Search

Multiple myeloma (MM) is an incurable bone marrow cancer characterized by the development of osteolytic lesions due to the myeloma-induced increase in osteoclastogenesis and decrease in osteoblastic activity. The standard treatment of MM often involves proteasome inhibitors (PIs), which can also have a beneficial off-target bone anabolic effect. However, long-term treatment with PIs is unadvised due to their high side-effect burden and inconvenient route of administration. Ixazomib is a new-generation, oral PI that is generally well tolerated; however, its bone effect remains unknown. Here, we describe the 3-month results of a single-center phase II clinical trial investigating the effect of ixazomib treatment on bone formation and bone microstructure. Thirty patients with MM in stable disease not receiving antimyeloma treatment for ≥3 months and presenting ≥2 osteolytic lesions received monthly ixazomib treatment cycles. Serum and plasma samples were collected at baseline and monthly thereafter. Sodium 18F-Fluoride positron emission tomography (NaF-PET) whole-body scans and trephine iliac crest bone biopsies were collected before and after three treatment cycles. The serum levels of bone remodeling biomarkers suggested an early ixazomib-induced decrease in bone resorption. NaF-PET scans indicated unchanged bone formation ratios; however, histological analyses of bone biopsies revealed a significant increase in bone volume per total volume after treatment. Further analyses of bone biopsies showed unchanged osteoclast number and COLL1A1High-expressing osteoblasts on bone surfaces. Next, we analyzed the superficial bone structural units (BSUs), which represent each recent microscopic bone remodeling event. Osteopontin staining revealed that following treatment, significantly more BSUs were enlarged (>200,000 μm2), and the distribution frequency of their shape was significantly different from baseline. Overall, our data suggest that ixazomib induces overflow remodeling-based bone formation by decreasing the level of bone resorption and promoting longer bone formation events, making it a potentially valuable candidate for future maintenance treatment.

BACKGROUND AND PURPOSE: Tumour growth during radiotherapy may lead to geographical misses of the target volume. This study investigates the evolution of the tumour extent and evaluates the need for plan adaptation to ensure dose coverage of the target in glioblastoma patients.MATERIALS AND METHODS: The prospective study included 29 patients referred for 59.4 Gy in 33 fractions. Magnetic resonance imaging (MRI) was performed at the time of treatment planning, at fraction 10, 20, 30, and three weeks after the end of radiotherapy. The gross tumour volume (GTV) was defined as the T1w contrast-enhanced region plus the surgical cavity on each MRI set. The relative GTV volume and the maximum distance (Dmax) of the extent of the actual GTV outside the original GTV were measured. Based on the location of the actual GTV during radiotherapy and the original planned dose, a prospective clinical decision was made whether to adapt the treatment.RESULTS: Dose coverage of the GTV during radiotherapy was not compromised, and none of the radiotherapy plans was adapted. The median Dmax (range) was 5.7 (2.0-18.9) mm, 8.0 (2.0-27.4) mm, 8.0 (1.9-27.3) mm, and 8.9 (1.9-34.4) mm at fraction 10, 20, 30, and follow-up. The relative GTV volume and Dmax observed at fraction 10 were correlated with the values observed at follow-up (R=0.74, pCONCLUSION: Large variations in the GTV extent were observed, and changes often occurred early in the treatment. Plan adaptation for geographical misses was not performed in our cohort due to sufficient CTV margins.

Sparse data exist on immune checkpoint inhibition (ICI) in NSCLC patients with brain metastasis (BM), especially for those with no local therapy (LT) (whole brain radiation therapy (WBRT), stereotactic RT (SRT) or neurosurgery) preceding ICI. Our aims were to investigate the prevalence of BM, rate of intracranial response (ICR), and survival and quality of life (QoL) in real-life patients with advanced NSCLC undergoing palliative ICI. This was a prospective non-randomized study (NCT03870464) with magnetic resonance imaging of the brain (MR-C) performed at baseline resulting in a clinical decision to administer LT or not. ICR evaluation (MR-C) at week 8–9 (mRECIST criteria) for group A (LT) and group B (untreated) was assessed. Change in QoL was assessed using EQ-5D-5L. Of 159 included patients, 45 (28%) had baseline BM. Median follow-up was 23.2 months (IQR 16.4–30.2). Of patients in group A (21) and B (16), 16/37 (43%) had symptomatic BM. ICR was 8/21, 38% (complete or partial response) for group A versus 8/16, 50% for group B. No statistical difference in median overall survival of patients with BM (group A: 12.3 (5.2-NR), group B: 20.5 months (4.9-NR)) and without (22.4 months (95% 16.2–26.3)) was obtained. Baseline QoL was comparable regardless of BM, but an improved QoL (at week 9) was found in those without BM. Patients with NSCLC and BM receiving ICI had long-term survival comparable to those without BM.

Purpose: We aimed to assess the association of fecal incontinence to the anatomy of the anal sphincter complex and lower bony spinal anomalies as investigated with magnetic resonance imaging (MRI) in adolescents and adults with anorectal malformations (ARM) after posterior sagittal anorectoplasty (PSARP). Methods: We conducted a cross-sectional study in 20 patients with ARM after PSARP. Anatomy of the anorectum and spine were examined with MRI and functional outcome assessed with the Wexner incontinence score. Results: We included 20 patient (12 males) had a median age of 19.5 years (14–27). One patient was excluded leaving 19 patients for outcome analysis. Fecal incontinence was found in 12 out of 19 patients (63%). Interposed fat was present in 9 patients (47%). The presence (r = 0.597, p = 0.012) and thickness of interposed fat (r = 0.832, p = 0.005) between the anal sphincter complex and bowel were positively correlated to the Wexner fecal incontinence score. No correlation was found between lower bony spinal anomalies and fecal incontinence. Conclusions: A positive correlation between interposed fat and higher Wexner fecal incontinence score was found indicating a more severe fecal incontinence but no other correlation between anatomy of the anal sphincter complex and neorectum to functional bowel outcome was observed.

We compared response categories and impacts on treatment decisions for metastatic breast cancer (MBC) patients that are response-monitored with contrast-enhanced computed-tomography (CE-CT) or fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). A comparative diagnostic study was performed on MBC patients undergoing response monitoring by CE-CT (n = 34) or FDG-PET/CT (n = 31) at the Odense University Hospital (Denmark). The responses were assessed visually and allocated into categories of complete response (CR/CMR), partial response (PR/PMR), stable disease (SD/SMD), and progressive disease (PD/PMD). Response categories, clinical impact, and positive predictive values (PPV) were compared for follow-up scans. A total of 286 CE-CT and 189 FDG-PET/CT response monitoring scans were performed. Response categories were distributed into CR (3.8%), PR (8.4%), SD (70.6%), PD (15%), and others (2.1%) by CE-CT and into CMR (22.2%), PMR (23.8%), SMD (31.2%), PMD (18.5%), and others (4.4%) by FDG-PET/CT, revealing a significant difference between the groups (P &lt, 0.001). PD and PMD caused changes of treatment in 79.1% and 60%, respectively (P = 0.083). PPV for CE-CT and FDG-PET/CT was 0.85 (95% CI: 0.72–0.97) and 0.70 (95% CI: 0.53–0.87), respectively (P = 0.17). FDG-PET/CT indicated regression of disease more frequently than CE-CT, while CE-CT indicated stable disease more often. FDG-PET/CT seems to be more sensitive than CE-CT for monitoring response in metastatic breast cancer.

Purpose: To compare multidisciplinary team conference (MDTC) decisions regarding treatment intent based on either chest X-ray + MRI of the head and neck (CXR/MRI) or 18 F-FDG-PET/CT (PET/CT) in patients with recurrent head and neck squamous cell carcinoma (HNSCC). Methods: Prospective blinded cohort study based on paired data. Consecutive patients with suspected recurrent HNSCC were invited to participate. All included patients underwent CXR/MRI and PET/CT before diagnostic biopsy. An ordinary MDTC using all available imaging data was conducted as per standard practice. After at least three months (to eliminate recall bias in the team), the first project MDTC, based on either CXR/MRI or PET/CT, was conducted, and the tumor board made conclusions regarding treatment. After an additional three months, a second project MDTC was conducted using the complementary imaging strategy. The separate treatment strategies were compared using McNemar's test. Results: A total of 110 patients (90 males and 20 females, median age 66 years, range 40–87) were included. The initial primary tumor originated from the pharynx in 56 (51%) patients, oral cavity in 17 (15%) patients, and larynx in 37 (34%) patients. Based on CXR/MRI, 87 patients (79%) were recommended curative treatment and 23 (21%) palliative treatment. Based on PET/CT, the MDTC decided that 52 (47%) patients were suitable for curative treatment and 58 (53%) for palliative treatment. The absolute difference of 32% was statistically significant (95% CI: 22–42%, p < 0.001). Conclusions: PET/CT affected MDTC decisions in patients with recurrent HNSCC towards less curative and more palliative treatment.

We aimed to evaluate the etiologies of constipation in patients with anorectal malformations having a good prognosis for bowel control but a high risk of constipation. We included twenty-five patients from the Odense university hospital in Denmark. Patients were subjected to colon transit time examination and high resolution anorectal manometry (HRAM). The median age was 18 (14–24) and 48% (12/25) were females. Fifty-two % (13/25) of patients were diagnosed with constipation. Types of anorectal malformation were perineal fistula (9/25), rectovestibular fistula (8/25), rectourethral bulbar fistula (5/25) and no fistula (3/25). No difference in neither total colon transit time nor segmental colon transit times were found based on the presence of constipation. Only four of the constipated patients fulfilled criteria for dyssynergic defecation with a dyssynergic pattern at HRAM and prolonged colon transit time. A Type I dyssynergic pattern was dominant in constipated patients (7/13). A Dyssynergic defecation pattern was due to isolated contraction of puborectalis muscle in 9 out of 13constipated patients. We found a dyssynergic pattern during attempted defecation in patients with anorectal malformations disregarded the presence of constipation. In the majority of constipated patients an isolated contraction of the puborectalis muscle was visualized with HRAM.

The lytic bone disease is a hallmark of multiple myeloma, being present in about 80% of patients with newly diagnosed MM, and in more during the disease course. The myeloma associated bone disease (MBD) severely affects the morbidity and quality of life of the patients. MBD defines treatment demanding MM. In recent years, knowledge of the underlying pathophysiology has increased, and novel imaging technologies, medical and non-pharmaceutical treatments have improved. In this review, we highlight the major achievements in understanding, diagnosing and treating MBD. For diagnosing MBD, low-dose whole-body CT is now recommended over conventional skeletal survey, but also more advanced functional imaging modalities, such as diffusion-weighted MRI and PET/CT are increasingly important in the assessment and monitoring of MBD. Bisphosphonates have, for many years, played a key role in management of MBD, but denosumab is now an alternative to bisphosphonates, especially in patients with renal impairment. Radiotherapy is used for uncontrolled pain, for impeding fractures and in treatment of impeding or symptomatic spinal cord compression. Cement augmentation has been shown to reduce pain from vertebral compression fractures. Cautious exercise programs are safe and feasible and may have the potential to improve the status of patients with MM.

Objective To examine the impact of spinal defects on urinary function, sexual outcome and quality of life in adult patients born with anorectal malformations. Materials and Methods A prospective cohort study at Odense University Hospital in Denmark was conducted. From 1985 to 2000, 93 patients were found eligible for participation. Twenty-seven (29%) consented to participate. One patient refrained from clinical examinations. Patients were examined with magnetic resonance imaging, uroflowmetry, and validated questionnaires on urinary function, sexual function, and quality of life. Results There were 14 were females and 13 were males, median age of 25 (range 19-31) years and 23 (18-32) years, respectively. The type of anorectal malformations in females were vestibular fistula (n = 6), anocutaneous fistula (n = 4), anal stenosis (n = 3), and cloaca (n = 1). In males the type of malformations were anocutaneous fistula (n = 4), bulbar fistula (n = 4), rectovesical fistula (n = 2), anal stenosis (n = 1), rectal atresia (n = 1), and anal atresia with no fistula (n = 1). Patients with spinal defects had a lower average voiding rate compared to patients with normal spinal anatomy (P .03), a lower voiding-related quality of life (P .02), and a tendency was observed toward a worse total urinary incontinence-related quality of life score (P .06). Moreover in patients with spinal defect a tendency was seen toward a worse general quality of life (P .09). Conclusion Spinal defects detected by magnetic resonance imaging in adults with anorectal malformations were found to be associated with urinary voiding function.

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 1 head and neck MRI (CXR/MRI) and chest CT 1 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.

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 3 (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.

Background We aimed to evaluate the etiologies of constipation in adolescents and adult patients with anorectal malformations with colon transit time and high resolution anorectal manometry Methods We included twenty-five patients from the Odense university hospital in Denmark. Written and verbal informed consent was obtained. Patients were subjected to colon transit time examination and high resolution anorectal manometry. Presence of constipation was diagnosed based on the Rome IV criteria. Questionnaires regarding functional bowel outcome and severity of constipation were filled in. Results The median age was 18(14-24) and 48% (12/25) were females. Fifty-two % (13/25) of patients were diagnosed with constipation. Most frequent type of anorectal malformation was anocutaneous fistula (9/25), vestibular fistula (8/25) and urethral bulbar fistula (4/25). No difference in neither total colon transit time nor segmental colon transit times were found based on the presence of constipation. Constipated patients and patients without constipation were equal on manometric parameters. Only four of the constipated patients fulfilled criteria for dyssynergic defecation with dyssynergic defecation pattern and prolonged colon transit time. A Type I dyssynergic pattern was dominant in constipated patients as it was detected in 54% (7/13). Dyssynergic defecation pattern was due to isolated contraction of puborectalis muscle in 69% (9/13) of constipated patients. Conclusions We found a dyssynergic defecation pattern during attempted defecation in patients with anorectal malformations disregarded the presence of constipation. In the majority of constipated patients an isolated contraction of the puborectalis muscle was visualized with high resolution anorectal manometry. Trial registration: Clinical.Trials.gov. (NCT02624232).

Objective: To investigate whether a 18F-FDG PET/CT (PET/CT)-based diagnostic strategy adds decisive new information compared to conventional imaging in the evaluation of salivary gland tumours and the detection of cervical lymph node metastases, distant metastases, and synchronous cancer in patients with salivary gland carcinoma. Methods: The study was a blinded prospective cohort study. Data were collected consecutively through almost 3 years. All patients underwent conventional imaging—magnetic resonance imaging (MRI) and chest X-ray (CXR)—in addition to PET/CT prior to surgery. Final diagnosis was obtained by histopathology. MRI/CXR and PET/CT were interpreted separately by experienced radiologists and nuclear medicine physicians. Interpretation included evaluation of tumour site, cervical lymph node metastases, distant metastases, and synchronous cancer. Results: Ninety-one patients were included in the study. Thirty-three patients had primary salivary gland carcinoma and eight had cervical lymph node metastases. With PET/CT, the sensitivity was 92% and specificity 29% regarding tumour site. With MRI/CXR, the sensitivity and specificity were 90% and 26%, respectively. Regarding cervical lymph node metastases in patients with salivary gland carcinoma, the sensitivity with PET/CT was 100% and with MRI/CXR 50%. PET/CT diagnosed distant metastases in five patients, while MRI/CXR detected these in two patients. Finally, PET/CT diagnosed two synchronous cancers, whereas MRI/CXR did not detect any synchronous cancers. Conclusions: Compared with MRI/CXR PET/CT did not improve discrimination of benign from malignant salivary gland lesions. However, PET/CT may be advantageous in primary staging and in the detection of distant metastases and synchronous cancers.

Acknowledging the increasingly important role of whole-body MRI for directing patient care in myeloma, a multidisciplinary, international, and expert panel of radiologists, medical physicists, and hematologists with specific expertise in whole-body MRI in myeloma convened to discuss the technical performance standards, merits, and limitations of currently available imaging methods. Following guidance from the International Myeloma Working Group and the National Institute for Clinical Excellence in the United Kingdom, the Myeloma Response Assessment and Diagnosis System (or MY-RADS) imaging recommendations are designed to promote standardization and diminish variations in the acquisition, interpretation, and reporting of whole-body MRI in myeloma and allow response assessment. This consensus proposes a core clinical protocol for whole-body MRI and an extended protocol for advanced assessments. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

IntroductionProstate cancer (PC) is one of the most frequent malignancies among men, with approximately 4500 new cases diagnosed every year in Denmark. PC is responsible for more than 1000 deaths every year in Denmark. Pivotal to the successful treatment of PC is establishing an early diagnosis, which is currently performed by transrectal ultrasound guided biopsy from the prostate. Biopsies are associated with discomfort and severe complications. Some of these complications can, in rare cases, prove fatal. As the biopsies are taken randomly throughout the gland, the procedure has a high risk of false negative result. Multiparametric magnetic resonance imaging (mpMRI) has shown promising results in curbing some of these inadequacies. Combined with advances in the field of liquid biomarkers we seek to establish a new predictive model significantly reducing the need for prostate biopsies.Materials & methodsWe plan to randomize a total of 456 men to either standard pathway (SP) or “mpMRI pathway (MP) in a 1:7 fashion. Blood and urine samples are taken prior to biopsies. We will perform a new type of biomarker sampling (liquid biopsy) on the collected urine and blood specimens. If suspicions lesions are found on the mpMRI additional targeted biopsy cores will be taken.Results, 41 men have completed the study with 37 randomised to MP and 4 to the standard pathway. 27.8% of men in MP had negative biopsy results compared with 50,0% in the SP. The negative predictive value of mpMRI was 80,0% (CI 59,3%- 93,17%) for Gleason Score > 6 PC, when using combined standard and targeted biopsies as reference test. The results of the liquid biopsies are still pending. ConclusionsOur preliminary results suggest that mpMRI adds importen additional information, that could better help select patients for biopsy. Combined with the results from the ´liquid biopsy´ we expect to be able to reduce the number of needed biopsies significantly

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 5 0.18 and P 5 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 5 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.

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/m(2)) and cisplatin 7.5 mg/m(2)) for non-colorectal cancer patients (PIPAC C/D), and oxaliplatin (92 mg/m(2)) 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. 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/m(2)) and cisplatin 7.5 mg/m(2)) for non-colorectal cancer patients (PIPAC C/D), and oxaliplatin (92 mg/m(2)) 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.

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 (x 2, 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 5 0.04) or CCT/MRI (C-index, 0.657; P 5 0.02). Finally, PET/CT was significantly associated with a positive net reclassification improvement when compared with CXR/MRI (0.184, P 5 0.03) but not CCT/MRI (0.094%, P 5 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.

PURPOSE: In patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), we wanted to examine the differences in overall treatment decisions, i.e. curative versus palliative treatment intent, reached by a multidisciplinary team conference (MDTC) based on 18F-fluoro-deoxy-glucose-positron emission tomography/computed tomography (PET/CT) or chest X-ray + MRI of the head and neck (CXR/MRI).PATIENTS AND METHODS: This was a prospective blinded cohort study based on paired data. Consecutive patients with histologically verified primary HNSCC were invited to participate. All included patients underwent CXR/MRI and PET/CT before diagnostic biopsy. An ordinary MDTC using all available imaging was conducted as per standard practice. After at least 3 months (to eliminate recall bias in the team), the first project MDTC was conducted, based on either CXR/MRI or PET/CT, and the tumor board drew conclusions regarding treatment. After an additional 3 months, a second project MDTC was conducted using the complementary imaging modality.RESULTS: A total of 307 patients were included. Based on CXR/MRI, 303 patients (99%) were recommended for curative treatment and only four patients (1%) for palliative treatment. Based on PET/CT, the MDTC concluded that 278 (91%) patients were suitable for curative treatment and 29 (9%) patients for palliative treatment. The absolute difference of 8% was statistically significant (95% CI: 4.8%-11.5%, p < 0.001).CONCLUSIONS: A PET/CT-based imaging strategy significantly changed the decisions regarding treatment intent made by a MDTC for patients diagnosed with HNSCC, when compared with the standard imaging strategy of CXR/MRI.

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.

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.

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.

Aim:In multiple myeloma (MM), high intensity of FDG uptake in focal lesions measured as the standard uptake value (SUV) at diagnosis is associated to aggressive disease and reduced overall survival. However, the reason for high intensity FDG uptake in some focal lesions is unknown, but hypothetically such "hot" lesions could represent evolving myeloma sub-clones with particular characteristics, e.g. higher proliferative activity. We aimed to explore and characterize focal lesions with high FDG uptake and to compare the findings with random diagnostic bone marrow biopsies with lower FDG intensity or a biopsy from another lesion with lower FDG uptake. Thus, we have created a paired biopsy biobank that will be explored for molecular, biological, physiological and myeloma prognostic markers. Here we present our first data including results on morphology, immunohistochemistry, mutational, proliferative and cytogenetic status in the biopsies Material and methods: CT-guided biopsies from FDG-PET positive CT-visible focal lesions in sternum, sacrum, humerus, femoral, pubic and iliac bones were taken without complications depending on accessibility and safety in 14 newly diagnosed, untreated MM patients, 2 females and 12 males, aged 53-77 years. Patients that had received steroids or bisphosphonates were excluded. Bone marrow biopsies were taken as part of the normal diagnostic work-up, but included an extra biopsy and aspirate for research. FDG uptake in the regions of interest (ROI) at focal and random bone marrow biopsy was quantified by dedicated software (ROVER, ABX, Radeberg, Germany) to obtain the following variables: Lesion volumes, SUVmax, SUVpeak, cSUVmean (SUVmean corrected for partial volume effect). The paired biopsies were analyzed for: Myeloma plasma cells percentage (PC%), myeloma cell proliferation (Ki67 positive fraction of CD138 positive cells (Ki67/CD138%), myeloma cell MYC protein expression (MYC/CD138%), FISH aberrations in % of myeloma cells (del17p, del13q, del1p, amp1q, t(11;14), t(4;14), BRAF mutation and specific p16, p27, and p53 protein expressions by IHC in % of MM cells. Results: 13 patients were evaluable for analysis with paired datasets. One patient was excluded due to a normal bone marrow examination (multifocal myeloma). ROI SUVmax values ranged from 2.6 to 22.16 and differences in SUVmax between paired biopsies ranged from 0.4 to 17.1. First of all, we found myeloma malignancy in all PET-positive CT-guided biopsies. Comparing the findings in "hot" versus "random" biopsy groups we found significantly higher PC%s in the "hot" biopsy group (p=0.01) but this was not a consistent finding in all patients. PC proliferation rate (Ki67/CD138) was higher in some of the "hot" biopsies but this was neither a uniform observation. No difference in "primary event" chromosome 14q translocations was observed, whereas we identified subclones with typical cytogenetic secondary or late events in several "hot" biopsies that were not present in the random bone marrow biopsy: amp1q in 3 patients, del1p in 1 patient, del13q and del17p in 1 patient. MYC protein expression was higher in "hot" biopsies in 4 patients, and downregulation of p27 was evident in 2 patients. We found no unbalanced expression of p53 or p16, and in only one patient we identified a BRAF mutated subclone that was equally present in the "hot" and "random" biopsy (20% vs 30%). Few patients presented more adverse findings in the "hot" biopsies. Overall, MM adverse findings were present unbalancedly in 8 of 13 patients. Conclusion: We did not identify a mutual factor that explained the more intense FDG uptake in CT guided biopsies than in random bone marrow, e.g. a higher PC Ki67 expression. However, in 8 of 13 patients we identified 1 or more prognostic adverse, unbalanced findings in the PET positive focal lesions indicating presence of more aggressive subclones. These findings are concordant with the adverse prognostic importance of finding high-intense PET-positive focal lesions on FDG-PET/CT in newly diagnosed MM patients. Disclosures No relevant conflicts of interest to declare.

The aim was to investigate the performance of (18)F-fluorodeoxyglucose PET/CT to rule out malignancy in patients with confirmed vocal cord palsy (VCP). Between January 2011 and June 2013, we retrospectively included consecutive patients referred to PET/CT with paresis or paralysis of one or both vocal cords. PET/CT results were compared to clinical workup and histopathology. The study comprised 65 patients (32 females) with a mean age of 66±12 years (range 37-89). Eleven patients (17%) had antecedent cancer. Twenty-seven (42%) were diagnosed with cancer during follow-up. The palsy was right-sided in 24 patients, left-sided in 37, and bilateral in 4. Median follow-up was 7 months (interquartile range 4-11 months). Patients without cancer were followed for at least three months. PET/CT suggested a malignancy in 35 patients (27 true positives, 8 false positives) and showed none in 30 (30 true negatives, 0 false negatives). Thus, the sensitivity, specificity, positive and negative predictive values, and accuracy were (95% confidence intervals in parenthesis): 100% (88%-100%), 79% (64%-89%), 77% (61%-88%), 100% (89%-100%), and 88% (78%-94%), respectively. Sixteen patients had palliative treatment, while 11 were treated with curative intent, emphasising the severity of VCP and the need for a rapid and accurate diagnostic work-up. In this retrospective survey, biopsy proven malignancy (whether newly diagnosed or relapsed) was the cause of VCP in almost half of patients (42%). PET/CT had a high sensitivity (100%) with a relatively high false positive rate, but was excellent in ruling out malignancy (negative predictive value 100%).

Introduction: FDG-PET/CT is a promising methodology for staging, prognostication, and response evaluation in multiple myeloma (MM). The number of focal FDG lesions and the intensity of FDG uptake (standard uptake value, SUV) at diagnosis are informative of disease aggressiveness. Osteolytic bone disease is a hallmark of MM. Hypothetically; increased focal metabolic activity will precede, induce and correlate to osteolytic lesions. We aimed to elucidate the association between focal FDG positive lesions and osteolytic bone disease in MM patients. Methods: Twenty-two newly diagnosed MM patients, 16 males and 6 females aged 53-81years, were prospectively enrolled and studied with a standardized baseline FDG-PET/CT at diagnosis. A nuclear medicine and a radiology specialist evaluated the PET and CT parts separately and independently. Focal FDG positive lesions were assessed by dedicated software (ROVER™, ABX, Germany) to yield volume and SUV measures. All osteolytic lesions identified on CT were noted by size and localization. Results: FDG-PET and CT together identified a total of 390 lesions. We found more osteolytic lesions on CT (335) than FDG-positive lesions (169); the concordance between the modalities was 30%. 34% (114/335) of lytic lesions were FDG-positive, whereas ⅔ (114/169) of focal FDG-PET positive lesions were lytic according to CT. We found a significant correlation between higher FDG uptake measured as SUVpeak and osteolytic lesions >10 mm, and focal lesions with high FDG uptake had more pronounced osteolysis than focal lesions with less FDG uptake. Still sparse follow-up data did not allow analysis of the predictive value of focal PET positivity and the risk of development of future osteolysis. More compulsive data will be presented at the meeting. Conclusion: FDG-PET/CT offers dual information including metabolic activity (FDG-avidity) and degree of lytic bone disease (low dose whole body CT) in MM. About ⅔ (221/335) of osteolytic lesions were FDG-negative, whereas ⅔ (114/169) of FDG-positive lesions had a lytic component. Disclosures Plesner: Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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.

The aim of the study was to identify the frequency of asymptomatic brain metastases detected by computed tomography (CT) scans in patients with metastatic cutaneous melanoma referred to first-line systemic treatment. Between 1995 and 2009, 697 Danish patients were screened with a contrast-enhanced CT scan of the brain before the start of interleukin-2 (IL-2)-based immunotherapy. Among the 697 patients, 80 had asymptomatic brain metastases (12%). Patients' characteristics did not differ significantly between groups with and without brain metastases. Patients received systemic treatment (IL-2-based or cytotoxic chemotherapy), local treatment (stereotactic radiotherapy, whole-brain radiotherapy or surgery), or best supportive care only. The survival was significantly shorter for patients with asymptomatic brain metastases compared with patients without brain metastases (P