Kruti Patel

Adjuvant chemoradiation for pancreatic cancer: what does the evidence tell us?

The role of adjuvant chemoradiation (CRT) for pancreas cancer remains unclear. A handful of randomized trials conducted decades of ago ignited a debate that continues today about whether CRT improves survival after surgery. The many flaws in these trials are well described in the literature, which include the use of antiquated radiation delivery techniques and suboptimal doses. Recent prospective randomized data is lacking, and we eagerly await the results the ongoing Radiation Therapy Oncology Group (RTOG) 0848 trial that is evaluating the utility of high quality adjuvant CRT in resected pancreas cancer patients. Until the results of RTOG 0848 are available we should look to other studies from the modern era to guide adjuvant treatment recommendations. Here we review the current state of the art for adjuvant pancreas CRT with respect to patient selection, radiation techniques, radiation dose, and integration with novel systemic agents.

Individually optimized contrast-enhanced 4D-CT for radiotherapy simulation in pancreatic ductal adenocarcinoma.

PURPOSE To develop an individually optimized contrast-enhanced (CE) 4D-computed tomography (CT) for radiotherapy simulation in pancreatic ductal adenocarcinomas (PDA). METHODS Ten PDA patients were enrolled. Each underwent three CT scans: a 4D-CT immediately following a CE 3D-CT and an individually optimized CE 4D-CT using test injection. Three physicians contoured the tumor and pancreatic tissues. Image quality scores, tumor volume, motion, tumor-to-pancreas contrast, and contrast-to-noise ratio (CNR) were compared in the three CTs. Interobserver variations were also evaluated in contouring the tumor using simultaneous truth and performance level estimation. RESULTS Average image quality scores for CE 3D-CT and CE 4D-CT were comparable (4.0 and 3.8, respectively; P = 0.082), and both were significantly better than that for 4D-CT (2.6, P < 0.001). Tumor-to-pancreas contrast results were comparable in CE 3D-CT and CE 4D-CT (15.5 and 16.7 Hounsfield units (HU), respectively; P = 0.21), and the latter was significantly higher than in 4D-CT (9.2 HU, P = 0.001). Image noise in CE 3D-CT (12.5 HU) was significantly lower than in CE 4D-CT (22.1 HU, P = 0.013) and 4D-CT (19.4 HU, P = 0.009). CNRs were comparable in CE 3D-CT and CE 4D-CT (1.4 and 0.8, respectively; P = 0.42), and both were significantly better in 4D-CT (0.6, P = 0.008 and 0.014). Mean tumor volumes were significantly smaller in CE 3D-CT (29.8 cm3, P = 0.03) and CE 4D-CT (22.8 cm3, P = 0.01) than in 4D-CT (42.0 cm3). Mean tumor motion was comparable in 4D-CT and CE 4D-CT (7.2 and 6.2 mm, P = 0.17). Interobserver variations were comparable in CE 3D-CT and CE 4D-CT (Jaccard index 66.0% and 61.9%, respectively) and were worse for 4D-CT (55.6%) than CE 3D-CT. CONCLUSIONS CE 4D-CT demonstrated characteristics comparable to CE 3D-CT, with high potential for simultaneously delineating the tumor and quantifying tumor motion with a single scan.

RTOG 9003: the untold story.

As most radiation oncologists are aware, Radiation Therapy Oncology Group (RTOG) 9003 (1) compared standard radiation therapy to 3 different altered fractionation schemas. These regimens were developed by prominent leaders of head and neck cancer management: Rodney Million at the University of Florida (UF), Lester Peters at MD Anderson Hospital (MDAH), and C.C. Wang at Massachusetts General Hospital (MGH). The UF approach entailed pure hyperfractionation, whereas the other 2 schemas relied on acceleration with or without a planned treatment break. Hyperfractionated radiation therapy theoretically decreases late side effects if the dose per day is equivalent to standard fractionation. Based on this principle, the total dose can be escalated to improve local control without increasing late side effects. Thirty-four years after the protocol’s inception, Dr Beitler (1) recently reported the final results of RTOG 9003, which clearly demonstrate the superiority of hyperfractionation. The results indicate that hyperfractionation confers an improvement in both local control and overall survival without a significant impact on late toxicity. If we delve deeper into the history of this trial, there is a meaningful lesson to be learned about the scientific process and how bias can have a significant impact on trial design, thereby influencing future studies. The initial outcomes of this study were reported at a plenary session at the 1999 American Society for Radiation Oncology (ASTRO) meeting (2), at which time both the UF and MDAH arms showed an improvement in local control

TH-EF-BRA-04: Individually Optimized Contrast-Enhanced 4D-CT for Radiotherapy Simulation in Pancreatic Ductal Adenocarcinoma

PURPOSE To develop an individually optimized contrast-enhanced (CE) 4D-CT for radiotherapy simulation in pancreatic ductal adenocarcinomas (PDA). METHODS Ten PDA patients were enrolled. Each underwent 3 CT scans: a 4D-CT immediately following a CE 3D-CT and an individually optimized CE 4D-CT using test injection. Three physicians contoured the tumor and pancreatic tissues. We compared image quality scores, tumor volume, motion, tumor-to-pancreas contrast, and contrast-to-noise ratio (CNR) in the 3 CTs. We also evaluated interobserver variations in contouring the tumor using simultaneous truth and performance level estimation (STAPLE). RESULTS Average image quality scores for CE 3DCT and CE 4D-CT were comparable (4.0 and 3.8, respectively; P=0.47), and both were significantly better than that for 4D-CT (2.6, P<0.001). Tumor-to-pancreas contrast results were comparable in CE 3D-CT and CE 4D-CT (15.5 and 16.7 HU, respectively; P=0.71), and the latter was significantly higher than in 4D-CT (9.2 HU, P=0.03). Image noise in CE 3D-CT (12.5 HU) was significantly lower than in CE 4D-CT (22.1 HU, P<0.001) and 4D-CT (19.4 HU, P=0.005). CNRs were comparable in CE 3D-CT and CE 4DCT (1.4 and 0.8, respectively; P=0.23), and the former was significantly better than in 4D-CT (0.6, P = 0.04). Mean tumor volumes were smaller in CE 3D-CT (29.8 cm3 ) and CE 4D-CT (22.8 cm3 ) than in 4D-CT (42.0 cm3 ), although these differences were not statistically significant. Mean tumor motion was comparable in 4D-CT and CE 4D-CT (7.2 and 6.2 mm, P=0.23). Interobserver variations were comparable in CE 3D-CT and CE 4D-CT (Jaccard index 66.0% and 61.9%, respectively) and were worse for 4D-CT (55.6%) than CE 3D-CT. CONCLUSION CE 4D-CT demonstrated characteristics comparable to CE 3D-CT, with high potential for simultaneously delineating the tumor and quantifying tumor motion with a single scan. Supported in part by Philips Healthcare.

Pelvic local recurrence in a patient with muscle-invasive bladder cancer treated with interstitial thermal therapy and interstitial brachytherapy

The patient was a 53-year-old man who developedhematuria in 2007. Cystoscopy revealed a 5- to 6-cm masson the left floor of the bladder near the ureteral orifice. Heunderwent transurethral resection of the tumor, whichrevealed extensive high-grade urothelial carcinoma invad-ing the detrusor muscle. Computed tomography (CT) ofthe abdomen revealed no appreciable evidence of adeno-pathy or metastatic disease. The patient underwent acystoprostatectomywithilealconduitdiversion.Pathologydemonstrated a high-grade urothelial carcinoma thatinvolved the posterior and left lateral wall, as well as thetrigone and dome of the bladder, and that had invaded thedeep muscularis propria. The closest margin was 8 mmposteriorly, with no lymphovascular space invasion. Onerightpelvicand2leftobturatorlymphnodeswerefoundtobe positive. Extracapsular extension was appreciated in aleft obturator node.The tumor was staged as T2bN2Mx (stage IV)urothelial carcinoma of the bladder. The patient completed4 cycles of adjuvant gemcitabine and cisplatin in April2008. In August 2013, CT of the abdomen/pelvis revealedinterval development of a soft tissue mass around thesurgical clips on the left pelvic sidewall, for which he wasinitially observed. He presented in January 2014 with a3-month history of weight loss, nausea, intermittent smallbowel obstruction, worsening pelvic pain, and shootingdiscomfort in the left sciatic distribution. Positronemission tomography/CT in February 2014 revealed a

SU-E-J-187: Individually Optimized Contrast-Enhancement 4D-CT for Pancreatic Adenocarcinoma in Radiotherapy Simulation

PURPOSE To study the feasibility of individually optimized contrastenhancement (CE) 4D-CT for pancreatic adenocarcinoma (PDA) in radiotherapy simulation. To evaluate the image quality and contrast enhancement of tumor in the CE 4D-CT, compared to the clinical standard of CE 3D-CT and 4D-CT. METHODS In this IRB-approved study, each of the 7 PDA patients enrolled underwent 3 CT scans: a free-breathing 3D-CT with contrast (CE 3D-CT) followed by a 4D-CT without contrast (4D-CT) in the first study session, and a 4D-CT with individually synchronized contrast injection (CE 4D-CT) in the second study session. In CE 4D-CT, the time of full contrast injection was determined based on the time of peak enhancement for the test injection, injection rate, table speed, and longitudinal location and span of the pancreatic region. Physicians contoured both the tumor (T) and the normal pancreatic parenchyma (P) on the three CTs (end-of-exhalation for 4D-CT). The contrast between the tumor and normal pancreatic tissue was computed as the difference of the mean enhancement level of three 1 cm3 regions of interests in T and P, respectively. Wilcoxon rank sum test was used to statistically compare the scores and contrasts. RESULTS In qualitative evaluations, both CE 3D-CT and CE 4D-CT scored significantly better than 4D-CT (4.0 and 3.6 vs. 2.6). There was no significant difference between CE 3D-CT and CE 4D-CT. In quantitative evaluations, the contrasts between the tumor and the normal pancreatic parenchyma were 0.6±23.4, -2.1±8.0, and -19.6±28.8 HU, in CE 3D-CT, 4D-CT, and CE 4D-CT, respectively. Although not statistically significant, CE 4D-CT achieved better contrast enhancement between the tumor and the normal pancreatic parenchyma than both CE 3D-CT and 4DCT. CONCLUSION CE 4D-CT achieved equivalent image quality and better contrast enhancement between tumor and normal pancreatic parenchyma than the clinical standard of CE 3D-CT and 4D-CT. This study was supported in part by Philips Healthcare.