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Biologically created subvolumes enable non-uniform dose distributions in prostate cancer radiotherapy (RT) thus potentially improving therapeutic ratio and reducing toxicity. We present the long-term outcome of men receiving focal boosting of carbon-11 acetate (ACE) PET-CT metabolically active areas in prostate carcinoma. Thirty men with hormone na��ve localized prostate carcinoma underwent ACE PET/CT for RT planning. There were five low-, 17 intermediate-, and eight high-risk patients. Based on thresholding of the standardized uptake values (SUVs) metabolic target volumes (MTVs) corresponding to intraprostatic lesions (IPLs) were contoured. Two planning target volumes (PTVs) were applied i.e., PTVlow-risk for the whole prostate with 8���10 mm margin and PTVhigh-risk for the MTV. Pelvic nodes were not irradiated. Late toxicity of biologically guided RT was reviewed after a median of 63 months and outcome after a median follow-up of 124 months. Median doses to PTVlow-risk, PTVhigh-risk, prostate, and MTV were 72.9 Gy, 79.4 Gy, 76.6 Gy, and 80.4 Gy, respectively, in 38 fractions. The 10-year cancer-specific survival was 86% and the biochemical failure-free ratio 68%, respectively. The median biochemical progression-free survival (PFS) was 37, 108, and 119 months in the high, intermediate, and low-risk groups, respectively, the difference being significant between high and intermediate-risk groups (p = 0.02). One patient (3%) presented with locoregional and 5 (17%) with distant nodal metastases. Five patients (17%) had a biochemical relapse. A larger MTV was associated with shorter PFS (r = ���0.41, p = 0.02), but had no influence on OS. No other statistically significant differences in the dose painting parameters were observed between recurrence-free and recurring patients. Biological guidance for dose-escalated prostate RT is feasible with ACE PET/CT. Since a larger MTV may be associated with a higher risk for progression, we encourage further study of dose-escalation to ACE-positive lesions considering the low toxicity of our protocol.

Purpose This phase 1 open-label study evaluated the uptake kinetics of a novel theranostic PET radiopharmaceutical, 18F-rhPSMA-7.3, to optimise its use for imaging of prostate cancer. Methods Nine men, three with high-risk localised prostate cancer, three with treatment-naïve hormone-sensitive metastatic disease and three with castration-resistant metastatic disease, underwent dynamic 45-min PET scanning of a target area immediately post-injection of 300 MBq 18F-rhPSMA-7.3, followed by two whole-body PET/CT scans acquired from 60 and 90 min post-injection. Volumes of interest (VoIs) corresponding to prostate cancer lesions and reference tissues were recorded. Standardised uptake values (SUV) and lesion-to-reference ratios were calculated for 3 time frames: 35–45, 60–88 and 90–118 min. Net influx rates (Ki) were calculated using Patlak plots. Results Altogether, 44 lesions from the target area were identified. Optimal visual lesion detection started 60 min post-injection. The 18F-rhPSMA-7.3 signal from prostate cancer lesions increased over time, while reference tissue signals remained stable or decreased. The mean (SD) SUV (g/mL) at the 3 time frames were 8.4 (5.6), 10.1 (7) and 10.6 (7.5), respectively, for prostate lesions, 11.2 (4.3), 13 (4.8) and 14 (5.2) for lymph node metastases, and 4.6 (2.6), 5.7 (3.1) and 6.4 (3.5) for bone metastases. The mean (SD) lesion-to-reference ratio increases from the earliest to the 2 later time frames were 40% (10) and 59% (9), respectively, for the prostate, 65% (27) and 125% (47) for metastatic lymph nodes and 25% (19) and 32% (30) for bone lesions. Patlak plots from lesion VoIs signified almost irreversible uptake kinetics. Ki, SUV and lesion-to-reference ratio estimates showed good agreement. Conclusion 18F-rhPSMA-7.3 uptake in prostate cancer lesions was high. Lesion-to-background ratios increased over time, with optimal visual detection starting from 60 min post-injection. Thus, 18F-rhPSMA-7.3 emerges as a very promising PET radiopharmaceutical for diagnostic imaging of prostate cancer. Trial Registration NCT03995888 (24 June 2019).

Introduction Prognostic biomarkers and novel therapeutic approaches have been slow to emerge in the treatment of head and neck squamous cell carcinoma (HNSCC). In this study, an HNSCC patient cohort is created and performance of putative prognostic biomarkers investigated in a population-validated setting. The overall goal is to develop a novel way to combine biomarker analyses with population-level clinical data on HNSCC patients and thus to improve the carryover of biomarkers into clinical practice. Materials and methods To avoid selection biases in retrospective study design, all HNSCC patients were identified and corresponding clinical data were collected from the Southwest Finland geographical area. A particular emphasis was laid on avoiding potential biases in sample selection for immunohistochemical staining analyses. Staining results were evaluated for potential prognostic resolution. Results After comprehensive evaluation, the patient cohort was found to be representative of the background population in terms of clinical characteristics such as patient age and TNM stage distribution. A negligible drop-out of 1.3% (6/476) was observed during the first follow-up year. By immunohistochemical analysis, the role of previously implicated HNSCC biomarkers (p53, EGFR, p16, CIP2A, Oct4, MET, and NDFIP1) was investigated. Discussion Our exceptionally representative patient material supports the use of population validation to improve the applicability of results to real-life situations. The failure of the putative prognostic biomarkers emphasizes the need for controlling bias in retrospective studies, especially in the heterogenous tumor environment of HNSCC. The resolution of simple prognostic examination is unlikely to be sufficient to identify biomarkers for clinical practice of HNSCC.

Highlights • Distribution of recurrent HNSCC in relation to radiotherapy volume was evaluated. • Both p16 positive and negative HNSCC recur in high-risk treatment volume. • This indicates potential failure of multimodality imaging to disclose significant disease. • A need for biomarkers other than p16 to predict radiosensitivity continues to exist., Background Locoregional recurrence remains a major cause of failure in head and neck squamous cell carcinoma (HNSCC). Human papilloma virus (HPV)-associated HNSCCs generally have a good prognosis but may recur even after standard photon radiotherapy (RT). Another incentive in observing patterns of recurrence is increased use of highly conformal techniques such as proton therapy. We therefore studied geographic distribution of recurrent tumors in relation to the high-risk treatment volume in a cohort of patients with HNSCC receiving combined modality therapy. Methods Medical records of 508 patients diagnosed with HNSCC in 2010–2015 were reviewed. We identified a subgroup that had local and/or regional recurrence at hybrid positron emission tomography (PET)/computed tomography (CT) and/or magnetic resonance imaging (MRI). We adapted p16 as a surrogate marker for HPV-positivity and only patients with known p16 status were eligible for a detailed analysis where recurrent tumor was copied on the planning CT and the dose received by the recurrent tumor volume was determined using dose-volume histograms. Results Twenty-five patients who had received either cisplatin (n = 23) or cetuximab-enhanced (n = 2) RT were identified. 31 locoregional recurrent tumors were detected among 18 p16 negative and 7 p16 positive patients. Of recurrent tumors 14 (45%) were classified as in-field, 5 (16%) as marginal miss, and 12 (39%) as true miss. p16 positive patients had 4 in-field, 2 marginal, and 1 true miss. By contrast, p16 negative patients had 10 in-field, 3 marginal, and 11 true miss recurrences. Conclusions Both p16 positive and negative HNSCC recur in high-risk treatment volume despite the common view of high radiosensitivity of the former. Biomarkers predicting radioresistance should be characterized in p16 positive tumors before widely embarking on de-escalated CRT protocols. Another concern is how to decrease the number of true or marginal misses in p16 negative cases despite multimodality imaging-based target delineation.

High-risk stage II colon cancer is defined in European and American guidelines as the presence of at least one of the following high-risk factors: T4 stage, tumor differentiation grade 3, bowel obs...

In the Nordic countries, as in the rest of the world, particle therapy as a radiotherapy modality, is evolving, albeit the hard evidence for the clinical benefit still is scarce. However, a common goal for the Nordic countries is to include a minimum of 80% of the patients treated with particle therapy into clinical trials. In this paper, we summarize the current status of clinical trials involving particle therapy in the Nordic countries, with an overview of both active and coming trials. So far, one is closed for inclusion and data are being analyzed, seven trials are actively recruiting patients and several more trials are underway. No common Nordic trial has yet been designed, nor is in the planning phase, and the authors will discuss the obstacles as well as the opportunities a common Nordic platform may represent.

The aim of this prospective single-institution clinical trial (NCT02002455) was to evaluate the potential of advanced post-processing methods for 18F-Fluciclovine PET and multisequence multiparametric MRI in the prediction of prostate cancer (PCa) aggressiveness, defined by Gleason Grade Group (GGG). 21 patients with PCa underwent PET/CT, PET/MRI and MRI before prostatectomy. DWI was post-processed using kurtosis (ADCk, K), mono- (ADCm), and biexponential functions (f, Dp, Df) while Logan plots were used to calculate volume of distribution (VT). In total, 16 unique PET (VT, SUV) and MRI derived quantitative parameters were evaluated. Univariate and multivariate analysis were carried out to estimate the potential of the quantitative parameters and their combinations to predict GGG 1 vs >1, using logistic regression with a nested leave-pair out cross validation (LPOCV) scheme and recursive feature elimination technique applied for feature selection. The second order rotating frame imaging (RAFF), monoexponential and kurtosis derived parameters had LPOCV AUC in the range of 0.72 to 0.92 while the corresponding value for VT was 0.85. The best performance for GGG prediction was achieved by K parameter of kurtosis function followed by quantitative parameters based on DWI, RAFF and 18F-FACBC PET. No major improvement was achieved using parameter combinations with or without feature selection. Addition of 18F-FACBC PET derived parameters (VT, SUV) to DWI and RAFF derived parameters did not improve LPOCV AUC.

Background To present the 18 months results from a prospective multicenter phase II randomized trial of short vs protracted urethra‐sparing stereotactic body radiotherapy (SBRT) for localized prostate cancer (PCa). Methods Between 2012 and 2015, a total of 170 PCa patients were randomized to 36.25 Gy in 5 fractions (6.5 Gy × 5 to the urethra) delivered either every other day (EOD, arm A, n = 84) or once a week (QW, arm B, n = 86). Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v4.0 scale), IPSS, and QoL scores were assessed at baseline, at the 5th fraction (5fx), 12th weeks (12W), and every 6 months after SBRT. The primary endpoint was biochemical control at 18 months and grade ≥ 3 toxicity (including grade ≥ 2 for urinary obstruction/retention) during the first 3 months. Results Among the 165 patients analyzed, the toxicity stopping rule was never activated during the acute phase. Maximum acute grade 2 GU toxicity rates at 5fx were 17% and 19% for arms A and B, respectively, with only 2 cases of grade 2 GI toxicity at 5fx in arm A. At month 18, grade ≥ 2 GU and GI toxicity decreased below 5% and 2% for both arms. No changes in EORTC QLQ‐PR25 scores for GU, GI, and sexual domains were observed in both arms between baseline and month 18. Four biochemical failures were observed, 2 in each arm, rejecting the null hypothesis of an unfavorable response rate ≤ 85% in favor of an acceptable ≥ 95% rate. Conclusions At 18 months, urethra‐sparing SBRT showed a low toxicity profile, with minimal impact on QoL and favorable biochemical control rates, regardless of overall treatment time (EOD vs QW)., Dose per fraction and overall treatment time can impact tolerance of prostate SBRT. Urethra‐sparing SBRT showed a low toxicity profile and minimal impact on QoL. An EOD or QW SBRT schedule had a comparable tolerance and efficacy at 18 months.

Background and purpose: Magnetic resonance imaging (MRI) is increasingly used in radiation therapy planning of prostate cancer (PC) to reduce target volume delineation uncertainty. This study aimed to assess and validate the performance of a fully automated segmentation tool (AST) in MRI based radiation therapy planning of PC. Material and methods: Pelvic structures of 65 PC patients delineated in an MRI-only workflow according to established guidelines were included in the analysis. Automatic vs manual segmentation by an experienced oncologist was compared with geometrical parameters, such as the dice similarity coefficient (DSC). Fifteen patients had a second MRI within 15 days to assess repeatability of the AST for prostate and seminal vesicles. Furthermore, we investigated whether hormonal therapy or body mass index (BMI) affected the AST results. Results: The AST showed high agreement with manual segmentation expressed as DSC (mean, SD) for delineating prostate (0.84, 0.04), bladder (0.92, 0.04) and rectum (0.86, 0.04). For seminal vesicles (0.56, 0.17) and penile bulb (0.69, 0.12) the respective agreement was moderate. Performance of AST was not influenced by neoadjuvant hormonal therapy, although those on treatment had significantly smaller prostates than the hormone-naïve patients (p

The aim of this guideline is to provide standards for the recommendation, performance, interpretation, and reporting of [18F]Fluciclovine PET/CT for prostate cancer imaging. These recommendations will help to improve accuracy, precision, and repeatability of [18F]Fluciclovine PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.

Purpose Radiation scattering from bone reconstruction materials can cause problems from prolonged healing to osteoradionecrosis. Glass fiber reinforced composite (FRC) has been introduced for bone reconstruction in craniofacial surgery but the effects during radiotherapy have not been previously studied. The purpose of this study was to compare the attenuation and back scatter caused by different reconstruction materials during radiotherapy, especially FRC with bioactive glass (BG) and titanium. Methods The effect of five different bone reconstruction materials on the surrounding tissue during radiotherapy was measured. The materials tested were titanium, glass FRC with and without BG, polyether ether ketone (PEEK) and bone. The samples were irradiated with 6 MV and 10 MV photon beams. Measurements of backscattering and dose changes behind the sample were made with radiochromic film and diamond detector dosimetry. Results An 18% dose enhancement was measured with a radiochromic film on the entrance side of irradiation for titanium with 6 MV energy while PEEK and FRC caused an enhancement of 10% and 4%, respectively. FRC‐BG did not cause any measurable enhancement. The change in dose immediately behind the sample was also greatest with titanium (15% reduction) compared with the other materials (0–1% enhancement). The trend is similar with diamond detector measurements, titanium caused a dose enhancement of up to 4% with a 1 mm sample and a reduction of 8.5% with 6 MV energy whereas FRC, FRC‐BG, PEEK or bone only caused a maximum dose reduction of 2.2%. Conclusions Glass fiber reinforced composite causes less interaction with radiation than titanium during radiotherapy and could provide a better healing environment after bone reconstruction.

Background In high-income countries, cancer is the leading cause of death among middle-aged adults. Prospective data on the effects of childhood risk exposures on subsequent cancer mortality are scarce. Methods We examined whether childhood body mass index (BMI), blood pressure, glucose and lipid levels were associated with adult cancer mortality, using data from 21,012 children enrolled aged 3–19 years in seven prospective cohort studies from the U.S., Australia, and Finland that have followed participants from childhood into adulthood. Cancer mortality (cancer as a primary or secondary cause of death) was captured using registries. Results 354 cancer deaths occurred over the follow-up. In age-, sex, and cohort-adjusted analyses, childhood BMI (Hazard ratio [HR], 1.13; 95% confidence interval [CI] 1.03–1.24 per 1-SD increase) and childhood glucose (HR 1.22; 95%CI 1.01–1.47 per 1-SD increase), were associated with subsequent cancer mortality. In a multivariable analysis adjusted for age, sex, cohort, and childhood measures of fasting glucose, total cholesterol, triglycerides, and systolic blood pressure, childhood BMI remained as an independent predictor of subsequent cancer mortality (HR, 1.24; 95%CI, 1.03–1.49). The association of childhood BMI and subsequent cancer mortality persisted after adjustment for adulthood BMI (HR for childhood BMI, 1.35; 95%CI 1.12–1.63). Conclusions Higher childhood BMI was independently associated with increased overall cancer mortality.

Purpose: Overexperssion of Gastrin-releasing-peptide receptor (GRPr) in prostate carcinoma (PCa) suggests new means in the detection of prostate cancer foci. The bombesin derivative RM2 (DOTA-4-amino-1-carboxy­methyl­piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) is a GRPr antagonist with strong binding affinity. Based on promising results from a first-in-man study on PCa detection in patients with local disease, a Phase I/II study was initiated and the ability of [68Ga]Ga-RM2 PET/CT to detect PCa lesions was compared with [18F]fluoromethylcholine ([18F]FCH) PET/CT and multiparameteric prostate Magnetic Resonance Imaging (mpMRI).Methods: This Phase I/II study was conductedwith a pre-specified interim analysis following the enrollment of 30 biopsy-positive PCa subjects, stratified into low, intermediate and high pretreatment risk of extra-glandular metastases with reference to NCCN criteria. Each subject had PCa detected by transrectal ultrasound guided prostate biopsy and subjects were scheduled to undergo prostatectomy with pelvic lymph node (LN) dissection in intermediate and high risk patients. Following administration of an intravenous dose of 140 MBq of [68Ga]Ga-RM2,imaging was conducted at 60 min. p.i.. Twenty-five (25/30) subjects had concomitant [18F]FCH PET/CT imaging. All patients underwent mpMRI. Intra-prostatic and pelvic nodal PET/CT findings were correlated with histopathologic results.Results: High uptake of [68Ga]Ga-RM2 was seen in pancreas and the urinary system with very low background uptake in the rest of the abdomen or thorax. Despite of high bladder activity, focal intraprostatic uptake was readily well detectable. Of overall 312 analyzed regions, 120 regions (4 to 8 lesions per-patient) showed abnormal finding in the prostate gland. In a region-based analysis overall sensitivity and specificity of [68Ga]Ga-RM2 PET/CT in the detection of primary tumor were 74% and 90%, respectively; while it was 60% and 80% for [18F]FCH PET/CT and 72% and 89% for mpMRI. Although, the overall sensitivity of [68Ga]Ga-RM2 PET/CT was higher comparing to [18F]FCH PET/CT and mpMRI; however, the statistical analysis showed only significant difference between [68Ga]Ga-RM2 PET/CT and [18F]FCH PET/CT in intermediate-risk group (P=0.01) and [68Ga]Ga-RM2 PET/CT and mpMRT in high-risk group (p=0.03). [68Ga]Ga-RM2 PET/CT correctly detected 2 histopathologically verified LN metastases in 2 high risk patients; while 18F-FCH PET/CT only identified the LN lesion in 1 patient.Conclusion: [68Ga]Ga-RM2 is a promising new PET-tracer with a high detection rate for intraprostatic PCa. While index lesion detection rates were similar in both PET/CT studies, the improved specificity of [68Ga]Ga-RM2 for canver versus BPH renders it notably better than [18F]FCH in the detection of intraprostatic lesions. In addition, GRP-R-based imaging seems to play a complementary role to Choline-based imaging for full characterization of PCa extent, biopsy guidance in low and intermediate metastatic risk PCa patients and has the potential to discriminate them from whom of those at higher risks.Trial Registeration number: EudraCT-Nr.: 2014-003027-21, Date: 10 June, 2014

BackgroundSomatostatin receptors (SSTR) and chemokine receptor CXCR4 are expressed in lymphomas, while the abundance is known to be heterogeneous in different subtypes of lymphomas. Targeting tumor cells expressing these receptors might add to therapeutic opportunities while radiolabeled ligands for both imaging and therapy have been developed. The aim of this study was to establish SSTR subtype 2, 3 and 5 and also CXCR4 status immunohistochemically in six different lymphoma subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), mucosa-associated marginal B-cell lymphoma (MALT), Hodgkin lymphoma (HL) and peripheral T-cell lymphoma (PTCL).Material and MethodsThis study included a total of 103 lymphoma patients (24 DLBCL, 22 FL, 18 HL, 9 MALT, 20 MCL and 10 PTCL) diagnosed in the Southwest hospital district of Finland during 2010-2019. SSTR 2, 3 and 5 and CXCR4 expression was analyzed immunohistochemically (IHC) in lymphoma samples obtained from local archival Biobank tissue repository. Immunopositivity of each receptor was scored on a four-point scale accounting for staining intensity and proportion of positively stained tumor cells.ResultsOf different SSTR subtypes SSTR2 immunopositivity was most common and seen predominantly at the cell membrane of the malignant cells in 46-56% of DLBCL, HL and FL. CXCR4 co-expression was frequently present in these cases. SSTR3 and SSTR5 IHC were negative in DLBCL and FL but in HL SSTR expression was more heterogenous and SSTR3 and SSTR5 positivity was found in cytoplasm in 35% and 25% of cases. 2/4 blastoid MCL variants and one pleomorphic MCL variant had positive CXCR4 IHC whilst all other MCL cases (85%) were negative for all receptors. 30% (n=3) of the PTCL patients had positive SSTR5 IHC and CXCR4. MALT lymphomas were negative for all receptors.ConclusionSSTR2 and CXCR4 are found in DLBCL, FL and HL and co-expression of these receptors is common. Although in general expression of SSTRs and CXCR4 is heterogenous and very low in some subtypes such as MCL and MALT there are also patients with abundant expression. The latter are candidates for trials studying SSTR2 and/or CXCR4 based treatments in the future.

Hypoxia dose painting is a radiotherapy technique to increase the dose to hypoxic regions of the tumour. Still, the clinical effect relies on the reproducibility of the hypoxic region shown in the medical image.Eight HNC patients undergoing twoThe mean (SD) correlation coefficient between DPBN prescription and plan was 0.92 (0.02) and 0.93 (0.02) for sessions A and B, respectively, with corresponding quality factors of 0.02 (0.002) and 0.02 (0.003), respectively. The mean correlation between dose prescriptions at day A and B was 0.72 (0.13), and 0.77 (0.12) for the corresponding plans. A mean correlation of 0.80 (0.08) was found between plan A, recalculated on image basis B, and plan B.Hypoxia DPBN planning based on

Background Persistent smoking after cancer diagnosis is associated with increased overall mortality (OM) and cancer mortality (CM). According to the 2020 Surgeon General's report, smoking cessation may reduce CM but supporting evidence is not wide. Use of deep learning-based modeling that enables universal natural language processing of medical narratives to acquire population-based real-life smoking data may help overcome the challenge. We assessed the effect of smoking status and within-1-year smoking cessation on CM by an in-house adapted freely available language processing algorithm. Materials and methods This cross-sectional real-world study included 29 823 patients diagnosed with cancer in 2009-2018 in Southwest Finland. The medical narrative, International Classification of Diseases-10th edition codes, histology, cancer treatment records, and death certificates were combined. Over 162 000 sentences describing tobacco smoking behavior were analyzed with ULMFiT and BERT algorithms. Results The language model classified the smoking status of 23 031 patients. Recent quitters had reduced CM [hazard ratio (HR) 0.80 (0.74-0.87)] and OM [HR 0.78 (0.72-0.84)] compared to persistent smokers. Compared to never smokers, persistent smokers had increased CM in head and neck, gastro-esophageal, pancreatic, lung, prostate, and breast cancer and Hodgkin's lymphoma, irrespective of age, comorbidities, performance status, or presence of metastatic disease. Increased CM was also observed in smokers with colorectal cancer, men with melanoma or bladder cancer, and lymphoid and myeloid leukemia, but no longer independently of the abovementioned covariates. Specificity and sensitivity were 96%/96%, 98%/68%, and 88%/99% for never, former, and current smokers, respectively, being essentially the same with both models. Conclusions Deep learning can be used to classify large amounts of smoking data from the medical narrative with good accuracy. The results highlight the detrimental effects of persistent smoking in oncologic patients and emphasize that smoking cessation should always be an essential element of patient counseling., Highlights • Deep learning/universal language modeling was used to extract smoking status of cancer patients. Good accuracy was observed. • Those who continue smoking after cancer diagnosis had increased CM compared to never smokers. • Recent within-1-year cessation reduced this mortality. • Detrimental effects of smoking were observed in multiple types of early- and advanced-stage cancers, including the elderly. • We conclude that smoking cessation support should always be included in cancer care.

PurposeTo evaluate fitting quality and repeatability of four mathematical models for diffusion weighted imaging (DWI) during tumor progression in mouse xenograft model of prostate cancer.MethodsHuman prostate cancer cells (PC-3) were implanted subcutaneously in right hind limbs of 11 immunodeficient mice. Tumor growth was followed by weekly DWI examinations using a 7T MR scanner. Additional DWI examination was performed after repositioning following the fourth DWI examination to evaluate short term repeatability. DWI was performed using 15 and 12 b-values in the ranges of 0-500 and 0-2000 s/mm2, respectively. Corrected Akaike information criteria and F-ratio were used to evaluate fitting quality of each model (mono-exponential, stretched exponential, kurtosis, and bi-exponential).ResultsSignificant changes were observed in DWI data during the tumor growth, indicated by ADCm, ADCs, and ADCk. Similar results were obtained using low as well as high b-values. No marked changes in model preference were present between the weeks 1−4. The parameters of the mono-exponential, stretched exponential, and kurtosis models had smaller confidence interval and coefficient of repeatability values than the parameters of the bi-exponential model.ConclusionStretched exponential and kurtosis models showed better fit to DWI data than the mono-exponential model and presented with good repeatability.

Background and purpose: The clinical feasibility of synthetic computed tomography (sCT) images derived from magnetic resonance imaging (MRI) images for external beam radiation therapy (EBRT) planning have been studied and adopted into clinical use recently. This paper evaluates the dosimetric and positioning performance of a sCT approach for different pelvic cancers. Materials and methods: Seventy-five patients receiving EBRT at Turku University Hospital (Turku, Finland) were enrolled in the study. The sCT images were generated as part of a clinical MRI-simulation procedure. Dose calculation accuracy was assessed by comparing the sCT-based calculation with a CT-based calculation. In addition, we evaluated the patient position verification accuracy for both digitally reconstructed radiograph (DRR) and cone beam computed tomography (CBCT) -based image guidance using a subset of the cohort. Furthermore, the relevance of using continuous Hounsfield unit values was assessed. Results: The mean (standard deviation) relative dose difference in the planning target volume mean dose computed over various cancer groups was less than 0.2 (0.4)% between sCT and CT. Among all groups, the average minimum gamma-index pass-rates were better than 95% with a 2%/2mm gamma-criteria. The difference between sCT- and CT-DRR-based patient positioning was less than 0.3 (1.4) mm in all directions. The registrations of sCT to CBCT produced similar results as compared with CT to CBCT registrations. Conclusions: The use of sCT for clinical EBRT dose calculation and patient positioning in the investigated types of pelvic cancers was dosimetrically and geometrically accurate for clinical use. Keywords: Radiotherapy, MRI-only, Image-guided radiotherapy, Position verification

ObjectiveHead and neck cancer follow-up length, interval and content are controversial. Therefore, this study aimed to evaluate the efficacy of the follow-up protocol after curative treatment in head and neck cancer patients.MethodClinical data of 456 patients with new malignancy of the head and neck from a tertiary care centre district from 1999 to 2008 were analysed. Time from treatment, symptoms and second-line treatment outcomes of patients with recurrent disease were evaluated.ResultsA total of 94 (22 per cent) patients relapsed during the 5-year follow-up period; 90 per cent of recurrences were found within 3 years. Fifty-six per cent of the patients had subjective symptoms indicating a recurrence of the tumour. All recurrent tumours found during routine follow-up visits without symptoms were found within 34 months after completion of treatment.ConclusionRoutine follow up after three years is questionable; recurrent disease beyond this point was detected in only 2 per cent of patients. In this study, all late tumour recurrences had symptoms of the disease. Easy access to extra follow-up visits when symptoms occur could cover the need for late follow up.

To quantitate gadolinium deposits in gliomas and adjacent normal brain specimens, and to evaluate their association with tumor contrast enhancement and the type of gadolinium-based contrast agent (GBCA) used. A total of 69 patients with primary glioma who underwent contrast-enhanced magnetic resonance imaging (MRI) prior to surgery were included in this retrospective study. Gadolinium was measured from histologically viable tumor, normal brain, and necrosis within the sample, when available, using inductively coupled plasma mass spectrometry (ICP-MS). Tumor contrast enhancement was categorized as none, minimal, or noticeable. Differences in gadolinium deposits by contrast enhancement and GBCA type were assessed. Seven patients received linear GBCA and 62 macrocyclic, respectively. At the time of surgery, gadolinium deposits were detected in 39 out of 69 (57%) tumor samples, 8 out of 13 (62%) normal brain, and 12 out of 14 (86%) necrotic specimens. Gadolinium was detected in both enhancing and non-enhancing tumors, but was greatest in gliomas with noticeable enhancement (p = 0.02). Administration of linear agents gadodiamide and gadopentetate dimeglumine resulted in significantly higher tumor gadolinium relative to macrocyclic gadoterate meglumine (p

Highlights • Using MRI-only for prostate cancer radiation therapy planning (RTP) can reduce costs. • An MRI-only workflow is particularly suitable for medium-sized and large departments. • Omitting CT in the RTP workflow saves scanner, staff, and patient time., Background and purpose In radiation therapy (RT), significant improvements have been made recently particularly in the practices of planning imaging. This study aimed to conduct a cost evaluation between magnetic resonance imaging (MRI) -only and combined computed tomography (CT) and MRI workflows. Materials and methods The time-driven activity-based costing (TDABC) model was used to conduct a cost evaluation between the two workflows in those steps, where cost differences were expected. Costs were divided into capital costs and operational costs. The former consisted of fixed, one-time expenses, e.g. the purchase of a scanner, whereas the latter were partially based on the amount of activity consumed i.e. time required for image acquisition, image registration and structure contouring. Results In a review over a period of 10 years for 300 annual prostate cancer patients, the total cost of the workflow steps included in the study for an individual patient applying the MRI-only workflow was 903 € (100%), comprised of 537 € (59%) capital costs and 366 € (41%) operational costs. The corresponding total cost for an individual patient applying the CT + MRI workflow was 922 € (100%), comprised of 197 € (21%) capital costs and 726 € (79%) operational costs. In 10 years for 3000 patients, a total saving of 58,544 € (2%) was achieved with the MRI-only workflow compared with the dual imaging workflow. Conclusions MRI-only workflow is a feasible and economic way to perform clinical RT for localized prostate cancer, in particular for medium- and large-sized departments treating a sufficient number of patients.

MRI is a common method of prostate cancer diagnosis. Several MRI-derived markers, including the apparent diffusion coefficient (ADC) based on diffusion-weighted imaging, have been shown to provide values for prostate cancer detection and characterization. The hypothesis of the study was that docetaxel chemotherapy response could be picked up earlier with rotating frame relaxation times TRAFF2 and TRAFF4 than with the continuous wave T1ρ , adiabatic T1ρ , adiabatic T2ρ , T1 , T2 or water ADC. Human PC3 prostate cancer cells expressing a red fluorescent protein were implanted in 21 male mice. Docetaxel chemotherapy was given once a week starting 1 week after cell implantation for 10 randomly selected mice, while the rest served as a control group (n = 11). The MRI consisted of relaxation along a fictitious field (RAFF) in the second (RAFF2) and fourth (RAFF4) rotating frames, T1 and T2 , continuous wave T1ρ , adiabatic T1ρ and adiabatic T2ρ relaxation time measurements and water ADC. MRI was conducted at 7 T, once a week up to 4 weeks from cell implantation. The tumor volume was monitored using T2 -weighted MRI and optical imaging. The histology was evaluated after the last imaging time point. Significantly reduced RAFFn, T1ρ, T2ρ and conventional relaxation times 4 weeks after tumor implantation were observed in the treated tumors compared with the controls. The clearest short- and long-term responses were obtained with T1 , while no clear improvement in response to treatment was detected with novel methods compared with conventional methods or with RAFFn compared with all others. The tumor volume decreased after a two-week time point for the treated group and increased significantly in the control group, which was supported by increasing red fluorescent light emission in the control tumors. Decreased relaxation times were associated with successful chemotherapy outcomes. The results indicate altered relaxation mechanisms compared with higher dose chemotherapies previously published.

Purpose: To present the radiation therapy quality assurance results from a prospective multicenter phase 2 randomized trial of short versus protracted urethra-sparing stereotactic body radiation therapy (SBRT) for localized prostate cancer. Methods and Materials: Between 2012 and 2015, 165 patients with prostate cancer from 9 centers were randomized and treated with SBRT delivered either every other day (arm A, n = 82) or once a week (arm B, n = 83); 36.25 Gy in 5 fractions were prescribed to the prostate with (n = 92) or without (n = 73) inclusion of the seminal vesicles (SV), and the urethra planning-risk volume received 32.5 Gy. Patients were treated either with volumetric modulated arc therapy (VMAT; n = 112) or with intensity modulated radiation therapy (IMRT; n = 53). Deviations from protocol dose constraints, planning target volume (PTV) homogeneity index, PTV Dice similarity coefficient, and number of monitor units for each treatment plan were retrospectively analyzed. Dosimetric results of VMAT versus IMRT and treatment plans with versus without inclusion of SV were compared. Results: At least 1 major protocol deviation occurred in 51 patients (31%), whereas none was observed in 41. Protocol violations were more frequent in the IMRT group (P 98% (31.1 vs 30.8 Gy, P 2% (37.9 vs 38.7 Gy, P 50% (24.5% vs 33.5%, P =.0001). To achieve its goals volumetric modulated arc therapy required fewer monitor units than IMRT (2275 vs 3378, P 90% (9.1% vs 10.4%, P =.0003) and V80% (13.2% vs 15.7%, P =.0003). Conclusions: Protocol deviations with potential impact on tumor control or toxicity occurred in 31% of patients in this prospective clinical trial. Protocol deviations were more frequent with IMRT. Prospective radiation therapy quality assurance protocols should be strongly recommended for SBRT trials to minimize potential protocol deviations.

Background:Smoking cessation after a cancer diagnosis is associated with improved overall survival. Few studies have reported oncologists' cessation practice patterns, but differences between the curative and palliative settings have not been described. We aimed to study the oncologist's perceptions on patients' tobacco use, current practices and barriers to providing smoking cessation support, while distinguishing between treatment with curative (C) and palliative (P) intent. Methods:In 2019, an online 34-item survey was sent to approximately 6235 oncologists from 16 European countries. Responses were descriptively reported and compared by treatment setting. Results:Responses from 544 oncologists were included. Oncologists appeared to favour addressing tobacco in the curative setting more than in the palliative setting. Oncologists believe that continued smoking impacts treatment outcomes (C: 94%, P: 74%) and that cessation support should be standard cancer care (C: 95%, P: 63%). Most routinely assess tobacco use (C: 93%, P: 78%) and advise patients to stop using tobacco (C: 88%, P: 54%), but only 24% (P)-39% (C) routinely discuss medication options, and only 18% (P)-31% (C) provide cessation support. Hesitation to remove a pleasurable habit (C: 13%, P: 43%) and disbelieve on smoking affecting outcomes (C: 3%, P: 14%) were disparate barriers between the curative and palliative settings (p < 0.001), but dominant barriers of time, resources, education and patient resistance were similar between settings. Conclusion:Oncologists appear to favour addressing tobacco use more in the curative setting; however, they discuss medication options and/or provide cessation support in a minority of cases. All patients who report current smoking should have access to evidence-based smoking cessation support, also patients treated with palliative intent given their increasing survival.

Introduction The increased radioresistance of hypoxic cells compared to well-oxygenated cells is quantified by the oxygen enhancement ratio (OER). In this study we created a FLUKA Monte Carlo based tool for inclusion of both OER and relative biological effectiveness (RBE) in biologically weighted dose (ROWD) calculations in proton therapy and applied this to explore the impact of hypoxia. Methods The RBE-weighted dose was adapted for hypoxia by making RBE model parameters dependent on the OER, in addition to the linear energy transfer (LET). The OER depends on the partial oxygen pressure (pO2) and LET. To demonstrate model performance, calculations were done with spread-out Bragg peaks (SOBP) in water phantoms with pO2 ranging from strongly hypoxic to normoxic (0.01–30 mmHg) and with a head and neck cancer proton plan optimized with an RBE of 1.1 and pO2 estimated voxel-by-voxel using [18F]-EF5 PET. An RBE of 1.1 and the Rorvik RBE model were used for the ROWD calculations. Results The SOBP in water had decreasing ROWD with decreasing pO2. In the plans accounting for oxygenation, the median target doses were approximately a factor 1.1 lower than the corresponding plans which did not consider the OER. Hypoxia adapted target ROWDs were considerably more heterogeneous than the RBE1.1-weighted doses. Conclusion We realized a Monte Carlo based tool for calculating the ROWD. Read-in of patient pO2 and estimation of ROWD with flexibility in choice of RBE model was achieved, giving a tool that may be useful in future clinical applications of hypoxia-guided particle therapy.

Reimbursement is a key factor in defining which resources are made available to ensure quality, efficiency, availability, and access to specific health-care interventions. This Policy Review assesses publicly funded radiotherapy reimbursement systems in Europe. We did a survey of the national societies of radiation oncology in Europe, focusing on the general features and global structure of the reimbursement system, the coverage scope, and level for typical indications. The annual expenditure covering radiotherapy in each country was also collected. Most countries have a predominantly budgetary-based system. Variability was the major finding, both in the components of the treatment considered for reimbursement, and in the fees paid for specific treatment techniques, fractionations, and indications. Annual expenses for radiotherapy, including capital investment, available in 12 countries, represented between 4·3% and 12·3% (average 7·8%) of the cancer care budget. Although an essential pillar in multidisciplinary oncology, radiotherapy is an inexpensive modality with a modest contribution to total cancer care costs. Scientific societies and policy makers across Europe need to discuss new strategies for reimbursement, combining flexibility with incentives to improve productivity and quality, allowing radiation oncology services to follow evolving evidence.

The purpose of this study was to evaluate 18F-FACBC PET/CT, PET/MRI, and multiparametric MRI (mpMRI) in detection of primary prostate cancer (PCa). Twenty-six men with histologically confirmed PCa underwent PET/CT immediately after injection of 369 ± 10 MBq 18F-FACBC (fluciclovine) followed by PET/MRI started 55 ± 7 min from injection. Maximum standardized uptake values (SUVmax) were measured for both hybrid PET acquisitions. A separate mpMRI was acquired within a week of the PET scans. Logan plots were used to calculate volume of distribution (VT). The presence of PCa was estimated in 12 regions with radical prostatectomy findings as ground truth. For each imaging modality, area under the curve (AUC) for detection of PCa was determined to predict diagnostic performance. The clinical trial registration number is NCT02002455. In the visual analysis, 164/312 (53%) regions contained PCa, and 41 tumor foci were identified. PET/CT demonstrated the highest sensitivity at 87% while its specificity was low at 56%. The AUC of both PET/MRI and mpMRI significantly (p 3 + 4 tumors were significantly (p

Hypoxia contributes to radiotherapy resistance and more aggressive behaviour of several types of cancer. This study was designed to evaluate the repeatability of intratumour uptake of the hypoxia tracer [18F]EF5 in paired PET/CT scans. Ten patients with newly diagnosed head and neck cancer (HNC) received three static PET/CT scans before chemoradiotherapy: two with [18F]EF5 a median of 7 days apart and one with [18F]FDG. Metabolically active primary tumour volumes were defined in [18F]FDG images and transferred to co-registered [18F]EF5 images for repeatability analysis. A tumour-to-muscle uptake ratio (TMR) of 1.5 at 3 h from injection of [18F]EF5 was used as a threshold representing hypoxic tissue. In 10 paired [18F]EF5 PET/CT image sets, SUVmean, SUVmax, and TMR showed a good correlation with the intraclass correlation coefficients of 0.81, 0.85, and 0.87, respectively. The relative coefficients of repeatability for these parameters were 15%, 17%, and 10%, respectively. Fractional hypoxic volumes of the tumours in the repeated scans had a high correlation using the Spearman rank correlation test (r = 0.94). In a voxel-by-voxel TMR analysis between the repeated scans, the mean of Pearson correlation coefficients of individual patients was 0.65. The mean (± SD) difference of TMR in the pooled data set was 0.03 ± 0.20. Pretreatment [18F]EF5 PET/CT within one week shows high repeatability and is feasible for the guiding of hypoxia-targeted treatment interventions in HNC.

Nasopharyngeal carcinoma (NPC) is uncommon in western countries and data on the outcome and histological presentation are scarce in nonendemic areas. We report here the outcome on all patients with NPC treated in Finland between 1990 and 2009.The Finnish Cancer Registry database was used to identify the patients. Histopathological specimens and clinical records were reviewed to confirm the histological subtypes, prognostic factors, treatment techniques and outcome across different stage groups.Primary NPC was identified in 207 patients and 42 (20%) had keratinizing squamous cell carcinoma (SCC). The stage distribution was: I, 11%; II, 25%; III, 39%; IV, 25%. Of 191 patients treated with curative intent 85 (44%) received radiotherapy and 106 (56%) chemoradiotherapy. The five-year overall survival for all patients was 57% and for stages I-IV 87%, 69%, 55% and 31%, respectively. The five-year disease-specific and overall survival of all patients treated between 1990 and 1999 were 58% and 49%, and those between 2000 and 2009 66% and 63%, respectively.While survival rates are improving and comparable to other western countries they remain inferior to those of endemic countries. This may reflect the different biology of NPC in nonendemic areas, where keratinizing SCC is common.

// Aida Kiviniemi 1, 2 , Maria Gardberg 3 , Katri Kivinen 4 , Jussi P. Posti 5 , Ville Vuorinen 5 , Jussi Sipila 6, 7 , Melissa Rahi 5 , Matti Sankinen 5 and Heikki Minn 8 1 Department of Radiology, Medical Imaging Center of Southwest Finland, Turku University Hospital and University of Turku, Turku, Finland 2 Turku PET Center, Turku University Hospital and University of Turku, Turku, Finland 3 Department of Pathology, Turku University Hospital and University of Turku, Turku, Finland 4 TYKSLAB, Laboratory of Molecular Genetics, Turku University Hospital, Turku, Finland 5 Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital and University of Turku, Turku, Finland 6 Department of Neurology, North Karelia Central Hospital, Joensuu, Finland 7 Division of Clinical Neurosciences, Department of Neurology, Turku University Hospital and University of Turku, Turku, Finland 8 Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland Correspondence to: Aida Kiviniemi, email: aida.kiviniemi@utu.fi Keywords: glioma, somatostatin receptor, oligodendroglioma, IDH mutation, prognosis Received: February 20, 2017 Accepted: April 03, 2017 Published: April 13, 2017 ABSTRACT Somatostatin receptor subtype 2A (SSTR2A) is a potential therapeutic target in gliomas. Data on SSTR2A expression in different glioma entities, however, is particularly conflicting. Our objective was to characterize SSTR2A status and explore its impact on survival in gliomas classified according to the specific molecular signatures of the updated WHO classification. In total, 184 glioma samples were retrospectively analyzed for SSTR2A expression using immunohistochemistry with monoclonal antibody UMB-1. Double staining with CD68 was used to exclude microglia and macrophages from analyses. SSTR2A staining intensity and its localization in tumor cells was evaluated and correlated with glioma entities and survival. Diagnoses included 101 glioblastomas (93 isocitrate dehydrogenase (IDH) -wildtype, 3 IDH -mutant, 5 not otherwise specified (NOS)), 60 astrocytomas (22 IDH -wildtype, 37 IDH -mutant, 1 NOS), and 23 oligodendrogliomas (19 IDH -mutant and 1p/19q-codeleted, 4 NOS). SSTR2A expression significantly associated with oligodendrogliomas (79% SSTR2A positive) compared to IDH -mutant or IDH -wildtype astrocytomas (27% and 23% SSTR2A positive, respectively), and especially glioblastomas of which only 13% were SSTR2A positive ( p < 0.001, Fisher’s exact test). The staining pattern in glioblastomas was patchy whereas more homogeneous membranous and cytoplasmic staining was detected in oligodendrogliomas. Positive SSTR2A was related to longer overall survival in grade II and III gliomas (HR 2.7, CI 1.2–5.8, p = 0.013). In conclusion, SSTR2A expression is infrequent in astrocytomas and negative in the majority of glioblastomas where it is of no prognostic significance. In contrast, oligodendrogliomas show intense membranous and cytoplasmic SSTR2A expression, which carries potential diagnostic, prognostic, and therapeutic value.

Treatment for patients with metastatic colorectal cancer is chemotherapy commonly combined with monoclonal antibodies against vascular endothelial growth factor (bevacizumab) or epidermal growth factor receptor (cetuximab or panitumumab), the efficacy of which has been proven in randomized controlled trials. The objective of the current retrospective study was to analyze the impact of targeted therapy, adverse events, and dose reduction on overall survival (OS) and metastasis resection rates. A hospital-based electronic informatics center was used to gather clinical data and outcome information in a “real-life” setting in a single academic hospital. A total of 178 patients were included in 2010–2013. In patients whose tumors expressed the KRAS wild type, the longest median OS was observed with irinotecan-based chemotherapy combined with bevacizumab (38 months), or with cetuximab (41 months). In the KRAS-mutated group, the longest median OS was observed with oxaliplatin with or without bevacizumab (34 months). Beneficial liver metastasis resections were observed in 12 out of 20 patients. Patients with KRAS wild-type tumors who received cetuximab were the most likely to undergo surgery. Age was a negative predictor of OS. Patients whose chemotherapy dose was reduced to below 80% had lower OS compared to those remaining above 80%. Treatment delays in chemotherapy did not affect OS. Pulmonary embolism and infections were common but did not have an impact on OS. A hospital-based electronic informatics center provides comparable OS results, even though adverse events were frequently observed in the present study.

BackgroundNasopharyngeal carcinoma (NPC) is a malignant disease with an enigmatic etiology. NPC associates with Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), while immunological factors also play a role in carcinogenesis. Toll-like receptors (TLRs) are pattern recognition receptors that participate in the immunological defence against pathogens, but their functions are also linked to cancer.MethodsIn our whole population-based study, we retrieved 150 Finnish NPC cases and studied their tumour samples for TLR1, TLR2, TLR4, TLR5, TLR7, and TLR9 expressions by immunohistochemistry, and for the presence of EBV and high-risk HPVs with EBV RNA and HPV E6/E7 mRNA in situ hybridizations. In addition, we analyzed the TLR expression patterns according to age, tumour histology, EBV/HPV status, and outcome.ResultsWe found that all TLRs studied were highly expressed in NPC. Viral status of the tumours varied, and 62% of them were EBV-positive, 14% HPV-positive, and 24% virus-negative. The tumours with strong TLR2(nucl) or TLR5 expression were mostly virus-negative or HPV-positive keratinizing squamous cell carcinomas, and the patients with these tumours were significantly older than those with mild or negative TLR2(nucl)/TLR5 expression. In Kaplan-Meier analysis, the patients with strong TLR5 expression had worse survival compared to the patients with negative or mild TLR5 expression, but the results were linked to other patient and tumour characteristics. In multivariable-adjusted Cox regression analysis, the patients with positive TLR7 tumour expression had better overall survival than those with no TLR7 expression. The 5-year overall survival rates according to TLR7 expression were 66% (mild), 52% (moderate or strong), and 22% (negative).ConclusionsTLRs are highly expressed in non-endemic NPC. Intensity of TLR2 and TLR5 expressions correlate with viral status, and TLR7 seems to be an independent prognostic factor of non-endemic NPC.

Purpose To evaluate the expression of alanine-serine-cysteine-transporter 2 (ASCT2) and L-type amino acid transporter1 (LAT1) in prostate cancer (PCa) and their impact on uptake of 18F-1-amino-3-fluorocyclobutane-1-carboxylic acid (18F-fluciclovine) which is approved for the detection of recurrent PCa. Methods Twenty-five hormone-naïve patients with histologically confirmed PCa underwent PET/CT before prostatectomy. Dynamic imaging was performed immediately after injection of 368 ± 10 MBq of 18F-fluciclovine and the uptake in PCa was expressed as SUVmax at six sequential 4-min time frames and as tracer distribution volume (V T) using Logan plots over 0–24 min. The expression of ASCT2 and LAT1 was studied with immunohistochemistry (IHC) on a tissue microarray (TMA) containing three cores per carcinoma lesion. The TMA slides were scored independently by two trained readers based on visual intensity of ASCT2/LAT1 expression on a four-tiered scale. The correlations between ASCT2/LAT1 staining intensity, SUVmax/V T, and Gleason grade group (GGG) were assessed using Spearman’s rank correlation coefficient (ρ). Results Forty tumor foci (> 0.5 mm in diameter, max. 3 per patient) were available for TMA. In visual scoring, low, moderate, and high staining intensity of ASCT2 was observed in 4 (10%), 24 (60%), and 12 (30%) tumors, respectively. No tumors showed high LAT1 staining intensity while moderate intensity was found in 10 (25%), 25 (63%) showed low, and the remaining 5 (12%) were negative for staining with LAT1. Tumors with GGG > 2 showed significantly higher uptake of 18F-fluciclovine and higher LAT1 staining intensity (p

Delineation of gross tumour volume in 3D is a critical step in the radiotherapy (RT) treatment planning for oropharyngeal cancer (OPC). Static [18F]-FDG PET/CT imaging has been suggested as a method to improve the reproducibility of tumour delineation, but it suffers from low specificity. We undertook this pilot study in which dynamic features in time-activity curves (TACs) of [18F]-FDG PET/CT images were applied to help the discrimination of tumour from inflammation and adjacent normal tissue. Five patients with OPC underwent dynamic [18F]-FDG PET/CT imaging in treatment position. Voxel-by-voxel analysis was performed to evaluate seven dynamic features developed with the knowledge of differences in glucose metabolism in different tissue types and visual inspection of TACs. The Gaussian mixture model and K-means algorithms were used to evaluate the performance of the dynamic features in discriminating tumour voxels compared to the performance of standardized uptake values obtained from static imaging. Some dynamic features showed a trend towards discrimination of different metabolic areas but lack of consistency means that clinical application is not recommended based on these results alone. Impact of inflammatory tissue remains a problem for volume delineation in RT of OPC, but a simple dynamic imaging protocol proved practicable and enabled simple data analysis techniques that show promise for complementing the information in static uptake values.

Aim The aim of this paper is to describe the development of an inter-professional screening instrument for cancer patients' cognitive resources, knowledge expectations and inter-professional collaboration within patient education. Design and methods Four empirical datasets during 2012-2014 were analyzed in order to identify main categories, subcategories and items for inter-professional screening instrument. Findings Our inter-professional screening instrument integrates the critical moments of cancer patient education and the knowledge expectation types obtained from patient datasets to assessment of patients' cognitive resources, knowledge expectations and comprehension; and intra; and inter-professional.

Background To evaluate the accuracy of 11C-acetate Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in bladder cancer (BC) staging and monitoring response to neoadjuvant chemotherapy (NAC). Methods Eighteen patients were prospectively enrolled. Fifteen treatment naive patients underwent 11C-acetate PET/MRI before transurethral resection of bladder tumor (TUR-BT) for primary tumor evaluation. Five patients with muscle invasive BC were imaged after NAC and prior to radical cystectomy (RC) with extended pelvic lymph node dissection (ePLND) for NAC treatment response evaluation. Two patients were part of both cohorts. 11C-acetate PET/MRI findings were correlated with histopathology. Accuracy for lymph node detection was evaluated on patient and the ePLND template (10 regions) levels. Results The sensitivity, specificity and accuracy of 11C-acetate PET/MRI for the detection of muscle invasive BC was 1.00, 0.69 and 0.73 while the area under the receiver operating characteristic curve (95% confidence interval) was 0.85 (0.55–1.0), respectively. All five NAC patients underwent chemotherapy as planned and 11C-acetate PET/MRI correctly staged three patients, overstaged one and understaged one patient compared with RC and ePLND findings. A total of 175 lymph node were removed, median of 35 (range, 27–43) per patient in five patients who had RC and ePLND while 12 (7%) harboured metastases. Sensitivity, specificity, accuracy and AUC for N-staging were 0.20, 0.96, 0.80 and 0.58 on the ePLND template (10 regions) level. Conclusions 11C-acetate PET/MRI is feasible for staging of BC although sensitivity for the detection of nodal metastases is low. Monitoring response to NAC shows promise and warrants evaluation in larger studies. Trial registration ClinicalTrials.gov Identifier: NCT01918592, registered August 8 2013

Background: Most survival data in colorectal cancer (CRC) is derived from clinical trials or register-based studies. Hospital Biobanks, linked with hospital electronic records, could serve as a data-gathering method based on consecutively collected tumor samples. The aim of this Biobank study was to analyze survival of colorectal patients diagnosed and treated in a single-center university hospital over a period of 12 years, and to evaluate factors contributing to outcome.Material and methods: A total of 1777 patients with CRC treated during 2001-2012 were identified from the Auria Biobank, Turku, Finland. Longitudinal clinical information was collected from various hospital electronic records and date and cause of death obtained from Statistics Finland.Results: Cancer-specific, overall and disease-free survival was higher in patients diagnosed during 2004-2008 as compared with patients diagnosed in 2001-2003. Further improvement was not seen during years 2009-2012. Potential factors contributing to the improvement were introduction of multidisciplinary meetings, centralization of rectal cancer surgery, use of adjuvant chemotherapy and systematic preoperative radiotherapy of rectal cancer. The proportion of patients with stage I-IV CRC remained similar over the study period, but a marked decrease in non-metastatic rectal cancer with biopsy only (locally advanced disease) was observed. In stage I-III rectal cancer, Cox multivariate analysis suggested age, comorbidity, R1 resection, T staging and tumor grade as prognostic factors. In colon cancer, prognostic factors were age, comorbidity, gender and presence of lymph node metastases.Conclusions: Organizational changes in the treatment of CRC patients made since 2004 coincide with improved survival in CRC and a marked reduction in locally advanced rectal cancers. The clinical presentation of CRC has remained similar between 2001 and 2012.

Purpose To investigate relaxation along a fictitious field (RAFF) and continuous wave (cw) T1ρ imaging of prostate cancer (PCa) in the terms of repeatability, PCa detection, and characterization. Methods Thirty-six patients (PSA 11.6 ± 7.6 ng/mL, mean ± standard deviation) with histologically confirmed PCa underwent two repeated 3T MR examinations using surface array coils before prostatectomy. Relaxation along fictitious field, cw T1ρ, and T2 relaxation times (TRAFF, T1ρcw, T2) were measured and averaged over regions of interest placed in PCa, normal peripheral zone (PZ), and normal central gland (CG) positioned using whole-mount prostatectomy sections and anatomical T2-weighted images. Receiver operating characteristic curve analysis with area under the curve (AUC) was calculated to distinguish PCa from PZ/CG and PCa with Gleason score (GS) of 3+3 from GS of 3+4/≥ 3+4. Results TRAFF and T1ρcw relaxation times were repeatable with coefficients of repeatability as a percentage of median value in the range of 7.8-23.2%. AUC (mean, 95% confidence interval) in the differentiation of PCa with GS of 3+3 from PCa with CS of ≥ 3+4 were 0.88 (0.72-0.99), 0.69 (0.46-0.90), and 0.68 (0.45-0.88), for TRAFF, T1ρcw, and T2, respectively. Conclusion In quantitative region of interest based analysis, TRAFF outperformed T1ρcw and T2 in PCa detection and characterization.

Summary Background Panitumumab is a fully human monoclonal antibody that targets EGFR. We aimed to compare chemoradiotherapy plus panitumumab with chemoradiotherapy alone in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. Methods In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 41 sites in nine countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0–1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (three cycles of cisplatin 100 mg/m 2 ) or panitumumab plus chemoradiotherapy (three cycles of intravenous panitumumab 9·0 mg/kg every 3 weeks plus cisplatin 75 mg/m 2 ) using stratified randomisation with a block size of five. All patients received 70 Gy to gross tumour and 50 Gy to areas at risk for subclinical disease with standard fractionation. The primary endpoint was local-regional control at 2 years, analysed in all randomised patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00500760. Findings Between Oct 26, 2007, and March 26, 2009, 153 patients were enrolled and 150 received treatment (63 in the chemoradiotherapy group and 87 in the panitumumab plus chemoradiotherapy group). Local-regional control at 2 years was 68% (95% CI 54–78) in the chemoradiotherapy group and 61% (50–71) in the panitumumab plus chemoradiotherapy group. The most frequent grade 3–4 adverse events were dysphagia (17 [27%] of 63 patients in the chemoradiotherapy group vs 35 [40%] of 87 in the panitumumab plus chemoradiotherapy group), mucosal inflammation (15 [24%] vs 48 [55%]), and radiation skin injury (eight [13%] vs 27 [31%]). Serious adverse events were reported in 20 (32%) of 63 patients in the chemoradiotherapy group and in 37 (43%) of 87 patients in the panitumumab plus chemoradiotherapy group. Interpretation In patients with locally advanced squamous-cell carcinoma of the head and neck, the addition of panitumumab to standard fractionation radiotherapy and cisplatin did not confer any benefit, and the role of EGFR inhibition in these patients needs to be reassessed. Funding Amgen.

The potential risks associated with cardiovascular imaging (CVI) have recently been debated, partly triggered by the rapid increase in the use of imaging procedures and new imaging modalities such as cardiac computed tomography (CT).1,2 The discussion has mainly focused only on a single-risk aspect such as radiation.3 However, the various procedures have several risks: stressors, contrast agents, invasiveness, radiation, etc. Even more important, the test must be related to the benefit of performing or not performing the test with the risk and drawbacks associated with the disease remaining undetected. We aimed to create a balanced analysis of immediate, short- and long-term risks associated with CVI in relation to the natural course of coronary artery disease (CAD) and to therapeutic interventions. The imaging tests for CAD were selected, since many CVI tests are commonly used. We analysed: (i) the risk of major cardiac events (MCEs) for each component of imaging test; (ii) the upper limit for each risk, in order to avoid underestimation of a risk; (iii) composite risks calculated for selected common diagnostic tests for CAD; (iv) the risks compared with the risk of the disease itself, to assess the potential benefits of tests; and (v) comparison with risks in regular life activities and that associated with trivial long-term prophylactic interventions such as aspirin use. This analysis is based on the data available from the literature. Data for risks related to some of the procedures are quite limited, for some variable, and for some of limited quality. Still we sought to present risk estimations from all the procedures using reliable studies and databases available from an extensive search of the literature. The detailed information about risk assessments is shown in Supplementary material. ### Definitions In the literature, risks are described in many different ways, e.g. ‘fatal, major, …

Background:68Ga-DOTANOC PET/CT is routinely used to image neuroendocrine tumors (NETs). A case of lymphoma initially thought to be NET based on a positive 68Ga-DOTANOC PET/CT was recently seen at our institution. This prompted us to determine prospectively somatostatin receptor (SSTR) status in patients with lymphoma by immunohistochemical analysis of SSTR subtypes 2, 3 and 5 (SSTR2,3,5) and 68Ga-DOTANOC PET/CT imaging. Material and methods: Twenty-one patients with newly diagnosed lymphoma were referred to 68Ga-DOTANOC and FDG PET/CT prior to any treatment. Tracer uptake was evaluated visually by two nuclear medicine specialists. Maximum standardized uptake values (SUVmax) were determined from 14 nodal and two extranodal regions with highest uptake in each patient. Lesions were then graded with Deauville score (1–5) on FDG PET/CT and modified Krenning score (0–4) on 68Ga-DOTANOC PET/CT, respectively. SSTR2,3,5 status was analyzed from routine biopsies of lymphomatous tissue and matched to corresponding PET/CT findings. Results: About 20/21 patients had FDG-positive lymphoma (Deauville score ≥3). Uptake of 68Ga-DOTANOC was regarded as positive if Krenning score was ≥2 and resulted in 13/21 (62%) patients having 68Ga-DOTANOC-positive lymphomas. The highest uptake of 68Ga-DOTANOC was seen in Hodgkin’s lymphoma of nodular sclerosis subtype and in diffuse large B-cell lymphoma (SUVmax median 9.8 and 9.7, respectively). Both cases showed strong SSTR2 immunopositivity in tumor cells. Some patients had SSTR2 immunopositivity predominantly in endothelial and dendritic cells and follicular centers of lymph nodes contributing to a positive PET/CT with probably low tumor-specific uptake. SSTR3 and SSTR5 were negative in most lymphoma subtypes. Conclusions: According to this pilot study, 68Ga-DOTANOC PET/CT is positive in some lymphoma subtypes which express SSTRs. These tumors present a potential risk of being misinterpreted as NETs if a representative tumor sample is not available. Lymphomas with high expression of SSTRs may be amenable to treatments targeting these receptors.

Purpose To evaluate monoexponential, stretched exponential, kurtosis, and biexponential models for diffusion-weighted imaging (DWI) of normal prostate and prostate cancer (PCa), using b-values up to 2000 s/mm2, in terms of fitting quality and repeatability. Methods Eight healthy volunteers and 16 PCa patients underwent a total of four repeated 3T DWI examinations using 16 and 12 b-values, respectively. The highest b-value was 2000 s/mm2. The normalized mean signal intensities of regions of interest, placed in normal tissue and PCa using anatomical images and prostatectomy sections, were fitted using the four models. The fitting quality was evaluated using Akaike information criteria and F-ratio. Repeatability of the fitted parameters was evaluated using intraclass correlation coefficient ICC(3,1). Results The biexponential model provided the best fit to normal prostate and PCa DWI data. The parameters of the monoexponential, kurtosis, and stretched exponential (with the exception of the α parameter) models had higher ICC(3,1) values compared with the biexponential model. The kurtosis model provided a better fit to DWI data of normal prostate and PCa than the monoexponential model, whereas these models had comparable reliability and repeatability based on ICC(3,1) values. Conclusion Considering the model fit and repeatability, the kurtosis model seems to be the preferred model for characterization of normal prostate and PCa DWI using b-values up to 2000 s/mm2. Magn Reson Med 73:1988–1998, 2015. © 2014 Wiley Periodicals, Inc.

Purpose To find the diagnostic accuracy of 3T multiparametric magnetic resonance imaging (mpMRI) and mpMRI targeted transrectal ultrasound (TRUS)-guided biopsy using visual coregistration (TB) in patients with elevated prostate-specific antigen (PSA), normal digital rectal examination, and no previous biopsy. Materials and Methods Fifty-five patients at two institutions underwent mpMRI, consisting of anatomical T2-weighted imaging (T2W), diffusion-weighted imaging (DWI), proton magnetic resonance spectroscopy (1H-MRS), and dynamic contrast-enhanced MRI (DCE-MRI), followed by TB in addition to 12 core systematic TRUS-guided biopsy (SB). Histopathological scorings of biopsy (n = 38) and prostatectomy (n = 17) specimens were used as the reference standard for calculation of diagnostic accuracy values. Clinically significant prostate cancer (SPCa) was defined as 3 mm core length of Gleason score 3+3 or any Gleason grade 4. Results The sensitivity, specificity, accuracy, and area under the curve (AUC) values for the detection of SPCa on the sextant level for T2W+DWI+1H-MRS+DCE-MRI were 72%, 89%, 85%, and 0.81, respectively. The corresponding values for T2wi+DWI were 61%, 96%, 87%, and 0.79, respectively. The overall PCa detection rate per core in 53 patients was 21% (138 of 648 cores) for SB and 43% (33 of 77 cores) for TB (P

Purpose In order to improve the treatment of squamous cell carcinoma of the head and neck, precise information on the treated tumour’s biology is required and the prognostic importance of different biological parameters needs to be determined. The aim of our study was to determine the predictive value of pretreatment PET/CT imaging using [18F]FDG, a new hypoxia tracer [18F]EF5 and the perfusion tracer [15O]H2O in patients with squamous cell cancer of the head and neck treated with radiochemotherapy.