Jon Thor Asmussen

MRI, PET/CT and ultrasound in the preoperative staging of endometrial cancer - a multicenter prospective comparative study.

OBJECTIVES The aim of this prospective multicenter study was to evaluate and compare the diagnostic performance of PET/CT, MRI and transvaginal two-dimensional ultrasound (2DUS) in the preoperative assessment of endometrial cancer (EC). METHODS 318 consecutive women with EC were included when referred to three Danish tertiary gynecological centers for surgical treatment. Preoperatively they were PET/CT-, MRI-, and 2DUS scanned. The imaging results were compared to the final pathological findings. This study was approved by the National Committee on Health Research Ethics. RESULTS For predicting myometrial invasion, we found sensitivity, specificity, PPV, NPV, and accuracy for PET/CT to be 93%, 49%, 41%, 95% and 61%, for MRI to be 87%, 57%, 44%, 92%, and 66% and for 2DUS to be 71%, 72%, 51%, 86% and 72%. For predicting cervical invasion, the values were 43%, 94%, 69%, 85% and 83%, respectively, for PET/CT, 33%, 95%, 60%, 85%, and 82%, respectively, for MRI, and 29%, 92%, 48%, 82% and 78% for 2DUS. Finally, for lymph node metastases, the values were 74%, 93%, 59%, 96%, and 91% for PET/CT and 59%, 93%, 40%, 97% and 90% for MRI. When comparing the diagnostic performance we found PET/CT, MRI and 2DUS to be comparable in predicting myometrial invasion. For cervical invasion and lymph node metastases, however, PET/CT was the best. CONCLUSIONS None of the modalities can yet replace surgical staging. However, they all contributed to important knowledge and were, furthermore, able to upstage low-risk patients who would not have been recommended lymph node resection based on histology and grade alone.

SUVmax of 18FDG PET/CT as a predictor of high-risk endometrial cancer patients

OBJECTIVE To evaluate SUVmax in the assessment of endometrial cancer preoperatively with particular focus on myometrial invasion (MI), cervical invasion (CI), FIGO stage, risk-stratification and lymph node metastases (LNM). METHODS A total of 268 women with endometrial cancer or atypical endometrial hyperplasia underwent FDG PET/CT imaging before surgical treatment. SUVmax of the primary tumour was compared with histological prognostic factors. RESULTS SUVmax was significantly higher in patients with high FIGO stages (p<0.0001), deep MI (p=0.002), CI (p=0.04), LNM (p=0.04) and high risk tumours (p=0.003). Linear regression found that SUVmax was dependent of MI (p=0.001, 95% CI 2.863-11.098), CI (p=0.001, 95% CI 2.896-11.499), risk (p=0.004, 95% CI 0.077-0.397), LNM (p=0.04, 95% CI 0.011-0.482) and FIGO stage (p<0.0001, 95% CI 0.158-0.473). CONCLUSIONS Preoperative PET/CT scanning and SUVmax measurements of the primary tumour may provide additional clinical and prognostic information about MI, CI, LNM and high risk disease in patients with endometrial cancer and allow for individualization of patient care. However, the sensitivity and specificity of the SUVmax in staging endometrial cancer is not high enough to reliably replace surgical staging.

Head-to-head comparison of chest x-ray/head and neck MRI, chest CT/head and neck MRI, and (18)F-FDG-PET/CT for detection of distant metastases and synchronous cancer in oral, pharyngeal, and laryngeal Cancer

The purpose of this study was to determine the detection rate of distant metastasis and synchronous cancer, comparing clinically used imaging strategies based on chest x-ray + head and neck MRI (CXR/MRI) and chest CT + head and neck MRI (CHCT/MRI) with 18F-FDG PET/CT upfront in the diagnostic workup of patients with oral, pharyngeal, or laryngeal cancer. Methods: This was a prospective cohort study based on paired data. Consecutive patients with histologically verified primary head and squamous cell carcinoma at Odense University Hospital from September 2013 to March 2016 were considered for the study. Included patients underwent CXR/MRI and CHCT/MRI as well as PET/CT on the same day and before biopsy. Scans were read masked by separate teams of experienced nuclear physicians or radiologists. The true detection rate of distant metastasis and synchronous cancer was assessed for CXR/MRI, CHCT/MRI, and PET/CT. Results: A total of 307 patients were included. CXR/MRI correctly detected 3 (1%) patients with distant metastasis, CHCT/MRI detected 11 (4%) patients, and PET/CT detected 18 (6%) patients. The absolute differences of 5% and 2%, respectively, were statistically significant in favor of PET/CT. Also, PET/CT correctly detected 25 (8%) synchronous cancers, which was significantly more than CXR/MRI (3 patients, 1%) and CHCT/MRI (6 patients, 2%). The true detection rate of distant metastasis or synchronous cancer with PET/CT was 13% (40 patients), which was significantly higher than 2% (6 patients) for CXR/MRI and 6% (17 patients) for CHCT/MRI. Conclusion: A clinical imaging strategy based on PET/CT demonstrated a significantly higher detection rate of distant metastasis or synchronous cancer than strategies in current clinical imaging guidelines, of which European ones primarily recommend CXR/MRI, whereas U.S. guidelines preferably point to CHCT/MRI in patients with head and neck squamous cell carcinoma.

Contouring and dose calculation in head and neck cancer radiotherapy after reduction of metal artifacts in CT images

Abstract Background: Delineation accuracy of the gross tumor volume (GTV) in radiotherapy planning for head and neck (H&N) cancer is affected by computed tomography (CT) artifacts from metal implants which obscure identification of tumor as well as organs at risk (OAR). This study investigates the impact of metal artifact reduction (MAR) in H&N patients in terms of delineation consistency and dose calculation precision in radiation treatment planning. Material and methods: Tumor and OAR delineations were evaluated in planning CT scans of eleven oropharynx patients with streaking artifacts in the tumor region preceding curative radiotherapy (RT). The GTV-tumor (GTV-T), GTV-node and parotid glands were contoured by four independent observers on standard CT images and MAR images. Dose calculation was evaluated on thirty H&N patients with dental implants near the treated volume. For each patient, the dose derived from the clinical treatment plan using the standard image set was compared with the recalculated dose on the MAR image dataset. Results: Reduction of metal artifacts resulted in larger volumes of all delineated structures compared to standard reconstruction. The GTV-T and the parotids were on average 22% (p < 0.06) and 7% larger (p = 0.005), respectively, in the MAR image plan compared to the standard image plan. Dice index showed reduced inter-observer variations after reduction of metal artifacts for all structures. The average surface distance between contours of different observers improved using the MAR images for GTV and parotids (p = 0.04 and p = 0.01). The median volume receiving a dose difference larger than ±3% was 2.3 cm3 (range 0–32 cm3). Conclusions: Delineation of structures in the head and neck were affected by metal artifacts and volumes were generally larger and more consistent after reduction of metal artifacts, however, only small changes were observed in the dose calculations.

Analysis of CT-verified loco-regional recurrences after definitive IMRT for HNSCC using site of origin estimation methods

Abstract Introduction: A significant part of patients with head and neck squamous cell carcinoma (HNSCC) develop recurrent disease after curative radiotherapy. We aimed to analyze loco-regional recurrence pattern by identifying possible points of recurrence origin by three different methods in relation to treatment volumes. Material and methods: A total of 455 patients completed IMRT-based treatment for HNSCC from 2006 to 2012. A total of 159 patients had remaining cancer after IMRT, developed loco-regional recurrence or distant disease during follow-up. Among those, 69 patients with loco-regional recurrences had affirmative CT or PET/CT scan. Possible points of origin (POs) of the recurrences were identified on scans by two independent observers, estimated as center of mass and as maximum surface distance. The recurrence position was analyzed in relation to high-dose treatment volume (CTV1) and 95% of prescription dose. Results: In total, 104 loco-regional recurrences (54 in T-site and 50 in N-site) were identified in 69 patients. Median time to recurrence for the 69 patients was 10 months. No clinically relevant difference was found between the four POs, with standard deviation between POs in x, y and z axes of 3, 3 and 6 mm. For recurrences inside CTV1, 0–5 mm and 5–10 mm outside CTV1 the standard deviation of dose differences between the POs were 1, 1.4 and 1 Gy, respectively. 56% and 25% of T-site and N-site recurrences were inside CTV1, respectively. Coverage by 95% prescription dose to high-dose treatment volume was achieved in 78% of T-site and 39% of N-site recurrences. Conclusions: For recurrences identified by possible points of recurrence origin, no significant difference between observer-based or mathematically estimated methods was found. More than half of T-site recurrences were inside high-dose treatment volume, whereas N-site recurrences were mainly outside.

Feasibility of FDG-PET/CT imaging during concurrent chemo-radiotherapy in patients with locally advanced pancreatic cancer.

1 Department of Oncology, Odense University Hospital, Denmark, 2 Department of Clinical Physiology and Nuclear Medicine, Hvidovre Hospital, Denmark, 3 Department of Nuclear Medicine, Odense University Hospital, Denmark, 4 Department of Surgery, Odense University Hospital, Denmark, 5 Laboratory of Radiation Physics, Odense University Hospital, Denmark and 6 Department of Radiology, Odense University Hospital, Denmark

Extent and computed tomography appearance of early radiation induced lung injury for non-small cell lung cancer

BACKGROUND AND PURPOSE The present study investigates the extent and appearance of radiologic injury in the lung after radiotherapy for non-small cell lung cancer (NSCLC) patients and correlates radiologic response with clinical and dosimetric factors. METHODS AND MATERIALS Eligible follow-up CT scans acquired up to six months after radiotherapy were evaluated for radiologic injuries in 220 NSCLC patients. Radiologic injuries were divided into three categories: (1) interstitial changes, (2) ground-glass opacity, or (3) consolidation. The relationship between the fraction of injured lung of each category and clinical or dosimetric factors was investigated. RESULTS Radiological injuries of category 1-3 were found in 67%, 52%, and 51% of the patients, and the mean (and maximum) fraction of injured lung was 4.4% (85.9%), 2.4% (46.0%), and 2.1% (22.9%), respectively. Traditional lung dose metrics and time to follow-up predicted lung injury of all categories. Older age increased the risk of interstitial changes and current smoking reduced the risk of consolidation in the lung. CONCLUSION Radiologic injuries were frequently found in follow-up CT scans after radiotherapy for NSCLC patients. The risk of a radiologic response increased with increasing time and lung dose metrics, and depended on patient age and smoking status.

PET/CT versus standard imaging for prediction of survival in patients with recurrent head and neck squamous cell carcinoma

The purpose of this study was to examine whether staging with 18F-FDG PET/CT better predicts survival in patients with recurrent head and neck squamous cell carcinoma (HNSCC) than chest x-ray (CXR) plus head and neck MRI or chest CT (CCT) plus head and neck MRI. Methods: This was a prospective cohort study based on paired data. Consecutive patients with histologically verified HNSCC recurrence were enrolled from September 2013 to March 2016. All patients underwent CXR/MRI, CCT/MRI, and PET/CT on the same day and before biopsy. All imaging studies underwent masked interpretation by separate teams of experienced nuclear physicians or radiologists. Recurrent carcinomas were categorized as localized (equivalent to primary stages I–II), locally advanced (equivalent to primary stages III–IVB), or metastatic (equivalent to primary stage IVC). Discriminative abilities for each imaging strategy with respect to cancer-specific and stage-based survival were compared using Kaplan–Meier analysis, Cox proportional-hazards regression with the Harrell concordance index (C-index), and net reclassification improvement. Results: In total, 110 patients (90 men and 20 women; median age, 66 y; range, 40–87 y) were included. PET/CT significantly changed the assigned tumor stage when compared with imaging strategies based on CXR/MRI or CCT/MRI (P < 0.001 for both). Kaplan–Meier analysis of PET/CT-based staging showed progressively worsened prognosis with localized, locally advanced, or metastatic disease (log-rank test, P < 0.001), whereas CXR/MRI and CCT/MRI were unable to distinguish between these groups in terms of survival (log-rank test, P = 0.18 and P = 0.58, respectively). Overall discriminative ability in predicting cancer-specific mortality was significantly greater for PET/CT (C-index, 0.72) than for CXR/MRI (C-index, 0.55) (P = 0.001) and CCT/MRI (C-index, 0.55)(P < 0.001). The addition of PET/CT to either CXR/MRI or CCT/MRI was associated with a significantly positive net reclassification improvement (P < 0.001 for both). Conclusion: Contrary to standard imaging strategies, PET/CT-based staging in recurrent HNSCC was able to significantly discriminate among the survival courses of patients with local, locally advanced, or metastatic disease and predict their respective survival probability.

Treatment of peritoneal carcinomatosis with Pressurized IntraPeritoneal Aerosol Chemotherapy – PIPAC-OPC2

Abstract Background Peritoneal carcinomatosis (PC) is a common endpoint in both gastrointestinal and non-gastrointestinal cancers, and PC is treated as other systemic metastases – unfortunately with disappointing results and considerable side-effects. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a new method of applying traditional chemotherapy, and preliminary data indicate that PIPAC is safe, able to stabilize or improve quality of life, and can induce an objectively measurable reduction in disease burden in PC. Methods PIPAC-OPC2 is a prospectively controlled Phase II, single center, one-arm, open-label clinical trial investigating the treatment effect of PIPAC in patients with histological or cytological proven PC from gastrointestinal, ovarian or primary peritoneal cancer. Eligible patients will receive PIPAC in series of three using a combination of doxorubicin (1.5 mg/m2) and cisplatin (7.5 mg/m2) for non-colorectal cancer patients (PIPAC C/D), and oxaliplatin (92 mg/m2) in patients with PC of colorectal origin (PIPAC OX). Patients are monitored by: (1) repeated measurements of the Peritoneal Regression Grading Score (PRGS) in biopsies obtained from metal clips marked areas, (2) Quality-of-Life (QoL) questionnaires, (3) Magnetic Resonance Imaging (MRI) and (4) Prognostic Nutritional Index (PNI). Adverse events and surgical complications will be recorded according to the 30 days definition. Results The primary outcome of PIPAC-OPC2 is to evaluate if PIPAC can induce major or complete response (PRGS 1 or 2) within a series of three PIPAC procedures. Secondarily this study investigates changes in QoL and MRI as a staging and response evaluation tool. The secondary outcomes will be used to create a model that may predict which of the patients will benefit from PIPAC treatment. Conclusions It is expected that PIPAC directed therapy can induce major or complete response in 50 % of patients with PC of colorectal origin and in 30 % of patients with PC of non-colorectal origin – and at the same time stabilize or even improve quality of life. This trial may provide data regarding the utility of MRI as a staging and response evaluation tool in patients with PC. Trial registration The study is registered with ClinicalTrials.gov Identifier NCT03287375 and the European Clinical Trials Database (EudraCT) number 2016-003394-18.

A PET/CT-Based Strategy Is a Stronger Predictor of Survival Than a Standard Imaging Strategy in Patients with Head and Neck Squamous Cell Carcinoma

Our purpose was to examine whether staging of head and neck squamous cell carcinoma (HNSCC) by upfront 18F-FDG PET/CT (i.e., on the day of biopsy and before the biopsy) discriminates survival better than the traditional imaging strategies based on chest x-ray plus head and neck MRI (CXR/MRI) or chest CT plus head and neck MRI (CCT/MRI). Methods: We performed a masked prospective cohort study based on paired data. Consecutive patients with histologically verified primary HNSCC were recruited from Odense University Hospital from September 2013 to March 2016. All patients underwent CXR/MRI, CCT/MRI, and PET/CT on the same day. Tumors were categorized as localized (stages I and II), locally advanced (stages III and IVB), or metastatic (stage IVC). Discriminative ability for each imaging modality with respect to HNSCC staging were compared using Kaplan–Meier analysis, Cox proportional hazards regression with the Harrell C-index, and net reclassification improvement. Results: In total, 307 patients with histologically verified HNSCC were included. Use of PET/CT significantly altered the stratification of tumor stage when compared with either CXR/MRI or CCT/MRI (χ2, P < 0.001 for both). Cancer stages based on PET/CT, but not CXR/MRI or CCT/MRI, were associated with significant differences in mortality risk on Kaplan–Meier analyses (P ≤ 0.002 for all PET/CT-based comparisons). Furthermore, overall discriminative ability was significantly greater for PET/CT (C-index, 0.712) than for CXR/MRI (C-index, 0.675; P = 0.04) or CCT/MRI (C-index, 0.657; P = 0.02). Finally, PET/CT was significantly associated with a positive net reclassification improvement when compared with CXR/MRI (0.184, P = 0.03) but not CCT/MRI (0.094%, P = 0.31). Conclusion: Tumor stages determined by PET/CT were associated with more distinct prognostic properties in terms of survival than those determined by standard imaging strategies.