Prognostic value of PET parameters in patients with pleomorphic lung cancer: Results from a single institution.

OBJECTIVES: Pleomorphic lung carcinoma (PLC) is a rare histotype of non-small cell lung cancer (NSCLC) characterized by aggressive clinical course, poor response to therapy and poor prognosis. Therefore, aim of our study is to analyze with 18F-FDG PET/CT a subset of patients affected by PLC to evaluate their metabolic characteristics in terms of SUVmax, MTV and TLG, in order to correlate them with overall survival (OS) and disease-free survival (DFS). MATERIAL AND METHODS: We retrospectively analyzed 49 consecutive patients with histologically defined PLC occurred to our Institution between 2003 and 2014. All patients underwent F18-FDG PET-CT before surgery and primary tumor was automatically segmented using an isocontour threshold method. SUV threshold for tumor segmentation was defined as the 41 % of lesion SUVmax. Total volume of the segmented VOI (MTV, centimeters cubed) and average SUV (SUVavg, grams per milliliter) in the segmented VOI were measured. RESULTS: In our population men were significantly more affected than women (42:7). According to Youden criteria, SUVmax, MTV41 and TLG41 best cut-off values to predict 2-year mortality were, 18.95, 27.89 and 290.45, respectively, with TLG41 showing best specificity (85 %) and positive predictive value (82.4 %). As concerning 2-year recurrence, SUVmax, MTV41 and TLG41 best cut-off values were 10.08, 27.89 and 134.85, with SUVmax showing best sensitivity (96.7 %) and negative predictive value (85.7 %). ROC curves confirmed that SUVmax, MTV41 and TLG41 were equally accurate to predict 2-year mortality and 2-year recurrence in our population. CONCLUSION: Metabolic biomarkers such as SUVmax, MTV and TLG can be used as a prognostic index for disease progression, recurrence and death in patients with PLC, independently from other clinical/pathological prognostic elements.

Does a 6-point scale approach to post-treatment 18F-FDG PET-CT allow to improve response assessment in head and neck squamous cell carcinoma? A multicenter study.

PURPOSE: Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale ("Cuneo score"). METHODS: We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients' information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. RESULTS: Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). CONCLUSIONS: In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy.

Radiotherapy of Hodgkin and Non-Hodgkin Lymphoma: A Nonrigid Image-Based Registration Method for Automatic Localization of Prechemotherapy Gross Tumor Volume.

PURPOSE: To improve the contouring of clinical target volume for the radiotherapy of neck Hodgkin/non-Hodgkin lymphoma by localizing the prechemotherapy gross target volume onto the simulation computed tomography using [18F]-fluorodeoxyglucose positron emission tomography/computed tomography. MATERIAL AND METHODS: The gross target volume delineated on prechemotherapy [18F]-fluorodeoxyglucose positron emission tomography/computed tomography images was warped onto simulation computed tomography using deformable image registration. Fifteen patients with neck Hodgkin/non-Hodgkin lymphoma were analyzed. Quality of image registration was measured by computing the Dice similarity coefficient on warped organs at risk. Five radiation oncologists visually scored the localization of automatic gross target volume, ranking it from 1 (wrong) to 5 (excellent). Deformable registration was compared to rigid registration by computing the overlap index between the automatic gross target volume and the planned clinical target volume and quantifying the V95 coverage. RESULTS: The Dice similarity coefficient was 0.80 ± 0.07 (median ± quartiles). The physicians' survey had a median score equal to 4 (good). By comparing the rigid versus deformable registration, the overlap index increased from a factor of about 4 and the V95 (percentage of volume receiving the 95% of the prescribed dose) went from 0.84 ± 0.38 to 0.99 ± 0.10 (median ± quartiles). CONCLUSION: This study demonstrates the impact of using deformable registration between prechemotherapy [18F]-fluorodeoxyglucose positron emission tomography/computed tomography and simulation computed tomography, in order to automatically localize the gross target volume for radiotherapy treatment of patients with Hodgkin/non-Hodgkin lymphoma.

Fluorodeoxyglucose positron emission tomography in pulmonary carcinoid tumors.

AIM: The role of fluorodeoxyglucose positron emission tomography (FDG-PET) as an additional investigation to computer tomography for pulmonary carcinoid tumors remains controversial. The aim of this study was to assess the role of FDG-PET for the diagnosis and staging of pulmonary carcinoid tumors. METHODS: We performed a retrospective mono-institutional analysis of data from 97 patients with pathologically confirmed pulmonary carcinoid tumor who had been operated on between July 1998 and April 2009 and had had a preoperative FDG-PET scan performed. RESULTS: Sixty-five (67%) of the 97 tumors were typical (TC) and 32 (33%) atypical (AC) carcinoid tumors. Overall FDG-PET sensitivity was 67% being lower for TC (60%) than for AC (81%) (P=0.04). FDG-PET negative tumors were smaller than FDG-PET positive tumors, with a respective median size of 15 and 17 mm (P=0.02). Median SUVmax for FDG-PET-positive tumors was 4.0 (2.8-5.1) with no difference between TC and AC tumors. Median Ki-67 expression was respectively 4.7% and 3.1% for FDG-PET positive and FDG-PET negative tumors (P=0.05). During a median follow-up of 49 months (interquartile range 30-63 months), 9 patients (4TC, 5AC) developed recurrent disease. Neither SUVmax nor Ki-67 expression resulted associated with disease-free survival. CONCLUSION: With an overall sensitivity of 67%, FDG-PET has shown to be useful in the preoperative work-up of patients with suspect lung carcinoid tumors. In particular it could have a role in larger tumors. These results warrant a prospective evaluation of FDG-PET in the staging of lung carcinoid tumor.

Lymphoscintigraphy in clinical routine practice: reproducibility and accuracy in melanoma patients with a long-term follow-up.

INTRODUCTION: The sentinel node status is the most important single factor determining overall survival for patients with localized melanoma. Preoperative lymphoscintigraphy (LS) is essential in locating the correct sentinel lymph node (SN) and the reproducibility of the method determines the accuracy of the sentinel node biopsy (SNB). This study aims at determining the reproducibility and accuracy of LS in routine clinical practice after long-term follow-up. PATIENTS AND METHODS: One hundred and eight melanoma patients with clinically unpredictable lymphatic drainage were prospectively enrolled to undergo two LS. The first LS was performed to determine the site and number of the lymphatic basins to plan SNB anesthesia and the second preoperative LS was to allow SN localization intra-operatively. RESULTS: Lymphatic drainage was demonstrated in all patients. In 84 of 108 cases, both LSs were concordant in terms of site and number of nodal basins visualized. After a median follow-up of 80 months, no nodal recurrence was observed in the five patients with a decreased number of lymph node basins. In the group with increased number of lymph node basins, one patient developed nodal metastases in the same regional lymph node basin visualized by both LS studies. CONCLUSION: LS is an accurate and reproducible method to determine the localization of the sentinel node in the day-to-day routine to clinical practice when primary melanoma is also located in body sites with variable lymphatic drainage.

High-dose chemotherapy in relapsed or refractory Hodgkin lymphoma patients: a reappraisal of prognostic factors.

High-dose chemotherapy (HDCT) has a consolidated role in the treatment of patients with refractory or relapsed Hodgkin lymphoma (HL). We report clinical results of 97 HL patients who underwent HDCT for refractory (62 patients) or relapsed (35 patients) diseases in Istituto Europeo di Oncologia, from 1995 to 2009. Treatment included high-dose carmustine, etoposide, cytarabine and melphalan in 84 patients and high-dose idarubicin and melphalan in 13 patients with subsequent peripheral hemopoietic stem cells transplant. Outcomes were evaluated in terms of progression-free survival (PFS) and overall survival (OS). In order to identify prognostic factors for outcome, a multivariate analysis for age, sex, disease status (refractory/relapsed), disease stage, B symptoms, presence of extranodal involvement, bulky disease, elevated lactate dehydrogenase, number of previous chemotherapy lines, remission status before transplant, 18F-fluoro-deoxy-d-glucose positron emission tomography ((18) FDG-PET) status before and after transplant was done. A clinical response was achieved in 91% of patients, with complete remissions in 76/97 patients. With a median follow-up of 45 months (range 1-164 months), 5-year PFS and OS were 64% and 71%, respectively. Remission status after induction therapy, 18F-fluoro-deoxy-d-glucose positron emission tomography status before and after transplant were the most important prognostic factors for PFS and OS in univariate or multivariate analyses. HDCT is able to induce a high remission rate and a prolonged PFS in more than 50% of the patients with refractory and relapsed HL.

An unusual breast lesion: the ultrasonographic, mammographic, MRI and nuclear medicine findings of mammary hibernoma.

We report the case of a 42-year-old woman being treated for an ovarian cancer who was diagnosed at the age of 40. A CT-positron emission tomography (PET) scan performed as follow-up documented abnormal uptake in the right breast. Mammograms were negative for malignancy, while a focal hyperechoic lesion was observed on ultrasonography in the same breast. Thus, she was referred to our institution for breast MRI, which showed a focal area of enhancement with atypical features. Percutaneous biopsy was performed, and a mammary hibernoma was diagnosed. Radiological and pathological correlation was provided. To our knowledge, this is the only report that describes the features of this rare tumour on four different imaging modalities (mammography, ultrasonography, MRI and CT-PET).

Peritoneal carcinomatosis from ovarian cancer: the role of CT and [¹8F]FDG-PET/CT.

PURPOSE: The diagnosis of peritoneal carcinomatosis secondary to ovarian cancer is a real challenge in the cancer imaging field. In this retrospective study, we evaluate the accuracy of Single Detector Computed Tomography (SDCT), Multi Detector Computed Tomography (MDCT), and Positron Emission Tomography-Computed Tomography with F18-fluorodeoxyglucose ([¹8F]FDG-PET/CT) in the diagnosis of peritoneal seeding and we evaluate the possible applications of MDCT to predict the complete surgical removal of the peritoneal deposits. METHODS AND MATERIALS: A total of 228 scans (91 SDCT, 89 MDCT, and 48 [¹8F]FDG-PET/CT) of patients with peritoneal carcinomatosis secondary to ovarian cancer proved at laparoscopy and confirmed by histopathology were retrospectively reviewed by two independent groups of Radiologists and Nuclear Medicine Physicians for the evaluation of ascites, peritoneal nodules, and omental cake signs. RESULTS: MDCT showed 81% of true positives, SDCT 72.5%, and [¹8F]FDG-PET/CT 77%. False negatives were 19% for MDCT, 27.5% for SDCT, and 23% for [¹8F]FDG-PET/CT. CONCLUSION: From our results, we concluded that MDCT is the technique of choice in the diagnosis of peritoneal seeding, while [¹8F]FDG-PET/CT, though showing similar accuracy, remains the most accurate technique for monitoring therapeutic response and disease recurrence. MDCT could play an important role due to its ability to predict the possibility of complete surgical removal of disease thus influencing the treatment plan aimed to improve quality of life.

Intensified ChlVPP/ABVVP chemotherapy regimen and pegfilgrastim support in advanced Hodgkin lymphoma.

We present feasibility, toxicity and efficacy results of an intensified six-cycle ChlVPP/ABVVP regimen in advanced Hodgkin lymphoma (HL). From February 2004 to August 2007, 82 consecutive eligible patients were enrolled. According to the Hasenclever index, 64 patients (78%) were considered at low risk, 15 (18%) at intermediate and 3 (4%) at high risk. The most relevant toxicity was haematological: grade 3-4 neutropenia occurred in 32% of patients, grade 3-4 anaemia in 26% of patients. Severe infections and febrile neutropenia were observed in 8% of patients. With a median follow-up of 35 months (range 12-55), the three-year freedom from treatment failure (FFTF) and overall survival (OS) were 75% (95% CI 65%-86%) and 94% (95% CI 87%-99%), respectively. The intensified ChlVPP/ABVVP regimen in advanced HL is effective, does not seem to differ from standard regimens in terms of FFTF and OS and showed a favourable toxicity profile.

Carcinoma, tuberculosis and elastofibroma in one patient: is [18F]FDG-PET/CT helpful?

We present the case of a woman with persistent dorsal pain and two solid lung lesions documented on multidetector CT which showed concomitant [18F]FDG uptake. One of the lesions proved to be adenocarcinoma at biopsy and presented a lower [18F]FDG uptake when compared to the second lesion, which was smaller in size, and was postsurgically diagnosed as tuberculoma. This case portrays the paradoxical metabolic behaviour of two lesions, leading to misdiagnosis and erroneous disease staging in an oncology patient. Incidentally, the patient also had an elastofibroma dorsi, a rare benign tumour which can also be a possible source of false results in the PET exam. We provide explanations and possible solutions to these findings in order to familiarise the physician with them, and optimise patient management.

The management of colorectal liver metastases: Expanding the role of hepatic resection in the age of multimodal therapy.

Colorectal cancer (CRC) caused nearly 204,000 deaths in Europe in 2004. Despite recent advances in the treatment of advanced disease, which include the incorporation of two new cytotoxic agents irinotecan and oxaliplatin into first-line regimens, the concept of planned sequential therapy involving three active agents during the course of a patient's treatment and the integrated use of targeted monoclonal antibodies, the 5-year survival rates for patients with advanced CRC remain unacceptably low. For patients with colorectal liver metastases, liver resection offers the only potential for cure. This review, based on the outcomes of a meeting of European experts (surgeons and medical oncologists), considers the current treatment strategies available to patients with CRC liver metastases, the criteria for the selection of those patients most likely to benefit and suggests where future progress may occur.

Role of multidetector CT and FDG-PET/CT in the diagnosis of local and distant recurrence of resected rectal cancer.

PURPOSE: The aim of this study was to compare the diagnostic value of multidetector computed tomography (MDCT) and F18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) for the detection of local and distant recurrence in patients operated on for rectal cancer. MATERIALS AND METHODS: Sixty-seven patients who underwent radical surgery for rectal cancer and were followed up with FDG-PET/CT and MDCT were included in this retrospective study. The FDG-PET/CT and MDCT findings were independently compared with histological sampling or 2 years' follow-up. RESULTS: Local recurrence occurred in 15/67 patients. MDCT diagnosed local recurrence in 15/15 cases and FDG-PET/CT in 14/15. Sensitivity and specificity were 100% and 98% for MDCT and 93% and 98% for FDG-PET/CT, respectively. Hepatic lesions were found in 17/67 patients. All hepatic metastases were detected by both techniques. Pulmonary metastases occurred in 8/67 patients: they were correctly identified in all cases by MDCT and in 6/8 by FDG-PET/CT. CONCLUSIONS: MDCT and FDG-PET/CT showed high sensitivity and specificity for the detection of local recurrence of rectal cancer. Both techniques were equally accurate for the detection of hepatic metastases. MDCT showed slightly higher sensitivity and positive predictive value in detecting pulmonary metastases compared with FDG-PET/CT.

Lymphatic mapping to tailor selective lymphadenectomy in cN0 tongue carcinoma: beyond the sentinel node concept.

PURPOSE: Cervical lymph node status is the most important pathological determinant of prognosis and decision making in head and neck squamous cell carcinoma (SCC). The aim of this study was to demonstrate that lymphoscintigraphy (LS) can supply a complete map of the lymphatic drainage before surgery, allowing planning of the type of intervention and serving to guide lymphadenectomy. METHODS: The study population comprised 14 patients with T2-4 SCCs of the tongue and clinically negative lymph nodes in the neck (cN0) who were scheduled to undergo tumour resection and selective level I-IV neck dissection extended to level V. LS was performed in all patients following the injection of (99m)Tc-colloidal sulphide in three aliquots around the primary lesion. Dynamic, static and tomographic images of the head and neck were acquired. The operative specimens were subjected to lymphoscintigraphic evaluation. Preoperative and postoperative imaging results were compared with the pathological findings. All nodes were examined using haematoxylin-eosin staining. RESULTS: Preoperative LS was successful in all patients. Preferential pathways of lymphatic drainage were identified: level II of the neck was the most common lymphatic drainage pattern, followed by levels IV and III. Contralateral drainage occurred in 11 patients and in two of them metastatic nodes were found on the contralateral side. Metastases were observed only in radioactive lymph nodes. CONCLUSION: LS is able to supply a complete map of the lymphatic drainage before surgery, making it possible to tailor selective neck dissection to each individual patient based on the results of preoperative mapping, thereby sparing healthy lymphatic tissue and reducing surgery-related morbidity.

Internal mammary node lymphoscintigraphy and biopsy in breast cancer.

BACKGROUND: In patients with breast cancer, sentinel nodes (SNs) are detected outside the axilla in 1-2% of cases after superficial injection of radiocolloid in the breast. We investigated whether deep injection of tracer visualized internal mammary chain lymph (IMC) nodes more often, and assessed the impact of IMC status on disease staging. METHODS: A total of 400 patients were enrolled in this trial. The study group included 200 patients with T1-T2 N0 breast cancer in an inner quadrant. Radio tracer was injected superficially in 100 (group A), and deeply under the tumor in the others (group B). If an IMC took up tracer in group B patients it was biopsied. An additional 200 patients with outer quadrant lesions were also studied lymphoscintigraphically following superficial (100 patients) or deep (100 patients) injection, but IMC nodes were not biopsied as this would have required an additional surgical excision. RESULTS: An SN was visualized in the IMC in 65.6% of inner quadrant patients after deep injection and in 2.1% after superficial injection. In outer quadrant patients, deep injection visualized an SN in the IMC in 10% of cases. The IMC SN was located mainly in the 2nd and 3rd intercostal spaces. Radioguided IMC biopsy was performed in 62 patients. Node removal proved simple and risks insignificant. Stage migration occurred in 8% of cases. CONCLUSIONS: Deep injection allows SN localization in the IMC in 65% of inner quadrant breast lesions. Biopsy of the axillary plus IMC resulted in stage migration in 8% of patients. It is unclear whether this additional information can lead to better survival.

Comparison of dual-head coincidence PET versus ring PET in tumor patients.

UNLABELLED: This study compared the multiring detector (Ring-PET) and the dual-head coincidence imaging system (DH-PET) for staging/ restaging neoplastic patients before or after surgery or radiochemotherapy. METHODS: Seventy patients with suspected tumor recurrence or metastatic dissemination received an intravenous dose of 18F-fluorodeoxyglucose (FDG) under overnight fasting and were studied in sequence with a dedicated positron emission tomograph with Ring-PET and a DH-PET. Ring-PET studies were performed 45-75 min postinjection and were followed by a DH-PET scan approximately 3 h postinjection. Number and location of the hypermetabolic lesions detected on DH-PET and Ring-PET reconstructed images were blindly assessed by three independent observers. RESULTS: DH-PET identified all 14 head lesions detected by Ring-PET, 53 of 63 thoracic lesions and 36 of 45 abdominal lesions. Of the 19 lesions not identified by DH-PET, 6 were smaller than 10 mm, 8 were between 10 and 15 mm and 1 was 18 mm; dimensions of 4 bone lesions were not available. A concordant restaging, based on location and number of lesions detected, was found in all 14 patients with head tumors, in 28 of 30 patients with thoracic tumors and in 24 of 26 patients with abdominal tumors. CONCLUSION: We found a good agreement between Ring-PET and DH-PET assessment of oncologic patients in detecting hypermetabolic lesions > or = 10-15 mm.