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.

scholarly journals Effectiveness of Carbon Ion Radiation in Locally Advanced Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jakob Liermann ◽  
Patrick Naumann ◽  
Fabian Weykamp ◽  
Philipp Hoegen ◽  
Juergen Debus ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Local Control ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Carbon Ion Radiotherapy ◽  
Free Survival ◽  
Carbon Ion

PurposeEffective treatment strategies for unresectable locally advanced pancreatic cancer (LAPC) patients are eagerly warranted. Recently, convincing oncological outcomes were demonstrated by carbon ion radiotherapy. Nevertheless, there is a lack of evidence for this modern radiation technique due to the limited number of carbon ion facilities worldwide. Here, we analyze feasibility and efficacy of carbon ion radiotherapy in the management of LAPC at Heidelberg Ion Beam Therapy Center (HIT).MethodsBetween 2015 and 2020, 21 LAPC patients were irradiated with carbon ions with a total dose of 48 Gy (RBE) in single doses of 4 Gy (RBE). Three patients (14%) were treated with concomitant chemotherapy with gemcitabine 300 mg/m2 body surface weekly. Toxicity rates were extracted from the charts. Overall survival, progression free survival, local control, and locoregional control were evaluated using Kaplan–Meier estimates.ResultsOne patient developed ascites CTCAE grade III during radiotherapy, which was related to a later histologically confirmed metachronous peritoneal carcinomatosis. No further higher-graded toxicity could be observed. The most common symptoms were nausea and abdominal pain. After a median estimated follow-up time of 19.1 months, the median progression free survival was 3.7 months, and the median overall survival was 11.9 months. The estimated 1-year local control and locoregional control rates were 89 and 84%, respectively.ConclusionCarbon ion radiotherapy of LAPC patients is safely feasible. Local tumor control rates were high. Nevertheless, compared to historical data, an overall survival improvement could not be observed. This could be explained by the poor prognosis of the selected underlying patients that mostly did not respond to prior chemotherapy as well as the early and frequent emergence of distant metastases that demonstrate the necessity of additional chemotherapy in further studies.

Comparison of concurrent chemoradiotherapy and chemotherapy alone for locally advanced pancreatic cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 351-351 ◽  
Author(s):  
Younak Choi ◽  
Tae-Yong Kim ◽  
Do-Youn Oh ◽  
Kyubo Kim ◽  
Eui Kyu Chie ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Outcomes ◽  
Palliative Chemotherapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Positive Lymph Node ◽  
Locally Advanced Pancreatic Cancer ◽  
Hematologic Toxicity

351 Background: The optimal treatment strategy for locally advanced pancreatic cancer (LAPC), especially the role of chemoradiotherapy (CCRT), is still in debate. We compared the clinical outcomes of CCRT and palliative chemotherapy alone (CA) in patients with LAPC. Methods: We consecutively enrolled LAPC patients treated between 2003 and 2010. AJCC 7th edition was followed for the diagnostic criteria of LAPC. We retrospectively evaluated the clinical outcomes according to treatment groups (CCRT vs CA). Results: A total of 86 patients were enrolled. Median age was 60 years. ECOG PS was 0-1 in 77 (89.5%) and 2 in 9 (10.5%). Forty five patients (52.3%) were treated with CCRT and 41 patients (47.7%) with CA. Baseline characteristics were not significantly different between CCRT and CA group. In the CCRT group, gemcitabine (n=7, 15.6%), 5-FU (n=10, 22.2%), and capecitabine (n=28, 62.2%) were concurrently used with radiation. Radiation was delivered with 55.8Gy/ 31fraction. All of the CA group patients were treated with gemcitabine-based chemotherapy. Median progression free survival (PFS) and overall survival (OS) of whole patients were 6.9 months [95%CI 4.8-9.0] and 12.7 months [95%CI 11.6-14.3]. PFS and OS of CCRT versus CA was 8.9 months [95%CI 6.8-11.0] vs 3.7 months [95%CI 2.9-4.5] (p<0.001) and 15.8 months [95%CI 13.5-18.1] vs 11.3 months [95%CI 9.3-13.3] (p=0.017). In multivariate analysis, tumor size (≥3cm), positive lymph node, elevated CA 19-9, decreased serum albumin and CCRT was significant for PFS and OS (adjusted hazard ratio of CCRT was 0.424 (p=0.002) in PFS and 0.472 (p=0.014) in OS). Grade 3-4 hematologic toxicity was less frequent during CCRT period (p=0.002). Conclusions: In LAPC, patients who received CCRT show better OS and PFS compared with patients who were treated with palliative chemotherapy alone. It’s worthy to further study the role of CCRT in LAPC.

scholarly journals Can Stereotactic Body Radiation Therapy Be a Viable and Efficient Therapeutic Option for Unresectable Locally Advanced Pancreatic Adenocarcinoma? Results of a Phase 2 Study

2016 ◽  
Vol 16 (3) ◽  
pp. 295-301 ◽  
Author(s):  
Tiziana Comito ◽  
L. Cozzi ◽  
E. Clerici ◽  
C. Franzese ◽  
A. Tozzi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Stereotactic Body Radiotherapy ◽  
Therapeutic Option ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Local Progression

Purpose: To assess the efficacy of stereotactic body radiotherapy in patients with unresectable locally advanced pancreatic cancer. Materials and Methods: All patients received a prescription dose of 45 Gy in 6 fractions. Primary end point was freedom from local progression. Secondary end points were overall survival, progression-free survival, and toxicity. Actuarial survival analysis and univariate or multivariate analysis were investigated. Results: Forty-five patients were enrolled in a phase 2 trial. Median follow-up was 13.5 months. Freedom from local progression was 90% at 2 years. On univariate ( P < .03) and multivariate analyses ( P < .001), lesion size was statistically significant for freedom from local progression. Median progression-free survival and overall survival were 8 and 13 months, respectively. On multivariate analysis, tumor size ( P < .001) and freedom from local progression ( P < .002) were significantly correlated with overall survival. Thirty-two (71%) patients with locally advanced pancreatic cancer received chemotherapy before stereotactic body radiotherapy. Median overall survival from diagnosis was 19 months. Multivariate analysis showed that freedom from local progression ( P < .035), tumor diameter ( P < .002), and computed tomography before stereotactic body radiotherapy ( P < .001) were significantly correlated with overall survival from diagnosis. Conclusion: Stereotactic body radiotherapy is a safe and effective treatment for patients with locally advanced pancreatic cancer with no G3 toxicity or greater and could be a promising therapeutic option in multimodality treatment regimen.

Phase II Study of Induction Chemotherapy with Gemcitabine plus 5-Fluorouracil Followed by Gemcitabine-Based Concurrent Chemoradiotherapy for Unresectable Locally Advanced Pancreatic Cancer

2006 ◽  
Vol 92 (6) ◽  
pp. 481-486 ◽  
Author(s):  
Ender Kurt ◽  
Meral Kurt ◽  
Ozkan Kanat ◽  
Sibel Kahraman Cetintas ◽  
Sevilcan Aygun ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
External Beam Radiotherapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Disease Stabilization ◽  
Grade 3

Aims and background To evaluate the efficacy and tolerability of a new treatment approach including induction chemotherapy (CT) and concurrent chemoradiotherapy (CRT) in unresectable, locally advanced pancreatic cancer (LAPC). Patients and methods Twenty-four patients with LAPC were enrolled in the study. They first received induction CT consisting of 5-fluorouracil (5FU) (500 mg/m2) and gemcitabine (1000 mg/m2), which were given weekly for 3 weeks of every 4. Patients showing a response or disease stabilization after 2 cycles of induction CT received CRT consisting of external beam radiotherapy (50.4-54 Gy in fractions of 1.8 Gy/day) and gemcitabine (350 mg/m2, weekly for 6 weeks). Patients without disease progression received 2 additional cycles of CT consisting of 5FU plus gemcitabine with the same doses and schedule as given in the induction CT. Results After the end of the study, 2 (8%) and 5 (21%) patients showed complete and partial responses, respectively. Five patients (21%) had disease stabilization. The grade 3 and 4 toxicities associated with CT were neutropenia (21%) and thrombocytopenia (4%). The grade 3 and 4 toxicities occurring in patients who received CRT were neutropenia (24%), thrombocytopenia (24%), diarrhea (18%), and nausea (12%). The median progression-free survival for all patients was 6 months (95% CI, 3.6-8.4), and the median overall survival was 11 months (95% CI, 8.16-13.84). Conclusions The CRT approach of this study is moderately active and has an acceptable toxicity profile. However, the incor-poration of combination CT into CRT at the present schedule could not produce any additional benefit over CRT alone. Newer agents with more systemic activity are clearly warranted.

scholarly journals Biologically effective doses of 60-70Gy vs. >70Gy of stereotactic body radiotherapy (SBRT) combined with chemotherapy in locally advanced pancreatic cancer: protocol of a phase III study

2020 ◽  
Author(s):  
Yusheng Ye ◽  
Xiaofei Zhu ◽  
Xianzhi Zhao ◽  
Lingong Jiang ◽  
Yangsen Cao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Phase Iii Study ◽  
Radiation Induced ◽  
Gi Toxicity ◽  
Effective Doses

Abstract Background: There is controversial on the correlation between biologically effective dose (BED, α/β=10) of stereotactic body radiation therapy (SBRT) and clinical outcomes of patients with locally advanced pancreatic cancer (LAPC). Therefore, the aim of the study is to compare the survival benefits of BED10 of 60-70Gy with those of BED10＞70Gy.Methods: This study is a multicenter study. Patients with LAPC are randomly allocated into two groups. Arm1: SBRT with BED10 of 60-70Gy in 5-6 fractions combined with gemcitabine plus albumin-bound paclitaxel; Arm2: SBRT with BED10＞70Gy in 5-6 fractions combined with gemcitabine plus albumin-bound paclitaxel. The primary outcome is progression-free survival (PFS). The secondary outcomes are radiation-induced gastrointestinal (GI) toxicity, local control (LC) and overall survival (OS).Discussion: The pilot phase Ⅲ study could provide evidence for further decision making of prescription doses of SBRT for LAPC, which may improve survival outcomes without compromise of quality of life. The trial protocol has been approved by the Ethics committee of Shanghai Changhai hospital. The ethics number is CHEC2020-100.Trial registration: Clinical trials number: NCT04603586. Date of registration: 10/27/2020.

Definitive chemoradiation therapy with capecitabine in locally advanced pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15558-e15558
Author(s):  
S. Yi ◽  
H. S. Kim ◽  
J. Lee ◽  
S. Park ◽  
Y. Park ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Disease Control ◽  
Combined Therapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Hematologic Toxicity ◽  
Group 2 ◽  
Adverse Factor

e15558 Background: We evaluated safety and efficacy of concurrent chemoradiotherapy (CCRT) with capecitabine in patients with locally advanced pancreatic cancer (LAPC). We also tried to devise a prognostic model for LAPC undergoing definitive CCRT. Methods: Between January 2004 and January 2008, 39 patients with LAPC treated with capecitabine CCRT were reviewed. Capecitabine was administered at 850 mg/m2 bid every day for 5 weeks. Radiotherapy was given 5 days per week, at 1.8 Gy fractions, over the 5 weeks. Results: Thirty seven (94.8%) patients completed CCRT, and 2 patients removed during the treatment for toxicity issues. Of the 36 evaluable patients, 15 (41.7 %) patients achieved partial response, and 13 (36.1 %) had a stable disease with 77.8% of disease control rate. Among the 28 patients who had achieved disease control after CCRT, 8 patients (21.6 %) received gemcitabine-based post-CCRT chemotherapy without dose reduction or delay. With median 1.8 years of follow- up, the overall survival was 14.3 months (95% confidence interval [CI]; 10.6–17.9 months). Median progression free survival was 11.1 (95% CI 7.2–15.1) for all patients, and 7.9 months (95% CI 6.6–9.2) for those not received post-CCRT chemotherapy. No patient had grade 4 hematologic or non-hematologic toxicity. Eight patients (21.6%) had severe grade 3 toxicities, 7 (18.9%) with gastrointestinal toxicity and 1 (2.7%) with hematologic toxicity. Prognostic factors for survival were serum albumin (P=0.014; relative risk [RR], 3.4; 95% CI, 1.4, 8.6), and adjuvant gemcitabine treatment (P = 0.005; RR, 3.5; 95% CI, 1.2, 10.6). The prognostic grouping resulted in three groups with significantly different prognosis: group 1 (0 adverse factor; n=8; 1-year survival, 87.5%), group 2 (1 adverse factor; n=23; 1-year survival, 52.9%) and group 3 (2 adverse factors; n=8; 1-year survival, 25.0%). Conclusions: Combined therapy with capecitabine CCRT was well tolerated. Capecitabine seems to be a promising regimen in the treatment of LAPC, in terms of response, survival, and tolerable adverse effects. No significant financial relationships to disclose.

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 &lt; 33 Gy for luminal OARs and D0.5cc &lt; 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 &lt; 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 &lt; 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 Dose Escalation Trial of the Wee1 Inhibitor Adavosertib (AZD1775) in Combination With Gemcitabine and Radiation for Patients With Locally Advanced Pancreatic Cancer

2019 ◽  
Vol 37 (29) ◽  
pp. 2643-2650 ◽  
Author(s):  
Kyle C. Cuneo ◽  
Meredith A. Morgan ◽  
Vaibhav Sahai ◽  
Matthew J. Schipper ◽  
Leslie A. Parsels ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Phase Ii ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Free Survival ◽  
Recommended Phase Ii Dose

PURPOSE AZD1775 (adavosertib) is an inhibitor of the Wee1 kinase. In this study, we built on our preclinical studies to evaluate the safety and efficacy of AZD1775 in combination with gemcitabine and radiation in patients with newly diagnosed locally advanced pancreatic cancer. PATIENTS AND METHODS Thirty-four patients with locally advanced pancreatic cancer were enrolled with the intention to receive four 21-day cycles of gemcitabine (1,000 mg/m2 days 1 and 8) with AZD1775 (once daily on days 1, 2, 8, and 9). Cycles 2 and 3 were administered concurrently with radiation, and cycles 5 to 8 were optional. AZD1775 was dose escalated using a time-to-event continual reassessment method on the basis of the rate of dose-limiting toxicities within the first 15 weeks of therapy. The primary objective was to determine the maximum tolerated dose of AZD1775 given in conjunction with gemcitabine and radiation. Secondary objectives were to estimate overall and progression-free survival and determine pharmacodynamic activity of AZD1775 in surrogate tissues. RESULTS The recommended phase II dose of AZD1775 was 150 mg/d. Eight patients (24%) experienced a dose-limiting toxicity, most commonly anorexia, nausea, or fatigue. The median overall survival for all patients was 21.7 months (90% CI, 16.7 to 24.8 months), and the median progression-free survival was 9.4 months (90% CI, 8.0 to 9.9 months). Hair follicle biopsy samples demonstrated evidence of Wee1 inhibition with decreased phosphorylation of cyclin-dependent kinase 1 staining by immunohistochemistry after AZD1775 administration at the recommended phase II dose. CONCLUSION AZD1775 in combination with gemcitabine and radiation therapy was well tolerated at a dose that produced target engagement in a surrogate tissue. The overall survival is substantially higher than prior results combining gemcitabine with radiation therapy and warrants additional investigation.

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