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Background: Intraoperative localisation of nodal disease in non-small cell lung cancer (NSCLC) can be challenging. Lymph node localisation via radiopharmaceuticals is used in many conditions; we tested the feasibility of this approach in NSCLC. Methods: NSCLC patients were prospectively recruited. Intraoperative peri-tumoral injections of [99mTc]Tc-albumin nanocolloids were performed, followed by removing the tumour and locoregional lymph nodes. These were examined ex vivo with a gamma probe and labelled sentinel lymph nodes (SLNs) if they showed any activity or non-sentinel lymph nodes (nSLNs) if they did not. Thereafter, the surgical field was scanned with the probe; any further radioactive lymph node was removed and labelled as “extra” SLNs (eSLNs). All specimens were sent to histology, and metastatic status was recorded. Results: 48 patients were enrolled, and 290 nodal stations were identified: 179 SLNs, 87 nSLNs, and 24 eSLNs. A total of 44 nodal metastases were identified in 22 patients, with 36 of them (82%) located within SLNs. Patients with nSLNs metastases had at least a co-existing positive SLN. No metastases were found in eSLNs. Conclusions: The technique shows high sensitivity for intraoperative nodal metastases identification. This information could allow selective lymphadenectomies in low-risk patients or more aggressive approaches in high-risk patients.

There is still debate over how reviewing oncological histories and addressing appropriate therapies in multidisciplinary team (MDT) discussions may affect patients’ overall survival (OS). The aim of this study was to describe MDT outcomes for a single cancer center’s patients affected by colorectal liver metastases (CRLMs). From 2010 to 2020, a total of 847 patients with CRLMs were discussed at our weekly MDT meeting. Patients’ characteristics and MDT decisions were analyzed in two groups: patients receiving systemic therapy (ST) versus patients receiving locoregional treatment (LRT). Propensity-score matching (PSM) was run to reduce the risk of selection bias. The median time from MDT indication to treatment was 27 (IQR 13–51) days. The median OS was 30 (95%CI = 27–34) months. After PSM, OS for patients undergoing LRT was 51 (95%CI = 36–64) months compared with 15 (95%CI = 13–20) months for ST patients (p < 0.0001). In this large retrospective study, the MDT discussions were useful in providing the patients with all available locoregional options.

Introduction and aimDiagnosis of hepatocellular carcinoma (HCC) often occurs when the disease is unresectable and therapeutic options are limited. The extent of disease and liver function according to Child-Pugh (C-P) classification are the main prognostic factors guiding clinicians in the management of HCC. The integration of albumin-bilirubin (ALBI) grade is emerging to assess liver function on account of its objectivity and reproducibility. Our aim was to investigate the value of the ALBI grade in predicting the outcome in patients treated with transarterial radioembolization (TARE).MethodsWe retrospectively enrolled patients with advanced and unresectable HCC treated with TARE in our institution. All patients underwent a preliminary dosimetric study before Yttrium-90 resin microsphere TARE. Barcelona Clinic Liver Cancer (BCLC), C-P, and ALBI scores were established at the time of TARE. Overall survival (OS), progression-free survival (PFS), and survival after TARE were assessed with the Kaplan-Meier method. Survival analyses were stratified according to ALBI grade, C-P, and BCLC classification. Univariate and multivariate Cox proportional regression models determined the association between prognostic factors and clinical outcomes.ResultsIn total, 72 patients were included in the study, showing an OS of 51 months. The ALBI grade identified groups of patients with different prognoses both in the whole cohort and within the C-P classes, especially between ALBI 1 and ALBI 2. This result is confirmed also within BCLC classes. In treatment naïve patients, the ALBI grade was not able to predict outcomes, whereas the presence and degree of portal vein thrombosis (PVT) significantly affected prognosis.ConclusionsThe ALBI grade provided a more accurate prognostic stratification than the C-P classification in patients with intermediate and advanced HCC treated with TARE. However, the outcome of HCC is affected not only by liver function but also by disease-related characteristics, such as disease burden and degree of PVT. Including the ALBI grade in clinical guidelines may improve the management of patients affected by HCC.

Radium-223 was associated with high incidence of non-vertebral fractures in patients with castration-resistant prostate cancer (CRPC). However, it is still unclear whether radium-223 may induce skeletal fragility regardless of other therapies for CRPC. We aimed at evaluating the prevalence, incidence, and determinants of vertebral fractures (VFs), i.e., the most frequent complication of skeletal fragility, in CRCP patients undergoing radium-223 therapy in the real-life clinical practice. We retrospectively reviewed 49 CRPC patients with symptomatic bone metastases treated with radium-223. Patients received median number of four radium-223 doses (range: 2–6) and were followed-up for a median period of 11 months (range: 6–44). VFs were assessed by a quantitative morphometry using lateral images of spine 11C-Choline PET/CT, excluding from the analysis the vertebral bodies affected by bone metastases. Before radium-223 administration, 24 patients (49%) had VFs significantly associated with duration of androgen deprivation therapy (ADT; odds ratio 1.29) and previous abiraterone therapy (odds ratio 3.80). During radium-223 therapy, incident VFs occurred in 25% of patients, in relationship with prevalent VFs (hazard ratio 6.89) and change in serum total alkaline phosphatase values (hazard ratio 0.97), whereas the correlations with ADT and abiraterone therapy were lost. Noteworthy, the risk of VFs did not correlate with the therapeutic end points of radium-223. This study provides a first evidence that in real-life clinical practice, radium-223 therapy may induce skeletal fragility with high risk of VFs, likely by inhibition of bone formation and independently of ADT and abiraterone therapy.

Background: The total marrow and lymph node irradiation (TMLI) target includes the bones, spleen, and lymph node chains, with the latter being the most challenging structures to contour. We evaluated the impact of introducing internal contour guidelines to reduce the inter- and intraobserver lymph node delineation variability in TMLI treatments. Methods: A total of 10 patients were randomly selected from our database of 104 TMLI patients so as to evaluate the guidelines’ efficacy. The lymph node clinical target volume (CTV_LN) was recontoured according to the guidelines (CTV_LN_GL_RO1) and compared to the historical guidelines (CTV_LN_Old). Both topological (i.e., Dice similarity coefficient (DSC)) and dosimetric (i.e., V95 (the volume receiving 95% of the prescription dose) metrics were calculated for all paired contours. Results: The mean DSCs were 0.82 ± 0.09, 0.97 ± 0.01, and 0.98 ± 0.02, respectively, for CTV_LN_Old vs. CTV_LN_GL_RO1, and between the inter- and intraobserver contours following the guidelines. Correspondingly, the mean CTV_LN-V95 dose differences were 4.8 ± 4.7%, 0.03 ± 0.5%, and 0.1 ± 0.1%. Conclusions: The guidelines reduced the CTV_LN contour variability. The high target coverage agreement revealed that historical CTV-to-planning-target-volume margins were safe, even if a relatively low DSC was observed.

Pancreatic neuroendocrine tumor (PNET) behavior assessment is a daily challenge for physicians. Modern PNET management varies from a watch-and-wait strategy to surgery depending on tumor aggressiveness. Therefore, the aggressiveness definition plays a pivotal role in the PNET work-up. The aggressiveness of PNETs is mainly based on the dimensions and histological grading, with sometimes a lack of specificity and sensibility. In the last twenty years, EUS has become a cornerstone in the diagnostic phase of PNET management for its high diagnostic yield and the possibility of obtaining a histological specimen. The number of EUS applications in the PNET work-up has been rapidly increasing with new and powerful possibilities. The application of contrast has led to an important step in PNET detection; in recent years, it has been gaining interesting applications in aggressiveness assessment. In this review, we underline the latest experiences and opportunities in the behavior assessment of PNETs using contact-enhanced EUS and contested enhanced harmonic EUS with a particular focus on the future application and possibility that these techniques could provide.

Background: Radioiodine (RAI) is a known risk factor for activation or de novo occurrence of Graves' orbitopathy (GO). Several studies demonstrated that GO can be prevented by glucocorticoids (GCs)...

We investigated the feasibility and activity of an intensified dose-dense ABVD (dd-ABVD) regimen in patients with early-stage unfavorable Hodgkin lymphoma (HL). This prospective, multicenter, phase II study enrolled 96 patients with newly diagnosed, unfavorable stage I or II classical HL. The patients received four cycles of dd-ABVD followed by radiotherapy. Interim PET (PET-2) was mandatory after two courses. Primary endpoints were the evaluation of dd-ABVD feasibility and activity (incidence of PET-2 negativity). The feasibility endpoint was achieved with 48/52 (92.3%) patients receiving > 85% of the programmed dose. The mean dose intensity in the overall patient population (n = 96) was 93.7%, and the median duration of dd-ABVD was 85 days (range, 14–115) versus an expected duration of 84 days. PET-2 was available for 92/96 (95.8%) patients, of whom 79 were PET-2 negative (85.9%). In total, 90 (93.8%) patients showed complete response at the end of treatment. With a follow-up of 80.9 months (3.3–103.2), the median progression-free survival (PFS) and overall survival (OS) were not reached. At 84 months, PFS and OS rates were 88.4% and 95.7%, respectively. No evidence for a difference in PFS or OS was observed for PET-2-negative and PET-2-positive patients. Infections were documented in 8.3% and febrile neutropenia in 6.2% of cases. Four patients died: one had alveolitis at cycle 3, one death was unrelated to treatment, and two died from a secondary cancer. dd-ABVD is feasible and demonstrates activity in early-stage unfavorable HL. The predictive role of PET-2 positivity in early-stage unfavorable HL remains controversial. The study was registered in the EudraCT (reference number, 2011–003,191-36) and the ClinicalTrials.gov (reference number, NCT02247869) databases.

To assess the feasibility of US-18FDG-PET/CT fusion-guided microwave ablation of liver metastases either poorly visible or totally undetectable with US, CEUS and CT, but visualized by PET imaging. Twenty-three patients with 58 liver metastases underwent microwave ablation guided by image fusion system that combines US with 18FDG-PET/CT images. In 28/58 tumors, 18FDG-PET/CT with contrast medium (PET/CECT) was used. The registration technical feasibility, registration time, rates of correct targeting, technical success at 24 h, final result at 1 year and complications were analyzed and compared between the PET/CT and PET/CECT groups. Registration was successfully performed in all cases with a mean time of 7.8 + 1.7 min (mean + standard deviation), (4.6 + 1.5 min for PET/CECT group versus 10.9 + 1.8 min for PET/CT group, P

To assess the feasibility of US-Twenty-three patients with 58 liver metastases underwent microwave ablation guided by image fusion system that combines US withRegistration was successfully performed in all cases with a mean time of 7.8 + 1.7 min (mean + standard deviation), (4.6 + 1.5 min for PET/CECT group versus 10.9 + 1.8 min for PET/CT group, P 0.01). In total, 46/58 (79.3%) tumors were correctly targeted, while 3/28 (10.7%) and 9/30 (30%) were incorrectly targeted in PET/CT and PET/CECT group, respectively (P 0.05). Complete ablation was obtained at 24 h in 70.0% of cases (n = 40 tumors), 23/28 (82.1%) in the PET/CECT group and 17/30 (56.7%) in the PET/CT group (P 0.037). Fourteen tumors underwent local retreatment (11 ablations, 2 with resection and 1 with stereotactic body radiation therapy), while 4 tumors could not be retreated because of distant disease progression and underwent systemic therapy. Finally, 54/58 (93.1%) tumors were completely treated at 1 year. One major complication occurred, a gastrointestinal hemorrhage which required surgical repair.Percutaneous ablation of

Introduction: Transarterial radioembolization (TARE) is a form of brachytherapy in which microspheres loaded with the radioactive isotope yttrium-90 (90Y) are injected selectively to the tumor-feeding arteries through a catheter using fluoroscopic guidance. The use of 90Y microspheres leads to tumor necrosis by delivering a high radiation dose (>70 Gy, tumoricidal threshold) directly to HCC nodules, sparing the non-tumoral liver, and with little or no embolic effect on the vessels. Resin 90Y microspheres are 20–60 μm in size, carry approximately 50 Bq/sphere, and contain 40–80 million microspheres per 3 GBq (1 vial).

Background We evaluated the feasibility and accuracy of 11C–choline PET-CT/TRUS fusion-guided prostate biopsy in men with persistently elevated PSA and negative mpMRI or contraindication to MRI, after previous negative biopsy. Clinical data were part of a prospective on-going observational clinical study: “Diagnostic accuracy of target mpMRI/US fusion biopsy in patients with suspected prostate cancer after initial negative biopsy”. Patients with a negative biopsy and negative mpMRI (PI-RADS v.2 6. Over 58 cores, 25 (43.1%) were positive. No statistically significant difference in terms of mean and median values for SUVmax and SUVratio between benign and malignant lesions was found. PCa lesions with GS 3 + 3 (n = 3) showed a median SUVmax and SUVratio of 4.01 and 1.46, compared to 5.45 and 1.57, respectively for lesions with GS >6 (n = 4). Conclusion Software PET-CT/TRUS fusion-guided target biopsy could be a diagnostic alternative in patients with a suspected primary PCa and negative mpMRI, but its specificity appeared low.

Standardization of FDG PET-CT is becoming a reality, at least in centers that perform clinical trials. Non-FDG radiopharmaceuticals used with PET/CT are far from standard in clinical trials and in clinical use. This article only gives an example of different protocols and indications related to the availability of different radiopharmaceuticals. This scenario will be probably the reality in the near future in many centers throughout the world. Starting from the FDG experience, it will be easy to implement standards for acquisition and interpretation of PET/CT studies with other radiopharmaceuticals.

Introduction: The programmed cell death 1 (PD-1) monoclonal antibodies (MoAbs) nivolumab and pembrolizumab induce response rates exceeding 70% in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). The lack of response to PD-1 MoAbs, and the relapse occurring in most patients who had responded to PD-1 blockade suggest that tools to identify the determinants of response/resistance to PD-1 MoAbs are urgently required. We hypothesized that the characterization of the mutational profile of circulating tumor DNA (ctDNA) could represent a valuable tool to track clonal evolution-driven resistance to checkpoint inhibitors. Patients and Methods: 21 R/R cHL (median age, 32 years; range, 19-51) who had received a median of 5 (range, 3-7) chemotherapy lines, including autologous stem cell transplantation (77%) and brentuximab vedotin (100%), were treated with PD-1 MoAbs. Blood samples were profiled by CAPP-Seq strategy. We analyzed ctDNA and paired DNA from peripheral blood mononuclear cells (PBMCs), as source of germline DNA to filter out polymorphism and sequencing errors. A targeted resequencing panel optimized to include the coding exons and splice sites of 133 genes (320 Kb) that are recurrently mutated in B-cell lymphomas was used. Libraries were prepared from ctDNA and germline gDNA according to the CAPP-seq targeted enrichment strategy (Nimblegen-Roche) and subjected to ultra-deep-next generation sequencing (NGS) using the Nextseq 500 platform (Illumina). The sequencing was performed to obtain a depth of coverage >2000x in >80% of the target region in all samples, which allowed a sensitivity of 3x10-3. A stringent and completely automated bioinformatic pipeline was applied to call non-synonymous somatic mutations, using the somatic function of VarScan2. Results: After a median of 26 (range, 9-63) cycles of PD-1 inhibitors best response was complete remission (CR) for 9 patients (42%), partial remission (PR) for 6 (29%) and progressive disease (PD) for 6 (29%). Patients achieving PR experienced a disease control lasting for 4.5 to 24 months and subsequently underwent PD. Plasma and PBMC samples were collected at baseline, every five cycles of therapy, and end-of-therapy (EOT). At baseline, 18 of 21 patients could be successfully genotyped, whereas three were not. Evaluable patients showed a mean (±SD) number of mutated genes and mutations per patient of 7.3±5.1 (range, 2-22) and 9.9±8.4 (range, 2-37), respectively. Genes recurrently affected by non-synonymous somatic mutations in >20% of R/R cHL included STAT6 (45%), SOCS1 (40%), ITPKB (35%), GNA13 (35%), TP53 (20%), TNFAIP3 (15%). At baseline, no association of distinct DNA mutations with resistance to PD-1 inhibitors could be demonstrated. Signaling pathways targeted by DNA mutations included JAK-STAT, NF-κB, PI3K-AKT, cytokine, NOTCH, immune evasion. The concentration of ctDNA reported as haploid genome equivalent per ml (hGE/ml) was 592.2 (range, 2-2,746), with values of hGE/ml detected in PD patients being significantly higher as compared to CR patients (P=.0437). As compared to cycle 0, the hGE/ml of ctDNA at cycle 5 showed a significant reduction (592.2 vs. 67, P Conclusions: Analysis of ctDNA allows detecting tumor-specific mutations in R/R cHL. The longitudinal tracking of circulating DNA mutations in these patients identifies two different patterns of clonal evolution associated with sensitivity (clonal reshaping) or resistance (clonal persistence) to checkpoint blockade. Disclosures Santoro: Eisai: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; Lilly: Speakers Bureau; Sandoz: Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene: Speakers Bureau; Servier: Consultancy, Speakers Bureau; Takeda: Speakers Bureau; BMS: Speakers Bureau; Roche: Speakers Bureau; Abb-Vie: Speakers Bureau; Amgen: Speakers Bureau; BMS: Consultancy; Bayer: Consultancy, Speakers Bureau; MSD: Speakers Bureau. Rossi:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria, Other: Scientific advisory board; Janseen: Honoraria, Other: Scientific advisory board; Roche: Honoraria, Other: Scientific advisory board; Astra Zeneca: Honoraria, Other: Scientific advisory board. Carlo-Stella:ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Sanofi: Consultancy, Research Funding; Celgene: Research Funding; Janssen Oncology: Honoraria; MSD: Honoraria; Servier: Consultancy, Honoraria, Other: Travel, accommodations; Amgen: Honoraria; Boehringer Ingelheim: Consultancy; Novartis: Consultancy, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; BMS: Honoraria; Janssen: Other: Travel, accommodations; Takeda: Other: Travel, accommodations; Rhizen Pharmaceuticals: Research Funding; AstraZeneca: Honoraria; Genenta Science srl: Consultancy.

This randomized, multicenter study evaluates the addition of bortezomib (13 mg/m(2)) to IGEV (B-IGEV) in patients with relapsed/refractory Hodgkin Lymphoma (HL). Patients received either four courses of IGEV alone (n = 40) or B-IGEV (n = 40). The primary endpoint was the complete response (CR) proportion, evaluated by FDG-PET, after induction chemotherapy. CR proportion was 39% with B-IGEV and 53% with IGEV. PFS and OS were similar between the two groups (two-year PFS: 58% vs 56%; two-year OS: 93% vs 81%). The PET-negative status after treatment was the only variable favorably influencing both PFS (two-year PFS: 77% vs 40%; p = 0.002) and OS (two-year OS: 100% vs 76%; p

The impact of fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) for patients with colorectal liver metastases (CLM) still is debated. Its relevance could be enhanced in the case of recurrent disease. The current study aimed to elucidate the role of PET-CT in restaging and treatment planning for recurrent CLM. A series of 352 consecutive patients undergoing their first liver resection for CLM between 2005 and 2014 was reviewed. Of these patients, 224 (63.6 %) had a recurrence. The 107 patients who had received PET-CT at diagnosis of recurrence before chemotherapy were analyzed. CT was available in all cases, and magnetic resonance imaging (MRI) was available in 64 cases. Extrahepatic lesions were found in 59 patients. Liver and lung recurrences were detected with excellent sensitivity by CT/MRI and PET-CT (liver: 100 vs. 96.7 %; lung: 95.8 vs. 95.8 %). In detecting other recurrence sites, PET-CT had higher sensitivity than CT/MRI (91.5 vs. 54.2 %, p

INTRODUCTION: The availability of novel monoclonal antibodies (moAbs) including the anti-CD30 Brentuximab Vedotin (BV) and the anti-programmed cell death-1 (anti-PD-1) Nivolumab and Pembrolizumab has introduced innovative options in the process of therapeutic decision making for relapsed/refractory classical Hodgkin lymphoma (R/R cHL). However, multiagent chemotherapy followed by autologous stem cell transplantation (auto-SCT) in chemosensitive patients still remains the standard-of-care treatment of R/R cHL. In a multicenter phase 2 study, the BEGEV (Bendamustine, Gemcitabine, Vinorelbine) regimen was previously reported as a highly effective treatment in the second-line salvage setting (Santoro et al., J Clin Oncol, 2016). Here, we report a retrospective analysis of efficacy and toxicity of the BEGEV regimen administered as second- or subsequent-line therapy to R/R cHL in a real-world setting. PATIENTS AND METHODS: From January 2013 to March 2018, 73 cHL patients (median age, 31 years; range, 16 - 69) were candidate to receive 4 courses of BEGEV as second-line (n= 50) or beyond second-line (n= 23) salvage therapy. Refractory patients were 56% in the second-line group and 78% in the group treated beyond second-line. This latter group received a median of 3 (range, 2-8) lines of therapy prior to BEGEV, including Brentuximab Vedotin (BV) (83%) and auto-SCT (43%). RESULTS: In keeping with the phase 2 study, hematological and non-hematological side effects were acceptable. In fact, 64 (88%) patients completed the planned treatment whereas only 9 (12%) patients experienced early therapy discontinuation due to progressive disease (n= 8) and sepsis (n= 1). Of 72 patients evaluable for response, 50 (69.4%) achieved complete remission (CR) and 7 partial remission (PR) with an overall response rate (ORR) of 79%; 1 patient experienced stable disease (SD) and 14 (19%) progressive disease (PD). All but one patient experiencing PD/SD were chemorefractory (14/15). The probability of achieving response (CR+PR) to BEGEV was significantly higher in chemosensitive vs chemorefractory patients (96% vs 70%, P=0.007) whereas no difference could be detected for patients receiving BEGEV as second-line vs those treated beyond second-line (84% vs 70%, P=0.217). All BEGEV responders (n=57) were offered SCT: 44 received auto-SCT, 9 allo-SCT and 1 tandem auto/allo-SCT; 1 patient is waiting for SCT, and 2 refused. With a median follow-up of 14 months, the 1-yr overall survival (OS) and progression-free survival (PFS) are 93% and 69%, respectively. Disease status (sensitive vsrefractory) at BEGEV had no impact on survival (1-yr OD: 94% vs 92%, P=0.57) likely due post-BEGEV consolidation therapy, whereas timing of BEGEV administraton (second-line vs subsequent-lines) significantly affected survival (1-yr OS: 97% vs 78%, P=0.018). CONCLUSION: Data from this real-world analysis further confirm that BEGEV is an effective and safe salvage treament in R/R cHL even when administered to heavily pre-treated patients, thus representing an optimal therapeutic platform prior to consolidation with SCT or immunotherapy. Disclosures Carlo-Stella: Sanofi: Consultancy; Genenta Science: Speakers Bureau; AstraZeneca: Speakers Bureau; Rhizen Pharmaceuticals: Research Funding; Amgen: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; MSD Italia: Speakers Bureau; Boehringher Ingelheim Italia: Consultancy; Janssen: Speakers Bureau; ADC Therapeutics: Research Funding, Speakers Bureau.

Introduction: Phase 1/2 trials using the programmed cell death-1 (PD-1) checkpoint inhibitors Nivolumab and Pembrolizumab in relapsed/refractory classic Hodgkin lymphoma (R/R cHL) who had failed autologous-SCT (Auto-SCT) showed high response rates and durable responses in the majority of patients. However, with extended follow-up, progression-free survival (PFS) curves from the CheckMate 205 trial failed to show a plateau, thus suggesting the need for a consolidation therapy in cHL responding to anti-PD-1. Reported here is the retrospective analysis of the outcome of 34 cHL patients who received an Allo-SCT after treatment with PD-1 inhibitors. Patients and Methods: From Nov 2014 to Apr 2017, 44 R/R cHL enrolled in the CA209-205, CA209-254 and MK3475087trials(median age, 31 years; range, 18-81) received nivolumab (n=42) or pembrolizumab (n=2) until complete remission (CR), very good partial remission (PR) defined as a tumor burden reduction >80%, or progressive disease (PD).At study entry, 30 patients (84%) had refractory disease, 39 (89%) had failed BV and 38 (86%) Auto-SCT. Tumor assessment was performed according to Cheson et al (JCO, 2014). Non-relapse mortality (NRM) was defined as death by any reason other than disease progression. Cumulative incidence of relapse, NRM, and graft-versus-host disease (GVHD) was assessed using the Kaplan-Meier method. Results: After a median duration of anti-PD-1 therapy of 10 months (range, 3-33), 18 patients (41%) experienced CR or PR whereas 26 (59%) progressed. Sixteen of 18 responding patients were allografted. Eighteen of 26 patients who progressed during anti-PD-1 therapy received additional chemotherapy and were finally allografted. Overall, 34 of 44 patients were allografted. Allografting was not performed due to age (n=1), PD (n=4), patient refusal (n=5). The median time from last nivolumab to Allo-SCT was 49 days (range, 23 - 372). At Allo-SCT, 22 patients (65%) were in CR, 11 (32%) in PR and 1 (3%) in PD. Donors were haploidentical sibling (n=23), matched sibling (n=5), or matched unrelated (n=6). Stem cell source was bone marrow (n=15) and peripheral blood (n=19).Acute graft-versus-host disease (aGVHD) was recorded in 15 patients.The cumulative incidence (CI) of grade 2-4 and grade 3-4 aGVHD at 100 days was 46% and 12%, respectively; the 2-year CI of cGVHD was 27%. Non-infectious complications including febrile syndrome, macrophage activation syndrome and cytokine release syndrome, as well as infectious complications occurring until day +100 post-allografting are detailed in a companion abstract.With a median follow-up of 18 months (range, 1.8-39.3), one patient died due to relapse and 5 to non-relapse mortality (NRM) [(acute Graft-versus-Host Disease (aGVHD) (n=1), CMV pneumonia (n=1), immune-mediated pneumonia (n=1) heart failure (n=1), post-transplant lymphoproliferative disorder (PTLD) (n=1)]. The 2-year cumulative incidence (CI) of relapse and NRM was 3.1% and 19.7%, respectively. The 2-year OS and PFS were 76% and 76%, respectively. Conclusions: With an extended follow-up, data reported herein clearly show that Allo-SCT performed after PD-1 inhibitors or the sequence PD-1 inhibitors/chemotherapy is a feasible consolidation strategy associated with an unprecedented low relapse incidence. Early transplant-related complications prompt at identification and implementation of risk-minimizing strategies. PD-1 inhibitors eventually combined with salvage chemotherapy and Allo-SCT represent a paradigm shift in the treatment of refractory cHL. Disclosures Carlo-Stella: Boehringher Ingelheim Italia: Consultancy; Sanofi: Consultancy; MSD Italia: Speakers Bureau; Amgen: Speakers Bureau; Janssen: Speakers Bureau; ADC Therapeutics: Research Funding, Speakers Bureau; AstraZeneca: Speakers Bureau; Genenta Science: Speakers Bureau; Rhizen Pharmaceuticals: Research Funding; Bristol-Myers Squibb: Speakers Bureau.

Unfortunately, the fourth author's middle name was missed out in the original publication of this article. The complete correct name should read as follows.

This retrospective study evaluated whether early 2-[fluorine-18]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) after two cycles of salvage chemotherapy (PET2) could predict survival after high-dose chemotherapy (HDC). Twenty-four Hodgkin lymphoma (HL) patients were included. PET2 was negative in 58% and positive in 42% of patients. Ninety per cent of patients (9/10) with positive PET2 relapsed after HDC while all but one patient with negative PET2 maintained a complete remission. The 2-year progression-free survival was 93% vs. 10% for patients with negative and positive PET2, respectively (P < 0.001). This study shows that interim PET can predict the outcome after high-dose chemotherapy in HL patients.

There is limited evidence regarding the impact of 11C-methionine positron emission tomography/computed tomography (MET-PET/CT) on radiation therapy planning of primary brain tumors. Our aim was to assess the effect of this imaging modality on treatment volumes and clinical outcome of patients eligible for radiation therapy in this oncologic setting.Between November 2009 and May 2012, 31 consecutive patients (male:female, 20:11; mean age, 53.0 years) with pathologically proven primary/relapsed glioma were treated with radiation therapy at the Humanitas Research Hospital. All patients were submitted to the same multi-imaging protocol including MET-PET/CT for biological target volume (PET) and contrast-enhanced magnetic resonance imaging/CT for gross tumor volume, in order to define the clinical target volume. Different volumes were compared and analyzed with respect to treatment planning modification after MET-PET/CT and impact on disease outcome. In 19/31 cases, patients were re-evaluated after completing radiotherapy, and in these cases, progression-free survival and overall survival were determined. The study was submitted to and data collection was approved by the local ethics committee.All patients completed the treatment. In 29 of 31 patients, a biological target volume was defined (mean volume, 18.3 cc), which in 20 cases (65%) resulted in a modification of the clinical target volume (mean, 65.9 cc; range, 8.5-165.6). In the other two cases, PET was negative and did not influence treatment planning. The mean percentage of added volume was 9.2%, ranging between -29% and 38%. With a mean follow-up of 5.4 months, treatment modification according to MET-PET/CT was the only predictor demonstrating a significant correlation with both progression-free survival ( P = 0.018) and overall survival (P = 0.003). None of the other factors evaluated in the analyses, including age, tumor histology, previous treatment, and tumor uptake, was correlated with the outcome.Despite the limited study population, our data indicate that MET-PET/CT can have a significant impact on radiation therapy planning in patients with primary brain tumors. Moreover, treatment modification according to PET appears to be a predictor of clinical outcome in this group of patients.

Standardization of FDG PET-CT is becoming a reality, at least in centers that perform clinical trials. Non-FDG radiopharmaceuticals used with PET/CT are far from standard in clinical trials and in clinical use. This article only gives an example of different protocols and indications related to the availability of different radiopharmaceuticals. This scenario will be probably the reality in the near future in many centers throughout the world. Starting from the FDG experience, it will be easy to implement standards for acquisition and interpretation of PET/CT studies with other radiopharmaceuticals.

The aim of this study was to evaluate the efficacy of post-operative radioiodine ablation with 1,850 MBq after recombinant human thyrotropin (rhTSH) administration in patients with differentiated thyroid carcinoma (DTC). We also aimed to assess the prognostic role of several patient features on the outcome of ablation. We retrospectively analyzed data from a total of 125 patients with DTC who underwent post-operative radioiodine ablation with 1,850 MBq of 131I after preparation with rhTSH. One injection of 0.9 mg rhTSH was administered on each of two consecutive days; 131I therapy was delivered 24 h after the last injection, followed by a post-therapy whole-body scan. Successful ablation was assessed 6–12 months later and defined as an rhTSH-stimulated serum thyroglobulin (Tg) level ≤1.0 ng/ml and a normal neck ultrasound. Patients were stratified according to the American Thyroid Association (ATA) Management Guidelines for Differentiated Thyroid Cancer. Successful ablation was achieved in 82.4 % of patients, with an ablation rate of 95.1 % in low-risk patients and 76.2 % in intermediate-risk patients. Analyzing the correlation between ablation outcome and patient characteristics, we found a statistically significant association between failure to ablate and class of risk based on ATA guidelines (p = 0.025) and a stimulated Tg value at ablation of above 5 ng/ml (p

Background The purpose of our study was to analyze the role of [ 11 C]choline–positron emission tomography/computed tomography (cho-PET/CT) in the management of patients with prostate cancer referred for radiotherapy. Patients and Methods Inclusion criteria for this retrospective study were (1) presence of prostate cancer, (2) referral for first radiotherapy course (for primary or recurrent tumor) between February 2007 and July 2010, and (3) performance of cho-PET/CT. All cho-PET/CT scans were classified according to whether they were positive in the prostate/prostate bed (T), pelvic lymph nodes (N), and distant metastases (M) or negative. Therapeutic strategy based on the cho-PET/CT evaluation was compared with the strategy that would have been proposed had cho-PET/CT imaging not been available, following international and national prostate cancer guidelines. Results Eighty-two cho-PET/CT scans performed in 74 patients were analyzed. Cho-PET/CT was positive in 49 studies (60%): T only in 22 (45% of all positive studies); N only in 4 (8%); T in combination with N in 3 (6%); and M in combination with T or N, or both, in 16 (33%). Treatment after positive cho-PET/CT examination included radiotherapy ± androgen deprivation (29 patients), surgery ± radiotherapy (6 patients), androgen deprivation only (8 patients), and other treatment (6 patients). In 22 cases, cho-PET/CT (27%) altered the treatment approach compared with the treatment that would have been adopted in the absence of cho-PET/CT analysis. Conclusion Cho-PET/CT is valuable in defining the extent of disease and supporting therapeutic decisions in the management of prostate cancer. The therapeutic strategy turned out to be influenced by cho-PET/CT imaging in about one third of the patients included in this study.

The authors describe an atypical case of a patient having giant cell arteritis presenting only with fever, diagnosed by positron emission tomography and subsequently confirmed by temporal artery biopsy.

Neuroendocrine tumours displaying somatostatin receptors have been successfully visualised with somatostatin receptor imaging (SRI). However, there may be differences in sensitivity depending on the site of the primary tumour and/or its metastases. We studied 131 patients affected by neuroendocrine tumours of the gastro-entero-pancreatic (GEP) tract. A pathological diagnosis was obtained in 116 patients, while in 15 the diagnosis was based on instrumental results and follow-up. Fifty-one patients were examined for staging purposes, 80 were in follow-up. Images were acquired 24 and 48 h after the injection of 150-220 MBq of indium-111 pentetreotide. Whole-body and SPET images were obtained in all patients. Patients were also studied with computed tomography (CT), ultrasound (US), and other procedures. Tumours were classified according to their site of origin: pancreas n = 39, ileum n = 32, stomach n = 16, appendix n = 9, duodenum n = 5, jejunum n = 5, rectum n = 3, biliary tract n = 2, colon n = 2, caecum n = 1, liver metastases from unknown primary = 15, widespread metastases from unknown primary = 2. Sensitivity for primary tumour localisation was as follows: SRI = 62%; CT = 43%; US = 36%; other procedures = 45%. Sensitivity for liver metastases: SRI = 90%; CT = 78%; US = 88%; other procedures = 71%. Sensitivity for the detection of extrahepatic soft tissue lesions was: SRI = 90%; CT = 66%; US = 47%; other procedures = 61%. Sensitivity for the detection of the primary tumour in patients with metastases from unknown primary sites: SRI 4/17; CT 0/13; US 0/12; other procedures 1/10. In 28% of the patients SRI revealed previously unknown lesions, and in 21% it determined a modification of the scheduled therapy. Our study confirms the important role of SRI in the management of GEP tumours. However, we feel that a critical investigation should address its role in locating primary tumours, in particular in patients with metastases from unknown primary sites.

The incidence of papillary thyroid cancer (PTC) is rapidly growing, the recorded increase being mainly related to tumors ≤2 cm. The re-classification of tumors >1 and ≤2 cm limited to the thyroid from the T2 to the T1 category triggered some concerns about their best management. In order to identify possible predictors of disease outcome, several clinico-pathological features were analyzed by uni- and multivariate analyses in a retrospective consecutive series of 251 PTCs ≤2 cm. Moreover, since 37% of cases were submitted to prophylactic central compartment node dissection (CLND, VI–VII levels) and radioiodine ablation was performed only when the tumor had an extrathyroidal extension, the impact of these therapeutic tools on the final outcome was evaluated. Among all outcome predictors analyzed, only lymph node metastases and extracapsular invasion were strongly associated with persistence/recurrence. It is worth noting that neither age nor tumor size was a significant indicator of the outcome. Interestingly, as far as the therapeutic interventions are concerned, CLND was strongly associated with remission, whereas radioiodine ablation did not influence the outcome. In conclusion, present results confirm the prognostic influence of node metastases and extra-thyroidal invasion, indicating the need for aggressive treatment in tumors extending beyond the capsule. On the contrary, all pT1N0 tumors, regardless of the diameter, the number of intrathyroidal foci, and the age can be effectively treated only by surgery. The major impact of prophylactic CLND on prognosis suggests to routinely associate it to total thyroidectomy in cases with a preoperative diagnosis of malignancy.

Neoadjuvant chemotherapy has been successfully used in the treatment of patients with colorectal liver metastases. The selection of patients for surgical resection after chemotherapy still poses a significant clinical challenge. (18)F-FDG PET is a useful tool in the assessment of liver metastases but the data regarding its sensitivity after chemotherapy is scarce. Our aim was to assess the value of this imaging modality in the selection of patients with colorectal liver metastasis for surgery following adjuvant chemotherapy.We reviewed the diagnostic performances of (18)F-FDG PET and contrast-enhanced CT scan data from patients with colorectal liver metastases following treatment with chemotherapy. Nineteen patients (12 males, 7 females; median age 61 years; range 41-79) were evaluated. Chemotherapy regimens were: FOLFOX (14 patients), FOLFIRI (3 patients), 5-FU/FA (1 patient) and UFT-irinotecan-oxaliplatin (1 patient). Median time between end of chemotherapy and CT scan was 3.4 weeks, between end of chemotherapy and PET was 5.9 weeks and between end of chemotherapy and surgery was 9.9 weeks. All patients underwent surgery and had histopathological confirmation of liver lesions. Nine patients had segmentectomy, 2 patients had wedge resection, 5 patients had right hepatectomy and 3 patients had explorative laparotomy with liver biopsies.Data from all 19 patients, comprising 65 liver lesions, were confirmed by histo-pathology. Results on a per-lesion basis showed a sensitivity of 62% for (18)F-FDG PET and 70% for CT scan. A complete agreement between (18)F-FDG PET or CT scan and histology was documented in 5 and 3 patients, respectively. The sensitivity of (18)F-FDG PET was shown to increase for lesions larger than 1 cm (74% vs. 18%).These results suggest that (18)F-FDG PET and CT scan have sub-optimal sensitivity in the evaluation of colorectal liver lesions after neo-adjuvant chemotherapy, especially for lesions1 cm. The combined use of the two imaging techniques does not significantly increase the sensitivity of lesion detection.

Most patients with malignant pleural mesothelioma (MPM) are candidates for chemotherapy during the course of their disease. Assessment of the response with conventional criteria based on computed tomography (CT) measurements is challenging, due to the circumferential and axial pattern of growth of MPM. Such difficulties hinder an accurate evaluation of clinical study results and make the clinical management of patients critical. Several radiological response systems have been proposed, but neither WHO criteria nor the more recent RECIST unidimensional criteria nor hybrid uni- and bidimensional criteria seem to apply to tumor measurement in this disease. Recently, modified RECIST criteria for MPM have been published. Although they are already being used in current clinical trials, they have been criticized based on the high grade of inter-observer variability and on theoretical studies of mesothelioma growth according to non-spherical models. Computer-assisted techniques for CT measurement are being developed. The use of FDG-PET for prediction of response and, more importantly, of survival outcomes of MPM patients is promising and warrants validation in large prospective series. New serum markers such as osteopontin and mesothelin-related proteins are under evaluation and in the future might play a role in assessing the response of MPM to treatment.

Radionuclide therapy using iodine-131 is widely employed in the work-up of differentiated thyroid carcinoma. After a brief introduction on physical and dosimetry characteristics of radioactive iodine, this paper suggests state of the arts protocol for the ablation of thyroid remnants and for the treatment of metastatic disease. Diagnostic applications of Nuclear Medicine in these tumors are critically evaluated as well, from the use of iodine-131 whole-body scan to 18F-FDG PET and other new diagnostic tools. Finally, a brief description of new radionuclide treatments is reported

PurposeResponse evaluation with conventional criteria based on computed tomography (CT) is particularly challenging in malignant pleural mesothelioma (MPM) due to its diffuse pattern of growth. There is growing evidence that therapy-induced changes in tumor [18F]fluorodeoxyglucose (FDG) uptake as measured by positron emission tomography (PET) may predict response and patient outcome early in the course of treatment.Patients and MethodsPatients with histologically proven MPM, not candidates to curative surgery, scheduled to undergo palliative chemotherapy with a pemetrexed-based regimen were eligible for this study. Patients were evaluated by FDG-PET and CT at baseline and after two cycles of therapy. A decrease of 25% or more in tumor FDG uptake as measured by standardized uptake value was defined as a metabolic response (MR). Best overall response from CT scans was determined according to previously published criteria.ResultsTwenty-two patients were included in the study, and 20 were assessable for early metabolic response with FDG-PET. Of these, eight were classified as responders (40%) and 12 as nonresponders (60%). Early MR was significantly correlated to median time-to-tumor progression (TTP) with a median TTP for metabolic responders of 14 months versus 7 months for nonresponders (P = .02). No correlation was found between TTP and radiologic response evaluated by CT. Patients with a MR had a trend toward longer overall survival.ConclusionThe use of MR evaluated by FDG-PET in the assessment of treatment efficacy in MPM appears promising. Our observations need to be validated in a larger prospective series.

This study aimed to evaluate the effects of radioiodine ((131)I), alone or in combination with lithium, on thyroid volume and the prevention of radioiodine-induced thyrotoxicosis. This is the first clinical trial including only patients with multinodular goitre, normal TSH values and negative anti-thyroid auto-antibodies at baseline.Eighty consecutive patients were randomised to receive (131)I plus lithium (group I+L) or (131)I alone (group I). Thyroid ultrasonography and biochemical analyses were performed at baseline and at 1, 3, 6, 12 and 24 months after treatment.At 1-4 weeks after treatment, (131)I-induced hyperthyroidism was observed in 58.8% of patients and was prevented by lithium administration. A low incidence of hypothyroidism (19%) was recorded at 24 months, whereas up to 44% of patients developed anti-thyroid antibodies. A significant reduction in thyroid volume was observed after (131)I, with a mean decrease of 47.2% (median 48.2%) at 24 months, without differences between the groups. Moreover, it was shown that the decrease in thyroid volume after (131)I was also due to the significant shrinkage of thyroid nodules.This demonstrates that adjunctive lithium is able to reduce radioiodine-induced hyperthyroidism. Therefore, such treatment appears to be safe in older patients and those with underlying cardiovascular disease. In the present large series, (131)I therapy was demonstrated to be highly effective in reducing thyroid and nodular volume even in patients treated with low (131)I doses (2.5 MBq/ml of thyroid tissue), further supporting the view that radioiodine therapy represents a real alternative to surgery.

Struma ovarii is a rare form of ovary tumour defined as the presence of ectopic thyroid tissue in the ovarian structures. It usually presents with a benign course, although in some cases carcinoma or other malignant tumours can be found in the context of the ectopic tissue. Herein we report the case of a young patient affected by struma ovarii visualized by means of 124I-NaPET/CT. Thanks to the excellent target-to-background ratio of the tracer and the high resolution of the method, we could well identify the presence of some minimal tumour at the level of the left ovary. To our knowledge, this is the first report of its kind.

PET Imaging with [11C]-choline has become a useful tool in the investigation of prostate cancer, with as main application the assessment of previously treated patients presenting with rising PSA and negative conventional imaging procedures. In this case report we describe [11C]-choline PET/CT findings in a patient with a locally advanced cancer, which could be successfully identified thanks to the early image acquisition and the delayed urinary excretion of the carbon-11 labeled tracer.

The aim of this case-control study was to determine the utility of the evaluation of changes in serum thyroglobulin (Tg) levels before and after 131I diagnostic total body scan (TBS) in patients with thyroid cancer to predict the efficacy of radioiodine ablation. Among 134 consecutive patients with differentiated thyroid carcinoma (DTC) who had undergone a thyroidectomy and TBS prior to radioiodine ablation, we selected those subjects with no evidence of distant metastases and with two consecutive assessments of Tg before TBS and radioiodine ablation within a period of four weeks. With this selection procedure 27 patients (22 with papillary and five with follicular carcinomas) were included in our evaluation. The ablation therapy was considered successful when the TBS performed one year after treatment did not show any or less than 1% cervical 131I uptake, Tg levels remained below 3 ng/mL, and clinical and instrumental examinations were negative for the presence of relapses. These criteria divided the selected patients into two subsets: patients with successful radioiodine ablation and patients with residual thyroid tissue. The majority of patients with unsuccessful ablation showed an increase in serum Tg levels, while most of the patients with successful ablation showed a steady decrease in Tg concentrations. Statistical analysis evidenced that the increase in Tg levels after TBS was related to unsuccessful ablation (P ≥0.01). By contrast, the rate of thyroid remnants with 131l uptake did not show any relationship with the outcome of ablation therapy. The group of patients with increasing Tg levels after TBS had a relative risk of 3.3 of unsuccessful ablative therapy compared to the group with stable or decreasing Tg levels. This study supports the concept that by monitoring Tg levels in patients who undergo diagnostic TBS before radioiodine ablation it is possible to obtain useful information about the efficacy of 131l therapy.