Adaptive Individualized high-dose preoperAtive (AIDA) chemoradiation in high-risk rectal cancer: a phase II trial.

PURPOSE: To evaluate the pathological complete response (pCR) rate of locally advanced rectal cancer (LARC) after adaptive high-dose neoadjuvant chemoradiation (CRT) based on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT). METHODS: The primary endpoint was the pCR rate. Secondary endpoints were the predictive value of 18 F-FDG-PET/CT on pathological response and acute and late toxicity. All patients performed 18 F-FDG-PET/CT at baseline (PET0) and after 2 weeks during CRT (PET1). The metabolic PET parameters were calculated both at the PET0 and PET1. The total CRT dose was 45 Gy to the pelvic lymph nodes and 50 Gy to the primary tumor, corresponding mesorectum, and to metastatic lymph nodes. Furthermore, a sequential boost was delivered to a biological target volume defined by PET1 with an additional dose of 5 Gy in 2 fractions. Capecitabine (825 mg/m2 twice daily orally) was prescribed for the entire treatment duration. RESULTS: Eighteen patients (13 males, 5 females; median age 55 years [range, 41-77 years]) were enrolled in the trial. Patients underwent surgical resection at 8-9 weeks after the end of neoadjuvant CRT. No patient showed grade > 1 acute radiation-induced toxicity. Seven patients (38.8%) had TRG = 0 (complete regression), 5 (27.0%) showed TRG = 2, and 6 (33.0%) had TRG = 3. Based on the TRG results, patients were classified in two groups: TRG = 0 (pCR) and TRG = 1, 2, 3 (non pCR). Accepting p < 0.05 as the level of significance, at the Kruskal-Wallis test, the medians of baseline-MTV, interim-SUVmax, interim-SUVmean, interim-MTV, interim-TLG, and the MTV reduction were significantly different between the two groups. 18 F-FDG-PET/CT was able to predict the pCR in 77.8% of cases through compared evaluation of both baseline PET/CT and interim PET/CT. CONCLUSIONS: Our results showed that a dose escalation on a reduced target in the final phase of CRT is well tolerated and able to provide a high pCR rate.

High dose brachytherapy with non sealed 188Re (rhenium) resin in patients with non-melanoma skin cancers (NMSCs): single center preliminary results.

BACKGROUND AND AIM: High dose brachytherapy using a non sealed 188Re-resin (Rhenium-SCT®, Oncobeta® GmbH, Munich, Germany) is a treatment option for non-melanoma skin cancer (NMSC). The aim of this prospective study was to assess the efficacy and the safety of a single application of Rhenium-SCT® in NMSC. MATERIALS AND METHOD: Fifty consecutive patients (15F, 35 M, range of age 56-97, mean 81) showing 60 histologically proven NMSCs were enrolled and treated with the Rhenium-SCT® between October 2017 and January 2020. Lesions were located on the face, ears, nose or scalp (n = 46), extremities (n = 9), and trunk (n = 5). Mean surface areas were 7.0 cm2 (1-36 cm2), mean thickness invasion was 1.1 mm (0.2-2.5 mm), and mean treatment time was 79 min (21-85 min). Superficial, mean, and target absorbed dose were 185 Gy, 63 Gy, and 31 Gy respectively. Patients were followed-up at 14, 30, 60, 90, and 180 days posttreatment, when dermoscopy and biopsy were performed. Mean follow-up was 20 months (range 3-33 months). Early skin toxicity was classified according to Common Terminology Criteria for Adverse Events (CTCAE). Cosmetic results were evaluated after at least 12 months according to Radiation Therapy Oncology Group (RTOG) scale. RESULTS: At 6 months follow-up, histology and dermoscopy were available for 54/60 lesions, of which 53/54 (98%) completely responded. One patient showed a 1-cm2 residual lesion that was subsequently surgically excised. Twelve months after treatment, 41/41 evaluable lesions were free from relapse. Twenty four months after treatment, 23/24 evaluable lesions were free of relapse. In 56/60 lesions early side effects, resolving within 32 days were classified as grades 1-2 (CTCAE). In the remaining 4/60 lesions, these findings were classified as grade 3 (CTCAE) and lasted up to 8-12 weeks but all resolved within 90 days. After at least 12 months (12-33 months), cosmetic results were excellent (30 lesions) or good (11 lesions). CONCLUSION: High dose brachytherapy with Rhenium-SCT® is a noninvasive, reasonably safe, easy to perform, effective and well-tolerated approach to treat NMSCs, and it seems to be a useful alternative option when surgery or radiation therapy are difficult to perform or not recommended. In our population 98% of the treated lesions resolved completely after a single application and only one relapsed after 2 years. Larger patients' population and longer follow-up are needed to confirm these preliminary data and to find the optimal dose to administer in order to achieve complete response without significant side effects.

Theragnostics in prostate cancer.

Prostate-specific membrane antigen (PSMA) is a molecular target for both imaging diagnostics and therapeutics, i.e., a theragnostics target. There has been a growing body of evidence supporting PSMA theragnostics approaches in the management of prostate cancer (PCa) for tailored precision medicine. Tumor characterization through PSMA-ligand PET imaging is crucial for assessing the molecular signature and eligibility for PSMA radioligand therapy. Recent U.S. Food and Drug Administration (FDA) approval of two new drug applications for PSMA PET imaging contribute to reinforce PSMA as an oncologic blockbuster. Additionally, relevant progress in the PSMA treatment has been made in the last five years. [177Lu]Lu-PSMA-617 radioligand therapy for patients with progressive PSMA-avid metastatic castration-resistant PCa (mCRPC) significantly increased overall survival and radiographic progression-free survival, according to the results of an international, prospective, open label, multicenter, randomized, phase III study (VISION trial). The objective of this comprehensive review is to highlight the recent advances in PCa theragnostics, focusing on actual clinical applications and future perspectives.

Prediction nomogram for 68Ga-PSMA-11 PET/CT in different clinical settings of PSA failure after radical treatment for prostate cancer.

OBJECTIVE: The objective of this study was to develop a clinical nomogram to predict gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA-11-PET/CT) positivity in different clinical settings of PSA failure. MATERIALS AND METHODS: Seven hundred three (n = 703) prostate cancer (PCa) patients with confirmed PSA failure after radical therapy were enrolled. Patients were stratified according to different clinical settings (first-time biochemical recurrence [BCR]: group 1; BCR after salvage therapy: group 2; biochemical persistence after radical prostatectomy [BCP]: group 3; advanced-stage PCa before second-line systemic therapies: group 4). First, we assessed 68Ga-PSMA-11-PET/CT positivity rate. Second, multivariable logistic regression analyses were used to determine predictors of positive scan. Third, regression-based coefficients were used to develop a nomogram predicting positive 68Ga-PSMA-11-PET/CT result and 200 bootstrap resamples were used for internal validation. Fourth, receiver operating characteristic (ROC) analysis was used to identify the most informative nomogram's derived cutoff. Decision curve analysis (DCA) was implemented to quantify nomogram's clinical benefit. RESULTS: 68Ga-PSMA-11-PET/CT overall positivity rate was 51.2%, while it was 40.3% in group 1, 54% in group 2, 60.5% in group 3, and 86.9% in group 4 (p < 0.001). At multivariable analyses, ISUP grade, PSA, PSA doubling time, and clinical setting were independent predictors of a positive scan (all p ≤ 0.04). A nomogram based on covariates included in the multivariate model demonstrated a bootstrap-corrected accuracy of 82%. The nomogram-derived best cutoff value was 40%. In DCA, the nomogram revealed clinical net benefit of > 10%. CONCLUSIONS: This novel nomogram proved its good accuracy in predicting a positive scan, with values ≥ 40% providing the most informative cutoff in counselling patients to 68Ga-PSMA-11-PET/CT. This tool might be important as a guide to clinicians in the best use of PSMA-based PET imaging.

Predictive accuracy and clinical benefit of a nomogram aimed to predict 68Ga-PSMA PET/CT positivity in patients with prostate cancer recurrence and PSA < 1 ng/ml external validation on a single institution database.

PURPOSE: To perform an external validation of a recently published nomogram aimed to predict positive 68Ga-PSMA-11 PET/CT in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) by Rauscher et al. (Eur Urol 73(5):656-661, 2018). METHODS: Overall, 413 PCa patients with BCR after RP (two consecutive PSA ≥ 0.2 ng/ml) and PSA value between 0.2 and 1 ng/ml were included. A multivariable logistic regression model was produced to assess the predictors of positive 68Ga-PSMA-11 PET/CT results. The performance characteristics of the model were assessed by quantifying the predictive accuracy, according to model calibration. Yuden's index was used to find the best nomogram's cut-off. Finally, decision curve analysis (DCA) was implemented to quantify the nomogram's clinical value. RESULTS: In the external cohort, the overall detection rate of 68Ga-PSMA-11 PET/CT was 44% vs. 64.7% in the original population. At multivariate analysis, PSA at 68Ga-PSMA-11 PET/CT (OR: 7.06, p < 0.001) and ongoing ADT at time of 68Ga-PSMA-11 PET/CT (OR: 2.07, p = 0.03) were the only independent predictors of PET/CT positivity. The predictive accuracy of nomogram was suboptimal and comparable to that reported in the original model (64% vs. 67%, respectively). The calibration plot indicated suboptimal concordance. The best nomogram's cut-off to predict positive 68Ga-PSMA-11 PET/CT was 35% (AUC = 0.61). In DCA, the nomogram revealed clinical net benefit when the threshold probabilities of positive 68Ga-PSMA-11 PET/CT is > 35%. CONCLUSION: We assessed similar suboptimal predictive accuracies in the external cohort compared to the original one. PSA and ongoing ADT were confirmed as positive predictors, and the most informative nomogram cut-off resulted 35%.

Clinical application of Fluciclovine PET, choline PET and gastrin-releasing polypeptide receptor (bombesin) targeting PET in prostate cancer.

PURPOSE OF REVIEW: The aim of this review is to explore the clinical application of different PET radiopharmaceuticals in prostate cancer (PCa), beyond inhibitors of the prostate-specific membrane antigen (PSMA). RECENT FINDINGS: Choline PET represented in the last decades the standard of reference for PET imaging in PCa and has been recently included in clinical trials evaluating the efficacy of metastasis-directed therapy in oligo-metastatic disease. Fluciclovine, as synthetic amino acid, has been proposed for investigating PCa. The results obtained by the first prospective studies led to FDA approval in 2016 in patients with biochemical recurrence. Recently, phase II/III trials explored its accuracy compared with PSMA PET and its impact on patient management. Imaging the gastrin-releasing polypeptide receptor (GRPR) recently drawn attention. Radio-labelled GRPR antagonists have the potential to be used as theranostic agents. Further evaluation is needed to understand the relation between GRPR expression and hormonal-resistant PCa, and for tumors characterized by heterogeneity of receptors expressed (e.g. PSMA-negative) on their cell surface. SUMMARY: Other new generation PET tracers may play an important role in PCa, namely in case of PSMA-negative phenotypes.

68Ga-PSMA-11 PET/CT in recurrent prostate cancer: efficacy in different clinical stages of PSA failure after radical therapy.

OBJECTIVES: The primary objective was the evaluation of Gallium 68 (68Ga)-prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computed tomography (PET/CT) detection rate, for identifying the site of prostate cancer (PCa) relapse (local vs systemic), stratifying the population according to different clinical stages of biochemical recurrence (BCR). Secondary aims were: 1) to evaluate the association of clinical/pathologic features and 68Ga-PSMA-11 PET/CT detection rate, 2) to compare 68Ga-PSMA-11 PET/CT with other imaging procedures, and 3) to evaluate the positive predictive value (PPV) in a per-patient analysis. MATERIAL AND METHODS: This population was enrolled through a prospective, open label, single-center trial performed at the Nuclear Medicine of the University Hospital of Bologna (Eudract: 2015-004589-27 OsSC). The inclusion criteria were: (1) proven PCa, (2) surgery or radiotherapy as definitive therapy, (3) proven BCR, (4) prostate-specific antigen (PSA) 0.2-2 ng/ml, (5) age ≥ 35 years, and 6() willing to sign an informed consent. Three-hundred and thirty-two (332) patients were enrolled between March 2016 and June 2017; mean/median PSA was 0.84/0.61 ng/ml, 97.9% (325/332) of patients received radical prostatectomy and 2.1% (7/332) radiotherapy. Different patterns of BCR were identified by referent physicians as follows: (a) persisting detectable PSA after radical prostatectomy in 13.5% (45/332) of patients (subgroup 1), (b) first-time PSA failure after radical therapy in 44.9% (149/332) (subgroup 2), and (c) PSA increase after salvage or hormonal therapy in 41.6% (138/332) (subgroup 3). RESULTS: Primary objective: 68Ga-PSMA-11 PET/CT detection rate was 53.6% (CI 95% 48.1%-59.1%). In a patient-based analysis, disease confined to pelvis (prostate bed and/or lymph-nodes) was detected in 24.7% of cases (82/332). The presence of at least one distant lesion was observed in 28.9% of cases (96/332). The detection rate in different subgroups was: subgroup 1 = 64.5%, subgroup 2 = 45.6%, and subgroup-3 = 58.7%. Secondary objectives: 1) PSA (p = 0.041) and PSAdt (p = 0.001) showed association with 68Ga-PSMA-11 PET/CT detection rate, and 2) correlative imaging was available in 73.2% of patients (243/332). When 68Ga-PSMA-11 PET/CT was positive, correlative imaging resulted negative in 83% of cases (108/130). 3) The calculated PPV was 96.2%. CONCLUSION: Our data confirmed the efficacy of 68Ga-PSMA-11 PET/CT for detecting local vs systemic disease in PCa patients presenting PSA failure after radical therapy. Furthermore, 68Ga-PSMA-11 PET/CT detection rate is different depending on the clinical stage of BCR, and this information should be taken into consideration by referring physicians.

68Ga-PSMA-11 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy and PSA <0.5 ng/ml. Efficacy and impact on treatment strategy.

PURPOSE: The primary aim of this retrospective, single-centre analysis was to assess the performance of 68Ga-PSMA-11 PET/CT in prostate cancer (PCa) patients in early PSA failure after radical prostatectomy (RP). The secondary aim was to assess the potential impact of 68Ga-PSMA-11 PET/CT on treatment strategy. METHODS: 68Ga-PSMA-11 PET/CT is performed in our institution within an investigational new drug (IND) trial in PCa patients with biochemical recurrence (BCR). The records of all patients enrolled between March 2016 and July 2017 were evaluated. These records were retrospectively analysed according to the following inclusion criteria: (a) RP as primary therapy, (b) proven BCR, ©) PSA levels in the range 0.2-0.5 ng/ml at the time of the 68Ga-PSMA-11 PET/CT investigation, and (d) no salvage radiotherapy (S-RT) performed after recurrence. The performance of 68Ga-PSMA-11 PET/CT was evaluated in terms of detection rate on a per-patient and a per-region basis (local vs. distant lesions). We further performed an intention-to-treat (ITT) analysis. The patient cohort was grouped into three subpopulations, blinded to the 68Ga-PSMA-11 PET/CT results, according to the patients' characteristics and different patterns of treatment: (1) S-RT (with or without systemic treatment), (2) stereotactic body radiotherapy (SBRT) (with or without systemic treatment), and (3) systemic treatment. The treatment strategy was re-evaluated for each patient taking into consideration the 68Ga-PSMA-11 PET/CT images. RESULTS: We enrolled 119 PCa patients (mean age 66 years, range 44-78 years) with a mean PSA level at the time of 68Ga-PSMA-11 PET/CT of 0.34 ng/ml (median 0.32 ng/ml, SD ±0.09, range 0.20-0.50 ng/ml). 68Ga-PSMA-1 1 PET/CT was positive in 41 of the 119 patients, resulting in an overall detection rate of 34.4%. 68Ga-PSMA-11 uptake was observed in the prostate bed (3 patients, 2.5%), in the pelvic lymph nodes (21, 17.6%), in the retroperitoneal lymph nodes (4, 3.4%) and in the skeleton (21, 17.6%). Regarding ITT, 81 patients (68.1%) were considered possible candidates for S-RT only in the prostate bed and none of the patients (0%) for SBRT. According to the 68Ga-PSMA-11 PET/CT results, the intended treatment was changed in 36 patients (30.2%). According to the PET/CT results, S-RT was recommended in 70 patients (58.8%), only to the prostate bed in 58 (48.7%) and SBRT in 29 (24.4%). The intended RT planning was modified in 36 (87.8%) of 41 patients with a positive 68Ga-PSMA-11 PET/CT result. CONCLUSION: In our patient series with PSA levels <0.5 ng/ml, 68Ga-PSMA-11 PET/CT had a detection rate of 34.4%. In the ITT analysis, 30.2% of patients had a change in the intended treatment. These data support the hypothesis that 68Ga-PSMA-11 PET/CT is a useful procedure in the management of PCa patients showing early recurrence after RP, and should be implemented in routine clinical practice.

Oligorecurrent prostate cancer limited to lymph nodes: getting our ducks in a row : Nodal oligorecurrent prostate cancer.

PURPOSE: Oligorecurrent prostate cancer with exclusive nodal involvement represents a common state of disease, amenable to local therapy. New radio-labeled tracers have enriched the possibility of cancer detection and treatment. In this review, we aim to illustrate the main nuclear medicine diagnostic options and the role of radiotherapy in this setting of patients. METHODS: We performed a PubMed search referring to the PRISMA guidelines to analyze the performance of PSMA- and choline-PET in detecting oligorecurrence limited to lymph nodes, and to review the main studies supporting either ablative stereotactic body radiotherapy or regional lymph node irradiation in this clinical setting. RESULTS: PSMA-PET has shown higher efficacy in the diagnosis of nodal lesions if compared with choline-PET. More specifically, for PSA ≤ 2 ng/ml, the median detection rate of choline-PET ranges from 19.5 to 44.5%, whereas PSMA ranges from 51.5 to 74%. SBRT achieves high local control rates positively affecting progression-free survival (PFS), with androgen deprivation therapy (ADT)-free survival ranging from 25 to 44 months and with low toxicity rates (0-15%). Prophylactic nodal irradiation shows 3-year PFS rates ranging from 62 to 75%, but with a potential higher risk of toxicity. However, the chosen treatment option needs to be tailored on the single patient. CONCLUSIONS: Newer PET/CT radio-labeled tracers have increased disease detection in oligorecurrent prostate cancer patients. Growing evidence of their impact on metastasis-directed therapy encourages the use of the most advanced radiotherapy techniques in the clinical management of such patients.

Current application and future perspectives of prostate specific membrane antigen PET imaging in prostate cancer.

As precision medicine evolves, the contribution of molecular imaging to the management of prostate cancer (PCa) patients, especially for positron-emission tomography (PET) imaging, is gaining importance. Highly successful approaches to measure the expression of the prostate specific membrane antigen (PSMA) have been introduced recently. PSMA, the glutamate carboxypeptidase II, is a membrane bound metallo-peptidase that is overexpressed in 90-100% of PCa cells. Due to its selective over-expression, PSMA is a reliable tissue marker for prostate cancer and is considered an ideal target for tumor specific imaging and therapy. A variety of PET and SPECT probes targeting this peptide receptor have been introduced. These are undergoing extensive clinical evaluations. Initial results attest to a high accuracy for disease detection compared conventional radiology (CT or MRI) and other nuclear medicine procedure (choline PET or fluciclovine PET). However, prospective evaluation of the impact on patient management for PSMA-ligand PET and its impact on patient outcome is currently missing. Finally, PSMA inhibitors can be radio-labeled with diagnostic (68Ga-PSMA-11), or therapeutic nuclides (177Lu/225Ac PSMA-617) to be used as theranostic agent. Initial results showed that PSMA-targeted radioligand therapy can potentially delay disease progression in metastatic castrate-resistant PCa. This review aims to explore the current application of PSMA based imaging in prostate cancer, reporting about main advantages and limitations of this new theranostic procedure. The future perspectives and potential the applications of this agent will be also discussed.

How does 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography impact the management of patients with prostate cancer recurrence after surgery?

OBJECTIVE: To evaluate the clinical impact of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography on the planned management of prostate cancer patients with biochemical recurrence after surgery. METHODS: We enrolled 276 prostate cancer patients referred to 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography due to biochemical recurrence after surgery (two consecutive prostate-specific antigen assays ≥0.2 ng/mL). First, the detection rate of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography was assessed according to different prostate-specific antigen levels. Second, the independent predictors of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography positive results were assessed. Finally, the intended treatment before revision of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography was assessed by a multidisciplinary team based on the European Association of Urology guidelines, patient clinical condition and clinical parameters. Then, re-assessment of the treatment plan was prospectively recorded by the same board after revision of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography. The effective clinical impact of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography was rated as major (change in therapeutic approach), minor (same treatment, but modified therapeutic strategy) or none. RESULTS: The overall detection rate of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography was 47.5%. Prostate-specific antigen at 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (odds ratio 3.52) and prostate-specific antigen doubling time <3 months (odds ratio 3.98) were independent predictors of positive 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography results (all P ≤ 0.03). 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography led to a major treatment change in 177 cases (64.1%), with a minor clinical impact of 2.5%. The overall clinical impact of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography was 42.4%, 27.7%, 21.2% and 8.7% in men with prostate-specific antigen at 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography of 0.2-0.4, 0.5-1, 1.1-2 and >2 ng/mL, respectively. CONCLUSIONS: 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography allows clinicians to radically change the intended treatment approach before imaging evaluation, in roughly two out three individuals.

State-of-the-art imaging techniques in the management of preoperative staging and re-staging of prostate cancer.

We aimed to review the current state-of-the-art imaging methods used for primary and secondary staging of prostate cancer, mainly focusing on multiparametric magnetic resonance imaging and positron-emission tomography/computed tomography with new radiotracers. An expert panel of urologists, radiologists and nuclear medicine physicians with wide experience in prostate cancer led a PubMed/MEDLINE search for prospective, retrospective original research, systematic review, meta-analyses and clinical guidelines for local and systemic staging of the primary tumor and recurrence disease after treatment. Despite magnetic resonance imaging having low sensitivity for microscopic extracapsular extension, it is now a mainstay of prostate cancer diagnosis and local staging, and is becoming a crucial tool in treatment planning. Cross-sectional imaging for nodal staging, such as computed tomography and magnetic resonance imaging, is clinically useless even in high-risk patients, but is still suggested by current clinical guidelines. Positron-emission tomography/computed tomography with newer tracers has some advantage over conventional images, but is not cost-effective. Bone scan and computed tomography are often useless in early biochemical relapse, when salvage treatments are potentially curative. New imaging modalities, such as prostate-specific membrane antigen positron-emission tomography/computed tomography and whole-body magnetic resonance imaging, are showing promising results for early local and systemic detection. Newer imaging techniques, such as multiparametric magnetic resonance imaging, whole-body magnetic resonance imaging and positron-emission tomography/computed tomography with prostate-specific membrane antigen, have the potential to fill the historical limitations of conventional imaging methods in some clinical situations of primary and secondary staging of prostate cancer.

Pathological and molecular diagnosis of bilateral inguinal lymph nodes metastases from low-grade endometrial adenocarcinoma: a case report with review of the literature.

BACKGROUND: Extra-abdominal metastases in low grade endometrial carcinoma are rare events. Inguinal lymphatic spread occurs usually in advanced disease and is associated with abdominal lymph nodes involvement. To our knowledge, isolated inguinal lymph node metastases in patients with early endometrial carcinoma have never been described thus far. CASE PRESENTATION: We present an uncommon case of inguinal lymph node metastasis in a 51-year old patient with early endometrial disease without other metastatic involvement. The metastatic loci were analyzed with the recently validated method of mitochondrial DNA sequencing to demonstrate clonality of the lesions. CONCLUSIONS: We describe the first case of inguinal metastasis from intramucous endometrial carcinoma; this case confirms the unpredictable spread of endometrial neoplasia and the importance of both patient's history and physical examination in good clinical practice.

New aspects of molecular imaging in prostate cancer.

Nowadays several new imaging modalities are available for investigating prostate cancer (PCa) such as magnet resonance imaging (MRI) in the form of whole body MRI and pelvic multiparametric MRI and positron emission tomography (PET) using choline as radiotracers. Nevertheless, these modalities proved sub-optimal accuracy for detecting PCa metastases, particularly in the recurrence setting. A new molecular probe targeting the prostate specific membrane antigen (PSMA) has been recently developed for PET imaging. PSMA, the glutamate carboxypeptidase II, is a membrane bound metallo-peptidase over-expressed in PCa cells. It has been shown that PSMA based imaging offers higher tumor detection rate compared to choline PET/CT and radiological conventional imaging, especially at very low PSA levels during biochemical recurrence. In addition PSMA, as theranostics agent, allows both radiolabeling with diagnostic (e.g. 68Ga, 18F) or therapeutic nuclides (e.g. 177Lu, 225Ac). Initial results show that PSMA-targeted radioligand therapy can potentially delay disease progression in metastatic castrate-resistant PCa. Despite still investigational, the bombesin-based radiotracers and antagonist of gastrin releasing-peptide receptor (GRP) (RM2) and anti1-amino-3-18Ffluorocyclobutane-1-carboxylic acid (18F-FACBC) are emerging as possible alternatives for investigating PCa. Considering the wide diffusion of PCa in the Europe and the United States, the presence of these new diagnostic techniques able to detect the disease with high sensitivity and specificity might have a clinical impact on the management of patients. PET/CT imaging with new radiopharmaceuticals can implement the patient management identifying lesion(s) not detectable with conventional imaging procedures. In this review article will be discussed the most promising new PET radiopharmaceuticals (68Ga-PSMA-11, 18F-FACBC, 68Ga-RM2) available at the moment, focusing the attention on their accuracy and their impact on treatment strategy.

Prognostic Impact of Pretreatment Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography SUVmax in Patients With Locally Advanced Cervical Cancer.

OBJECTIVE: The aim of this study was to investigate the impact of SUVmax fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) measured in the primary tumor, pelvic and para-aortic node with disease-free survival (DFS) and overall survival (OS) in patients with locally advanced cervical cancer. METHODS AND MATERIALS: A total of 92 patients with histological diagnosis of locally advanced cervical cancer are treated with radiochemotherapy plus brachytherapy boost from January 2008 to April 2014 in our Institution. A pretreatment FDG-PET/CT for staging and radiotherapy planning was performed, and the value of SUVmax measured in primary tumor and positive nodes was related to DFS and OS. RESULTS: Univariate analysis showed that DFS is related to FDG-PET/CT positive para-aortic nodes (P = 0.01), International Federation of Gynecology and Obstetrics (FIGO) stage of disease (P = 0.01), and primary tumor SUVmax (P = 0.02), and OS is related to positive para-aortic nodes (P = 0.01) and primary tumor SUVmax (P = 0.02).In multivariate analysis, DFS is modified by FDG-PET/CT positive para-aortic lymph nodes, stage and high T SUVmax (P = 0.02; P = 0.003; P = 0.04), but the only worse prognostic factor of OS is the high SUVmax in the primary tumor (P = 0.01). CONCLUSIONS: We found that T SUVmax, stage, and para-aortic lymph node status assessed by FDG-PET were independent prognostic factors of DFS, whereas only T SUVmax correlated with OS.

Therapy assessment in prostate cancer using choline and PSMA PET/CT.

While PET with non-FDG tracers (mainly choline and Ga-PSMA) has commonly been used for restaging in men with biochemically recurrent prostate cancer, as well as for primary staging, it is only recently that a few preliminary studies have addressed the possible use of PET for monitoring the response to systemic therapy of metastatic disease, especially innovative treatments such as abiraterone and enzalutamide. This article aims to evaluate the role of PET imaging with different non-FDG radiotracers for assessment of therapy in advanced prostate cancer patients.

The role of 18F-FDG PET/CT in the detection of osteosarcoma recurrence.

AIM: The aim of this study was to investigate the diagnostic accuracy of 18F-FDG-PET/CT in osteosarcoma patients suspicious for disease recurrence after adequate surgical therapy. METHODS: Inclusion criteria were: a) adequate surgical treatment for proven osteosarcoma and documented complete remission after therapy; b) 18F-FDG-PET/CT performed during follow-up for clinical/diagnostic suspicion of relapse; c) new surgical treatment with excision of the suspected lesions; d) histological validation of 18F-FDG-PET/CT findings. Thirty-seven patients matching all inclusion criteria were retrospectively enrolled (20 men and 17 female). Primary surgical treatment consists of resection (31 cases) or amputation (six cases). 18F-FDG-PET/CT performance was assessed with a per-patient and per-site evaluation of sensitivity, specificity, accuracy, positive predicting value (PPV), and negative predicting value (NPV). The sites of relapse were classified as local, lung, lymphnodes (LNs), and distant (other skeletal segments and/or distant soft tissue). The disease-free survival (DFS) and the overall survival (OS) after 18F-FDG PET/CT were evaluated. RESULTS: 18F-FDG-PET/CT was positive in 89.2% (33/37) of patients. Local uptake only was observed in 35.1% patients (13/37); lung uptake only in 18.9% (7/37); distant uptake only in 2.7% (1/37) case; multiple sites of uptake in 32.4% (12/37). Histology resulted positive in 92% (34/37) of patients. A total of 51 pathologic lesions were evaluated (22 local relapse, 11 lung metastasis, 10 metastatic LNs, eight distant metastatic lesions). On a per-patient analysis 18F-FDG-PET/CT showed a sensitivity, specificity, accuracy, PPV, and NPV of 91%, 75%, 89%, 97%, 50%. On a per-site analysis the performance for local relapse was 96%, 100%, 97%, 100%, 93%, while for lung relapse detection was 80%, 100%, 92%, 100%, 88%. The mean follow-up after 18F-FDG-PET/CT was 21.5 months. At the last follow-up, 19% (7/37) of patients were death with disease, 38% (14/37) were alive with disease, and 43% (16/37) had no evidence of disease. Overall survival was 90% and 75% at 24 and 60 months, respectively. CONCLUSION: 18F-FDG-PET/CT showed valuable results for detecting recurrence(s) in osteosarcoma patients with suspicious of relapse after treatment, particularly in the detection of local relapse and lung metastasis.