Induction Gemcitabine Plus Concurrent Gemcitabine and Radiotherapy for Locally Advanced Unresectable or Resected Pancreatic Cancer

Youl, M.; Hashem, Sameh; Brade, Anthony; Dawson, Laura A.; Gallinger, Steven; Hedley, David W.; Jiang, Haiyan; Kim, J.; Krzyzanowska, Monika K.; Ringash, Jolie; Wong, Rebecca; Brierley, James D.

doi:10.1016/j.clon.2014.01.003

Cited by 15 publications

(22 citation statements)

References 36 publications

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“…Among the chemotherapy regimens, Gem+Radio presented the principal improvement in extending OS and PFS. This finding suggested that radiotherapy may block the progressive deterioration associated with advanced cancer and is consistent with the previous study of Youl et al (26), which identified that a gross tumor volume <48 cm 3 may be successfully targeted with radiotherapy. An additional three regimens, Gem+Cis, Gem+Erl+Bev and Gem+Cap+Erl, were better compared with Gem monotherapy in terms of OS and PFS.…”

Section: Discussionsupporting

confidence: 91%

Meta‑analysis of current chemotherapy regimens in advanced pancreatic cancer to prolong survival and reduce treatment‑associated toxicities

Chen

et al. 2018

Mol Med Report

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Unresectable advanced pancreatic cancer (APC) is a highly lethal malignancy. Although numerous chemotherapeutic regimens are available, evidence regarding the survival extension, the life quality improvement, the associated risks and occurrence rates of adverse effects, is required. The effects of 19 chemotherapy regimens on survival and treatment-associated toxicities in the context of APC treatment were comparatively assessed. A total of 23 randomized controlled trials were included in this network meta-analysis. For overall survival, five regimens, Gemcitabine (Gem)+radiotherapy (Radio), Gem+cisplatin (Cis), Gem+erlotinib (Erl)+bevacizumab (Bev), Gem+capecitabine (Cap)+Erl, and Gem+exatecan, were the most effective treatments, according to their respective high surface under the cumulative ranking (SUCRA) probabilities. Regarding the progression-free survival, five regimens, including Gem+Radio, Gem+Erl+Bev, Gem+Cis, Gem+Cap+Erl and Gem+pemetrexed, were the most effective treatments based on their SUCRA probabilities. Each regimen exhibited advantages and disadvantages, and 14 common treatment-associated toxicities were present in different proportions. The three principal toxic effects included haematological, gastrointestinal and constitutional symptoms. To improve survival, chemotherapy regimens with high SUCRA probabilities require prioritizing. Although treatment-associated toxicities are unavoidable, the regimens presented toxicities in distinct proportions. Therefore, clinicians should assess the disease status of the patients, and balance the benefits and risks of the selected treatment.

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Section: Discussionsupporting

confidence: 91%

Meta‑analysis of current chemotherapy regimens in advanced pancreatic cancer to prolong survival and reduce treatment‑associated toxicities

Chen

et al. 2018

Mol Med Report

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“…The primary endpoints of this study were the feasibility of and compliance with induction chemotherapy with gemcitabine and cisplatin followed by SIB-IMRT for patients with locally advanced unresectable pancreatic cancer. Because approximately 20% of patients with locally advanced disease develop early distant metastasis [ 4 , 17 ], it was expected that at least 80% of all patients would be eligible for SIB-IMRT upon completion of induction chemotherapy. The null hypothesis set the true compliance rate of patients eligible for SIB-IMRT at ≤ 60%.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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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.

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“…Moreover, OS and PFS were poor in patients with a large GTV in the present study, and some past studies showed that tumor size was a prognostic factor in CRT and surgery for pancreatic cancer. [32][33][34] Those results indicate that it may be better to perform IFRT by dose escalation for LAPC with a large tumor size.…”

Section: Discussionmentioning

confidence: 91%

How Much Was the Elective Lymph Node Region Covered in Involved-Field Radiation Therapy for Locally Advanced Pancreatic Cancer? Evaluation of Overlap Between Gross Target Volume and Celiac Artery–Superior Mesenteric Artery Lymph Node Regions

Umezawa

Ito

Wakita

et al. 2020

Advances in Radiation Oncology

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Purpose: The purpose of this study was to investigate the overlaps between gross target volume (GTV) and the celiac artery (CA) and superior mesenteric artery (SMA) lymph node regions and to examine the dose incidentally irradiated to the CA and SMA lymph node regions by involved-field radiation therapy (IFRT) for locally advanced pancreatic cancer (LAPC). Methods and Materials: Fifty-nine patients who had LAPC without distant metastasis were included. They received IFRT at 50.4 Gy in 28 fractions with 3-dimensional conformal radiation therapy. We calculated the percentages of overlap of GTV in the CA and SMA lymph node regions and examined what cases tend to have an overlap. We also investigated the dose metrics of CA and SMA lymph node regions by IFRT and the frequency of CA or SMA lymph node metastasis after IFRT. Results: The median GTV volume was 52.2 mL. Median overlap percentages in the CA and SMA lymph node regions were 39.2% and 28.6%, respectively. There was a significant correlation between GTV volume and SMA overlap percentage (P < .001). Although the SMA overlap percentage was higher in the pancreas head (P Z .028), the CA overlap percentage was higher in the pancreas body or tail (P Z .002). Median mean dose, D95, and minimum dose in the CA lymph node region were 50.1 Gy, 48.7 Gy, and 45.9 Gy, respectively, and those in the SMA lymph node region 49.9 Gy, 47.3 Gy, and 39.2 Gy, respectively. CA lymph node metastases after IFRT were detected in 4 patients (6.8%).

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Induction Gemcitabine Plus Concurrent Gemcitabine and Radiotherapy for Locally Advanced Unresectable or Resected Pancreatic Cancer

Cited by 15 publications

References 36 publications

Meta‑analysis of current chemotherapy regimens in advanced pancreatic cancer to prolong survival and reduce treatment‑associated toxicities

Meta‑analysis of current chemotherapy regimens in advanced pancreatic cancer to prolong survival and reduce treatment‑associated toxicities

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

How Much Was the Elective Lymph Node Region Covered in Involved-Field Radiation Therapy for Locally Advanced Pancreatic Cancer? Evaluation of Overlap Between Gross Target Volume and Celiac Artery–Superior Mesenteric Artery Lymph Node Regions

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