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Considerable interobserver variation in delineation of pancreatic cancer on 3DCT and 4DCT: a multi-institutional study.

ABSTRACT: The delineation of pancreatic tumors on CT is challenging. In this study, we quantified the interobserver variation for pancreatic tumor delineation on 3DCT as well as on 4DCT.Eight observers (radiation oncologists) from six institutions delineated pancreatic tumors of four patients with (borderline) resectable pancreatic cancer. The study consisted of two stages. In the 3DCT-stage, the gross tumor volume (GTV) was delineated on a contrast-enhanced scan. In the 4DCT-stage, the internal GTV (iGTV) was delineated, accounting for the respiratory motion. We calculated the volumes of the (i)GTV, the overlap of the delineated volumes (expressed as generalized conformity index: CIgen), the local observer variation (local standard deviation: SD) and the overall observer variation (overall SD). We compared these results between GTVs and iGTVs. Additionally, observers were asked to fill out a questionnaire concerning the difficulty of the delineation and their experience in delineating pancreatic tumors.The ratios of the largest to the smallest delineated GTV and iGTV within the same patient were 6.8 and 16.5, respectively. As the iGTV incorporates the GTV during all respiratory phases, the mean volumes of the iGTV (40.07 cm3) were larger than those of the GTV (29.91 cm3). For all patients, CIgen was larger for the iGTV than for the GTV. The mean overall observer variation (root-mean-square of all local SDs over four patients) was 0.63 cm and 0.80 cm for GTV and iGTV, respectively. The largest local observer variations were seen close to biliary stents and suspicious pathological enlarged lymph nodes, as some observers included them and some did not. This variation was more pronounced for the iGTV than for the GTV. The observers rated the 3DCT-stage and 4DCT-stage equally difficult and treated on average three to four pancreatic cancer patients per year.A considerable interobserver variation in delineation of pancreatic tumors was observed. This variation was larger for 4D than for 3D delineation. The largest local observer variation was found around biliary stents and suspicious pathological enlarged lymph nodes.

SUBMITTER: Versteijne E

PROVIDER: S-EPMC5364627 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Considerable interobserver variation in delineation of pancreatic cancer on 3DCT and 4DCT: a multi-institutional study.

Versteijne Eva E Gurney-Champion Oliver J OJ van der Horst Astrid A Lens Eelco E Kolff M Willemijn MW Buijsen Jeroen J Ebrahimi Gati G Neelis Karen J KJ Rasch Coen R N CR Stoker Jaap J van Herk Marcel M Bel Arjan A van Tienhoven Geertjan G

Radiation oncology (London, England) 20170323 1

<h4>Background</h4>The delineation of pancreatic tumors on CT is challenging. In this study, we quantified the interobserver variation for pancreatic tumor delineation on 3DCT as well as on 4DCT.<h4>Methods</h4>Eight observers (radiation oncologists) from six institutions delineated pancreatic tumors of four patients with (borderline) resectable pancreatic cancer. The study consisted of two stages. In the 3DCT-stage, the gross tumor volume (GTV) was delineated on a contrast-enhanced scan. In the ...[more]

PMID: 28335780

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Project description:BackgroundIn radiotherapy inaccuracy in organ at risk (OAR) delineation can impact treatment plan optimisation and treatment plan evaluation. Brouwer et al. showed significant interobserver variability (IOV) in OAR delineation in head and neck cancer (HNC) and published international consensus guidelines (ICG) for OAR delineation in 2015. The aim of our study was to evaluate IOV in the presence of these guidelines.MethodsHNC radiation oncologists (RO) from each Belgian radiotherapy centre were invited to complete a survey and submit contours for 5 HNC cases. Reference contours (OARref) were obtained by a clinically validated artificial intelligence-tool trained using ICG. Dice similarity coefficients (DSC), mean surface distance (MSD) and 95% Hausdorff distances (HD95) were used for comparison.ResultsFourteen of twenty-two RO (64%) completed the survey and submitted delineations. Thirteen (93%) confirmed the use of delineation guidelines, of which six (43%) used the ICG. The OARs whose delineations agreed best with the OARref were mandible [median DSC 0.9, range (0.8-0.9); median MSD 1.1 mm, range (0.8-8.3), median HD95 3.4 mm, range (1.5-38.7)], brainstem [median DSC 0.9 (0.6-0.9); median MSD 1.5 mm (1.1-4.0), median HD95 4.0 mm (2.3-15.0)], submandibular glands [median DSC 0.8 (0.5-0.9); median MSD 1.2 mm (0.9-2.5), median HD95 3.1 mm (1.8-12.2)] and parotids [median DSC 0.9 (0.6-0.9); median MSD 1.9 mm (1.2-4.2), median HD95 5.1 mm (3.1-19.2)]. Oral cavity, cochleas, PCMs, supraglottic larynx and glottic area showed more variation. RO who used the consensus guidelines showed significantly less IOV (p = 0.008).ConclusionsAlthough ICG for delineation of OARs in HNC exist, they are only implemented by about half of RO participating in this study, which partly explains the delineation variability. However, this study highlights that guidelines alone do not suffice to eliminate IOV and that more effort needs to be done to accomplish further treatment standardisation, for example with artificial intelligence.

Project description:BACKGROUND:When clinical practice is governed by evidence-based guidelines and there is consensus about their validity, practice variation should be minimal. For areas in which evidence gaps exist, greater variation is expected. OBJECTIVE:To systematically assess interinstitutional variation in management decisions for 4 common types of cancer. DESIGN:Multi-institutional, observational cohort study of patients with cancer diagnosed between July 2006 through May 2011 and observed through 31 December 2011. SETTING:18 cancer centers participating in the formulation of treatment guidelines and systematic outcomes assessment through the National Comprehensive Cancer Network. PATIENTS:25 589 patients with incident breast cancer, colorectal cancer, lung cancer, or non-Hodgkin lymphoma. MEASUREMENTS:Interinstitutional variation for 171 binary management decisions with varying levels of supporting evidence. For each decision, variation was characterized by the median absolute deviation of the center-specific proportions. RESULTS:Interinstitutional variation was high (median absolute deviation >10%) for 35 of 171 (20%) oncology management decisions, including 9 of 22 (41%) decisions for non-Hodgkin lymphoma, 16 of 76 (21%) for breast cancer, 7 of 47 (15%) for lung cancer, and 3 of 26 (12%) for colorectal cancer. Forty-six percent of high-variance decisions involved imaging or diagnostic procedures and 37% involved choice of chemotherapy regimen. The evidence grade underpinning the 35 high-variance decisions was category 1 for 0%, 2A for 49%, and 2B/other for 51%. LIMITATION:Physician identifiers were unavailable, and results may not generalize outside of major cancer centers. CONCLUSION:The substantial variation in institutional practice manifest among cancer centers reveals a lack of consensus about optimal management for common clinical scenarios. For clinicians, awareness of management decisions with high variation should prompt attention to patient preferences. For health systems, high variation can be used to prioritize comparative effectiveness research, patient-provider education, or pathway development. PRIMARY FUNDING SOURCE:National Cancer Institute and National Comprehensive Cancer Network.

Project description:BackgroundAmong patients with stage I breast cancer, there is significant uncertainty concerning the optimal threshold at which to consider chemotherapy, and when considered, there is controversy regarding whether to consider non-intensive versus intensive regimens. The authors examined the types and costs of adjuvant chemotherapy received among patients with stage I breast cancer.MethodsThe current study was a prospective cohort study including patients with stage I breast cancer who were treated at a National Comprehensive Cancer Network center from 2000 through 2009. Stage was defined according to the version of the American Joint Committee on Cancer Staging Manual applicable at the time of diagnosis. Stratifying by human epidermal growth factor receptor 2 (HER2), the authors examined the percentage of patients receiving intensive versus non-intensive chemotherapy regimens and the factors associated with type of chemotherapy administered using multivariable logistic regression. Costs of the most common regimens were estimated.ResultsOf 8907 patients, 33% received adjuvant chemotherapy. Among those individuals, there was an increase in the use of intensive chemotherapy within the last decade, from 31% in 2000 through 2005 to 63% in 2008 through 2009 (including an increase in the use of the combination of docetaxel, carboplatin, and trastuzumab) among patients with HER2-positive disease and from 15% in 2000 through 2005 to 41% in 2008 through 2009 among patients with HER2-negative disease (32% of patients with hormone receptor-positive and 59% of patients with triple-negative disease). Among patients treated with non-intensive regimens, there was an increase in the use of the combination of docetaxel and cyclophosphamide noted, with a decrease in the use of the doxorubicin and cyclophosphamide combination. The choice of regimen varied significantly by institution. The major drivers of cost variation were the incorporation of biologics (eg, trastuzumab) and growth factors, with significant variation even within non-intensive and intensive regimens.ConclusionsOver time, there was an increase in use of intensive regimens among Stage I breast cancer, with striking institutional and cost variations.

Project description:The purpose of this study was to evaluate preoperative treatment with full-dose gemcitabine, oxaliplatin, and radiation therapy (RT) in patients with localized pancreatic cancer.Eligibility included confirmation of adenocarcinoma, resectable or borderline resectable disease, a performance status ?2, and adequate organ function. Treatment consisted of two 28-day cycles of gemcitabine (1 g/m(2) over 30 minutes on days 1, 8, and 15) and oxaliplatin (85 mg/m(2) on days 1 and 15) with RT during cycle 1 (30 Gray [Gy] in 2-Gy fractions). Patients were evaluated for surgery after cycle 2. Patients who underwent resection received 2 cycles of adjuvant chemotherapy.Sixty-eight evaluable patients received treatment at 4 centers. By central radiology review, 23 patients had resectable disease, 39 patients had borderline resectable disease, and 6 patients had unresectable disease. Sixty-six patients (97%) completed cycle 1 with RT, and 61 patients (90%) completed cycle 2. Grade ?3 adverse events during preoperative therapy included neutropenia (32%), thrombocytopenia (25%), and biliary obstruction/cholangitis (14%). Forty-three patients underwent resection (63%), and complete (R0) resection was achieved in 36 of those 43 patients (84%). The median overall survival was 18.2 months (95% confidence interval, 13-26.9 months) for all patients, 27.1 months (95% confidence interval, 21.2-47.1 months) for those who underwent resection, and 10.9 months (95% confidence interval, 6.1-12.6 months) for those who did not undergo resection. A decrease in CA 19-9 level after neoadjuvant therapy was associated with R0 resection (P = .02), which resulted in a median survival of 34.6 months (95% confidence interval, 20.3-47.1 months). Fourteen patients (21%) are alive and disease free at a median follow-up of 31.4 months (range, 24-47.6 months).Preoperative therapy with full-dose gemcitabine, oxaliplatin, and RT was feasible and resulted in a high percentage of R0 resections. The current results are particularly encouraging, because the majority of patients had borderline resectable disease.

Project description:PurposeTNFerade biologic is a novel means of delivering tumor necrosis factor alpha to tumor cells by gene transfer. We herein report final results of the largest randomized phase III trial performed to date among patients with locally advanced pancreatic cancer (LAPC) and the first to test gene transfer against this malignancy.Patients and methodsIn all, 304 patients were randomly assigned 2:1 to standard of care plus TNFerade (SOC + TNFerade) versus standard of care alone (SOC). SOC consisted of 50.4 Gy in 28 fractions with concurrent fluorouracil (200 mg/m(2) per day continuous infusion). TNFerade was injected intratumorally before the first fraction of radiotherapy each week at a dose of 4 × 10(11) particle units by using either a percutaneous transabdominal or an endoscopic ultrasound approach. Four weeks after chemoradiotherapy, patients began gemcitabine (1,000 mg/m(2) intravenously) with or without erlotinib (100 to 150 mg per day orally) until progression or toxicity.ResultsThe analysis included 187 patients randomly assigned to SOC + TNFerade and 90 to SOC by using a modified intention-to-treat approach. Median follow-up was 9.1 months (range, 0.1 to 50.5 months). Median survival was 10.0 months for patients in both the SOC + TNFerade and SOC arms (hazard ratio [HR], 0.90; 95% CI, 0.66 to 1.22; P = .26). Median progression-free survival (PFS) was 6.8 months for SOC + TNFerade versus 7.0 months for SOC (HR, 0.96; 95% CI, 0.69 to 1.32; P = .51). Among patients treated on the SOC + TNFerade arm, multivariate analysis showed that TNFerade injection by an endoscopic ultrasound-guided transgastric/transduodenal approach rather than a percutaneous transabdominal approach was a risk factor for inferior PFS (HR, 2.08; 95% CI, 1.06 to 4.06; P = .032). The patients in the SOC + TNFerade arm experienced more grade 1 to 2 fever and chills than those in the SOC arm (P < .001) but both arms had similar rates of grade 3 to 4 toxicities (all P > .05).ConclusionSOC + TNFerade is safe but not effective for prolonging survival in patients with LAPC.

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Considerable interobserver variation in delineation of pancreatic cancer on 3DCT and 4DCT: a multi-institutional study.

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Considerable interobserver variation in delineation of pancreatic cancer on 3DCT and 4DCT: a multi-institutional study.

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