Background: Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer. We investigated the cost... Show moreBackground: Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer. We investigated the cost-effectiveness of colorectal cancer surveillance in Dutch Hodgkin lymphoma survivors to determine the optimal surveillance strategy for different Hodgkin lymphoma subgroups. Methods: The Microsimulation Screening Analysis-Colon model was adjusted to reflect colorectal cancer and other-cause mortality risk in Hodgkin lymphoma survivors. Ninety colorectal cancer surveillance strategies were evaluated varying in starting and stopping age, interval, and modality [colonoscopy, fecal inamunochemical test (FIT, OC-Sensor, cutoffs: 10/20/47 mu g Hb/g feces), and multi-target stool DNA test (Cologuard)]. Analyses were also stratified per primary treatment (IRT and procarbazine or procarbazine without IRT). Colorectal cancer deaths averted (compared with no surveillance) and incremental cost-effectiveness ratios (ICER) were primary outcomes. The optimal surveillance strategy was identified assuming a willingness-to-pay threshold of (sic)20,000 per life-years gained (LYG). Results: Overall, the optimal surveillance strategy was annual FIT (47 mu g) from age 45 to 70 years, which might avert 70% of colorectal cancer deaths in Hodgkin lymphoma survivors (compared with no surveillance; ICER:(sic)18,000/LYG). The optimal surveillance strategy in Hodgkin lymphoma survivors treated with procarbazine without IRT was biennial FIT (47 mu g) from age 45 to 70 years (colorectal cancer mortality averted 56%; ICER(sic)15,000/ LYG), and when treated with IRT and procarbazine, annual FIT (47 mu g) surveillance from age 40 to 70 was most cost-effective (colorectal cancer mortality averted 75%; ICER:(sic)13,000/LYG). Conclusions: Colorectal cancer surveillance in Hodgkin lymphoma survivors is cost-effective and should commence earlier than screening occurs in population screening programs. For all subgroups, FIT surveillance was the most cost-effective strategy. Impact: Colorectal cancer surveillance should be implemented in Hodgkin lymphoma survivors. Show less
Background Hodgkin's lymphoma (HL) survivors treated with abdominal radiotherapy and/or procarbazine have an increased risk of developing colorectal neoplasia.Aims We evaluated the... Show moreBackground Hodgkin's lymphoma (HL) survivors treated with abdominal radiotherapy and/or procarbazine have an increased risk of developing colorectal neoplasia.Aims We evaluated the clinicopathological characteristics and risk factors for developing (advanced) neoplasia (AN) in HL survivors.Methods In all, 101 HL survivors (median age 51 years, median age of HL diagnosis 25 years) underwent colonoscopy and 350 neoplasia and 44 AN (classified as advanced adenomas/serrated lesions or colorectal cancer), mostly right-sided, were detected, as published previously. An average-risk asymptomatic cohort who underwent screening colonoscopy were controls (median age 60 years). Clinicopathological characteristics of AN were evaluated in both groups. Mismatch repair (MMR) status was assessed using immunohistochemistry (MLH1/MSH2/MSH6/PMS2). Logistic regression analysis was performed to evaluate the risk factors for AN in HL survivors, including age at HL diagnosis and interval between HL and colonoscopy.Results In 101 colonoscopies in HL survivors, AN was primarily classified based on polyp size >= 10 mm, whereas (high-grade)dysplasia was more often seen in AN in controls. An interval between HL diagnosis and colonoscopy >26 years was associated with more AN compared with an interval of <26 years, with an odds ratio for AN of 3.8 (95% confidence interval 1.4-9.1) (p < 0.01). All 39 AN that were assessed were MMR proficient.Conclusions Colorectal neoplasia in HL survivors differ from average-risk controls; classification AN was primarily based on polyp size (>= 10 mm) in HL survivors. Longer follow-up between HL diagnosis and colonoscopy was associated with a higher prevalence of AN in HL survivors. Show less
Hodgkin lymphoma (HL) survivors are at increased risk of developing second primary esophageal squamous cell cancer (ESCC). We aimed to gain insight in the driving events of ESCC in HL survivors ... Show moreHodgkin lymphoma (HL) survivors are at increased risk of developing second primary esophageal squamous cell cancer (ESCC). We aimed to gain insight in the driving events of ESCC in HL survivors (hESCC) by using RNA sequencing and NanoString profiling. Objectives were to investigate differences in RNA signaling between hESCC and sporadic ESCC (sESCC), and to look for early malignant changes in non-neoplastic esophageal tissue of HL survivors (hNN-tissue). We analyzed material of 26 hESCC cases, identified via the Dutch pathology registry (PALGA) and 17 sESCC cases from one academic institute and RNA sequencing data of 44 sESCC cases from TCGA. Gene expression profiles for the NanoString panel PanCancer IO 360 were obtained from 16/26 hESCC and four hNN-tissue, while non-neoplastic squamous tissue of four sporadic cases (sNN-tissue) served as reference profile. Hierarchical clustering, differential expression and pathway analyses were performed. Overall, the molecular profiles of hESCC and sESCC were similar. There was increased immune, HMGB1 and ILK signaling compared to sNN-tissue. The profiles of hNN-tissue were distinct from sNN-tissue, indicating early field effects in the esophagus of HL survivors. The BRCA1 pathway was upregulated in hESCC tissue, compared to hNN tissue. Analysis of expression profiles reveals overlap between hESCC and sESCC, and differences between hESCC and its surrounding hNN-tissue. Further research is required to validate our results and to investigate whether the changes observed in hNN-tissue are already detectable before development of hESCC. In the future, our findings could be used to improve hESCC patient management. Show less
Purpose: To accurately quantify esophageal tumor position variability and to optimize image guided correction strategies.Material and Methods: Esophageal cancer patients receiving chemoradiotherapy... Show morePurpose: To accurately quantify esophageal tumor position variability and to optimize image guided correction strategies.Material and Methods: Esophageal cancer patients receiving chemoradiotherapy (41.4-50.4 Gy in 23-28 fractions combined with carboplatin plus paclitaxel) were included in a prospective cohort study (NCT02139488). Gold fiducial markers were inserted into the esophageal tumors during diagnostic endoscopic ultrasound. Four-dimensional (4D) planning computed tomography (CT) and daily 4D cone beam (CB) CT scans were acquired. Each CBCT was registered to the planning CT using different regions of interest (bone; 3D), and carina, diaphragm, clinical target volume (CTV), and fiducial markers (4D) for alignment and using the fiducial markers as the true tumor position. Subsequently, a planning target volume (PTV) margin accounting for residual uncertainties, including the average respiratory motion, was calculated for each of these registrations.Results: Fifty-six patients with tumors located in the proximal (n=1), mid (n=7), or distal esophagus (n=25) or at the gastroesophageal junction (n=23) were included. The average peak-to-peak respiratory tumor motion was 0.20, 0.92, and 0.34 cm on the planning CT in left-right (LR), cranial-caudal (CC), and anterior-posterior (AP) directions, respectively. The required PTV margin with average motion amplitude, depending on the correction strategy used for image guidance, ranged from 0.8 cm to 1.0 cm, 1.1 cm to 1.6 cm, and 0.7 cm to 0.9 cm in LR, CC, and AP direction, respectively. A registration based on the CTV resulted in the smallest PTV margins (0.8, 1.1, and 0.7 cm in LR, CC, and AP direction, respectively). For bone registration the calculated PTV margins were 1.0, 1.3, and 0.7 cm in LR, CC, and AP directions, respectively. The registration based on the diaphragm increased PTV margins.Conclusions: Substantial and anisotropic position variability of esophageal tumors was observed during radiation therapy, and nonuniform margins should be considered. Cranial-caudal PTV margins need to be larger than those commonly used. Target positioning during image-guided radiotherapy could be improved with a CTV registration-based correction strategy. (C) 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. Show less
Rigter, L.S.; Schaapveld, M.; Janus, C.P.M.; Krol, A.D.G.; Maazen, R.W.M. van der; Roesink, J.; ... ; Leerdam, M.E. van 2019
