Early regression index (ERI) on MR images as response predictor in esophageal cancer treated with neoadjuvant chemo-radiotherapy: Interim analysis of the prospective ESCAPE trial.

PURPOSE: The early regression index (ERI) predicts treatment response in rectal cancer patients. Aim of current study was to prospectively assess tumor response to neoadjuvant chemo-radiotherapy (nCRT) of locally advanced esophageal cancer using ERI, based on MRI. MATERIAL AND METHODS: From January 2020 to May 2023, 30 patients with esophageal cancer were enrolled in a prospective study (ESCAPE). PET-MRI was performed: i) before nCRT (tpre); ii) at mid-radiotherapy, tmid; iii) after nCRT, 2-6 weeks before surgery (tpost); nCRT delivered 41.4 Gy/23fr with concurrent carboplatin and paclitaxel. For patients that skipped surgery, complete clinical response (cCR) was assessed if patients showed no local relapse after 18 months; patients with pathological complete response (pCR) or with cCR were considered as complete responders (pCR + cCR). GTV volumes were delineated by two observers (Vpre, Vmid, Vpost) on T2w MRI: ERI and other volume regression parameters at tmid and tpost were tested as predictors of pCR + cCR. RESULTS: Complete data of 25 patients were available at the time of the analysis: 3/25 with complete response at imaging refused surgery and 2/3 were cCR; in total, 10/25 patients showed pCR + cCR (pCR = 8/22). Both ERImid and ERIpost classified pCR + cCR patients, with ERImid showing better performance (AUC:0.78, p = 0.014): A two-variable logistic model combining ERImid and Vpre improved performances (AUC:0.93, p < 0.0001). Inter-observer variability in contouring GTV did not affect the results. CONCLUSIONS: Despite the limited numbers, interim analysis of ESCAPE study suggests ERI as a potential predictor of complete response after nCRT for esophageal cancer. Further validation on larger populations is warranted.

Extended nodal radiotherapy for prostate cancer relapse guided with [11C]-choline PET/CT: ten-year results in patients enrolled in a prospective trial.

AIMS: To report long-term outcomes of relapsed prostate cancer (PC) patients treated in a prospective single-arm study with extended-nodal radiotherapy (ENRT) and [11C]-choline positron emission tomography (PET)/computed tomography (CT)-guided simultaneous integrated boost (SIB) to positive lymph nodes (LNs). METHODS: From 12/2009 to 04/2015, 60 PC patients with biochemical relapse and positive LNs only were treated in this study. ENRT at a median total dose (TD) = 51.8 Gy/28 fr and PET/CT-guided SIB to positive LNs at a median TD = 65.5 Gy was prescribed. Median PSA at relapse was 2.3 (interquartile range, IQR:1.3-4.0) ng/ml. Median number of positive LNs: 2 (range: 1-18). Androgen deprivation therapy (ADT) was prescribed for 48 patients for a median of 30.7 (IQR: 18.5-43.1) months. RESULTS: Median follow-up from the end of salvage treatment was 121.8 (IQR: 116.1, 130.9) months; 3-, 5-, and 10-year BRFS were 45.0%, 36.0%, and 24.0%, respectively; DMFS: 67.9%, 57.2%, and 45.2%; CRFS: 62.9%, 53.9%, and 42.0%; and OS: 88.2%, 76.3%, and 47.9%, respectively. Castration resistance (p < 0.0001) and ≥ 6 positive LN (p = 0.0024) significantly influenced OS at multivariate analysis. Castration resistance (p < 0.0001 for both) influenced DMFS and CRFS in multivariate analysis. CONCLUSIONS: In PC relapsed patients treated with ENRT and [11C]-choline-PET/CT-guided SIB for positive LNs, with 10-year follow-up, a median Kaplan-Meier estimate CRFS of 67 months and OS of 110 months were obtained. These highly favorable results should be confirmed in a prospective, randomized trial.

Recurrence-specific supervised graph clustering for subtyping Hodgkin Lymphoma radiomic phenotypes.

The prediction at baseline of patients at high risk for therapy failure or recurrence would significantly impact on Hodgkin Lymphoma patients treatment, informing clinical practice. Current literature is extensively searching insights in radiomics, a promising framework for high-throughput imaging feature extraction, to derive biomarkers and quantitative prognostic factors from images. However, existing studies are limited by intrinsic radiomic limitations, high dimensionality among others. We propose an exhaustive patient representation and a recurrence-specific multi-view supervised clustering algorithm for estimating patient-to-patient similarity graph and learning recurrence probability. We stratified patients in two risk classes and characterize each group in terms of clinical variables.

r-Process elements from magnetorotational hypernovae.

Neutron-star mergers were recently confirmed as sites of rapid-neutron-capture (r-process) nucleosynthesis1-3. However, in Galactic chemical evolution models, neutron-star mergers alone cannot reproduce the observed element abundance patterns of extremely metal-poor stars, which indicates the existence of other sites of r-process nucleosynthesis4-6. These sites may be investigated by studying the element abundance patterns of chemically primitive stars in the halo of the Milky Way, because these objects retain the nucleosynthetic signatures of the earliest generation of stars7-13. Here we report the element abundance pattern of the extremely metal-poor star SMSS J200322.54-114203.3. We observe a large enhancement in r-process elements, with very low overall metallicity. The element abundance pattern is well matched by the yields of a single 25-solar-mass magnetorotational hypernova. Such a hypernova could produce not only the r-process elements, but also light elements during stellar evolution, and iron-peak elements during explosive nuclear burning. Hypernovae are often associated with long-duration γ-ray bursts in the nearby Universe8. This connection indicates that similar explosions of fast-spinning strongly magnetized stars occurred during the earliest epochs of star formation in our Galaxy.

PSMA-PET and micro-ultrasound potential in the diagnostic pathway of prostate cancer

To compare the diagnostic performance of 68Ga-PSMA PET/TC with PRI-MUS (prostate risk identification using micro-ultrasound) in the primary diagnosis of prostate cancer (PCa). Methods From September till December 2018, we prospectively enrolled 25 candidates to 68Ga-PSMA PET/TRUS (transrectal ultrasound) fusion biopsy and compared them with PRI-MUS. This included patients with persistently elevated PSA and/or PHI (prostate health index) suspicious for PCa, negative digital rectal examination, with either negative or contraindication to mpMRI, and at least one negative biopsy. The diagnostic performance of the two modalities was calculated based on pathology results. Results Overall, 20 patients were addressed to 68Ga-PSMA PET/TRUS fusion biopsy. Mean SUVmax and SUVratio for PCa lesions resulted significantly higher than in benign lesions (p = 0.041 and 0.011, respectively). Using optimal cut-off points, 68Ga-PSMA PET/CT demonstrated an overall accuracy of 83% for SUVmax ≥ 5.4 and 94% for SUVratio ≥ 2.2 in the detection of clinically significant PCa (GS ≥ 7). On counterpart, PRI-MUS results were: score 3 in nine patients (45%), score 4 in ten patients (50%), and one patient with score 5. PRI-MUS score 4 and 5 demonstrated an overall accuracy of 61% in detecting clinically significant PCa. Conclusion In this highly-selected patient population, in comparison to PRI-MUS, 68Ga-PSMA PET/CT shows a higher diagnostic performance (AU)

PSMA-PET and micro-ultrasound potential in the diagnostic pathway of prostate cancer.

PURPOSE: To compare the diagnostic performance of 68Ga-PSMA PET/TC with PRI-MUS (prostate risk identification using micro-ultrasound) in the primary diagnosis of prostate cancer (PCa). METHODS: From September till December 2018, we prospectively enrolled 25 candidates to 68Ga-PSMA PET/TRUS (transrectal ultrasound) fusion biopsy and compared them with PRI-MUS. This included patients with persistently elevated PSA and/or PHI (prostate health index) suspicious for PCa, negative digital rectal examination, with either negative or contraindication to mpMRI, and at least one negative biopsy. The diagnostic performance of the two modalities was calculated based on pathology results. RESULTS: Overall, 20 patients were addressed to 68Ga-PSMA PET/TRUS fusion biopsy. Mean SUVmax and SUVratio for PCa lesions resulted significantly higher than in benign lesions (p = 0.041 and 0.011, respectively). Using optimal cut-off points, 68Ga-PSMA PET/CT demonstrated an overall accuracy of 83% for SUVmax ≥ 5.4 and 94% for SUVratio ≥ 2.2 in the detection of clinically significant PCa (GS ≥ 7). On counterpart, PRI-MUS results were: score 3 in nine patients (45%), score 4 in ten patients (50%), and one patient with score 5. PRI-MUS score 4 and 5 demonstrated an overall accuracy of 61% in detecting clinically significant PCa. CONCLUSION: In this highly-selected patient population, in comparison to PRI-MUS, 68Ga-PSMA PET/CT shows a higher diagnostic performance.

Interdisciplinaridad: un requerimiento esencial para la traslación de investigación en radiómica a la práctica clínica / Interdisciplinarity: an essential requirement for translation of radiomics research into clinical practice - a systematic review focused on thoracic oncologys

INTRODUCCIÓN: En los últimos años, se ha generado evidencia que demuestra el potencial que tiene la radiómica para futuras aplicaciones en numerosas situaciones clínicas, incluyendo la oncología torácica. Se han identificado varias razones metodológicas que justifican la inmadurez de los estudios sobre la minería de la imagen (basada en radiómica y en inteligencia artificial). No obstante, faltan datos sobre la influencia de la composición del equipo investigador sobre la calidad de las investigaciones en radiómica. OBJETIVOS: Esta revisión tiene como objetivo evaluar el carácter interdisciplinar dentro de los estudios sobre radiómica en oncología torácica, para evaluar su influencia sobre la calidad de la investigación (puntuación QUADAS-2) en el campo de la minería de la imagen. MÉTODOS: Se consideraron para inclusión estudios de radiómica con objetivos relacionados con la práctica clínica en oncología torácica. A continuación, se entrevistó a los autores responsables de la correspondencia de cada estudio seleccionado. El campo de conocimiento o el nivel educativo fue utilizado para evaluar el carácter interdisciplinar de los equipos investigadores. Después, todos los estudios fueron evaluados aplicando la previamente establecida puntuación QUADAS-2, asignando una fase de investigación de 0 a IV. RESULTADOS: En conjunto se incluyeron 27 estudios. La calidad de los estudios, basada en la puntuación QUADAS-2, fue baja (puntuación ≤ 5) en 8, moderada (= 6) en 12 y alta (≥ 7) en 7 artículos. Un equipo interdisciplinar (al menos 3 diferentes categorías de expertos) participó en la mitad de los estudios sin ningún tipo de confirmación y en todos los estudios con confirmación independiente. Los clínicos no participaron en los estudios fase 0, mientras que contribuyeron a todos los artículos clasificados como fase I y a 4 de 5 artículos clasificados como fase II con confirmación independiente. CONCLUSIONES: La composición del equipo de investigación influencia la calidad de las investigaciones en radiómica. También el incremento en el carácter interdisciplinar de los equipos de investigación aparentemente refleja el desarrollo de la investigación desde una fase temprana a una fase de mayor madurez y de mayor orientación clínica de la investigación

BACKGROUND: Recently, evidence has accumulated that demonstrates the potential for future applications of radiomics in many clinical settings, including thoracic oncology. Methodological reasons for the immaturity of image mining (radiomics and artificial intelligence-based) studies have been identified. However, data on the influence of the composition of the research team on the quality of investigations in radiomics are lacking. AIM: This review aims to evaluate the interdisciplinarity within studies on radiomics in thoracic oncology in order to assess its influence on the quality of research (QUADAS-2 score) in the image mining field. METHODS: We considered for inclusion radiomics investigations with objectives relating to clinical practice in thoracic oncology. Subsequently, we interviewed the corresponding authors. The field of expertise and/or educational degree was then used to assess interdisciplinarity. Subsequently, all studies were evaluated applying the QUADAS-2 score and assigned to a research phase from 0 to IV. RESULTS: Overall, 27 studies were included. The study quality according to the QUADAS-2 score was low (score ≤5) in 8, moderate (=6) in 12, and high (≥7) in 7 papers. An interdisciplinary team (at least 3 different expertise categories) was involved in half of the papers without any type of validation and in all papers with independent validation. Clinicians were not involved in phase 0 studies while they contributed to all papers classified as phase I and to 4/5 papers classified as phase II with independent validation. CONCLUSIONS: The composition of the research team influences the quality of investigations in radiomics. Also, growth in interdisciplinarity appears to reflect research development from the early phase to a more mature, clinically oriented stage of investigation

Correction to: Nuclear medicine services after COVID-19: gearing up back to normality.

The authors P. Orellana and N. El-Haj were inadvertently deleted in the original paper.

Interdisciplinarity: An essential requirement for translation of radiomics research into clinical practice -a systematic review focused on thoracic oncology. / Interdisciplinaridad: un requerimiento esencial para la traslación de investigación en radiómica a la práctica clínica.

BACKGROUND: Recently, evidence has accumulated that demonstrates the potential for future applications of radiomics in many clinical settings, including thoracic oncology. Methodological reasons for the immaturity of image mining (radiomics and artificial intelligence-based) studies have been identified. However, data on the influence of the composition of the research team on the quality of investigations in radiomics are lacking. AIM: This review aims to evaluate the interdisciplinarity within studies on radiomics in thoracic oncology in order to assess its influence on the quality of research (QUADAS-2 score) in the image mining field. METHODS: We considered for inclusion radiomics investigations with objectives relating to clinical practice in thoracic oncology. Subsequently, we interviewed the corresponding authors. The field of expertise and/or educational degree was then used to assess interdisciplinarity. Subsequently, all studies were evaluated applying the QUADAS-2 score and assigned to a research phase from 0 to IV. RESULTS: Overall, 27 studies were included. The study quality according to the QUADAS-2 score was low (score ≤5) in 8, moderate (=6) in 12, and high (≥7) in 7 papers. An interdisciplinary team (at least 3 different expertise categories) was involved in half of the papers without any type of validation and in all papers with independent validation. Clinicians were not involved in phase 0 studies while they contributed to all papers classified as phase I and to 4/5 papers classified as phase II with independent validation. CONCLUSIONS: The composition of the research team influences the quality of investigations in radiomics. Also, growth in interdisciplinarity appears to reflect research development from the early phase to a more mature, clinically oriented stage of investigation.

EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees†.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

Combined PET/MRI: Global Warming-Summary Report of the 6th International Workshop on PET/MRI, March 27-29, 2017, Tübingen, Germany.

The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tübingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we are in a position to describe the in vivo nature of disease processes, metabolism, evolution of cancer and the monitoring of response to pharmacological interventions and therapies. As such, PET/MRI is a key to advancing medicine and patient care.

Liver metastases from prostate cancer at 11C-Choline PET/CT: a multicenter, retrospective analysis.

AIM: During our daily clinical practice using 11C-Choline PET/CT for restaging patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but significant occurrence of hypodense hepatic lesions with a different tracer uptake. Thus, we decided to evaluate the possible correlation between rPCa and these lesions as possible hepatic metastases. MATERIALS AND METHODS: We retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse after a radical treatment (surgery and/or radiotherapy). Among these, patients with a second tumor or other benign hepatic diseases were excluded. All patients underwent 11C-Choline PET/CT during the standard restaging workup of their disease. We analyzed CT images to evaluate the presence of hypodense lesions and PET images to identify the relative tracer uptake. In accordance to the subsequent oncological history, five clinical scenarios were recognized [Table 1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence of previously unknown hepatic round hypodense areas at ldCT with normal rim uptake (Group B); evidence of previously known hepatic round hypodense areas at ldCT stable over time and with normal rim uptake (Group C); evidence of previously known hepatic round hypodense areas at ldCT, in a previous PET/CT scan, with or without rim uptake and significantly changing over time in terms of size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT with or without rim uptake confirmed as prostate liver metastases by histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical evaluation (Group E). We evaluated the correlation with PSA level at time of scan, rim SUVmax and association with local relapse or non-hepatic metastases (lymph nodes, bone, other parenchyma). RESULTS: Five hundred and forty-two consecutive patients were retrospectively enrolled. In 140 of the 542 patients more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193). CONCLUSION: Our results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.

Real-life management and outcome of thyroid carcinoma-related bone metastases: results from a nationwide multicenter experience.

PURPOSE AND PATIENTS: The M.O.S.CA.TI. (Metastases of the Skeleton from CArcinoma of the ThyroId) is a multicenter, retrospective study investigating the real-life outcome and management of bone metastases (BM) in 143 patients (63 M, 80 F; median age 64 years, range 11-87) with differentiated thyroid carcinoma (DTC). RESULTS: Radio-active iodine (RAI) treatment was performed in 131 patients (91.6%), surgical approach and/or external radiotherapy in 68 patients (47.6%), and anti-resorptive bone-active drugs in 32 patients (22.4%; in 31 zoledronate and in one denosumab). At the start of treatment, 24 patients (75.0%) receiving anti-resorptive bone-active drugs had at least one clinical skeletal-related event (SRE) (p < 0.001). One or more clinical SREs (pathological fractures and/or malignant hypercalcemia and/or spinal cord compression) developed in 53 patients (37.1%). Development of SREs was significantly associated with metachronous BM (hazard ratio (HR) 2.04; p = 0.04), localization of BM to cervical spine (HR 3.89; p = 0.01), and lack of avid RAI uptake (HR 2.66; p = 0.02). Thirty-nine patients (27.3%) died in correlation with development of SREs (HR 6.97; p = 0.006) and localization of BM to the hip (HR 3.86; p = 0.02). Moreover, overall mortality was significantly decreased by RAI therapy (HR 0.10; p = 0.02), whereas no significant effects were induced by bone-active drugs (p = 0.36), external radiotherapy (p = 0.54), and surgery (p = 0.43) of BM. CONCLUSIONS: SREs are very frequent in BM from DTC and they impact patient survival. In the real life, the use of bone-active drugs is currently limited to zoledronate in patients with pre-existing SREs. In this clinical setting, RAI therapy, but not zoledronate, decreased mortality.

PET Radiomics in NSCLC: state of the art and a proposal for harmonization of methodology.

Imaging with positron emission tomography (PET)/computed tomography (CT) is crucial in the management of cancer because of its value in tumor staging, response assessment, restaging, prognosis and treatment responsiveness prediction. In the last years, interest has grown in texture analysis which provides an "in-vivo" lesion characterization, and predictive information in several malignances including NSCLC; however several drawbacks and limitations affect these studies, especially because of lack of standardization in features calculation, definitions and methodology reporting. The present paper provides a comprehensive review of literature describing the state-of-the-art of FDG-PET/CT texture analysis in NSCLC, suggesting a proposal for harmonization of methodology.

Position statement on radiopharmaceutical production for clinical trials.

The EU regulation 536/2014 aims to facilitate the experimental use of diagnostic radiopharmaceuticals in particular for GMP requirements and needs to be applied in EU countries. As definitely clarified by this survey, the application is still far from being completed due to national restrictions that are conflicting with the content of the above EU regulation. Although the nuclear medicine centers are obliged to be compliant with national regulatory, national authorities have to be required to work towards full application of the regulation. On the other hand, an update of 536/2014 that includes therapeutic radiopharmaceuticals would also be beneficial to a rational and safe advance of nuclear medicine.