Prospective Assessment of Fluorine-18-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) for Early Identification of Checkpoint-Inhibitor-Induced Pseudoprogression.

The activity of immune checkpoint inhibitors (ICIs) in patients with metastatic melanoma is often monitored using fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scans. However, distinguishing disease progression (PD) from pseudoprogression (PsPD), where increased FDG uptake might reflect immune cell activity rather than tumor growth, remains a challenge. This prospective study compared the efficacy of dual-time point (DTP) FDG-PET/CT with modified response criteria (PERCIMT) in differentiating PsPD from PD. From July 2017-January 2021, 41 patients suspected to have PsPD on an evaluation scan were prospectively included (29 evaluable). A subsequent DTP FDG-PET/CT scan was conducted within 14 days, followed by a confirmatory FDG-PET/CT scan. Additionally, PERCIMT were applied. DTP FDG-PET/CT identified 24% with PsPD and 76% with PD. Applying PERCIMT criteria, 69% showed PsPD, while 31% had PD. On follow-up, 10 patients (34%) demonstrated confirmed PsPD, while 19 (66%) exhibited PD. The sensitivity and specificity of DTP FDG-PET/CT were 20% and 74%, respectively, and for PERCIMT this was 80% and 37%, respectively. Our findings suggest limited efficacy of DTP FDG-PET/CT in distinguishing PsPD from PD in ICI-treated patients with metastatic melanoma. The use of PERCIMT could complement clinical assessment and be incorporated in multidisciplinary team conferences for enhanced decision-making.

Earlier Recurrence Detection Using Routine FDG PET-CT Scans in Surveillance of Stage IIB to IIID Melanoma: A National Cohort Study of 1480 Patients.

BACKGROUND: The effect of routine imaging in melanoma surveillance is unknown. In 2016, Denmark was the first country in the world to implement routine imaging with positron emission tomography-computed tomography with fluorodeoxyglucose (FDG PET-CT) in a nationwide, population-based surveillance program. This study aimed to determine the impact of surveillance with routine FDG PET-CT on hazard, cumulative incidence, and absolute risk of overall, locoregional, and distant recurrence detection in patients with stage IIB to IIID cutaneous melanoma. METHODS: This retrospective, population-based, nationwide cohort study used prospectively collected data from five national health registries to compare hazard, cumulative incidence, and absolute risk of recurrence in patients with cutaneous melanoma diagnosed in 2008-2010 (cohort 1, followed with clinical examinations) and patients with cutaneous melanoma diagnosed in 2016-2017 (cohort 2, followed with clinical examinations and routine FDG PET-CT at 6, 12, 24, and 36 months). RESULTS: The study included 1480 patients with stage IIB to IIID cutaneous melanoma. Cumulative incidences of overall and distant recurrence were higher in cohort 2, with a peak difference at three years (32.3 % vs 27.5 % and 25.8 % vs. 18.5 %, respectively). The hazard of recurrence was higher in cohort 2 during the first two years, with hazard rates for overall and distant recurrence of 1.16 (95 % confidence interval [CI], 0.93-1.44) and 1.51 (95 % CI, 1.16-1.96), respectively. The patterns persisted in absolute risk estimates. CONCLUSIONS: Patients with stage IIB to IIID melanoma followed with routine FDG PET-CT had a 51 % increased hazard of distant recurrence detection within the first two years of surveillance. Future studies must determine whether this earlier recurrence detection translates into improved survival.

Randomised phase II trial of stereotactic body radiotherapy in combination with checkpoint inhibitors in metastatic castration-resistant prostate cancer (CheckPRO): a study protocol.

INTRODUCTION: Immunotherapy with checkpoint inhibitors (CPIs) has revolutionised cancer treatment but has no convincing effect in metastatic castration-resistant prostate cancer (mCRPC). It has been suggested that a combination of CPI and hypofractionated stereotactic body radiotherapy (SBRT) may work synergistically, and recent trials have supported this. We hypothesise that adding SBRT to CPI treatment can improve response rates in patients with mCRPC. METHODS AND ANALYSIS: The CheckPRO trial is an open-label, randomised, two-stage, phase II trial. We aim to enrol and randomise 80 evaluable patients with mCRPC who progressed following ≥2 lines of treatment. Enrolment started in November 2019 with 38 months expected enrolment period. The participants receive treatment for 52 weeks including four cycles of ipilimumab and nivolumab with or without concomitant SBRT (24 Gray in three fractions) to a single soft tissue or bone metastasis, followed by 10 cycles of nivolumab. Participants are followed until progression, death, or for 12 months after the end of treatment.Co-primary endpoints are the objective response rate and prostate-specific antigen (PSA) response rate. Secondary endpoints include safety, radiographic progression-free survival, clinical benefit rate, duration of response, PSA-progression-free survival beyond 12 weeks, quality of life and overall survival. Exploratory endpoints include translational analyses of tumour biopsies and consecutive blood samples. Biopsies from metastatic sites are collected at baseline, before the third treatment and at the end of treatment. Blood sampling for immune monitoring and circulating tumour DNA is performed consecutively at baseline and every radiographic assessment. ETHICS AND DISSEMINATION: This study follows the Helsinki Declaration and is approved by the Danish Ethics Committee System (journal no. H-19016100). All participants must receive written and oral information and provide a signed informed consent document prior to inclusion. The study results will be published in an international peer-review journal. TRIAL REGISTRATION NUMBER: EudraCT number: 2018-003461-34. CLINICALTRIALS: gov ID NCT05655715.

Clinical value of routine [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography scans as a decision tool for early immunotherapy discontinuation in advanced melanoma.

Routine [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) may help predict clinical outcomes after response to immunotherapy. With a European Medicines Agency-recommended treatment length until disease progression or unacceptable toxicity, the optimal duration of immunotherapy remains to be defined. In a retrospective study, we retrieved from the Danish Metastatic Melanoma Database (DAMMED), all patients that were annotated as a partial or complete response based on the computed tomography (CT) of serial FDG-PET-CT scans. Patients treated with an anti-Programmed Death (PD)-1-containing regimen for <18 months, and ≥4 months without disease progression after halting anti-PD-1 were included. Cases were divided into an "elective" and a "toxicity" group based on the reason for treatment discontinuation. A total of 140 patients were included. At 29.3 months of median follow-up, a higher proportion of patients remained alive in the "elective" group (93% vs 75%, P = .0031) with an improved melanoma-specific (HR 0.07, 95% CI 0.02-0.32, P = .0041) survival (MSS). Patients without FDG-avid lesions at the time of treatment discontinuation had an improved MSS (HR 0.03, 95% CI 0.01-0.17, P = .0002), and the absence of FDG-avid lesions was the only independent predictive feature of improved MSS in multivariate analysis. In conclusion, patients with metastatic melanoma who obtain an early response and early discontinue immunotherapy have an excellent prognosis, especially in the absence of FDG-PET avid lesions when discontinuing treatment. These data support the option of early discontinuation, limiting possible overtreatment and thereby toxicity, health and economic expenses and improving logistics.

A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma.

Anti-programmed death (PD)-1 (aPD1) therapy is an effective treatment for metastatic melanoma (MM); however, over 50% of patients progress due to resistance. We tested a first-in-class immune-modulatory vaccine (IO102/IO103) against indoleamine 2,3-dioxygenase (IDO) and PD ligand 1 (PD-L1), targeting immunosuppressive cells and tumor cells expressing IDO and/or PD-L1 (IDO/PD-L1), combined with nivolumab. Thirty aPD1 therapy-naive patients with MM were treated in a phase 1/2 study ( https://clinicaltrials.gov/ , NCT03047928). The primary endpoint was feasibility and safety; the systemic toxicity profile was comparable to that of nivolumab monotherapy. Secondary endpoints were efficacy and immunogenicity; an objective response rate (ORR) of 80% (confidence interval (CI), 62.7-90.5%) was reached, with 43% (CI, 27.4-60.8%) complete responses. After a median follow-up of 22.9 months, the median progression-free survival (PFS) was 26 months (CI, 15.4-69 months). Median overall survival (OS) was not reached. Vaccine-specific responses assessed in vitro were detected in the blood of >93% of patients during vaccination. Vaccine-reactive T cells comprised CD4+ and CD8+ T cells with activity against IDO- and PD-L1-expressing cancer and immune cells. T cell influx of peripherally expanded T cells into tumor sites was observed in responding patients, and general enrichment of IDO- and PD-L1-specific clones after treatment was documented. These clinical efficacy and favorable safety data support further validation in a larger randomized trial to confirm the clinical potential of this immunomodulating approach.

Routine PET-CT scans provide early and accurate recurrence detection in asymptomatic stage IIB-III melanoma patients.

INTRODUCTION: The use of routine imaging with 18F-FDG PET-CT (PET-CT) in melanoma surveillance is debated and evidence of its diagnostic value and yield in asymptomatic patients is limited. Denmark introduced nationwide routine surveillance with PET-CT in high-risk patients in 2016. The aim of this study was to examine the sensitivity, specificity, negative and positive predictive values, numbers-needed-to-scan and clinical impact of routine PET-CT in the surveillance of asymptomatic stage IIB-III melanoma patients. MATERIALS AND METHODS: Data was retrieved from the population-based Danish Melanoma Database and patient records. All patients diagnosed with stage IIB-III melanoma at two University Hospitals in 2016 and 2017 were included. Patients underwent surveillance with clinical examinations and PET-CT scans at 6, 12, 24 and 36 months. RESULTS: In 138 patients, 243 routine PET-CTs were performed within a median follow-up time of 17.7 months. Routine PET-CT detected recurrence at least once in 25 patients (18.1%), including distant recurrence in 19 patients (13.8%). Stage IIB patients had the lowest recurrence rate (11.1%). Numbers-needed-to-scan to detect one distant recurrence was 12.8 patients and median time-to-recurrence was 6.8 months. Sensitivity was 100%, specificity was 94.7% and negative and positive predictive values were 100% and 74.4%, respectively. False positive findings prompted 22 additional investigations (of which ten invasive) in 17 patients (12.3%). CONCLUSION: Routine PET-CT has a high sensitivity and specificity when used in high-risk melanoma surveillance. Time-to-recurrence and stage-specific recurrence rates indicate high gain of early routine imaging at six months especially for stage IIC and III patients.

Automated synthesis of 68 Ga/177 Lu-PSMA on the Trasis miniAllinOne.

Prostate-specific membrane antigen (PSMA)-based radioligands for positron emission tomography (PET)/computed tomography (CT) studies represent the gold standard for detection of recurrent prostate cancer (PCa). [68 Ga]PSMA-HBED-CC is a PET radiotracer suitable for detection of PCa, and its clinical use has become widespread over the last few years. In this contribution, we detail our GMP-compliant production of [68 Ga]PSMA-HBED-CC using the Trasis miniAllinOne radiosynthesizer and report synthetic and clinical data for the first 100 productions of 2019. Additionally, we detail our efforts towards a GMP-compliant production of the radiotherapeutic [177 Lu]PSMA-I&T using the same synthesis module. PSMA-based radioligand therapy (RLT) offers a possible future treatment in cases of metastatic castration-resistant PCa, and GMP-compliant routine production methods are therefore called for. This report highlights how PSMA-based agents for theranostic purposes can be conveniently produced at a single radiochemistry Good Manufacturing Practice (GMP) site, thereby facilitating optimized detection and treatment of PCa.

The DAHANCA 32 study: Electrochemotherapy for recurrent mucosal head and neck cancer.

BACKGROUND: Electrochemotherapy is an established treatment for cutaneous tumors. This study aimed at determining efficacy of electrochemotherapy in recurrent head and neck cancer. METHODS: Phase II clinical trial in patients with recurrent head and neck carcinomas with no curative treatment options. Electrochemotherapy was performed under general anesthesia. Primary endpoint was tumor response (CT scanning) evaluated at week 8. Secondary endpoints included biopsy results, MRI and fluorodeoxyglucose-positron emission tomography scanning, safety, toxicity, pain score, and quality-of-life questionnaires. RESULTS: Of 26 patients treated, 5 (19%) achieved complete response, 10 (39%) partial response, resulting in an objective response of 58%. Two responders remain without recurrence. No serious adverse events occurred during treatment. Four events occurred posttreatment: one bleeding episode, two episodes with mucosal swelling, and one patient died due to disease progression. CONCLUSION: Electrochemotherapy is efficient against local recurrence of head and neck cancer with an overall response rate of 58%.

Adoptive cell therapy with tumor-infiltrating lymphocytes in patients with metastatic ovarian cancer: a pilot study.

Objective:Ovarian cancer (OC) is often diagnosed at an advanced stage with two thirds of patients experiencing recurrent disease with a poor prognosis. Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has shown curative potential in malignant melanoma, but has only been investigated scarcely in other cancers. In this pilot study, we tested TIL based ACT in patients with metastatic OC. Methods:Six patients with progressive platinum-resistant metastatic OC were treated with an infusion of TIL preceded by standard lymphodepleting chemotherapy and followed by decrescendo intravenous interleukin-2 (IL-2). Primarily, the feasibility and tolerability of the treatment was assessed. Secondarily, disease control rate was described and immune responses against tumor cells were monitored. Results:Treatment was well tolerated with manageable toxicities. Four patients had stable disease for three months and two patients for five months with five patients having a decrease in target lesions. Progression was primarily due to new lesions while target lesions in general remained stable or in regression. Antitumor reactivity was observed in TIL infusion products from five patients but no antitumor reactivity was detectable in peripheral blood lymphocytes collected after treatment. High numbers of infused TIL expressed exhaustion markers including LAG3 and PD-1, and immunostaining of tumor tissue demonstrated substantial MHCII and PD-L1 expression. Conclusions:ACT with TIL in combination with decrescendo IL-2 is feasible in patients with metastatic OC. Early indications of clinical activity were found. However, TIL ACT efficacy was incomplete with possible involvement of the inhibitory immune checkpoint pathways LAG3/MHCII and PD1/PD-L1.

Gene therapy for patients with advanced solid tumors: a phase I study using gene electrotransfer to muscle with the integrin inhibitor plasmid AMEP.

BACKGROUND: Gene electrotrotransfer describes the use of electric pulses to transfer DNA to cells. Particularly skeletal muscle has potential for systemic secretion of therapeutic proteins. Gene electrotransfer to muscle using the integrin inhibitor plasmid AMEP (Antiangiogenic MEtargidin Peptide) was investigated in a phase I dose escalation study. Primary objective was safety. MATERIAL AND METHODS: Patients with metastatic or locally advanced solid tumors, without further standard treatments available, were treated with once-only gene electrotransfer of plasmid AMEP to the femoral muscle. Safety was monitored by adverse events registration, visual analog scale (VAS) after procedure and magnetic resonance imaging (MRI) of treated muscles. Pharmacokinetics of plasmid AMEP in plasma and urine was determined by quantitative polymerase chain reaction. Response was evaluated by positron emission tomography-computed tomography (PET-CT) scans. RESULTS: Seven patients were enrolled and treated at dose levels from 50 to 250 µg of plasmid AMEP, the study was terminated early due to cessation of plasmid production. Minimal systemic toxicity was observed and only transient mild pain was associated with the delivery of the electric pulses. MRI of the treated muscles revealed discrete intramuscular edema 24 h after treatment. The changes in the muscle tissue resolved within 2 weeks after treatment. Peak concentrations of plasmid AMEP was detected only in plasma within the first 24 hours after injection. Protein AMEP could not be detected, which could be due to the limit of detection. No objective responses were seen. CONCLUSIONS: Gene electrotransfer of plasmid AMEP was found to be safe and tolerable. No objective responses were observed but other DNA drugs may be tested in the future using this procedure.

Routine X-ray of the chest is not justified in staging of cutaneous melanoma patients.

INTRODUCTION: The incidence of cutaneous melanoma is increasing in Denmark and worldwide. However, the prevalence of distant metastases at the time of diagnosis has decreased to 1%. We therefore questioned the value of routine preoperative chest X-ray (CXR) for staging asymptomatic melanoma patients and hypothesised that routine CXR is not justified. METHODS: A retrospective study was conducted on patients undergoing wide local excision and sentinel lymph node biopsy for cutaneous melanoma in the period from 2010 to 2014. RESULTS: A total of 603 patients were included. The mean time of follow-up was 34 months (range: 13-75 months). Of the 603 patients, 25 (4%) had a positive CXR and 578 (96%) had a negative CXR. Four (0.7%) patients had lung metastases of whom two had a true positive and two a false negative CXR, respectively. The sensitivity was 50%, specificity was 96%, the positive predictive value was 8%, and the negative predictive value was 100%. CONCLUSION: Our results suggest that CXR cannot be justified in the initial staging of cutaneous melanoma patients. The guideline for the treatment of melanoma in Denmark is under revision: The use of CXR has been omitted. FUNDING: This study received funding from the Department of Plastic Surgery, the Research Council at Herlev Gentofte Hospital and the Danish Cancer Society. TRIAL REGISTRATION: The Danish Regional Committee on Biomedical Research Ethics (r. no.: H-4-2014-127), the Danish Data Protection Agency (2012-58-0004, local record no.: HEH-2015-003, I-Suite no.: 03436) and the Danish Melan-oma Group.

Early 18F-FDG-PET/CT as a predictive marker for treatment response and survival in patients with metastatic colorectal cancer treated with irinotecan and cetuximab.

BACKGROUND: To clarify if early reduction in standard uptake value (SUV) could predict metabolic response, radiologic response and overall survival (OS) in patients with metastatic colorectal cancer receiving third-line treatment. MATERIAL AND METHODS: Patients were regardless of KRAS status, included in this phase II trial. They were treated with the monoclonal antibody, cetuximab, and the chemotherapeutic drug, irinotecan, every second week. A F18-fluorodeoxy glucose positron emission tomography/computed tomography (FDG-PET/CT) was scheduled before the first and second treatment, respectively, and then after every fourth treatment. Early metabolic response after one treatment and best overall metabolic response was calculated according to EORTC criteria (responders: ≥15% decrease in ∑SUVmax) and PERCIST (responders: ≥30% decrease in SULpeak). Best overall radiologic response was calculated according to RECIST 1.0. RESULTS: By EORTC criteria, early metabolic response predicted partial metabolic response (PMR) with a high positive predictive value (PPV) of 0.875 and a high negative predictive value (NPV) of 0.714. Partial radiologic response was predicted with a low PPV of 0.368 but a high NPV of 1.0. By PERCIST, PMR was predicted with a high PPV of 0.826 and an intermediate NPV of 0.667 and partial radiologic response was predicted with a low PPV of 0.5 but a high NPV of 1.0. Median OS was nearly the same with the two criteria sets; 14.1 months for early metabolic responders and 9.9 months for non-responders using EORTC criteria and 13.5 and 10.1 months, respectively, using PERCIST. CONCLUSIONS: With both EORTC criteria and PERCIST, early reduction in FDG uptake was predictive of a later partial metabolic and partial radiologic response to treatment. It was also predictive of significantly longer survival of early metabolic responders compared to non-responders. However, the sensitivities and specificities were not high enough to support clinical routine use.

Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen.

PURPOSE: Adoptive cell transfer therapy (ACT) based on autologous tumor-infiltrating lymphocytes (TIL) has achieved impressive clinical results in several phase I and II trials performed outside of Europe. Although transient, the toxicities associated with high-dose (HD) bolus IL2 classically administered together with TILs are severe. To further scrutinize whether similar results can be achieved with lower doses of IL2, we have carried out a phase I/II trial of TIL transfer after classical lymphodepleting chemotherapy followed by an attenuated IL2 regimen. EXPERIMENTAL DESIGN: Twenty-five patients with progressive treatment-refractory metastatic melanoma, good clinical performance, age < 70 years, and at least one resectable metastasis were eligible. TIL infusion was preceded by standard lymphodepleting chemotherapy and followed by attenuated doses of IL2 administered in an intravenous, continuous decrescendo regimen (ClinicalTrials.gov Identifier: NCT00937625). RESULTS: Classical IL2-related toxicities were observed but patients were manageable in a general oncology ward without the need for intervention from the intensive care unit. RECIST 1.0 evaluation displayed three complete responses and seven partial responses (ORR 42%). Median overall survival was 21.8 months. Tumor regression was associated with a higher absolute number of infused tumor-reactive T cells. Moreover, induction and persistence of antimelanoma T-cell responses in the peripheral blood was strongly correlated to clinical response to treatment. CONCLUSIONS: TIL-ACT with a reduced IL2 decrescendo regimen results in long-lasting complete responses in patients with treatment-refractory melanoma. Larger randomized trials are needed to elucidate whether clinical efficacy is comparable with TIL-ACT followed by HD bolus IL2. Clin Cancer Res; 22(15); 3734-45. ©2016 AACR.

CT versus FDG-PET/CT response evaluation in patients with metastatic colorectal cancer treated with irinotecan and cetuximab.

We compared morphologic computed tomography (CT)-based to metabolic fluoro-deoxy-glucose (FDG) positron emission tomography (PET)/CT-based response evaluation in patients with metastatic colorectal cancer and correlated the findings with survival and KRAS status. From 2006 to 2009, patients were included in a phase II trial and treated with cetuximab and irinotecan every second week. They underwent FDG-PET/CT examination at baseline and after every fourth treatment cycle. Response evaluation was performed prospectively according to Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and retrospectively according to Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Best overall responses were registered. Sixty-one patients were eligible for response evaluation. Partial response (PR) rate was 18%, stable disease (SD) rate 64%, and progressive disease (PD) rate 18%. Partial metabolic response (PMR) rate was 56%, stable metabolic disease rate 33%, and progressive metabolic disease (PMD) rate 11%. Response agreement was poor, κ-coefficient 0.19. Hazard ratio for overall survival for responders (PR/PMR) versus nonresponders (PD/PMD) was higher for CT- than for FDG-PET/CT evaluation. Within patients with KRAS mutations, none had PR but 44% had PMR. In conclusion, morphologic and metabolic response agreement was poor primarily because a large part of the patients shifted from SD with CT evaluation to PMR when evaluated with FDG-PET/CT. Furthermore, a larger fraction of the patients with KRAS mutations had a metabolic treatment response.

Dual time point imaging fluorine-18 flourodeoxyglucose positron emission tomography for evaluation of large loco-regional recurrences of breast cancer treated with electrochemotherapy.

BACKGROUND: Electrochemotherapy is a local anticancer treatment very efficient for treatment of small cutaneous metastases. The method is now being investigated for large cutaneous recurrences of breast cancer that are often confluent masses of malignant tumour with various degrees of inflammation. To this end 18-Flourine-Flourodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) could be a method for response evaluation. However, a standard FDG-PET/CT scan cannot differentiate inflammatory tissue from malignant tissue. Dual point time imaging (DTPI) FDG-PET has the potential of doing so. The purpose of this study was to investigate if DTPI FDG-PET/CT could assess response to electrochemotherapy and to assess the optimal timing of imaging. PATIENTS AND METHODS: Within a phase II clinical trial 11 patients with cutaneous recurrences had FDG-PET/CT scans at three time points: 60 min, 120 min and 180 min after FDG injection. The scans were performed before and 3 weeks after electrochemotherapy. RESULTS: A significant reduction in maximum standard uptake value at 60 min post injection was seen after treatment. Furthermore a change in the FDG uptake pattern was observed; from increasing uptake in up to 180 min post injection before treatment to stabilization of FDG uptake at 120 min post injection after treatment. The change in FDG uptake pattern over time lead to change of response in three target lesions; two lesions changed from stable metabolic disease to partial metabolic response and one lesion changed from partial metabolic response to stable metabolic disease. To ensure detection of the change in uptake pattern, scanning 60 and 180 min post injection seems optimal. CONCLUSIONS: The present study shows that FDG-PET/CT 60 and 180 min after tracer injection is a promising tool for response evaluation of cutaneous recurrences of breast cancer treated with electrochemotherapy.

Promising results using sentinel node biopsy as a substitute for radical lymphadenectomy in endometrial cancer staging.

INTRODUCTION: The objective of this study was to evaluate the efficacy of the sentinel node (SN) procedure in endometrial cancer patients. MATERIAL AND METHODS: This was a prospective follow-up study including patients referred to Herlev Hospital, Denmark, to be treated for endometrial cancer in the period from October 2005 to December 2008. Hysteroscopy was performed with a 4.5 mm hysteroscope. Injections of 100-150 MBq (99m)Tc-traced colloid were administered subendometrially, and a dynamic scintigram was made. SN(s) identified with a gammaprobe were resected at the operation, and frozen sections were performed, followed by radical pelvic and para-aortic lymphadenectomy. RESULTS: A total of 32 patients were included. Among patients without clinical macro-metastases (n = 27), the SNs were detected by gamma probe in 23 (85.2%), and in most patients (n = 17, 74.0%) one (n = 12) or two (n = 5) SNs were found. The consistency between the scintigram and peroperative findings increased from 50.0% to 78.9% when the dose of (99m)Tc was increased to 150 MBq, mostly because the detection failure rate was lower at the higher dose: 4.8% versus 18.2%. By frozen section all macro-metastases were confirmed, but only one micro-metastasis was diagnosed. All subsequent lymph node metastases found in the final histology were found in SNs, i.e. no false negative SNs were found. CONCLUSION: The SN procedure can be used for endometrial cancer and it has a high detection rate and no false negative SNs were detected. The sensitivity of the SN procedure may be increased by the use of single-photon emission computed tomography (SPECT)/computed tomography (CT) and peroperative cytokeratin (CK) staining of the SN(s). FUNDING: External funding was received from the following University Foundation, Copenhagen County Research, Manufacturer Einar Willumsen's Memorial Foundation, Toyota Foundation Denmark, Lilly Benthine Lund Foundation. TRIAL REGISTRATION: The study was registered with the Danish Data Protection Agency.

Comparison of EORTC criteria and PERCIST for PET/CT response evaluation of patients with metastatic colorectal cancer treated with irinotecan and cetuximab.

UNLABELLED: The study aim was to compare European Organization for Research and Treatment of Cancer (EORTC) criteria with PET Response Criteria in Solid Tumors (PERCIST) for response evaluation of patients with metastatic colorectal cancer treated with a combination of the chemotherapeutic drug irinotecan and the monoclonal antibody cetuximab. METHODS: From 2006 to 2009, patients with metastatic colorectal cancer were prospectively included in a phase II trial evaluating the combination of irinotecan and cetuximab every second week, as third-line treatment. (18)F-FDG PET/CT was performed between 1 and 14 d before the first treatment and after every fourth treatment cycle until progression was identified by CT with Response Evaluation Criteria in Solid Tumors (RECIST). Response evaluation with (18)F-FDG PET/CT was retrospectively performed according to both EORTC criteria and PERCIST, classifying the patients into 4 response categories: complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). Individual best overall metabolic response (BOmR) was registered with both sets of criteria, as well as survival within response categories, and compared. RESULTS: A total of 61 patients and 203 PET/CT scans were eligible for response evaluation. With EORTC criteria, 38 had PMR, 16 had SMD, and 7 had PMD as their BOmR. With PERCIST, 34 had PMR, 20 had SMD, and 7 had PMD as their BOmR. None of the patients had CMR. There was agreement between EORTC criteria and PERCIST in 87% of the patients, and the corresponding κ-coefficient was 0.76. Disagreements were confined to PMR and SMD. Median overall survival (OS) in months with EORTC criteria was 14.2 in the PMR group and 7.2 in the combined SMD + PMD group. With PERCIST, it was 14.5 in the PMR group and 7.9 in the SMD + PMD group. CONCLUSION: Response evaluation with EORTC criteria and PERCIST gave similar responses and OS outcomes with good agreement on BOmR (κ-coefficient, 0.76) and similar significant differences in median OS between response groups. Compared with EORTC criteria, we find PERCIST unambiguous because of clear definitions and therefore more straightforward to use.