A Prospective Randomized Multicenter Study on the Impact of [18F]F-Choline PET/CT Versus Conventional Imaging for Staging Intermediate- to High-Risk Prostate Cancer.

This study aimed to compare the efficacy of [18F]F-choline PET/CT with conventional imaging for staging and managing intermediate- to high-risk prostate cancer (PCa). The primary objective was to assess the ability of PET/CT with [18F]F-choline to identify lymph node and systemic involvement during initial staging. Secondary objectives included evaluating the impact of [18F]F-choline PET/CT on unnecessary local treatments and assessing the safety of [18F]F-choline agents. Additionally, the study aimed to analyze recurrence-free survival and overall survival 5 y after randomization. Methods: A prospective controlled, open, randomized multicenter phase III trial involving 7 Italian centers was conducted. Eligible patients with intermediate- to high-risk PCa were randomized in a 1:1 ratio. Two groups were formed: one undergoing conventional imaging (abdominopelvic contrast-enhanced CT and bone scanning) and the other receiving conventional imaging plus [18F]F-choline PET/CT. The study was terminated prematurely; however, all the endpoints were thoroughly analyzed and enriched. Results: Between February 2016 and December 2020, 256 patients were randomly assigned. In total, 236 patients (117 in the control arm and 119 in the experimental arm) were considered for the final assessment. In the experimental arm, the sensitivity for lymph node metastases, determined by final pathology and serial prostate-specific antigen evaluations, was higher than in the control arm (77.78% vs. 28.57% and 65.62% vs. 17.65%, respectively). The [18F]F-choline was tolerated well. The use of [18F]F-choline PET/CT resulted in an approximately 8% reduction in unnecessary extended lymphadenectomy compared with contrast-enhanced CT. Additionally, [18F]F-choline PET/CT had a marginal impact on 5-y overall survival, contributing to a 4% increase in survival rates. Conclusion: In the initial staging of PCa, [18F]F-choline PET/CT exhibited diagnostic performance superior to that of conventional imaging for detecting metastases. [18F]F-choline PET/CT reduced the rate of unnecessary extensive lymphadenectomy by up to 8%. These findings support the consideration of discontinuing conventional imaging for staging PCa.

Concurrent chemoradiotherapy with tomotherapy in locally advanced Non-Small Cell Lung Cancer: a phase I, docetaxel dose-escalation study, with hypofractionated radiation regimen.

BACKGROUND: Concurrent chemo-radiotherapy is demonstrately superior to sequential chemo-radiotherapy in the treatment of advanced Non-Small-Cell Lung Cancer not suitable for surgery. Docetaxel is considered to enhance the cytotoxic effect of radiotherapy on the tumour cells. Tomotherapy (HT) is a novel radiotherapeutic technique, which allows the delivery of Image Guided-IMRT (IG-IMRT), with a highly conformal radiation dose distribution.The goal of the study was to estimate tolerability of Docetaxel concurrent with IMRT and to find the maximum tolerated dose of weekly Docetaxel concurrent with IMRT delivered with HT Tomotherapy after induction chemotherapy with Cisplatin and Docetaxel in patients affected with stage III Non-Small Cell Lung Cancer. METHODS: We designed a phase I, dose-finding study to determine the dose of weekly Docetaxel concurrent with Tomotherapy after induction chemotherapy, in patients affected by Non-Small Cell Lung Cancer with Stage III disease, not suitable for surgery. RESULTS: Concurrent weekly Docetaxel and Tomotherapy are feasible; we did not reach a maximum tolerated dose, because no life-threatening toxicity was observed, stopping the accrual at a level of weekly docetaxel 38 mg/m2, a greater dose than in previous assessments, from both phase-I studies with weekly docetaxel alone and with Docetaxel concomitant with standard radiotherapy. CONCLUSIONS: Concurrent weekly Docetaxel and Tomotherapy are feasible, and even with Docetaxel at 38 mg/m2/week we did not observe any limiting toxicity. For those patients who completed the combined chemo-radio treatment, median progression-free survival (PFS) was 20 months and median overall survival (OS) was 24 months.

Radical Hemithoracic Radiotherapy Versus Palliative Radiotherapy in Non-metastatic Malignant Pleural Mesothelioma: Results from a Phase 3 Randomized Clinical Trial.

PURPOSE: We conducted a phase 3 randomized clinical trial to assess whether radical hemithoracic radiation therapy (RHR) compared with palliative radiation therapy (PR) can achieve overall survival (OS) advantages in patients with malignant pleural mesothelioma (MPM). METHODS AND MATERIALS: From August 2014 to May 2018, patients with histologically diagnosed nonmetastatic MPM, who underwent nonradical lung-sparing surgery and chemotherapy (CHT), were randomly assigned (1:1) to receive RHR or PR. RHR total dose to the involved pleural cavity was 50 Gy in 25 fractions, and the gross residual disease received a simultaneous integrated boost of 60 Gy. The primary endpoint was OS. Secondary endpoints were local control, distant metastasis-free survival, progression-free survival, and acute and late toxicity rates. A sample size of 108 patients considering a type I error (α) of 0.05 and a statistical power of 80% was calculated to prove that RHR could improve the 2-year OS. OS was estimated with the Kaplan-Meier method and the log-rank test (2-sided) tested differences between arms. The univariate and multivariate analyses were performed using Cox proportional hazard model. Possible prognostic factors investigated: age, sex, performance status, lung surgery, gross residual disease, and histology. RESULTS: One hundred eight patients were randomized: 53 to the PR arm and 55 to the RHR arm. Median follow-up was 14.6 months. The 2-year OS rate was 58% in the RHR arm versus 28% in the PR arm (hazard ratio, 0.54; 95% confidence interval, 0.31-0.95; P = .031). In the RHR arm: 11 patients experienced acute toxicity grade ≥3, 17 patients had grade 3 to 4 late toxicity. Nine patients experience a grade ≥2 pneumonitis, including 1 patient with grade 5. CONCLUSIONS: RHR significantly improves survival in patients with MPM treated with nonradical lung-sparing surgery and CHT compared with palliative treatments, although it is associated with a nonnegligible toxicity profile.

Probe-based confocal laser endomicroscopy (pCLE) is a suitable method for extrapulmonary high grade neuroendocrine rectal carcinoma (HGNEC) evaluation.

The potential role of the probe-based confocal laser endomicroscopy (pCLE) has been analyzed in different pathologic conditions of the gastrointestinal tract. Here, we analyzed a case of extrapulmonary high grade neuroendocrine rectal carcinoma (HGNEC) using, for the first time, the pCLE system. A 72-year old man was diagnosed with an 8 cm diameter rectal HGNEC by standard colonoscopy integrated with the pCLE system. The diagnosis of neuroendocrine carcinoma was confirmed by immunohistochemical analyses. By using the pCLE system, we well defined and resolved vascular structures and mucosal architecture. An altered mucosal pattern and vascular defects, peculiar for HGNEC, were observed at high magnification, allowing the identification of a pattern which was quite different from that observed in poorly differentiated adenocarcinomas (PDA) where tissues appear darker, very irregular, even if glandular structures can still be recognized. This underlines the usefulness of pCLE in discriminating HGNECs from PDAs. In conclusion, pCLE could represent a valid and helpful method for in vivo HGNEC diagnosis, allowing prompt and careful management of the patient.

Ectopic Adrenocorticotropic Hormone-Secreting Pituitary Adenoma Localized by 18F-Choline PET/CT.

The criterion standard of treatment of an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is complete surgical excision. However, ectopic location of these adenomas is an extremely rare condition, which may affect the diagnosis and treatment success. We report a case of a 49-year-old man who was referred to our institution with persistent hypercortisolemia after an unsuccessful attempt of surgical resection. F-choline PET/CT revealed increased radiopharmaceutical uptake in a nodule localized in the left maxillary sinus, which was proved at histology to be an ectopic ACTH-secreting pituitary adenoma staining positive for ACTH. Imaging with F-FDG PET/CT and Ga-DOTA-NOC PET/CT was not diagnostic.

Malignant struma ovarii harboring a unique NRAS mutation: case report and review of the literature.

Struma ovarii (SO), a rare tumor containing at least 50% of thyroid tissue, represents approximately 5% of all ovarian teratomas; its malignant transformation rate is reported to occur in up to 10% of cases and metastases occur in about 5-6% of them. We describe a 36-year old woman who underwent laparoscopic left annessectomy two years earlier because of an ovarian cyst. Follow-up imaging revealed a right adnexal mass, ascitis and peritoneal nodes that were diagnosed as comprising a malignant SO with peritoneal secondary localizations at histopathology performed after intervention. Restaging with 18F-FDG-PET/CT scan, abdominal CT and ultrasonography showed abnormalities in the perihepatic region and presacral space and left hypochondrium localizations. The patient underwent thyroidectomy, hepatic nodulectomy and cytoreductive peritonectomy: histopathological examination did not show any malignant disease in the thyroid and confirmed the presence of peritoneal localizations due to malignant SO; molecular analysis detected NRAS Q61K mutation in exon 3, whereas no mutations were identified on the BRAF gene. The patient underwent radioiodine treatment: serum Tg was decreased at first follow-up after three months of 131I-therapy. We believe that our case raises some interesting considerations. First, pathologists should be aware of this entity and should check for the presence of point mutations suggesting an aggressive disease behavior, which could be beneficial for an optimal therapeutic approach. Second, although most of the knowledge in this field comes from case reports, efforts should be made to standardize the management of patients affected by malignant SO, including use of practice guidelines.

[18F]fluorocholine PET/CT imaging for the detection of recurrent prostate cancer at PSA relapse: experience in 100 consecutive patients.

PURPOSE: We evaluated the potential of PET/CT and [(18)F]fluoromethylcholine (FCH) in the assessment of suspected recurrence of prostate cancer after treatment. METHODS: One hundred consecutive prostate cancer patients with a persistent increase in serum PSA (>0.1 ng/ml) after radical prostatectomy (58 cases), radiotherapy (21 cases) or hormonal therapy alone (21 cases) were investigated. After injection of 3.7-4.07 MBq/kg of FCH, both early (at <15 min) and delayed (at >60 min) PET/CT scans were performed in 43 patients, delayed PET/CT scans in 53 patients and early PET/CT scans in four patients. RESULTS: Of the 100 patients, 54 (PSA 0.22-511.79 ng/ml) showed positive FCH PET/CT scans. Thirty-seven patients had bone and/or abdominal lymph node uptake, while 17 showed pelvic activity. Malignant disease was confirmed in all but one. Delayed SUV(max) of bone metastases was significantly higher (p<0.0001 by paired t test) than that measured at <15 min, whereas no differences were observed between early and delayed SUVs of malignant lymph nodes or pelvic disease. Forty-six patients (PSA 0.12-14.3 ng/ml) showed negative FCH PET/CT scans. Of the negative PET/CT scans, 89% were obtained in patients with serum PSA <4 ng/ml and 87% in patients with a Gleason score <8. In none of these cases could recurrent tumour be proven clinically during a follow-up of 6 months. CONCLUSION: FCH PET/CT is not likely to have a significant impact on the care of prostate cancer patients with biochemical recurrence until PSA increases to above 4 ng/ml. However, in selected patients, FCH PET/CT helps to exclude distant metastases when salvage local treatment is intended.

Malignant cardiac tumors: diagnosis and treatment.

Primary malignant cardiac tumors are represented by sarcomas and non-Hodgkin lymphomas. They are rare, affect mostly patients in the fourth decade of life and have a severe prognosis. Both the diagnosis and the treatment require a multidisciplinary approach, and the cardiologist plays a central role both in the diagnosis and in the follow-up. The prognosis may be improved by a careful planning of surgery and by the use of multimodality treatment, including complementary chemotherapy and radiation therapy. A strict follow-up must be planned even after apparently complete cure.

Bartter's syndrome and captopril scintigraphy: a case report.

We report a case of a woman who came to our attention because of hypokalemia, hyperreninemia and hyperaldosteronemia but with normal blood pressure. Under suspicion of a normotensive renal artery stenosis captopril and baseline scintigraphies were performed. Captopril scintigraphy demonstrated a bilateral progressive retention of radiopharmaceutical without significant excretion. The baseline study revealed a complete normalization of the scintigraphyc picture. A Magnetic Resonance Angiography (Angio-MRI) performed to evaluate renal arteries gave completely normal results. On the basis of the clinical picture and imaging findings a diagnosis of Bartter's syndrome was formulated. Renal function in Bartter's syndrome patients is maintained by hyperactivation of the renin angiotensin system. Acute administration of captopril in these patients induces an increase of renal plasma flow whereas it has no effects on glomerular filtration rate thus inducing a decrease of the filtration fraction: post captopril renal scintigraphy of our patient depicted exactly this feature. Although the diagnosis of Bartter's syndrome is based on the clinical picture and biochemical abnormalities, scintigraphic tests could be useful in differentiating Bartter's syndrome from other causes of hypokalemia.

Complete metabolic remission with Gefitinib in a hemodialysis patient with bone metastases from non-small cell lung cancer.

Gefitinib is highly active in patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring activating mutation of the epidermal growth factor receptor (EGFR) gene. The feasibility and the degree of response to treatment with gefitinib in patients with chronic renal failure (CRF) undergoing hemodialysis has not yet been fully described in literature. We describe the case of a 70-year-old man with CRF undergoing hemodialysis three times-a-week who developed vertebral and rib bone metastasis three years after lobectomy. The bone biopsy confirmed the pulmonary origin and pyrosequencing analysis revealed deletion in E746-E750 of exon 19. We started daily administration of 250 mg gefitinib with no changes in the hemodialysis schedule. Gefitinib was well-tolerated without any adverse event. After three months, the (18)F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG PET/CT) showed complete metabolic remission of bone lesions. The patient is still under treatment and maintains response (30 months to date). To our knowledge, this is the first description of complete metabolic remission in this type of patient. In conclusion, gefitinib has been safely administered to a patient with NSCLC with EGFR-activating mutation undergoing chronic hemodialysis and its use has achieved an excellent and prolonged response on bone metastases.

Chemo/tomotherapy stereotactic body radiation therapy (chemo/SBRT) for the salvage treatment of esophageal carcinoma following trimodality therapy: a case report.

BACKGROUND: Esophageal cancer (EC) patients presenting a local recurrence following trimodality therapy (chemoradiaton and surgery) have limited palliative treatment options when the three major modalities of therapy have been exhausted. In addition, some patients experience a local recurrence or develop a metachronous cancer in a previously irradiated site, without evidence of systemic disease. For these patients there is a potential for cure, although the risk of further distant recurrences remains high. CASE REPORT: We report of a successful concomitant chemo/SBRT treatment in a case of locally advanced metachronous squamous cervical EC, which was diagnosed in a patient previously treated with trimodality therapy for a squamous tonsillar carcinoma. RESULT: Chemo/SBRT seems to be a reasonable salvage option for patients without distant metastases who have exhausted standard therapies. CONCLUSIONS: Our experience also suggests that a concomitant chemo/SBRT treatment appears to be either feasible or effective and chemo/SBRT can be considered also in selected patients affected by EC with squamous histology and with neoplastic infiltration of the trachea.

Revisiting the clinical value of 18F-FDG PET/CT in detection of recurrent epithelial ovarian carcinomas: correlation with histology, serum CA-125 assay, and conventional radiological modalities.

OBJECTIVE: This study aimed to evaluate the efficiency of 18F-FDG PET/CT in suspected recurrence of epithelial ovarian cancer, after treatment, comparing outcomes of PET/CT with histological tumor subtype, CA-125 serum levels, and findings of conventional diagnostic imaging modalities (CI). METHODS: Data from 121 women who underwent FDG PET/CT for suspected recurrence of epithelial ovarian cancer after treatment were reviewed retrospectively. RESULTS: Of all patients, 80% had recurrent disease and 20% were disease-free on the final clinical diagnosis. PET/CT showed true-positive findings in 82% of patients, whereas CI demonstrated true-positives in 70% of cases. At the time of PET/CT scanning, only 55 patients had serum CA-125 level greater than 35 U/mL, whereas 52 patients presented with CA-125 levels in a reference range. PET/CT sensitivity (82%) was significantly higher than that of CA-125 (59%), whereas difference in sensitivity between PET/CT and CI (69%) was limited. PET/CT specificity (87%) was significantly better than that of CI (47%), although no difference in specificity between PET/CT and CA-125 (80%) was found. However, no difference in CA-125 serum levels between patients with local tumor relapse and those with distant metastases was found. PET/CT showed the highest positive predictive value (96%) and negative predictive value (55%) when compared with other modalities. In high-grade tumors (n = 66), PET/CT accuracy was 80%, better than that of serum CA-125 (64%) and that of CI (62%). Equally in low-grade ovarian carcinomas (n = 55), PET/CT accuracy (87%) was significantly higher than that of the tumor marker (60%) and also higher than that of CI (70%). CONCLUSIONS: FDG PET/CT was proven to be more efficient than serum CA-125 assay and CI in detecting recurrences of ovarian cancer after treatment. The sensitivity of FDG PET/CT is not influenced by tumor histology. FDG PET/CT should be considered a useful diagnostic tool in the surveillance of patients that received treatment for epithelial ovarian carcinoma.