Cost-effectiveness analysis of personalised versus standard dosimetry for selective internal radiation therapy with TheraSphere in patients with hepatocellular carcinoma.

Aims: To perform a cost-effectiveness analysis (CEA) comparing personalised dosimetry with standard dosimetry in the context of selective internal radiation therapy (SIRT) with TheraSphere for the management of adult patients with locally advanced hepatocellular carcinoma (HCC) from the Italian Healthcare Service perspective. Materials and methods: A partition survival model was developed to project costs and the quality-adjusted life years (QALYs) over a lifetime horizon. Clinical inputs were retrieved from a published randomised controlled trial. Health resource utilisation inputs were extracted from the questionnaires administered to clinicians in three oncology centres in Italy, respectively. Cost parameters were based on Italian official tariffs. Results: Over a lifetime horizon, the model estimated the average QALYs of 1.292 and 0.578, respectively, for patients undergoing personalised and standard dosimetry approaches. The estimated mean costs per patient were €23,487 and €19,877, respectively. The incremental cost-utility ratio (ICUR) of personalised versus standard dosimetry approaches was €5,056/QALY. Conclusions: Personalised dosimetry may be considered a cost-effective option compared to standard dosimetry for patients undergoing SIRT for HCC in Italy. These findings provide evidence for clinicians and payers on the value of personalised dosimetry as a treatment option for patients with HCC.

Event-free survival after 68 Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC) patients eligible for salvage therapy.

BACKGROUND/AIM: Prostate-specific-membrane-antigen/positron emission tomography (PSMA-PET) detects with high accuracy disease-recurrence, leading to changes in the management of biochemically-recurrent (BCR) prostate cancer (PCa). However, data regarding the oncological outcomes of patients who performed PSMA-PET are needed. The aim of this study was to evaluate the incidence of clinically relevant events during follow-up in patients who performed PSMA-PET for BCR after radical treatment. MATERIALS AND METHODS: This analysis included consecutive, hormone-sensitive, hormone-free, recurrent PCa patients (HSPC) enrolled through a prospective study. All patients were eligible for salvage therapy, having at least 24 months of follow-up after PSMA-PET. The primary endpoint was the Event-Free Survival (EFS), defined as the time between the PSMA-PET and the date of event/last follow-up. The Kaplan-Meier method was used to estimate the EFS curves. EFS was also investigated by Cox proportional hazards regression. Events were defined as death, radiological progression, or PSA recurrence after therapy. RESULTS: One-hundred and seventy-six (n = 176) patients were analyzed (median PSA 0.62 [IQR: 0.43-1.00] ng/mL; median follow-up of 35.4 [IQR: 26.5-40.3] months). The EFS was 78.8% at 1 year, 65.2% (2 years), and 52.2% (3 years). Patients experiencing events during study follow-up had a significantly higher median PSA (0.81 [IQR: 0.53-1.28] vs 0.51 [IQR: 0.36-0.80] ng/mL) and a lower PSA doubling time (PSAdt) (5.4 [IQR: 3.7-11.6] vs 12.7 [IQR: 6.6-24.3] months) (p < 0.001) compared to event-free patients. The Kaplan-Meier curves showed that PSA > 0.5 ng/mL, PSAdt ≤ 6 months, and a positive PSMA-PET result were associated with a higher event rate (p < 0.01). No significant differences of event rates were observed in patients who received changes in therapy management after PSMA-PET vs. patients who did not receive therapy changes. Finally, PSA > 0.5 ng/mL and PSAdt ≤ 6 months were statistically significant event-predictors in multivariate model (p < 0.001). CONCLUSION: Low PSA and long PSAdt were significant predictors of longer EFS. A lower incidence of events was observed in patients having negative PSMA-PET, since longer EFS was significantly more probable in case of a negative scan.

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

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

68Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC): a prospective single-centre study in patients eligible for salvage therapy.

OBJECTIVES: The primary objective is to assess the efficacy of 68Ga-PSMA-11-PET/CT to detect recurrent location(s) in hormone-sensitive prostate cancer (PCa). Secondary objectives are (1) to evaluate changes in clinical management; (2) to determine which covariates independently predict positive scan; (3) to assess 68Ga-PSMA-11-PET/CT performance in different settings of PSA relapse. MATERIALS AND METHODS: Inclusion criteria include (1) histologically diagnosed PCa; (2) previous radical therapy; (3) proven biochemical recurrence (BCR) or biochemical persistence (BCP); (4) hormone-sensitive PCa (HSPC); (5) androgen deprivation therapy (ADT)-free for at least 6 months; (6) PSA < 1.5 ng/mL or any PSA in case of negative choline-PET/CT (n = 38). Changes in clinical management were defined by multidisciplinary tumour-board. Clinical settings were BCP (group-1, n = 25); first-time BCR (group-2, n = 121); BCR after salvage therapy (group-3, n = 77). RESULTS: Two hundred twenty-three (223) consecutive patients were enrolled: median PSA = 0.65 ng/mL (0.2-8.9) and median PSAdt = 9.3 months (0.4-144.6). 96.9% received RP as primary therapy. 68Ga-PSMA-11-PET/CT positivity rate was 39.9% (CI95% 33.5-46.7%). Disease confined to pelvis was detected in 23.3% of cases. At least one distant lesion was observed in 16.6% of cases. Secondary objectives are as follows: (1) changes in clinical management were observed in 34.5% of patients; (2) PSA, PSAdt and T stage > 3a were independent predictors (all p < 0.03); (3) 68Ga-PSMA-11-PET/CT positivity rate was 56% (in group 1, 36.3% in group 2, 40.3% in group 3. CONCLUSION: This study attested the overall good performance of 68Ga-PSMA-11-PET/CT to detect PCa locations in HSPC patients eligible for salvage therapy, influencing the therapy management in 35.4% of cases. Furthermore, patient characteristics are influencing factors of 68Ga-PSMA-11-PET/CT positivity rate and should be considered to reduce false negative scan.

68Ga-Prostate-Specific Membrane Antigen 11 PET/CT Detects Residual Glioblastoma After Radical Surgery in a Patient With Synchronous Recurrent Prostate Cancer: A Case Report.

Prostate-specific membrane antigen (PSMA) is a transmembrane enzyme also known as folate hydrolase 1 highly expressed by prostate cancer (PCa) cells. However, PSMA overexpression by tumor-associated neovasculature of a variety of solid tumors, including glioblastoma (GBM), has also been proven. This clinical case reports about a 67-year-old man with a history of PCa who underwent radical surgery for GBM and performed a Ga-PSMA-11 PET/CT to restage PCa. PET imaging showed PSMA uptake in GBM residual disease after surgery. This finding suggests a possible role of PSMA inhibitors as diagnostic and therapeutic agents in patients affected by GBM.

Yttrium-90 ibritumomab tiuxetan (Zevalin) followed by BEAM (Z-BEAM) conditioning regimen and autologous stem cell transplantation (ASCT) in relapsed or refractory high-risk B-cell non-Hodgkin lymphoma (NHL): a single institution Italian experience.

Chemo-refractory NHL has a very poor outcome; the addiction of RIT to salvage regiment pre ASCT had recently demonstrated promising results.We performed a retrospective sequential study to determine the feasibility of standard Zevalin with BEAM in high-risk relapse/refractory NHL. A matched cohort analysis with a group treated with standard BEAM without Zevalin was performed as secondary endpoint. Between October 2006 and January 2013, 37 NHL patients at high risk for progression or early (< 1 year) or multiple relapses were treated with Z-BEAM and ASCT after R-DHAP or R-ICE as salvage therapy. Clinical characteristics were 19 refractory and 18 early or multiple relapse; 16 patients received 1, and 21 had 2 or more previous rituximab-containing chemotherapy. At the end of treatment, response was CR 22 (59%), PR 10 (27%), PD 4 (11%), and toxic death (TD) 1 (3%). With a median follow up of 61 months, 3-year PFS was 61% and OS 61%. Fifteen patients died, 12 of lymphoma. Comparison with 21 treated with BEAM alone showed a numerical higher 3-yr PFS rate in favor of Z-BEAM but not statistically significant (57 vs 48%). With the limitation of the small sample subgroup analysis, a significant benefit was observed in relapsed patients for PFS (78% Z-BEAM vs 22% BEAM p = 0.016) and OS (83% Z-BEAM vs 22% BEAM p = 0.001). In relapsed/refractory high-risk NHL, Z-BEAM+ASCT is able to achieve a good ORR. Three-year PFS is promising for early relapsed patients but is not satisfactory for those with refractory disease.

Interpretation criteria for FDG PET/CT in multiple myeloma (IMPeTUs): final results. IMPeTUs (Italian myeloma criteria for PET USe).

ᅟ: FDG PET/CT (18F-fluoro-deoxy-glucose positron emission tomography/computed tomography) is a useful tool to image multiple myeloma (MM). However, simple and reproducible reporting criteria are still lacking and there is the need for harmonization. Recently, a group of Italian nuclear medicine experts defined new visual descriptive criteria (Italian Myeloma criteria for Pet Use: IMPeTUs) to standardize FDG PET/CT evaluation in MM patients. The aim of this study was to assess IMPeTUs reproducibility on a large prospective cohort of MM patients. MATERIALS AND METHODS: Patients affected by symptomatic MM who had performed an FDG PET/CT at baseline (PET0), after induction (PET-AI), and the end of treatment (PET-EoT) were prospectively enrolled in a multicenter trial (EMN02)(NCT01910987; MMY3033). After anonymization, PET images were uploaded in the web platform WIDEN® and hence distributed to five expert nuclear medicine reviewers for a blinded independent central review according to the IMPeTUs criteria. Consensus among reviewers was measured by the percentage of agreement and the Krippendorff's alpha. Furthermore, on a patient-based analysis, the concordance among all the reviewers in terms of positivity or negativity of the FDG PET/CT scan was tested for different thresholds of positivity (Deauville score (DS 2, 3, 4, 5) for the main parameters (bone marrow, focal score, extra-medullary disease). RESULTS: Eighty-six patients (211 FDG PET/CT scans) were included in this analysis. Median patient age was 58 years (range, 35-66 years), 45% were male, 15% of them were in stage ISS (International Staging System) III, and 42% had high-risk cytogenetics. The percentage agreement was superior to 75% for all the time points, reaching 100% of agreement in assessing the presence skull lesions after therapy. Comparable results were obtained when the agreement analysis was performed using the Krippendorff's alpha coefficient, either in every single time point of scanning (PET0, PET-AI or PET-EoT) or overall for all the scans together. DS proved highly reproducible with the highest reproducibility for score 4. CONCLUSIONS: IMPeTUs criteria proved highly reproducible and could therefore be considered as a base for harmonizing PET interpretation in multiple myeloma. A prospective clinical validation of IMPeTUs criteria is underway.

Interventional locoregional treatment and metabolic response: advantages of using PET/CT in the evaluation of response to treatment.

INTRODUCTION: Interventional oncology locoregional therapies are validated treatment modalities for primary and secondary tumors in liver, lung, kidney and bone. At this time, there is no accordance in the choice of imaging modality to assess treatment response. Morphological imaging and RECIST 1.1 criteria based on size variation are limited by several critical points. On the other hand the role of functional imaging, in particular by [18F]-fluorodeoxyglucose ([18F]-FDG) positron emission tomography (PET), in both staging and response evaluation of locoregional treatments remains unclear because of the heterogeneous nature of available data. The aim of this paper was to summarize the available literature illustrating the state of art of metabolic evaluation of response after locoregional therapies in the three major organs of interest: liver, lung and bone. EVIDENCE ACQUISITION: Medline database was searched for relevant original paper evaluating the role of [18F]-FDG PET in interventional oncology treatment published up to June 2017 excluding case reports. EVIDENCE SYNTHESIS: Finally 41 studies papers evaluating the role of [18F]-FDG PET in both staging and in response evaluation of locoregional treatments focused on liver tumoral lesions (N.=29), on lung lesions (N.=10) and on bone lesions (N.=2) were considered for this review. CONCLUSIONS: PET/CT appears to perform well in the assessment of response to interventional therapies compared to conventional imaging, not only in terms of response evaluation but also as a possible prognostic tool. Nevertheless further prospective, homogenous studies are required to confirm these data, in particular for lung and bone lesions.

Prognostic Role of Pre-Radiation Therapy (18)F-Fluorodeoxyglucose Positron Emission Tomography for Primary Mediastinal B-Cell Lymphomas Treated with R-CHOP or R-CHOP-Like Chemotherapy Plus Radiation.

PURPOSE: To validate, in a monoinstitutional cohort with extended follow-up, that post-rituximab chemotherapy (R-CT) (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) is a prognostic factor allowing discrimination of primary mediastinal B-cell lymphoma (PMBCL) patients at higher risk for progression after radiation therapy. METHODS AND MATERIALS: We analyzed 51 patients, and (18)FDG-PET scans were re-examined evaluating both the Deauville 5-point scale (D5PS) score and the standardized uptake value (SUV) of residual activity, if present. These parameters were then tested by univariate analysis for a potential correlation with progression-free survival (PFS) as the primary study endpoint. RESULTS: Median follow-up time was 51 months (range, 9-153 months). After R-CT, D5PS score was 1 in 10 (19.6%), 2 in 11 (21.6%), 3 in 7 (13.8%), 4 in 17 (33.3%), and 5 in 6 patients (11.7%). Forty-three out of 51 patients (84.3%) had an SUVmax ≤5, and 8 out of 51 (15.7%) had an SUVmax ≥5. Overall, 6 patients experienced progression or relapse: 1 had a D5PS score 2 (with SUVmax ≤5), and 5 had a D5PS score 5 (and SUVmax ≥5). Patients with a D5PS score 5 showed significantly lower PFS rates versus all other scores (log-rank P<.001), as did patients with SUVmax ≥5 when compared with those with SUVmax ≤5 (log-rank P<.001). CONCLUSIONS: The present study confirmed the prognostic role of (18)FDG-PET after R-CT, with patients with a D5PS score of 5 and/or an SUVmax ≥5 being at high risk of progression/relapse after RT.

Image interpretation criteria for FDG PET/CT in multiple myeloma: a new proposal from an Italian expert panel. IMPeTUs (Italian Myeloma criteria for PET USe).

PURPOSE: FDG PET/CT is able to detect active disease in patients with multiple myeloma (MM) and can be helpful for staging and assessing therapy response, but no standard interpretation criteria have been proposed for the evaluation of FDG PET/CT in MM. METHODS: A group of Italian nuclear medicine physicians and haematologists met to propose new visual interpretation criteria to standardize FDG PET/CT evaluation in MM patients (Italian Myeloma criteria for PET USe; IMPeTUs) and the reproducibility of these criteria was tested. This Italian multicentre protocol was set up as a subprotocol of EMN02, an international prospective multicentre trial of the European Myeloma Network. The criteria were agreed at multidisciplinary consensus meetings. They include a description of the metabolic state of the bone marrow (BM), number and site of focal PET-positive lesions, the number of osteolytic lesions, and the presence and site of extramedullary disease, paramedullary disease and fractures. A visual degree of uptake was defined for the target lesion and extramedullary lesions according to modified Deauville criteria. MM patients who had undergone FDG PET/CT at baseline (PET-0), after induction (PET-AI) and at the end of treatment (PET-EoT) were enrolled. The patients had been prospectively enrolled in EMN02 and their PET scans were a posteriori reinterpreted in a blinded independent central review process managed by WIDEN®. Five expert nuclear medicine physicians scored the scans according to the new criteria. A case was considered read when four out of the five reviewers completed the report. Concordance among reviewers on different metrics was calculated using Krippendorff's alpha coefficient. RESULTS: A total of 17 consecutive patients were enrolled. On PET-0, the alpha coefficients for the BM score, the score for the hottest focal lesion, the number of focal lesions and the number of lytic lesions were 0.33 and 0.47, 0.40 and 0.32, respectively. On PET-AI, the alpha coefficients were 0.09 and 0.43, 0.22 and 0.21, respectively, and on PET-EoT, the alpha coefficients were 0.07, 0.28, 0.25 and 0.21, respectively. BM was generally difficult to score since grades 2 and 3 are difficult to discriminate. However, since neither of the two grades is related to BM myelomatous involvement, the difference was not clinically relevant. Agreement on focal lesion scores and on the number of focal lesions was good. CONCLUSION: The new visual criteria for interpreting FDG PET/CT imaging in MM patients, IMPeTUs, were found to be feasible in clinical practice.

Radiation therapy in primary mediastinal B-cell lymphoma with positron emission tomography positivity after rituximab chemotherapy.

PURPOSE: To investigate the role of radiation therapy (RT) in patients affected with primary mediastinal B-cell lymphoma (PMBCL) with residual (18)fluorodeoxyglucose positron emission tomography ((18)FDG-PET)-positive disease after rituximab chemotherapy (R-CT). METHODS AND MATERIALS: Thirty-seven patients treated with R-CT and RT, all with (18)FDG-PET scan at diagnosis and before RT, were included. All (18)FDG-PET scans were reviewed, and responses were classified according to the Deauville 5-point scoring system. Outcomes measures were overall survival (OS) and progression-free survival (PFS), estimated for the whole cohort and for subgroups according to (18)FDG-PET score after R-CT. RESULTS: The median follow-up time was 40.9 months. Three patients were assigned to Deauville score 1 (8.1%), 9 to score 2 (24.3%), 7 to score 3 (19%), 14 to score 4 (37.8%), and 4 to score 5 (10.8%). After RT, all patients with score 3-4 experienced a complete response (CR). Among patients with score 5, 1 was in CR (25%), 2 had persistent positivity (50%), and 1 showed progressive disease (25%). A total of 4 patients experienced progression or relapse: 1 of 33 (3%) with scores 1-4, and 3 of 4 (75%) with score 5. The 3-year OS and PFS of the whole cohort were 89.8% and 88.7%, respectively. OS was significantly different between scores 1-3 and scores 4-5 (100% vs 77% at 3 years, P<.05). Patients with a score of 5 had a significantly worse outcome than did all other patients (OS at 2 years, 33.3% vs 100%). CONCLUSIONS: Approximately 50% of PMBCL patients show residual disease at (18)FDG-PET scan after R-CT. RT is able to convert to CR approximately 85% of these patients, but those with a Deauville score of 5 (10%) appear at high risk of progression and death, and they might be candidates for intensified programs.

Interim positron emission tomography and clinical outcome in patients with early stage Hodgkin lymphoma treated with combined modality therapy.

The aim of the study was to investigate whether interim positron emission tomography (iPET) is prognostic in a cohort of patients with early stage Hodgkin lymphoma (HL) homogeneously treated with 3-4 cycles of ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) followed by 30 Gy involved field radiotherapy. Eighty patients were selected (stage I-IIA HL, availability of iPET, minimum follow-up of 12 months), and after central review, 70 were judged negative (iPET-: 87.5%) and 10 positive (iPET+: 12.5%). The two groups were then analyzed for response, progression-free survival (PFS) and overall survival (OS). Only one out of 70 iPET- patients relapsed, with 69 in continuous complete remission (CCR). All 10 iPET + patients achieved a complete response and maintained persistent CCR at follow-up. The 3-year PFS and OS were, respectively, 97% and 98.4% for iPET- and 100% and 100% for iPET+ (p = 0.63). iPET positivity does not seem to be a significant prognostic factor, and change in therapeutic strategy on the basis of iPET does not appear currently advisable outside clinical trials.

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

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

Interim 18-FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP.

Role of interim-PET (I-PET) in diffuse large B-cell Lymphoma (DLBCL) is controversial. To determine predictive value of I-PET on progression-free survival (PFS), we enrolled 88 first-line DLBCL patients treated with 6-8 R-CHOP courses regardless of I-PET. PET/CT were performed at diagnosis, after 2 to 4 courses and at the end of therapy with central reviewing according to visual dichotomous criteria. Results are as follows: I-PET, 72% negative, 28% positive; final-PET (F-PET), 88% negative, 12% positive; clinical complete response 90%. Concordance between clinical response and F-PET negativity was 97% because of 2 false positive. With a median follow-up of 26.2 months, 2-year overall survival and PFS were 91% and 77%, respectively. Two-year PFS for I-PET and F-PET negative versus positive were as follows: I-PET 85% versus 72% (P = .0475); F-PET 83% versus 64% (P < .001). Because of a small number of events, 2 independent bivariate Cox models were tested for PFS. In model 1, F-PET contradicted I-PET (hazard ratio [HR] = 5.03, P = .015 vs 1.27, P = 691); in model 2, F-PET (HR = 4.54) and International propnostic Index score (HR = 5.36, P = .001) remained independent prognostic factors. In conclusion, positive I-PET is not predictive of a worse outcome in DLBCL; larger prospective studies and harmonization of I-PET reading criteria are needed.

Comparison of positron emission tomography scanning and sentinel node biopsy in the detection of inguinal node metastases in patients with anal cancer.

BACKGROUND: Inguinal lymph node metastases in patients with anal cancer are an independent prognostic factor for local failure and overall mortality. Inguinal lymph node status can be adequately assessed with sentinel node biopsy, and the radiotherapy strategy can subsequently be changed. We compared this technique vs. dedicated 18F-fluorodeoxyglucose positron emission tomography (PET) to determine which was the better tool for staging inguinal lymph nodes. METHODS AND MATERIALS: In our department, 27 patients (9 men and 18 women) underwent both inguinal sentinel node biopsy and PET-CT. PET-CT was performed before treatment and then at 1 and 3 months after treatment. RESULTS: PET-CT scans detected no inguinal metastases in 20 of 27 patients and metastases in the remaining 7. Histologic analysis of the sentinel lymph node detected metastases in only three patients (four PET-CT false positives). HIV status was not found to influence the results. None of the patients negative at sentinel node biopsy developed metastases during the follow-up period. PET-CT had a sensitivity of 100%, with a negative predictive value of 100%. Owing to the high number of false positives, PET-CT specificity was 83%, and positive predictive value was 43%. CONCLUSIONS: In this series of patients with anal cancer, inguinal sentinel node biopsy was superior to PET-CT for staging inguinal lymph nodes.

Lymphoscintigraphic localization of sentinel node in early colorectal cancer: results of a monocentric study.

BACKGROUND AND OBJECTIVES: Evaluation of the feasibility of the sentinel node technique in early colorectal neoplasms and its overall accuracy in predicting nodal metastases. METHODS: Thirty-five patients with colon or rectal lesions or degenerate polyps not radically excised by endoscopy were included. Lymphatic mapping was performed with 99mTc labeled albumin colloid injected submucosally by an endoscopic route the afternoon before the surgical procedure. The day of the intervention, 2.5% patent blue V dye (S.A.L.F: Italy) was injected circumferentially around the tumor. A hand held gamma detecting probe (Scintiprobe m100, Pol-Hi-Tech, Italy) was employed to detect "hot" nodes, in vivo and ex vivo. All sentinel nodes were embedded separately for haematoxylin and eosin staining. No IHC or PCR techniques were employed. RESULTS: Sentinel lymph nodes (SLN) were successfully identified in 35 out of 35 patients. Concordance between SLN and nodal status was observed in 32 out of 35 cases (91.4%); four patients (11.4%) were upstaged. Three skip nodal metastases were observed (false-negative rate: 8.5%). CONCLUSIONS: The sentinel node technique with blue dye and radiotracer seems valuable in early colorectal cancers detected by screening programs: a good organization and a learning curve are needed, as further multicentric studies.

In vivo migration of labeled autologous natural killer cells to liver metastases in patients with colon carcinoma.

BACKGROUND: Besides being the effectors of native anti-tumor cytotoxicity, NK cells participate in T-lymphocyte responses by promoting the maturation of dendritic cells (DC). Adherent NK (A-NK) cells constitute a subset of IL-2-stimulated NK cells which show increased expression of integrins and the ability to adhere to solid surface and to migrate, infiltrate, and destroy cancer. A critical issue in therapy of metastatic disease is the optimization of NK cell migration to tumor tissues and their persistence therein. This study compares localization to liver metastases of autologous A-NK cells administered via the systemic (intravenous, i.v.) versus locoregional (intraarterial, i.a.) routes. PATIENTS AND METHODS: A-NK cells expanded ex-vivo with IL-2 and labeled with (111)In-oxine were injected i.a. in the liver of three colon carcinoma patients. After 30 days, each patient had a new preparation of (111)In-A-NK cells injected i.v. Migration of these cells to various organs was evaluated by SPET and their differential localization to normal and neoplastic liver was demonstrated after i.v. injection of 99mTc-phytate. RESULTS: A-NK cells expressed a donor-dependent CD56+ CD16+ CD3- (NK) or CD56+ CD16+ CD3+ (NKT) phenotype. When injected i.v., these cells localized to the lung before being visible in the spleen and liver. By contrast, localization of i.a. injected A-NK cells was virtually confined to the spleen and liver. Binding of A-NK cells to liver neoplastic tissues was observed only after i.a. injections. CONCLUSION: This unique study design demonstrates that A-NK cells adoptively transferred to the liver via the intraarterial route have preferential access and substantial accumulation to the tumor site.

Impact of axillary nodal metastases on lymphatic mapping and sentinel lymph node identification rate in patients with early stage breast cancer.

PURPOSE: The aim of this study was to define the impact of the presence of axillary nodal metastases on lymphatic mapping and sentinel lymph node (SLN) identification rate in patients with early breast cancer. METHODS: Two hundred and forty-six lymphatic mapping procedures were performed with both labelled nanocolloid and blue dye, followed by SLN biopsy and/or complete axillary dissection. The following parameters were recorded: patient's age, tumour laterality and location, tumour size, tumour histology, tumour stage, tumour grade, lymphovascular invasion, radiotracer injection site (subdermal-peritumoural/peri-areolar), SLN visualisation at lymphoscintigraphy, SLN metastases (presence/absence, size) and other axillary metastases (presence/absence, number). Discriminant analysis was used to analyse the data. RESULTS: SLNs were identified by labelled nanocolloid alone in 94.7% of tumours, by blue dye alone in 93.5% and by the combined technique in 99.2%. Discriminant analysis showed the gamma probe SLN identification rate to be significantly limited by the presence of axillary nodal metastases. In particular, the size of SLN metastases and the number of other axillary metastases were the most important variables in reducing the gamma probe SLN identification rate (p = 0.004 and p = 0.002, respectively). On the other hand, high tumour grade was the only parameter limiting the blue dye SLN identification rate. CONCLUSION: The accuracy of lymphatic mapping with labelled nanocolloid is limited by the presence of axillary nodal metastases, and particularly by the degree of SLN tumoural invasion and the presence and number of other axillary nodal metastases. Neither of these elements seems to interfere with the blue dye identification rate. The combination of the two tracers maximises the SLN identification rate.

99mTc-HMPAO-leukocyte scintigraphy in patients with symptomatic total hip or knee arthroplasty: improved diagnostic accuracy by means of semiquantitative evaluation.

UNLABELLED: The aim of this study was to evaluate the diagnostic value, in suspected infectious prostheses, of (99m)Tc-labeled hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) leukocyte scintigraphy interpreted with the addition of a semiquantitative analysis. METHODS: By means of a retrospective review, we included a group of 78 consecutive patients with suspected hip or knee prosthesis infection. We performed 91 (99m)Tc-HMPAO-leukocyte scintigraphies and examined 95 localizations that were suspect. Images were acquired at 3 different time points after the injection of the labeled leukocytes: 50 min (early images), 4 h, and 24 h (late images). The scintigraphic examinations were independently evaluated by 3 observers; qualitative and semiquantitative analyses were performed. The final diagnosis of infection was based on surgical, histologic, and bacteriologic data and follow-up. RESULTS: On qualitative analysis, sensitivity, specificity, and accuracy were 80.4%-87%, 65.3%-71.4%, and 75.8%-77.9%, respectively. On semiquantitative analysis, sensitivity, specificity, and accuracy were 95.6%, 95.8%, and 95.8%, respectively. The analysis of 95% confidential intervals showed statistically significant differences in specificity and accuracy between semiquantitative and qualitative analyses. CONCLUSION: In those patients who underwent (99m)Tc-HMPAO-leukocyte scintigraphy for suspected hip or knee prosthesis infection, the addition of a semiquantitative evaluation to the qualitative analysis of early and late images leads to a significant improvement in both specificity and accuracy.

Sentinel lymph node detection in patients with early-stage breast cancer: comparison of periareolar and subdermal/peritumoral injection techniques.

UNLABELLED: Periareolar (PA) injection offers several potential advantages over other techniques for visualizing sentinel lymph nodes (SLNs) in patients with early breast cancer. However, few studies have been published on this procedure. This study was designed to validate PA injection technique and compare it with the subdermal/peritumoral (SD/PT) injection technique. METHODS: The study included 324 patients in whom 330 breast cancers (T) had been identified by biopsy. This population was divided in 4 groups: (A) 148 patients (150 T) in whom lymphatic mapping was performed by injecting radiotracer with the SD/PT technique; (B) 59 patients (60 T) in whom lymphatic mapping was performed with a combination of blue dye injected with the PA technique and radiotracer injected with the SD/PT technique; (C) 58 patients (60 T) in whom blue dye was injected subdermally and radiotracer was injected periareolarly; and (D) 59 patients (60 T) in whom both blue dye and radiotracer were injected periareolarly. RESULTS: Concordances in the SLN detection rate between blue dye and radiotracer in groups B, C, and D were 98.1%, 100%, and 100%, respectively. The SLN identification rates with the PA technique were 98.3% and 95%, respectively, for radiotracer and blue dye. With the SD/PT technique, these rates were 90.5% and 88.3%, respectively, for radiotracer and blue dye. At lymphoscintigraphy, SLN visualization required the acquisition of late images (3 h after the injection) in 20% of patients who received PA injections and 39.5% of patients who received SD/PT injections. CONCLUSION: These findings validate the PA injection technique and underline some of its reported advantages in comparison with the SD/PT technique.