undergo resection, which remains the only potentially curative treatment option. The management of locally advanced (unresectable) pancreatic cancer is controversial; however, treatment with either chemotherapy or chemoradiation is associated with high rates of local tumor progression and metastases development, resulting in low survival rates. An emerging local modality is stereotactic body radiation therapy (SBRT), which uses image-guided, conformal, high-dose radiation. SBRT has demonstrated promising local control rates and resultant quality of life with acceptable rates of toxicity. Over the past decade, increasing clinical experience and data have supported SBRT as a local treatment modality. Nevertheless, additional research is required to further evaluate the role of SBRT and improve upon the persistently poor outcomes associated with pancreatic cancer. This review discusses the existing clinical experience and technical implementation of SBRT for pancreatic cancer and highlights the directions for ongoing and future studies.
| S-EPMC5096771 | biostudies-literature
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| S-EPMC5845878 | biostudies-literature
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.
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Project description:PurposeRadiation-induced lymphopenia (RIL) is associated with inferior survival in patients with glioblastoma, lung cancer, and pancreatic cancer. We asked whether stereotactic body radiation therapy (SBRT) decreases severity of RIL compared to conventional chemoradiation therapy (CRT) in locally advanced pancreatic cancer (LAPC).Methods and materialsSerial total lymphocyte counts (TLCs) from patients enrolled in a prospective trial of SBRT for LAPC were compared to TLCs from an existing database of LAPC patients undergoing definitive CRT. SBRT patients received 33 Gy (6.6 Gy × 5 fractions). CRT patients received a median dose of 50.4 Gy (1.8 Gy × 28 fractions) with concurrent 5-fluorouracil (77%) or gemcitabine (23%) therapy. Univariate and multivariate analyses (MVA) were used to identify associations between clinical factors and post-treatment TLC and between TLC and survival.ResultsThirty-two patients received SBRT and 101 received CRT. Median planning target volume (PTV) was smaller in SBRT (88.7 cm(3)) than in CRT (344.6 cm(3); P<.001); median tumor diameter was larger for SBRT (4.6 cm) than for CRT (3.6 cm; P=.01). SBRT and CRT groups had similar median baseline TLCs. One month after starting radiation, 71.7% of CRT patients had severe lymphopenia (ie, TLC <500 cells/mm(3) vs 13.8% of SBRT patients; P<.001). At 2 months, 46.0% of CRT patients remained severely lymphopenic compared with 13.6% of SBRT patients (P=.007). MVA demonstrated that treatment technique and baseline TLCs were significantly associated with post-treatment TLC at 1 but not 2 months after treatment. Higher post-treatment TLC was associated with improved survival regardless of treatment technique (hazard ratio [HR] for death: 2.059; 95% confidence interval: 1.310-3.237; P=.002).ConclusionsSBRT is associated with significantly less severe RIL than CRT at 1 month in LAPC, suggesting that radiation technique affects RIL and supporting previous modeling studies. Given the association of severe RIL with survival in LAPC, further study of the effect of radiation technique on immune status is warranted.
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Project description:In todays practice most institutions individualize the use of adjuvant, neoadjuvant, and definitive RT based on their interpretation of the available data. This review highlights novel concepts and approaches to the use of RT that should be considered by the surgical oncologist.
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Project description:BackgroundWe explored the safety and efficacy of ablative doses of stereotactic body radiation therapy (SBRT) for unresectable pancreatic cancer.MethodsThis phase I/II trial included patients with unresectable pancreatic cancer previously treated with any number of cycles of induction chemotherapy. Patients were enrolled according to a 3+3 dose escalation design at 10, 12.5, and 15 Gy ×3, with subsequent patients at the maximally tolerated dose (MTD). Treatment was delivered to gross tumor delineated with MRI fusion using image-guidance to fiducial markers. Dose-limiting toxicity (DLT) was defined as grade 3+ toxicity within 30 days. Secondary endpoints included late gastrointestinal (GI) toxicity, freedom from local failure (FFLF), and survival.ResultsFifteen patients received a median 10 cycles of chemotherapy. There were no DLTs, and the MTD was 15 Gy ×3. Thirty-day toxicity included grade 2 nausea (46%) and grade 2 diarrhea (7%). Median survival after SBRT was 12.8 months (23 months after diagnosis) and median relapse-free survival was 7 months. At 1-year, FFLF was 80%. Four patients had grade 3+ GI bleeding after 30 days (median 6 months). Grade 3+ GI bleeding was associated with tumor volume (P=0.01), heterogeneity of dose within the planning target volume (PTV) (V120, P=0.03), and duodenal dose (V26-30 Gy, P<0.2).ConclusionsThis aggressive SBRT regimen demonstrated limited 30-day morbidity, a moderate degree of local control, and a moderate risk for late GI bleeding. Further work is necessary to define the most appropriate hypofractionated radiation therapy (RT) regimen in the ablative dose range.
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Project description:ObjectivesThe purpose of this study was to determine if vertebral body and splenic dosimetry was associated with the development of lymphopenia in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiation therapy (SBRT).MethodsPatients with BRPC/LAPC who were treated with SBRT and who had lymphocyte counts and radiation treatment plans available for review were included in the study. Vertebral body levels T11-L3 and the spleen were retrospectively contoured for each patient. Univariate (UVA) and multivariable analyses (MVA) were performed to identify associations between vertebral body and splenic dosimetric parameters with absolute lymphocyte count (ALC) and grade ≥ 2 lymphopenia. Receiver operator characteristic curves were generated to identify dose-volume thresholds in predicting grade ≥ 2 lymphopenia.ResultsA total of 132 patients were included in the study. On UVA and MVA, vertebral V15 (regression coefficient [β]: - 0.026, 95% CI - 0.044 to - 0.009, p = 0.003), vertebral V2.5 (β: - 0.011, 95% CI - 0.020 to - 0.002, p = 0.015), and log10PTV (β: - 0.15, 95% CI - 0.30 to - 0.005, p = 0.042) were associated with post-SBRT ALC. On UVA and MVA, vertebral V15 (odds ratio [OR]: 3.98, 95% CI 1.09-14.51, p = 0.027), vertebral V2.5 (OR: 1.04, 95% CI 1.00-1.09, p = 0.032), and spleen V10 (OR: 1.05, 95% CI 1.09-1.95, p = 0.004) were associated with development of grade ≥ 2 lymphopenia. Development of grade ≥ 2 lymphopenia was more likely in patients with vertebral V15 ≥ 5.84% (65.5% vs 34.0%, p = 0.002), vertebral V2.5 ≥ 48.36% (48.9% vs 23.8%, p = 0.005), and spleen V10 ≥ 4.17% (56.2% vs 26.9%, p < 0.001).ConclusionsIncreasing radiation dose to vertebral bodies and spleen were associated with the development of lymphopenia in BRPC/LAPC treated with SBRT. Optimization of vertebral body and splenic dosimetry may reduce the risk of developing lymphopenia and improve clinical outcomes in this population.
| S-EPMC8709967 | biostudies-literature
Project description:BACKGROUND:This study evaluates the outcomes and toxicity of stereotactic body radiation therapy (SBRT) in ovarian cancer. METHODS:This retrospective analysis considered all patients treated with SBRT from 2009 to 2018 with a primary ovarian tumor. Follow-up included PET-CT and CT scans at 2-3?month intervals. Statistical analysis primarily consisted of univariate analysis, Cox proportional hazards analysis, and the Kaplan-Meier method. RESULTS:The study included 35 patients with 98 treatments for lymph nodes (51), local recurrence (21), and de novo solid metastases (26). Median biologically effective dose (BED), gross tumor volume, and planning target volume were 38.40?Gy, 10.41?cc, and 25.21?cc, respectively. 52 lesions showed complete radiographic response, and two-year local control was 80%. Median overall survival (OS) was 35.2?months, and two-year progression-free survival (PFS) was 12%. On univariate analysis, Eastern Cooperative Oncology Group performance status >?0 was predictive of decreased OS (p?=?0.0024) and PFS (p?=?0.044). Factors predictive of local failure included lower BED (p?=?0.016), treatment for recurrence (p?=?0.029), and higher pre-treatment SUV (p?=?0.026). Kaplan-Meier analysis showed BED ?35?Gy (p?<?0.005) and treatment for recurrence (p?=?0.01) to be predictive of local failure. On Cox proportional hazards analysis, treatment of lymph nodes was predictive of complete radiographic response (hazard ratio (HR)?=?4.95), as was higher BED (HR?=?1.03). Toxicity included 27 cases of grade?<?3 toxicity, and one grade 5 late toxicity of GI bleed from a radiation therapy-induced duodenal ulcer. CONCLUSIONS:SBRT provides durable local control with minimal toxicity in ovarian cancer, especially with BED >?35?Gy and treatment for lymph nodes.
| S-EPMC7222303 | biostudies-literature