The gastrin-releasing peptide receptor (GRPR) is overexpressed in prostate cancer (PCa) and in hormone-driven breast cancer (BCa). The aim of this phase I clinical trial was to evaluate safety, biodistribution, and dosimetry after the administration of the recently developed GRPR-targeting antagonistic bombesin analogue [^99mTc]Tc-maSSS-PEG₂-RM26 in PCa and BCa patients. Planar and whole-body SPECT/CT imaging was performed in six PCa patients and seven BCa patients 2, 4, 6, and 24 h post the intravenous administration of 40 µg of [^99mTc]Tc-maSSS-PEG₂-RM26 (600–700 MBq). No adverse events or pathological changes were observed. The rapid blood clearance of [^99mTc]Tc-maSSS-PEG₂-RM26 was observed with predominantly hepatobiliary excretion. The effective doses were 0.0053 ± 0.0007 for male patients and 0.008 ± 0.003 mSv/MBq for female patients. The accumulation of [^99mTc]Tc-maSSS-PEG₂-RM26 in tumors was observed in four out of six PCa and in seven out of seven BCa patients. In four BCa patients, a high uptake of the agent into the axillary lymph nodes was detected. Immunohistochemistry revealed positive GRPR expression in 60% of primary PCa, 71.4% of BCa tumors, and 50% of examined BCa lymph nodes. In conclusion, a single administration of [^99mTc]Tc-maSSS-PEG₂-RM26 was safe and well tolerated. [^99mTc]Tc-maSSS-PEG₂-RM26 SPECT may be useful for tumor detection in PCa and BCa patients, pending further studies. Full article

The globally accepted surgical strategy in glioblastomas is removing the enhancing tumor. However, the peritumoral region harbors infiltration areas responsible for future tumor recurrence. This study aimed to evaluate a predictive model that identifies areas of future recurrence using a voxel-based radiomics analysis of magnetic resonance imaging (MRI) data. This multi-institutional study included a retrospective analysis of patients diagnosed with glioblastoma who underwent surgery with complete resection of the enhancing tumor. Fifty-five patients met the selection criteria. The study sample was split into training (N = 40) and testing (N = 15) datasets. Follow-up MRI was used for ground truth definition, and postoperative structural multiparametric MRI was used to extract voxel-based radiomic features. Deformable coregistration was used to register the MRI sequences for each patient, followed by segmentation of the peritumoral region in the postoperative scan and the enhancing tumor in the follow-up scan. Peritumoral voxels overlapping with enhancing tumor voxels were labeled as recurrence, while non-overlapping voxels were labeled as nonrecurrence. Voxel-based radiomic features were extracted from the peritumoral region. Four machine learning-based classifiers were trained for recurrence prediction. A region-based evaluation approach was used for model evaluation. The Categorical Boosting (CatBoost) classifier obtained the best performance on the testing dataset with an average area under the curve (AUC) of 0.81 ± 0.09 and an accuracy of 0.84 ± 0.06, using region-based evaluation. There was a clear visual correspondence between predicted and actual recurrence regions. We have developed a method that accurately predicts the region of future tumor recurrence in MRI scans of glioblastoma patients. This could enable the adaptation of surgical and radiotherapy treatment to these areas to potentially prolong the survival of these patients. Full article

Background: Bridging therapy (BT) with systemic therapy (ST), radiation therapy (RT), or combined-modality therapy (CMT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). We report the long-term outcomes of the patients who received commercial CAR T-cell therapy with or without BT. Methods: The patients with LBCL who underwent infusion of a commercial CD19 CAR T product were eligible. The radiation was stratified as comprehensive or focal. The efficacy outcomes and toxicity were analyzed. Results: In total, 156 patients were included and, of them, 52.5% of the patients received BT. The median progression-free survival (PFS) was 0.65 years in the BT cohort compared to 1.45 years in the non-BT cohort. The median overall survival (OS) was 3.16 years in the BT cohort and was not reached in the non-BT cohort. The patients who received comprehensive radiation (versus focal) had significantly improved PFS and OS, achieving a 1-year PFS of 100% vs. 9.1% and 1-year OS of 100% vs. 45.5%. There was no difference in the severe toxicity between any of the nonbridging or BT cohorts. Conclusions: BT did not appear to compromise outcomes with respect to response rates, disease control, survival, and toxicity. The patients with limited disease treated with RT had favorable outcomes. Full article

The advantages of prehabilitation in surgical oncology are unclear. This systematic review aims to (1) evaluate the latest evidence of preoperative prehabilitation interventions on postoperative outcomes after gastrointestinal (GI) cancer surgery and (2) discuss new potential therapeutic targets as part of prehabilitation. Randomized controlled trials published between January 2017 and August 2022 were identified through Medline. The population of interest was oncological patients undergoing GI surgery. Trials were considered if they evaluated prehabilitation interventions (nutrition, physical activity, probiotics and symbiotics, fecal microbiota transplantation, and ghrelin receptor agonists), alone or combined, on postoperative outcomes. Out of 1180 records initially identified, 15 studies were retained. Evidence for the benefits of unimodal interventions was limited. Preoperative multimodal programs, including nutrition and physical activity with or without psychological support, showed improvement in postoperative physical performance, muscle strength, and quality of life in patients with esophagogastric and colorectal cancers. However, there was no benefit for postoperative complications, hospital length of stay, hospital readmissions, and mortality. No trial evaluated the impact of fecal microbiota transplantation or oral ghrelin receptor agonists. Further studies are needed to confirm our findings, identify patients who are more likely to benefit from surgical prehabilitation, and harmonize interventions. Full article

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of severe, dysregulated inflammation driven by the inability of T cells to clear an antigenic target. When associated with malignancy (mHLH), the HLH syndrome is typically associated with extremely poor survival. Here, we review the diagnosis of secondary HLH (sHLH) syndromes in adults, with emphasis on the appropriate workup and treatment of mHLH. At present, the management of HLH in adults, including most forms of mHLH, is based on the use of corticosteroids and etoposide following the HLH-94 regimen. In some cases, this therapeutic approach may be cohesively incorporated into malignancy-directed therapy, while in other cases, the decision about whether to treat HLH prior to initiating other therapies may be more complicated. Recent studies exploring the efficacy of other agents in HLH, in particular ruxolitinib, offer hope for better outcomes in the management of mHLH. Considerations for the management of lymphoma-associated mHLH, as well as other forms of mHLH and immunotherapy treatment-related HLH, are discussed. Full article

Metastatic spine disease (MSD) and metastatic spinal cord compression (MSCC) are major causes of permanent neurological damage and long-term disability for cancer patients. The development of MSD is pathophysiologically framed by a cooperative interaction between general mechanisms of bone growth and specific mechanisms of spinal metastases (SM) expansion. SM most commonly affects the thoracic spine, even though multiple segments may be affected concomitantly. The great majority of SM are extradural, while intradural-extramedullary and intramedullary metastases are less frequently seen. The management of patients with SM is particularly complex and challenging, with multiple factors—such as the spinal stability status, primary tumor radio and chemosensitivity, cancer biological burden, patient performance status and comorbidities, and patient’s oncological prognosis—influencing the clinical decision-making process. Different frameworks were developed in order to systematize and support this process. A multidisciplinary, personalized approach, enriched by the expertise of each involved specialty, is crucial. We reviewed the most recent evidence and proposed an updated algorithmic approach to patients with MSD according to the clinical scenario of each patient. A flowchart-based approach offers an evidence-based management of MSD, providing a valuable clinical decision tool in a context of high uncertainty and quick-acting need. Full article

In the area of evidence-based medicine, the IPDfromKM-Shiny method is an innovative method of survival analysis, midway between artificial intelligence and advanced statistics. Its main characteristic is that an original software investigates the Kaplan-Meier graphs of trials so that individual-patient data are reconstructed. These reconstructed patients represent a new form of original clinical material. The typical objective of investigations based on this method is to analyze the available evidence, especially in oncology, to perform indirect comparisons, and determine the place in therapy of individual agents. This review examined the most recent applications of the IPDfromKM-Shiny method, in which a new web-based software—published in 2021—was used. Reported here are 14 analyses, mostly focused on oncological treatments. Indirect comparisons were based on overall survival or progression free survival. Each of these analyses provided original information to compare treatments with one another and select the most appropriate depending on patient characteristics. These analyses can also be useful to assess equivalence from a regulatory viewpoint. All investigations stressed the importance of heterogeneity to better interpret the evidence generated by IPDfromKM-Shiny investigations. In conclusion, these investigations showed that the reconstruction of individual patient data through this online tool is a promising new method for analyzing trials based on survival endpoints. This new approach deserves further investigation, particularly in the area of indirect comparisons. Full article

There is a lack of investigations assessing the performance of systemic inflammation indices as outcome predictive tools in African Americans with prostate cancer. This study aims to assess the relationships between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation (SII), and systemic inflammation response index (SIRI) with survival outcomes among 680 diverse men with prostate cancer. Routine blood results were collected from self-identified African American and European American patients. We applied multivariable Cox regression modeling to examine the associations of systemic inflammation indices with overall and prostate cancer-specific survival. The median survival follow-up was 5.9 years, with 194 deaths. NLR, SII, and SIRI, but not PLR, showed associations with all-cause and prostate cancer-specific mortality when coded as dichotomized and continuous variables. NLR and SIRI were significantly associated with prostate cancer-specific mortality among all men (hazard ratio (HR) 2.56 for high vs. low NLR; HR 3.24 for high vs. low SIRI) and African American men (HR 2.96 for high vs. low NLR; HR 3.19 for high vs. low SIRI). Among European Americans, only SII showed an association with prostate cancer-specific survival. These observations suggest that inflammation indices merit further study as predictors of prostate cancer mortality. Full article

Poly-adenosine diphosphate-ribose polymerase plays an essential role in cell function by regulating apoptosis, genomic stability and DNA repair. PARPi is a promising drug class that has gained significant traction in the last decade with good outcomes in different cancers. Several trials have sought to test its effectiveness in metastatic castration resistant prostate cancer (mCRPC). We conducted a comprehensive literature review to evaluate the current role of PARPi in this setting. To this effect, we conducted queries in the PubMed, Embase and Cochrane databases. We reviewed and compared all major contemporary publications on the topic. In particular, recent phase II and III studies have also demonstrated the benefits of olaparib, rucaparib, niraparib, talazoparib in CRPC. Drug effectiveness has been assessed through radiological progression or overall response. Given the notion of synthetic lethality and potential synergy with other oncological therapies, several trials are looking to integrate PARPi in combined therapies. There remains ongoing controversy on the need for genetic screening prior to treatment initiation as well as the optimal patient population, which would benefit most from PARPi. PARPi is an important asset in the oncological arsenal for mCRPC. New combinations with PARPi may improve outcomes in earlier phases of prostate cancer. Full article

An accurate diagnosis of bone tumours on imaging is crucial for appropriate and successful treatment. The advent of Artificial intelligence (AI) and machine learning methods to characterize and assess bone tumours on various imaging modalities may assist in the diagnostic workflow. The purpose of this review article is to summarise the most recent evidence for AI techniques using imaging for differentiating benign from malignant lesions, the characterization of various malignant bone lesions, and their potential clinical application. A systematic search through electronic databases (PubMed, MEDLINE, Web of Science, and clinicaltrials.gov) was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 34 articles were retrieved from the databases and the key findings were compiled and summarised. A total of 34 articles reported the use of AI techniques to distinguish between benign vs. malignant bone lesions, of which 12 (35.3%) focused on radiographs, 12 (35.3%) on MRI, 5 (14.7%) on CT and 5 (14.7%) on PET/CT. The overall reported accuracy, sensitivity, and specificity of AI in distinguishing between benign vs. malignant bone lesions ranges from 0.44–0.99, 0.63–1.00, and 0.73–0.96, respectively, with AUCs of 0.73–0.96. In conclusion, the use of AI to discriminate bone lesions on imaging has achieved a relatively good performance in various imaging modalities, with high sensitivity, specificity, and accuracy for distinguishing between benign vs. malignant lesions in several cohort studies. However, further research is necessary to test the clinical performance of these algorithms before they can be facilitated and integrated into routine clinical practice. Full article

Breast cancer is the most frequently diagnosed tumor pathology on a global scale, being the leading cause of mortality in women. In light of this problem, screening programs have been implemented on the population at risk in the form of mammograms, starting in the 20th century. This has considerably reduced the associated deaths, as well as improved the prognosis of the patients who suffer from this disease. In spite of this, the evaluation of mammograms is not without certain variability and depends, to a large extent, on the experience and training of the medical team carrying out the assessment. With the aim of supporting the evaluation process of mammogram images and improving the diagnosis process, this work presents the design, development and proof of concept of a novel intelligent clinical decision support system, grounded on two predictive approaches that work concurrently. The first of them applies a series of expert systems based on fuzzy inferential engines, geared towards the treatment of the characteristics associated with the main findings present in mammograms. This allows the determination of a series of risk indicators, the Symbolic Risks, related to the risk of developing breast cancer according to the different findings. The second one implements a classification machine learning algorithm, which using data related to mammography findings as well as general patient information determines another metric, the Statistical Risk, also linked to the risk of developing breast cancer. These risk indicators are then combined, resulting in a new indicator, the Global Risk. This could then be corrected using a weighting factor according to the BI-RADS category, allocated to each patient by the medical team in charge. Thus, the Corrected Global Risk is obtained, which after interpretation can be used to establish the patient’s status as well as generate personalized recommendations. The proof of concept and software implementation of the system were carried out using a data set with 130 patients from a database from the School of Medicine and Public Health of the University of Wisconsin-Madison. The results obtained were encouraging, highlighting the potential use of the application, albeit pending intensive clinical validation in real environments. Moreover, its possible integration in hospital computer systems is expected to improve diagnostic processes as well as patient prognosis. Full article

Maximal-effort upfront or interval debulking surgery is the recommended approach for advanced-stage ovarian cancer. The role of diagnostic imaging is to provide a systematic and structured report on tumour dissemination with emphasis on key sites for resectability. Imaging methods, such as pelvic and abdominal ultrasound, contrast-enhanced computed tomography, whole-body diffusion-weighted magnetic resonance imaging and positron emission tomography, yield high diagnostic performance for diagnosing bulky disease, but they are less accurate for depicting small-volume carcinomatosis, which may lead to unnecessary explorative laparotomies. Diagnostic laparoscopy, on the other hand, may directly visualize intraperitoneal involvement but has limitations in detecting tumours beyond the gastrosplenic ligament, in the lesser sac, mesenteric root or in the retroperitoneum. Laparoscopy has its place in combination with imaging in cases where ima-ging results regarding resectability are unclear. Different imaging models predicting tumour resectability have been developed as an adjunctional objective tool. Incorporating results from tumour quantitative analyses (e.g., radiomics), preoperative biopsies and biomarkers into predictive models may allow for more precise selection of patients eligible for extensive surgery. This review will discuss the ability of imaging and laparoscopy to predict non-resectable disease in patients with advanced ovarian cancer. Full article

Pre-clinical studies have suggested sex hormone signalling pathways may influence tumorigenesis in neuroendocrine neoplasia (NEN). We conducted a retrospective, population-based study to compare overall survival (OS) between males and females with NEN. A total of 14,834 cases of NEN diagnosed between 2012 and 2018, recorded in England’s National Cancer Registry and Analysis Service (NCRAS), were analysed. The primary outcome was OS with 5 years maximum follow-up. Multivariable analysis, restricted mean survival time and mediation analysis were performed. Appendiceal, pulmonary and early-stage NEN were most commonly diagnosed in females; stomach, pancreatic, small intestinal, colonic, rectal and later-stage NEN were more often diagnosed in males. Females displayed increased survival irrespective of the stage, morphology or level of deprivation. On average, they survived 3.62 (95% CI 1.73–5.90) to 10.26 (6.6–14.45) months longer than males; this was statistically significant in NEN of the lung, pancreas, rectum and stomach (p < 0.001). The stage mediated improved survival in stomach, lung, and pancreatic NEN but not in rectal NEN. The reasons underlying these differences are not yet understood. Overall, females diagnosed with NEN tend to survive longer than males, and the stage at presentation only partially explains this. Future research, as well as prognostication and treatment, should consider sex as an important factor. Full article

Some cancer patients display a less aggressive form of metastatic disease, characterized by a low tumor burden and involving a smaller number of sites, which is referred to as “oligometastatic disease” (OMD). This review discusses new biomarkers, as well as methodological challenges and perspectives characterizing OMD. Recent studies have revealed that specific microRNA profiles, chromosome patterns, driver gene mutations (ERBB2, PBRM1, SETD2, KRAS, PIK3CA, SMAD4), polymorphisms (TCF7L2), and levels of immune cell infiltration into metastases, depending on the tumor type, are associated with an oligometastatic behavior. This suggests that OMD could be a distinct disease with specific biological and molecular characteristics. Therefore, the heterogeneity of initial tumor burden and inclusion of OMD patients in clinical trials pose a crucial methodological question that requires responses in the near future. Additionally, a solid understanding of the molecular and biological features of OMD will be necessary to support and complete the clinical staging systems, enabling a better distinction of metastatic behavior and tailored treatments. Full article

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Immune checkpoint inhibitors (ICIs) have become the new reference standard in first-line HCC treatment, replacing tyrosine kinase inhibitors (TKIs) such as sorafenib. Many clinical trials with different combinations are already in development to validate novel immunotherapies for the treatment of patients with HCC. Adoptive cell therapy (ACT), also known as cellular immunotherapy, with chimeric antigen receptors (CAR) or gene-modified T cells expressing novel T cell receptors (TCR) may represent a promising alternative approach to modify the immune system to recognize tumor cells with better clinical outcomes. In this review, we briefly discuss the overview of ACT as a promising treatment modality in HCC, along with recent updates of ongoing clinical trials. Full article