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BACKGROUND: Neoadjuvant/induction chemotherapy (NAIC) improves survival in patients with muscle-invasive bladder carcinoma (MIBC). On-treatment response assessment may aid in decisions to continue or cease NAIC. OBJECTIVE: We investigated whether 18F-fluoro-2-deoxy-D-glucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) could predict response to NAIC and compared to contrast-enhanced Computed Tomography (CECT). METHODS: We prospectively included 83 patients treated for MIBC (i.e. high-risk cT2-4N0M0 or cT1-4N+M0-1a) between 2014 and 2018. Response to NAIC was assessed after 2-3 cycles with FDG-PET/CT (Peter-Mac and EORTC criteria) and CECT (RECIST1.1 criteria). We assessed prediction of complete pathological response (pCR; ypT0N0), complete pathological down-staging (pCD;≤ypT1N0), any down-staging from baseline (ypTN

Aim: To improve identification of peritoneal and distant metastases in locally advanced gastric cancer using [18F]FDG-PET radiomics. Methods: [18F]FDG-PET scans of 206 patients acquired in 16 different Dutch hospitals in the prospective multicentre PLASTIC-study were analysed. Tumours were delineated and 105 radiomic features were extracted. Three classification models were developed to identify peritoneal and distant metastases (incidence: 21%): a model with clinical variables, a model with radiomic features, and a clinicoradiomic model, combining clinical variables and radiomic features. A least absolute shrinkage and selection operator (LASSO) regression classifier was trained and evaluated in a 100-times repeated random split, stratified for the presence of peritoneal and distant metastases. To exclude features with high mutual correlations, redundancy filtering of the Pearson correlation matrix was performed (r = 0.9). Model performances were expressed by the area under the receiver operating characteristic curve (AUC). In addition, subgroup analyses based on Lauren classification were performed. Results: None of the models could identify metastases with low AUCs of 0.59, 0.51, and 0.56, for the clinical, radiomic, and clinicoradiomic model, respectively. Subgroup analysis of intestinal and mixed-type tumours resulted in low AUCs of 0.67 and 0.60 for the clinical and radiomic models, and a moderate AUC of 0.71 in the clinicoradiomic model. Subgroup analysis of diffuse-type tumours did not improve the classification performance. Conclusion: Overall, [18F]FDG-PET-based radiomics did not contribute to the preoperative identification of peritoneal and distant metastases in patients with locally advanced gastric carcinoma. In intestinal and mixed-type tumours, the classification performance of the clinical model slightly improved with the addition of radiomic features, but this slight improvement does not outweigh the laborious radiomic analysis.

The safety and efficacy of 166Ho radioembolization was first determined in the HEPAR and HEPAR II studies, which, however, excluded patients with hepatocellular carcinoma (HCC). The aim of this prospective clinical early phase II study was to establish the toxicity profile of 166Ho radioembolization in patients with measurable, liver-dominant HCC; Barcelona clinic liver cancer stage B or C; a Child-Pugh score of no more than B7; and an Eastern Cooperative Oncology Group performance status of 0-1 without curative treatment options. Methods: The primary endpoint was a rate of unacceptable toxicity defined as grade 3 hyperbilirubinemia (Common Terminology Cancer Adverse Events, version 4.03) in combination with a low albumin or ascites level in the absence of disease progression or treatment-related serious adverse events. Secondary endpoints included overall toxicity, response, survival, change in α-fetoprotein, and quality of life. Thirty-one patients with Barcelona clinic liver cancer stage B (71%) or C (29%) HCC were included, mostly multifocal (87%) or bilobar (55%) disease. Results: Common grade 1 or 2 clinical toxicity included fatigue (71%), back pain (55%), ascites (32%), dyspnea (23%), nausea (23%), and abdominal pain (23%), with no more than 10% grade 3-5 toxicity. Grade 3 laboratory toxicity (>10%) included an aspartate transaminase and γ-glutamyltransferase increase (16%), hyperglycemia (19%), and lymphopenia (29%). Treatment-related unacceptable toxicity occurred in 3 of 31 patients. At 3 mo, 54% of target lesions showed a complete or partial response according to modified RECIST. Median overall survival was 14.9 mo (95% CI, 10.4-24.9 mo). No significant changes in quality of life or pain were observed. Conclusion: The safety of 166Ho radioembolization was confirmed in HCC, with less than 10% unacceptable toxicity. Efficacy data support further evaluation.

PurposeRespiratory-induced motion of oesophageal tumours and lymph nodes can influence positron emission tomography/computed tomography (PET/CT). The aim was to compare standard three-dimensional (3D) and motion-compensated PET/CT regarding standardized uptake value (SUV), metabolic tumour volume (MTV) and detection of lymph node metastases. MethodsThis prospective observational study (NCT02424864) included thirty-seven newly diagnosed oesophageal cancer patients. Diagnostic PET/CT was reconstructed in 3D and motion-compensated PET/CT. MTVs of the primary tumour were calculated using an automated region-growing algorithm with SUV thresholds of 2.5 (MTV2.5) and ≥50% of SUVmax (MTV50%). Blinded for reconstruction method, a nuclear medicine physician assessed all lymph nodes showing 18F-fluorodeoxyglucose uptake for their degree of suspicion. ResultsThe mean (95% CI) SUVmax of the primary tumour was 13.1(10.6-15.5) versus 13.0(10.4-15.6) for 3D and motion-compensated PET/CT, respectively. MTVs were also similar between the two techniques. Bland-Altman analysis showed mean differences between both measurements (95% limits of agreement) of 0.08(-3.60 - 3.75), -0.26(-2.34 – 1.82), 4.66(-29.61 – 38.92)cm3 and -0.95(-19.9 – 18.0)cm3 for tumour SUVmax, lymph node SUVmax, for MTV2.5 and MTV50%, respectively. Lymph nodes were classified as highly suspicious (30/34 nodes), suspicious (20/22) and dubious (66/59) for metastases on 3D/motion-compensated PET/CT. No additional lymph node metastases were found on motion-compensated PET/CT. SUVmax of the most intense lymph nodes was similar for both scans: mean (95% CI) 6.6(4.3-8.8) and 6.8(4.5-9.1) for 3D and motion-compensated, respectively.ConclusionsSUVmax of the primary oesophageal tumour and lymph nodes was comparable on 3D and motion-compensated PET/CT. The use of motion-compensated PET/CT did not improve lymph node detection. Trial registration(www.clinicaltrials.gov: NCT02424864)

Background The role of 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) has increased in the preoperative staging of gastric cancer. Dutch national guidelines have recommended the use of FDG-PET/CT and SL for patients with locally advanced tumors since July 2016. Objective The aim of this study was to evaluate the implementation of FDG-PET/CT and SL in The Netherlands. Methods Between 2011 and 2018, all patients who underwent surgery for gastric cancer were included from the Dutch Upper GI Cancer Audit. The use of FDG-PET/CT and SL was evaluated before and after revision of the Dutch guidelines. Outcomes included the number of non-curative procedures (e.g. palliative and futile procedures) and the association of FDG-PET/CT and SL, with waiting times from diagnosis to the start of treatment. Results A total of 3310 patients were analyzed. After July 2016, the use of FDG-PET/CT (23% vs. 61%; p p Conclusion During implementation of FDG-PET/CT and SL after revision of the guidelines, both have increasingly been used in The Netherlands. The addition of these staging methods was associated with increased waiting time to treatment. The number of non-curative procedures did not differ after performing none, solely one, or both staging modalities.

Highlights • Nitroglycerin didn’t improve overall survival of NSCLC patients. • The toxicity of combining nitroglycerin with standard treatment was mild. • Increased uptake of HX4 showed negative prognostic significance in NSCLC patients. • Tumor perfusion after nitroglycerin treatment did not correlate with outcome., Background Nitroglycerin is proposed as an agent to reduce tumour hypoxia by improving tumour perfusion. We investigated the potential of nitroglycerin as a radio-sensitizer in non-small cell lung cancer (NSCLC) and the potential of functional imaging for patient selection. Material and methods Trial NCT01210378 is a single arm phase II trial, designed to detect 15% improvement in 2-year overall survival (primary endpoint) in stage IB-IV NSCLC patients treated with radical (chemo-) radiotherapy and a Transiderm-Nitro 5 patch during radiotherapy. Patients underwent dynamic contrast-enhanced CTs (DCE-CT) and HX4 (hypoxia) PET/CTs before and after nitroglycerin. Secondary endpoints were progression-free survival, toxicity and the prognostic value of tumour perfusion/hypoxia at baseline and after nitroglycerin. Results The trial stopped after a futility analysis after 42 patients. At median follow-up of 41 months, two-year and median OS were 58% (95% CI: 44–78%) and 38 months (95% CI: 22–54 months), respectively. Nitroglycerin could not reduce tumour hypoxia. DCE-CT parameters did not correlate with OS, whereas hypoxic tumours had a worse OS (p = 0.029). Changes in high-uptake fraction of HX4 and tumour blood flow were negatively correlated (r = -0.650, p = 0.022). The heterogeneity in treatment modalities and patient characteristics combined with a small sample size made further subgroup analysis of survival results impossible. Toxicity related to nitroglyerin was limited to headache (17%) and hypotension (2.4%). Conclusion Nitroglycerin did not improve OS of NSCLC patients treated with (chemo-)radiotherapy. A general ability of nitroglycerin to reduce hypoxia was not shown.

The ALSYMPCA study established a 3.6 month Overall Survival (OS) benefit in metastatic Castration Resistant Prostate Cancer (mCRPC) patients treated with Radium‐223 dichloride (Ra‐223) over placebo. Here we report clinical outcomes of Ra‐223 treatment in a nonstudy population. In this prospective registry, patients from 20 Dutch hospitals were included prior to Ra‐223 treatment. Clinical parameters collected included previous treatments and Adverse Events. Primary outcome was 6 months Symptomatic Skeletal Event (SSE)‐free survival, while secondary outcomes included Progression‐Free Survival (PFS) and Overall Survival (OS). Of the 305 patients included, 300 were evaluable. The mean age was 73.6 years, 90% had ≥6 bone metastases and 74.1% were pretreated with Docetaxel, 19.5% with Cabazitaxel and 80.5% with Abiraterone and/or Enzalutamide. Of all patients, 96.7% were treated with Ra‐223 and received a median of 5 cycles. After a median follow‐up of 13.2 months, 6 months SSE‐free survival rate was 83%, median PFS was 5.1 months and median OS was 15.2 months. Six months SSE‐free survival rate and OS were comparable with those reported in ALSYMPCA. “Previous Cabazitaxel treatment” and “bone‐only metastases” were independent predictors of a shorter and longer PFS, respectively, while above‐median LDH and “bone‐only metastases” were independent predictors of shorter and longer OS, respectively. Toxicity was similar as reported in the ALSYMPCA trial. These results suggest that in a nonstudy population, Ra‐223 treatment is well‐tolerated, equally effective as in the ALSYMPCA population and that patients not previously treated with Cabazitaxel benefit most from Ra‐223., What's new? The ALSYMCA phase III trial reported a survival benefit from Radium‐223 treatment in patients with metastatic castration‐resistant prostate cancer (mCRPC). These patients, however, were not treated previously with newer life‐prolonging drugs, raising questions about whether the ALSYMCA population reflects current populations of mCRPC patients. In this prospective study, men with mCRPC who were pretreated with newer generation drugs prior to receiving Radium‐223 experienced improvements in disease‐free and overall survival that were comparable to those reported in the ALSYMPCA study. Prior treatment with cabazitaxel independently predicted shorter progression‐free survival. The findings suggest that, overall, Radium‐233 is effective in men with mCRPC.

The safety and efficacy of (166)Ho radioembolization was first determined in the HEPAR and HEPAR II studies, which, however, excluded patients with hepatocellular carcinoma (HCC). The aim of this prospective clinical early phase II study was to establish the toxicity profile of (166)Ho radioembolization in patients with measurable, liver-dominant HCC; Barcelona clinic liver cancer stage B or C; a Child–Pugh score of no more than B7; and an Eastern Cooperative Oncology Group performance status of 0–1 without curative treatment options. Methods: The primary endpoint was a rate of unacceptable toxicity defined as grade 3 hyperbilirubinemia (Common Terminology Cancer Adverse Events, version 4.03) in combination with a low albumin or ascites level in the absence of disease progression or treatment-related serious adverse events. Secondary endpoints included overall toxicity, response, survival, change in α-fetoprotein, and quality of life. Thirty-one patients with Barcelona clinic liver cancer stage B (71%) or C (29%) HCC were included, mostly multifocal (87%) or bilobar (55%) disease. Results: Common grade 1 or 2 clinical toxicity included fatigue (71%), back pain (55%), ascites (32%), dyspnea (23%), nausea (23%), and abdominal pain (23%), with no more than 10% grade 3–5 toxicity. Grade 3 laboratory toxicity (>10%) included an aspartate transaminase and γ-glutamyltransferase increase (16%), hyperglycemia (19%), and lymphopenia (29%). Treatment-related unacceptable toxicity occurred in 3 of 31 patients. At 3 mo, 54% of target lesions showed a complete or partial response according to modified RECIST. Median overall survival was 14.9 mo (95% CI, 10.4–24.9 mo). No significant changes in quality of life or pain were observed. Conclusion: The safety of (166)Ho radioembolization was confirmed in HCC, with less than 10% unacceptable toxicity. Efficacy data support further evaluation.

Abdominal cancer patients increasingly undergo multimodality imaging. This study evaluates effects of integrated reading of PET/CT and abdominal MRI on staging outcomes and diagnostic confidence compared to “routine” separate reading. In total, N = 201 patients who underwent abdominal MRI and whole-body F-18 FDG-PET/CT within 14 days were retrospectively analyzed. Original MRI and PET/CT reports were retrieved and reported findings translated into a 5-point confidence score (1 = definitely benign to 5 = definitely malignant) for 7 standardized regions (primary tumor/regional lymph nodes/distant lymph nodes/liver/lung/bone/peritoneum) per patient. Two-reader teams (radiologist + nuclear medicine physician) then performed integrated reading of the images using the same scoring system. Integrated reading led to discrepant findings in 59 of 201 (29%) of patients, with potential clinical impact in 25 of 201 (12%). Equivocal scores decreased from 5.7% (PET/CT) and 5.4% (MRI) to 3.2% (p = 0.05 and p = 0.14). Compared to the original PET/CT reports, integrated reading led to increased diagnostic confidence in 8.9% versus decreased confidence in 6.6% (p = 0.26). Compared with the original MRI reports, an increase in confidence occurred in 9.6% versus a decrease in 6.9% (p = 0.18). The effect on diagnostic confidence was most pronounced in lymph nodes (p = 0.08 vs. MRI), cervical cancer (p = 0.03 vs. MRI), and recurrent disease staging (p = 0.06 vs. PET/CT). Integrated PET/CT+MRI reading alters staging outcomes in a substantial proportion of cases with potential clinical impact in ± 1 out of 9 patients. It can also have a small positive effect on diagnostic confidence, particularly in lymph nodes and cervical cancer, and in post-treatment settings. These findings support further collaboration between radiology and nuclear medicine disciplines. • Increasing numbers of patients undergo multimodality imaging consisting of both MRI and PET/CT for staging of abdominal malignancies. • Integrated reading of FDG-PET/CT and abdominal MR images by a team, consisting of a radiologist and a nuclear medicine physician, can alter staging outcomes compared to separate reporting of the exams in a substantial proportion of cases and with potential clinical impact in ± 1 out of 9 patients. • Integrated PET/CT+MRI reading can have a small positive effect on diagnostic confidence.

Background Radium-223 (Ra-223), an alpha-emitting radiopharmaceutical, established an improved overall survival and health-related quality of life (HRQoL) in symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients. However, effects on pain were not specifically evaluated. Here we assess integrated HRQoL, pain, and opioid use in a contemporary, more extensively pretreated, symptomatic and asymptomatic mCRPC population. Methods mCRPC patients scheduled for Ra-223 treatment were included and analyzed for HRQoL, pain, and opioid use, using Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory-Short Form (BPI-SF) questionnaires and recording of opioid use and dosage, respectively. Primary outcome measure was the percentage of patients experiencing a complete pain response (score of 0 on the BPI-SF Worst pain item and no increase in daily use of analgesics). A complete or partial pain response (better BPI-SF score and decrease in opioid use) and a better or no change in HRQoL was evaluated as an integrated overall clinical response (IOCR). Secondary endpoints included the time to pain progression (TPP) and Total FACT-P deterioration (TTFD), defined as time from first Ra-223 treatment to clinical meaningful increase in BPI-SF Worst pain item score and Total FACT-P score, respectively. Results This registry included 300 patients, of whom 105 (35%) were evaluable for FACT-P and BPI-SF during Ra-223 treatment. Forty-five (43%) patients had pain at baseline (PAB) (BPI-SF Worst pain score 5–10 points) and 60 (57%) had no pain at baseline (no-PAB) (BPI-SF Worst pain score 0–4 points). Complete pain response was achieved in 31.4% of the patients, while 58% had an IOCR. The median TTP and TTFD were 5.6 and 5.7 months, respectively, while the difference between PAB and no-PAB patients was not significant. Conclusions In contemporary, extensively pretreated mCRPC patients, Ra-223 treatment induced complete pain responses while integrated analysis of HRQoL, pain response, and opioid use demonstrated that the majority of patients derive clinical benefit.

Given the high risk of systemic relapse following initial therapy for muscle-invasive bladder cancer (MIBC), improved pretreatment staging is needed. We evaluated the incremental value of

Respiratory-induced motion of oesophageal tumours and lymph nodes can influence positron-emission tomography/computed tomography (PET/CT). The aim was to compare standard three-dimensional (3D) and motion-compensated PET/CT regarding standardized uptake value (SUV), metabolic tumour volume (MTV) and detection of lymph node metastases.This prospective observational study (NCT02424864) included 37 newly diagnosed oesophageal cancer patients. Diagnostic PET/CT was reconstructed in 3D and motion-compensated PET/CT. MTVs of the primary tumour were calculated using an automated region-growing algorithm with SUV thresholds of 2.5 (MTV2.5) and ≥ 50% of SUVmax (MTV50%). Blinded for reconstruction method, a nuclear medicine physician assessed all lymph nodes showingThe mean (95% CI) SUVmax of the primary tumour was 13.1 (10.6-15.5) versus 13.0 (10.4-15.6) for 3D and motion-compensated PET/CT, respectively. MTVs were also similar between the two techniques. Bland-Altman analysis showed mean differences between both measurements (95% limits of agreement) of 0.08 (-3.60-3.75), -0.26 (-2.34-1.82), 4.66 (-29.61-38.92) cmSUVmax of the primary oesophageal tumour and lymph nodes was comparable on 3D and motion-compensated PET/CT. The use of motion-compensated PET/CT did not improve lymph node detection.

In about 30% of patients treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection for locally advanced oesophageal cancer no vital tumour is found in the resection specimen. Accurate clinical response assessment is critical if deferral from surgery is considered in complete responders. Our study aimed to compare the performance of MRI and of FDG-PET/CT for the detection of residual disease after nCRT.Patients with oesophageal cancer eligible for nCRT and oesophagectomy were prospectively included. All patients underwent FDG-PET/CT and MRI before and between 6 and 8 weeks after nCRT. Two radiologists scored the MRI scans, and two nuclear medicine physicians scored the FDG-PET/CT scans using a 5-point score for residual disease. Histopathology after oesophagectomy represented the reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated for detection of residual tumour (ypT+), residual nodal disease (ypN+), and any residual disease (ypT+Nx/ypT0N+).Seven out of 33 (21%) patients had a pathological complete response. The AUCs for individual readers to detect ypT+ were 0.71/0.70 on diffusion-weighted (DW)-MRI and 0.54/0.57 on FDG-PET/CT, and to detect ypN+ were 0.89/0.81 on DW-MRI and 0.75/0.71 on FDG-PET/CT. The AUCs/sensitivities/specificities for the individual readers to detect any residual disease were 0.74/92%/57% and 0.70/96%/43% on MRI; these were 0.49/69%/29% and 0.60/69%/43% on FDG-PET/CT, respectively.MRI reached higher diagnostic accuracies than FDG-PET/CT for the detection of residual tumour in oesophageal cancer patients at 6 to 8 weeks after nCRT.

BACKGROUND: Presence of lymph node metastases (LNM) is an important prognostic factor for cancer-specific survival (CSS) in patients with upper tract urothelial carcinoma (UTUC). In various neoplasms, 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) is an established modality for preoperative lymph node (LN) staging. In UTUC, the diagnostic value of FDG-PET/CT for LN staging is unknown.OBJECTIVE: To determine the diagnostic value of FDG-PET/CT for LN staging in patients with UTUC.DESIGN, SETTING, AND PARTICIPANTS: Data of 152 patients with UTUC who underwent FDG-PET/CT followed by surgical treatment in eight centers between 2007 and 2017 were retrospectively collected. Patients receiving neoadjuvant chemotherapy were excluded.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: FDG-PET/CT results were compared with histopathology after lymph node dissection (LND). Recurrence-free survival (RFS), CSS, and overall survival (OS) were analyzed using Kaplan-Meier estimates, and compared for patients with and without suspicious LNs on FDG-PET/CT.RESULTS AND LIMITATIONS: We included 117 patients, of whom 62 underwent LND. Seventeen patients had LNM at histopathological evaluation. Sensitivity and specificity of FDG-PET/CT for diagnosis of LNM were 82% (95% confidence interval [CI]: 57-96) and 84% (95% CI: 71-94), respectively. RFS was significantly worse in patients with LN-positive FDG-PET/CT than in those with LN-negative FDG-PET/CT (p=0.03). CSS (p=0.11) and OS (p=0.5) were similar between groups. This study is limited by its retrospective design and by its sample size. Our results warrant further validation.CONCLUSIONS: FDG-PET/CT has 82% sensitivity and 84% specificity for the detection of LNM in patients with UTUC. Presence of suspicious LNs on FDG-PET/CT is associated with worse RFS.PATIENT SUMMARY: In patients with upper tract urothelial cancer, positron emission tomography with computed tomography (PET/CT) scans can detect lymph node metastases with noteworthy accuracy. Presence of suspicious lymph nodes on 18F-fluorodeoxyglucose PET/CT is associated with worse recurrence-free survival.

Positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose (FDG) combined with computed tomography (CT) provides functional imaging combined with anatomic information, improving diagnostic accuracy and confidence. Although virtually all primary penile tumors are FDG-avid, PET/CT is not recommended for primary tumor staging as it has limited spatial resolution and is hampered by urinary FDG excretion. The accuracy of PET/CT for lymph node staging seems to improve with the pretest likelihood of metastatic nodes. In groins with normal physical examination, sensitivity is only 57%. In groins with palpably enlarged lymph nodes, sensitivity of PET/CT reaches 96%. For pelvic lymph nodes and distant metastases, PET/CT is more accurate if inguinal metastases are present. However, these results are based on a very limited number of studies. Overall, the role of PET/CT imaging in penile cancer remains ambiguous, especially in inguinal lymph nodes. During staging and follow-up, it may be particularly useful in detecting pelvic lymph node metastases and occult distant metastases prior to systemic chemotherapy and/or extensive surgery, improving selection of patients that are most likely to benefit from such therapies.

Purpose To assess the efficacy of robotic-assisted laparoscopic sentinel lymph node (SLN) dissection (SLND) to select those patients with prostate cancer (PCa) who would benefit from additional pelvic external beam radiation therapy and long-term androgen deprivation therapy (ADT). Methods and Materials Radioisotope-guided SLND was performed in 224 clinically node-negative patients scheduled to undergo external beam radiation therapy. Patients with histologically positive SLNs (pN1) were also offered radiation therapy to the pelvic lymph nodes, combined with 3 years of ADT. Biochemical recurrence (BCR), overall survival, and metastasis-free (including pelvic and nonregional lymph nodes) survival (MFS) rates were retrospectively calculated. The Briganti and Kattan nomogram predictions were compared with the observed pN status and BCR. Results The median prostate-specific antigen (PSA) value was 15.4 ng/mL (interquartile range [IQR] 8-29). A total number of 834 SLNs (median 3 per patient; IQR 2-5) were removed. Nodal metastases were diagnosed in 42% of the patients, with 150 SLNs affected (median 1; IQR 1-2). The 5-year BCR-free and MFS rates for pN0 patients were 67.9% and 87.8%, respectively. The corresponding values for pN1 patients were 43% and 66.6%. The PSA level and number of removed SLNs were independent predictors of BCR and MFS, and pN status was an additional independent predictor of BCR. The 5-year overall survival rate was 97.6% and correlated only with pN status. The predictive accuracy of the Briganti nomogram was 0.665. Patients in the higher quartiles of Kattan nomogram prediction of BCR had better than expected outcomes. The complication rate from SLND was 8.9%. Conclusions For radioisotope-guided SLND, the high staging accuracy is accompanied by low morbidity. The better than expected outcomes observed in the lower quartiles of BCR prediction suggest a role for SLN biopsy as a potential selection tool for the addition of pelvic radiation therapy and ADT intensification in pN1 patients.

Objectives: To report the long-term results of the sentinel node (SN) approach in patients with clinical stage I testicular tumours in our facility. Patients and Methods: We conducted an analysis of 27 consecutive patients suspected of clinical stage I testicular germ cell tumour (TGCT) and treated with an SN procedure at our tertiary referral centre. SNs were identified using lymphoscintigraphy with or without single-photo-emission computed tomography with CT (SPECT/CT). Patients underwent laparoscopic retroperitoneal SN excision with inguinal orchiectomy. Patients with a tumour-positive SN underwent adjuvant treatment. Follow-up was conducted according to then-current guidelines. Results: In two patients, no SNs were visualized on scintigraphy. In the remaining 25 patients, a median (range) of 3 (1–4) SNs per patient were removed. Two patients showed no malignancy on histopathological examination of the testis. Of the 23 patients diagnosed with TGCT (16 seminomas, seven non-seminomas), three (13.0%) had occult metastatic disease. All 23 patients were without evidence of disease at a median (range) follow-up of 63.9 (29.0–143.4) months. Conclusion: The SN procedure allows early identification of patients with occult metastatic disease in clinical stage I TGCT, enabling early treatment.

Presence of lymph node metastases (LNM) is an important prognostic factor for cancer-specific survival (CSS) in patients with upper tract urothelial carcinoma (UTUC). In various neoplasms,To determine the diagnostic value of FDG-PET/CT for LN staging in patients with UTUC.Data of 152 patients with UTUC who underwent FDG-PET/CT followed by surgical treatment in eight centers between 2007 and 2017 were retrospectively collected. Patients receiving neoadjuvant chemotherapy were excluded.FDG-PET/CT results were compared with histopathology after lymph node dissection (LND). Recurrence-free survival (RFS), CSS, and overall survival (OS) were analyzed using Kaplan-Meier estimates, and compared for patients with and without suspicious LNs on FDG-PET/CT.We included 117 patients, of whom 62 underwent LND. Seventeen patients had LNM at histopathological evaluation. Sensitivity and specificity of FDG-PET/CT for diagnosis of LNM were 82% (95% confidence interval [CI]: 57-96) and 84% (95% CI: 71-94), respectively. RFS was significantly worse in patients with LN-positive FDG-PET/CT than in those with LN-negative FDG-PET/CT (p=0.03). CSS (p=0.11) and OS (p=0.5) were similar between groups. This study is limited by its retrospective design and by its sample size. Our results warrant further validation.FDG-PET/CT has 82% sensitivity and 84% specificity for the detection of LNM in patients with UTUC. Presence of suspicious LNs on FDG-PET/CT is associated with worse RFS.In patients with upper tract urothelial cancer, positron emission tomography with computed tomography (PET/CT) scans can detect lymph node metastases with noteworthy accuracy. Presence of suspicious lymph nodes on

Purpose of review This review discusses new findings in penile cancer imaging in relation to the European Association of Urology and National Comprehensive Cancer Network guidelines. Recent findings For imaging in penile cancer patients who are candidates for organ-sparing primary treatment, ultrasound with Doppler seems to be the method of choice in addition to physical examination. The sentinel node biopsy (SNB) procedure is used to detect small nodal metastases in clinically node-negative patients. In recent years, this procedure has been enhanced by 3D imaging using single photon emission computed tomography (SPECT) with computed tomography (CT) to improve preoperative localization and interpretation of sentinel nodes, as well as hybrid fluorescent and radioactive tracers to increase intraoperative localization of sentinel nodes. 18F-fluorodeoxyglucose PET (FDG-PET) with CT appears to be mainly useful for pelvic and distant staging in clinically node-positive patients. Other modalities with a potential future role in penile cancer are ultrasound with shear wave elastography, FDG-PET with MRI and ultrasmall paramagnetic iron oxide-enhanced MRI. Summary Imaging modalities in penile cancer have advanced throughout the years, assisting in treatment decision-making and during invasive procedures.

Het doel van deze studie was het bepalen van de klinische relevantie van incidentele prostaatopname (IPO) op een FDG-PET/CT-scan. We analyseerden 108 mannelijke patienten met blaascarcinoom (BCa) die een FDG-PET/CT-scan ondergingen en vervolgens een cystoprostatectomie, in de periode 2009–2014. IPO had een slechte voorspellende waarde voor de aanwezigheid van prostaatcarcinoom (PCa). Diagnostische nauwkeurigheid verbeterde niet wanneer een nucleair geneeskundige de laesies classificeerde op basis van de mate van verdenking op PCa. Gebaseerd op deze resultaten, zouden artsen bij IPO op een FDG-PET/CT-scan terughoudend moeten zijn met het toepassen van invasieve diagnostiek naar PCa.

Purpose Radical prostatectomy and complementary extended pelvic lymph node dissection (ePLND) of sentinel lymph nodes (SNs) and non-sentinel lymph nodes (LNs) at risk of containing metastases are increasingly being performed using high-tech robot-assisted approaches. Although this technological evolution has clear advantages, the physical nature of robotic systems limits the integrated use of routine radioguided surgery technologies. Hence, engineering effort in robotics are focused on the integration of fluorescence guidance technologies. Using the hybrid SN tracer indocyanine green-99mTc-nanocolloid (radioactive and fluorescent), for the first time in combination with a robot-integrated laparoscope, we investigated whether the robot-assisted approach affects the accuracy of fluorescence detection of SNs identified preoperatively using nuclear medicine. Methods The study included 55 patients (Briganti nomogram-based risk >5 % on LN metastases) scheduled for robot-assisted radical prostatectomy, SN biopsy and ePLND. Following indocyanine green-99mTc-nanocolloid injection, preoperative nuclear imaging (lymphoscintigraphy and SPECT/CT) was used to locate the SN(s). The fluorescence laparoscope was used intraoperatively to identify the SN(s) with standard fluorescence settings (in 50 patients) and with customized settings (in 5 patients). The number and location of the SNs, the radioactive, fluorescence (both in vivo and ex vivo) and tumour status of the resected SNs/LNs, and postoperative complications were recorded and analysed. Results Combined, preoperative lymphoscintigraphy and SPECT/CT imaging identified 212 SNs (median 4 per patient). Intraoperative fluorescence imaging using standard fluorescence settings visualized 80.4 % (148/184 SNs; 50 patients; ex vivo 97.8 %). This increased to 85.7 % (12/14 SNs; 5 patients; ex vivo 100 %) with customized fluorescence settings. SPECT/CT images provided guidance towards the residual SNs. Ex vivo all removed SNs were radioactive. SNs were tumour-positive in 25.4 % of patients (14/55; false-negative rate 7 %, 1/14 patients). In ten patients, the SN was the only tumour-positive LN. Surgical complications were minimal. Conclusion Directly linking 3D preoperative nuclear imaging information on SNs to a robot-integrated fluorescence laparoscope improved the surgeon’s use of the technology and did not influence the sensitivity or morbidity of the procedure. To our surprise, however, the detection rates with the current fluorescence camera did not improve.

Introduction/Background Neoadjuvant taxane-based combination chemotherapy has shown promising results in unresectable squamous cell carcinoma of the head and neck area, and the penis. Our primary aim was to assess the objective response in penile cancer patients neoadjuvantly treated with taxane-based combination chemotherapy. Secondary outcomes were progression-free survival (PFS), disease-specific survival (DSS), and toxicity. Patients and Methods Twenty-six patients were treated within the framework of a nonrandomized institutional registration study with 4 courses of TPF (docetaxel, cisplatin, and 5-fluorouracil) for advanced penile cancer between 2008 and 2012. Response was measured using computed tomography (CT) and/or fluorodeoxyglucose positron emission tomography/CT according to Response Evaluation Criteria in Solid Tumours 1.1 criteria and European Organisation for Research and Treatment of Cancer recommendations, respectively. Toxicity, PFS, and DSS were analyzed using either the Common Toxicity Criteria of Adverse Events version 4.0 or the Kaplan-Meier methods. To analyze possible association with survival, univariable and multivariable Cox regression analyses were performed for tumor differentiation, N-category, recurrent disease, tumor margins, and administration of radiotherapy. Results During a median follow-up of 30 months, an imaging-based response was obtained in 60% (95% confidence interval [CI], 39%-79%) (15/25) of patients. However, pathologic complete response was observed in 1 of 25 evaluable patients (4%; 95% CI, 0%-20%). Toxicity was considerable with registered toxicity in every patient. The 2-year PFS and DSS probability were 12% and 28%, respectively. Patients responsive to chemotherapy had significantly better survival than nonresponsive patients. Conclusion Despite a fairly good response percentage, TPF chemotherapy was poorly tolerated with disappointing survival rates. Therefore, other treatment options should be considered.

Resumen Objetivo El proposito del estudio es evaluar el valor anadido de la SPECT-TC en la valoracion preoperatoria de los ganglios centinelas de las regiones presacral y pararrectal, los cuales se localizan fuera del area estandar de la linfadenectomia extendida utilizada para la estadificacion de la pelvis en cancer de prostata. La SPECT-TC puede servir de guia para la escision de estos ganglios mediante linfadenectomia por cirugia abierta o laparoscopia. Material y Metodos Se evaluaron 4 pacientes con cancer de prostata los cuales presentaban en la SPECT-TC realizada adicionalmente a la linfogammagrafia ganglios centinelas en las regiones pararrectal y/o presacral. Estos pacientes se sometieron a prostatectomia y linfadenectomia laparoscopica asistida con robot con posterior analisis de los ganglios mediante anatomia patologica. Resultados Un promedio de 6 ganglios centinelas por paciente fueron hallados en la SPECT-TC con una media de 2 ganglios centinelas en la region presacral/pararrectal. La linfadenectomia fue realizada incluyendo dichas areas. Los ganglios centinelas presacrales/pararrectales de todos los pacientes, detectados por la SPECT-TC, resultaron libres de tumor en la histopatologia. En un unico paciente la histopatologia, incluyendo los ganglios centinelas (no presacrales/pararrectales), resulto positiva para malignidad. Conclusion La SPECT-TC preoperatoria es una herramienta util para localizar los ganglios centinelas en las regiones presacral y pararrectal, constituyendo una guia anatomica que puede ser de ayuda para nuevas modalidades de cirugia laparoscopica como los procedimientos asistidos por robot, los cuales pueden acceder a estas areas permitiendo la escision de dichos ganglios.

Aim This study has aimed to evaluate the added value of SPECT-CT scan in the preoperative assessment of sentinel nodes of the presacral and pararectal regions localized outside the standard area of extended pelvic lymphadenectomy for the staging of the pelvis in prostate cancer. SPECT-CT scan can serve as a guide for the excision of these nodes by lymphadenectomy by open surgery or laparoscopy. Materials and methods We evaluated 4 patients with prostate cancer presenting sentinel nodes in the pararectal and presacral regions on SPECT-CT scan performed in addition to lymphoscintigraphy. These patients underwent lymphadenectomy with robot-assisted laparoscopy together with prostatectomy. All of the excised lymph nodes were sent for histopathology study. Results An average of 6 sentinel nodes per patient were found on SPECT-CT scan with a mean of 2 sentinel nodes in presacral/pararectal region. Lymphadenectomy including these areas was performed. Pararectal/presacral sentinel nodes of all patients depicted by SPECT-CT scan were tumor-free on histopathology study. Sentinel nodes (no pararectal/presacral) were positive for malignancy in only one patient. Conclusion Preoperative SPECT-CT scan is a useful tool to localize the sentinel nodes in pararectal/presacral regions. It can be an anatomic guide for new modalities of laparoscopic surgery such as robot-assisted procedures that can access the pelvic areas visualized with SPECT-CT scan, making excision of these nodes possible.

We review recent advancements in staging and imaging of penile cancer, including surveillance after therapy.For cN0 patients, the sentinel lymph node biopsy is currently considered the preferred way for invasive staging. It has largely replaced other modalities such as staging inguinal lymphadenectomy. Its diagnostic value increases when combined with other staging modalities such as ultrasound with fine-needle aspiration cytology (US-FNAC) or fluorodeoxyglucose-PET with computed tomography (PET/CT). In patients with palpably suspicious nodes (cN+), imaging is more useful. PET/CT has shown good accuracy in a limited number of small studies. US-FNAC can confirm nodal metastatic disease. A staging inguinal lymphadenectomy is of therapeutic value but is associated with significant morbidity. Omitting staging inguinal lymphadenectomy was recently described; one study showed well tolerated use of sentinel lymph node biopsy combined with intraoperative ultrasound-guided resection of suspicious nodes in cN+ patients. Therapeutic inguinal lymphadenectomy was only performed in the 42% of groins with metastases confirmed by disorder. For M-staging, PET/CT has shown good sensitivity, and its role should be further evaluated. Follow-up and surveillance rely on physical examination and US-FNAC.Over the past decade, staging and treatment of penile cancer have become less invasive, while survival tends to improve.

PURPOSE: We investigated the accuracy of FDG-PET/CT response identification following neoadjuvant or induction chemotherapy (NAIC) for invasive bladder cancer (BC) as to better select patients for radical cystectomy (RC).METHODS: Between 2010 and 2014, 37 cT1-4N1-3 BC patients received a FDG-PET/CT before and after NAIC followed by RC. Metabolic lymph node (LN) response was evaluated according to EORTC recommendations. Additionally, primary tumor response was evaluated for 23 patients by means of delayed pelvic imaging after forced diuresis. Gold standard was response on pathologic analysis of RC specimens. Response was defined as partial response (pPR, any pathologic downstaging) or complete response (pCR, RESULTS: Twenty-four cN+ patients achieved LN pCR. FDG-PET/CT identified pCR with 67% sensitivity and 46% specificity. Primary tumor response was evaluable for 17/23 patients, of whom 12 were responders. Tumor downstaging (pPR or pCR) was identified with 83% sensitivity and 80% specificity. Tumor pCR was detected with 70% sensitivity and 71% specificity. pCR of overall disease (primary tumor and LNs, n = 17) was detected with 67% sensitivity and 75% specificity. CSS was positively associated with pathologic CR (HR 0.16, p = 0.027), but not with metabolic CR (HR 0.560, p = 0.612).CONCLUSION: FDG-PET/CT can accurately distinguish primary tumor downstaging from non-response, which suggests that response monitoring (in cN0 patients) might be used to adjust neoadjuvant treatment. pCR identification is less accurate, especially for LN metastases, which suggests that FDG-PET/CT cannot be used to select patients for RC.

323 Background: In 2012 the ALSYMPCA study established a 3.6 month Overall Survival (OS) benefit of mCRPC patients treated with Ra-223 over placebo. To date clinical outcomes of Ra-223 treatment in a non-study population have not been prospectively evaluated. Methods: The ROTOR registry aimed to include 300 patients in 20 Dutch hospitals prior to Ra-223 treatment at the physician’s discretion. Clinical parameters collected included: positioning of Ra-223, Adverse Events (AE’s; CTCAE v4.03), Skeletal Related Events (SRE) and survival data. SRE was defined as radiotherapy to a bone metastasis, a new pathological fracture, spinal cord compression and/or bone surgery. Progression-Free Survival (PFS) was defined as survival until radiological or clinical progression, subsequent treatment or death. Results: Between April 2014 and September 2017, 305 patients were included of whom 300 were evaluable. The mean age of patients was 72.6 (range 46.3-91.5) years, 255 (85%) had ≥ 6 bone metastases and 197 (65.5%) were pretreated with taxanes and/or abiraterone or enzalutamide (214 (71.3%)). Two-hundred and ninety (96.7%) patients were treated with Ra-223. Twenty-nine (9.7%), 104 (34.7%), 96 (32%) and 66 (22%) patients received Ra-223 as a first, second, third, ≥ fourth mCRPC treatment line, respectively. Patients received an average of 4.6 (SD 1.8) cycles of Ra-223, while 140 (46.7%) completed all six cycles. After a median follow-up of 13.2 months, PFS was 5.1 (CI 4.5-5.8) months and OS 15.2 (CI 12.8-17.6) months. Eighty-two (27.3%) patients were hospitalized during Ra-223 treatment (Serious AE). Grade ≥ 3 anemia, neutropenia and thrombocytopenia was found in 54 (18.0%), 8 (2.7%) and 11 (3.7%) patients, respectively. Other frequent AE’s (all grades) were nausea (90 (30%)), diarrhea (83 (27.7%)) and fatigue (178 (59.3%)). SREs were observed in 46 (15.3%) patients; 22 (7.3%) received radiotherapy, 6 (2%) developed pathologic fractures, 17 (5.6%) spinal cord compression and 1 (0.3%) received bone surgery during Ra-223 therapy. Conclusions: The non-study ROTOR population had characteristics, all grade AEs and OS comparable with the treatment arm of ALSYMPCA. Clinical trial information: NCT03223597.

Objective To evaluate the clinical impact of 18F-fluorodeoxyglucose (FDG)-positron-emission tomography/computed tomography (PET/CT) scanning, compared with conventional staging with contrast-enhanced CT imaging (CECT). Patients and Methods The FDG-PET/CT results of 96 consecutive patients with bladder cancer were analysed. Patients included in this study underwent standard CECT imaging of the chest and abdomen/pelvis

For esophageal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), restaging using F‑18-fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET-CT) following nCRT can detect interval metastases, including liver metastases, in almost 10% of patients. However, in clinical practice, focal FDG liver uptake, unrelated to liver metastases, is observed after chemoradiotherapy. This radiation-induced liver injury (RILI) can potentially lead to overstaging. A systematic search for potential cases of RILI after (chemo)radiotherapy for esophageal cancer was performed in the electronic reports from all PET-CT scans made between 2006 and 2015 in our hospital. Additional data about potential cases were obtained from the electronic medical records. A literature review of RILI was also performed. Of 205 patients undergoing nCRT, 6 cases with localized increased FDG uptake in the caudate or left liver lobe following nCRT for esophageal cancer were identified. None of these patients had signs of liver metastases with additional imaging, during surgery, on biopsy, or during follow-up (range 11–46 months). At our institute, the incidence of RILI after neoadjuvant chemoradiotherapy for esophageal cancer was 3%. In the literature, RILI is described in about 8% of patients at the time of restaging. FDG-avid lesions occur in the high radiation dose area, usually corresponding to the caudate or left liver lobe. FDG accumulation in the caudate or left liver lobe after CRT in the area that received a high radiation dose may be caused by metastases or RILI. Awareness of the pitfall of high FDG uptake in RILI is crucial to avoid misinterpretation and overstaging.

In vivo biodistribution imaging of platinum-based compounds may allow better patient selection for treatment with chemo(radio)therapy. Radiolabeling with Platinum-195m (195mPt) allows SPECT imaging, without altering the chemical structure or biological activity of the compound. We have assessed the feasibility of 195mPt SPECT imaging in mice, with the aim to determine the image quality and accuracy of quantification for current preclinical imaging equipment. Enriched (>96%) 194Pt was irradiated in the High Flux Reactor (HFR) in Petten, The Netherlands (NRG). A 0.05 M HCl 195mPt-solution with a specific activity of 33 MBq/mg was obtained. Image quality was assessed for the NanoSPECT/CT (Bioscan Inc., Washington DC, USA) and U-SPECT+/CT (MILabs BV, Utrecht, the Netherlands) scanners. A radioactivity-filled rod phantom (rod diameter 0.85-1.7 mm) filled with 1 MBq 195mPt was scanned with different acquisition durations (10-120 min). Four healthy mice were injected intravenously with 3-4 MBq 195mPt. Mouse images were acquired with the NanoSPECT for 120 min at 0, 2, 4, or 24 h after injection. Organs were delineated to quantify 195mPt concentrations. Immediately after scanning, the mice were sacrificed, and the platinum concentration was determined in organs using a gamma counter and graphite furnace – atomic absorption spectroscopy (GF-AAS) as reference standards. A 30-min acquisition of the phantom provided visually adequate image quality for both scanners. The smallest visible rods were 0.95 mm in diameter on the NanoSPECT and 0.85 mm in diameter on the U-SPECT+. The image quality in mice was visually adequate. Uptake was seen in the kidneys with excretion to the bladder, and in the liver, blood, and intestine. No uptake was seen in the brain. The Spearman correlation between SPECT and gamma counter was 0.92, between SPECT and GF-AAS it was 0.84, and between GF-AAS and gamma counter it was0.97 (all p

OBJECTIVE The purpose of this study was to prospectively investigate the value of a standardized 18F-fluorodeoxyglucose (18F-FDG)-PET/computed tomography (CT) protocol for imaging of primary bladder cancer, using standardized bladder flushing and filling. METHODS We included 19 patients with cT1-4 bladder cancer. A Foley catheter was inserted before 18F-FDG injection. PET/CT imaging was performed according to four bladder protocols: (1) bladder empty; (2) bladder empty after flushing; (3) bladder filled with 50 ml saline; and (4) bladder filled with 100 ml saline. Tumour visibility was assessed and compared with histopathology or CT and cystoscopy. RESULTS The procedure was successfully completed in 16 out of 19 patients. The reference standard revealed a bladder tumour in 16 out of 19 patients. Sensitivity of protocols 1 and 2 was 0.38 [95% confidence interval (CI), 0.16-0.64] compared with 0.63 (95% CI, 0.36-0.84) for protocols 3 and 4. CONCLUSION Flushing and subsequent retrograde filling of the bladder results in the highest rate of tumour visualization and quantification. Flushing alone is inferior.

Purpose Our hypothesis was that pretreatment inflammation in the lung makes pulmonary tissue more susceptible to radiation damage. The relationship between pretreatment [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) uptake in the lungs (as a surrogate for inflammation) and the delivered radiation dose and radiation-induced lung toxicity (RILT) was investigated. Methods and Materials We retrospectively studied a prospectively obtained cohort of 101 non-small-cell lung cancer patients treated with (chemo)radiation therapy (RT). [ 18 F]FDG-positron emission tomography-computed tomography (PET-CT) scans used for treatment planning were studied. Different parameters were used to describe [ 18 F]FDG uptake patterns in the lungs, excluding clinical target volumes, and the interaction with radiation dose. An increase in the dyspnea grade of 1 (Common Terminology Criteria for Adverse Events version 3.0) or more points compared to the pre-RT score was used as an endpoint for analysis of RILT. The effect of [ 18 F]FDG and CT-based variables, dose, and other patient or treatment characteristics that effected RILT was studied using logistic regression. Results Increased lung density and pretreatment [ 18 F]FDG uptake were related to RILT after RT with univariable logistic regression. The 95th percentile of the [ 18 F]FDG uptake in the lungs remained significant in multivariable logistic regression ( p = 0.016; odds ratio [OR] = 4.3), together with age ( p = 0.029; OR=1.06), and a pre-RT dyspnea score of ≥1 ( p = 0.005; OR=0.20). Significant interaction effects were demonstrated among the 80th, 90th, and 95th percentiles and the relative lung volume receiving more than 2 and 5 Gy. Conclusions The risk of RILT increased with the 95th percentile of the [ 18 F]FDG uptake in the lungs, excluding clinical tumor volume (OR = 4.3). The effect became more pronounced as the fraction of the 5%, 10%, and 20% highest standardized uptake value voxels that received more than 2 Gy to 5 Gy increased. Therefore, the risk of RILT may be decreased by applying sophisticated radiotherapy techniques to avoid areas in the lung with high [ 18 F]FDG uptake.

Background: Many patients with stage I-Ill small cell lung cancer (SCLC) experience disease progression short after the completion of concurrent chemoradiotherapy (CRT). The purpose of the current study was to evaluate whether CT or FOG metabolic response early after the start of chemotherapy, but before the beginning of chest RT, is predictive for survival in SCLC. Methods: Fifteen stage I-Ill SCLC patients treated with concurrent CRT with an FDG-PET and CT scan available before the start of chemotherapy and after or during the first cycle of chemotherapy, but before the start of radiotherapy, were selected. The metabolic volume (MV) was defined both within the primary tumour and in the involved nodal stations using the 40% (MV40) and 50% (MV50) threshold of the maximum SUV. Metabolic and CT response was assessed by the relative change in MV and CT volume, respectively, between both time points. The association between response and overall survival (OS) was analysed by univariate cox regression analysis. The minimum follow-up was 18 months. Results: Reductions in MV40 and MV50 were -36 +/- 38% (126.4 to 68.7 cm(3)) and -44 +/- 38% (90.2 to 27.8 cm(3)), respectively. The median CT volume reduction was -40 +/- 64% (190.6 to 113.8 cm(3)). MV40 and MV50 changes showed a significant association with survival (HR = 1.02, 95% Cl: 1.00-1.04 (p = 0.042); HR = 1.02, 95% Cl: 1.00-1.04 (p = 0.048), respectively), indicating a 2% increase in survival probability for 1% reduction in metabolic volume. The CT volume change was also significantly correlated with survival (HR = 1.01, 95% Cl: 1.00-1.03, p = 0.007). Conclusions: This hypothesis generating study shows that both the early CT and the MV changes show a significant correlation with survival in SCLC. A prospective study is planned in a larger patient cohort to allow multivariate analysis, with the final aim to select patients early during treatment that could benefit from dose intensification or alternative treatment.

Contains fulltext : 98302.pdf (Publisher’s version ) (Closed access) PURPOSE: Radiolabelled peptides used for peptide receptor radionuclide therapy are excreted mainly via the kidneys and are partly reabsorbed and retained in the proximal tubular cells. The resulting high renal radiation dose can cause nephrotoxicity, limiting the maximum activity dose and the effectiveness of peptide receptor radionuclide therapy. The mechanisms of kidney reabsorption of these peptides are incompletely understood, but the scavenger receptor megalin has been shown to play a role in the reabsorption of (111)In-octreotide. In this study, the role of megalin in the renal reabsorption of various relevant radiolabelled peptides was investigated. METHODS: Groups of kidney-specific megalin-deficient mice and wild-type mice were injected with (111)In-labelled somatostatin, exendin, neurotensin or minigastrin analogues. Single photon emission computed tomographic (SPECT) images of the kidneys were acquired and analysed quantitatively, or the animals were killed 3 h after injection and the activity concentration in the kidneys was measured. RESULTS: Megalin-deficient mice showed significantly lower uptake of all studied radiolabelled peptides in the kidneys, ranging from 22% ((111)In-octreotide) to 65% ((111)In-exendin) of uptake in wild-type kidneys. Quantitative analysis of renal uptake by SPECT and ex vivo measurements showed a very good correlation. CONCLUSION: Megalin is involved in the renal reabsorption of radiolabelled octreotide, octreotate, exendin, neurotensin and minigastrin. This knowledge may help in the design of strategies to reduce this reabsorption and the resulting nephrotoxicity in peptide receptor radionuclide therapy, enabling more effective therapy. Small-animal SPECT is an accurate tool, allowing in vivo quantification of renal uptake and serial measurements in individual mice.

Contains fulltext : 89547.pdf (Publisher’s version ) (Closed access) We determined the renal radiation dose of a series of (111)In-labeled peptides using animal SPECT. Because the animals' health deteriorated, renal toxicity was assessed. METHODS: Wild-type and megalin-deficient mice were imaged repeatedly at 3- to 6-wk intervals to quantify renal retention after injection of 40-50 MBq of (111)In-diethylenetriaminepentaacetic acid-labeled peptides (octreotide, exendin, octreotate, neurotensin, and minigastrin analogs), and the absorbed kidney radiation doses were estimated. Body weight, renal function parameters, and renal histology were determined at 16-20 wk after the first scan and compared with those in naive animals. RESULTS: Because of high renal retention, (111)In-diethylenetriaminepentaacetic acid-exendin-4 scans resulted in a 70-Gy kidney radiation dose in wild-type mice. Megalin-deficient kidneys received 20-40 Gy. The other peptides resulted in much lower renal doses. Kidney function monitoring indicated renal damage in imaged animals. CONCLUSION: Micro-SPECT enables longitudinal studies in 1 animal. However, long-term nephrotoxic effects may be induced after high renal radiation doses, even with (111)In-labeled radiotracers. 01 juni 2010

550 Background: Approximately 20 – 30% of patients with testicular germ cell tumors (TGCTs) in clinical stage I (CS I) have occult metastatic disease at the time of presentation and will relapse under surveillance. The availability of a sentinel node procedure would enable early identification of patients with occult metastases. We report the long-term results of the sentinel node approach in CS I testicular tumor patients in our facility. Methods: Between 2001 and 2015, patients suspected of CS I TGCT in our third echelon referral center were asked to participate. SNs were identified using SPECT/CT and/or lymphoscintigraphy. Participants underwent laparoscopic retroperitoneal SN excision together with inguinal orchiectomy. Patients with a SN positive for occult metastases were treated with adjuvant chemotherapy. Follow-up was according to then current guidelines and consisted of clinical examination, tumor markers, abdominal/thoracic CT-scanning and chest X-rays. Results: Twenty-seven patients were included. In two patients, no sentinel nodes were visualized on scintigraphy. In twenty-five patients, a median of 3 SNs (range 1 – 4) per patient were removed. Two patients showed no malignancy on histopathologic examination of the testis. Of the 23 patients diagnosed with TGCT, three (13.0%) had occult metastatic disease. All 23 patients were without evidence of disease at a median follow-up of 62.2 months (range 22.3 – 143.4). Conclusions: The SN procedure enables early identification of patients with occult metastatic disease in CS I TGCT. Clinical trial information: M00LMT.

Patients and their peers need to be adequately informed to ensure proper treatment selection, and to facilitate optimal realisation and outcome of treatment. Written patient information can contribute, but only when brochures are of sufficient quality. An evaluation of patient brochures for radium-223 therapy in the Netherlands revealed significant differences in the information provided, as well as discrepancies between the brochures and national guidelines and product documentation. This potentially leads to confusion, false expectations, wrong treatment decisions, suboptimal realisation and outcome of treatment, and unnecessary toxicity and in radiation hygiene risks. Here we discuss the option of national patient information brochures that can be used by all centres in order to circumvent such issues. This would require collaboration between all medical professions, patient organisations and other groups involved, and responsibilities for medical information, distribution and updates must be properly defined. A national patient information brochure of this kind is currently under development for radium-223 therapy.

Superoxide dismutase: the balance between prevention and induction of oxidative damage.den Hartog GJ, Haenen GR, Vegt E, van der Vijgh WJ, Bast A.Department of Pharmacology and Toxicology, University Maastricht, PO Box 616, 6200 MD Maastricht, The Netherlands. gj.denhartog@farmaco.unimaas.nlCu,Zn-superoxide dismutase (SOD1) has been shown to be effective in several free radical mediated diseases, although some studies have pointed toward SOD1 toxicity at a high concentrations. In the present study, the balance between prevention and induction of damage by SOD1 has been investigated both in vitro and in vivo. In vitro superoxide was generated using xanthine/xanthine oxidase. In vivo superoxide was generated using the redox cycling compound doxorubicin. Furthermore, we determined the pharmacokinetics of lecithinized SOD1 (PC-SOD) in order to compare the results obtained in vivo with those obtained in vitro. It was found that in vitro high concentrations of SOD1 induce hydroxylation of coumarin 3-carboxylic acid (3-CCA). This could be caused by a peroxidative action of SOD1 or formation of the highly reactive hydroxyl radicals. Any signs of toxicity are absent in vivo because these concentrations are not reached. It can be concluded that SOD1 possesses a large therapeutic window and application of SOD1 or its derivatives for strengthening the body's defenses against oxidative stress in a variety of pathologies seems safe