Search

Aim: We aimed to evaluate the role of Positron Emission Tomography (PET) targeting the Prostate-Specific Membrane Antigen (PSMA) for response assessment in metastatic prostate cancer (mPCa) patients treated with taxane-based chemotherapy (docetaxel or cabazitaxel) and its predictive value on patient outcome. Methods: We retrospectively evaluated 37 patients with metastatic hormone-sensitive or castration-resistant prostate cancer (mHSPC or mCRPC) who underwent 68Ga-PSMA-11 PET/CT at baseline and after the last cycle of taxane-based chemotherapy (docetaxel or cabazitaxel) without treatment modification between scans. Biochemical response (BR) was defined as an undetectable or decreased prostate-specific antigen (PSA) by ≥50% compared to baseline. Association between BR and different PET parameters were tested. A cut-off of ≥30% change in PSMA total tumor volume (PSMA-TV) was used to define PSMA responders (PSMA-R) vs PSMA non-responders (PSMA-NR). Correlation between PSMA-PET/CT response and BR was evaluated using the Phi coefficient. Association between PET-response and overall survival (OS) was performed using Cox regression and Kaplan-Meier method. Results: Our cohort was composed of 8 (22%) mHSPC and 29 (78%) mCRPC patients. Twenty-one patients received docetaxel, and 16 received cabazitaxel treatment (median: 6 cycles, interquartile (IQR):5-8). BR was found in 18/37 patients. Using PSMA-TV, PSMA-PET/CT response was concordant with BR in 35/37 patients (Phi=0.89, p

Introduction [177Lu]Lu-DOTATATE is an effective systemic targeted radionuclide therapy for somatostatin receptor (SSTR) positive metastatic or inoperable neuroendocrine tumours (NET). However, for a given injected activity, tumour responses are variable. Our aim was to investigate whether SSTR expression/functionality and known characteristics of intrinsic radiosensitivity, namely proliferation rate, glucose metabolism, cell cycle phase, DNA repair and antioxidant defences were predictors of sensitivity to [177Lu]Lu-DOTATATE in SSTR expressing human cancer cell lines. Methods In six human cancer cell lines and under basal condition, SSTR expression was assessed by qRT-PCR and immunocytochemistry. Its functionality was evaluated by binding/uptake assays with [68Ga]Ga- and [177Lu]Lu-DOTATATE. The radiosensitivity parameters were evaluated as follows: proliferation rate (cell counting), glucose metabolism ([18F]FDG uptake), antioxidant defences (qRT-PCR, colorimetric assay, flow cytometry), DNA repair (qRT-PCR) and cell cycle (flow cytometry). Effect of [177Lu]Lu-DOTATATE on cell viability was assessed 3, 7 and 10 days after 4 h incubation with [177Lu]Lu-DOTATATE using crystal violet. Results Based on cell survival at day 10, cell lines were classified into two groups of sensitivity to [177Lu]Lu-DOTATATE. One group with 20% of survival decrease (−22 to −33%) compared to the untreated control cell lines. The latter had significantly lower total antioxidant capacity, glutathione (GSH) levels and glucose metabolism (p 0.22), combined catalase and GSH peroxidase expression (p = 0.42) and superoxide dismutase (SOD) activity (p = 0.41) were not significantly different between the two groups. Conclusion Antioxidant defences may be major determinants in [177Lu]Lu-DOTATATE radiosensitivity.

We present a case of Grade II, well-differentiated rectal neuroendocrine tumor in a 39-year-old patient. Following different sequential treatment modalities, the disease progressed both on metabolic (18F-fluorodeoxyglucose positron emission tomography-computed tomography [18F-FDG PET/CT]) and somatostatin receptor (SSTR)-imaging (68Ga-DOTA-Tyr3-octreotate [68Ga-DOTATATE] PET/CT), and the patient received three cycles of peptide receptor radiotherapy (PRRT). Two years later, upon new progression due to the appearance of metabolically active, 68Ga-DOTATATE PET/CT-negative liver lesions, targeted treatment with everolimus was introduced. Further morphologic and metabolic progression occurred 4 months after everolimus initiation, however, this time liver lesions demonstrated increased SSTR-expression on68Ga-DOTATATE PET/CT. Thus, the patient became eligible for a second PRRT course.

Follicular thyroid cancer (FTC) is a less common form of differentiated thyroid cancer. Liver metastasis of differentiated thyroid cancer frequently occurs in the late onset of the metastatic disease, are often unrescetable and noniodine avid, leading to a poor prognosis. A 69-year-old man with a 14-year history of multi-metastatic follicular thyroid cancer was treated iteratively with 131-Iodine allowing to maintain a stable disease. Upon a recent exponential increase of the thyroglobulin, a peritoneal mass and a voluminous hepatic metastasis were discovered, comorbidities and an insufficient future remnant liver function excluded liver surgical resection. The tumour board proposed a resection of the peritoneal mass followed by selective internal radiation therapy of the liver mass. Due to the already impaired liver function, personalized dosimetry allowed a safe treatment delivering low activity to the nontumoral liver followed by a clinical and imaging response of the liver mass at 3 months. At our knowledge, this is the first case of thyroid liver metastasis treated by selective internal radiation therapy. Keywords: Liver metastasis, Personalized dosimetry, Radioembolization, Thyroid Cancer

Background: The combination of everolimus and an endocrine agent has shown a progression-free survival (PFS) benefit but also significant toxicity in locally advanced and/or metastatic breast cancer (MBC) patients. Disappointingly, all translational research efforts conducted so far on primary/metastatic tissue or baseline ctDNA samples have failed to identify clinically useful biomarkers of benefit with the possible exception of p4EBP1 which requires fresh metastatic biopsies (Bachelot at al, ASCO 2019). Methods: Forty-seven patients were included in the PEARL trial in six Belgian centres. All patients underwent one baseline and one “early” 18FDG-PET/CT on day 14 (blinded to the treating oncologist) after treatment initiation. Eligible patients had prior progression on NSAI and at least one measurable lesion on baseline 18FDG-PET/CT (fulfilling PERCIST). Twenty seven of the 47 patients were treated in a pilot phase aiming to characterize 18FDG-PET/CT metabolic responses 14 and 28 days after treatment initiation. Day 14 18FDG-PET/CT was selected for the second phase in which 20 more patients were included to answer the primary endpoint of the trial, namely the potential of an early FDG-PET/CT to select patients who will not derive a long-term benefit from everolimus-exemestane combination. We considered as “metabolic responders” those patients in whom at least a 25% homogenous decrease in SUVmax was seen in all their target lesions; the so called “consistent” patient-based response, here correlated to PFS. Results: Seventy-four percent of the patients had visceral metastasis, 26% were pretreated with CDK 4/6 inhibitors and 58% with at least one line of chemotherapy (28% ≥ 2 lines) for the treatment of MBC. Metabolic non-response rate on day 14 was 64%. Two patients were considered non-evaluable because they stopped everolimus 3 and 8 days before early 18FDG-PET/CT respectively. The median PFS in non-responding patients was 2.3 months compared to 6 months in those who showed a consistent metabolic response (HR-1.96, 95%CI: 0.98-3.95, p=0.05). We’ll be able to assess whether day 14 ctDNA measurements add predictive value to imaging. Conclusion: Absence of 18FDG-PET/CT metabolic response after 14 days of everolimus-exemestane combination is associated with a low probability to derive benefit from this treatment. The advanced stage of the patients included in this trial (75% visceral metastasis) and their extensive prior treatments can explain the poorer outcome seen with exemestane-everolimus compared to the Bolero2 trial. Citation Format: Andrea Gombos, Martine Piccart-Gebhart, Lieveke Ameye, Peter Vuylsteke, Patrick Neven, Vincent Richard, Francois P Duhoux, Marianne Paesmans, Michail Ignatiadis, Patrick Flamen, Géraldine Gebhart. Pearl or the use of FDG positron emission tomography imaging as an early dynamic biomarker of everolimus efficacy in advanced luminal breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-22.

Background Immunotherapy represents a promising option for treatment of hepatocellular carcinoma (HCC) in cirrhotic patients but its efficacy is currently inconsistent and unpredictable. Locoregional therapies inducing immunogenic cell death, such as transarterial chemoembolization (TACE) or selective internal radiation therapy (SIRT), have the potential to act synergistically with immunotherapy. For the development of new approaches combining locoregional treatments with immunotherapy, a better understanding of the respective effects of TACE and SIRT on recruitment and activation of immune cells in HCC is needed. To address this question, we compared intra-tumor immune infiltrates in resected HCC after preoperative treatment with TACE or SIRT. Methods Data fromr patients undergoing partial hepatectomy for HCC, without preoperative treatment (SURG, n = 32), after preoperative TACE (TACE, n = 16), or preoperative SIRT (n = 12) were analyzed. Clinicopathological factors, tumor-infiltrating lymphocytes (TILs), CD4+ and CD8+ T cells, and granzyme B (GZB) expression in resected HCC, and postoperative overall and progression-free survival were compared between the three groups. Results Clinicopathological and surgical characteristics were similar in the three groups. A significant increase in TILs, CD4+ and CD8+ T cells, and GZB expression was observed in resected HCC in SIRT as compared to TACE and SURG groups. No difference in immune infiltrates was observed between TACE and SURG patients. Within the SIRT group, the dose of irradiation affected the type of immune infiltrate. A significantly higher ratio of CD3+ cells was observed in the peri-tumoral area in patients receiving + cells was observed in patients receiving > 100 Gy. Postoperative outcomes were similar in all groups. Irrespective of the preoperative treatment, the type and extent of immune infiltrates did not influence postoperative survival. Conclusions SIRT significantly promotes recruitment/activation of intra-tumor effector-type immune cells compared to TACE or no preoperative treatment. These results suggest that SIRT is a better candidate than TACE to be combined with immunotherapy for treatment of HCC. Evaluation of the optimal doses for SIRT for producing an immunogenic effect and the type of immunotherapy to be used require further evaluation in prospective studies.

Simple Summary The early treatment of oligometastatic disease (OMD) is a promising therapeutic option for prostate cancer as it has the potential of delaying androgen-deprivation therapy (ADT) and disease progression. Next-generation imaging targeting the prostate-specific membrane antigen (PSMA-PET/CT) is considered the most accurate technique for recurrent prostate cancer. Finding clinico-pathological factors predicting positivity with OMD detection on PSMA-PET/CT, as well as assessing its impact on treatment management, were the main objectives of our study. We selected a homogenous population of ADT-free prostate cancer patients with a PSMA-PET/CT performed at biochemical recurrence (BCR) after radical prostatectomy (RP). OMD was detected in 44% of patients for a total positivity rate of 60%. PSA at the moment of PET, PSAdt, and the absence of previous salvage treatment were factors predicting PSMA-PET/CT positivity with OMD. A change in clinical management occurred in more than half of the patients, mostly to perform metastasis-directed therapy after OMD detection. Abstract Metastasis-directed therapy (MDT) in oligometastatic prostate cancer has the potential of delaying the start of androgen deprivation therapy (ADT) and disease progression. We aimed to analyze the efficacy of PSMA-PET/CT in detecting oligometastatic disease (OMD), to look for predictive factors of OMD, and to evaluate the impact of PSMA-PET/CT findings on clinical management. We retrospectively analyzed a homogeneous population of 196 hormone-sensitive prostate cancer patients (HSPC), considered potential candidates for MDT, with a PSMA-PET/CT performed at biochemical recurrence (BCR) after radical prostatectomy (RP). Multivariable logistic regression analysis was performed based on several clinico-pathological factors. Changes in clinical management before and after PSMA-PET/CT were analyzed. The OMD detection rate was 44% for a total positivity rate of 60%. PSMA-PET/CT positivity was independently related to PSA (OR (95% CI), p) (1.7 (1.3–2.3), p < 0.0001) and PSAdt (0.4 (0.2–0.8), p = 0.013), and OMD detection was independently related to PSA (1.6 (1.2–2.2), p = 0.001) and no previous salvage therapy (0.3 (0.1–0.9), p = 0.038). A treatment change was observed in 58% of patients, mostly to perform MDT after OMD detection (60% of changes). This study showed that PSMA-PET/CT is an excellent imaging technique to detect OMD early in HSPC patients with BCR after RP, changing therapeutic management mostly into MDT.

Biomarkers to identify patients without benefit from adding everolimus to endocrine treatment in metastatic breast cancer (MBC) are needed. We report the results of the Pearl trial conducted in five Belgian centers assessing 18F-FDG-PET/CT non-response (n = 45) and ctDNA detection (n = 46) after 14 days of exemestane-everolimus (EXE-EVE) to identify MBC patients who will not benefit. The metabolic non-response rate was 66.6%. Median PFS in non-responding patients (using as cut-off 25% for SUVmax decrease) was 3.1 months compared to 6.0 months in those showing response (HR: 0.77, 95% CI: 0.40–1.50, p = 0.44). The difference was significant when using a “post-hoc” cut-off of 15% (PFS 2.2 months vs 6.4 months). ctDNA detection at D14 was associated with PFS: 2.1 months vs 5.0 months (HR-2.5, 95% CI: 1.3–5.0, p = 0.012). Detection of ctDNA and/or the absence of 18F-FDG-PET/CT response after 14 days of EXE-EVE identifies patients with a low probability of benefiting from treatment. Independent validation is needed., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND Early prediction of nonresponse is essential in order to avoid inefficient treatments. PURPOSE To evaluate if parametrical response mapping (PRM)-derived biomarkers could predict early morphological response (EMR) and pathological complete response (pCR) 24-72 hours after initiation of chemotherapy treatment and whether concentric analysis of nonresponding PRM regions could better predict response. STUDY TYPE This was a retrospective analysis of prospectively acquired cohort, nonrandomized, monocentric, diagnostic study. POPULATION Sixty patients were initially recruited, with 39 women participating in the final cohort. FIELD STRENGTH/SEQUENCE A 1.5T scanner was used for MRI examinations. ASSESSMENT Dynamic contrast-enhanced (DCE)-MR images were acquired at baseline (timepoint 1, TP1), 24-72 hours after the first chemotherapy (TP2), and after the end of anthracycline treatment (TP3). PRM was performed after fusion of T1 subtraction images from TP1 and TP2 using an affine registration algorithm. Pixels with an increase of more than 10% of their value (PRMdce+) were corresponding nonresponding regions of the tumor. Patients with a decrease of maximum diameter (%dDmax) between TP1 and TP3 of more than 30% were defined as EMR responders. pCR patients achieved a residual cancer burden score of 0. STATISTICAL TESTS T-test, receiver operating characteristic (ROC) curves, and logistic regression were used for the analysis. RESULTS PRM showed a statistical difference between pCR response groups (P < 0.01) and AUC of 0.88 for the prediction of non-pCR. Logistic regression analysis demonstrated that PRMdce+ and Grade II were significant (P < 0.01) for non-pCR prediction (AUC = 0.94). Peripheral tumor region demonstrated higher performance for the prediction of non-pCR (AUC = 0.85) than intermediate and central zones; however, statistical comparison showed no significant difference. DATA CONCLUSION PRM could be predictive of non-pCR 24-72 hours after initiation of chemotherapy treatment. Moreover, the peripheral region showed increased AUC for non-pCR prediction and increased signal intensity during treatment for non-pCR tumors, information that could be used for optimal tissue sampling. LEVEL OF EVIDENCE 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;51:1403-1411.

Background and Objectives: Selection for surgery in patients with colorectal liver metastases (CRLM) remains inaccurate. We evaluated if CRLM baseline metabolic characteristics, assessed by [18]F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT), could predict postoperative outcomes. Methods: In a retrospective series of patients undergoing surgery for CRLM, we defined two groups: the long-term survival (LTS) and early relapse (ER) groups, where the postoperative recurrence-free survivals were ≥5 years or 4.3, defining low- and high-risk mCRS by scores of 0 to 2 and 3 to 6, respectively. Results: From a series of 450 patients operated for CRLM (mean follow-up of 58 months), we included for analysis 23 and 30 patients in the LTS and ER groups, respectively. Clinicopathologic parameters and CRS were similar in the LTS and ER groups. Median SUVmax/SUVmean(liver) ratios were higher in ER vs LTS patients (4.2 and 2.8, P =.008, respectively). mCRS was increased in ER patients (P =.024); 61% of LTS patients had low-risk mCRS and 73% of the ER patients had high-risk mCRS (P =.023). Conclusions: 18FDG-PET/CT characteristics combined with traditional CRS may represent a new tool to improve selection for surgery in patients with CRLM., SCOPUS: ar.j, info:eu-repo/semantics/published

To investigate the association between Prostate-Specific Membrane Antigen (PSMA) expression changes on positron emission tomography–computed tomography (PET/CT) and the response to treatment following the start of enzalutamide or abiraterone in metastatic castration-resistant prostate cancer (mCRPC) patients. All consecutive 68Ga-PSMA-11 PET/CT scans routinely performed at our institution during more than 4 years were retrospectively screened for inclusion. We included mCRPC patients with a baseline PSMA PET/CT performed less than 2 months before the start of either enzalutamide or abiraterone, and a follow-up PSMA PET/CT performed no more than a year after, while still under those novel antiandrogen drugs (NAD). The associated clinical records were reviewed. Patients were considered treatment responders if they presented decreasing PSA levels > 50% or a radiological response based on RECIST 1.1 criteria. PSMA expression changes on the follow-up PET/CT were assessed using per-patient dominant response criteria to classify patients as PSMA-responders (complete disappearance of pathologic PSMA uptake, or a decreased uptake of the majority of lesions) or PSMA-non-responders (new PSMA-expressing lesions, increased uptake of the majority of lesions, or stable PSMA expression of the disease). Descriptive statistics and measures of associations (two-sided Fisher’s exact test and Phi coefficient) were calculated. A total of 11 and 15 patients were included in the enzalutamide and abiraterone groups. Median follow-up was 110 (IQR 76–124) and 87 (IQR 71–242) days, respectively. All treatment responders (3 enzalutamide and 4 abiraterone) were considered PSMA-responders, and all treatment non-responders (8 enzalutamide, 11 abiraterone) were considered PSMA-non-responders. PSMA PET response was thus perfectly associated with conventional response criteria (p = 0.006, Phi = 1 for enzalutamide; p = 0.001, Phi = 1 for abiraterone). In our cohort, no PSMA expression flare phenomenon was detected on follow-up PET/CT scans at a median follow-up of 3 months. However, an early and short-lived flare cannot be excluded. This retrospective study suggests that, after a median follow-up of 3 months under enzalutamide or abiraterone, PSMA expression changes on PET/CT are strongly associated with response to treatment. Prospective studies are needed to better understand PSMA expression dynamics following the start of enzalutamide and abiraterone, along with the role of PSMA PET/CT in response assessment.

Purpose: Reported outcomes of patients with intra-hepatic cholangiocarcinoma (IH-CCA) treated with radioembolization are highly variable, which indicates differences in included patients’ characteristics and/or procedure-related variables. This study aimed to identify patient- and treatment-related variables predictive for radioembolization outcome. Methods: This retrospective multicenter study enrolled 58 patients with unresectable and chemorefractory IH-CCA treated with resin 90Y-microspheres. Clinicopathologic data were collected from patient records. Metabolic parameters of liver tumor(s) and presence of lymph node metastasis were measured on baseline 18F-FDG-PET/CT. 99mTc-MAA tumor to liver uptake ratio (TLRMAA) was computed for each lesion on the SPECT-CT. Activity prescription using body-surface-area (BSA) or more personalized partition-model was recorded. The study endpoint was overall survival (OS) starting from date of radioembolization. Statistical analysis was performed by the log-rank test and multivariate Cox’s proportional hazards model. Results: Median OS (mOS) post-radioembolization of the entire cohort was 10.3 months. Variables associated with significant differences in terms of OS were serum albumin (hazard ratio (HR) = 2.78, 95%CI:1.29–5.98, p = 0.002), total bilirubin (HR = 2.17, 95%CI:1.14–4.12, p = 0.009), aspartate aminotransferase (HR = 2.96, 95%CI:1.50–5.84, p < 0.001), alanine aminotransferase (HR = 2.02, 95%CI:1.05–3.90, p = 0.01) and γ-GT (HR = 2.61, 95%CI:1.31–5.22, p < 0.001). The presence of lymph node metastasis as well as a TLRMAA < 1.9 were associated with shorter mOS: HR = 2.35, 95%CI:1.08–5.11, p = 0.008 and HR = 2.92, 95%CI:1.01–8.44, p = 0.009, respectively. Finally, mOS was significantly shorter in patients treated according to the BSA method compared to the partition-model: mOS of 5.5 vs 14.9 months (HR = 2.52, 95%CI:1.23–5.16, p < 0.001). Multivariate analysis indicated that the only variable that increased outcome prediction above the clinical variables was the activity prescription method with HR of 2.26 (95%CI:1.09–4.70, p = 0.03). The average mean radiation dose to tumors was significantly higher with the partition-model (86Gy) versus BSA (38Gy). Conclusion: Radioembolization efficacy in patients with unresectable recurrent and/or chemorefractory IH-CCA strongly depends on the tumor radiation dose. Personalized activity prescription should be performed., SCOPUS: ar.j, info:eu-repo/semantics/published

The aim of this communication was to assess the efficacy of directed oligometastatic radiotherapy (RT) based on 68Ga-PSMA PET/CT in patients with prostate cancer (PCa) biochemical relapse (BCR) after primary treatment with curative intent., SCOPUS: ar.j, info:eu-repo/semantics/published

Radioembolization of liver metastases of neuroendocrine neoplasms (NEN) has shown promising results; however, the current literature is of limited quality. A large international, multicentre retrospective study was designed to address several shortcomings of the current literature. 244 NEN patients with different NEN grades were included. Primary outcome parameters were radiologic response 3 and 6 months after treatment according to RECIST 1.1 and mRECIST. Secondary outcome parameters included clinical response, clinical and biochemical toxicities. Radioembolization resulted in CR in 2%, PR in 14%, SD in 75% and PD 9% according to RECIST 1.1 and in CR in 8%, PR in 35%, SD in 48% and PD in 9% according to mRECIST. Objective response rates improved over time in 20% and 26% according to RECIST 1.1. and mRECIST, respectively. Most common new grade 3–4 biochemical toxicity was lymphocytopenia (6.7%). No unexpected clinical toxicities occurred. Radioembolization-specific complications occurred in

Purpose of review Targeted radionuclide therapy (TRNT) is characterized by systemic administration of radiolabelled drugs, targeting specific molecular alterations expressed on the tumour cells. Small molecules, labelled with β- or α- emitting radioisotopes, are used to deliver radiation directly to the tumour sites. Pretreatment imaging to visualize whole body biodistribution of the target, using the same drugs labelled with positron or γ-emitting radionuclides, completes the concept of theranostic. This review will briefly summarize the current clinical research findings and applications of TRNT in solid tumours, mostly focusing on neuroendocrine and prostate neoplasms. Recent findings Peptide receptor radionuclide therapy is a major component in the management of gastroentropancreatic neuroendocrine tumours, with favourable safety profile, quality-of-life improvement and survival benefit. On the NETTER-1 study, it proved to be more effective than high-dose long-acting-release octreotide, leading to its regulatory approval. Prostate-specific membrane antigen (PSMA) is an excellent target for TRNT in prostate cancer. 177Lu-PSMA radioligand therapy demonstrated higher response rates in patients with metastatic castration resistant prostate cancer, when compared with second-line chemotherapy. New developments, including targeting of fibroblast activation proteins overexpressed in the tumour stroma, show promising preliminary results in the theranostic setting. Summary Recent research has demonstrated and consolidated the use of TRNT against well established targets in neuroendocrine tumours and prostate cancer. The identification of new promising molecular targets for TRNT, will further expand the theranostic applications of radionuclides in the field of nuclear medicine.

Purpose A multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 ( 90 Y)-resin microspheres. Methods A steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90 Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%–79%, no agreement ≤ 49%). Results Forty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99m Tc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90 Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100–120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90 Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement). Conclusion Practitioners are encouraged to work towards adoption of these recommendations., info:eu-repo/semantics/published

Predictive factors for adverse events in metastatic colorectal cancer patients treated with regorafenib are currently lacking. In this safety analysis of a prospective phase II clinical trial, we assess the association between several clinical, laboratory, and imaging parameters and the occurrence of adverse events. Our results show that female sex is an independent risk factor for increased toxicity. Background: Regorafenib is a standard treatment for refractory metastatic colorectal cancer (mCRC). In view of the toxicity burden, significant research efforts have been made to increase the therapeutic ratio of this multikinase inhibitor. Predictive factors for treatment-related adverse events (TRAEs), however, are still lacking. Materials and Methods: We assessed the association between a number of baseline clinical, laboratory and imaging parameters and the occurrence of TRAEs in 136 patients who had received regorafenib (160 mg/day, 3-weeks-on/1-week-off) in a prospective phase II clinical trial. Results: Grade >= 2 TRAEs during the first cycle of treatment (84% vs. 60%, P=.002) and grade >= 3 TRAEs throughout the whole treatment (71% vs. 53%, P=.035) occurred more frequently in females, with sex being the only independent predictive factor of early and any-time toxicity (OR 3.4; 95% CI: 1.2-11.1, P=.02 and OR 2.1; 95% CI: 1.0-4.4, P=.045, respectively). Fatigue, anorexia, hypertension, and rash were reported significantly more frequently by females than males (P

Stratification of metastatic colorectal cancer (mCRC) patients is mostly based on clinical and biologic characteristics. This study aimed to validate the prognostic value of 18F-FDG PET/CT-based biomarkers such as baseline whole-body metabolically active tumor volume (WB-MATV) and early metabolic response (mR) in mCRC. Methods: The development cohort included chemorefractory mCRC patients enrolled in 2 prospective Belgian multicenter trials evaluating last-line treatments (multikinase inhibitors). The validation cohort included mCRC patients from an Italian center treated with chemotherapy and bevacizumab as first-line. Baseline WB-MATV was defined as the sum of metabolically active volumes of all target lesions identified on the baseline 18F-FDG PET/CT. Early mR assessment was performed following usual response criteria (response threshold of 30% [PERCIST-30%], response threshold of 15% [PERCIST-15%], European Organization for Research and Treatment of Cancer) and the so-called CONSIST method, which defines response as a decrease of SULmax ≥ 15% for all target lesions. Baseline WB-MATV and early mR assessment were investigated along with usual clinical factors and correlated with overall survival (OS) and progression-free survival (PFS). Results: Clinical factors, baseline WB-MATV, and early mR were evaluable in 192 of 239 and 94 of 125 patients of the development and validation cohorts, respectively. Except for PERCIST-30%, all response methods were equivalent in terms of outcome prediction, and CONSIST was found to be the most accurate. Baseline WB-MATV and early mR using the CONSIST method were independent prognostic parameters after adjustment for clinical factors in the development and validation sets for both OS (hazard ratio [HR] WB-MATV: 1.87 [95% CI, 1.17-2.97], P = 0.005, and HR early mR: 1.79 [95% CI, 1.08-2.95], P = 0.02 for the validation set) and PFS (HR WB-MATV: 1.94 [95% CI, 1.27-2.97], P = 0.002, and HR early mR: 1.69 [95% CI, 1.04-2.73], P = 0.03 for the validation set). Conclusion: Baseline WB-MATV and early mR are strong independent prognostic biomarkers for OS and PFS in mCRC, regardless of treatment received. Therefore, combining these biomarkers improves risk stratification for OS and PFS in mCRC. ispartof: JOURNAL OF NUCLEAR MEDICINE vol:63 issue:4 pages:549-555 ispartof: location:United States status: published

SCOPUS: le.j, info:eu-repo/semantics/published

Background and Objectives The histological growth pattern (HGP) represents a strong prognostic factor in patients undergoing surgery for colorectal liver metastases (CRLM). We evaluated whether the combination of HGP with clinico-metabolic parameters could improve its prognostic value. Methods In a series of 108 patients undergoing resection of CRLM, the HGP of CRLM was scored according to international guidelines. Baseline clinico-metabolic clinical status was evaluated using a metabolic-Clinical Risk Score (mCRS), combining traditional Memorial Sloan Kettering-CRS parameters with the tumor-to-liver glucose uptake ratio as measured with (18)Fluorodeoxyglucose/positron emission tomography. Results In patients with desmoplastic HGP (DHGP) CRLM (20% of all patients), 5- and 10-years overall survival (OS) and disease free survival (DFS) were 66% and 43% and 37% and 24.5%, as compared with 35% and 21% and 11% and 11% in the non-DHGP group (p = 0.07 and 0.054). Among DHGP patients, those with a low-risk mCRS had improved postoperative outcomes, 5- and 10-years OS and DFS reaching 83.3% and 62.5% and 50% and 33%, as compared with 18% and 0% and 0% and 0% in high-risk mCRS patients (p = 0.007 and 0.003). In contrast, mCRS did not influence postoperative survivals in non-DHGP patients. Conclusions Combining the clinico-metabolic characteristics with the HGP may improve prognostication in patients undergoing surgery for CRLM.

Background The relationship between the mean absorbed dose delivered to the tumour and the outcome in liver metastases from colorectal cancer patients treated with radioembolization has already been presented in several studies. The optimization of the personalized therapeutic activity to be administered is still an open challenge. In this context, how well the 99mTc-MAA SPECT/CT predicts the absorbed dose delivered by radioembolization is essential. This work aimed to analyse the differences between predictive 99mTc-MAA-SPECT/CT and post-treatment 90Y-microsphere PET/CT dosimetry at different levels. Dose heterogeneity was compared voxel-to-voxel using the quality-volume histograms, subsequently used to demonstrate how it could be used to identify potential clinical parameters that are responsible for quantitative discrepancies between predictive and post-treatment dosimetry. Results We analysed 130 lesions delineated in twenty-six patients. Dose-volume histograms were computed from predictive and post-treatment dosimetry for all volumes: individual lesion, whole tumoural liver (TL) and non-tumoural liver (NTL). For all dose-volume histograms, the following indices were extracted: D90, D70, D50, Dmean and D20. The results showed mostly no statistical differences between predictive and post-treatment dosimetries across all volumes and for all indices. Notably, the analysis showed no difference in terms of Dmean, confirming the results from previous studies. Quality factors representing the spread of the quality-volume histogram (QVH) curve around 0 (ideal QF = 0) were determined for lesions, TL and NTL. QVHs were classified into good (QF < 0.18), acceptable (0.18 ≤ QF < 0.3) and poor (QF ≥ 0.3) correspondence. For lesions and TL, dose- and quality-volume histograms are mostly concordant: 69% of lesions had a QF within good/acceptable categories (40% good) and 65% of TL had a QF within good/acceptable categories (23% good). For NTL, the results showed mixed results with 48% QF within the poor concordance category. Finally, it was demonstrated how QVH analysis could be used to define the parameters that predict the significant differences between predictive and post-treatment dose distributions. Conclusion It was shown that the use of the QVH is feasible in assessing the predictive value of 99mTc-MAA SPECT/CT dosimetry and in estimating the absorbed dose delivered to liver metastases from colorectal cancer via 90Y-microspheres. QVH analyses could be used in combination with DVH to enhance the predictive value of 99mTc-MAA SPECT/CT dosimetry and to assist personalized activity prescription.

Introduction: Decision making in refractory colorectal cancer (rCRC) is challenging, with limited data available to predict patient outcome. We conducted a study to assess the pace of cancer progression as a potential prognostic and decision tool. Methods: CORIOLAN was a prospective, single-center, single-arm trial recruiting refractory CRC patients with an ECOG performance status of &le, 1 and an estimated life expectancy of &ge, 12 weeks. 18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan and blood sample collection were carried out at baseline and after 2 weeks with no cancer treatment given between these timepoints. The primary objective was to evaluate the association between pace of cancer progression as defined by changes of the whole-body metabolically active tumor volume (WB-MATV) and overall survival (OS). Exploratory objectives included evaluation of the prognostic value of circulating cell-free DNA (cfDNA), circulating tumor cells (CTCs) and carcinoembryonic antigen (CEA). Results: 47 eligible patients who had received a median number of 5 (range 2&ndash, 8) prior treatments were enrolled. At the time of analysis, 45 deaths had occurred, with 26% of patients dying within 12 weeks. The median OS was 6.3 months (range 0.4&ndash, 14.3). The median relative delta between WB-MATV at baseline and 2 weeks was +21%. Changes of WB-MATV, however, failed to predict OS (hazard ratio (HR) 1.3, p = 0.383). Similarly, no association was observed between changes of any of the circulating biomarkers investigated and prognosis. By contrast, high WB-MATV (4.2 versus 9.4 months, HR 3.1, p = 0.003), high CEA (4.4 versus 7.0 months, HR 1.9, p = 0.053), high cfDNA (4.7 versus 7.0 months, HR 2.2, p = 0.015) and high CTC count (3.3 versus 7.5 months, HR 6.5, p &lt, 0.001) at baseline were associated with worse OS. Conclusions: In this study, approximately 1 out of 4 refractory CRC patients who were judged to have a life expectancy &gt, 12 weeks actually died within 12 weeks. Baseline assessment of WB-MATV, cfDNA, CTCs and CEA, but not early change evaluation of the same, may help to refine patient prognostication and guide management decisions.

Background & aims: While long-term obesity is a well-known risk factor for esophageal adenocarcinoma (ADC), recent weight loss represents a significant concern in esophageal cancer (EC), in relation with dysphagia and disease aggressiveness. These phenomenons may diversely impact the adipose tissue density, suggested in other cancer settings as an important prognostic biomarker. The analysis of body mass composition (BMC) parameters, including adipose tissue attenuation is studied here in a population of EC operated with curative intent. Methods: BMC was retrospectively evaluated on Computed-Tomography (CT)-scan images from fluorodeoxyglucose (FDG)-positron-emitting (PET)/CT scans performed as a diagnostic procedure in a cohort of 145 EC patients operated with curative intent The mean subcutaneous (SFD) and visceral fat (VFD) density along with the index (area/height2) (SF index (SFI), VF index (VFI)) were assessed on two adjacent slides at the third lumbar vertebra level by two independent investigators. Overall survival (OS) was calculated from the date of the baseline FDG-PET/CT scan. Results: Inter-observer correlations are excellent for all BMC parameters (r = 0.94–0.99). As expected, weight loss is associated with worse outcome. We show that low SFD (HR 0.5 (95% CI: 0.3–0.7), p < 0.001) and low VFD (HR 0.6 (95% CI: 0.4–0.9), p = 0.04) at diagnosis are associated with better OS. In contrast, body mass index (BMI) fails to show any relevance in predicting survival. Conclusions: Adipose tissue density is an important prognostic factor in EC., SCOPUS: ar.j, info:eu-repo/semantics/published

Purpose: Peptide receptor radionuclide therapy (PRRT) and radioembolization are increasingly used in neuroendocrine neoplasms patients. However, concerns have been raised on cumulative hepatotoxicity. The aim of this sub-analysis was to investigate hepatotoxicity of yttrium-90 resin microspheres radioembolization in patients who were previously treated with PRRT. Methods: Patients treated with radioembolization after systemic radionuclide treatment were retrospectively analysed. Imaging response according to response evaluation criteria in solid tumours (RECIST) v1.1 and clinical response after 3 months were collected. Clinical, biochemical and haematological toxicities according to common terminology criteria for adverse events (CTCAE) v4.03 were also collected. Specifics on prior PRRT, subsequent radioembolization treatments, treatments after radioembolization and overall survival (OS) were collected. Results: Forty-four patients were included, who underwent a total of 58 radioembolization procedures, of which 55% whole liver treatments, at a median of 353 days after prior PRRT. According to RECIST 1.1, an objective response rate of 16% and disease control rate of 91% were found after 3 months. Clinical response was seen in 65% (15/23) of symptomatic patients after 3 months. Within 3 months, clinical toxicities occurred in 26%. Biochemical and haematological toxicities CTCAE grade 3–4 occurred in ≤ 10%, apart from lymphocytopenia (42%). Radioembolization-related complications occurred in 5% and fatal radioembolization-induced liver disease in 2% (one patient). A median OS of 3.5 years [95% confidence interval 1.8–5.1 years] after radioembolization for the entire study population was found. Conclusion: Radioembolization after systemic radionuclide treatments is safe, and the occurrence of radioembolization-induced liver disease is rare. Level of Evidence: 4, case series., SCOPUS: ar.j, info:eu-repo/semantics/published

SCOPUS: ar.j, info:eu-repo/semantics/published

Background The aim of this work was to confirm that post-selective internal radiation therapy (SIRT) 90Y-PET/CT-based dosimetry correlates with lesion metabolic response and to determine its correlation with overall survival (OS) in liver-only metastases from colorectal cancer (mCRC) patients treated with SIRT. Twenty-four mCRC patients underwent pre/post-SIRT FDG-PET/CT and post-SIRT 90Y-PET/CT. Lesions delineated on pre/post-SIRT FDG-PET/CT were classified as non-metabolic responders (total lesion glycolysis (TLG)-decrease < 15%) and high-metabolic responders (TLG-decrease ≥ 50%). Lesion delineations were projected on the anatomically registered 90Y-PET/CT. Voxel-based 3D dosimetrywas performed on the 90Y-PET/CT and lesions’ mean absorbed dose (Dmean) was measured. The coefficient of correlation between Dmean and TLG-decrease was calculated. The ability of lesion Dmean to predict non-metabolic response and high-metabolic response was tested and two cutoff values (Dmean-under-treated and Dmean-well-treated) were determined using ROC analysis. Patients were dichotomised in the “treated” group (all the lesions received a Dmean > Dmean-under-treated) and in the “under-treated” group (at least one lesion received a Dmean < Dmean-under-treated). Kaplan-Meier product limit method was used to describe OS curves. Results Fifty-seven evaluable mCRC lesions were included. The coefficient of correlation between Dmean and TLG-decrease was 0.82. Two lesion Dmean cutoffs of 39 Gy (sensitivity 80%, specificity 95%, predictive-positive-value 86% and negative-predictive-value 92%) and 60 Gy (sensitivity 70%, specificity 95%, predictive positive-value 96% and negative-predictive-value 63%) were defined to predict non-metabolic response and high-metabolic response respectively. Patients with all lesions Dmean> 39 Gy had a significantly longer OS (13 months) than patients with at least one lesion Dmean < 39 Gy (OS = 5 months) (p = 0.012;hazard-ratio, 2.6 (95% CI 0.98–7.00)). Conclusions In chemorefractory mCRC patients treated with SIRT, lesion Dmean determined on post-SIRT 90Y-PET/CT correlates with metabolic response and higher lesion Dmean is associated with prolonged OS.

BACKGROUND Validation of new biomarkers is essential for the early evaluation of neoadjuvant treatments. PURPOSE To determine whether measurements of total choline (tCho) by 1H spectroscopy could predict morphological or pathological complete response (pCR) of neoadjuvant treatment and whether breast cancer subgroups are related to prediction accuracy. STUDY TYPE Prospective, nonrandomized, monocentric, diagnostic study. POPULATION Sixty patients were initially included with 39 women participating in the final cohort. FIELD STRENGTH/SEQUENCE A 1.5T scanner was used for acquisition and MRS was performed using the syngo GRACE sequence. ASSESSMENT MRS and MRI examinations were performed at baseline (TP1), 24-72 hours after first chemotherapy (TP2), after the end of anthracycline treatment (TP3), and MRI only after the end of taxane treatment (TP4). Early (EMR) and late (LMR) morphological response were defined as %ΔDmax13 or %ΔDmax14, respectively. Responders were patients with %ΔDmax >30. Pathological complete response (pCR) patients achieved a residual cancer burden score of 0. STATISTICAL TESTS T-test, receiver operating characteristic (ROC) curves, multiple regression, logistic regression, one-way analysis of variance (ANOVA) analysis were used for the analysis. RESULTS At TP1 there was a significant difference between response groups for tCho1 concerning EMR prediction (P = 0.05) and pCR (P

Introduction Circulating tumour (ct)DNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III CC treated with surgery +/- adjuvant chemotherapy. No study, however, has ever analysed the prognostic value of this biomarker in CC patients (pts) treated with neoadjuvant chemotherapy. We sought to evaluate the prognostic value of baseline and early, on-treatment changes of cfDNA and ctDNA in stage II-III CC pts who were treated with one cycle of neoadjuvant FOLFOX chemotherapy followed by surgery +/- adjuvant FOLFOX chemotherapy in the PePiTA trial. Methods PePITA was a multicentre, single-arm, prospective phase II trial aiming to test in vivo tumour chemosensitivity as assessd by metabolic response using 18F-FDG PET/CT scan of early stage CC and to evaluate its association with survival outcome (NCT00994864). Plasma samples were prospectively collected at baseline and 2 weeks (ie, after one cycle of neoadjuvant FOLFOX chemotherapy). cfDNA was isolated with the QIAmp circulating nucleic acid kit (Qiagen), and quantified with the Qubit fluorometer (Life-Technologies). cfDNA samples were bisulfite converted using the EZ DNA Methylation-Gold™ Kit (Zymo Research), with NPY and WIF1 being selected as universal methylation markers for ctDNA and analysed with digital droplet (dd)PCR technology. Data from ddPCR were processed with the QuantaSoft V1.6 software (BioRad). The primary outcome measure was 3-year disease-free survival (DFS). Receiver operating characteristics curve analyses, Kaplan-Meier method, cox proportional hazards models and log-rank tests were used. Statistical analyses were carried out with the SPSS for MacOS version 25.0 (SPSS Inc). Results 80 pts were included (ypStage I-II 56%, ypStage III 44%). After a median follow-up of 52.5 months, 3-year DFS was 80% (95%CI 71.2-90.8) and 5-year OS 84% (95%CI 75.2-94.9). Pts with high (≥1.2 ng/µl) baseline cfDNA level had worse 3-year DFS (48% vs 80%; HR 2.72, 95%CI 1.02-7.25; p=0.036) and 5-year OS (71% vs 90%; HR 5.36, 95%CI 1.14-25.28; p=0.017) than those with low baseline cfDNA level. In a multivariable analysis (including sex, ypStage and CEA), baseline cfDNA was the only factor showing a trend towards statistical significance (HR DFS 2.6, 95%CI 0.96-7.01; p=0.059; HR OS 4.65, 95%CI 0.97-22.32; p=0.055). Early changes of cfDNA (Δ ≥11%) after one cycle of neoadjuvant FOLFOX chemotherapy failed to predict survival (HR DFS 1.08, 95%CI 0.42-2.81; p=0.873; HR OS 0.68, 95%CI 0.19-2.39; p=0.543). ctDNA analyses are ongoing and will be presented at the meeting. Conclusions For the first time, we have shown that baseline cfDNA may predict survival outcome in early stage CC pts treated with neoadjuvant chemotherapy. Pending confirmation in larger series, testing for cfDNA at baseline could help select high-risk pts who may benefit from neoadjuvant, FOXTROT-like, treatment strategies. Citation Format: Giacomo Bregni, Elena Trevisi, Chiara Senti, Andrea Pretta, Caroline Vandeputte, Pashalina Kehagias, Elena Acedo Reina, Amélie Deleporte, Paraskevas Gkolfakis, Jean-Luc Van Laethem, Philippe Vergauwe, Marc Van den Eynde, Guido Deboever, Jos Janssens, Gauthier Demolin, Stephane Holbrechts, Marylene Clausse, Thierry De Grez, Marc Peeters, Lionel D'Hondt, Karen Geboes, Tatiana Besse-Hammer, Alexis Buggenhout, Françoise Rothé, Patrick Flamen, Alain Hendlisz, Francesco Sclafani. Prognostic value of baseline and early changes of circulating cell-free (cf)DNA in the neoadjuvant setting of early stage colon cancer (CC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 28.

Objective The non-invasive diagnosis of endometriosis remains challenging. Recent data suggested that somatostatin might be involved in its pathogenesis. High sensitive visualization of somatostatin receptors expression is possible using PET-CT imaging after the administration of a 68Ga-labeled somatostatin analog (DOTATATE) that will bind to the somatostatin receptor sub-types 2 and 5. The aim of the present study was to assess the usefulness of 68Ga-DOTATATE PET-CT in the diagnosis of endometriosis. Study design This is a prospective, single center pilot study. A pre operative 68Ga-DOTATATE PET-CT was performed in all of the patients who presented with suspected endometriosis and who were scheduled for a laparoscopy. Surgical endometriosis staging and histopathological analysis, including somatostatin receptors SST1, 2 and 5 immunohistochemistry (IHC) of removed specimens, were confronted to the results of the 68Ga-DOTATATE PET-CT. Results 12 patients were included in this study. 68Ga-DOTATATE PET-CT performed pre operatively showed increased pathologic uptake in four patients with a deep infiltrating endometriosis (DIE) recto-vaginal lesion and in another patient with an adenomyoma. Expression of SST1, 2 and 5 receptors in surgical specimens was confirmed by IHC in these five lesions. Neither superficial peritoneal endometriosis, nor ovarian endometrioma were found to show an increased pathologic uptake on 68Ga-DOTATATE PET-CT. IHC analysis confirmed that SST1, 2, and 5 receptors were not present in these lesions. Conclusion The results observed in this small size series of patients seem to confirm expression of somatostatin receptors only in recto-vaginal DIE and focal adenomyosis lesions. The usefulness of 68Ga-DOTATATE PET-CT in the diagnosis of this entity is uncertain. Future research should concentrate on studying the role of somatostatin in the pathogenesis of DIE.

Background/aim Neoadjuvant chemotherapy may be administered to patients with peritoneal carcinomatosis (PC) of colorectal cancer (CRC) origin. This study evaluated the performance of 18fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography (CT) in detection of PC from CRC and correlated the most metabolically active quadrant with the most affected peritoneal area determined during surgery. Patients and methods This retrospective study compared the performance of FDG-PET/CT for PC diagnosis in 26 patients with CRC with histopathologically-confirmed PC with a control group of 26 patients. An FDG-PET/CT score established for each patient diagnosed with PC was compared with the peritoneal cancer index (PCI) performed during surgery. Results The sensitivity and specificity of FDG-PET/CT for PC detection were 85% (22/26) and 88% (23/26), respectively. The most scored quadrant by FDG-PET/CT corresponded to the most scored quadrant at surgery in 77.3%. Conclusion FDG-PET/CT may represent a useful tool for evaluating response to neoadjuvant chemotherapy in patients with PC of CRC origin.

Objective To assess the impact of a novel molecular imaging technique, 68Ga-(HBED-CC)-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT), in the clinical management of patients with prostate cancer with rising prostate-specific antigen (PSA) after treatment with curative intent. Patients and Methods In all, 131 consecutive patients were referred to our centre for a 68Ga-PSMA PET/CT in the setting of recurring prostate cancer. Of these patients, 11/131(8%) presented with persistent PSA after radical prostatectomy, while 120/131 (92%) were referred for biochemical recurrence after surgery, radiotherapy or both. The images where taken 1 h after injection of 2 MBq/kg of the 68Ga-(HBED-CC)-PSMA ligand. All examinations were interpreted by two experienced nuclear medicine specialists. Using the results of the examination, a multidisciplinary oncology committee (MOC) reported on the treatment strategy. A positive impact on clinical management was considered if the examination determined a modification in the treatment strategy compared to the MOC decision before PSMA imaging. Results All patients completed the examination with no adverse reactions. The median (interquartile range) PSA level at the time of the examination was 2.2 (0.72–6.7) ng/mL. Overall, 68Ga-PSMA PET/CT detected at least one lesion suspicious for prostate cancer in 98/131 (75%) patients. There was an impact on subsequent management in 99/131 patients (76%). The main modifications included continuing surveillance (withholding hormonal therapy), hormonal manipulations, stereotaxic radiotherapy, salvage radiotherapy, salvage node dissection or salvage local treatment (prostatectomy, high-intensity focussed ultrasound). Conclusion Our preliminary experience suggests that performing 68Ga-PSMA PET/CT in patients with prostate cancer with rising PSA after treatment with curative intent can be clinically useful as it changes the treatment strategy in a significant proportion of patients. However, larger prospective trials are needed to validate our present findings.

Within a few months, coronavirus disease 2019 (COVID-19) has become a pandemic with more than 2 million patients infected and a high mortality rate. Early detection of COVID-19 in oncologic patients is crucial in order to rapidly apply isolation measures and avoid nosocomial spread. However, early diagnosis may be challenging, especially in cancer patients under treatment with immunotherapy as drug-induced pneumonitis can present similar clinical and radiological features. We describe the findings of a SARS-CoV-2 infection on PET/CT with 18F-FDG in a 51-year-old man with metastatic renal cell carcinoma under treatment with nivolumab.

Endogenous Clostridium septicum endophthalmitis is a rare and fulminant ocular infection, usually encountered in immunocompromised or diabetic patients. It is also highly associated with both gastrointestinal and hematologic malignancies. We describe herein the detection of an adenocarcinoma of the cecum on PET/CT with F-FDG in a patient with an active endogenous C. septicum endophthalmitis of the right eye. FDG PET/CT should be considered for all patients with endogenous endophthalmitis to exclude an occult malignancy, especially colorectal cancer.

Prostate cancer (PCa) treatment monitoring usually relies on prostate-specific antigen to detect disease progression or relapse. PET/CT with prostate-specific membrane antigen (PSMA) ligands has shown high accuracy in detecting metastatic PCa lesions and could help assess response to therapy. We describe herein the early relapse detection of a hormone-sensitive metastatic upfront PCa treated with docetaxel on Ga-PSMA-11 PET/CT before biochemical progression. PSMA PET/CT should be considered to monitor PCa response to chemotherapy to detect early relapse, regardless of prostate-specific antigen levels, increasing the chances of finding low-volume oligoprogressive disease.

Baseline whole-body metabolically active tumor volume (WB-MATV) measured by 18F-FDG PET/CT and circulating cell-free DNA (cfDNA) have been separately validated as predictors of overall and progression-free survival (OS/PFS) in chemorefractory metastatic colorectal cancer (mCRC) patients. This study assessed the correlation between WB-MATV and cfDNA, evaluating the added prognostic value of these in combination, along with clinical parameters. Methods: Of 141 mCRC patients included in a prospective multicenter trial, 132 were evaluable for OS/PFS. cfDNA was extracted from 3 mL of plasma and quantified using a fluorometer. All target lesions were delineated on 18F-FDG PET/CT, and their metabolic volumes were summed to obtain the WB-MATV. Results: Baseline WB-MATV and cfDNA were strongly correlated (r 5 0.70; P, 0.001) but showed discordance in 23 of 132 (17%) patients. A multivariate analysis identified 3 independent negative predictors of PFS (high cfDNA, short time since diagnosis, and body mass index, 30) and 5 of OS (high cfDNA, high WB-MATV, body mass index, 30, poor performance status, and short time since diagnosis). Combining WB-MATV and cfDNA increased the overall prognostic value and allowed identification of a subgroup of patients with low cfDNA and high WB-MATV who were associated with intermediate survival (median OS of 8.1 for low-cfDNA/high-MATV patients vs. 12.7 mo for low-cfDNA/low-MATV patients; hazard ratio, 2.04; P 5 0.02). Conclusion: This study confirms the added prognostic value of combined circulating cfDNA and PET-based WB-MATV in chemorefractory mCRC patients. The combination of these two biomarkers should provide a firm basis for risk stratification, both in clinical practice and in research trials., SCOPUS: ar.j, info:eu-repo/semantics/published

Radiation-induced sarcoma is a rare complication of radiation therapy. We describe the incidental detection of a radiation-induced undifferentiated soft-tissue sarcoma with increased uptake on Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT in a prostate cancer patient previously treated with surgery and external-beam radiotherapy. Results were confirmed by histological analysis. Ga-PSMA is known to bind not only to PSMA-expressing prostate cancer cells but also to the neovasculature of various other solid tumors. A careful Ga-PSMA PET/CT review of previously irradiated areas is warranted so as not to miss radiation-induced sarcoma in prostate cancer patients.

Nodular fasciitis is an uncommon benign mass-forming myofibroblastic proliferation, most frequently found in the upper limbs, with only rare intramuscular cases. We describe herein a case of chronic nodular fasciitis of the left triceps muscle with a low Ga-labeled prostate-specific membrane antigen (PSMA) ligand uptake on PET/CT. Ga-PSMA ligands bind to PSMA-expressing prostate cancer cells, but uptake has also been demonstrated in other solid neoplasms and various benign lesions. Nodular fasciitis should be included in the differential diagnosis of soft tissue lesions with variable Ga-PSMA uptake.

Fibrous dysplasia is an uncommon benign bone pathology with only rare potential for malignant transformation. We describe the heterogeneous uptake of fibrous dysplasia of a whole rib on Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT. Ga-PSMA binds to PSMA-expressing prostate cancer cells, but it can also bind to the neovasculature of various solid tumors, as well as to some benign lesions. Ga-PSMA expression in fibrous dysplasia should not automatically be equated with malignant transformation or confused with prostate cancer metastases.

Background: The prognostic value of body composition in cancer patients has been widely studied during the last decade. The main finding of these studies is that sarcopenia, or skeletal muscle depletion, assessed by CT imaging correlates with a reduced overall survival (OS). By contrast, the prognostic value of fat mass remains ill-defined. This study aims to analyze the influence of body composition including both muscle mass and adipose tissue on OS in a homogeneous population of advanced colorectal cancer (CRC) patients. Methods: Among 235 patients with chemorefractory advanced CRC included in the SoMore and RegARd-C trials, body composition was assessed in 217 patients on baseline CT images. The relationship between body composition (sarcopenia, muscle density, subcutaneous and visceral fat index and density), body mass index (BMI) and OS were evaluated. Results: Patients with a higher BMI had a better OS (≥30 versus < 30, HR: 0.50; 0.33-0.76). Those with low muscle index and muscle density had an increased mortality (HR: 2.06; 1.45-2.93 and HR: 1.54; 1.09-2.18, respectively). Likewise, low subcutaneous and visceral fat index were associated with an increased risk of dying (HR: 1.63; 1.23-2.17 and 1.48; 1.09-2.02 respectively), as were a high subcutaneous and visceral adipose tissue density (HR: 1.93; 1.44-2.57 and 2.40; 1.79-3.20 respectively). In multivariate analysis, a high visceral fat density was the main predictor of poor survival. Conclusions: Our results confirm the protective role of obesity in CRC patients at an advanced stage, as well as the negative prognostic impact of muscle depletion on survival. More importantly, our data show for the first time that visceral adipose tissue density is an important prognostic factor in metastatic CRC. Trial registration: NCT01290926, 07/02/2011 and NCT01929616, 28/08/2013., SCOPUS: ar.j, info:eu-repo/semantics/published

3600 Background: ctDNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III CC treated with surgery +/- adjuvant chemotherapy (CT). No study, however, has ever analysed the prognostic value of this biomarker in CC patients (pts) treated with NACT. We sought to evaluate the prognostic value of baseline and early changes of cf/ctDNA in stage II-III CC pts who were treated with one cycle of NA FOLFOX CT followed by surgery +/- adjuvant FOLFOX CT in the PePiTA trial. Methods: PePiTA was a multicentre, single-arm, prospective phase II trial testing in vivo tumour chemosensitivity of early stage CC (as assessed by 18F-FDG PET/CT-based metabolic response to one cycle of NA FOLFOX) and its association with long-term outcome (NCT00994864). Plasma samples were prospectively collected at baseline, 2 weeks after one cycle of NA FOLFOX CT, and before surgery. NPY and WIF1 were selected as universal methylation markers for ctDNA and analysed with digital droplet (dd)PCR technology. Data from ddPCR were processed with the QuantaSoft v1.6 software (Bio-Rad). Survival outcome measures were 5-year disease-free survival (DFS) and 6-year overall survival (OS). ROC curve analyses, Kaplan-Meier method, cox proportional hazards models and log-rank tests were used. Statistical analyses were carried out with SPSS v25.0 (SPSS Inc.). Results: 80 pts were included (44 ypStage I-II and 36 ypStage III). After a median follow-up of 52.5 months, 5-year DFS and 6-year OS were 68% (95%CI 52-84) and 84% (95%CI 74-94), respectively. Pts with high (≥1600 ng/ml) baseline cfDNA had worse 6-year OS (HR 6.45, 95%CI 1.61-25.84; p = 0.008). Early changes of cfDNA after one cycle of NA FOLFOX CT failed to predict survival (HR DFS 0.96, 95%CI 0.38-2.43; p = 0.92; HR OS 0.62, 95%CI 0.16-2.50; p = 0.50). At baseline, 25 out of 60 (42%) ctDNA-assessable patients were positive. Detectable ctDNA at baseline (HR DFS 2.06, 95%CI 0.65-6.49; p = 0.22; HR OS 3.11, 95%CI 0.57-16.99; p = 0.19) or at any timepoint before surgery (HR DFS 1.65, 95%CI 0.54-5.04; p = 0.38; HR OS 2.80, 95%CI 0.54-14.44; p = 0.22) was not significantly associated with survival. A trend toward a significant association between ctDNA increase at surgery and 5-year DFS was found (HR 3.66, 95%CI 0.81-16.44; p = 0.09). Data on the correlation between early changes of cf/ctDNA and 18F-FDG PET/CT-based metabolic response will be presented at the meeting. Conclusions: For the first time, we have shown that baseline cfDNA may predict survival outcome in early stage CC pts treated with NACT. Pending confirmation in larger series, testing for cfDNA at baseline could help select high-risk pts who may benefit from FOxTROT-like, NACT treatment strategies. While analysis of ctDNA in this setting did not appear useful to predict prognosis, these results might be secondary to the small sample size.

35 Background: Imaging-based response to systemic therapies in metastatic prostate cancer is still challenging. The aim of this study was to retrospectively investigate the association between Prostate-Specific Membrane Antigen (PSMA) expression changes on 68Ga PSMA PET/CT and the response to treatment following the start of taxane-based chemotherapies (docetaxel or cabazitaxel) in both metastatic hormonosensitive (mHSPC) and castration-resistant prostate cancer (mCRPC) patients. Methods: We retrospectively reviewed all 68Ga-PSMA-11 PET/CT scans performed at our institution from November 2014 to June 2020. We included mHSPC and mCRPC patients with a baseline 68Ga-PSMA PET/CT performed < 2 months before, and a second 68Ga-PSMA PET/CT performed < 3 months after docetaxel or cabazitaxel (with no modification in therapy between scans). The biological data was used to distinguish PSA-non-responders (increasing PSA or decreasing PSA by < 50% from pretherapy level) and PSA-responders (decreasing PSA > 50% following the start of therapy or the peak thereafter). The PSMA PET/CT response was assessed visually by two independent nuclear medicine physicians blinded to clinical data and patient outcomes. Patients were classified as PSMA-non-responders (≥1 new PSMA-expressing metastases, majority of PSMA-expressing metastases increasing in intensity, or stable PSMA-expression of the disease) or PSMA-responders (complete disappearance of pathologic PSMA uptake, or majority of PSMA-expressing metastases decreasing in intensity). Majority of lesions was defined as > 50% of registered lesions. Descriptive statistics and measures of associations (two-sided Fisher’s exact test and Phi coefficient) were calculated. Results: A total of 37 patients were included (8 mHSPC and 29 mCRPC), 21 patients under docetaxel and 16 cabazitaxel. All patients received at least 3 cycles [median 6 (range 3-10)]. The mean time (±standard deviation) between the first 68Ga-PSMA PET/CT and the start of therapy was 22±16 days. The mean time between the the last cycleand the second 68Ga-PSMA PET/CT was 36±27 days. PSA-response and PSMA-response were concordant in 95% of cases with 18 patients PSA/PSMA-non-responders and 17 PSA/PSMA-responders (Phi = 0.90, p = 0.0001). Two discordant patients presented with PSMA-response but PSA-non-response. No isolated PSMA flare was observed, as PSA-response was always associated with a decrease in PSMA-expression on the second PET/CT. Conclusions: This retrospective study suggests PSMA expression changes on PET/CT at least after 3 cycles of chemotherapy (docetaxel or cabazitaxel) are strongly associated with PSA response. No flare phenomenon was found at this evaluation. Prospective studies are needed to better define the potential role of PSMA-PET/CT in response assessment.

Molecular imaging of metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer reveals marked intra- and interpatient heterogeneity in HER2 mapping, which correlates with clinical outcome under T-DM1 therapy.Only human epidermal growth factor receptor (HER)2 status determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) has been validated to predict efficacy of HER2-targeting antibody-drug-conjugate trastuzumab emtansine (T-DM1). We propose molecular imaging to explore intra-/interpatient heterogeneity in HER2 mapping of metastatic disease and to identify patients unlikely to benefit from T-DM1.HER2-positive mBC patients with IHC3+ or FISH a parts per thousand yen2.2 scheduled for T-DM1 underwent a pretreatment HER2-positron emission tomography (PET)/computed tomography (CT) with Zr-89-trastuzumab. [F-18]2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT was performed at baseline and before T-DM1 cycle 2. Patients were grouped into four HER2-PET/CT patterns according to the proportion of FDG-avid tumor load showing relevant Zr-89-trastuzumab uptake (> blood pool activity): patterns A and B were considered positive (> 50% or all of the tumor load 'positive'); patterns C and D were considered negative (> 50% or all of the tumor load 'negative'). Early FDG-PET/CT was defined as nonresponding when > 50% of the tumor load showed no significant reduction of FDG uptake (In the 56 patients analyzed, 29% had negative HER2-PET/CT while intrapatient heterogeneity (patterns B and C) was found in 46% of patients. Compared with RECIST1.1, respective NPV/PPV for HER2-PET/CT were 88%/72% and 83%/96% for early FDG-PET/CT. Combining HER2-PET/CT and FDG-PET/CT accurately predicted morphological response (PPV and NPV: 100%) and discriminated patients with a median TTF of only 2.8 months [n = 12, 95% confidence interval (CI) 1.4-7.6] from those with a TTF of 15 months (n = 25, 95% CI 9.7-not calculable).Pretreatment imaging of HER2 targeting, combined with early metabolic response assessment holds great promise for improving the understanding of tumor heterogeneity in mBC and for selecting patients who will/will not benefit from T-DM1.NCT01565200.

Purpose: Peptide receptor radionuclide therapy with 177Lu-DOTATATE has become a standard treatment modality in neuroendocrine tumours (NETs). No consensus has yet been reached however regarding the absorbed dose threshold for lesion response, the absorbed dose limit to organs-at-risk, and the optimal fractionation and activity to be administered. This is partly due to a lack of uniform and comparable dosimetry protocols. The present article details the development of an organ-at-risk dosimetry procedure, which could be implemented and used routinely in a clinical context. Methods: Forty-seven patients with NETs underwent 177Lu-DOTATATE therapy. Three SPECT/CT images were acquired at 4, 24 and 144–192 h post-injection. Three blood samples were obtained together with the SPECT/CT acquisitions and 2 additional samples were obtained around 30 min and 1 h post-injection. A bi-exponential fit was used to compute the source organ time-integrated activity coefficients. Coefficients were introduced into OLINDA/EXM software to compute organ-at-risk absorbed doses. Median values for all patients were computed for absorbed dose coefficient D/A0 and for late effective half-life T1/2eff for kidneys, spleen and red marrow. Results: Dosimetry resulted in a median[interquartile range] of 0.78[0.35], 1.07[0.58] and 0.028[0.010] Gy/GBq for D/A0 and of 55[9], 71[9] and 52[18] h for T1/2eff for kidneys, spleen and red marrow respectively. Conclusions: A dosimetry procedure for organs-at-risk in 177Lu-DOTATATE therapy based on serial SPECT/CT images and blood samples can be implemented routinely in a clinical context with limited patient burden. The results obtained were in accordance with those of other centres., SCOPUS: ar.j, info:eu-repo/semantics/published

Predictive biomarkers are eagerly awaited in advanced colorectal cancer (aCRC). Targeted sequencing performed on tumor and baseline plasma samples in 20 patients with aCRC treated with regorafenib identified 89 tumor-specific mutations of which ≥50% are also present in baseline plasma. Droplet digital PCR (ddPCR) assays were optimized to monitor circulating tumor DNA (ctDNA) levels in plasmatic samples collected throughout the treatment course and showed the importance of using the absolute value for ctDNA rather than the mutant/wild type ratio in monitoring the therapy outcome. High baseline cell free DNA (cfDNA) levels are associated with shorter overall survival (OS) (HR 7.38, P=0.001). An early increase (D14) in mutated copies/mL is associated with a significantly worse PFS (HR 6.12, P=0.008) and OS (HR 8.02, P=0.004). These data suggest a high prognostic value for early ctDNA level changes and support the use of blood-born genomic markers as a tool for treatment., SCOPUS: ar.j, info:eu-repo/semantics/published

This study aimed to validate the prognostic value of baseline whole-body metabolic active tumor volume (WB-MATV) and total lesion glycolysis (WB-TLG) measured with [18F]fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in a large cohort of chemorefractory metastatic colorectal cancer (mCRC) patients treated with multikinase inhibitors (MKI). The secondary objective of this study was to compare WB-MATV and WB-TLG respective prognostic values to commonly used clinical prognostic factors. Methods: Out of 238 patients pooled from two successive prospective multicenter trials investigating MKI in chemorefractory mCRC, 224 were considered suitable for analysis. The patients were retrospectively randomly assigned to a development set (n = 155 patients) and a validation set (n = 69 patients). WB-MATV and WB-TLG optimal cutoffs for prediction of overall survival (OS) were determined by Contal and O'Quigley's method. Univariate analyses were performed to assess the prognostic values of WB-MATV and WB-TLG. Multivariate analyses were performed for WB-MATV and WB-TLG along with clinical factors to identify the independent prognostic factors of OS. The prognostic weight for each parameter was obtained from the Cox's model. Results: WB-MATV and WB-TLG optimal cutoffs for OS prediction were 100 cm3 and 500 g, respectively. Univariate analyses showed that WB-MATV and WB-TLG parameters were strongly related to outcome in both the development and validation sets. In the validation set, the median OS was 5.2 months vs 12.8 months for high vs low WB-MATV (HR: 3.12, P < 0.001), and 4.7 months vs 13.9 months for high vs low WB-TLG (HR: 3.67, P < 0.001). The multivariate analyses identified that both high WB-MATV and WB-TLG were independent negative prognostic parameters for OS, with the highest prognostic weight among the well-known clinical prognostic factors (HR: 2.46 and 2.23, respectively, P < 0.001). Conclusion: Baseline WB-MATV and WB-TLG parameters were validated as strong prognosticators of outcome in a large cohort of chemorefractory mCRC patients treated with MKI. These parameters were identified as independent prognostic imaging biomarkers with the highest prognostic values among the commonly used clinical factors. These biomarkers should therefore be used to support the optimal therapeutic strategy., info:eu-repo/semantics/published

18F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) complements conventional imaging for diagnosing and staging lung cancer. Two literature-based meta-analyses suggest that maximum standardised uptake value (SUVmax) on PET has univariate prognostic value in nonsmall cell lung cancer (NSCLC). We analysed individual data pooled from 12 studies to assess the independent prognostic value of binary SUVmax for overall survival.After searching the published literature and identifying unpublished data, study coordinators were contacted and requested to provide data on individual patients. Cox regression models stratified for study were used.Data were collected for 1526 patients (median age 64 years, 60% male, 34% squamous cell carcinoma, 47% adenocarcinoma, 58% stage I–II). The combined univariate hazard ratio for SUVmax was 1.43 (95% CI 1.22–1.66) and nearly identical if the SUV threshold was calculated stratifying for histology. Multivariate analysis of patients with stage I–III disease identified age, stage, tumour size and receipt of surgery as independent prognostic factors; adding SUV (HR 1.58, 95% CI 1.27–1.96) improved the model significantly. The only detected interaction was between SUV and stage IV disease.SUV seems to have independent prognostic value in stage I–III NSCLC, for squamous cell carcinoma and for adenocarcinoma.