C. Eccles

Radiotherapy and chemotherapy as therapeutic strategies in extrahepatic biliary duct carcinoma.

AbstractPurpose:This report aims to provide an overview on radiotherapy and chemotherapy in extrahepatic biliary duct carcinoma (BDC).Patients and Methods:A PubMed research identified clinical trials in BDC through April 1, 2010 including randomised controlled trials, SEER analyses and retrospective trials. Additionally, publications on the technical progress of radiotherapy in or close to the liver were analysed.Results:Most patients with cholangiocarcinoma present with unresectable disease (80–90%), and more than half of the resected patients relapse within 1 year. Adjuvant and palliative treatment options need to be chosen carefully since 50% of the patients are older than 70 years at diagnosis. Adjuvant radiotherapy or chemotherapy after complete resection (R0) has not convincingly shown a prolongation of survival but radiotherapy did after R1 resection. However, data suggest that liver transplantation could offer long-term survival in selected patients when combined with neoadjuvant chemoradiotherapy in patients with marginally resectable disease. For patients with unresectable biliary tract carcinoma (BTC), palliative stenting was previously the treatment of choice. But recent SEER analyses show that radiotherapy prolongs survival, relieves symptoms and contributes to biliary decompression and should be regarded as the new standard. Novel technical advances in radiotherapy may allow for dose-escalation and could significantly improve outcome for patients with cholangiocarcinoma.Conclusion:Both the literature and recent technical progress corroborate the role of radiotherapy in BDC offering chances for novel clinical trials. Progress is less pronounced in chemotherapy.ZusammenfassungZiel:Dieser Bericht gibt eine Übersicht über die Rolle der Radio- und Chemotherapie beim extrahepatischen Gallengangskarzinom (BDC).Patienten und Methodik:Eine PubMed-Suche identifizierte klinische Studien zum BDT bis 1. April , 2010 und schloss randomisierte kontrollierte Studien, SEER Analysen und retrospektive Studien ein. Außerdem wurden Arbeiten zum technischen Fortschritt der Radiotherapie in und nahe der Leber analysiert.Ergebnisse:Die Mehrzahl der Patienten mit cholangiozellulärem Karzinom befindet sich zum Zeitpunkt der Diagnose bereits in fortgeschrittenen irresektablen Tumorstadien, und auch unter den primär operablen Patienten kommt es in den meisten Fällen zum Rezidiv innerhalb eines Jahres. Adjuvante und palliative Behandlungsoptionen müssen sorgfältig gewählt werden, weil 50% der Patienten bei Daignose älter als 70 Jahre sind. Die adjuvante Radio- bzw. Chemotherapie zeigt nach R0-Resektion keinen überzeugenden Überlebensvorteil, hingegen die Radiotherapie nach R1-Resektion. Bei sorgfältig selektierten Patientengruppen gibt es Daten zum Langzeitüberleben nach neoadjuvanter Radiochemotherapie mit anschließender Lebertransplantation. In der palliativen Situation war bislang die Einlage von Endoprothesen Methode der Wahl. Jedoch zeigen neueste SEER-Analysen, dass die Radiotherapie nicht nur eine Besserung der Lebensqualität durch Besserung der Cholestase bewirkt, nsondern auch das Überleben verlängert, weshlab sie als neue Standardtherapie angesehen werden sollte. Neueste technische Entwicklungen in der Strahlentherapie eröffnen die Perspektive einer Dosiseskalation und könnten die Ergebnisse bei Patienten mit cholangiozellulären Karzinomen dramatisch verbessern.Schlussfolgerung:Sowohl die Literatur als auch der jüngste technische Fortschritt stärken die Rolle der Radiotherapie beim BDC und eröffnen Chancen für klinische Studien. Für die Chemotherapie ist der Fortschritt weniger ausgeprägt.

Comparison of simple and complex liver intensity modulated radiotherapy

BackgroundIntensity-modulated radiotherapy (IMRT) may allow improvement in plan quality for treatment of liver cancer, however increasing radiation modulation complexity can lead to increased uncertainties and requirements for quality assurance. This study assesses whether target coverage and normal tissue avoidance can be maintained in liver cancer intensity-modulated radiotherapy (IMRT) plans by systematically reducing the complexity of the delivered fluence.MethodsAn optimal baseline six fraction individualized IMRT plan for 27 patients with 45 liver cancers was developed which provided a median minimum dose to 0.5 cc of the planning target volume (PTV) of 38.3 Gy (range, 25.9-59.5 Gy), in 6 fractions, while maintaining liver toxicity risk <5% and maximum luminal gastrointestinal structure doses of 30 Gy. The number of segments was systematically reduced until normal tissue constraints were exceeded while maintaining equivalent dose coverage to 95% of PTV (PTVD95). Radiotherapy doses were compared between the plans.ResultsReduction in the number of segments was achieved for all 27 plans from a median of 48 segments (range 34-52) to 19 segments (range 6-30), without exceeding normal tissue dose objectives and maintaining equivalent PTVD95 and similar PTV Equivalent Uniform Dose (EUD(-20)) IMRT plans with fewer segments had significantly less monitor units (mean, 1892 reduced to 1695, p = 0.012), but also reduced dose conformity (mean, RTOG Conformity Index 1.42 increased to 1.53 p = 0.001).ConclusionsTumour coverage and normal tissue objectives were maintained with simplified liver IMRT, at the expense of reduced conformity.

A treatment planning comparison of four target volume contouring guidelines for locally advanced pancreatic cancer radiotherapy.

BACKGROUND AND PURPOSE Contouring of target volumes varies significantly in radiotherapy of pancreatic ductal adenocarcinoma (PDAC). There is a lack of consensus as to whether elective lymph nodes (eLNs) should be included or not in the planning target volume (PTV). In the present study we analyzed the dosimetric coverage of the eLNs and organs at risk (OAR) by comparing four different contouring guidelines. METHODS AND MATERIALS PTVs were delineated with (Oxford and RTOG guidelines) or without (Michigan and SCALOP guidelines) including the eLNs in eleven patients with PDAC. eLNs included the peripancreatic, paraaortic, paracaval, celiac trunk, superior mesenteric and portal vein clinical target volumes (CTVs). A 3D-CRT plan (50.40 Gy in 28 fractions) was performed to analyze and compare the dosimetric coverage of all eLNs and OAR between the 4 contouring guidelines. RESULTS The size of Oxford and RTOG PTVs was comparable and significantly larger than the SCALOP and Michigan PTVs. Interestingly the eLNs received a significant amount of incidental dose irradiation by PTV-based plans that only aimed to treat the tumor without the eLNs. The dosimetric coverage of eLN presented a large variability according to the respective contouring methods. The difference in the size of the 4 PTVs was reflected to the dose distribution at the OAR. CONCLUSIONS Our study provides important information regarding the impact of different contouring guidelines on the dose distribution to the eLNs and the OAR in patients with locally advanced PDAC treated with radiotherapy.

In reply to letter to the editor by Dr Willems et al. re: Eccles et al. Change in diffusion weighted MRI during liver cancer radiotherapy: Preliminary observations.

1CRUK/MRC Gray Institute for Radiation Oncology & Biology, University of Oxford, Oxford Cancer Centre, Churchill Hospital, Oxford, UK, 2University of Toronto, Head of Abdominal MRI, Department of Medical Imaging University Health Network, Princess Margaret Hospital and Mount Sinai Hospital, Toronto, Ontario, Canada and 3Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada

Intravenous contrast-enhanced cone beam computed tomography (IVCBCT) of intrahepatic tumors and vessels

Purpose Liver tumors are challenging to visualize on cone beam computed tomography (CBCT) without intravenous (IV) contrast. Image guidance for liver cancer stereotactic body ablative radiation therapy (SABR) could be improved with the direct visualization of hepatic tumors and vasculature. This study investigated the feasibility of the use of IV contrast-enhanced CBCT (IV-CBCT) as a means to improve liver target visualization. Methods and Materials Patients on a liver SABR protocol underwent IV-CBCT before 1 or more treatment fractions in addition to a noncontrast CBCT. Image acquisition was initiated 0 to 30 seconds following injection and acquired over 60 to 120 seconds. “Stop and go” exhale breath-hold CBCT scans were used whenever feasible. Changes in mean CT number in regions of interest within visible vasculature, tumor, and adjacent liver were quantified between CBCT and IV-CBCT. Results Twelve pairs of contrast and noncontrast CBCTs were obtained in 7 patients. Intravenous-CBCT improved hepatic tumor visibility in breath-hold scans only for 3 patients (2 metastases, 1 hepatocellular carcinoma). Visible tumors ranged in volume from 124 to 564 mL. Small tumors in free-breathing patients did not show enhancement on IVCBT. Conclusions Intravenous-CBCT may enhance the visibility of hepatic vessels and tumor in CBCT scans obtained during breath hold. Optimization of IV contrast timing and reduction of artifacts to improve tumor visualization warrant further investigation.