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Background Salvage external beam radiotherapy (sEBRT) for patients with a biochemical recurrence (BCR) after radical prostatectomy provides a 5-year biochemical progression-free survival up to 60%. Multiple studies have shown that dose escalation to the primary prostate tumour improves treatment outcome. However, data is lacking on the role of dose escalation in the recurrent salvage setting. The main objective of the PERYTON-trial is to investigate whether treatment outcome of sEBRT for patients with a BCR after prostatectomy can be improved by increasing the biological effective radiation dose using hypofractionation. Moreover, patients will be staged using the PSMA PET/CT scan, which is superior to conventional imaging modalities in detecting oligometastases. Methods The PERYTON-study is a prospective multicentre open phase III randomised controlled trial. We aim to include 538 participants (269 participants per treatment arm) with a BCR after prostatectomy, a PSA-value of Discussion Firstly, the high rate of BCR after sEBRT may be due to the presence of oligometastases, for which local sEBRT is inappropriate. With the use of the PSMA PET/CT before sEBRT, patients with oligometastases will be excluded from intensive local treatment to avoid unnecessary toxicity. Secondly, the currently applied radiation dose for sEBRT may be too low to achieve adequate local control, which may offer opportunity to enhance treatment outcome of sEBRT by increasing the biologically effective radiotherapy dose to the prostate bed. Trial registration This study is registered at ClinicalTrials.gov (Identifier: NCT04642027). Registered on 24 November 2020 – Retrospectively registered. The study protocol was approved by the accredited Medical Ethical Committee (METc) of all participating hospitals (date METc review: 23-06-2020, METc registration number: 202000239). Written informed consent will be obtained from all participants.

Background: This study was conducted to compare the early static (3–6 min post-injection (p.i.)) and standard whole body (1 h, p.i.) 68Ga-PSMA-11 PET/CT imaging for detection of lesions in prostate cancer (PC) patients. Materials and methods: In this study, PC patients suspected of recurrence underwent 68Ga-PSMA-11 PET/CT. Early static images were acquired from the pelvis and the lower abdomen 3-5 minutes after radiotracer injection and, a routine whole body scan was performed from the skull to the mid-thigh 1 h after injection. Quantitative analysis (SUVmax) was evaluated in suspicious lesions. Results: Of 19 evaluated PC patients with a median age of 72 ± 1.66 years (range: 55–85 years) and prostate-specific antigen (PSA) of 1.72 ± 6.11 ng/ml (range: 0.1–100 ng/ml) (median ± SE), 16 showed positive in the whole body PET/CT. All of the patients with positive whole body scans due to pelvic involvement had positive early scan results. Totally, 22 lesions were detected in both early and delay scans in the pelvic which 16 were related to prostate involvement, 4 were related to lymph node involvement, and 2 were related to bone involvement. Moreover, in addition to the mentioned 22 lesions, early PET imaging successfully detected local recurrence in a patient who was negative on WB PET/ CT; this lesion was masked in the delay scan due to bladder activity. The median SUVmax values of the early and delay scans were 3.69 ± 1.07 (median ± SE) (range: 1.2–14.5) and 5.85 ± 1.69 (range: 3.1–23.4), respectively. ( p = 0.005). Conclusion: Early static 68Ga-PSMA-11 PET/CT imaging might discriminate metastases from urinary bladder activity. Therefore, early static imaging in combination with whole body 60-min p.i. imaging can improve the detection of local involvement pelvic disease.

Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography with computerized tomography (PET-CT) upstages 10 to 60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Inclusion criteria were: RT alone for untreated stage I to II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow-up ≥3 months. End points were freedom from progression (FFP), local control, and overall survival (OS). A total of 512 patients treated between 2000 and 2017 at 16 centers were eligible for analysis; median age was 58 years (range, 20-90); 410 patients (80.1%) had stage I disease; median RT dose was 30 Gy (24-52); and median follow-up was 52 months (3.2-174.6). Five-year FFP and OS were 68.9% and 96%. For stage I, FFP was 74.1% vs 49.1% for stage II (P < .0001). Eight patients relapsed in-field (1.6%). Four had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.44-3.10) and BCL2 expression (HR, 1.62; 95% CI, 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.

The optimal follow-up (FU) strategy for patients treated for localised renal cell carcinoma (RCC) remains unclear. Using the RECUR database, we studied imaging intensity utilised in contemporary FU to evaluate its association with outcome after detection of disease recurrence. Consecutive patients with nonmetastatic RCC (n = 1612) treated with curative intent at 12 institutes across eight European countries between 2006 and 2011 were included. Recurrence occurred in 336 patients. Cross-sectional (computed tomography, magnetic resonance imaging) and conventional (chest X-ray, ultrasound) methods were used in 47% and 53%, respectively. More intensive FU imaging (more than twofold) than recommended by the European Association of Urology (EAU) was not associated with improved overall survival (OS) after recurrence. Overall, per patient treated for recurrence remaining alive with no evidence of disease, the number of FU images needed was 542, and 697 for high-risk patients. The study results suggest that use of more imaging during FU than that recommended in the 2017 EAU guidelines is unlikely to improve OS after recurrence. Prospective studies are needed to design optimal FU strategies for the future. Patient summary: After curative treatment for localised kidney cancer, follow-up is necessary to detect any recurrence. This study illustrates that increasing the imaging frequency during follow-up, even to double the number of follow-up imaging procedures recommended by the European Association of Urology guidelines, does not translate into improved survival for those with recurrence. After curative treatment for localised kidney cancer, a more intensive follow-up regimen than that recommended in the 2017 European Association of Urology guidelines did not improve overall survival among those experiencing recurrence, irrespective of the risk of recurrence. This suggests that an increase in follow-up imaging frequency is not cost-efficient. Prospective studies to identify more optimal follow-up strategies are needed.

OBJECTIVE: It is unclear whether endoscopic assessment of scars after colorectal endoscopic mucosal resection (EMR) has to include biopsies, even if endoscopy is negative. Vice versa, endoscopic diagnosis of recurrent adenoma may not require biopsy before endoscopic reinterventions. We prospectively analysed various endoscopic modalities in the diagnosis of recurrence following EMR. DESIGN: We conducted a prospective study of patients undergoing colonoscopy after EMR of large (≥20 mm) colorectal neoplasia. Endoscopists predicted recurrence and confidence level with four imaging modes: high-definition white light (WL) and narrow-band imaging (NBI) with and without near focus (NF). Separately, 26 experienced endoscopists assessed offline images. RESULTS: Two hundred and thirty patients with 255 EMR scars were included. The prevalence of recurrent adenoma was 24%. Diagnostic values were high for all modes (negative predictive value (NPV) ≥97%, positive predictive value (PPV) ≥81%, sensitivity ≥90%, specificity ≥93% and accuracy ≥93%). In high-confidence cases, NBI with NF had NPV of 100% (95% CI 98% to 100%) and sensitivity of 100% (95% CI 93% to 100%). Use of clips at initial EMR increased diagnostic inaccuracy (adjusted OR=1.68(95% CI 1.01 to 2.75)). In offline assessment, specificity was high for all imaging modes (mean: ≥93% (range: 55%-100%)), while sensitivity was significantly higher for NBI-NF (82%(72%-93%)%)) compared with WL (69%(38%-86%); p

WHO first recognised extranodal NK/T-cell lymphoma (ENKTCL) in 2001, thanks to technical advances in anatomopathology and immunohistochemistry. It is divided into nasal and extranasal subgroups depending on the primary site. Primary isolated NK/T-cell lymphoma of the testis is rare. Typical recurrence sites of primary testicular NK/T-cell lymphoma are the gastrointestinal tract, lymph nodes, skin, spleen and central nervous system. Nasal relapses of a primary NK/T-cell lymphoma of the testis are very rare and according to our knowledge, no other case has been reported yet in the literature. The authors report the case of a 35-year-old Caucasian man relapsing twice in the nasal cavity 1 year after initial diagnosis and treatment of a primary isolated, stage IE, ENKTCL of the testis. We report the clinical and radiological presentation of the nasal relapses and the different modalities of treatment that were applied. Sinonasal relapses of an isolated primary NK/T-cell lymphoma of the testis are very rare. ENKTCL is a very aggressive entity, even at an early stage, therefore, requiring a multimodal treatment approach including chemotherapy and radiotherapy. New strategies to treat this disease are needed.

Objective: Modality and frequency of image-based renal cell carcinoma (R.C.C.) follow-up strategies are based on risk of recurrence. Using the R.E.C.U.R.-database, frequency of imaging was studied in regard to prognostic risk groups. Furthermore, it was investigated whether imaging modality utilized in contemporary follow-up were associated with outcome after detection of recurrence. Moreover, outcome was compared based on whether the assessment of potential curability was a pre-defined set of criteria’s (per-protocol) or stated by the investigator. Materials and methods: Consecutive non-metastatic R.C.C. patients (n = 1,612) treated with curative intent at 12 institutes across eight European countries between 2006 and 2011 were included. Leibovich or U.I.S.S. risk group, recurrence characteristics, imaging modality, frequency and survival were recorded. Primary endpoints were overall survival (O.S.) after detection of recurrence and frequency of features associated with favourable outcome (non-symptomatic recurrences and detection within the follow-up-programme). Results: Recurrence occurred in 336 patients. Within low, intermediate and high risk for recurrence groups, the frequency of follow-up imaging was highest in the early phase of follow-up and decreased significantly over time (p < 0.001). However, neither the image modality for detection nor ≥ 50% cross-sectional imaging during follow-up were associated with improved O.S. after recurrence. Differences between per protocol and investigator based assessment of curability did not translate into differences in O.S. Conclusions: As expected, the frequency of imaging was highest during early follow-up. Cross-sectional imaging use for detection of recurrences following surgery for localized R.C.C. did not improve O.S. post-recurrence. Prospective studies are needed to determine the value of imaging in follow-up.

Purpose The purpose of the study was to provide a systematic evaluation of the computed tomography(CT) findings after radiofrequency ablation (RFA) in locally advanced pancreatic cancer(LAPC). Methods Eighteen patients with intra-operative RFA-treated LAPC were included in a prospective case series. All CT-scans performed prior to RFA and 1 week and 3 months of post-RFA, according to standard regimen, were assessed by two radiologists in consensus, using standardized radiological scoring lists. Results 51 CT-scans were assessed. One week after RFA, the ablation zone was visible in all patients as a (partially) sharply defined (83%), heterogeneous area (94%). At 3 months of follow-up, the ablation zone was completely invaded by tumor in 67% of patients and still present, but decreased in 33%. In two patients (11%), local thrombosis and/or occlusion of the superior mesenteric vein occurred. The occlusions persisted without clinical consequences and the thrombosis disappeared. A peripancreatic fluid collection was visible 1 week after RFA in 3 patients, wherein the ablation zone extended ventrally outside of the pancreas. Conclusions Directly after RFA for LAPC, a well-defined ablation zone is visible on CT-imaging. This ablation zone is usually replaced by tumor ingrowth after 3 months. Moreover, the ablation zone regularly included vascular structures, with rare asymptomatic venous occlusion or thrombosis and without adverse effects on arteries. Electronic supplementary material The online version of this article (10.1007/s00261-018-1519-y) contains supplementary material, which is available to authorized users.

IntroductionAdditional robust criteria to predict early postoperative recurrence of non-functioning pituitary macroadenomas (NFMAs) are needed. Recently, a new classification of pituitary tumors has been proposed, which is based on both radiological and histological criteria and allows the grading into 5 groups of different potential aggressiveness. The aim of this study was to use this classification to further characterize predictive factors of recurrence in an independent series of NFMA.Cases and methods120 patients operated for a NFMA were analyzed retrospectively. For each of them, the invasion of the cavernous and/or sphenoidal sinuses by the tumor was studied on the preoperative MRI and the proliferative character was based on precise histological and immunohistological examination.Results26% (n = 31) of the adenomas were proliferative and 57% (n = 68) were invasive. The invasive lesions were larger (P P DiscussionThe new clinicopathological classification proves to be very useful in predicting the risk of recurrence of non-functioning pituitary macroadenomas after a first surgery. In particular, grade 2b lesions showed an overall likelihood of recurrence that was 8.6 times greater than those of grade 1a.

Objectives To estimate the diagnostic accuracy of sentinel lymph node biopsy (SNB) in patients with penile cancer and assess SNB complications in a national multicentre setting. Patients and methods Retrospectively data were collected from records in four university centres by one medical doctor covering all SNBs performed in Denmark between 1 January 2000 and 31 December 2010. Patients had either impalpable lymph nodes (LNs) in one or both groins, or had a palpable inguinal mass from which aspiration cytology failed to reveal malignancy. Patients were injected with nanocolloid technetium and had a scintigram recorded before the SNB. The primary endpoint was LN recurrence on follow-up. The secondary endpoint was complications after SNB. Diagnostic accuracy was computed. Results In all, 409 groins in 222 patients were examined by SNB. The median (interquartile range) follow-up of patients who survived was 6.6 (5–10) years. Of 343 negative groins, eight were false negatives. The sensitivity was 89.2% (95% confidence interval 79.8–95.2%) per groin. Interestingly, four of 67 T1G1 patients had a positive SNB. In all, 28 of 222 (13%) patients had complications of Clavien-Dindo grade I–IIIa. Conclusion Penile cancer SNB with a close follow-up stages LN involvement reliably and has few complications in a national multicentre setting. Inguinal LN dissection was avoided in 76% of patients.

PURPOSE: Development of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknown.METHODS: We retrospectively analysed patients with diffuse large B-cell lymphoma diagnosed between 2001 and 2013, staged with PET/CT and treated with R-CHOP(-like) regimens. Baseline clinicopathologic characteristics, treatments, and outcome data were collected from clinical databases and medical files. We evaluated the association between candidate prognostic factors and modelled different risk models for predicting SCNS.RESULTS: Of 1532 patients, 62 (4%) subsequently developed SCNS. By multivariate analysis, disease stage III/IV, elevated serum LDH, kidney/adrenal and uterine/testicular involvement were independently associated with SCNS. There was a strong correlation between absolute number of extranodal sites and risk of SCNS; the 144 patients (9%) with >2 extranodal sites had a 3-year cumulative incidence of SCNS of 15.2% (95% confidence interval [CI] 9.2-21.2%) compared with 2.6% (95% CI 1.7-3.5) among those with ≤2 sites (P < 0.001). The 3-year cumulative risks of SCNS for CNS-IPI defined risk groups were 11.2%, 3.1% and 0.4% for high-, intermediate- and low-risk patients, respectively. All risk models analysed had high negative predictive values, but only modest positive predictive values.CONCLUSIONS: Patients with >2 extranodal sites or high-risk disease according to the CNS-IPI should be considered for baseline CNS staging. Clinical risk prediction models suffer from limited positive predictive ability, highlighting the need for more sensitive biomarkers to identify patients at highest risk of this devastating complication.

Objective This prospective study aims to test if MRI including diffusion weighted images can replace FDG PET-CT in the diagnosis of patients with suspicion of local recurrent head and neck squamous cell carcinomas after (chemo)radiation. Methods Seventy-five patients suspected of local recurrence underwent a MRI and a FDG PET-CT. Qualitative assessment of the images was performed. Reference standard was the results of biopsy or the absence of a recurrence during follow up. Results Seventy patients were included. Fifty percent had local recurrence. FDG PET-CT had accuracy of 71% compared to 73% for MRI. The sensitivity and specificity were 97% compared to 69% and 46% compared to 77% for FDG PET-CT and MRI respectively. Conclusions MRI showed similar diagnostic accuracy, superior specificity but inferior sensitivity compared to FDG PET-CT. Based on current results, we consider MRI including diffusion weighted sequences unable to replace FDG PET-CT as a single imaging modality when local recurrent disease of HNSCC after (C)RT is suspected.

Background. Adaptive strategy with daily online tumour match is a treatment option when treating locally advanced lung cancer patients with curative intended radiotherapy (RT).Material and methods. Fifty-two consecutive lung cancer patients treated with soft tissue match, adaptive RT and small planning target volumes (PTV) margins were analysed. A control group of 52 consecutive patients treated with bone match, no adaptive strategy and larger margins was included. Patients were followed with computed tomography (CT) scans every third month. CT-images showing loco-regional recurrences were identified. The recurrence gross tumour volume was delineated and registered with the original radiation treatment plan to identify site of failure. All patients were toxicity-scored using CTCAE 4.03 grading scale. Data were analysed using the Kaplan-Meier analysis.Results. The median follow-up time was 16 months (3–35). Within a year, 35% of the patients in the adaptive group (ART-group) and 53% in the control group (No-ART-group) experienced loco-regional failure, showing improved loco-regional control in the ART group (p = 0.05). One patient in the ART-group and four patients in the No-ART-group showed marginal failure. Median overall progression-free survival time for the ART-group was 10 months (95% CI 8–12), and 8 months (95% CI 6–9) for the No-ART-group. Severe pneumonitis (grade 3–5) decreased from 22% in the No-ART-group to 18% in the ART-group (non-significant, p = 0.6). No significant difference in severe dysphagia was found between the two groups.Conclusion. In the first small cohort of patients investigated, implementation of soft-tissue tumour match and adaptive strategies for locally advanced lung cancer patients increased the loco-regional control rate without increasing treatment-related toxicity.

After first-line therapy, patients with Hodgkin and aggressive non-Hodgkin lymphomas are followed closely for early signs of relapse. The current follow-up practice with frequent use of surveillance imaging is highly controversial and warrants a critical evaluation. Therefore a retrospective multicenter study of relapsed Hodgkin and aggressive non-Hodgkin lymphomas (nodal T-cell and diffuse large B-cell lymphomas) was conducted. All included patients had been diagnosed during the period 2002-2011 and relapsed after achieving complete remission on first-line therapy. Characteristics and outcome of imaging-detected relapses were compared to other relapses. A total of 258 patients with recurrent lymphoma were included in the study. Relapse investigations were initiated outside preplanned visits in 52% of the patients. Relapse detection could be attributed to patient-reported symptoms alone or in combination with abnormal blood tests or physical examination in 64% of the patients. Routine imaging prompted relapse investigations in 27% of the patients. The estimated number of routine scans per relapse was 91-255 depending on the lymphoma subtype. Patients with imaging-detected relapse had lower disease burden (P=.045) and reduced risk of death following relapse (hazard ratio 0.62, P=.02 in multivariate analysis). Patient reported symptoms are still the most common factor for detecting lymphoma relapse and the high number of scans per relapse calls for improved criteria for use of surveillance imaging. However, imaging-detected relapse was associated with lower disease burden and a possible survival advantage. The future role of routine surveillance imaging should be defined in a randomized trial.

The main curative treatment for localized colon cancer is surgical resection. However when tumor residuals are left positive margins are found during the histological examinations and additional treatment is needed to inhibit recurrence. Hyperspectral imaging (HSI) can offer non-invasive surgical guidance with the potential of optimizing the surgical effectiveness. In this paper we investigate the capability of HSI for automated colon cancer detection in six ex-vivo specimens employing a spectral-spatial patch-based classification approach. The results demonstrate the feasibility in assessing the benign and malignant boundaries of the lesion with a sensitivity of 0.88 and specificity of 0.78. The results are compared with the state-of-the-art deep learning based approaches. The method with a new hybrid CNN outperforms the state-of the-art approaches (0.74 vs. 0.82 AUC). This study paves the way for further investigation towards improving surgical outcomes with HSI.