Dataset Information

Induction Chemotherapy with Gemcitabine and Cisplatin Followed by Simultaneous Integrated Boost-Intensity Modulated Radiotherapy with Concurrent Gemcitabine for Locally Advanced Unresectable Pancreatic Cancer: Results from a Feasibility Study.

ABSTRACT:

Purpose

This study assessed the feasibility and compliance of induction chemotherapy with gemcitabine and cisplatin followed by simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) with concurrent gemcitabine in patients with locally advanced unresectable pancreatic cancer.

Materials and methods

In this trial, patients received induction chemotherapy consisting of gemcitabine (1,000 mg/m2) and cisplatin (25 mg/m2) on days 1, 8, and 15 of each treatment cycle. Patients were subsequently treated with gemcitabine (300 mg/m2/wk) during SIB-IMRT. The patients received total doses of 55 and 44 Gy in 22 fractions to planning target volume 1 and 2, respectively. As an ancillary study, digital polymerase chain reaction was performed to screen for the seven most common mutations in codons 12 and 13 of the KRAS oncogene of circulating cell free DNA (cfDNA).

Results

Forty-four patients were enrolled between 2012 and 2015. Of these, 33 (75%) completed the treatment. The most common toxicities during induction chemotherapy were grades 3 and 4 neutropenia (18.2%), grade 3 nausea (6.8%) and vomiting (6.8%). The most common toxicities during SIB-IMRT were grade 3 neutropenia (24.2%) and grade 3 anemia (12.1%). Ten patients (23%) underwent a curative resection after therapy. Median overall survival was significantly longer in patients who underwent curative resection (16.8 months vs. 11 months, p < 0.01). The median cfDNA concentration was significantly lower after treatment (108.5 ng/mL vs. 18.4 ng/mL, p < 0.001).

Conclusion

Induction chemotherapy with gemcitabine and cisplatin followed by concurrent SIB-IMRT was well tolerated and active.

SUBMITTER: Woo SM

PROVIDER: S-EPMC5654154 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Publications

Induction Chemotherapy with Gemcitabine and Cisplatin Followed by Simultaneous Integrated Boost-Intensity Modulated Radiotherapy with Concurrent Gemcitabine for Locally Advanced Unresectable Pancreatic Cancer: Results from a Feasibility Study.

Woo Sang Myung SM Kim Min Kyeong MK Joo Jungnam J Yoon Kyong-Ah KA Park Boram B Park Sang-Jae SJ Han Sung-Sik SS Lee Ju Hee JH Hong Eun Kyung EK Kim Yun-Hee YH Moon Hae H Kong Sun-Young SY Kim Tae Hyun TH Lee Woo Jin WJ

Cancer research and treatment 20170119 4

<h4>Purpose</h4>This study assessed the feasibility and compliance of induction chemotherapy with gemcitabine and cisplatin followed by simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) with concurrent gemcitabine in patients with locally advanced unresectable pancreatic cancer.<h4>Materials and methods</h4>In this trial, patients received induction chemotherapy consisting of gemcitabine (1,000 mg/m2) and cisplatin (25 mg/m2) on days 1, 8, and 15 of each treatment cycle. ...[more]

PMID: 28111423

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Project description:Background and purposeA phase 2 study LAPACT indicated nab-paclitaxel plus gemcitabine (AG) improved outcomes of patients with locally advanced pancreatic cancer (LAPC). Conventional radiotherapy failed to show benefit, indicating high dose to volume with high risk of recurrence is needed. The high dose can be delivered through hypofractionated tomotherapy with simultaneous integrated boost (SIB). However, there is a lack of such prospective trials and more data are needed to validate the role of AG plus hypofractionated tomotherapy with SIB in patients with LAPC.Materials and methodsPatients with LAPC receiving AG plus tomotherapy at the Nanjing Drum Tower Hospital between 2018 and 2021 were retrospectively analyzed. The treatment was scheduled as follows: nab-paclitaxel 125 mg/m2 plus gemcitabine 1,000 mg/m2 on days 1 and 8 every three weeks for at least two cycles, followed by hypofractionated tomotherapy with SIB (high dose field: 50 Gy/10 fractions, the remainder: 30 Gy/10 fractions). Then patients were given AG until intolerance or disease progression.ResultsOverall, 22 patients completing the chemoradiotherapy were included. The median follow-up was 15.2 months. After the chemoradiotherapy, 5 patients achieved a partial response (PR), 15 had a stable disease (SD), and another 2 patients were with progressive disease (PD). The median progression-free survival (PFS) and overall survival (OS) were 12.8 months (95% confidence interval [CI] 4.3-21.3 months) and 16.3 months (95% CI 10.9-21.6 months), respectively. The optimal carbohydrate antigen (CA) 19-9 response and chemotherapy cycles ≥6 were correlated with favorable PFS and OS. The most common recurrent pattern was peritoneal dissemination (22.7%) and the locoregional recurrence rate was relatively low (4.5%). Treatments were well-tolerated. The most common grade ≥3 adverse event was thrombocytopenia (13.6%).ConclusionThis study demonstrated the feasibility of AG followed by hypofractionated tomotherapy with SIB in patients with LAPC. The hypofractionated tomotherapy with SIB was safe and showed high local control rate. Further study with a larger population to validate our data is underway.

Project description:PurposeThe use of concurrent doublet chemotherapy with radiation for locoregionally advanced cervical cancer (LACC) is limited by gastrointestinal and hematologic toxicity. By reducing radiation dose to bowel and bone marrow, image guided intensity modulated radiation therapy (IG-IMRT) may improve chemotherapy tolerance. The goal of this study was to determine whether IG-IMRT could lead to improved tolerance to concurrent cisplatin and gemcitabine for LACC.Methods and materialsWe conducted an open-label, nonrandomized, prospective phase 1 dose escalation trial at a tertiary academic cancer center (ClinicalTrials.gov identifier: NCT01554410). We enrolled patients with stage IB-IVA cervical cancer, with either an intact cervix or posthysterectomy with residual/recurrent pelvic or paraortic nodal involvement, undergoing radical pelvic or extended field chemoradiation therapy. Treatment consisted of chemoradiation with IG-IMRT (45-47.6 Gy, 25-28 fractions to the pelvis ± paraortic nodes with simultaneous nodal boost to 53.2-59.4 Gy, 28 fractions) plus 5 cycles of concurrent weekly cisplatin 40 mg/m2 with escalating doses of gemcitabine (50, 75, 100, or 125 mg/m2). Cohorts were separated preregistration according to whether the patient received pelvic or extended field IG-IMRT and whether gemcitabine followed (CG) or preceded (GC) cisplatin delivery. Dose-limiting toxicity (DLT) events were monitored up to 30 days after chemoradiation therapy. The primary endpoint was maximum tolerated dose (MTD) resulting in DLT probability ≤20%.ResultsBetween February 2011 and June 2019, 35 patients were registered. Overall, 7 patients (20.0%) experienced DLTs. For the pelvic field cohort, the estimated MTD was 100 mg/m2 with GC sequencing, which is higher than the previously reported MTD for this regimen. The extended field cohort was closed after 2 of 3 patients experienced a DLT at the first dose level.ConclusionsIG-IMRT can permit higher doses of concurrent gemcitabine with cisplatin and pelvic radiation for LACC. However, acute toxicity remains a factor with this regimen, depending on radiation volume and chemotherapy sequencing.

Project description:ObjectiveThis study aimed to evaluate the efficacy and safety of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) versus standard-dose intensity-modulated radiotherapy (SD-IMRT) in the treatment of locally advanced esophageal squamous cell carcinoma.MethodsFrom July 2003 to March 2014, 1748 patients in a single center who received definitive chemoradiotherapy were included in the analysis. A total of 109 patients who underwent SIB-IMRT and fulfilled all inclusion and exclusion criteria were identified as the study group. A total of 266 patients who underwent SD-IMRT (60 Gy/30 fractions, 2 Gy/fraction, 1 time/day, 5 times/week) during the same period were selected as the control group. Propensity score matching (PSM) was used to balance the baseline characteristics. Survival status, treatment failure mode, and the occurrence of adverse events were compared between the two groups.ResultsThere were more women and more cervical and upper thoracic cancers (P = 0.038, < 0.001, respectively) in the SIB-IMRT group before case matching. The median progression-free survival (PFS) in the SD-IMRT and SIB-IMRT groups was 22 and 19 months, respectively, and the median overall survival duration was 24 and 22 months, respectively, with χ2 = 0.244 and P = 0.621. After PSM of 1:1, 138 patients entered the final analysis (69 cases from each group). The median PFS of the SD-IMRT group and the SIB-IMRT group was 13 and 18 months, respectively, with χ2 = 8.776 and P = 0.003. The 1‑, 3‑, and 5‑year overall survival rates were 66.7, 21.7, and 8.7% and 65.2, 36.2, and 27.3%, respectively, and the median overall survival duration was 16 and 22 months, respectively, with χ2 = 5.362 and P = 0.021. Treatment failure mode: 5‑year local regional recurrence rates of SD-IMRT and SIB-IMRT were 50.7 and 36.2%, respectively, with χ2 = 2.949 and P = 0.086. The 5‑year distant metastasis rates of the two groups were 36.2 and 24.6%, respectively, with χ2 = 2.190 and P = 0.139.Adverse events3 patients experienced grade 4-5 toxicity (2.2%), including one case of grade 4 radiation esophagitis and two cases of grade 5 radiation pneumonitis, all in the SD-IMRT group; 14 patients experienced grade 3 adverse events (10.1%), primarily including radiation esophagitis, radiation pneumonitis, and hematological toxicity.ConclusionThe technique of SIB-IMRT was safe and reliable compared with SD-IMRT. In addition, SIB-IMRT had locoregional control advantages and potential survival benefits.

Project description:PurposeWhile intensity modulated proton therapy can deliver simultaneous integrated boost (SIB) to the dominant intraprostatic lesion (DIL) with high precision, it is sensitive to anatomic changes. We investigated the dosimetric effects from these changes based on pretreatment cone-beam computed tomographic (CBCT) images and identified the most important factors using a multilayer perceptron neural network (MLPNN).Methods and materialsDILs were contoured based on coregistered multiparametric magnetic resonance images for 25 previously treated prostate cancer patients. SIB plans were created with (1) prostate clinical target volume - V70 Gy = 98%; (2) DIL - V98 Gy > 95%; and (3) all organs at risk (OARs)"?> within clinical constraints. SIB plans were applied to daily CBCT-based deformed planning computed tomography (CT)"?>. DIL - V98 Gy, bladder/rectum maximum dose (Dmax) and volume changes, femur shifts, and the distance from DIL to organs at riskOARs"?> in both planning computed tomogramsCT"?> and CBCT were calculated. Wilcoxon signed-ranks tests were used to compare the changes. MLPNNs were used to model the change in ΔDIL - V98 Gy > 10% and bladder/rectum Dmax > 80 Gy, and the relative importance factors for the model were provided. The performances of the models were evaluated with receiver operating characteristic curves.ResultsComparing initial plan to the average from evaluation plans, respectively, DIL - V98 Gy was 89.3% ± 19.9% versus 86.2% ± 21.3% (P = .151); bladder Dmax 71.9 ± 0.6 Gy versus 74.5 ± 2.9 Gy (P < .001); and rectum Dmax 70.1 ± 2.4 Gy versus 74.9 ± 9.1Gy (P = .007). Bladder and rectal volumes were 99.6% ± 39.5% and 112.8% ± 27.2%, respectively, of their initial volume. The femur shift was 3.16 ± 2.52 mm. In the modeling of ΔDIL V98 Gy > 10%, DIL to rectum distance changes, DIL to bladder distance changes, and rectum volume changes ratio are the 3 most important factors. The areas under the receiver operating characteristic curves were 0.89, 1.00, and 0.99 for the modeling of ΔDIL - V98 Gy > 10%, and bladder and rectum Dmax > 80 Gy, respectively.ConclusionsDosimetric changes in DIL SIB with intensity modulated proton therapy can be modeled and classified based on anatomic changes on pretreatment images by an MLPNN.

Dataset Information

Induction Chemotherapy with Gemcitabine and Cisplatin Followed by Simultaneous Integrated Boost-Intensity Modulated Radiotherapy with Concurrent Gemcitabine for Locally Advanced Unresectable Pancreatic Cancer: Results from a Feasibility Study.

Purpose

Materials and methods

Results

Conclusion

Publications

Induction Chemotherapy with Gemcitabine and Cisplatin Followed by Simultaneous Integrated Boost-Intensity Modulated Radiotherapy with Concurrent Gemcitabine for Locally Advanced Unresectable Pancreatic Cancer: Results from a Feasibility Study.

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