[18F]DOPA PET for lesion definition and contouring using different thresholds in patients with gliomas.

BACKGROUND: Amino-acid (AA) PET has recently been endorsed by the ESTRO-EANO guidelines for RT-planning in glioblastomas, with recommended lesion-to-brain-ratio thresholds (1.6-1.8) derived from a biopsy-controlled FET-PET study. We aimed to compare target definition at [18F]DOPA-PET between the ESTRO-EANO thresholds and other biological-tumor-volume (BTV) thresholds (derived from the striatum) typically used in [18F]DOPA-PET. METHODS: A retrospective analysis was conducted on glioma patients scanned with [18F]DOPA-PET/CT at our center between April 2021 and January 2024. 3D BTV was semi-automatically computed using a dedicated workstation (Philips HealthCare) with four thresholds: 1.6xSUVmean of background, 1.8xSUVmean of background, SUVmean and SUVmax of the contralateral striatum. The delineation accuracy of different thresholds was visually evaluated and a t-test was used to compare the different VOIs volumes (0.05 significance-level). RESULTS: 50 patients were included (36 previously received surgery). Volume definition based on the striatum SUVmax was significantly smaller compared to other thresholds (2.1 cm3), resulting in inaccurate VOIs at visual inspection in 21/50 patients. No significant differences were highlighted in BTV defined based on 1.6 or 1.8xSUVmean of background (15.7 vs. 12.7 cm3; VOIs accurate in 49/50 and 46/50 patients, respectively). BTV based on striatum SUVmean was significantly smaller compared to the 1.6xSUVmean threshold only in surgically-treated patients (p=0.04), while no significant differences were highlighted compared to the 1.8xSUVmean threshold regardless of the patients' group. CONCLUSIONS: The ESTRO-EANO FET-PET thresholds proved to be interchangeable in patients scanned with [18F]DOPA-PET, while the use of a threshold based on the contralateral-striatum SUVmean provided partially overlapping results prompting further investigation.

Cognitive dysfunction, social behavior disorder, cerebellar ataxia, and atypical brain FDG-PET presentation in spinocerebellar ataxia 17: a case report.

BACKGROUND: Spinocerebellar ataxia 17 (SCA17) is a rare autosomal dominant form of inherited ataxia, caused by heterozygous trinucleotide repeat expansions encoding glutamine in the TATA box-binding protein (TBP) gene. CASE DESCRIPTION: We describe the clinical history, neuropsychological, and neuroimaging findings of a 42-year-old patient who presented for medical attention showing prevalent behavioral and cognitive problems along with progressively worsening gait disturbances. The patient's family history indicated the presence of SCA17 in the maternal lineage. Genetic analysis confirmed a heterozygous 52-CAG pathological expansion repeat in TBP (normal interval, 25-40 CAG. Brain 18-fluorodeoxyglucose positron emission tomography (FDG-PET) showed bilateral hypometabolism in the sensorimotor cortex, with a slight predominance on the right, as well as in the striatal nuclei and thalamic hypermetabolism, a finding similar to what is observed in Huntington's disease. The patient also underwent neuropsychological evaluation, which revealed mild cognitive impairment and difficulties in social interaction and understanding other's emotions (Faux Pas Test and Reading the Mind in the Eyes Test). CONCLUSION: Our report emphasizes the importance of considering SCA17 as a possible diagnosis in patients with a prevalent progressive cognitive and behavioral disorders, even with a pattern of FDG-PET hypometabolism not primarily indicative of this disease.

Accuracy of 18F-FDG in Detecting Stage I Lung Adenocarcinomas According to IASLC/ATS/ERS Classification.

BACKGROUND: Only a small number of studies have explored the clinicopathological features of pulmonary adenocarcinoma (PA) associated with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) false-negative (FN) results. Herein, we investigated the FDG-PET diagnostic performance by stratifying PAs according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification. METHODS: From January 2002 to December 2016, all consecutive patients who underwent pulmonary resection for stage I PA at six thoracic surgery institutions were retrospectively reviewed. The diagnostic performance of FDG-PET was analysed according to IASLC/ATS/ERS classification and two validated subclassifications. Univariable and multivariable logistic analysis were used to identify predictors of FDG-PET FN results. RESULTS: Five hundred and fifty (550) patients with stage I PA were included in the analyses. Most of the patients were male (n=354 [64.4%]) and smokers (n=369 [67.1%]). Ninety-seven (n=97 [17.6%]) FN cases were observed at FDG-PET imaging. On multivariable analysis, a lepidic pattern was found to be independently associated with FDG-PET FN results (odds ratio [OR], 3.20; p<0.001), while a solid pattern more commonly presented with a positive finding (OR, 0.40; p=0.066). According to Nakamura's classification, we observed an independent association between lepidic pattern and FDG-PET FN results (OR, 3.17; p<0.001), while solid/micropapillary patterns were independently related with increased FDG uptake (OR, 0.35; p=0.021). According to Yoshizawa's classification, Intermediate-grade tumours were independently correlated with FN FDG-PET results (OR, 2.78; p=0.005). CONCLUSIONS: In our cohort, histopathological features were significantly associated with FDG uptake. In particular, some adenocarcinoma subtypes (mostly Lepidic pattern) have a tendency towards FN FDG-PET findings. The correlation between computed tomography findings, clinical characteristics, and FDG uptake is mandatory, in order to tailor the precise diagnostic and therapeutic pathway for each patient.

Tailoring the radiotherapy approach in patients with anal squamous cell carcinoma based on inguinal sentinel lymph node biopsy.

BACKGROUND AND OBJECTIVES: The aim of our study was to analyze the results of selective inguinal node irradiation in patients with anal cancer, based on the biopsy of the inguinal sentinel lymph node (SLN), in terms of local control and prognosis. METHODS: Records of patients with anal squamous cell carcinoma from January 2001 to December 2016 were retrospectively reviewed. Tc99 lymphoscintigraphy was performed in all the clinically inguinal negative patients, followed by radio-guided surgical removal of the inguinal SLN. All patients were treated with combined radiochemotherapy. In patients with negative sentinel nodes, the inguinal area was excluded in the radiotherapy field. RESULTS: A total of 123 patients, 76 females (61.8%), mean age 60.1 ± 12.19 years old, underwent intraoperative lymph node retrieval. The histological analysis showed metastasis in the SLN in 28 patients (22.8%). The mean follow-up was 43.44 ± 31.86 months. No inguinal recurrence was observed in patients with negative inguinal sentinel node(s). A statistically significant difference was observed for overall and disease-free survivals in a patient with positive and negative inguinal sentinel nodes. CONCLUSIONS: In patients with anal canal cancer, the exclusion of the inguinal regions from the radiotherapy field, in patients with negative SLN, does not compromise locoregional control nor prognosis.

Dose to Pelvic Bone Marrow Defined with FDG-PET Predicts for Hematologic Nadirs in Anal Cancer Patients Treated with Concurrent Chemo-radiation.

PURPOSE: To investigate whether irradiated volume of pelvic active bone marrow (ACTBM) may predict decreased blood cells nadirs in anal cancer patients undergoing concurrent chemo-radiation. METHODS: Forty-four patients were analyzed and pelvic active bone marrow (ACTBM) was characterized employing 18FDG-PET. Dosimetric parameters on dose-volume histograms were correlated to nadirs with generalized linear modeling. RESULTS: ACTBM mean dose was significantly correlated to white blood cell (ß = -1.338; 95%CI: -2.455/-0.221; p = 0.020), absolute neutrophil count (ß = -1.651; 95%CI: -3.284/-0.183; p = 0.048), and platelets (ß = -0.031; 95%CI: -0.057/-0.004; p = 0.024) nadirs. Other dosimetric parameters were found to be correlated (ACTBM-V10,-V20,-V30and-V40). CONCLUSIONS: 18FDG-PET is able to define active bone marrow and may predict for decreased blood cells count nadirs.

Sentinel Lymph Node Biopsy in Malignant Melanoma of the Head and Neck: A Single Center Experience.

Purpose: This study evaluated the characteristics of patients with head and neck (H&N) melanoma who underwent sentinel lymph node biopsy (SNLB) and assessed the clinical course of patients categorizing subjects according to SLNB status and melanoma location (scalp area vs. non-scalp areas). Methods: Patients undergoing SLNB for melanoma of H&N from 2015 to 2021 were prospectively characterized according to sentinel lymph node (SLN) status. SPECT/CT had been previously performed. Patients were followed until the first adverse event to evaluate progression-free survival. Results: 93 patients were enrolled. SLNB was negative in 75 patients. The median Breslow index was higher for patients with positive SLNB compared with patients with negative SLNB. In addition, the Breslow index was higher for melanoma of the scalp compared with non-scalp melanoma. The median follow-up was 24.8 months. Progression occurred at the systemic level in the 62.5% of cases. There was a significant association between positive SLNB and progression (p-value < 0.01) of disease, with lower progression-free survival for patients with melanoma of the scalp compared with those with melanoma at other anatomic sites (p-value: 0.15). Conclusions: Scalp melanomas are more aggressive than other types of H&N melanomas. Sentinel lymph node status is the strongest prognostic criterion for recurrence.

SPECT/CT-Guided Surgical Removal of a Positive External Iliac Sentinel Node in Primary Umbilical Melanoma: Report of a Case, and Up-to-Date Review of the Literature.

Primary umbilical melanoma is rare tumor, representing about 5% of all umbilical malignancies.The lymphatic drainage from the tumor is challenging and can be to inguinal, axillary and retroperitoneal nodes. Dynamic and static lymphoscintigraphy with single-photon emission tomography/computed tomography (SPECT/CT) and sentinel lymph node biopsy (SLNB) is a widely validated technique in patients with clinically localized melanoma to search for and quantify nodal spread of cutaneous melanoma. Moreover, it offers the surgeon the preoperative information about the number and location of the sentinel lymph nodes (SLNs), which makes SLNB easier and quicker. This is the first report of an ulcerated thick melanoma of the umbilicus metastasizing only to an external iliac lymph-node without involvement of superficial inguinal SLNs. The preoperative high-resolution ultrasound (HR-US) examination of the regional lymph node field had been normal. This case-report shows how addition of SPECT/CT to planar imaging in a patient with clinically localized umbilical melanoma can help avoid incomplete SLNB when a deep SLN is not removed. A literature review of umbilical melanoma is also provided.

Non-Sentinel Lymph Node Detection during Sentinel Lymph Node Biopsy in Not-Complete-Lymph-Node-Dissection Era: A New Technique for Better Staging and Treating Melanoma Patients.

Sentinel lymph node biopsy has been demonstrated to be an effective staging procedure since its introduction in 1992. The new American Joint Committee on Cancer (AJCC) classification did not consider the lack of information that would result from the less usage of the complete lymph node dissection as for a diagnostic purpose. Thus, this makes it difficult the correct staging and would leave about 20% of the further positive non-sentinel lymph nodes in the lymph node basin. In this paper, we aim to describe a new surgical technique that, combined with single-photon emission computed tomography-computed tomography (SPECT-CT), allows for better staging of melanoma patients. This is a prospective study that includes 104 patients with cutaneous melanoma. Sentinel lymph node biopsy was offered according to the AJCC guideline. Planar lymphoscintigraphy was performed in association with SPECT-CT, identifying and removing all non-biologically "excluded" lymph nodes, guiding the surgeon's hand in detection and removal of lymph nodes. Even if identification and removal of non-sentinel lymph nodes is unable to increase overall survival, it definitely gives better disease control in the basin. With a "classic" setting, the risk of leaving further lymph nodes out of the sentinel lymph node procedure is around 20%, thus, basically, the surgical sentinel lymph node of first and second lymph nodes would have therapeutic value and complete lymph node dissection classically performed.

Predictive Value of Baseline [18F]FDG PET/CT for Response to Systemic Therapy in Patients with Advanced Melanoma.

BACKGROUND/AIM: To evaluate the association between baseline [18F]FDG-PET/CT tumor burden parameters and disease progression rate after first-line target therapy or immunotherapy in advanced melanoma patients. MATERIALS AND METHODS: Forty four melanoma patients, who underwent [18F]FDG-PET/CT before first-line target therapy (28/44) or immunotherapy (16/44), were retrospectively analyzed. Whole-body and per-district metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. Therapy response was assessed according to RECIST 1.1 on CT scan at 3 (early) and 12 (late) months. PET parameters were compared using the Mann-Whitney test. Optimal cut-offs for predicting progression were defined using the ROC curve. PFS and OS were studied using Kaplan-Meier analysis. RESULTS: Median (IQR) MTVwb and TLGwb were 13.1 mL and 72.4, respectively. Non-responder patients were 38/44, 26/28 and 12/16 at early evaluation, and 33/44, 21/28 and 12/16 at late evaluation in the whole-cohort, target, and immunotherapy subgroup, respectively. At late evaluation, MTVbone and TLGbone were higher in non-responders compared to responder patients (all p < 0.037) in the whole-cohort and target subgroup and MTVwb and TLGwb (all p < 0.022) in target subgroup. No significant differences were found for the immunotherapy subgroup. No metabolic parameters were able to predict PFS. Controversially, MTVlfn, TLGlfn, MTVsoft + lfn, TLGsoft + lfn, MTVwb and TLGwb were significantly associated (all p < 0.05) with OS in both the whole-cohort and target therapy subgroup. CONCLUSIONS: Higher values of whole-body and bone metabolic parameters were correlated with poorer outcome, while higher values of whole-body, lymph node and soft tissue metabolic parameters were correlated with OS.

Concurrent Chemoradiation in Anal Cancer Patients Delivered with Bone Marrow-Sparing IMRT: Final Results of a Prospective Phase II Trial.

We investigated the role of the selective avoidance of haematopoietically active pelvic bone marrow (BM), with a targeted intensity-modulated radiotherapy (IMRT) approach, to reduce acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation. We designed a one-armed two-stage Simon's design study to test the hypothesis that BM-sparing IMRT would improve by 20% the rate of G0-G2 (vs. G3-G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05; ß = 0.20). A minimum of 21/39 (54%) with G0-G2 toxicity represented the threshold for the fulfilment of the criteria to define this approach as 'promising'. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. From December 2017 to October 2020, we enrolled 39 patients. Maximum observed acute HT comprised 20% rate of ≥G3 leukopenia and 11% rate of ≥G3 thrombocytopenia. Overall, 11 out of 39 treated patients (28%) experienced ≥G3 acute HT. Conversely, in 28 patients (72%) G0-G2 HT events were observed, above the threshold set. Hence, 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in this clinical setting.

Bone Marrow-Sparing IMRT in Anal Cancer Patients Undergoing Concurrent Chemo-Radiation: Results of the First Phase of a Prospective Phase II Trial.

PURPOSE: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with 18FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation. METHODS: a one-armed two-stage Simon's design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0-G2 (vs. G3-G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05 and the ß = 0.20). At the first stage, among 21 enrolled patients, at least 9 should report G0-G2 acute HT to further proceed with the trial. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. RESULTS: from December 2017 to October 2019, 21 patients were enrolled. Maximum observed acute HT comprised 9% rate of ≥G3 leukopenia and 5% rate of ≥G3 neutropenia and anemia. Overall, only 4 out of 21 treated patients (19%) experienced ≥G3 acute HT. Conversely, 17 patients (81%) experienced G0-G2 events, way above the threshold set by the trial design. CONCLUSION: 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial.

Dose to specific subregions of pelvic bone marrow defined with FDG-PET as a predictor of hematologic nadirs during concomitant chemoradiation in anal cancer patients.

To test the hypothesis that irradiated volume of specific subregions of pelvic active bone marrow as detected by (18)FDG-PET may be a predictor of decreased blood cells nadirs in anal cancer patients undergoing concurrent chemoradiation, we analyzed 44 patients submitted to IMRT and concurrent chemotherapy. Several bony structures were defined: pelvic and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. Active BM was characterized employing (18)FDG-PET and characterized in all subregions as the volume having standard uptake values (SUVs) higher than SUVmean. All other regions were defined as inactive BM. On dose-volume histograms, dosimetric parameters were taken. Endpoints included white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin (Hb) and platelet (Plt) nadirs. Generalized linear modeling was used to find correlations between dosimetric variables and blood cells nadirs. WBC nadir was significantly correlated with LSBM mean dose (ß = -1.852; 95 % CI -3.205/-0.500; p = 0.009), V10 (ß = -2.153; 95 % CI -4.263/-0.721; p = 0.002), V20 (ß = -2.081; 95 % CI -4.880/-0.112; p = 0.003), V30 (ß = -1.971; 95 % CI -4.748/-0.090; p = 0.023) and IBM V10 (ß = -0.073; 95 % CI -0.106/-0.023; p = 0.016). ANC nadir found to be significantly associated with LSBM V10 (ß = -1.878; 95 % CI -4.799/-0.643; p = 0.025), V20 (ß = -1.765; 95 % CI -4.050/-0.613; p = 0.030) and IBM V10 (ß = -0.039; 95 % CI -0.066/-0.010; p = 0.027). Borderline significance was found for correlation between Plt nadir and LSBM V30 (ß = -0.056; 95 % CI -2.748/-0.187; p = 0.060), V40 (ß = -0.059; 95 % CI -3.112/-0.150; p = 0.060) and IBM V30 (ß = -0.028; 95 % CI -0.074/-0.023; p = 0.056). No inactive BM subsites were found to be correlated with any blood cell nadir. (18)FDG-PET is able to define active bone marrow within pelvic osseous structures. LSBM is the strongest predictor of decreased blood cells nadirs in anal cancer patients undergoing concurrent chemoradiation.

Role of positron emission tomography-computed tomography in the management of anal cancer.

PURPOSE: Pre- and post-treatment staging of anal cancer are often inaccurate. The role of positron emission tomograpy-computed tomography (PET-CT) in anal cancer is yet to be defined. The aim of the study was to compare PET-CT with CT scan, sentinel node biopsy results of inguinal lymph nodes, and anal biopsy results in staging and in follow-up of anal cancer. METHODS AND MATERIALS: Fifty-three consecutive patients diagnosed with anal cancer underwent PET-CT. Results were compared with computed tomography (CT), performed in 40 patients, and with sentinel node biopsy (SNB) (41 patients) at pretreatment workup. Early follow-up consisted of a digital rectal examination, an anoscopy, a PET-CT scan, and anal biopsies performed at 1 and 3 months after the end of treatment. Data sets were then compared. RESULTS: At pretreatment assessment, anal cancer was identified by PET-CT in 47 patients (88.7%) and by CT in 30 patients (75%). The detection rates rose to 97.9% with PET-CT and to 82.9% with CT (P=.042) when the 5 patients who had undergone surgery prior to this assessment and whose margins were positive at histological examination were censored. Perirectal and/or pelvic nodes were considered metastatic by PET-CT in 14 of 53 patients (26.4%) and by CT in 7 of 40 patients (17.5%). SNB was superior to both PET-CT and CT in detecting inguinal lymph nodes. PET-CT upstaged 37.5% of patients and downstaged 25% of patients. Radiation fields were changed in 12.6% of patients. PET-CT at 3 months was more accurate than PET-CT at 1 month in evaluating outcomes after chemoradiation therapy treatment: sensitivity was 100% vs 66.6%, and specificity was 97.4% vs 92.5%, respectively. Median follow-up was 20.3 months. CONCLUSIONS: In this series, PET-CT detected the primary tumor more often than CT. Staging of perirectal/pelvic or inguinal lymph nodes was better with PET-CT. SNB was more accurate in staging inguinal lymph nodes.