Therapy Response Evaluation Research Articles

Comparative Evaluation of 99mTc-Octreotide for Diagnostic Accuracy Assessment and Localization of 177Lu-DOTA-TATE in Neuroendocrine Tumors.

Neuroendocrine tumors, due to uncommon and multi-centric origin, pose a clinical challenge for their diagnosis and treatment. Developing countries where Ga-68 DOTA-TOC/NOC PET imaging is very limited and costly, 99mTc based SSR imaging can be used as the key tool for its diagnosis and assessment of therapy response. Hence we used two different 99mTc-radiopharmaceuticals for NET imaging designated as RP-1 and RP-2 for clinical assessment and peptide receptor therapy response of 177Lu-DOTA-TATE by manually synthesized acetate buffer. 99mTc- labeled RP-1 and RP-2 sensitivity, specificity; positive and negative predictive values were calculated and compared by SPECT/CT images for utilization in peptide receptor radionuclide therapy (PRRT). Sodium-pertechnetate was used for labeling both radiopharmaceuticals, while 177Lu nca (0.04 N HCl) DOTA-TATE was synthesized by 0.1M ammonium acetate/ascorbic acid. 75 patients of known primary NET imaging with RP-1 and RP-2 were evaluated for SRR avidity and 3 were selected for PRRT. All images were correlated with 68Ga-DOTA-TOC scan, histopathology, CT and/or MRI reports. Out of 75 patients, the somatostatin receptor imaging of 39 patients of neuro-endocrine was performed with RP-1, found 23 as true positive, 7 as true negative with sensitivity, specificity, PPV and NPV of 71.87%, 100%, 100% and 43.75%, whereas 36 images with RP-2 calculated 22 T/P, 6 as T/N, 8 as F/N, with 75.8%, 100%, 100% and 50% respectively. Their 177Lu-DOTA-TATE SPECT/CT revealed specific localization of therapeutic radionuclide. 99mTc-imaging of RP-2, as compared to RP-1, had better efficiency and sensitivity and could effectively be used as an alternative to Ga-68 DOTA/TOC PET imaging and Lu-177 DOTA-TATE PRRT therapy response evaluation.

PET-CT Diagnostic and Evaluation Role in Patients with Nodal Lymphoma

Background: The most prevalent hematological malignancy, malignant lymphoma, makes up around 8% of all adult malignancies. Non-Hodgkin lymphoma (NHL) and Hodgkin disorder (HD) are two types of lymphoid neoplasms. Aim of the Work: Examine how PET/CT may be used to diagnose nodal lymphoma. Analyze the effectiveness of (18 FDG PET/CT) in the first staging of nodal lymphoma. Analyze the function of PET-CT in patient monitoring both during and after the therapeutic course. Examine the function of PET-CT in foretelling and spotting relapses. Patients and Methods: Thirty patients (12 female and 18 males; 11 HD, 19 NHD) with histologically confirmed malignant lymphoma were enrolled in this investigation. They were split into three groups judging by the outcomes of the PET/CT examination. Results: CT for diagnosis was compared to PET/CT results. The current study demonstrated the critical relevance of PET/CT in lymphoma staging, monitoring therapeutic response, and follow-up. The present investigation demonstrated the significance of 18F-FDG. When it comes to the early staging of lymphomas, PET/CT has shown to be a valuable tool in the treatment of lymphomas. PET/CT exhibited substantial effects on early and delayed therapy response evaluation. Conclusion: The outcomes of the present research highlighted the value of 18F- FDG PET/CT as a technique for the first staging of lymphomas. Comparing PET/CT to diagnostic CT has major consequences for early and delayed evaluation of therapy response.

Evaluation of Current Antiemetic Therapy Response in Patients Undergoing MEC or HEC Regimens in Portugal.

Chemotherapy-induced nausea and vomiting (CINV) negatively impact cancer patients' quality of life and treatment outcomes. This study evaluated the achievement of complete response to CINV prophylaxis during the first five days after chemotherapy in adult outpatient cancer clinics with solid malignant tumours receiving Moderate or Highly Emetogenic Chemotherapy (MEC or HEC) in Portugal. During the study, patients completed three evaluations, and nausea severity and CINV impact on patients' daily life was assessed. A complete response (no emetic episodes, no use of rescue antiemetic medication, and no more than mild nausea) was observed in 72% of the cycles (N = 161) throughout the five days after chemotherapy. Amongst the patient population, 25% classified their CINV episodes as severe. Though more than half of the patients achieved a complete response, suggesting that a therapeutic effort is being made to minimise this side effect, the overall scenario is barely optimistic. Significantly, new CINV-control measures in MEC/HEC patients should be adopted, specifically avoiding the single use of dexamethasone and 5-HT3 and raising awareness of using NK1-RAs. Thus, it is critical to improve CINV prophylactic treatment and implement practical international antiemetic guidelines in Portuguese clinical practice, envisaging the improvement of supportive care for cancer patients.

Hibridne dijagnostičke procedure u evaluaciji melanoma

Aim: To evaluate the usefulness of 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) in patients with advanced melanoma. Method: This study included 264 consecutive patients with melanoma who were sent for the 18F-FDG PET/CT. The inclusion criteria were as follows: histopathologically verified melanoma stage III or IV, the absence of other malignancy/infection; glycemia ≤ 11 mmol/l. The final study population consisted of 220 patients. After the first 18F-FDG PET/CT, the follow-up examination was performed after 11.81±7.99 months, for therapy response evaluation. Results: Pathological 18F-FDG PET/CT was present in 154 patients. Sensitivity of 18F-FDG PET/CT was estimated as 99%, specificity as 47%. There was no statistically significant difference between 18F-FDG PET/CT findings and gender (p> 0.05), and MDCT examination (p = 0.678). However, 18F-FDG PET/CT upstaged 45% patients, especially these with widespread disease. SUV max and inguinal disease localization (in patients who had lower extremities as primary localization of disease) were associated with progression free survival (PFS) (p < 0.05). SUV max (HR 1.03, CI 1.00-1.12, p=0.05) and locally advanced disease (HR 12.02, CI 1.13-148.00, p=0.04) were independent predictors of PFS. A follow up 18F-FDG PET/CT revealed active disease in 22/26 patients. Therapy type (immunotherapy or target therapy) did not correlate significantly with the 18F-FDG PET/CT follow up result (p=0.760, r=-0.354). Conclusion: 18F-FDG PET/CT has good sensitivity in the evaluation of advanced melanoma. Small lesions and brain localization reduce specificity of the examination, then MDCT, Mr are advised. Predictive factors SUV max and locally advanced disease, are more important than the timing of follow-up 18F-FDG PET/CT, since they were predictors of PFS. Follow up 18F-FDG PET/CT should be done at least in 6 months, only if there is suspicion of the presence of active disease.

Noninvasive Evaluation of Angiogenesis and Therapeutic Response after Hindlimb Ischemia with an Integrin-Targeted Tracer by PET.

Peripheral arterial disease (PAD) can severely compromise limb vitality and function. Angiogenesis plays an important role in healing of ischemic lesions. Radiolabeled RGD (Arg-Gly-Asp) peptides specifically targeting v 3 integrin are promising tracers for imaging angiogenesis. In this study, we investigated the application of a one-step labeled RGD in evaluation of angiogenesis and therapy response in a mouse model of hindlimb ischemia (HI) by positron emission tomography (PET). HI was induced by ablation of the femoral artery in mice. PET imaging using 18F-AlF-NOTA-PRGD2 (18F-PRGD2) tracer was performed at day 0 (pre-surgery) and days 3, 7, 14, and 21 after surgery to evaluate hindlimb angiogenesis longitudinally and noninvasively. The control peptide RAD (Arg-Ala-Asp) labeled with a similar procedure and a block agent were used to confirm the specific binding of 18F-PRGD2 to v 3 integrin. Ex vivo CD31 staining was performed to detect angiogenesis. In addition, the angiogenic therapy response was monitored with 18F-PRGD2 tracer and immunofluorescence staining to confirm the imaging data. The successful establishment of HI model was confirmed by ultrasound imaging and laser doppler perfusion imaging (LDPI). Specific binding of 18F-PRGD2 to v 3 integrin was validated by minimal tracer uptake of the control peptide RAD and significant decrease of tracer accumulation when a block agent was added. Local accumulation of 18F-RRGD2 in ischemic hindlimb was detected as early as 3 days and reached a peak at 7 days after surgery. The temporal change of focal tracer uptake was positively correlated with the pattern of vascular density. Moreover, vascular endothelial growth factor (VEGF) treatment increased the tracer uptake and enhanced angiogenesis, which is consistent with integrin 3 expression. PET imaging of a one-step labeled tracer 18F-PRGD2 targeted to v 3 integrin allows longitudinal monitoring of ischemia-induced angiogenesis and noninvasive assessment of VEGF treatment response in a mouse model of hindlimb ischemia. The simple synthesis procedure and in vivo performance of this PET tracer enables the feasibility of future clinical translation in ischemic cardiovascular diseases.

3D spheroid culture to examine adaptive therapy response in invading tumor cells

3D in vitro culture models of cancer cells in extracellular matrix (ECM) have been developed to investigate drug targeting and resistance or, alternatively, mechanisms of invasion; however, models allowing analysis of shared pathways mediating invasion and therapy resistance are lacking. To evaluate therapy response associated with cancer cell invasion, we here used 3D invasion culture of tumor spheroids in 3D fibrillar collagen and applied Ethanol-Ethyl cinnamate (EtOH-ECi) based optical clearing to detect both spheroid core and invasion zone by subcellular-resolved 3D microscopy. When subjected to a single dose of irradiation (4 Gy), we detected significant cell survival in the invasion zone. By physical separation of the core and invasion zone, we identified differentially regulated genes preferentially engaged in invading cells controlling cell division, repair, and survival. This imaging-based 3D invasion culture may be useful for the analysis of complex therapy-response patterns in cancer cells in drug discovery and invasion-associated resistance development.

Re: Aducanumab-Related ARIA: Paean or Lament?

Høilund-Carlsen and colleagues raise concern regarding the reliability of amyloid PET to exclude Alzheimer disease. We present additional studies of amyloid PET and discuss the diagnostic challenges in Alzheimer disease. We discuss the limitations of amyloid in diagnosis and evaluation of therapy response in AD.

Prospective Evaluation of Different Methods for Volumetric Analysis on [18F]FDG PET/CT in Pediatric Hodgkin Lymphoma.

Rationale: Therapy response evaluation by 18F-fluorodeoxyglucose PET/CT (FDG PET) has become a powerful tool for the discrimination of responders from non-responders in pediatric Hodgkin lymphoma (HL). Recently, volumetric analyses have been regarded as a valuable tool for disease prognostication and biological characterization in cancer. Given the multitude of methods available for volumetric analysis in HL, the AIEOP Hodgkin Lymphoma Study Group has designed a prospective analysis of the Italian cohort enrolled in the EuroNet-PHL-C2 trial. Methods: Primarily, the study aimed to compare the different segmentation techniques used for volumetric assessment in HL patients at baseline (PET1) and during therapy: early (PET2) and late assessment (PET3). Overall, 50 patients and 150 scans were investigated for the current analysis. A dedicated software was used to semi-automatically delineate contours of the lesions by using different threshold methods. More specifically, four methods were applied: (1) fixed 41% threshold of the maximum standardized uptake value (SUVmax) within the respective lymphoma site (V41%), (2) fixed absolute SUV threshold of 2.5 (V2.5); (3) SUVmax(lesion)/SUVmean liver >1.5 (Vliver); (4) adaptive method (AM). All parameters obtained from the different methods were analyzed with respect to response. Results: Among the different methods investigated, the strongest correlation was observed between AM and Vliver (rho > 0.9; p < 0.001 for SUVmean, MTV and TLG at all scan timing), along with V2.5 and AM or Vliver (rho 0.98, p < 0.001 for TLG at baseline; rho > 0.9; p < 0.001 for SUVmean, MTV and TLG at PET2 and PET3, respectively). To determine the best segmentation method, we applied logistic regression and correlated different results with Deauville scores at late evaluation. Logistic regression demonstrated that MTV (metabolic tumor volume) and TLG (total lesion glycolysis) computation according to V2.5 and Vliver significantly correlated to response to treatment (p = 0.01 and 0.04 for MTV and 0.03 and 0.04 for TLG, respectively). SUVmean also resulted in significant correlation as absolute value or variation. Conclusions: The best correlation for volumetric analysis was documented for AM and Vliver, followed by V2.5. The volumetric analyses obtained from V2.5 and Vliver significantly correlated to response to therapy, proving to be preferred thresholds in our pediatric HL cohort.

Immune-checkpoint inhibitor therapy response evaluation using oncophysics-based mathematical models.

The field of oncology has transformed with the advent of immunotherapies. The standard of care for multiple cancers now includes novel drugs that target key checkpoints that function to modulate immune responses, enabling the patient's immune system to elicit an effective anti-tumor response. While these immune-based approaches can have dramatic effects in terms of significantly reducing tumor burden and prolonging survival for patients, the therapeutic approach remains active only in a minority of patients and is often not durable. Multiple biological investigations have identified key markers that predict response to the most common form of immunotherapy-immune checkpoint inhibitors (ICI). These biomarkers help enrich patients for ICI but are not 100% predictive. Understanding the complex interactions of these biomarkers with other pathways and factors that lead to ICI resistance remains a major goal. Principles of oncophysics-the idea that cancer can be described as a multiscale physical aberration-have shown promise in recent years in terms of capturing the essence of the complexities of ICI interactions. Here, we review the biological knowledge of mechanisms of ICI action and how these are incorporated into modern oncophysics-based mathematical models. Building on the success of oncophysics-based mathematical models may help to discover new, rational methods to engineer immunotherapy for patients in the future. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Association of Interleukin-2 (IL-2) Levels With Acid-Fast Bacillus (AFB) Sputum Conversion In Drug-Resistant Pulmonary Tuberculosis Patient

Background: Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb) which can be found on multiple organs, but mostly infect the lung. AFB smear is used to diagnose and evaluate therapy response, to show bacterial burden and the patient’s infectious status. Combination of antituberculosis drugs for a long period of time could cause poor compliance and increased risk of resistance. Mtb infection induce immune response and release cytokines, one of which is interleukin-2 (IL-2) that regulate T lymphocyte cell. Higher IL-2 levels is found on patient with high bacterial burdern. This study aims to see the assossciation between IL-2 levels before and 30 days after DR-TB treatment, to see pre and post-treatment IL-2 levels with conversion of AFB smear, and correlation between pre-treatment IL-2 levels and AFB smear. Method: This was a cohort prospective study at RSUD dr Saiful Anwar Malang. Thirty nine DR-TB patients underwent AFB smear before and 30 days after treatment, while IL-2 levels was also measured by Enzym-Linked Immunosorbent Assay (ELISA) technique. Results: The levels of IL-2 before treatment was significantly higher compared to 30 days after treatment (P&lt;0.001). There was no significant IL-2 levels difference between conversion and non-conversion group (P=0.23), and a weak, not-significant correlation between IL-2 levels and AFB smear (r=0.28; P=0.06). Conclusion: The levels of IL-2 was significantly higher before than after treatment and it cannot be used to determine the positivity of acid-resistant bacilli smears in the sputum of patients with DR-TB. The limited timeframe and biomarker in this study raise the possibility to observe IL-2 as well as other biomarkers after intensive phase of TB treatment for future studies.

Contrast-Enhanced Mammography Versus MRI in the Evaluation of Neoadjuvant Therapy Response in Patients With Breast Cancer: A Prospective Study.

BACKGROUND. Contrast-enhanced mammography (CEM) is rapidly expanding as a credible alternative to MRI in various clinical settings. OBJECTIVE. The purpose of this study was to compare CEM and MRI for neoadjuvant therapy (NAT) response assessment in patients with breast cancer. METHODS. This prospective study included 51 patients (mean age, 46 ± 11 [SD] years) with biopsy-proven breast cancer who were candidates for NAT from May 2015 to April 2018. Patients underwent both CEM and MRI before, during, and after NAT (pre-NAT, mid-NAT, and post-NAT, respectively). Post-NAT CEM included a 6-minute delayed acquisition. One breast radiologist with experience in CEM reviewed CEM examinations; one breast radiologist with experience in MRI reviewed MRI examinations. The radiologists assessed for the presence of an enhancing lesion; if an enhancing lesion was detected, its size was measured. RECIST version 1.1 response assessment categories were derived. Pathologic complete response (pCR) was defined as absence of both invasive cancer and ductal carcinoma in situ (DCIS). RESULTS. Of 51 patients, 16 achieved pCR. CEM yielded systematically lower size measurements compared with MRI (mean difference, -0.2 mm for pre-NAT, -0.7 mm for mid-NAT, and -0.3 mm for post-NAT). All post-NAT imaging tests yielded systematically larger size measurements compared with pathology (mean difference, 0.8 mm for CEM, 1.2 mm for MRI, and 1.9 mm for delayed CEM). Of 12 patients with residual DCIS, an enhancing lesion was detected in seven on post-NAT CEM, eight on post-NAT MRI, and nine on post-NAT delayed CEM. Agreement of RECIST response categories between CEM and MRI, expressed as kappa coefficient, was 0.791 at mid-NAT and 0.871 at post-NAT. For detecting pCR by post-NAT imaging, sensitivity and specificity were 81% and 83% for CEM, 100% and 86% for MRI, and 81% and 89% for delayed CEM. Sensitivity was significantly higher for MRI than CEM (p = .001) and delayed CEM (p = .002); remaining comparisons were not significant (p > .05). CONCLUSION. After NAT for breast cancer, CEM and MRI yielded comparable assessments of lesion size (both slightly overestimated vs pathology) and RECIST categories and showed no significant difference in specificity for pCR. MRI had higher sensitivity for pCR. Delayed CEM acquisition may help detect residual DCIS. CLINICAL IMPACT. Although MRI remains the preferred test for NAT response monitoring, the findings support CEM as a useful alternative when MRI is contraindicated or not tolerated.

The role of PET/CT in large vessel vasculitis and related disorders: diagnosis, extent evaluation and assessment of therapy response

Large vessel vasculitides (LVV) are defined as chronic inflammatory disorders that affect the arteries with two major variants being distinguished: giant cell arteritis (GCA) and Takayasu's arteritis (TAK). These often present with nonspecific constitutional symptoms which makes an accurate diagnosis often challenging. Nevertheless, timely diagnosis is of utmost importance to initiate treatment and to avoid potential life-threatening complications. [18F]FDG-PET/CT is nowadays widely accepted as useful tool to aid in the diagnosis of large vessel vasculitis. However, its role to monitor disease activity and to predict disease relapse during follow-up is less obvious since vascular [18F]FDG uptake can be detected in the absence of clinical or biochemical signs of disease activity. In addition to the two major variants, [18F]FDG-PET/CT has shown promise in (peri-)aortitis and related disorders. This article aims to provide an update on the current knowledge and limitations of [18F]FDG-PET/CT for the diagnosis and assessment of treatment response in LVV. Furthermore, other radiopharmaceuticals targeting key components of the vascular immune system are being discussed which could provide an interesting alternative to image vascular inflammation in LVV.

Systemic therapy response evaluation in prostate carcinoma with [68Ga]Ga-PSMA-11 PET/CT

BackgroundConsensus statements was published by EAU and EANM to clarify some uncertainties on PSMA PET/CT response assessment in 2020. We aimed to investigate the response criteria for PSMA PET/CT according to published criteria by comparing with serum PSA changes and determine the factors affecting therapy response evaluation.ResultsA high concordance was found between [68Ga]Ga-PSMA-11 PET/CT and serum PSA responses and 0.84 of Gamma coefficient was obtained. Between concordant and discordant group, statistically significant difference was not found in terms of received therapies and castration resistance status. Statistically significant but low correlation was found between serum PSA and SUV values of prostate, moderate correlation was found serum PSA and SUVmax values of metastatic lymph nodes and bones.ConclusionsThe response evaluation of PSMA PET/CT according to the published criteria shows high concordance with serum PSA values without being affected by received therapies or castration resistance. This criteria can be used with contribution of serum PSA values in response evaluation of prostate cancer according to our results and literature data.

Immune cell subset profiling in multiple sclerosis after fingolimod initiation and continued treatment: The FLUENT study.

BackgroundFingolimod is a sphingosine 1-phosphate receptor modulator approved for relapsing MS. Long-term effects on the immunological profile are not fully understood.ObjectiveInvestigate fingolimod's temporal effects on immune cell subsets, and safety outcomes.MethodsIn FLUENT, a 12-month, prospective, non-randomized, open-label, phase IV study, adult participants received fingolimod 0.5 mg/day. Changes in immune cell subsets, anti-John Cunningham virus (JCV) antibody index, and serum neurofilament levels were assessed.Results165 fingolimod-naive and 217 participants treated for 2–12 years in routine clinical practice were enrolled. Levels of all monitored peripheral lymphocyte subsets were reduced from month 3 in fingolimod-naive participants. Greatest reductions occurred in naive and central memory CD4+ and CD8+ T cells, and in naive and memory B cells. Most lymphocyte subset levels remained stable in the continuous fingolimod group. Components of the innate immune system remained within reference ranges. No increase in JCV seropositivity was observed. No single cellular subset correlated with anti-JCV antibody index at any time point. Neurofilament levels remained within healthy adult reference limits throughout. No opportunistic infections were reported; no new or unexpected safety signals were observed.ConclusionFLUENT provides insights into the utility of immunological profiling to evaluate therapy response and potential infection risk.

Demography and Characteristics of Lung Cancer Patients Evaluated by 18F-FDG PET- CT imaging - Retrospective Analysis in NINMAS

Introduction: Carcinoma of the lung is one of the most common cancer in Bangladesh. Fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) plays an important role in staging and evaluating therapy response. Currently, limited data is available about the demography and characteristics of lung cancer patients in Bangladesh by 18F-FDG PET-CT scan. Objectives: To evaluate the demographic pattern and pattern of findings in lung cancer patients by 18F-FDG PET-CT scan in the National Institute of Nuclear Medicine and Allied Sciences (NINMAS), Dhaka. Materials and Methods: This retrospective study was conducted in the PET-CT division of NINMAS. A total of 53 patients out of 103 patients with lung cancer were enrolled who were referred to NINMAS from October 2020 to December 2021 for either baseline PET CT or for assessment of therapy response. Data were collected in a predesigned format from old documents and analyzed for demographic characteristics, histopathologic, morphologic and metabolic patterns as well as a comparison of the overall number of lung cancer patients with previous years. Results: Among the enrolled 53 lung cancer patients the majority (34%) are in the 6th to 7th decades with 56.6% male and 43.4 % female. Adenocarcinoma (62%) and squamous cell carcinoma (24%) were the most common lung cancer subtypes. The majority of patients (53%) came for a therapeutic response evaluation; among them, 32% had a good response following therapy, 25% with progressive disease and others had mixed response, partial response, and stable disease. Nine percent of the patients came for follow up and among them, recurrence is detected in 20%. Lung cancer patients who came for baseline study, (38%) were upstaged (80%) mainly with 20% remaining in the same stage. Conclusion: The demographic pattern of lung cancer patients observed in this study belonged to 6th &amp; 7th decades having male predominance. Most of the patients were diagnosed with advanced stages of lung cancer. The use of 18FDG PET-CT is crucial for the staging and diagnosis of suspected lung cancer, as well as therapeutic response and follow-up. Bangladesh J. Nuclear Med. 25(1): 22-27, 2022

Highly Sensitive Nanomagnetic Quantification of Extracellular Vesicles by Immunochromatographic Strips: A Tool for Liquid Biopsy.

Extracellular vesicles (EVs) are promising agents for liquid biopsy—a non-invasive approach for the diagnosis of cancer and evaluation of therapy response. However, EV potential is limited by the lack of sufficiently sensitive, time-, and cost-efficient methods for their registration. This research aimed at developing a highly sensitive and easy-to-use immunochromatographic tool based on magnetic nanoparticles for EV quantification. The tool is demonstrated by detection of EVs isolated from cell culture supernatants and various body fluids using characteristic biomarkers, CD9 and CD81, and a tumor-associated marker—epithelial cell adhesion molecules. The detection limit of 3.7 × 105 EV/µL is one to two orders better than the most sensitive traditional lateral flow system and commercial ELISA kits. The detection specificity is ensured by an isotype control line on the test strip. The tool’s advantages are due to the spatial quantification of EV-bound magnetic nanolabels within the strip volume by an original electronic technique. The inexpensive tool, promising for liquid biopsy in daily clinical routines, can be extended to other relevant biomarkers.

The Role and Potential of 18F-FDG PET/CT in Malignant Melanoma: Prognostication, Monitoring Response to Targeted and Immunotherapy, and Radiomics.

Novel therapeutic approaches, consisting of immune check-point inhibitors (ICIs) and molecularly targeted therapy, have thoroughly changed the clinical management of malignant melanoma (MM), the most frequent and deadly skin cancer. Since only 30–40% of MM patients respond to ICIs, imaging biomarkers suitable for the pre-therapeutic stratification and response assessment are warmly welcome. In this scenario, positron emission computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) has been successfully utilized for advanced MM staging and therapy response evaluation. Furthermore, several PET-derived parameters (SUVmax, MTV, TLG) were particularly impactful for the prognostic evaluation of patients submitted to targeted and immunotherapy. In this review, we performed a web-based and desktop research on the clinical applications of 18F-FDG PET/CT in MM, with a particular emphasis on the various metabolic criteria developed for interpreting PET/CT scan in patients undergoing immunotherapy or targeted therapy or a combination of both. Furthermore, the emerging role of radiomics, a quantitative approach to medical imaging applying analysis methodology derived by the field of artificial intelligence, was examined in the peculiar context, putting a particular emphasis on the potential of this discipline to support clinicians in the delicate process of building patient-tailored pathways of care.

Imaging of Neuroendocrine Neoplasms: Monitoring Treatment Response-AJR Expert Panel Narrative Review.

Neuroendocrine neoplasms (NENs) encompass a broad spectrum of tumors throughout the body and range in biologic behavior from indolent to aggressive. Consequently, a wide spectrum of treatment options are available for NENs, including observation, somatostatin analogues, targeted therapy, chemotherapy, surgical resection, liver-directed therapy (embolization and ablation), and peptide receptor radionuclide therapy. Given the wide variety of tumor behaviors and treatments, precise criteria for treatment response in NENs are lacking. Though conventional anatomic imaging with CT and MRI remains important for NEN response assessment, the use of somatostatin receptor (SSR) PET is increasing and often provides synergistic and complementary information. Additionally, in certain clinical scenarios, a particular imaging strategy may prove superior or inferior to others for the detection of metastatic disease and evaluation of therapy response. A strong need exists to further define appropriate and standardized assessment criteria for tumor response and progression in NEN. This article presents the strengths and weaknesses of individual imaging modalities for evaluating NEN therapy response, including conventional anatomic imaging, SSR PET, FDG PET, dual-tracer PET, and PET/MRI. Ongoing challenges and unmet needs in the use of imaging for NEN response evaluation are explored.

Characterization of Anti-Angiogenic Chemo-Sensitization via Longitudinal Ultrasound Localization Microscopy in Colorectal Carcinoma Tumor Xenografts.

Objective:Super-resolution ultrasound localization microscopy (ULM) has unprecedented vascular resolution at clinically relevant imaging penetration depths. This technology can potentially screen for the transient microvascular changes that are thought to be critical to the synergistic effect(s) of combined chemotherapy-antiangiogenic agent regimens for cancer.Methods:In this paper, we apply this technology to a high-throughput colorectal carcinoma xenograft model treated with either the antiangiogenic agent sorafenib, FOLFOX-6 chemotherapy, a combination of the two treatments, or vehicle control.Results:Longitudinal ULM demonstrated morphological changes in the antiangiogenic treated cohorts, and evidence of vascular disruption caused by chemotherapy. Gold-standard histological measurements revealed reduced levels of hypoxia in the sorafenib treated cohort for both of the human cell lines tested (HCT-116 and HT-29). Therapy resistance was associated with an increase in tumor vascular fractal dimension as measured by a box-counting technique on ULM images.Conclusion:These results imply that the morphological changes evident on ULM signify a functional change in the tumor microvasculature, which may be indicative of chemo-sensitivity.Significance:ULM provides additional utility for tumor therapy response evaluation by offering a myriad of morphological and functional quantitative indices for gauging treatment effect(s).

18F-FDG PET/CT value in the detection of seminoma and correlation with CT and tumor marker levels - up to 8 years of follow-up.

Positron emission tomography/computed tomography using fluorine-18 fluoro-deoxyglucose (18F-FDG PET/CT) is not routinely used for diagnosis of testicular carcinoma. Unlike CT which cannot confirm with certainty the nature of the lesions, especially in post-therapy setting, 18F-FDG PET/CT detects active disease by showing increased glucose metabolism within the lesions. Determination of 18F-FDG PET/CT usefulness in detection of seminoma, therapy response evaluation and comparison to CT findings and tumor marker levels. Eighty-two men (age 39.8±10.1) after orchiectomy and histopathological confirmation of seminoma were included in this study. Indications for 18F-FDG PET/CT were initial staging, restaging after chemo/radiotherapy with positive/uncertain CT, suspected recurrence on CT, elevated tumor markers. All patients had clinical follow-up of up to 8 years (median 33.5) after the first 18F-FDG PET/CT examination. Degree of metabolic activity was analyzed visually and semi-quantitatively using maximum standardized uptake value(SUVmax). Fluorine-18-FDG PET/CT was true positive in 36 patients (43.9%) with average SUVmax of 7.9±4.8.Recurrence was mostly found in retroperitoneal lymph nodes and distant metastases in lungs, bones, liver. Six findings were false positive and 3 false negative. Sensitivity, specificity, accuracy of 18F-FDG PET/CT were 92.3%, 86.0%, 89.0% and of CT 60.8%, 66.6%, 63.4%. Pearson Chi-square test showed statistically significant difference between the results of 18F-FDG PET/CT and CT (P=0.016). Significant correlation was found between positive 18F-FDG PET/CT findings and levels of LDH (P=0.043), while non-significant between AFP, β-hCG (P>0.05). Fluorine-18-FDG PET/CT was superior to CT in evaluation of therapy response, active disease in residual tissue and normal size lymph nodes, as well as when CT was negative and tumor markers were elevated. Elevated lactate dehydrogenase (LDH) contributes to positive 18F-FDG PET/CT findings.