Superior Outcomes With Gemcitabine-Based Systemic and Concurrent Administration With Radiation Therapy in Inoperable or Unresectable Cholangiocarcinomas

Abstract

Neoadjuvant rectal (NAR) score is a validated surrogate endpoint that predicts for overall survival better than pathologic complete response in rectal cancer patients treated with neoadjuvant chemoradiation (CRT) and surgery. The NAR score is calculated using clinical and pathologic staging information. We aimed to determine if there is an association between several FDG-PET parameters and the NAR score so that clinicians can preoperatively predict the NAR score. Materials/Methods: A retrospective review of rectal cancer patients treated at a single institution between May 2004 and May 2015 found 60 patients that underwent a pre-CRT FDG-PET scan, CRT treatment, a post-CRT FDG-PET scan, and surgical resection. The NAR score was categorized into three groups: low (<8), intermediate (8-16), and high (>16). PET-based tumor dimensions were calculated using threshold values of 45% of the peak standardized uptake value (SUV) inside the visualized tumor region of the PET images. Commercially available PET software was also used to generate tumor dimensions by identifying the tumor edge as where the SUV change was the most dramatic. The parameters that were evaluated were tumor glycolytic activity calculated with a threshold of 45% of the peak SUV (TGA), tumor glycolytic activity as calculated by software (TGAedge), metabolic tumor volume as calculated with a threshold of 45% of the peak SUV (MTV), metabolic tumor volume as calculated by software (MTVedge), and maximum SUV (SUVmax). The two-sided Kruskal-Wallis test was used to compare groups at the 5% significance level. Results: Ninety-three percent of patients had a clinical T3 tumor. Fortyseven percent of patients had a clinical nodal stage of N1 or higher. The median time from the completion of CRT to the post-CRT FDG-PET scan was 28 days (8 e 53 days). The number of patients in each NAR score group: 24 had a low score, 23 had an intermediate score, and 13 had a high score. The decrease between pre-CRT and post-CRT TGA was strongly associated with a lower NAR score (P Z 0.004). A decrease in TGAedge between pre-CRT and post-CRT scans was also associated with a lower NAR score (P Z 0.0009). There was no correlation between the change from pre-CRT to post-CRT SUVmax, MTV, or MTVedge and the NAR score (P Z 0.7, P Z 0.23, P Z 0.64 respectively). Conclusion: There is a direct association between the change in pre-CRT and post-CRT TGA and TGAedge and the NAR score. By analyzing the pre-CRT and post-CRT FDG-PET scans, it may be possible for clinicians to pre-operatively predict their rectal cancer patient's NAR score and longterm outcome. As novel therapeutic strategies, including total neoadjuvant therapy, are being studied, imaging-based evaluation of treatment effectiveness is becoming more important.

The Isoquinoline Alkaloid Berberine Augments Radiation Effect by Enhancing the DNA Damage at Molecular Level in HeLa Cells Irradiated with Various Doses of γ-Radiation: Correlation Between DNA Damage and Clonogenicity

“…Although successful in the experimental setup, clinical success has always been elusive, which has led to the use of alternative approach, where radiotherapy has been combined with chemotherapeutic drugs with a remarkable success to treat various malignant tumors [6,7]. Several chemoptherapeutic agents including cis-dichlorodiammine-platinum (II), 5-fluorouracil, mitomycin C, paclitaxel, docetaxel, topotecan, irinotecan, crytophycins, camptothecin and combretastatin A-4, and gemcitabine have been successfully combined with radiotherapy to treat difficult neoplasia [8][9][10][11][12][13][14][15]. The use of chemotherapy in conjunction with radiotherapy proved beneficial in the treatment of solid neoplastic disorders in randomized clinical trials, however, it is fraught with consequences of high toxicity and development of second malignancies [16,17].…”