Programmed death-ligand 1 (PD-L1) immunohistochemistry is a predictive biomarker for anti-PD-(L)1 therapy in non-small cell lung cancer (NSCLC). It is not a reliable predictor of clinical benefit with non-invasive imaging providing a potential solution. We present the PECan study, the aim of which to assess the relationship of [99mTc]-labeled anti-PD-L1 single-domain antibody (NM-01) single-photon emission computed tomography (SPECT)/CT with metabolic response to anti-PD-(L)1.

PD-L1 tumour proportion score (TPS) measured using SP263 assay. [99mTc]NM-01 SPECT/CT and [18F]FDG PET/CT performed before and 9-weeks following pembrolizumab with/without chemotherapy in patients with advanced NSCLC. Tumor (T) to blood pool (BP) maximum region of interest (ROImax) measurements performed in primary and metastatic lesions using SPECT/CT images.

Fifteen patients were included (median age 63 years, 9 male). Intertumoural heterogeneity evident in 10(67%) patients. Mean [99mTc]NM-01 T:BP demonstrated moderate correlation with PD-L1 TPS (r = 0.45, p < 0.05). Depth of [18F]FDG PET/CT metabolic response at 9-weeks (n = 13), correlated strongly with baseline [99mTc]NM-01 T:BP (r = -0.73, p < 0.05), but only moderately with PD-L1 TPS (r = -0.46, p = 0.06).

[99mTc]NM-01 SPECT/CT allows non-invasive quantification of PD-L1 in primary tumour and metastases in NSCLC. [99mTc]NM-01 uptake moderately correlates with PD-L1 immunohistochemistry, determines heterogeneity, and is associated with early metabolic response to anti-PD-1 pembrolizumab.

PD-L1 Expression in Cancer (PECan) study (NCT04436406), registered 18 June 2020 https://clinicaltrials.gov/ct2/show/NCT04436406.

Assessing treatment response in neuroendocrine tumors (NET) remains a significant challenge due to their typically indolent growth and heterogenity, the frequent occurrence of disease stabilization rather than tumor shrinkage after therapy, and the inherent limitations of conventional imaging criteria. While molecular imaging-primarily somatostatin receptor (SST) PET/CT-has improved lesion detection, the absence of standardized response criteria limits its clinical utility and prevents its use as full replacement of conventional imaging. Emerging strategies, including revised thresholds for dimensional changes, criteria evaluating different features, such as lesions' density and functional tumor volumes, offer potential improvements in response evaluation but require further validation for routine clinical implementation. This review examines the current challenges in assessing NET treatment response, evaluates the strengths and limitations of available imaging modalities, and discusses emerging approaches and future directions for optimizing therapeutic monitoring in the heterogeneous panorama of NET.

Interventional radiology (IR) is a super specialised branch where imaging modalities are employed to guide disease specific diagnostic and therapeutic interventions. IR interventions have gained popularity in various oncological and non-oncological indications due to it's ability to effectively diagnose the disease and direct specific targeted treatment. Hybrid imaging using PET CT and PET MRI combines the best of morphological and functional informations and offers improved sensitivity and specificity for detection of lesion; helps in accurate mapping of tumour burden, thereby aiding in planning curative vs palliative intent intervention; more accurate response evaluation to plan redo session in cases of residual / recurrent disease or for follow up evaluation and for prognostication and predicting response. Albeit visual analysis of PET images by specialist is most commonly performed for reading PET scans, PET has a remarkable capability to provide quantitative information. The present review provides a comprehensive assessment of the role of various aspects of quantitative PET parameters in assessing the efficacy of IR interventions. The insights provided will help clinicians, researchers, and medical professionals understand the role of PET imaging in advancing patient care and enhancing the therapeutic outcomes of IR procedures.

Cisplatin-based chemoradiation (CRT) plus brachytherapy for locally advanced cervical cancer (LACC) is standard. Intrinsic overexpression of ribonucleotide reductase (RNR) may enhance DNA damage repair from CRT. We report on outcomes of adding RNR inhibitor, triapine (T), to CRT.

NRG-GY006 is an open-label randomized phase III trial. FIGO 2009 LACC (stages IB2, II, IIIB or IVA) without para-aortic nodal involvement or stages II-IV vaginal cancer were eligible. Random assignment to CRT or in combination with thrice-weekly T (CRT + T) occurred. Radiation consisted of either 3D conformal (3DCRT) or image-guided intensity modulated RT (IG-IMRT) followed by intracavitary brachytherapy. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was secondary. Exploratory endpoints included complete metabolic response rate on post treatment PET/CT imaging and comparative toxicity and outcomes for 3DCRT vs. IG-IMRT.

Four-hundred-fifty patients were randomized including 448 eligible (224 in CRT and 224 in CRT + T). Median age was 47 (range 23-85). The majority had cervical cancer (93.3 %) with squamous histology (82 %). 52 % had FIGO stage II disease. Racial/ethnic distribution included non-Hispanic white (53.8 %), black (15.2 %) and Hispanic/Latina (22.5 %). At randomization, IG-IMRT was planned in 74.3 % and HDR brachytherapy in 98.2 %. No differences in Grade 3-5 toxicities were observed: CRT: 52 % and CRT + T: 49 %, with two G5 toxicities (cardiac arrest and acidosis) in the CRT + T arm. The median patient follow-up was 28 months (IQR 15-45). HR for death was 1.018 (95 % CI 0.634-1.635) while HR for progression was 1.021 (95 % CI 0.694-1.501).

Triapine added to CRT did not improve OS.

The purpose of this study was to assess the prognostic value of 18F-FDG PET parameter variation between baseline and 42 Gy (PET2) of radiochemotherapy at 6 mo and 1 y of evaluation in patients with stage III inoperable nonsmall cell lung cancer based on RECIST 1.1. Methods: In total, 158 patients in a prospective multicenter phase II/III study were analyzed. Patients were randomized into 2 groups: an experimental arm (group A) and a standard arm (group B). Patients from group A with residual metabolism on PET2 (group A+) at 42 Gy received a radiation boost (74 Gy). Patients without residual uptake on 18F-FDG PET at 42 Gy (group A-) and patients in group B received a standard radiotherapy dose (66 Gy). We compared group A with group B. The 18F-FDG PET parameters SUVmax, SUVmean, SUVpeak, peak SUV normalized on lean body mass, mean SUV normalized on lean body mass, total lesion glycolysis, total metabolic tumor volume (MTV) (tumor and nodes), and tumor MTV were measured. All patients were evaluated with RECIST 1.1 using CT at 6 mo and 1 y after radiochemotherapy. Progression-free survival and overall survival were evaluated. Results: Except for the radiotherapy dose (P < 0.001), patient demographic characteristics were similar between the 2 groups (A vs. B). All 18F-FDG PET uptake and volume parameter measurements were correlated. Therefore, only the change in SUVmax (ΔSUVmax) and total MTV were selected for the analysis. There was no significant difference in any variable between the 2 groups. In the multivariate analysis, ΔSUVmax appeared to be the most important prognostic factor for overall survival, and SUVmax of PET2 appeared to be the most important prognostic factor for progression-free survival. Conclusion: 18F-FDG PET at 42 Gy can be used to identify good responders to radiochemotherapy in patients with inoperable stage III nonsmall cell lung cancer. The SUVmax of PET2 and ΔSUVmax are independent prognostic factors.

Neoadjuvant immunotherapy has become the new standard of care for stage III melanoma. This study sought to describe the metabolic changes seen with fludeoxyglucose-18-positron emission tomography (FDG-PET) following neoadjuvant immunotherapy in patients with melanoma and explore associations with pathological response and recurrence-free survival (RFS).

Data from patients with macroscopic stage III nodal melanoma treated with neoadjuvant checkpoint inhibitor therapy were pooled from five melanoma centers. All patients underwent baseline and preoperative FDG-PET and CT assessments, and all had surgery. Pathological response was determined using the International Neoadjuvant Melanoma Consortium criteria, radiological response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and FDG-PET response using European Organization for Research and Treatment of Cancer (EORTC) criteria. The primary endpoint was to explore the associations of metabolic and radiological responses with pathological response; secondary endpoints were RFS outcomes stratified by each response category.

115 patients were included, 69% male, median age 59 years (27-92), 43% BRAF mutant, and median follow-up was 22.2 months (95% CI 13.7 to 26.4). 40 patients received anti-PD-1 monotherapy, 20 patients received pembrolizumab combined with lenvatinib, and 55 patients received ipilimumab and nivolumab. The major pathological response (MPR) rate was 62%, and the pathological complete response rate was 51%. RECIST response underestimated pathological response; patients achieving RECIST stable disease (38%) had a 50% chance of achieving MPR. The FDG-PET metabolic response rate was 73%, with most achieving an MPR (80%), especially in patients with a complete metabolic response (CMR, 96% MPR). A small proportion of patients (10%) had stable metabolic disease on FDG-PET, and all these patients were non-MPR. Patients with progressive metabolic disease were also in the majority non-MPR (79%). Patients with MPR, complete response/partial response on CT, and CMR/partial metabolic response on FDG-PET had a favorable 24-month RFS (95.6%, 97.3%, and 93.7%, respectively), with FDG-PET able to identify a greater proportion of patients with favorable progression-free survival (PFS) than pathology or CT (73%, 62%, and 43%, respectively).

Neoadjuvant immunotherapy has high FDG-PET response rates in melanoma. FDG-PET response associates with pathological response and confers impressive RFS, suggesting this could be an important clinical tool.

The phase I induction trial (NCT04287894) assessed the feasibility and safety of induction immunotherapy (IIT) prior to concurrent chemoradiotherapy (cCRT) in patients with locally advanced non-small cell lung cancer (NSCLC).

Patients with unresectable stage II/III NSCLC were eligible for inclusion. Patients received either one cycle of tremelimumab (75 mg) with two cycles of durvalumab (1,500 mg) in cohort I, one cycle of tremelimumab (300 mg) with two cycles of durvalumab in cohort II, or one cycle of tremelimumab (300 mg) with one cycle of durvalumab in cohort III. After IIT, a comprehensive radiological and pathological restaging was performed followed by cCRT. The combined primary endpoint was the feasibility and safety of IIT-cCRT.

Fifteen of 17 included patients were treated per protocol. IIT-cCRT was completed in 13 of the 15 patients within the predefined feasibility criteria. Grade ≥3 immune-related adverse events occurred in seven of the 15 patients, of which six were treated in the high-dose tremelimumab cohorts, thereby violating the safety criteria in cohorts II and III. The low-dose tremelimumab cohort (I) complied with safety criteria. Eleven patients had multilevel N2 or N3 disease at baseline; eight of these patients were downstaged to either N0/N1 or single-level N2 after IIT. Multiparametric MRI accurately identified nodal downstaging in all seven patients.

Induction with high-dose tremelimumab plus durvalumab prior to cCRT in unresectable locally advanced NSCLC was associated with unacceptable toxicity, although IIT resulted in clinically relevant nodal downstaging in eight of the 11 patients with baseline multilevel N2 or N3 disease. Multiparametric MRI showed potential for evaluating treatment response.

Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer characterized by its unique growth patterns, presenting substantial diagnostic challenges. With the shift toward immunotherapy for MPM treatment, assessing therapeutic responses has become increasingly complex. Recent studies indicate that FDG PET/CT may provide more effective response criteria compared to traditional CT-based methods. This review emphasizes the important role of PET/CT in offering deep insights into the disease state and monitoring treatment responses. It also addresses the challenges associated with current imaging criteria, particularly the nonspecificity of FDG uptake that may represent inflammatory responses following treatments or procedures rather than tumor activity. Furthermore, the review discusses the potential of emerging radiopharmaceuticals and advanced volumetric assessments, discussing their implications for improving diagnostic accuracy and treatment evaluation in MPM.

Radiation treatments [radiotherapy and radionuclide treatments (RNTs)] are one of the main and effective treatment modalities of cancer. Globally, the number of cancer patients treated with radionuclides are much less as compared to number of radiotherapy cases but with the development of new radiotracers, most notably 177 Lu and 225 Ac-labeled prostate-specific membrane antigen ligands, and 223 Ra-dichloride for prostate cancer and 177 Lu-somatostatin analogs for neuroendocrine tumors, there is a significant rise in RNTs in the last decade. As therapeutic applications of nuclear medicine is on the rise, the aim of this review is to summarize biological responses to radiation treatments and molecular mechanisms of radiation-induced cell death (e.g. ionization, DNA damages such as double-strand breaks, DNA repair mechanisms, types of cell deaths such as apoptosis, necrosis, and immunogenic cell death), histopathological changes with radiation treatments, and role of PET imaging in RNTs as part of radionuclide theranostics for selecting and planning patients for RNTs, dosimetry, predicting and assessing response to RNTs, predicting toxicities, and other possible PET findings which may be seen after RNTs such as activation of immune system.

A considerable proportion of metastatic melanoma (mM) patients do not respond to immune checkpoint inhibitors (ICIs). There is a great need to develop noninvasive biomarkers to detect patients, who do not respond to ICIs early during the course of treatment. The aim of this study was to evaluate the role of early [18F]2fluoro-2-deoxy-D-glucose PET/CT (18F-FDG PET/CT) at week four (W4) and other possible prognostic biomarkers of survival in mM patients receiving ICIs.

. In this prospective noninterventional clinical study, mM patients receiving ICIs regularly underwent 18F-FDG PET/CT: at baseline, at W4 after ICI initiation, at week sixteen and every 16 weeks thereafter. The tumor response to ICIs at W4 was assessed via modified European Organisation for Research and Treatment of Cancer (EORTC) criteria. Patients with progressive metabolic disease (PMD) were classified into the no clinical benefit group (no-CB), and those with other response types were classified into the clinical benefit group (CB). The primary end point was survival analysis on the basis of the W4 18F-FDG PET/CT response. The secondary endpoints were survival analysis on the basis of LDH, the number of metastatic localizations, and immune-related adverse events (irAEs). Kaplan-Meier analysis and univariate Cox regression analysis were used to assess the impact on survival.

Overall, 71 patients were included. The median follow-up was 37.1 months (952% CI = 30.1-38.0). Three (4%) patients had only baseline scans due to rapid disease progression and death prior to W4 18F-FDG-PET/CT. Fifty-one (72%) patients were classified into the CB group, and 17 (24%) were classified into the no-CB group. There was a statistically significant difference in median overall survival (OS) between the CB group (median OS not reached [NR]; 95% CI = 17.8 months - NR) and the no-CB group (median OS 6.2 months; 95% CI = 4.6 months - NR; p = 0.003). Univariate Cox analysis showed HR of 0.4 (95% CI = 0.18 - 0.72; p = 0.004). median OS was also significantly longer in the group with normal serum LDH levels and the group with irAEs and cutaneous irAEs.

Evaluation of mM patients with early 18F-FDG-PET/CT at W4, who were treated with ICIs, could serve as prognostic imaging biomarkers. Other recognized prognostic biomarkers were the serum LDH level and occurrence of cutaneous irAEs.

To investigate the predictive value of 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) PET/CT for evaluating primary tumor (PT) and lymph node (LN) responses after neoadjuvant programmed death-ligand 1 (PD-L1) blockade monotherapy in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC).

In the single-arm phase 1b NATION-1907 trial (NCT04215471), 23 patients with LA-ESCC received two cycles of neoadjuvant PD-L1 blockade Adebrelimab followed by surgery. Among these, 18 patients underwent [18F]FDG PET/CT scans both before immunotherapy and prior to surgery. Standardized uptake value corrected for lean body mass (SUL)-derived parameters, including SULmax and SULpeak, were documented for PTs and LNs. Lesions > 1cm3 were segmented using thresholds of 41% and 50% of SULmax, respectively, following European Association of Nuclear Medicine (EANM) guidelines, with metabolic tumor volume (MTV) and total lesion glycolysis (TLG) calculated. Percentage changes of all metabolic parameters were also recorded. Residual viable tumor ≤ 33% were classified as well-responders, whereas residual viable tumor > 33% were classified as poor-responders based on histological evaluation.

In the PT analysis, 10 patients were classified as PT well-responders and 8 as PT poor-responders. All post-treatment metabolic parameters, except MTV, were significantly lower in well-responders compared to poor-responders. The %ΔMTV, %ΔTLG were significantly higher in the poor-responder group (all P < 0.05). ROC curves indicated %ΔMTV41 exhibited optimum performance in predicting well-responders, with an AUC of 0.875 (cut-off: -31.01). Furthermore, %ΔMTV41 significantly predicted patients' recurrence-free survival (RFS) (P < 0.1). In the LN analysis, 7 LNs were classified as well-responders and 10 as poor-responders. Pre-treatment SULmax, SULpeak were significantly lower in poor-responders compared to well-responders. Post-treatment MTV50 and all percentage changes in parameters were significantly higher in the poor-responder group (all P < 0.05). Receiver operating characteristic curve (ROC) analysis indicated %ΔTLG50 had excellent predictive performance for well-responders, with an AUC of 1.000 (cut-off: -7.5). However, there was no significant correlation between the metabolic response evaluations for PTs and LNs.

The metabolic parameters of [18F]FDG PET/CT, particularly %ΔMTV and %ΔTLG, could effectively predict well-responders among both PTs and LNs to neoadjuvant PD-L1 blockade monotherapy in LA-ESCC, which may facilitate personalized immunotherapy and serve as a stratification tool in future larger-scale studies.

Malignant pleural mesothelioma (MPM) is the most frequent aggressive tumor affecting the pleura, accounting for over 38,000 deaths worldwide. It originates from the mesothelial cells and is mostly associated to asbestos exposure. Depending on the extent of the disease, the management of MPM varies from surgical intervention to a combination of systemic chemotherapy, immunotherapy, and radiation therapy. Major International scientific societies provide continuous updates on proper management of the disease, including recommendations on the optimal imaging algorithms, which are crucial for determining effective treatment options and optimizing clinical outcomes. However, despite the continuous efforts to improve patients' prognosis, median overall survival remains poor, ranging from 8 to 14 months. And even in case of initial response to treatment, local or distant recurrences represent almost a certainty, requiring appropriate imaging for the assessment of tumor sites. The aim of the present article is to illustrate the current status of imaging for staging and restaging of MPM, not forgetting most recent novelties in the diagnostic work-up of the disease.

18-Fluoro-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is a valuable imaging tool widely used in the management of cancer patients. Deep learning models excel at segmenting highly metabolic tumors but face challenges in regions with complex anatomy and normal cell uptake, such as the gastro-intestinal tract. Despite these challenges, it remains important to achieve accurate segmentation of gastro-intestinal tumors.

Here, we present an international multicenter comparative study between a novel organ-focused approach and a whole-body training method to evaluate the effectiveness of training data homogeneity in accurately identifying gastro-intestinal tumors. In the organ-focused method, the training data is limited to cases with intestinal tumors which makes the network trained with more homogeneous data and with stronger presence of intestinal tumor signals. The whole body approach extracts the intestinal tumors from the results of a model trained on the whole-body scans. Both approaches were trained using diffuse large B cell (DLBCL) patients from a large multi-center clinical trial (NCT01287741).

We report an improved mean(±std) Dice score of 0.78(±0.21) for the organ-based approach on the hold-out set, compared to 0.63(±0.30) for the whole-body approach, with the p-value of less than 0.0001. At the lesion level, the proposed organ-based approach also shows increased precision, recall, and F1-score. An independent trial was used to evaluate the generalizability of the proposed method to non-Hodgkin's lymphoma (NHL) patients with follicular lymphoma (FL).

Given the variability in structure and metabolism across tissues in the body, our quantitative findings suggest organ-focused training enhances intestinal tumor segmentation by leveraging tissue homogeneity in the training data, contrasting with the whole-body training approach, which, by its very nature, is a more heterogeneous data set.

The aim of this post hoc study was to assess the prognostic value of 18F-FDG PET/CT quantitative parameters recorded before and after treatment for anal canal neoplasm for the disease free survival.

Consecutive, previously untreated patients with histologically proved anal cancer, with 18F-FDG PET/CT pre- and 2 months post treatment were included. The following criteria were analyzed: baseline primary tumor lesion glycolysis (TLG), metabolic tumor volume (MTV), standardized tumor volume (SUV) max and mean, SUV normalized by lean body mass (SUL) max, mean and peak, variations between pre- and post-treatment examinations for SUVmax (Delta SUVmax), TLG (Delta TLG), MTV (Delta MTV), as well as post-treatment SULpeak and SUVmax for the primary tumor, and baseline sum of lesions TLG and MTV.

About 78 consecutive patients were included in this study. Median follow-up was 49 months. Baseline TLG, SUVmax, SULpeak, SULmax, sum of lesions for TLG and MTV, Delta SUVmax, and post-therapeutic SULpeak and SUVmax for the primary tumor, were statistically significant for disease free survival.

Pretherapeutic 18F-FDG PET/CT has a statistically significant prognostic value. The wide variability of results published in literature compels us to specifically explore the interest of uptake variations between pre- and post-treatment examinations.

Anti-epidermal growth factor receptor (EGFR) therapy (cetuximab) shows a limited clinical benefit for patients with locally advanced or recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), due to the frequent occurrence of secondary resistance mechanisms. Here we report that cetuximab-resistant HNSCC cells display a peroxisome proliferator-activated receptor alpha (PPARα)-mediated lipid metabolism reprogramming, with increased fatty acid uptake and oxidation capacities, while glycolysis is not modified. This metabolic shift makes cetuximab-resistant HNSCC cells particularly sensitive to a pharmacological inhibition of either carnitine palmitoyltransferase 1A (CPT1A) or PPARα in 3D spheroids and tumor xenografts in mice. Importantly, the PPARα-related gene signature, in human clinical datasets, correlates with lower response to anti-EGFR therapy and poor survival in HNSCC patients, thereby validating its clinical relevance. This study points out lipid metabolism rewiring as a non-genetic resistance-causing mechanism in HNSCC that may be therapeutically targeted to overcome acquired resistance to anti-EGFR therapy.

Immunotherapy is likely the most remarkable advancement in lung cancer treatment during the past decade. Although immunotherapy provides substantial benefits, their therapeutic responses differ from those of conventional chemotherapy and targeted therapy, and some patients present unique immunotherapy response patterns that cannot be judged under the current measurement standards. Therefore, the response monitoring of immunotherapy can be challenging, such as the differentiation between real response and pseudo-response. This review outlines the various tumor response patterns to immunotherapy and discusses methods for quantifying computed tomography (CT) and 18 F-fluorodeoxyglucose positron emission tomography (PET) in the field of lung cancer. Emerging technologies in magnetic resonance imaging (MRI) and non-FDG PET tracers are also explored. With immunotherapy responses, the role for imaging is essential in both anatomical radiological responses (CT/MRI) and molecular changes (PET imaging). Multiple aspects must be considered when assessing treatment responses using CT and PET. Finally, we introduce multimodal approaches that integrate imaging and nonimaging data, and we discuss future directions for the assessment and prediction of lung cancer responses to immunotherapy.

to assess the utility of response monitoring to enzalutamide by using [68Ga]Ga-PSMA PET in mCRPC patients treated with enzalutamide as first-line therapy.

patients underwent [68Ga]Ga-PSMA PET less than 8 weeks before and 3 months after starting enzalutamide. On the basis of EAU/EANM criteria, patients were categorized as PSMA responders (PET-R) or PSMA non-responders (PET-NR), whilst, based on PSA, they were classified as biochemical responders (PSA-R) or non-responders (PSA-NR). Survival analysis was performed using the Cox regression hazard model and the Kaplan-Meier method.

69 patients were considered fully evaluable. We observed 47.8% of concordance between [68Ga]Ga-PSMA PET and PSA monitoring at 3 months after starting enzalutamide. For discordant cases, the PSA reduction has a weak impact on PFS and a significant impact on OS in PET-NR patients, whilst this change has no impact either for PFS and OS in PET-R ones.

[68Ga]Ga-PSMA PET could be a useful imaging tool for monitoring response to enzalutamide in mCRPC patients, being more informative than PSA in this setting, and possibly better guiding clinicians in therapeutic decisions.

Mucosal melanoma (MucM) is a rare cancer with a poor prognosis and low response rate to immune checkpoint inhibition (ICI) compared with cutaneous melanoma (CM). To explore the immune microenvironment and potential drivers of MucM's relative resistance to ICI drugs, we characterized 101 MucM tumors (43 head and neck [H&N], 31 female urogenital, 13 male urogenital, 11 anorectal, and 3 other gastrointestinal) using bulk RNA-Seq and immunofluorescence. RNA-Seq data show that MucM has a significantly lower IFN-γ signature levels than CM. MucM tumors of the H&N region show a significantly greater abundance of CD8+ T cells, cytotoxic cells, and higher IFN-γ signature levels than MucM from lower body sites. In the subcohort of 35 patients with MucM treated with ICI, hierarchical clustering reveals clusters with a high and low degree of immune infiltration, with a differential ICI response rate. Immune-associated gene sets were enriched in responders. Signatures associated with cancer-associated fibroblasts, macrophages, and TGF-β signaling may be higher in immune-infiltrated, but ICI-unresponsive tumors, suggesting a role for these resistance mechanisms in MucM. Our data show organ region-specific differences in immune infiltration and IFN-γ signature levels in MucM, with H&N MucM displaying the most favorable immune profile. Our study might offer a starting point for developing more personalized treatment strategies for this disease.

The systemic immune-inflammation index (SII) is an effective tool for predicting the prognosis of patients with cancer. However, its value in patients with locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) undergoing definitive chemoradiotherapy has yet to be addressed. Therefore, we aimed to retrospectively investigate the prognostic significance of the pretreatment SII on the survival outcomes of patients with unresectable LA-PDAC treated with concurrent chemoradiotherapy (C-CRT).

The study included 163 patients with LA-PDAC who had received C-CRT. Using receiver operating characteristic (ROC) curve analysis, the utility of a pre-C-CRT cutoff that could stratify survival results was investigated. The primary and secondary endpoints were the correlations between SII levels and overall survival (OS) and progression-free survival (PFS).

At a median follow-up period of 15 months (range: 3.2-94.5), the median OS and PFS rates for the entire group were 15.7 months (95% confidence interval [CI]: 13.4-17.9), and 7.8 months (95% CI: 6.1-9.4), respectively. We divided the patients into 2 SII cohorts based on the ROC curve analysis (area under the curve [AUC]: 71.9%; sensitivity: 68.9%; specificity: 66.7%): SII < 538 (N = 70) and SII ⩾ 538 (N = 93). Comparative survival analysis showed significantly inferior median OS (13.0 vs 25.4 months; P < .001) and PFS (7.0 vs 15.2 months; P = .003) in patients with SII ⩾ 538 compared with those with SII < 538 before treatment. In multivariate analyses, the Eastern Cooperative Oncology Group (ECOG) performance of 2, N1-2 lymph node, CA 19-9 > 90 U/mL, and SII ⩾ 538 status emerged as independent prognosticators of inferior OS and PFS.

Present results indicate that patients with unresectable LA-PDAC who underwent C-CRT and had a pretreatment SII ⩾ 538 had significantly worse OS and PFS outcomes compared with those with lower SII values.

This was a multicenter, single-arm, open-label, phase Ib/II study (NCT04255576), aimed to evaluate the efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone (GCTB). JMT103 (2 mg/kg) was administered subcutaneously every four weeks, with loading doses on days 8 and 15. The primary endpoint was the objective tumor response rate (OTR) based on best response, defined as the proportion of patients who achieved elimination of at least 90% of the giant cells or radiologic complete or partial response per the modified Inverse Choi density/size (mICDS) or modified European Organization for Research and Treatment of Cancer (mEORTC) within 12 weeks. Secondary endpoints included objective response rate (ORR) per mICDS and mEORTC, and safety. A total of 139 patients were enrolled, and 135 were analyzed for efficacy. OTR, determined by the independent review committee (IRC) was 93.3% (95% CI 87.7-96.9). Treatment-related adverse events occurred in 90 (64.7%) patients, with hypophosphatemia and hypocalcemia being the most common. No serious treatment-related adverse events were observed. Thus, JMT103 demonstrates potential as a therapeutic option for GCTB.

The assessment of response to therapy in prostate cancer (PCa) patients is an ongoing, open issue. Prostate-specific antigen has limitations, especially in advanced metastatic PCa, which often displays intratumor variability in terms of response to therapy. Conventional imaging (i.e. computerized tomography and bone scan) is of limited use for its low sensitivity and specificity. Positron-emission tomography (PET) with prostate-specific membrane antigen (PSMA) demonstrated higher sensitivity and specificity, and novel PSMA-based criteria have been recently proposed for treatment response, with promising results in different scenarios, from chemotherapy to radioligand therapy. PSMA-based criteria have been found to outperform the current RECIST 1.1 and Prostate Cancer Working Group 3 frameworks in describing the behavior of PCa, precisely assessing tumor phenotypes through molecular-imaging-derived parameters. This review critically explores the current evidence about the role of PSMA PET/computed tomography in the assessment of treatment response.

The advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment paradigm of lung cancer, resulting in notable enhancements in patient survival. Nevertheless, evaluating treatment response in patients undergoing immunotherapy poses distinct challenges due to unconventional response patterns like pseudoprogressive disease (PPD), dissociated response (DR), and hyperprogressive disease (HPD). Conventional response criteria such as the RECIST 1.1 may not adequately address these complexities. To tackle this issue, novel response criteria such as the iRECIST and imRECIST have been proposed, enabling a more comprehensive assessment of treatment response by incorporating additional scans and considering the best overall response even after radiologic progressive disease evaluation. Additionally, [18F]FDG PET/CT imaging has emerged as a valuable modality for evaluating treatment response, with various metabolic response criteria such as the PERCIMT, imPERCIST, and iPERCIST developed to overcome the limitations of traditional criteria, particularly in detecting pseudoprogression. A multidisciplinary approach involving oncologists, radiologists, and nuclear medicine specialists is crucial for effectively navigating these complexities and enhancing patient outcomes in the era of immunotherapy for lung cancer. In this review, we delineate the key components of these guidelines, summarizing essential aspects for radiologists and nuclear medicine physicians. Furthermore, we provide insights into how imaging can guide the management of individual lung cancer patients in real-world multidisciplinary settings.

The recently released EANM/SNMMI guideline, endorsed by several important clinical and imaging societies in the field of breast cancer (BC) care (ACR, ESSO, ESTRO, EUSOBI/ESR, EUSOMA), emphasized the role of [18F]FDG PET/CT in management of patients with no special type (NST) BC. This review identifies and summarizes similarities, discrepancies and novelties of the EANM/SNMMI guideline compared to NCCN, ESMO and ABC recommendations.

The EANM/SNMMI guideline was based on a systematic literature search and the AGREE tool. The level of evidence was determined according to NICE criteria, and 85 % agreement or higher was reached regarding each statement. Comparisons with NCCN, ESMO and ABC guidelines were examined for specific clinical scenarios in patients with early stage through advanced and metastatic BC.

Regarding initial staging of patients with NST BC, [18F]FDG PET/CT is the preferred modality in the EANM-SNMMI guideline, showing superiority as a single modality to a combination of contrast-enhanced CT of thorax-abdomen-pelvis plus bone scan in head-to-head comparisons and a randomized study. Its use is recommended in patients with clinical stage IIB or higher and may be useful in certain stage IIA cases of NST BC. In NCCN, ESMO, and ABC guidelines, [18F]FDG PET/CT is instead recommended as complementary to conventional imaging to solve inconclusive findings, although ESMO and ABC also suggest [18F]FDG PET/CT can replace conventional imaging for staging patients with high-risk and metastatic NST BC. During follow up, NCCN and ESMO only recommend diagnostic imaging if there is suspicion of recurrence. Similarly, EANM-SNMMI states that [18F]FDG PET/CT is useful to detect the site and extent of recurrence only when there is clinical or laboratory suspicion of recurrence, or when conventional imaging methods are equivocal. The EANM-SNMMI guideline is the first to emphasize a role of [18F]FDG PET/CT for assessing early metabolic response to primary systemic therapy, particularly for HER2+ BC and TNBC. In the metastatic setting, EANM-SNMMI state that [18F]FDG PET/CT may help evaluate bone metastases and determine early response to treatment, in agreement with guidelines from ESMO.

The recently released EANM/SNMMI guideline reinforces the role of [18F]FDG PET/CT in the management of patients with NST BC supported by extensive evidence of its utility in several clinical scenarios.

This study aimed to evaluate the measurement and prognostic ability of the SUVmax of whole-body tumors (SUVmaxwb) in non-small cell lung cancer (NSCLC) patients, comparing high-definition (HD) PET imaging with standard-definition (SD) PET imaging. Methods: The study included 242 consecutive NSCLC patients who underwent baseline 18F-FDG PET/CT from April 2018 to January 2021. Two imaging techniques were used: HD PET (using ordered-subsets expectation maximization with point-spread function modeling and time-of-flight techniques and smaller voxels) and SD PET (with ordered-subsets expectation maximization and time-of-flight techniques). SUVmaxwb was determined by measuring all the tumor lesions in the whole body, and tumor-to-background ratio (TBR) was calculated using the background SUVmean of various body parts. Results: The patient cohort had an average age of 68.3 y, with 59.1% being female. During a median follow-up of 29.6 mo, 83 deaths occurred. SUVmaxwb was significantly higher in HD PET than SD PET, with respective medians of 17.4 and 11.8. The TBR of 1,125 tumoral lesions was also higher in HD PET. Univariate Cox regression analysis showed that SUVmaxwb from both HD and SD PET were significantly associated with overall survival. However, after adjusting for TNM (tumor, node, metastasis) stage, only SUVmaxwb from SD PET remained significantly associated with survival. Conclusion: HD PET imaging in NSCLC patients yields higher SUVmaxwb and TBR, enhancing tumor visibility. Despite this, its prognostic value is less significant than SD PET after adjusting clinical TNM stage. Thus, consideration should be given to using HD PET reconstruction to increase tumor visibility, and SD PET is recommended for NSCLC patient prognostication and therapeutic evaluation, as well as for the classification of lung nodules.

Artificial intelligence can reduce the time used by physicians on radiological assessments. For 18F-fluorodeoxyglucose-avid lymphomas, obtaining complete metabolic response (CMR) by end of treatment is prognostic.

Here, we present a deep learning-based algorithm for fully automated treatment response assessments according to the Lugano 2014 classification. The proposed four-stage method, trained on a multicountry clinical trial (ClinicalTrials.gov identifier: NCT01287741) and tested in three independent multicenter and multicountry test sets on different non-Hodgkin lymphoma subtypes and different lines of treatment (ClinicalTrials.gov identifiers NCT02257567, NCT02500407; 20% holdout in ClinicalTrials.gov identifier NCT01287741), outputs the detected lesions at baseline and follow-up to enable focused radiologist review.

The method's response assessment achieved high agreement with the adjudicated radiologic responses (eg, agreement for overall response assessment of 93%, 87%, and 85% in ClinicalTrials.gov identifiers NCT01287741, NCT02500407, and NCT02257567, respectively) similar to inter-radiologist agreement and was strongly prognostic of outcomes with a trend toward higher accuracy for death risk than adjudicated radiologic responses (hazard ratio for end of treatment by-model CMR of 0.123, 0.054, and 0.205 in ClinicalTrials.gov identifiers NCT01287741, NCT02500407, and NCT02257567, compared with, respectively, 0.226, 0.292, and 0.272 for CMR by the adjudicated responses). Furthermore, a radiologist review of the algorithm's assessments was conducted. The radiologist median review time was 1.38 minutes/assessment, and no statistically significant differences were observed in the level of agreement of the radiologist with the model's response compared with the level of agreement of the radiologist with the adjudicated responses.

These results suggest that the proposed method can be incorporated into radiologic response assessment workflows in cancer imaging for significant time savings and with performance similar to trained medical experts.

Immune checkpoint inhibitors and BRAF-targeted therapy each improve survival in melanoma. Immune changes early during targeted therapy suggest the mechanisms of each drug class could work synergistically. In the non-comparative, randomized, phase 2 NeoTrio trial, we investigated whether targeted therapy could boost the proportion of patients achieving long-term recurrence-free survival with neoadjuvant immunotherapy in resectable stage III BRAFV600-mutant melanoma. Sixty patients (42% females) were randomized to pembrolizumab alone (n = 20), sequential therapy (dabrafenib plus trametinib followed by pembrolizumab; n = 20) or concurrent (triple) therapy (n = 20), followed by surgery and adjuvant therapy. The primary outcome was pathological response; secondary outcomes included radiographic response, recurrence-free survival, overall survival, surgical outcomes, peripheral blood and tumor analyses and safety. The pathological response rate was 55% (11/20; including six pathological complete responses (pCRs)) with pembrolizumab, 50% (10/20; three pCRs) with sequential therapy and 80% (16/20; ten pCRs) with concurrent therapy, which met the primary outcome in each arm. Treatment-related adverse events affected 75-100% of patients during neoadjuvant treatment, with seven early discontinuations (all in the concurrent arm). At 2 years, event-free survival was 60% with pembrolizumab, 80% with sequential therapy and 71% with concurrent therapy. Recurrences after major pathological response were more common in the targeted therapy arms, suggesting a reduction in response 'quality' when targeted therapy is added to neoadjuvant immunotherapy. Risking the curative potential of immunotherapy in melanoma cannot be justified. Pending longer follow-up, we suggest that immunotherapy and targeted therapy should not be combined in the neoadjuvant setting for melanoma. ClinicalTrials.gov registration: NCT02858921 .

[18F]FDG PET denoising by SubtlePET™ using deep learning artificial intelligence (AI) was previously found to induce slight modifications in lesion and reference organs' quantification and in lesion detection. As a next step, we aimed to evaluate its clinical impact on [18F]FDG PET solid tumour treatment response assessments, while comparing "standard PET" to "AI denoised half-duration PET" ("AI PET") during follow-up.

110 patients referred for baseline and follow-up standard digital [18F]FDG PET/CT were prospectively included. "Standard" EORTC and, if applicable, PERCIST response classifications by 2 readers between baseline standard PET1 and follow-up standard PET2 as a "gold standard" were compared to "mixed" classifications between standard PET1 and AI PET2 (group 1; n = 64), or between AI PET1 and standard PET2 (group 2; n = 46). Separate classifications were established using either standardized uptake values from ultra-high definition PET with or without AI denoising (simplified to "UHD") or EANM research limited v2 (EARL2)-compliant values (by Gaussian filtering in standard PET and using the same filter in AI PET). Overall, pooling both study groups, in 11/110 (10%) patients at least one EORTCUHD or EARL2 or PERCISTUHD or EARL2 mixed vs. standard classification was discordant, with 369/397 (93%) concordant classifications, unweighted Cohen's kappa = 0.86 (95% CI: 0.78-0.94). These modified mixed vs. standard classifications could have impacted management in 2% of patients.

Although comparing similar PET images is preferable for therapy response assessment, the comparison between a standard [18F]FDG PET and an AI denoised half-duration PET is feasible and seems clinically satisfactory.

We aimed to develop a nomogram able to predict treatment failure, skeletal events, and overall survival (OS) in patients with castration-resistant prostate cancer with bone metastases (CRPC-BM) treated with Radium-223 dichloride (223Ra).

Patients from the Castilla-La Mancha Spanish region were prospectively included in the ChoPET-Rad multicenter study from January 2015 to December 2022. Patients underwent baseline, interim, and end-of-treatment bone scintigraphy (BS) and 18F-Fluorocholine PET/CT (FCH PET/CT) scans, obtaining multiple imaging radiomics as well as clinical and biochemical variables during follow-up and studying their association with the previously defined end-points. Survival analysis was performed using the Kaplan-Meier method and Cox regression. Multivariate logistic and Cox regression models were calculated, and these models were depicted by means of nomograms.

Median progression-free survival (PFS) and OS were 4 and 14 months (mo), respectively. The variables that showed independent and significant association with therapeutic failure were baseline alkaline phosphatase (AP) levels (p = 0.022) and the characteristics of BM on the CT portion of PET/CT (p = 0.017). In the case of OS, the significant variables were therapeutic failure (p = 0.038), the number of lines received after 223Ra (p < 0.001), average SUVmax (p = 0.002), bone marrow infiltration in FCH PET/CT (p = 0.006), and interim FCH PET/CT response (p = 0.048). Final nomograms included these variables, showing good discrimination among the 100 patients included in our study. In the study of skeletal events, only OS showed a significant association in the multivariate analysis, resulting in an inconsistent nomogram design.

FCH PET/CT appears to be a good tool for evaluating patients eligible for treatment with 223Ra, as well as for their follow-up. Thus, findings derived from it, such as the morphological characteristics of BM in the CT, bone marrow infiltration, or the response to 223Ra in the interim study, have proven to be solid and useful variables in the creation of nomograms for predicting therapeutic failure and OS.

There is much literature about the role of 2-[18F]FDG PET/CT in patients with breast cancer (BC). However, there exists no international guideline with involvement of the nuclear medicine societies about this subject.

To provide an organized, international, state-of-the-art, and multidisciplinary guideline, led by experts of two nuclear medicine societies (EANM and SNMMI) and representation of important societies in the field of BC (ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA).

Literature review and expert discussion were performed with the aim of collecting updated information regarding the role of 2-[18F]FDG PET/CT in patients with no special type (NST) BC and summarizing its indications according to scientific evidence. Recommendations were scored according to the National Institute for Health and Care Excellence (NICE) criteria.

Quantitative PET features (SUV, MTV, TLG) are valuable prognostic parameters. In baseline staging, 2-[18F]FDG PET/CT plays a role from stage IIB through stage IV. When assessing response to therapy, 2-[18F]FDG PET/CT should be performed on certified scanners, and reported either according to PERCIST, EORTC PET, or EANM immunotherapy response criteria, as appropriate. 2-[18F]FDG PET/CT may be useful to assess early metabolic response, particularly in non-metastatic triple-negative and HER2+ tumours. 2-[18F]FDG PET/CT is useful to detect the site and extent of recurrence when conventional imaging methods are equivocal and when there is clinical and/or laboratorial suspicion of relapse. Recent developments are promising.

2-[18F]FDG PET/CT is extremely useful in BC management, as supported by extensive evidence of its utility compared to other imaging modalities in several clinical scenarios.