Treatment Of Abdominal Cancers Research Articles

Couch and multileaf collimator tracking: A clinical feasibility study for pancreas and liver treatment.

Real-time tumor tracking through active correction by the multileaf collimator or treatment couch offers a promising strategy to mitigate delivery uncertainty due to intrafractional tumor motion. This study evaluated the performance of MLC and couch tracking using the prototype iTools Tracking system in TrueBeam Developer Mode and the application for abdominal cancer treatments. Experiments were carried out using a phantom with embedded Calypso transponders and a motion simulation platform. Geometric evaluations were performed using a circular conformal field with sinusoidal traces and pancreatic tumor motion traces. Geometric tracking accuracy was retrospectively calculated by comparing the compensational MLC or couch motion extracted from machine log files to the target motion reconstructed from real-time MV and kV images. Dosimetric tracking accuracy was measured with radiochromic films using clinical abdominal VMAT plans and pancreatic tumor traces. Geometrically, the root-mean-square errors for MLC tracking were 0.5 and 1.8mm parallel and perpendicular to leaf travel direction, respectively. Couch tracking, in contrast, showed an average of 0.8mm or less geometric error in all directions. Dosimetrically, both MLC and couch tracking reduced motion-induced local dose errors compared to no tracking. Evaluated with five pancreatic tumor motion traces, the average 2%/2mm global gamma pass rate of eight clinical abdominal VMAT plans was 67.4% (range: 26.4%-92.7%) without tracking, which was improved to 86.0% (range: 67.9%-95.6%) with MLC tracking, and 98.1% (range: 94.9%-100.0%) with couch tracking. In 16 out of 40 deliveries with different plans and motion traces, MLC tracking did not achieve clinically acceptable dosimetric accuracy with 3%/3mm gamma pass rate below 95%. This study demonstrated the capability of MLC and couch tracking to reduce motion-induced dose errors in abdominal cases using a prototype tracking system. Clinically significant dose errors were observed with MLC tracking for certain plans which could be attributed to the inferior MLC tracking accuracy in the direction perpendicular to leaf travel, as well as the interplay between motion tracking and plan delivery for highly modulated plans. Couch tracking outperformed MLC tracking with consistently high dosimetric accuracy in all plans evaluated, indicating its clinical potential in the treatment of abdominal cancers.

TU‐G‐217A‐09: Feasibility of Bowel Tracking Using Onboard Cine MRI for Gated Radiotherapy

Purpose: Bowel toxicity can be difficult to manage in the treatment of abdominal cancers. The bowel experiences large motion during treatment, causing it to enter high‐dose regions. Real‐time MR imaging during radiotherapy allows for potential visualization and dosimetric avoidance of the bowel during treatment. To investigate the feasibility of real‐time ‘bowel‐gated’ treatment using onboard MRI, we assessed two bowel‐tracking algorithms on 32 cine imagesets acquired with the ViewRay hybrid MR‐ radiotherapy unit. Methods: The Viewray(TM) System, which is an integrated 0.35T MR‐Co‐60 system that is pending 510k approval, was used to acquire 32 cine image sets in 5 patients under an IRB‐approved trial. Each imageset was acquired in 2D (coronal or sagittal orientation) for an average duration of 0.5‐2.5 minutes at a frame rate of 4 frames/s. The initial position of the bowel was manually contoured on the first image frame. Two algorithms were evaluated in tracking bowel from its initial position throughout its motion for the duration of the cine set ‐ a normalized cross‐ correlation (NCC) algorithm, and a weighted NCC (WNCC) algorithm. To assess the tracking feasibility and accuracy of these two methods, the initial contour was virtually shifted with the tracked motion and displayed on tracked cine images. The agreement between the shifted contour and the border of the bowel was manually inspected and noted for each frame. Results: Both algorithms successfully tracked 31/32 cases in 100% of frames. The WNCC algorithm outperformed the NCC algorithm in speed, with a mean processing speed of .007s versus .013s, respectively, and captured a greater range of motion in all cases. Conclusions: The demonstrated feasibility of bowel tracking on cine MR imagesets indicates its potential successful use in real‐time bowel tracking and gated radiotherapy. While both algorithms performed well, the WNCC algorithm was superior in processing speed and sensitivity to bowel motion.

Clinical Relevance of Nanoparticle Induced Hyperthermia for Drug Delivery and Treatment of Abdominal Cancers

Clinical Relevance of Nanoparticle Induced Hyperthermia for Drug Delivery and Treatment of Abdominal Cancers

Induction of Proteases in Peritoneal Carcinomatosis, the Role of ICAM-1/CD43 Interaction

IntroductionThe development of peritoneal metastases is a significant clinical issue in the treatment of abdominal cancers and is associated with poor prognosis. We have previously shown that ICAM-1-CD43 interaction plays a significant role in tumor adhesion. However, an invasive phenotype is critical to establish tumor progression via cell associated and secreted proteases including matrix metalloproteinases. High metalloproteinases level significantly enhanced metastasis phenotype on tumors, a detrimental effect on surgical outcome. We investigated the role of direct and indirect signaling between the mesothelium and the tumor cells in enhancing tumor invasion and possible therapeutic intervention.MethodsMesothelial cells were enzymatically derived from human omental tissue and implanted in 24 wells plates. Colorectal cancer cells were then introduced and allowed a direct and an indirect contact with the mesothelial layer. Anti-ICAM antibodies, anti-CD43 antibodies, and heparin were used to block MMP production. Gelatin zymography was performed on the supernatant to detect MMPs activity.ResultsMMP production was observed in mesothelial and tumor cells. Direct contact between cell types enhanced MMP9 and 2 (p < 0.05). Indirect contact also stimulate MMPs but at a lower degree. ICAM-1 blocking antibodies attenuated MMP production in direct contact to that observed in the indirect. Heparin introduction achieved a similar outcome.ConclusionsICAM-1-CD43 interaction plays a vital role in tumor cells-peritoneum adhesion and invasion, which is manifested by the increased production of MMPs leading to tumor invasion and peritoneal loco-regional. Blocking this interaction with heparin can provide a new therapeutic option.

ICAM-1 Mediated Peritoneal Carcinomatosis, A Target for Therapeutic Intervention

Development of peritoneal metastasis is a significant issue in the treatment of abdominal cancers. Primary interaction between tumour cells and the mesothelium is a vital step in initiating this process. Our aim was to determine the role of the intercellular adhesion molecule-1 (ICAM-1) in mesothelial-tumour adhesion and the effectiveness of therapeutic intervention. Mesothelial cells were derived from omental tissue. ICAM-1 expression in resting state, in the presence of TNF-alpha or after the application of heparin or hyaluronan was determined by flow cytometry. Functional effects on tumour adhesion to a mesothelial monolayer were determined via a Calcein-AM in vitro adhesion assay. In vivo studies were performed utilising 30 WAG/rij rats, which underwent mini-laparotomy with the injection of 1 x 10(5 )CC 513 tumour cells intraperitoneally. Tumour growth was assessed macroscopically and microscopically by two independent examiners. Mesothelial cells expressed high level of ICAM-1, which was up-regulated by the presence of TNF-alpha. The introduction of heparin caused a decrease in ICAM-1 expression, however hyaluronan did not affect the expression. A significant decrease in tumour-mesothelial cell adhesion in vitro and complete aberration of tumour growth in vivo was observed with heparin application. In vitro studies showed utilisation of high molecular weight hyaluronan, which was more limited in vivo. These data imply that heparin may be used as a potential therapeutic through a defined molecular mechanism both in vitro and in vivo. Hyaluronan appears to function as a barrier and hence may be unreliable in blocking peritoneal recurrence.

Irradiation injury to the gastro-intestinal tract: clinical features, management and pathogenesis.

SUMMARYCure of cancer by radiotherapy may be achieved only at the expense of some damage to healthy tissue. In so far as the abdomen is concerned, the bowel is particularly vulnerable. In the treatment of abdominal cancer, it may be justifiable, on occasions, to risk limited bowel necrosis to produce adequate tumour destruction if there is a reasonable chance of a net gain in health status. In the present communication the signs, symptoms and pathology of irradiation injury to the stomach and bowel are illustrated by the description of three patients, treated for carcinoma of the cervix uteri, seminoma of the testis and malignant teratoma of the testis respectively. In all three cases the primary tumour had been removed, and irradiation was given for proven or suspected recurrence of the cancer. The irradiation caused both direct irradiation injury to the intestinal epithelium and injury to blood vessels with depletion of blood supply ; the latter process probably produced the greater damage. A variety of lesions occurred in the bowel, including ulceration, hæmorrhage, perforation, fibrosis, obstruction and malabsorption. Limited bowel resection became necessary in all three cases. Two patients have survived, with impaired health but without clinical evidence of recurrence ; the one treated for carcinoma of the cervix is surviving after two years, and the one treated for seminoma of the testis is surviving after three years. Improved methods of irradiation are discussed.