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.

Effectiveness and Safety of Simultaneous Integrated Boost-Proton Beam Therapy for Localized Pancreatic Cancer

“…However, the median OS and incidence of grade ≥3 toxicity in the present study were at the higher and lower end of the wide range reported previously, respectively. 9 – 15 , 25 …”

“…The prescribed doses for PTV1 and PTV2 were 45 GyE (EQD2, 54.4 GyE 10 ) and 30 GyE (EQD2, 32.5 GyE 10 ) in 10 fractions, 5 times a week, respectively ( Figure 1 ). The dose–volume constraints for the normal tissues have been described in our previous reports 9 , 20 – 23 : The maximum dose to the spinal cord were <27 GyE; the absolute volumes of the stomach and esophagus receiving ≥37 GyE were <2 cm 3 ; the absolute volumes of the duodenum and bowel receiving ≥35 GyE were <2 cm 3 ; the relative volumes of the liver receiving ≥27 GyE were below 60%; and the relative volumes of the kidney receiving ≥18 GyE were below 35%. The dose–volumetric parameters for target volumes and OARs are summarized in Supplementary Table 1.…”

Plasma Cell-Free DNA as a Predictive Marker after Radiotherapy for Hepatocellular Carcinoma

“…In a study of patients with head and neck squamous carcinoma, Mazurek, et al 12 reported that higher levels of cfDNA were observed in patients with advanced N stage and overall. Woo, et al 13 reported that cfDNA declined significantly after concurrent chemoradiotherapy in a study of patients with pancreatic cancer.…”

“…Investigations of the kinetics of circulating tumor-derived DNA in serum or plasma revealed that the amounts of cfDNA were found to increase at the beginning of RT and to decrease to or below initial levels by the end of treatment. 12 13 19 31 Therefore, the persistent elevation of cfDNA after treatment completion may indicate the presence of remnant lesions or progression in other sites. 32 33 After adjusting for other factors, a high post-RT cfDNA level was revealed to be an independent factor for poor intrahepatic tumor control.…”

“… 10 However, limited reports on the clinical significance of cfDNA in RT are available for non-small cell lung cancer, 11 head and neck cancer, 12 and pancreatic cancer. 13 To our knowledge, no studies have reported the prognostic or predictive value of cfDNA in patients who received RT for HCC. Thus, we investigated the feasibility of quantitative analysis and the clinical significance of cfDNA in patients with HCC treated with RT.…”