Machine learning-based differentiation between multiple sclerosis and glioma WHO II°-IV° using O-(2-[18F] fluoroethyl)-L-tyrosine positron emission tomography.

INTRODUCTION: This study aimed to test the diagnostic significance of FET-PET imaging combined with machine learning for the differentiation between multiple sclerosis (MS) and glioma II°-IV°. METHODS: Our database was screened for patients in whom FET-PET imaging was performed for the diagnostic workup of newly diagnosed lesions evident on MRI and suggestive of glioma. Among those, we identified patients with histologically confirmed glioma II°-IV°, and those who later turned out to have MS. For each group, tumor-to-brain ratio (TBR) derived features of FET were determined. A support vector machine (SVM) based machine learning algorithm was constructed to enhance classification ability, and Receiver Operating Characteristic (ROC) analysis with area under the curve (AUC) metric served to ascertain model performance. RESULTS: A total of 41 patients met selection criteria, including seven patients with MS and 34 patients with glioma. TBR values were significantly higher in the glioma group (TBRmax glioma vs. MS: p = 0.002; TBRmean glioma vs. MS: p = 0.014). In a subgroup analysis, TBR values significantly differentiated between MS and glioblastoma (TBRmax glioblastoma vs. MS: p = 0.0003, TBRmean glioblastoma vs. MS: p = 0.0003) and between MS and oligodendroglioma (ODG) (TBRmax ODG vs. MS: p = 0.003; TBRmean ODG vs. MS: p = 0.01). The ability to differentiate between MS and glioma II°-IV° increased from 0.79 using standard TBR analysis to 0.94 using a SVM based machine learning algorithm. CONCLUSIONS: FET-PET imaging may help differentiate MS from glioma II°-IV° and SVM based machine learning approaches can enhance classification performance.

A new mobile self-dispensing and administering system for 18F-FDG: evaluation of operator dose reduction.

PURPOSE: Recently new mobile systems for dispensing positron emitters have been produced, designed to guarantee dispensing cycles in an aseptic environment. The aim of the present work was to assess the advantage of one of these systems in radiation protection of operators in clinical settings. METHODS: Recently, in our centre the new self-dispensing system named KARL100 by Tema Sinergie was adopted for 18F-FDG radiopharmaceuticals. The system is associated with an automatic Rad-inject infuser. The system that was previously used was a fixed isolator NMC DSI (Tema Sinergie), equipped with a µDDS-An activity fractioning system, together with a pneumatic post for the syringe delivery. The dosimetric evaluations on both systems were carried out through environmental measurements with an ionisation chamber and with the use of personal dosimeters. RESULTS: The operations of preparation and administration of 18F-FDG dose to the patient, with the use of Karl100 + RadInject, involve exposures much lower than those obtained by the fixed isolator. The average body exposure of the technician was reduced by 31%, and for the physician by 77%. On the extremities, the equivalent dose to the hands of the technician was reduced by 78%, and for the physician by 96%. Also the additional dosimeters worn by the technician confirmed the estimated environmental assessments. CONCLUSIONS: The exposures of the working personnel were significantly reduced with the introduction of the new KARL100 system.

European Association of Nuclear Medicine Practice Guideline/Society of Nuclear Medicine and Molecular Imaging Procedure Standard 2019 for radionuclide imaging of phaeochromocytoma and paraganglioma.

PURPOSE: Diverse radionuclide imaging techniques are available for the diagnosis, staging, and follow-up of phaeochromocytoma and paraganglioma (PPGL). Beyond their ability to detect and localise the disease, these imaging approaches variably characterise these tumours at the cellular and molecular levels and can guide therapy. Here we present updated guidelines jointly approved by the EANM and SNMMI for assisting nuclear medicine practitioners in not only the selection and performance of currently available single-photon emission computed tomography and positron emission tomography procedures, but also the interpretation and reporting of the results. METHODS: Guidelines from related fields and relevant literature have been considered in consultation with leading experts involved in the management of PPGL. The provided information should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals. CONCLUSION: Since the European Association of Nuclear Medicine 2012 guidelines, the excellent results obtained with gallium-68 (68Ga)-labelled somatostatin analogues (SSAs) in recent years have simplified the imaging approach for PPGL patients that can also be used for selecting patients for peptide receptor radionuclide therapy as a potential alternative or complement to the traditional theranostic approach with iodine-123 (123I)/iodine-131 (131I)-labelled meta-iodobenzylguanidine. Genomic characterisation of subgroups with differing risk of lesion development and subsequent metastatic spread is refining the use of molecular imaging in the personalised approach to hereditary PPGL patients for detection, staging, and follow-up surveillance.

The EANM practical guidelines for sentinel lymph node localisation in oral cavity squamous cell carcinoma.

PURPOSE: Sentinel lymph node biopsy is an essential staging tool in patients with clinically localized oral cavity squamous cell carcinoma. The harvesting of a sentinel lymph node entails a sequence of procedures with participation of specialists in nuclear medicine, radiology, surgery, and pathology. The aim of this document is to provide guidelines for nuclear medicine physicians performing lymphoscintigraphy for sentinel lymph node detection in patients with early N0 oral cavity squamous cell carcinoma. METHODS: These practice guidelines were written and have been approved by the European Association of Nuclear Medicine (EANM) and the International Atomic Energy Agency (IAEA) to promote high-quality lymphoscintigraphy. The final result has been discussed by distinguished experts from the EANM Oncology Committee, and national nuclear medicine societies. The document has been endorsed by the Society of Nuclear Medicine and Molecular Imaging (SNMMI). These guidelines, together with another two focused on Surgery and Pathology (and published in specialised journals), are part of the synergistic efforts developed in preparation for the "2018 Sentinel Node Biopsy in Head and Neck Consensus Conference". CONCLUSION: The present practice guidelines will help nuclear medicine practitioners play their essential role in providing high-quality lymphatic mapping for the care of early N0 oral cavity squamous cell carcinoma patients.

Guideline for PET/CT imaging of neuroendocrine neoplasms with 68Ga-DOTA-conjugated somatostatin receptor targeting peptides and 18F-DOPA.

PURPOSE & METHODS: Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using 68Ga-DOTA-conjugated peptides, as well as 18F-DOPA imaging for various neuroendocrine neoplasms. RESULTS & CONCLUSION: The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with 68Ga-conjugated peptides has been revised and updated with the relevant and recent literature in the field with contribution of distinguished experts.

Advances in radioguided surgery in oncology.

The sentinel lymph node (SLN) biopsy is probably the most well-known radioguided technique in surgical oncology. Today SLN biopsy reduces the morbidity associated with lymphadenectomy and increases the identification rate of occult lymphatic metastases by offering the pathologist the lymph nodes with the highest probability of containing metastatic cells. These advantages may result in a change in clinical management both in melanoma and breast cancer patients. The SLN evaluation by pathology currently implies tumor burden stratification for further prognostic information. The concept of SLN biopsy includes pre-surgical lymphoscintigraphy as a "roadmap" to guide the surgeon toward the SLNs and to localize unpredictable lymphatic drainage patterns. In addition to planar images, SPECT/CT improves SLN detection, especially in sites closer to the injection site, providing anatomic landmarks which are helpful in localizing SLNs in difficult to interpret studies. The use of intraoperative imaging devices allows a better surgical approach and SLN localization. Several studies report the value of such devices for excision of additional sentinel nodes and for monitoring the whole procedure. The combination of preoperative imaging and radioguided localization constitutes the basis for a whole spectrum of basic and advanced nuclear medicine procedures, which recently have been encompassed under the term "guided intraoperative scintigraphic tumor targeting" (GOSTT). Excepting SLN biopsy, GOSTT includes procedures based on the detection of target lesions with visible uptake of tumor-seeking radiotracers on SPECT/CT or PET/CT enabling their subsequent radioguided excisional biopsy for diagnostic of therapeutic purposes. The incorporation of new PET-tracers into nuclear medicine has reinforced this field delineating new strategies for radioguided excision. In cases with insufficient lesion uptake after systemic radiotracer administration, intralesional injection of a tracer without migration may enable subsequent excision of the targeted tissue. This approach has been helpful in non-palpable breast cancer and in solitary pulmonary nodules. The introduction of allied technologies like fluorescence constitutes a recent advance aimed to refine the search for SLNs and tracer-avid lesions in the operation theatre in combination with radioguidance.

Aberrant right subclavian artery ("arteria lusoria") without the known associated nerve anomaly: an "anomaly of the anomaly"? A clinical case and review of the literature.

The "non-recurrent" course of the inferior laryngeal nerve (ILN) is an anatomical variant which must be borne in mind during thyroid surgery. The "non-recurrent" course of the ILN on the right side is associated with the aberrant right subclavian artery (arteria lusoria), and, on the left, is described in situs viscerum inversus. We present a case in which the "arteria lusoria" was not associated with the non-recurrent right ILN. The aims of this paper are to report this "anomaly of the anomaly" to surgeons who may be unaware of it on the one hand and on the other to emphasize that this is the only case so far reported in the literature. Moreover we proposed to explain embryologically these unexpected findings.

(18)F-FDG PET/CT quantification in head and neck squamous cell cancer: principles, technical issues and clinical applications.

(18)F-FDG PET/CT plays a crucial role in the diagnosis and management of patients with head and neck squamous cell cancer (HNSCC). The major clinical applications of this method include diagnosing an unknown primary tumour, identifying regional lymph node involvement and distant metastases, and providing prognostic information. (18)F-FDG PET/CT is also used for precise delineation of the tumour volume for radiation therapy planning and dose painting, and for treatment response monitoring, by detecting residual or recurrent disease. Most of these applications would benefit from a quantitative approach to the disease, but the quantitative capability of (18)F-FDG PET/CT is still underused in HNSCC. Innovations in PET/CT technology promise to overcome the issues that until now have hindered the employment of dynamic procedures in clinical practice and have limited "quantification" to the evaluation of standardized uptake values (SUV), de facto a semiquantitative parameter, the limits of which are well known to the nuclear medicine community. In this paper the principles of quantitative imaging and the related technical issues are reviewed so that professionals involved in HNSCC management can reflect on the advantages of "true" quantification. A discussion is then presented on how semiquantitative information is currently used in clinical (18)F-FDG PET/CT applications in HNSCC, by discussing the improvements that could be obtained with more advanced and "personalized" quantification techniques.

Diagnostic accuracy and impact on management of (18)F-FDG PET and PET/CT in colorectal liver metastasis: a meta-analysis and systematic review.

PURPOSE: The first aim of the review (aim 1) was to obtain the diagnostic performance values of (18)F-FDG PET for the detection and staging of liver metastases in patients with colorectal cancer (CRC), the second aim (aim 2) was to compare PET and conventional imaging modalities, and the third aim (aim 3) was to evaluate the impact of PET on patient management. The incidence of extrahepatic disease (EHD) detected by PET is also reviewed. METHODS: A comprehensive search was performed on PubMed/MEDLINE for studies evaluating PET and PET/CT in CRC patients with liver metastases up to June 2014. For inclusion PET had to have been performed prior to surgery, there had to be at least 18 patients in the study, and the reported data had to allow calculation of 2 × 2 contingency tables (for aim 1). A total of 18 studies were eligible for at least one of the three intended subanalyses including a total of 1,059 patients. Pooled sensitivity, specificity and accuracy and the corresponding 95 % confidence intervals were derived from the contingency tables on a patient basis (patient-based analysis, PBA) and a lesion basis (lesion-based analysis, LBA) for eight studies. RESULTS: Pooled sensitivity and specificity of PET on PBA were both 93 %. Corresponding values for LBA were 60 % and 79 %, respectively. Areas under the summary ROC were 0.97 for PBA and 0.67 for LBA. Regarding aim 2, PET had a slightly lower sensitivity than MRI and CT on PBA (93 %, 100 % and 98 %, respectively) and LBA (66 %, 89 % and 79 %, respectively) but appeared to be more specific than MRI and CT (86 %, 81 % and 67 %, respectively). PET findings resulted in changes in the management of a mean of 24 % of patients. The mean incidence of PET-based EHD was 32 %. CONCLUSION: This meta-analysis suggests that FDG PET/CT is highly accurate for the detection of liver metastases on a patient basis but less accurate on a lesion basis. Compared to MRI, PET is less sensitive but more specific and affects the management of about one-quarter of patients.

Sentinel lymph node biopsy in oral and oropharyngeal squamous cell carcinoma: current status and unresolved challenges.

Because imaging with ultrasound, computed tomography, magnetic resonance imaging or positron emission tomography is unreliable for preoperative lymph node staging of early-stage oral and oropharyngeal squamous cell carcinoma (OSCC), elective neck dissection has been typically performed. The targeted sampling of sentinel lymph nodes (SLN) identified by lymphoscintigraphy and detected by gamma probe has become an effective alternative for the selection of patients for regional nodal resection. With careful consideration to technique, high SLN detection rates have been reported. Advanced techniques including intraoperative handheld gamma camera imaging and freehand single photon emission computed tomography (SPECT) are expected to increase surgical confidence in these procedures. This review gives an update on SLN biopsy in patients with OSCC including clinical standards and controversial aspects.

EANM practice guidelines for lymphoscintigraphy and sentinel lymph node biopsy in melanoma.

PURPOSE: Sentinel lymph node biopsy is an essential staging tool in patients with clinically localized melanoma. The harvesting of a sentinel lymph node entails a sequence of procedures with participation of specialists in nuclear medicine, radiology, surgery and pathology. The aim of this document is to provide guidelines for nuclear medicine physicians performing lymphoscintigraphy for sentinel lymph node detection in patients with melanoma. METHODS: These practice guidelines were written and have been approved by the European Association of Nuclear Medicine (EANM) to promote high-quality lymphoscintigraphy. The final result has been discussed by distinguished experts from the EANM Oncology Committee, national nuclear medicine societies, the European Society of Surgical Oncology (ESSO) and the European Association for Research and Treatment of Cancer (EORTC) melanoma group. The document has been endorsed by the Society of Nuclear Medicine and Molecular Imaging (SNMMI). CONCLUSION: The present practice guidelines will help nuclear medicine practitioners play their essential role in providing high-quality lymphatic mapping for the care of melanoma patients.

Value of (18)F-FDG PET for Predicting Response to Neoadjuvant Therapy in Rectal Cancer: Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study was to assess the predictive value of (18)F-FDG PET/ CT for pathologic response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. MATERIALS AND METHODS: A systematic search was performed (PubMed and Cochrane databases) for potentially relevant studies up to January 2014. Pooled sensitivity and specificity were calculated. The AUCs of the global cohort and for "major response," "complete response," "only PET after chemoradiotherapy," "ad interim PET," "major response excluding ad interim studies," "complete response excluding ad interim studies," "response index (RI)," "posttreatment maximum standardized uptake value (SUV(max) post)," "visual response analysis (VRA)," "percentage reduction of the total lesion glycolysis (ΔTLG)," and "percentage reduction of the metabolic tumor volume (ΔMTV)" were analyzed. Heterogeneity was explored for multiple variables. Pooled prevalence and 95% CI were calculated. RESULTS: Thirty-four of 131 (26%) initial articles met the inclusion criteria. Those articles included 1526 patients. PET/CT showed good pooled accuracy both in the global cohort (pooled sensitivity, 73%; pooled specificity, 77%; pooled AUC, 0.83) and for subgroups. Pooled accuracy was similar for early PET restaging and at 1 and 2 weeks after beginning chemoradiotherapy (pooled sensitivity, 84%; pooled specificity, 81%; pooled AUC, 0.89). The major response group showed similar sensitivity to the complete response group (74% and 71%, respectively). RI, SUV(max), and VRA were the most frequent parameters used. Pooled RI and SUV(max) postcutoff values were 63% and 4.4. Pooled time to PET during and after chemoradiotherapy was 1.5 and 6.5 weeks, respectively. CONCLUSION: This meta-analysis supports the use of FDG PET for restaging locally advanced rectal cancer.

18F-FDG PET/CT impact on testicular tumours clinical management.

PURPOSE: Testicular tumour is the most common malignancy in young men. The diagnostic work-up is mainly based on morphological imaging. The aim of our study was to evaluate the clinical impact of (18)F-FDG PET/CT in patients with testicular tumour. METHODS: We retrospectively evaluated all patients studied by (18)F-FDG PET/CT at our centre. Inclusion criteria were: pathological confirmation of testicular tumour, contrast-enhanced CT scan performed within a month of the PET/CT scan, and clinical/imaging follow-up performed at the Oncology Unit of our hospital. Overall, 56 patients were enrolled and 121 PET/CT scans were evaluated. (18)F-FDG PET/CT was performed following standard procedures and the results were compared with clinical, imaging and follow-up data. Clinicians were contacted to inquire whether the PET/CT scan influenced the patient's management. Answers were scored as follows: start/continue chemotherapy or radiotherapy, indication for surgery of secondary lesions, and clinical surveillance. RESULTS: On a scan basis, 51 seminoma and 70 nonseminoma (NS) cases were reviewed. Of the 121 cases. 32 were found to be true-positive, 74 true-negative, 8 false-positive and 6 false-negative by PET/CT. PET/CT showed good sensitivity and specificity for seminoma lesion detection (92% and 84%, respectively), but its sensitivity was lower for NS forms (sensitivity and specificity 77% and 95%, respectively). The PET/CT scan influenced the clinical management of 47 of 51 seminomas (in 6 chemotherapy was started/continued, in 3 radiotherapy was started/continued, in 2 surgery of secondary lesions was performed, and in 36 clinical surveillance was considered appropriate), and 59 of 70 NS (in 18 therapy/surgery was started/continued, and in 41 clinical surveillance was considered appropriate). CONCLUSION: Our preliminary data demonstrate the potential usefulness of PET/CT for the assessment of patients with testicular tumour. It provides valuable information for the clinical management, particularly for clinical surveillance, post-therapy assessment and when relapse is suspected.

Is the detection rate of 18F-choline PET/CT influenced by androgen-deprivation therapy?

PURPOSE: To evaluate if the detection rate (DR) of (18)F-choline (18F-CH) PET/CT is influenced by androgen-deprivation therapy (ADT) in patients with prostate cancer (PC) already treated with radical intent and presenting biochemical relapse. MATERIALS AND METHODS: We have retrospectively evaluated (18)F-CH PET/CT scans of 325 consecutive PC patients enrolled in the period November 2009 to December 2012 previously treated with radical intent and referred to our centre to perform (18)F-CH PET/CT for biochemical relapse. Two different groups of patients were evaluated. group A included the whole sample of 325 patients (mean age 70 years, range: 49-86) who presented trigger PSA between 0.1 and 80 ng/ml (mean 5.5 ng/ml), and group B included 187 patients (mean age 70 years, range 49-86) with medium-low levels of trigger PSA ranging between 0.5 and 5 ng/ml (mean PSA 2.1 ng/ml); group B was chosen in order to obtain a more homogeneous group of patients in terms of PSA values also excluding both very low and very high PSA levels avoiding the "a priori" higher probability of negative or positive PET scan, respectively. At the time of examination, 139 patients from group A and 72 patients from group B were under ADT: these patients were considered to be hormone-resistant PC patients because from their oncologic history (>18 months) an increase of PSA levels emerged despite the ongoing ADT. The relationship between (18)F-CH PET/CT findings and possible clinical predictors was investigated using both univariate and multivariate binary logistic regression analyses, including trigger PSA and ADT. RESULTS: Considering the whole population, overall DR of (18)F-CH PET was 58.2 % (189/325 patients). In the whole sample of patients (group A), both at the univariate and multivariate logistic regression analysis, trigger PSA and ADT were significantly correlated with the DR of (18)F-CH PET (p < 0.05). Moreover, the DR in patients under ADT (mean PSA 7.8 ng/ml) was higher than in patients not under ADT (mean PSA 3.9 ng/ml), (DR was 70.5 % and 48.9 %, respectively; p < 0.001), therefore, demonstrating the existence of a significant correlation between the DR of (18)F-CH PET and ADT. In group B patients only trigger PSA resulted a reliable predictor of the (18)F-CH positivity, since ADT was not correlated to the DR of (18)F-CH PET (p = 0.061). Also in group B the DR of (18)F-CH PET in patients under ADT was higher than in patients not under ADT (65.3 % and 51.3 %, respectively) but the difference was not significant without a statistically significant correlation in the Mann Whitney test (p = 0.456) therefore, suggesting the lack of correlation between DR (18)F-CH PET/CT and ADT. CONCLUSION: Similarly to previous published studies, in our series the overall DR of (18)F-CH PET/CT was 58 % and was significantly correlated to trigger PSA. The most important finding of the present study is that ADT does not negatively influence DR of (18)F-CH PET/CT in PC patients with biochemical relapse; therefore, it can be suggested that it is not necessary to withdraw ADT before performing (18)F-CH PET/CT.

Indeterminate lung nodules in cancer patients: pretest probability of malignancy and the role of 18F-FDG PET/CT.

OBJECTIVE: The purpose of this study was to determine likelihood of malignancy for indeterminate lung nodules identified on CT comparing two standardized models with (18)F-FDG PET/CT. MATERIALS AND METHODS: Fifty-nine cancer patients with indeterminate lung nodules (solid tumors; diameter, ≥5 mm) on CT had FDG PET/CT for lesion characterization. Mayo Clinic and Veterans Affairs Cooperative Study models of likelihood of malignancy were applied to solitary pulmonary nodules. High probability of malignancy was assigned a priori for multiple nodules. Low (<5%), intermediate (5-60%), and high (>60%) pretest malignancy probabilities were analyzed separately. Patients were reclassified with PET/CT. Histopathology or 2-year imaging follow-up established diagnosis. Outcome-based reclassification differences were defined as net reclassification improvement. A null hypothesis of asymptotic test was applied. RESULTS: Thirty-one patients had histology-proven malignancy. PET/CT was true-positive in 24 and true-negative in 25 cases. Negative predictive value was 78% and positive predictive value was 89%. On the basis of the Mayo Clinic model (n=31), 18 patients had low, 12 had intermediate, and one had high pretest likelihood; on the basis of the Veterans Affairs model (n=26), 5 patients had low, 20 had intermediate, and one had high pretest likelihood. Because of multiple lung nodules, 28 patients were classified as having high malignancy risk. PET/CT showed 32 negative and 27 positive scans. Net reclassification improvements respectively were 0.95 and 1.6 for Mayo Clinic and Veterans Affairs models (both p<0.0001). Fourteen of 31 (45.2%) and 12 of 26 (46.2%) patients with low and intermediate pretest likelihood, respectively, had positive findings on PET/CT for the Mayo Clinic and Veterans Affairs models, respectively. Of 15 patients with high pretest likelihood and negative findings on PET/CT, 13 (86.7%) did not have lung malignancy. CONCLUSION: PET/CT improves stratification of cancer patients with indeterminate pulmonary nodules. A substantial number of patients considered at low and intermediate pretest likelihood of malignancy with histology-proven lung malignancy showed abnormal PET/CT findings.

Molecular imaging of pulmonary nodules.

OBJECTIVE: Lung nodules can be benign or malignant, reflecting many possible causes, ranging from inflammatory and infectious processes to neoplasms. Incidental detection on chest x-ray or thoracic CT often requires further evaluation by imaging or invasive procedures. CONCLUSION: Currently, 18F-FDG PET/CT offers both anatomic and metabolic characterization of lung nodules. Fluorine-18-thymidine, 11C-methionine, 68Ga-DOTA-somatostatin analogs, and 18F-dihydroxyphenylalanine may offer additional molecular information useful for diagnosis and treatment planning.

Neoadjuvant therapy with weekly docetaxel and cisplatin, 5-fluorouracil continuous infusion, and concurrent radiotherapy in patients with locally advanced esophageal cancer produced a high percentage of long-lasting pathological complete response: a phase 2 study.

BACKGROUND: This phase 2 study was aimed at defining the pathological response rate of a neoadjuvant schedule including weekly docetaxel and cisplatin, continuous infusion (c.i.) of 5-fluorouracil (5-FU) and concomitant radiotherapy (RT) in untreated stage II-III adenocarcinoma and squamous cell carcinoma of mid-distal thoracic esophagus. METHODS: The schedule consisted of a first phase of chemotherapy alone and of a second phase of concurrent chemoradiation. Doses were as follows: docetaxel 35 mg/m(2) and cisplatin 25 mg/m(2) on days 1, 8, 15, 29, 36, 43, 50, and 57 plus 5-FU c.i. (180 mg/m(2) on days 1-21 and 150 mg/m(2) on days 29-63); RT (50 Gy) started at day 29. Surgery was planned 6 to 8 weeks after the completion of chemoradiation. RESULTS: A total of 74 patients were enrolled; pathological complete remission (pCR) was found in 47% (35 of 74) and near pCR (microfoci of tumor cells on the primary tumor without lymph nodal metastases) (pnCR) in 15% of the patients (11 of 74). Grade 3-4 neutropenia, nonhematological toxicity, and toxic deaths occurred in 13.5%, 32.4%, and 4% of the patients, respectively. Median follow-up was 55 months (range, 3-108 months). Median survival of all 74 patients was 55 months, whereas it was not reached in the pCR subset. The 3- and 5-year survival rates were, respectively, 83% and 77% for pCR, 73% and 44% for pnCR, and 21% and 14% for Residual Tumor subsets (P < .001). CONCLUSIONS: This study shows that 1) this intensive weekly schedule produced a high pathological response rate, 2) responders had high and long-term durable survival rates.

Role of ¹8F-choline PET/CT in suspicion of relapse following definitive radiotherapy for prostate cancer.

PURPOSE: The aims of the study were (a) to evaluate the diagnostic role, by means of positive detection rate (PDR), of ¹8F-choline (CH) positron emission tomography (PET)/CT in patients with prostate cancer treated with radiotherapy, with curative intent, and suspicion of relapse during follow-up, (b) to correlate the PDR with trigger prostate-specific antigen (PSA), (c) to investigate the possible influence of androgen deprivation therapy (ADT) at the time of scan on PDR and (d) to assess distribution of metastatic spread. METHODS: ¹8F-CH PET/CT exams from 46 consecutive patients (mean age 71.3 years, range 51-84 years) with prostate cancer (mean Gleason score 6.4, range 5-8) previously treated by definitive radiotherapy and with suspicion of relapse with negative or inconclusive conventional imaging were retrospectively evaluated. Of the 46 patients, 12 were treated with brachytherapy and 34 with external beam radiation therapy. Twenty-three patients were under ADT at the time of the examination. Trigger PSA was measured within 1 month before the exam (mean value 6.5 ng/ml, range 1.1-49.4 ng/ml). Patients were subdivided into four groups according to their PSA level: 1.0 < PSA ≤ 2.0 ng/ml (11 patients), 2.0 < PSA ≤ 4.0 ng/ml (16 patients), 4.0 < PSA ≤ 6.0 ng/ml (9 patients) and PSA > 6.0 ng/ml (10 patients). Correlation between ADT and PDR was investigated as well as between PSA and distribution of metastatic spread. RESULTS: The overall PDR of ¹8F-CH PET/CT was 80.4% (37/46 patients), increasing with the increase of trigger PSA. PDR of ¹8F-CH PET/CT is not influenced by ADT (p = 0.710) even if PET performed under ADT demonstrated an overall higher PDR (82.6%). The majority of the patients (59%, 22/37 patients) showed local relapse only, confined to the prostatic bed; 22% of the PET/CT-positive patients (8/37 patients) showed distant relapse only (bone localizations in all of them), while the remaining 19% (7/37 patients) showed both local and distant (lymph node and bone) spread. CONCLUSION: ¹8F-CH PET/CT showed a high overall detection rate (80%), proportional to the trigger PSA (both for local and distant relapse) not influenced by ADT. ¹8F-CH PET/CT is proposed as a first-line imaging procedure in restaging prostate cancer patients primarily treated with radiotherapy.

(11)C-Choline PET/CT in patients with hormone-resistant prostate cancer showing biochemical relapse after radical prostatectomy.

PURPOSE: To determine the diagnostic efficacy of (11)C-choline PET/CT in patients with prostate cancer (PC) after radical prostatectomy who presented with increasing PSA levels during follow-up in spite of being on hormone treatment (HT), and therefore showing HT resistance. METHODS: We evaluated a large series of 157 consecutive PC patients previously treated by radical prostatectomy who presented with biochemical recurrence with increasing PSA levels in spite of ongoing HT (HT-resistant patients). At the time of (11)C-choline PET/CT, the mean value of trigger PSA level was 8.3 (range 0.2 - 60.6 ng/mL), the mean PSA doubling time (PSAdt) was 5.3 (range 0.4 - 35 months), and the mean PSA velocity (PSAvel) was 22.1 ng/mL/year (range 0.12 - 82 ng/mL/year). (11)C-Choline PET/CT was performed following a standard procedure at our centre to investigate increasing PSA levels, either as the first imaging procedure or in patients with negative conventional imaging. At the time of (11)C-choline PET/CT all patients were receiving HT (61 were receiving monotherapy and 96 multidrug therapy). PET-positive findings were validated by: (a) transrectal US-guided biopsy in patients with recurrence in the prostatic bed, (b) surgical pelvic lymphadenectomy, (c) other imaging modalities, including repeated (11)C-choline PET/CT, performed during a minimum follow-up of 12-months. RESULTS: (11)C-Choline PET/CT showed positive findings in 104 of the 157 patients (66 %). (11)C-choline PET/CT detected: a single lesion in 40 patients (7 in the prostate bed, 10 in lymph nodes, 22 in bone, 1 at another site); two lesions in 18 patients (7 in lymph nodes, 7 in bone, 4 in both lymph nodes and bone); three or four lesions in 7 patients (4 in lymph nodes, 2 in bone, 1 at another site); and more than four lesions in the remaining 39 patients (2 in the prostate bed, 12 in lymph nodes, 12 in bone, 11 in both lymph nodes and bone, 2 at other sites). In (11)C-choline PET-negative patients, the mean values of trigger PSA, PSAdt and PSAvel were 3.8 ng/mL (range 0.2-11.9 ng/mL) 7.0 months (range 1.21 - 35 months) and 5.8 ng/mL/year (range 0.12 - 30.1) respectively, while in (11)C-Choline-PET-positive patients they were 10.5 ng/mL (range 0.2 - 60.6), 4.4 months (range 0.4 - 19.7) and 15.9 ng/mL/year (range 0.5 - 82.0) respectively. The differences between PET-negative and PET-positive patients were statistically significant for all these parameters: trigger PSA, p < 0.01; PSAdt, p < 0.01; PSAvel, p = 0.03. CONCLUSION: In our patient population, (11)C-choline PET/CT was able to detect relapsed disease in a large proportion of HT-resistant PC patients during HT. These data, obtained in a large series, suggest that HT withdrawal before performing a (11)C-choline PET/CT scan may not be necessary for the detection of recurrent disease if PSA levels are increasing and PSA kinetics are rapid.

Fifteen different 18F-FDG PET/CT qualitative and quantitative parameters investigated as pathological response predictors of locally advanced rectal cancer treated by neoadjuvant chemoradiation therapy.

PURPOSE: The aim of this study was to correlate qualitative visual response and various PET quantification factors with the tumour regression grade (TRG) classification of pathological response to neoadjuvant chemoradiotherapy (CRT) proposed by Mandard. METHODS: Included in this retrospective study were 69 consecutive patients with locally advanced rectal cancer (LARC). FDG PET/CT scans were performed at staging and after CRT (mean 6.7 weeks). Tumour SUVmax and its related arithmetic and percentage decrease (response index, RI) were calculated. Qualitative analysis was performed by visual response assessment (VRA), PERCIST 1.0 and response cut-off classification based on a new definition of residual disease. Metabolic tumour volume (MTV) was calculated using a 40 % SUVmax threshold, and the total lesion glycolysis (TLG) both before and after CRT and their arithmetic and percentage change were also calculated. We split the patients into responders (TRG 1 or 2) and nonresponders (TRG 3-5). RESULTS: SUVmax MTV and TLG after CRT, RI, ΔMTV% and ΔTLG% parameters were significantly correlated with pathological treatment response (p < 0.01) with a ROC curve cut-off values of 5.1, 2.1 cm(3), 23.4 cm(3), 61.8 %, 81.4 % and 94.2 %, respectively. SUVmax after CRT had the highest ROC AUC (0.846), with a sensitivity of 86 % and a specificity of 80 %. VRA and response cut-off classification were also significantly predictive of TRG response (VRA with the best accuracy: sensitivity 86 % and specificity 55 %). In contrast, assessment using PERCIST was not significantly correlated with TRG. CONCLUSION: FDG PET/CT can accurately stratify patients with LARC preoperatively, independently of the method chosen to interpret the images. Among many PET parameters, some of which are not immediately obtainable, the most commonly used in clinical practice (SUVmax after CRT and VRA) showed the best accuracy in predicting TRG.