The prognostic utility of 18F-FDG PET parameters in lymphoma patients under CAR-T-cell therapy: a systematic review and meta-analysis.

Background: Chimeric antigen receptor (CAR) T-cell therapy has attracted considerable attention since its recent endorsement by the Food and Drug Administration, as it has emerged as a promising immunotherapeutic modality within the landscape of oncology. This study explores the prognostic utility of [18F]Fluorodeoxyglucose positron emission tomography ([18F]FDG PET) in lymphoma patients undergoing CAR T-cell therapy. Through meta-analysis, pooled hazard ratio (HR) values were calculated for specific PET metrics in this context. Methods: PubMed, Scopus, and Ovid databases were explored to search for relevant topics. Dataset retrieval from inception until March 12, 2024, was carried out. The primary endpoints were impact of specific PET metrics on overall survival (OS) and progression-free survival (PFS) before and after treatment. Data from the studies were extracted for a meta-analysis using Stata 17.0. Results: Out of 27 studies identified for systematic review, 15 met the criteria for meta-analysis. Baseline OS analysis showed that total metabolic tumor volume (TMTV) had the highest HR of 2.66 (95% CI: 1.52-4.66), followed by Total-body total lesion glycolysis (TTLG) at 2.45 (95% CI: 0.98-6.08), and maximum standardized uptake values (SUVmax) at 1.30 (95% CI: 0.77-2.19). TMTV and TTLG were statistically significant (p < 0.0001), whereas SUVmax was not (p = 0.33). For PFS, TMTV again showed the highest HR at 2.65 (95% CI: 1.63-4.30), with TTLG at 2.35 (95% CI: 1.40-3.93), and SUVmax at 1.48 (95% CI: 1.08-2.04), all statistically significant (p ≤ 0.01). The ΔSUVmax was a significant predictor for PFS with an HR of 2.05 (95% CI: 1.13-3.69, p = 0.015). Conclusion: [18F]FDG PET parameters are valuable prognostic tools for predicting outcome of lymphoma patients undergoing CAR T-cell therapy.

Primary Central Nervous System Lymphoma Presenting as a Solitary Fourth Ventricular Mass: A Case Report.

The occurrence of primary fourth ventricular lymphoma is an exceptionally uncommon phenomenon. Here, we present a case of lymphoma in the fourth ventricle in a 30-year-old male who presented with progressive headache and vertigo over the last one month of his presentation. Preoperative MRI revealed a space-occupying lesion of the fourth ventricle. Pathological analysis following complete resection confirmed the lesion as primary central nervous system lymphoma. The patient underwent chemotherapy following the MTR (methotrexate, temozolomide, and rituximab) protocol with four months of uneventful follow-up, indicating no disease recurrence. Therefore, clinicians are advised to consider the potential presence of lymphoma as part of the differential diagnosis for space-occupying lesions, especially when there is a combination of clinical deterioration and rapid imaging progression.

Diagnostic Accuracy of [18F]FDG PET/MRI in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Metaanalysis.

This study evaluates the diagnostic utility of PET/MRI for primary, locoregional, and nodal head and neck squamous cell carcinoma (HNSCC) through systematic review and metaanalysis. Methods: A systematic search was conducted using PubMed and Scopus to identify studies on the diagnostic accuracy of PET/MRI for HNSCC. The search included specific terms and excluded nonhybrid PET/MRI studies, and those with a sample size of fewer than 10 patients were excluded. Results: In total, 15 studies encompassing 638 patients were found addressing the diagnostic test accuracy for PET/MRI within the chosen subject domain. Squamous cell carcinoma of the nasopharynx was the most observed HNSCC subtype (n = 198). The metaanalysis included 12 studies, with pooled sensitivity and specificity values of 93% and 95% per patient for primary disease evaluation, 93% and 96% for locoregional evaluation, and 89% and 98% per lesion for nodal disease detection, respectively. An examination of a subset of studies comparing PET/MRI against PET/CT or MRI alone for evaluating nodal and locoregional HNSCC found that PET/MRI may offer slightly higher accuracy than other modalities. However, this difference was not statistically significant. Conclusion: PET/MRI has excellent potential for identifying primary, locoregional, and nodal HNSCC.

Comprehensive Analysis of Metastatic Prostate Cancer: Real-World Data From the Middle East.

PURPOSE: Metastatic prostate cancer (Pca) is a complex disease with diverse clinical characteristics and outcomes across the geographical distribution. Herein, we present a series of patients from the Middle East, aiming at identifying disease outcomes and prognostic factors specific to this regional context. METHODS AND MATERIALS: This is a retrospective study of patients with metastatic Pca, diagnosed at King Hussein Cancer Center, Jordan, between 2006 and 2018. Survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Factors that significantly affected overall survival (OS) in the univariable analysis were examined in a multivariable Cox regression analysis. RESULTS: A total of 188 patients with metastatic Pca were included in this analysis, of whom 168 (89%) had de novo metastatic disease. The median age at diagnosis was 68 years, 144 (77%) had bone metastasis, 32 (17%) had visceral metastasis, and 126 (67%) had high-volume disease. At a median follow-up of 67 months, the median OS was 44.3 months. The following factors predicted inferior OS in univariable analysis: smoking, normal BMI, high-volume disease, high alkaline phosphatase (ALP), previous local therapy for prostate, and orchiectomy versus medical androgen deprivation therapy (ADT). On multivariable analysis, high-volume disease (hazard ratio [HR], 1.92 [95% CI, 1.17 to 3.13]; P = .0094), high ALP (HR, 2.136 [95% CI, 1.38 to 3.31]; P < .001), and orchiectomy (HR, 2.40 [95% CI, 1.51 to 3.82]; P < .001) emerged as independent factors for inferior OS. CONCLUSION: Metastatic Pca outcomes in our population closely align with the global benchmark. High volume status, elevated ALP, and performance of surgical as opposed to medical ADT emerge as prognostic indicators of poor survival.

Initial clinical experience using 68Ga-FAPI-46 PET/CT for detecting various cancer types.

OBJECTIVE: Numerous studies have shown that gallium-68-labeled fibroblast activation protein inhibitor (68Ga-FAPI) positron emission tomography/computed tomography (PET/CT) scans would yield high intra-tumoral tracer uptake and low uptake in normal tissues as background, thus allowing for excellent visualization of lesions in the cancer microenvironment. This study set out to compare the suitability of novel 68Ga-FAPI-46 PET versus routine fluorine-18-fluorodeoxyglucose (18F-FDG) PET and other few cases of 68Ga-DOTATATE/68Ga-Pentixafor PET/CT for the assessment of different types of cancer. SUBJECTS AND METHODS: A retrospective analysis of 11 patients (6 males, 5 females; average age: 53 years, range: 10-58 years) with histopathologically confirmed, well-differentiated adenocarcinoma, medullar thyroid cancer (MTC), papillary thyroid carcinoma (PTC), cervical, gastric, glioblastoma multiform (GBM), colon, Ewing's sarcoma, and breast cancer was performed. These patients underwent PET/CT scans using four different radiotracers (9 18F-FDG, 11 68Ga- FAPI, 3 68Ga-DOTATATE, and 1 68Ga-Pentixafor). The patients' PET/CT images were visually evaluated for cancer detection, and analyzed semi-quantitatively through image- derived metrics, such as target-to-background ratio (TBR) and maximum standardized uptake value (SUVmax), for recurrence and metastasis. RESULTS: The study of 11 patients revealed that 68Ga-FAPI-46 was more effective than other tracers for detecting metastases, with 55 vs. 49 metastases in the lymph nodes, 4 vs. 3 in the liver, and 4 vs. 3 in the bones detected in comparison to 18F-FDG. No significant differences were observed in 68Ga-DOTATATE and 68Ga-Pentixafor PET images. In addition, in five patients, the SUVmax and TBR values in 68Ga-FAPI-46 PET images were significantly higher than those in 18F-FDG PET images for lymph nodes and bone metastases. Although the SUVmax in 68Ga-FAPI-46 and 18F-FDG PET images for liver metastases was comparable, 68Ga-FAPI- 46 had a significantly higher TBR than 18F-FDG. CONCLUSION: Our findings suggest that FAPI PET/CT is not suitable for evaluating GBM and Ewing sarcoma but generally outperforms 18F-FDG PET/CT in various types of breast cancer, gastrointestinal, gynecological, PTC and MTC. However, larger trials are needed to validate these preliminary findings.

Peer Review in Radiation Oncology: Where Does the Middle East, North Africa, and Türkiye Region Stand?

PURPOSE: This study aims to assess the status of radiation oncology peer review procedures across the Middle East, North Africa, and Türkiye (MENAT) region. METHODS: A cross-sectional electronic survey was conducted among radiotherapy centers in the MENAT region in March 2024. It assessed peer review practices, departmental demographics, perceived importance of peer review, and potential barriers. RESULTS: Data from 177 radiation oncology centers revealed varying peer review implementation across the MENAT region. Egypt had the highest participation (16.4%) among all responders. Most centers (31%) treated 500-1,000 cases annually. The majority (77.4%) implemented peer review, with varying levels between countries and across different centers. Advanced radiotherapy techniques significantly correlated with implementation of peer review (P < .05). Peer review meetings were mostly scheduled on a weekly basis (46%) and organized by radiation oncologists (84.7%). Target volume contouring (89%) and radiotherapy prescription (82%) were frequently peer-reviewed. Respondents with peer review at their institutions significantly valued peer review for education, adherence to guidelines, improving planning protocols, and reducing variation in practice institutions without peer review (P < .05). The most frequently reported barriers to peer review were having a high number of patients (56%) and shortage of time (54%). CONCLUSION: Peer review is essential for improving the quality of practice in radiation oncology. Despite some discrepancies, numerous obstacles, and challenges in implementation, it is instrumental in the improvement of patient care in most centers throughout the region. Raising awareness among radiation oncologists about the importance of peer review is paramount to lead to better outcomes.

A New Era for PET/CT: Applications in Non-Tumorous Renal Pathologies.

Non-tumorous kidney diseases include a variety of conditions affecting both the structure and function of the kidneys, thereby causing a range of health-related problems. Positron emission tomography/computed tomography (PET/CT) has emerged as a potential diagnostic tool, offering a multifaceted approach to evaluating non-tumorous kidney diseases. Its clinical significance extends beyond its conventional role in cancer imaging, enabling a comprehensive assessment of renal structure and function. This review explores the diverse applications of PET/CT imaging in the evaluation of non-cancerous kidney diseases. It examines PET/CT's role in assessing acute kidney injuries, including acute pyelonephritis and other forms of nephritis, as well as chronic conditions such as immune complex-mediated glomerulonephritis and chronic kidney disease. Additionally, the review delves into PET/CT's utility in evaluating complications in renal transplant recipients, identifying renal histiocytosis and detecting renal amyloidosis. The current review aims to promote further research and technological advancements to popularize PET/CT's clinical utility in diagnosing and treating non-tumorous kidney diseases.

An Overview of Appropriate Medical Practice and Preparedness in Radiation Emergency Response.

Radiation emergencies involving high doses of nuclear radiation pose significant risks from exposure to ionizing radiation in various scenarios. These situations include transportation accidents involving radioactive materials, occupational exposure, nuclear detonations, dirty bombs, and nuclear power plant accidents. In addition to the immediate risks of acute radiation syndrome (ARS) and related diseases, long-term exposure can increase the risk of other health issues such as cardiovascular disease and cancer. Vulnerable populations, including pregnant women and children, face particular concern due to potential impacts on their health and the health of unborn babies. The severity of ARS depends on several factors such as radiation dose, quality, dose rate, exposure uniformity, and individual biological responses. Bioindicators are biological responses or markers that help assess the severity and effects of radiation exposure on an individual. Bioindicators can include physical symptoms such as nausea, vomiting, and diarrhea, or laboratory tests such as changes in blood cell counts and gene expression that can help in assessing and treating exposed individuals. Additionally, early prodromal symptoms such as vomiting, diarrhea, and erythema can provide important clues for diagnosis and treatment. Developing a comprehensive plan for radiation emergencies is vital for safeguarding public health, infrastructure, and the environment. First responders play a critical role in establishing safety perimeters, triage, and coordination with various stakeholders. Education and training are essential for medical personnel and the public. This article provides general recommendations and identifies challenges to effective radiation emergency preparedness and response.

A rare presentation of thyroid malignant peripheral nerve sheath tumor in neurofibromatosis type 1 delineated by FDG PET/CT: A case report and literature review.

Malignant peripheral nerve sheath tumors (MPNST) are rare, aggressive soft tissue sarcomas that arise from peripheral nerves and often present a diagnostic and therapeutic challenge. They can occur sporadically or in association with neurofibromatosis type 1 (NF1), a genetic disorder caused by mutations in the NF1 gene. This report presents the unique case of a 33-year-old male with progressive dry cough, hoarseness, and neck swelling who underwent a total thyroidectomy, revealing a high-grade malignant peripheral nerve sheath tumor invading the thyroid. FDG PET/CT led to the additional diagnosis of NF1. This case stands out due to the rarity of finding an MPNST within the thyroid and the simultaneous identification of NF1. It underscores the importance of screening MPNST patients for NF1 and vice versa, spotlighting the expanding role of FDG PET/CT in comprehensive evaluations. To our knowledge, this report presents the first case of NF1-associated MPNST with thyroid involvement worldwide.

Clinical Characteristics and Outcomes of CML in Adolescents and Young Adults.

BACKGROUND: While Chronic Myeloid Leukemia (CML) is a disease of older adults, there is a growing population of adolescent and young adults (AYAs) with CML. This study evaluated the clinical characteristics and outcomes of CML in AYAs. PATIENTS AND METHODS: Data from medical records of adults with chronic phase CML diagnosed and treated at our center from 2011until 2021were retrospectively analyzed. Age between 18 and 29 years was used to define AYAs. Response to tyrosine kinase inhibitors (TKIs), progression to accelerated phase (AP) or blast crisis (BC), event-free survival (EFS) and overall survival (OS) were compared between AYAs and older adults. RESULTS: Among 163 patients included, 41 (25.1%) were AYAs. AYAs were more likely to be males (P = .02), to present with symptoms (P = .004), had a higher median white blood cell count (P = .007), neutrophil count (P = .029), eosinophil count (P = 0.01), low-risk Sokal (P = .033) and Hasford (P = .005) groups. TKI-sensitivity as well as median times for achievement of complete cytogenetic and major molecular response were comparable between both groups. After a median follow-up of 76 (range: 11-235) months, there was no difference in OS (P = .528), or cumulative incidence of transformation to accelerated phase or blast crisis (P = .11). On the other hand, AYA had an inferior EFS (P = .034). CONCLUSION: A quarter of the patients diagnosed with CML in our population were AYAs. Despite being characterized as "lower-risk," they presented with a greater disease burden, had a shorter EFS but comparable OS. Further studies are needed to better understand the disease biology of this group.

18 F-FDG PET/CT Unveils Coexistent Myelomatous Hepatosplenic and Thyroid Cartilage Involvement : A Rare Presentation in Multiple Myeloma.

ABSTRACT: Extramedullary myelomatous disease is an aggressive condition where clonal plasma cells proliferate outside the bone marrow, allowing independent survival. This state is generally associated with negative outcomes. A 65-year-old woman presented with progressive bilateral hypochondrial pain, was initially misattributed to an inflammatory etiology, and was consequently managed with corticosteroid therapy. A bone marrow biopsy was offered after further deterioration confirming plasma cell myeloma. Afterward, 18 F-FDG PET/CT revealed medullary and extramedullary hepatosplenic and thyroid cartilage involvement, concluding an overall picture of an atypical and extensive extramedullary myelomatous disease.

[18F]F-Poly(ADP-Ribose) Polymerase Inhibitor Radiotracers for Imaging PARP Expression and Their Potential Clinical Applications in Oncology.

Including poly(ADP-ribose) polymerase (PARP) inhibitors in managing patients with inoperable tumors has significantly improved outcomes. The PARP inhibitors hamper single-strand deoxyribonucleic acid (DNA) repair by trapping poly(ADP-ribose)polymerase (PARP) at sites of DNA damage, forming a non-functional "PARP enzyme-inhibitor complex" leading to cell cytotoxicity. The effect is more pronounced in the presence of PARP upregulation and homologous recombination (HR) deficiencies such as breast cancer-associated gene (BRCA1/2). Hence, identifying HR-deficiencies by genomic analysis-for instance, BRCA1/2 used in triple-negative breast cancer-should be a part of the selection process for PARP inhibitor therapy. Published data suggest BRCA1/2 germline mutations do not consistently predict favorable responses to PARP inhibitors, suggesting that other factors beyond tumor mutation status may be at play. A variety of factors, including tumor heterogeneity in PARP expression and intrinsic and/or acquired resistance to PARP inhibitors, may be contributing factors. This justifies the use of an additional tool for appropriate patient selection, which is noninvasive, and capable of assessing whole-body in vivo PARP expression and evaluating PARP inhibitor pharmacokinetics as complementary to the currently available BRCA1/2 analysis. In this review, we discuss [18F]Fluorine PARP inhibitor radiotracers and their potential in the imaging of PARP expression and PARP inhibitor pharmacokinetics. To provide context we also briefly discuss possible causes of PARP inhibitor resistance or ineffectiveness. The discussion focuses on TNBC, which is a tumor type where PARP inhibitors are used as part of the standard-of-care treatment strategy.

Incidental Intense Fibroblast Activation Protein Inhibitor (FAPI) Uptake in Bilateral Gluteal Myositis Ossificans: A Case Report.

Positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose ([18F]-FDG) is a widely adopted imaging modality for detecting hypermetabolic lesions. However, emerging positron-emitting tracers, such as radiopharmaceuticals featuring fibroblast activation protein (FAP) inhibitors (FAPI) labeled with [18F] or [68Ga], have opened new avenues in nuclear medicine. This case report focuses on the unique behavior of [68Ga]-FAPI in bilateral gluteal myositis ossificans, an infrequent condition characterized by soft tissue ossification. A 45-year-old woman with gastric adenocarcinoma underwent subtotal gastrectomy and received neoadjuvant and adjuvant chemotherapy; [68Ga]-FAPI PET revealed metastatic processes and unexpected [68Ga]-FAPI avid intramuscular ossifications in the pelvic and bilateral thigh muscles. Even though there was no history of trauma, the patient was diagnosed with myositis ossificans, a condition marked by non-cancerous ectopic ossifications. Diagnosis relies on history, radiology, and/or histology. FAPI imaging, increasingly used for inflammatory and infectious diseases, can exhibit uptake in benign conditions, including those involving bones and joints. This case report is the first to document incidental bilateral [68Ga]-FAPI uptake in bilateral gluteal myositis ossificans. The robust [68Ga]-FAPI activity in myositis ossificans highlights the importance of considering myositis ossificans in the context of soft tissue calcifications with intense [68Ga]-FAPI uptake.

From Despair to Hope: First Arabic Experience of 177Lu-PSMA and 161Tb-PSMA Therapy for Metastatic Castration-Resistant Prostate Cancer.

The objective of this retrospective study is to assess the effectiveness and safety of two beta-emitting prostate-specific membrane antigen (PSMA) radioligands, [177Lu]Lu and [161Tb]Tb, in heavily treated patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 148 cycles of beta-emitting PSMA radioligand therapy were given to 53 patients at a specialized cancer care center in Amman, Jordan. This treatment was offered following the exhaustion of all prior treatment modalities. Approximately half of the cases (n = 26) demonstrated an initial partial response to PSMA radioligand therapy. Moreover, roughly one-fourth of the patients (n = 13) exhibited a sustained satisfactory biochemical response, which qualified them to receive a total of six PSMA radioligand therapy cycles and maintain continued follow-up for additional treatment cycles. This was reflected by an adequate prostate-specific antigen (PSA) decline and a concomitant partial response evident on [68Ga]Ga-PSMA positron emission tomography/computed tomography imaging. A minority of patients (n= 18; 34%) experienced side effects. Generally, these were low-grade and self-limiting toxicities. This study endorses previous research evidence about PSMA radioligand therapy's safety and efficacy. It also provides the first clinical insight from patients of Arab ethnicity. This should facilitate and promote further evidence, both regionally and internationally.

Comparative analysis through propensity score matching in thyroid cancer: unveiling the impact of multiple malignancies.

Background: The incidence of thyroid cancer is on the rise worldwide, with childhood exposure to radiation being the sole acknowledged catalyst for its emergence. Nonetheless, numerous other factors that may pose risks are awaiting thorough examination and validation. This retrospective study aims to explore the malignancies linked to thyroid cancer and contrast the survival rates of those afflicted with a solitary tumor versus those with multiple primary neoplasms (MPN). Methods: This retrospective study examined data from King Hussein Cancer Center (KHCC), Jordan. Among 563 patients diagnosed with thyroid cancer, 30 patients had thyroid malignancy as part of MPN. For a 1:3 propensity score-matched analysis, 90 patients with only a primary thyroid malignancy were also enrolled. Results: Hematologic and breast malignancies were among the most frequent observed cancers alongside thyroid neoplasm. Patients who had MPN were diagnosed at older age, had higher body mass index and presented with higher thyroglobulin antibody levels (p < 0.05 for each). Additionally, MPN patient displayed a stronger family history for cancers (p= 0.002). A median follow-up duration of 135 months unveiled that MPN patients faced a worse 5-year survival compared to their counterparts with a singular neoplasm (87% vs 100% respectively; p < 0.01). However, no distinction emerged in the 5-year event-free survival between these two groups. Conclusion: MPN correlates with a significantly altered survival outcome of thyroid cancer patients. The diagnosis of thyroid carcinoma at an older age, accompanied by elevated initial thyroglobulin antibody levels and a notable familial predisposition, may raise concerns about the potential occurrence of synchronous or metachronous tumors.

False-Negative 68 Ga-FAPI PET/CT in Pediatric Thyroid Medullary Carcinoma Seen With 68 Ga-DOTATOC PET/CT and 18 F-FDG PET/CT.

ABSTRACT: In adults, 68 Ga-FAP inhibitor ( 68 Ga-FAPI) PET/CT outperforms 68 Ga-radiolabeled somatostatin analog peptides ( 68 Ga PET/CT) and 18 F-FDG PET/CT in detecting thyroid lesions. This is the case of a 13-year-old boy newly diagnosed with medullary thyroid cancer with high calcitonin level. 68 Ga PET/CT revealed the presence of only a primary thyroid lesion. Proven to be superior in detecting metastasis, 68 Ga-FAPI PET/CT was performed. The results came out negative for primary and potential metastatic lesions. This case sheds shed light on false-negatives reported in 68 Ga-FAPI PET/CT scans in pediatric patients, emphasizing the need for alternate radiotracers when a negative study is met.