Criteria for the diagnosis of extranodal extension detected on radiological imaging in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.

Extranodal extension of tumour on histopathology is known to be a negative prognostic factor in head and neck cancer. Compelling evidence suggests that extranodal extension detected on radiological imaging is also a negative prognostic factor. Furthermore, if imaging detected extranodal extension could be identified reliably before the start of treatment, it could be used to guide treatment selection, as patients might be better managed with non-surgical approaches to avoid the toxicity and cost of trimodality therapy (surgery, chemotherapy, and radiotherapy together). There are many aspects of imaging detected extranodal extension that remain unresolved or are without consensus, such as the criteria to best diagnose them and the associated terminology. The Head and Neck Cancer International Group conducted a five-round modified Delphi process with a group of 18 international radiology experts, representing 14 national clinical research groups. We generated consensus recommendations on the terminology and diagnostic criteria for imaging detected extranodal extension to harmonise clinical practice and research. These recommendations have been endorsed by 19 national and international organisations, representing 34 countries. We propose a new classification system to aid diagnosis, which was supported by most of the participating experts over existing systems, and which will require validation in the future. Additionally, we have created an online educational resource for grading imaging detected extranodal extensions.

Cost-effectiveness of 2-[18F]FDG-PET/CT versus CE-CT for response monitoring in patients with metastatic breast cancer: a register-based comparative study.

We evaluated the cost-effectiveness of 2-[18F]FDG-PET/CT compared to CE-CT for response monitoring in metastatic breast cancer (MBC) patients. The study included 300 biopsy-verified MBC patients treated at Odense University Hospital (Denmark). CE-CT was used in 144 patients, 83 patients underwent 2-[18F]FDG-PET/CT, and 73 patients received a combination of both. Hospital resource-based costs (2007-2019) were adjusted to the 2019 level. The incremental cost-effectiveness ratio (ICER) was calculated by comparing average costs per patient and gained survival with CE-CT. During a median follow-up of 33.0 months, patients in the 2-[18F]FDG-PET/CT group had more short admissions (median 6 vs. 2) and fewer overnight admissions (5 vs. 12) compared to the CE-CT group. The mean total cost per patient was €91,547 for CE-CT, €83,965 for 2-[18F]FDG-PET/CT, and €165,784 for the combined group. The ICER for 2-[18F]FDG-PET/CT compared to CE-CT was €-527/month, indicating gaining an extra month of survival at a lower cost (€527). 2-[18F]FDG-PET/CT was more cost-effective in patients with favorable prognostic factors (oligometastatic or estrogen receptor-positive disease), while CE-CT was more cost-effective in poor prognosis patients (liver/lung metastases or performance status ≥ 2 at baseline). In conclusion, our study suggests that 2-[18F]FDG-PET/CT is a cost-effective modality for response monitoring in metastatic breast cancer.

A randomised trial of [18F]PSMA-1007-PET/CT versus NaF-PET/CT for staging primary prostate cancer: A trial protocol.

Background: Prostate-specific membrane antigen (PSMA)-positron emission tomography/contrast-enhanced computed tomography (PET/CT) is a sensitive imaging modality for prostate cancer (PCa). Due to lack of knowledge of the patient benefit, PSMA-PET/CT is not yet recommended in the European guidelines for staging and treatment planning of patients with newly diagnosed PCa. We will investigate the potential difference in progression-free survival (PFS) and quality of life (QoL) of using PSMA-PET/CT versus sodium fluoride (NaF)-PET/CT for staging and treatment planning in patients with newly diagnosed PCa. Study Design: This is a prospective randomised controlled multicentre trial carried out at three centres in the Region of Southern Denmark. Endpoints: The primary endpoint is PFS. Secondary endpoints are residual disease, stage migration, impact on treatment strategies, stage distribution, QoL and diagnostic accuracy measures. Patients and Methods: Patients eligible for the study have newly diagnosed unfavourable intermediate- or high-risk PCa. A total of 448 patients will be randomised 1:1 into two groups: (A) a control group staged with Na[18F]F-PET/CT and (B) an intervention group staged with [18F]PSMA-1007-PET/CT. A subgroup in the intervention group will have a supplementary blinded Na[18F]F-PET/CT performed for the purpose of performing accuracy analyses. QoL will be assessed at baseline and with regular intervals (3-12 months) during the study period. Treatment decisions are achieved at multidisciplinary team conferences based on the results of the respective scans and according to current Danish guidelines. Trial Registration: The Regional Committees on Health Research Ethics for Southern Denmark (S-20190161) and the Danish Medicines Agency (EudraCT Number 2021-000123-12) approved the study, and it has been registered on clinicaltrials.gov (Record 2020110469).

2-[18F]FDG-PET/CT is a better predictor of survival than conventional CT: a prospective study of response monitoring in metastatic breast cancer.

This study aimed to compare CE-CT and 2-[18F]FDG-PET/CT for response monitoring metastatic breast cancer (MBC). The primary objective was to predict progression-free and disease-specific survival for responders vs. non-responders on CE-CT and 2-[18F]FDG-PET/CT. The secondary objective was to assess agreement between response categorization for the two modalities. Treatment response in women with MBC was monitored prospectively by simultaneous CE-CT and 2-[18F]FDG-PET/CT, allowing participants to serve as their own controls. The standardized response evaluation criteria in solid tumors (RECIST 1.1) and PET response criteria in solid tumors (PERCIST) were used for response categorization. For prediction of progression-free and disease-specific survival, treatment response was dichotomized into responders (partial and complete response) and non-responders (stable and progressive disease) at the first follow-up scan. Progression-free survival was defined as the time from baseline until disease progression or death from any cause. Disease-specific survival was defined as the time from baseline until breast cancer-specific death. Agreement between response categorization for both modalities was analyzed for all response categories and responders vs. non-responders. At the first follow-up, tumor response was reported more often by 2-[18F]FDG-PET/CT than CE-CT, with only fair agreement on response categorization between the two modalities (weighted Kappa 0.28). Two-year progression-free survival for responders vs. non-responders by CE-CT was 54.2% vs. 46.0%, compared with 59.1% vs. 14.3% by 2-[18F]FDG-PET/CT. Correspondingly, 2-year disease-specific survival were 83.3% vs. 77.8% for CE-CT and 84.6% vs. 61.9% for 2-[18F]FDG-PET/CT. Tumor response on 2-[18F]FDG-PET/CT was significantly associated with progression-free (HR: 3.49, P < 0.001) and disease-specific survival (HR 2.35, P = 0.008), while no association was found for tumor response on CE-CT. In conclusion, 2-[18F]FDG-PET/CT appears a better predictor of progression-free and disease-specific survival than CE-CT when used to monitor metastatic breast cancer. In addition, we found low concordance between response categorization between the two modalities. TRIAL REGISTRATION: Clinical. TRIALS: gov. NCT03358589. Registered 30/11/2017-Retrospectively registered, http://www. CLINICALTRIALS: gov.

Head-to-Head Comparison of Tc-99m-sestamibi SPECT/CT and C-11-L-Methionin PET/CT in Parathyroid Scanning Before Operation for Primary Hyperparathyroidism.

PURPOSE: The preferred nuclear medicine method for identification of hyperfunctioning parathyroid glands in hyperparathyroidism (HPT) develops continuously in relation to the technological progress. Diagnostic methods based on PET/CT have during recent years evolved with new tracer possibilities competing with traditional scintigraphic methods. This investigation is a head-to-head comparison of Tc-99m-sestamibi SPECT/CT gamma camera scintigraphy (sestamibi SPECT/CT) and C-11-L-methionin PET/CT imaging (methionine PET/CT) for preoperative identification of hyperfunctioning parathyroid glands. PROCEDURES: The study is a prospective cohort study including 27 patients diagnosed with primary hyperparathyroidism (PHPT). Two nuclear medicine physicians assessed all examinations independently and blinded. All scanning assessments were matched to the final surgical diagnosis as confirmed by histopathology. Biochemical monitoring of the therapeutical effects was performed preoperatively by PTH-measurements and followed postoperatively for up to 12 months. Comparisons were made for differences in sensitivity and positive predictive value (PPV). RESULTS: Twenty-seven patients (18 females, 9 males; mean age (range): 58.9 years (34.1-79)) were enrolled into the study. The 27 patients had a total of 33 identified sites of lesions of which 28 (85%) turned out to be histopathological verified hyperfunctioning parathyroid glands. The sensitivity and PPV for sestamibi SPECT/CT were 0.71 and 0.95; that of methionine PET/CT was 0.82 and 1, respectively. Both sensitivity and PPV were slightly lower for sestamibi SPECT/CT than for methionine PET PET/CT (-0.11, 95% confidence interval (95% CI): -0.29 to 0.08; -0.05, 95% CI: -0.14 to 0.04, respectively), but not to a statistically significant extent (p=0.38 and p=0.31). The sensitivity and PPV for diagnostic CT were 0.64 (95% CI: 0.44 to 0.81) and 1 (95% CI: 0.81 to 1). CONCLUSIONS: Methionine PET/CT performed comparable to sestamibi SPECT/CT with respect to identification and localization of hyperfunctioning parathyroid glands prior to surgery.

Multiparametric magnetic resonance imaging for characterizing renal tumors: A validation study of the algorithm presented by Cornelis et al.

Objectives: In the last decade, the incidence of renal cell carcinoma (RCC) has been rising, with the greatest increase observed for solid tumors. Magnetic resonance imaging (MRI) protocols and algorithms have recently been available for classifying RCC subtypes and benign subtypes. The objective of this study was to prospectively validate the MRI algorithm presented by Cornelis et al. for RCC classification. Material and Methods: Over a 7-month period, 38 patients with 44 renal tumors were prospectively included in the study and received an MRI examination in addition to the conventional investigation program. The MRI sequences were: T2-weighted, dual chemical shift MRI, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced T1-weighted in wash-in and wash-out phases. The images were evaluated according to the algorithm by two experienced, blinded radiologists, and the histopathological diagnosis served as the gold standard. Results: Of 44 tumors in 38 patients, only 8 tumors (18.2%) received the same MRI diagnosis according to the algorithm as the histopathological diagnosis. MRI diagnosed 16 angiomyolipoma, 14 clear cell RCC (ccRCC), 12 chromophobe RCC (chRCC), and two papillary RCC (pRCC), while histopathological examination diagnosed 24 ccRCC, four pRCC, one chRCC, and one mixed tumor of both pRCC and chRCC. Malignant tumors were statistically significantly larger than the benign (3.16 ± 1.34 cm vs. 2.00 ± 1.04 cm, P = 0.006). Conclusion: This prospective study could not reproduce Cornelis et al.'s results and does not support differentiating renal masses using multiparametric MRI without percutaneous biopsy in the future. The MRI algorithm showed few promising results to categorize renal tumors, indicating histopathology for clinical decisions and follow-up regimes of renal masses are still required.

Increased Bone Volume by Ixazomib in Multiple Myeloma: 3-Month Results from an Open Label Phase 2 Study.

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 18 F-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. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Clinical impact of venous thromboembolism in non-small cell lung cancer patients receiving immunotherapy.

BACKGROUND: Prospective investigation on cancer-associated venous thromboembolism (VTE) in non-small cell lung cancer (NSCLC) during treatment with immune checkpoint inhibitors (ICIs) is lacking. PATIENTS AND METHODS: A prospective real-world study using combined computed tomography venography and pulmonary angiography (CTVPA) to screen patients with NSCLC for VTE (cohort A). A retrospective multicenter cohort without additional screening with CTVPA was included as control (cohort B). A model with VTE as a time-dependent event using competing risk analysis model with death as a competing event was used to evaluate outcomes and differences in cumulative VTE incidences. RESULTS: Cohort A (n = 146) and cohort B (n = 426) had median follow-up for VTE of 16.5 months (IQR 6.7-35.6). Cumulative VTE events at 1, 3, 6, and 12 months were 7.5 %, 9.6 %, 13.0 %, 14.4 % for cohort A and 1.9 %, 3.8 %, 4.9 %, 5.6 % for cohort B with SHR 2.42 (CI 95 % 1.37-4.27) p = 0.0024. Recurrent VTE comprised 52 % and 37 %, respectively. In multivariate overall survival analysis, VTE was significantly associated with impaired OS (HR 2.12 CI 95 % [1.49-3.03], p < 0.0001). Risk factors for VTE comprised prior VTE and ICI administered in first line. CONCLUSION: Cumulative VTE incidence in NSCLC patients following palliative ICI may be significantly higher than reported in randomised clinical trials and retrospective real-world reports. VTE development during ICI impair OS significantly. Thus, more focus on VTE during ICI is warranted to optimise both prevention and management of VTE. Whether there is a causal relationship between VTE and ICI remains to be explored.

Response Monitoring in Metastatic Breast Cancer: A Prospective Study Comparing 18F-FDG PET/CT with Conventional CT.

This study aimed to compare contrast-enhanced CT (CE-CT) and 18F-FDG PET/CT for response monitoring in metastatic breast cancer using the standardized response evaluation criteria RECIST 1.1 and PERCIST. The objective was to examine whether progressive disease was detected systematically earlier by one of the modalities. Methods: Women with biopsy-verified metastatic breast cancer were enrolled prospectively and monitored using combined CE-CT and 18F-FDG PET/CT every 9-12 wk to evaluate response to first-line treatment. CE-CT scans and RECIST 1.1 were used for clinical decision-making without accessing the 18F-FDG PET/CT scans. At study completion, 18F-FDG PET/CT scans were unmasked and assessed according to PERCIST. Visual assessment was used if response criteria could not be applied. The modality-specific time to progression was defined as the time from the baseline scan until the first scan demonstrating progression. Paired comparative analyses for CE-CT versus 18F-FDG PET/CT were applied, and the primary endpoint was earlier detection of progression by one modality. Secondary endpoints were time to detection of progression, response categorization, visualization of changes in response over time, and measurable disease according to RECIST and PERCIST. Results: In total, 87 women were evaluable, with a median of 6 (1-11) follow-up scans. Progression was detected first by 18F-FDG PET/CT in 43 (49.4%) of 87 patients and first by CE-CT in 1 (1.15%) of 87 patients (P < 0.0001). Excluding patients without progression (n = 32), progression was seen first on 18F-FDG PET/CT in 78.2% (43/55) of patients. The median time from detection of progression by 18F-FDG PET/CT to that of CE-CT was 6 mo (95% CI, 4.3-6.4 mo). At baseline, 76 (87.4%) of 87 patients had measurable disease according to PERCIST and 51 (58.6%) of 87 patients had measurable disease according to RECIST 1.1. Moreover, 18F-FDG PET/CT provided improved visualization of changes in response over time, as seen in the graphical abstract. Conclusion: Disease progression was detected earlier by 18F-FDG PET/CT than by CE-CT in most patients, with a potentially clinically relevant median 6-mo delay for CE-CT. More patients had measurable disease according to PERCIST than according to RECIST 1.1. The magnitude of the final benefit for patients is a perspective for future research.

Effect and Tolerability of Immunotherapy in Patients with NSCLC with or without Brain Metastasis.

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.

A prospective study of Skeletal survey versus Low-dose whole-body CT for Osteolytic lesions in Multiple Myeloma.

Whole-body low-dose CT (WBLDCT) is recommended over classical skeletal surveys (CSS) for investigating bone disease in multiple myeloma (MM) based on retrospective studies. No prospective studies with serial follow-up scans exist. OBJECTIVE: To compare WBLDCT to CSS for identifying progressive bone disease in MM in a prospective setting. METHODS: Ninety-six patients with MM at Odense University Hospital and Stavanger Hospital were followed for up to four years. Patients were scanned with WBLDCT and CSS every year for the first two years and every six months thereafter or at suspicion of progression. RESULTS: Nineteen cases of progressive bone disease were found using WBLDCT vs eight cases using CSS (p < 0.001). All cases of progressive bone disease using CSS were also identified by WBLDCT. Progression not found by CSS was primarily in the spine, sternum, and pelvis. Of the 19 cases, five patients had progressive bone disease only without other criteria for clinical progression. WBLDCT consistently identified more bone lesions per patient, 8.2 CI(6.8;9.6) vs CSS, 3.6 CI(2.7;4.5). CONCLUSION: WBLDCT outperformed CSS for finding progressive bone disease and osteolytic lesions. More new lesions were found during follow-up by WBLDCT than CSS. Using CSS for lytic lesions will underestimate progression rates. Our data offer prospective evidence for the current recommendation using WBLDCT for skeletal evaluations in patients with multiple myeloma.

Response monitoring in metastatic breast cancer: a comparison of survival times between FDG-PET/CT and CE-CT.

BACKGROUND: We compared overall survival for metastatic breast cancer (MBC) patients monitored with CE-CT, FDG-PET/CT or a combination of them in an observational setting. METHODS: Patients with biopsy-verified (recurrent or de novo) MBC (n = 300) who were treated at Odense university hospital (Denmark) and response monitored with FDG-PET/CT (n = 83), CE-CT (n = 144), or a combination of these (n = 73) were followed until 2019. Survival was compared between the scan groups, and were adjusted for clinico-histopathological variables representing potential confounders in a Cox proportional-hazard regression model. RESULTS: The study groups were mostly comparable regarding baseline characteristics, but liver metastases were reported more frequently in CE-CT group (38.9%) than in FDG-PET/CT group (19.3%) and combined group (24.7%). Median survival was 30.0 months for CE-CT group, 44.3 months for FDG-PET/CT group and 54.0 months for Combined group. Five-year survival rates were significantly higher for FDG-PET/CT group (41.9%) and combined group (43.3%), than for CE-CT group (15.8%). Using the CE-CT group as reference, the hazard ratio was 0.44 (95% CI: 0.29-0.68, P = 0.001) for the FDG-PET/CT group after adjusting for baseline characteristics. FDG-PET/CT detected the first progression 4.7 months earlier than CE-CT, leading to earlier treatment change. CONCLUSIONS: In this single-center, observational study, patients with metastatic breast cancer who were response monitored with FDG-PET/CT alone or in combination with CE-CT had longer overall survival than patients monitored with CE-CT alone. Confirmation of these findings by further, preferably randomised clinical trials is warranted.

Benefits and harms of implementing [18F]FDG-PET/CT for diagnosing recurrent breast cancer: a prospective clinical study.

BACKGROUND: [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) has been implemented sporadically in hospital settings as the standard of care examination for recurrent breast cancer. We aimed to explore the clinical impact of implementing [18F]FDG-PET/CT for patients with clinically suspected recurrent breast cancer and validate the diagnostic accuracy. METHODS: Women with suspected distant recurrent breast cancer were prospectively enrolled in the study between September 2017 and August 2019. [18F]FDG-PET/CT was performed, and the appearance of incidental benign and malignant findings was registered. Additional examinations, complications, and the final diagnosis were registered to reflect the clinical consequence of such findings. The diagnostic accuracy of [18F]FDG-PET/CT as a stand-alone examination was analyzed. Biopsy and follow-up were used as a reference standard. RESULTS: [18F]FDG-PET/CT reported breast cancer metastases in 72 of 225 women (32.0%), and metastases were verified by biopsy in 52 (52/225, 23.1%). Prior probability and posterior probability of a positive test for suspected metastatic cancer and incidental malignancies were 27%/85% and 4%/20%, respectively. Suspected malignant incidental findings were reported in 46 patients (46/225, 20.4%), leading to further examinations and final detection of nine synchronous cancers (9/225, 4.0%). These cancers originated from the lung, thyroid, skin, pancreas, peritoneum, breast, kidney, one was malignant melanoma, and one was hematological cancer. False-positive incidental malignant findings were examined in 37/225 patients (16.4%), mainly in the colon (n = 12) and thyroid gland (n = 12). Ten incidental findings suspicious for benign disease were suggested by [18F]FDG-PET/CT, and further examinations resulted in the detection of three benign conditions requiring treatment. Sensitivity, specificity, and AUC-ROC for diagnosing distant metastases were 1.00 (0.93-1.0), 0.88 (0.82-0.92), and 0.98 (95% CI 0.97-0.99), respectively. CONCLUSION: [18F]FDG-PET/CT provided a high posterior probability of positive test, and a negative test was able to rule out distant metastases in women with clinically suspected recurrent breast cancer. One-fifth of patients examined for incidental findings detected on [18F]FDG-PET/CT were diagnosed with clinically relevant conditions. Further examinations of false-positive incidental findings in one of six women should be weighed against the high accuracy for diagnosing metastatic breast cancer. Trial registration Clinical.Trials.gov. NCT03358589. Registered 30 November 2017-Retrospectively registered, http://www.ClinicalTrials.gov.

Clinical Impact of FDG-PET/CT Compared with CE-CT in Response Monitoring of Metastatic Breast Cancer.

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 < 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.

Evolution of the gross tumour volume extent during radiotherapy for glioblastomas.

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, p < 0.001 and R = 0.79, p < 0.001, respectively). CONCLUSION: 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.

Magnetic resonance imaging of the anal sphincter and spine in patients with anorectal malformations after posterior sagittal anorectoplasty: a late follow-up cross-sectional study.

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.

Dyssynergic patterns of defecation in constipated adolescents and young adults with anorectal malformations.

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.

Multiple Myeloma Associated Bone Disease.

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.