Multimodal Therapy Versus Primary Surgery for Gastric and Gastroesophageal Junction Diffuse Type Carcinoma, with a Focus on Signet Ring Cell Carcinoma: A Nationwide Study.

BACKGROUND: Diffuse type adenocarcinoma and, more specifically, signet ring cell carcinoma (SRCC) of the stomach and gastroesophageal junction (GEJ) have a poor prognosis and the value of neoadjuvant chemo(radio)therapy (nCRT) is unclear. METHODS: All patients who underwent surgery for diffuse type gastric and GEJ carcinoma between 2004 and 2015 were retrospectively included from the Netherlands Cancer Registry. The primary outcome was overall survival after surgery. Kaplan-Meier curves were plotted. Furthermore, multivariable Poisson and Cox regressions were performed, correcting for confounders. To comply with the Cox regression proportional hazard assumption, gastric cancer survival was split into two groups, i.e. <90 days and >90 days, postoperatively by adding an interaction variable. RESULTS: Analyses included 2046 patients with diffuse type cancer: 1728 gastric cancers (50% SRCC) and 318 GEJ cancers (39% SRCC). In the gastric cancer group, 49% received neoadjuvant chemotherapy (nCT) and 51% received primary surgery (PS). All-cause mortality within 90 days postoperatively was lower after nCT (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.20-0.44; p < 0.001). Also after 90 days, mortality was lower in the nCT group (HR for the interaction variable 2.84, 95% CI 1.87-4.30, p < 0.001; total HR 0.29*2.84 = 0.84). In the GEJ group, 38% received nCT, 22% received nCRT, and 39% received PS. All-cause mortality was lower after nCT (HR 0.63, 95% CI 0.43-0.93; p = 0.020) compared with PS. The nCRT group was removed from the Cox regression analysis since the Kaplan-Meier curves of nCRT and PS intersected. The results for gastric and GEJ carcinomas were similar between the SRCC and non-SRCC subgroups. CONCLUSION: For gastric and GEJ diffuse type cancer, including SRCC, nCT was associated with increased survival.

Impact of 18FFDG-PET/CT and Laparoscopy in Staging of Locally Advanced Gastric Cancer: A Cost Analysis in the Prospective Multicenter PLASTIC-Study.

BACKGROUND: Unnecessary D2-gastrectomy and associated costs can be prevented after detecting non-curable gastric cancer, but impact of staging on treatment costs is unclear. This study determined the cost impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) and staging laparoscopy (SL) in gastric cancer staging. MATERIALS AND METHODS: In this cost analysis, four staging strategies were modeled in a decision tree: (1) 18FFDG-PET/CT first, then SL, (2) SL only, (3) 18FFDG-PET/CT only, and (4) neither SL nor 18FFDG-PET/CT. Costs were assessed on the basis of the prospective PLASTIC-study, which evaluated adding 18FFDG-PET/CT and SL to staging advanced gastric cancer (cT3-4 and/or cN+) in 18 Dutch hospitals. The Dutch Healthcare Authority provided 18FFDG-PET/CT unit costs. SL unit costs were calculated bottom-up. Gastrectomy-associated costs were collected with hospital claim data until 30 days postoperatively. Uncertainty was assessed in a probabilistic sensitivity analysis (1000 iterations). RESULTS: 18FFDG-PET/CT costs were €1104 including biopsy/cytology. Bottom-up calculations totaled €1537 per SL. D2-gastrectomy costs were €19,308. Total costs per patient were €18,137 for strategy 1, €17,079 for strategy 2, and €19,805 for strategy 3. If all patients undergo gastrectomy, total costs were €18,959 per patient (strategy 4). Performing SL only reduced costs by €1880 per patient. Adding 18FFDG-PET/CT to SL increased costs by €1058 per patient; IQR €870-1253 in the sensitivity analysis. CONCLUSIONS: For advanced gastric cancer, performing SL resulted in substantial cost savings by reducing unnecessary gastrectomies. In contrast, routine 18FFDG-PET/CT increased costs without substantially reducing unnecessary gastrectomies, and is not recommended due to limited impact with major costs. TRIAL REGISTRATION: NCT03208621. This trial was registered prospectively on 30-06-2017.

Dose finding study for unilobar radioembolization using holmium-166 microspheres to improve resectability in patients with HCC: the RALLY protocol.

BACKGROUND: High dose unilobar radioembolization (also termed 'radiation lobectomy')-the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy-has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant. METHODS: The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose-response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank. DISCUSSION: This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice. TRIAL REGISTRATION: Netherlands Trial Register NL8902 , registered on 2020-09-15.

Evaluation of the Implementation of FDG-PET/CT and Staging Laparoscopy for Gastric Cancer in The Netherlands.

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 < 0.001) and SL (21% vs. 58%; p < 0.001) increased. FDG-PET/CT was associated with additional waiting time to neoadjuvant therapy (4 days), as well as primary surgical treatment (20 days), and SL was associated with 8 additional days of waiting time to neoadjuvant therapy. Performing SL or both modalities consecutively in patients in whom it was indicated was not associated with the number of non-curative procedures. 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.

Motion-compensated FDG PET/CT for oesophageal cancer.

PURPOSE: 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. METHODS: 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 showing 18F­fluorodeoxyglucose uptake for their degree of suspicion. RESULTS: The 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, 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. CONCLUSION: SUVmax 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.

Clinical response assessment on DW-MRI compared with FDG-PET/CT after neoadjuvant chemoradiotherapy in patients with oesophageal cancer.

PURPOSE: 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. METHODS: 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+). RESULTS: 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. CONCLUSION: 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.

False positive FDG uptake in melanoma patients treated with talimogene laherparepvec (T-VEC).

Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex virus-1-based oncolytic immunotherapy and has been approved for the local treatment of unresectable (stage IIIB/C and IVM1a) cutaneous melanoma. During T-VEC treatment, tumor response is often evaluated using [18F]2-fluoro-2-deoxy- d-glucose(FDG) positron emission tomography/computed tomography (PET/CT). In a Dutch cohort (n = 173), almost one-third of patients developed new-onset FDG uptake in uninjected locoregional lymph nodes during T-VEC. In 36 out of 53 (68%) patients with new nodal FDG uptake, nuclear medicine physicians classified this FDG uptake as "suspected metastases" without clinical or pathological confirmation in the majority of patients. These false positive results indicate that new-onset FDG uptake in locoregional lymph nodes during T-VEC treatment does not necessarily reflect progressive disease, but may be associated with immune infiltration. In current clinical practice, physicians should be aware of the high false positive rate of FDG uptake during treatment with T-VEC in patients with melanoma. Therefore, pathological examination of lymph node lesions with new FDG uptake is recommended to differentiate between progressive disease and immune infiltration after treatment with T-VEC.

A prospective observational registry evaluating clinical outcomes of Radium-223 treatment in a nonstudy population.

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.

Clinical impact of PSMA PET/CT in primary prostate cancer compared to conventional nodal and distant staging: a retrospective single center study.

BACKGROUND: To evaluate the impact of Gallium-68 [68Ga] labeled prostate specific membrane antigen (PSMA) positron emission tomography (PET)/X-ray computed tomography (CT) compared with conventional imaging on staging and clinical management of men evaluated for primary prostate cancer (PCa). METHODS: Men with newly diagnosed biopsy-proven PCa who had been staged with a conventional staging protocol including bone scintigraphy (BS) and additionally underwent [68Ga]PSMA PET/CT, were evaluated retrospectively. Imaging findings from BS, magnetic resonance imaging (MRI) and/or CT were categorized regarding locoregional nodal (N) and distant metastasis (M) status as negative, positive or equivocal before and after addition of the information of PET/CT. Also, the imaging-based level of confidence (LoC) in correct assessment of N and M status was scored. Impact of PET/CT on clinical management was evaluated by the percentage of treatment category changes after PET/CT as determined in the multidisciplinary tumour board. RESULTS: Sixty-four men with intermediate and high-risk PCa were evaluated. With additional information of PET/CT, N status was upstaged in 23%, and downstaged in 9%. M status was upstaged in 13%, and downstaged in 23%. A net increase in LoC of 20% was noted, mainly regarding M status. Treatment category changed from palliative to curative in 9%, and from curative to palliative in 3%. An undecided treatment plan changed to curative in 14%, as well as to palliative in another 9%. In total, a 36% treatment category change was noted. High negative predictive value of PET/CT for M status was indicated by 27 patients that underwent robot-assisted radical prostatectomy and reached postoperative biochemical disease-free status or had a likely other site of disease recurrence. CONCLUSIONS: PSMA PET/CT can cause considerable changes in N and M staging, as well as in management compared to conventional staging. Findings of this study support the replacement of BS and CT by PSMA PET/CT in staging primary PCa.

Sentinel node biopsy in clinical stage I testicular cancer enables early detection of occult metastatic disease.

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.

Integrated versus separate reading of F-18 FDG-PET/CT and MRI for abdominal malignancies - effect on staging outcomes and diagnostic confidence.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. KEY POINTS: • 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.

Recent developments in penile cancer imaging.

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.

Radiation-induced liver injury mimicking liver metastases on FDG-PET-CT after chemoradiotherapy for esophageal cancer : A retrospective study and literature review.

BACKGROUND: For esophageal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), restaging using F­18-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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Advancements in staging and imaging for penile cancer.

PURPOSE OF REVIEW: We review recent advancements in staging and imaging of penile cancer, including surveillance after therapy. RECENT FINDINGS: 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. SUMMARY: Over the past decade, staging and treatment of penile cancer have become less invasive, while survival tends to improve.

Clinical Relevance of Incidental Prostatic Lesions on FDG-Positron Emission Tomography/Computerized Tomography-Should Patients Receive Further Evaluation?

PURPOSE: FDG ((18)F-fluoro-2-deoxy-D-glucose)-PET/CT (positron emission tomography)/(computerized tomography) is a widely used diagnostic tool for whole body imaging. Incidental prostatic uptake is often found on FDG-PET/CT. The objective of this study was to determine the clinical relevance of incidental prostatic uptake on FDG-PET/CT. MATERIALS AND METHODS: We analyzed 108 consecutive male patients with bladder cancer who underwent FDG-PET/CT and subsequently radical cystoprostatectomy between May 2009 and November 2014. PET/CT scans were blindly reviewed by a dedicated nuclear medicine physician for incidental prostatic FDG uptake. If present, the maximum standardized uptake value was determined. Subsequently incidental prostatic uptake was categorized as suspect, indeterminate or nonsuspect for prostate cancer. RESULTS: Incidental prostatic uptake was present in 43 of 108 patients (40%). Of these 43 patients 13 (30%) had occult prostate cancer in cystoprostatectomy specimens. Overall prostate cancer was found in 25 of 108 specimens (23%). If all incidental prostatic uptake was regarded as prostate cancer, the sensitivity and specificity of FDG-PET/CT for prostate cancer detection were 52% and 64%, respectively. Positive and negative predictive values were 30% and 82%, respectively. If only lesions labeled suspect or indeterminate were regarded as prostate cancer, sensitivity, specificity, and positive and negative predictive values were 32%, 76%, 29% and 79%, respectively. Categorizing indeterminate lesions as nonprostate cancer did not improve diagnostic accuracy. Gleason score did not correlate with maximum standardized uptake value or serum prostate specific antigen. CONCLUSIONS: Incidental prostatic uptake on FDG-PET/CT has a low positive predictive value for prostate cancer. An attempt to classify lesions as suspect or nonsuspect did not increase diagnostic accuracy. Based on these results physicians should be cautious about applying invasive diagnostic methods to detect prostate cancer in case of incidental prostatic uptake on FDG-PET/CT.

Multimodal hybrid imaging agents for sentinel node mapping as a means to (re)connect nuclear medicine to advances made in robot-assisted surgery.

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-(99m)Tc-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-(99m)Tc-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.

Reduction of [68Ga]Ga-DOTA-TATE injected activity for digital PET/MR in comparison with analogue PET/CT.

BACKGROUND: New digital detectors and block-sequential regularized expectation maximization (BSREM) reconstruction algorithm improve positron emission tomography (PET)/magnetic resonance (MR) image quality. The impact on image quality may differ from analogue PET/computed tomography (CT) protocol. The aim of this study is to determine the potential reduction of injected [68Ga]Ga-DOTA-TATE activity for digital PET/MR with BSREM reconstruction while maintaining at least equal image quality compared to the current analogue PET/CT protocol. METHODS: NEMA IQ phantom data and 25 patients scheduled for a diagnostic PET/MR were included. According to our current protocol, 1.5 MBq [68Ga]Ga-DOTA-TATE per kilogram (kg) was injected. After 60 min, scans were acquired with 3 (≤ 70 kg) or 4 (> 70 kg) minutes per bedposition. PET/MR scans were reconstructed using BSREM and factors ß 150, 300, 450 and 600. List mode data with reduced counts were reconstructed to simulate scans with 17%, 33%, 50% and 67% activity reduction. Image quality was measured quantitatively for PET/CT and PET/MR phantom and patient data. Experienced nuclear medicine physicians performed visual image quality scoring and lesion counting in the PET/MR patient data. RESULTS: Phantom analysis resulted in a possible injected activity reduction of 50% with factor ß = 600. Quantitative analysis of patient images revealed a possible injected activity reduction of 67% with factor ß = 600. Both with equal or improved image quality as compared to PET/CT. However, based on visual scoring a maximum activity reduction of 33% with factor ß = 450 was acceptable, which was further limited by lesion detectability analysis to an injected activity reduction of 17% with factor ß = 450. CONCLUSION: A digital [68Ga]Ga-DOTA-TATE PET/MR together with BSREM using factor ß = 450 result in 17% injected activity reduction with quantitative values at least similar to analogue PET/CT, without compromising on PET/MR visual image quality and lesion detectability.

FDG-positron emission tomography/computerized tomography for monitoring the response of pelvic lymph node metastasis to neoadjuvant chemotherapy for bladder cancer.

PURPOSE: We evaluated FDG-positron emission tomography/computerized tomography for monitoring the response of pelvic lymph node metastasis to neoadjuvant chemotherapy for bladder cancer. We compared this to contrast enhanced computerized tomography. MATERIALS AND METHODS: Included in study were 19 consecutive patients with lymph node positive bladder cancer who underwent FDG-positron emission tomography/computerized tomography and contrast enhanced computerized tomography before and after a median of 4 cycles (range 2 to 4) of neoadjuvant chemotherapy between September 2011 and April 2012. Metabolic response was assessed according to EORTC (European Organisation for Research and Treatment of Cancer) recommendations based on the change in FDG uptake on FDG-positron emission tomography/computerized tomography. Radiological response was assessed on contrast enhanced computerized tomography according to RECIST (Response Evaluation Criteria in Solid Tumors) 1.1. All patients underwent pelvic lymph node dissection. Histopathological evaluation served as the gold standard for the nodal response. RESULTS: Before neoadjuvant chemotherapy, hypermetabolic FDG uptake was seen in all 19 patients, which matched the lymph node metastasis. Evaluating the nodal response with positron emission tomography/computerized tomography was feasible in all patients. On histopathology 16 patients were responders, including 14 with a complete pathological response of the lymph nodes. Positron emission tomography/computerized tomography and contrast enhanced computerized tomography correctly distinguished responders from nonresponders (18 of 19 patients or 94.7% and 15 of 19 or 78.9%) and complete responders from patients with residual disease (13 of 19 or 68.4% and 12 of 19 or 63.2%, respectively). CONCLUSIONS: Although no definitive conclusions can be drawn from these preliminary data, positron emission tomography/computerized tomography appears feasible for evaluating the nodal response to neoadjuvant chemotherapy and distinguishing responders from nonresponders.

Impact of (18) F-fluorodeoxyglucose (FDG)-positron-emission tomography/computed tomography (PET/CT) on management of patients with carcinoma invading bladder muscle.

OBJECTIVE: To evaluate the clinical impact of (18) F-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 <4 weeks before FDG-PET/CT. Based on the original imaging reports and recorded tumour stage before and after FDG-PET/CT imaging, the preferred treatment strategies before FDG-PET/CT and after FDG-PET/CT were determined for each patient using an institutional multidisciplinary guideline. One of the following treatment strategies was chosen: (i) local curative treatment; (ii) neoadjuvant/induction chemotherapy; or (iii) palliation. The changes in management decisions before and after FDG-PET/CT were assessed. RESULTS: The median (range) interval between CECT and FDG-PET/CT was 0 (029) days. In 21.9% of the patients, stage on FDG-PET/CT and CECT were different. Upstaging by FDG-PET/CT was more frequent than downstaging (19.8 vs 2.1%). Clinical management changed for 13.5% of patients as a result of FDG-PET/CT upstaging. In eight patients, FDG-PET/CT detected second primary tumours. This led to changes of bladder cancer treatment in another four of 96 patients (4.2%). All the management changes were validated by tissue confirmation of the additional lesions. CONCLUSIONS: FDG-PET/CT provides important additional staging information, which influences the treatment of carcinoma invading bladder muscle in almost 20% of cases. Patient selection for neoadjuvant/induction chemotherapy was improved and futile attempts at curative treatment in patients found to have metastases were avoided.

Pigmented villonodular synovitis: current concepts about diagnosis and management.

At present, the treatment strategies in patients with localized and diffuse forms of pigmented villonodular synovitis have more or less been standardized. However, these strategies are not optimal because high recurrence rates persist and studies with a sufficient level of evidence are lacking. This systematic review article describes all known treatment options for intra-articular pigmented villonodular synovitis and their clinical results. Based on this research, we provide guidelines to support physicians in making the optimal treatment decisions. Given the rarity of the disease, randomized studies are not to be expected, but an international registry through existing networks would offer the benefit of getting a better insight into the outcome of this disease. Therefore, we propose a basic set of data to be investigated and ideally to be reported on in such a registry.