Negative PET-CT Research Articles

PET/CT Response Assessment in Pediatric Hodgkin Lymphoma: Does Deauville Score 3 Reflect Negativity?

FDG PET is required for the staging and response evaluation of pediatric Hodgkin lymphoma. This study aimed to evaluate the outcomes of pediatric patients with Hodgkin's lymphoma based on interim PET CT assessments of early response following second-cycle chemotherapy using the Deauville score (DS). It also determines whether DS-3 is providing an adequate or inadequate response. We conducted a retrospective cohort study including 504 pediatric patients with classic Hodgkin lymphoma who were treated with chemotherapy based on the Euro-Net protocol at the Children Cancer Hospital Egypt from March 2019 till the end of October 2022. Patients with adequate response DS 1/2 and DS 3 showed nearly the same 3-year event-free survival (EFS) of 91.9% and 91.5%, respectively, compared with those patients with inadequate response DS 4/5, who showed an EFS of 80.4% ( P =0.001). Patients with a DS 3 at interim PET evaluation were considered negative as DS 1/2. Patients of DS 3 group who did not receive radiotherapy had a much worse 3-year EFS by the existence of positive B symptoms, an ESR>30, or an advanced stage. Radiation therapy did not improve the 3-year EFS in patients with an inadequate response (DS4/5) and poor prognostic characteristics. They still need more advanced treatment. DS 1/2 and DS 3 had about the same 3-year EFS, which is better than the 3-year EFS of patients with DS 4/5. Therefore, we can classify DS 3 as having negative FDG PET CT uptake.

Accuracy of positron emission tomography-computed tomography in the assessment of metabolically negative axillary lymph nodes in breast cancer

Background Breast cancer is a significant public health concern, and early detection of breast lesions is crucial for improved patient outcomes. Accurate assessment of axillary lymph node involvement in breast cancer is vital for staging and treatment decisions. The purpose of this study was to assess to what extent positron emission tomography (PET)-computed tomography (CT) can be used in the assessment of negative axillary lymph nodes in breast cancer and to determine if pathological variability can affect the result of the PET-CT. Patients and methods This prospective study was carried out on 50 female patients with locally advanced breast cancer and with negative PET-CT scans for active axillary lymph nodes. All studied cases underwent postoperative pathological examination to be compared with preoperative PET-CT results. Results Of the studied cases, 84% showed negative axillary lymph node involvement. PET/CT exhibited high sensitivity (95.24%) and specificity (87.5%) in predicting positive nodes, with an axillary maximum standardized uptake value cutoff value of 4.22 (area under the curve=0.923). Logistic regression revealed a significant association between higher T stage and positive lymph nodes (P<0.05). Conclusion PET/CT demonstrates strong predictive accuracy in detecting metabolically negative axillary lymph nodes in breast cancer patients.

SAT307 Intraoperative Radiofrequency Ablation Of An Unresectable Abdominal Paraganglioma Promoted Objective Tumor Response And Complete Biochemical Remission

Abstract Disclosure: I.P. de Magalhães: None. B.S. Boger: None. N.L. Gomes: None. G.L. Martins: None. L.A. Bomfim Jr: None. G.F. Fagundes: None. A.F. Afonso: None. J. Petenuci: None. F.M. Coelho: None. V. Srougi: None. F.Y. Tanno: None. J.L. Chambo: None. A. Latronico: None. M.B. Fragoso: None. A.O. Hoff: None. B.B. Mendonca: None. M.R. Menezes: None. M.Q. Almeida: None. Background: Metastatic pheochromocytoma and paraganglioma (PPGL) are incurable neuroendocrine tumors. Few reports demonstrated the efficacy of radiofrequency ablation (RFA) in achieving tumor control of metastatic lesions (usually <3 cm). However, intraoperative RFA of large and unresectable primary PPGLs was not previously demonstrated. Case Report: A 31-year-old male patient was diagnosed with symptoms of catecholamine excess, high levels of plasma metanephrines and a 9 cm retroperitoneal tumor. The patient underwent an open laparotomy, which revealed unresectable disease. Anatomopathological and immunohistochemical analysis was compatible with the diagnosis of paraganglioma. The patient was treated with 13 cycles of cytotoxic chemotherapy (cyclophosphamide, vincristine and dacarbazine) without objective tumor response by RECIST. Then, he was referred to our Institution for evaluation of additional therapies. Blood pressured was well controlled with doxazosin 16 mg/d, propranolol 40 mg/d and losartan 100 mg/d. A magnetic resonance imaging (MRI) revealed an extensive retroperitoneal mass with 9.0 x 8.6 x 6.0 cm (208 ml) that involved the inferior portion of the vein inferior vena cava, inferior mesenteric artery and infrarenal aorta. Biochemical evaluation demonstrated very high levels of plasma normetanephrine (20.2 nmol/L; normal range <0.9 nmol/L) and normal metanephrine level (0.2 nmol/L; <0.5 nmol/L). The genetic investigation showed the germline pathogenic variant c.1591delC (p.Ser198Alafs*22) in SDHB gene. I131-metaiodobenzylguanidine scintigraphy was negative and Ga68-dotatate PET-CT scan displayed a high uptake in the abdominal mass without metastatic disease. Unfortunately, lutetium177 treatment is not available in our Institution. Due to the lack of alternative therapies, we proposed a debulking open laparotomy with intraoperative RFA in the remaining tumoral lesion. Nevertheless, the tumor did not present a clear cleavage plane with the large vessels and had a large caliber intratumoral vasculature. Intraoperative RFA was performed by a very experienced team (interventional radiologist and anesthesiologist to control blood pressure during the procedure). After 2 months, the dose of doxazosin decreased from 16 mg to 8 mg (50% reduction), plasma normetanephrines dropped to 4.6 nmol/L (79%), and the largest tumor diameter at MRI reduced to 6.8 cm (88.8 ml, 57% reduction). After 7 months of the RFA procedure, the tumor continues shrinking (4.8 cm, 45 ml, 78% reduction) and plasma normetanephrine completely normalized. Conclusion: This is the first report of intraoperative RFA of a large primary unresectable paraganglioma. The patient presented a striking clinical success, complete biochemical remission and an objective tumor response. Support: Sao Paulo Research Foundation (FAPESP) grant 2019/15873-6 (to M.Q. Almeida). Presentation: Saturday, June 17, 2023

Outcomes in participants with a false positive multi-cancer early detection (MCED) test: Results from >4 years follow-up from DETECT-A, the first large, prospective, interventional MCED study.

3039 Background: Recommended standard of care (SOC) early detection tests are solely available for four cancer types and fewer than 20% of incident cancers in the US are being diagnosed as a result of screening. Advances in detection of tumor-derived analytes in the blood are enabling the development of MCED tests that may expand early cancer detection. While MCED tests are being designed with high specificity, false positive (FP) results remain a concern for clinicians and patients alike, as no long-term outcomes of individuals with a FP MCED test have been reported. DETECT-A was the first prospective interventional clinical trial to evaluate an MCED blood test. The test used was an early version of CancerSEEK, evaluated in 9,911 women without history of cancer ( Science, 369:6499, 2020). This prospectively planned analysis evaluates cancer incidence among DETECT-A participants with FP results, with the intention of providing key long-term data on test effectiveness. Methods: This analysis included 98 DETECT-A participants with FP results, where a FP was defined as a positive CancerSEEK result with subsequent PET-CT and clinical evaluation with no evidence of cancer within 1 year of the initial CancerSEEK test. Sixty-three of 98 participants had no follow-up procedure performed after imaging, and 35 subjects had noninvasive/minimally invasive follow-up procedures performed. Electronic medical records were analyzed from January 2020 through November 2022 for cancer diagnosis, treatment, remission, recurrence, and mortality. Results: Ninety-six of 98 participants with a FP result remained free of cancer with a median follow-up of 4.3 years (IQR: 3.9-4.9) from the initial CancerSEEK test. One stage I breast cancer and one stage III ovarian cancer were diagnosed 2.7 and 2.9 years respectively from the initial CancerSEEK test. Conclusions: Patients with a negative PET-CT and initial clinical evaluation after a positive CancerSEEK test had low (<1% per year) risk for cancer in the ensuing four years after the initial CancerSEEK test. If confirmed, this result should prove reassuring to clinicians and to patients who have no evidence of cancer on comprehensive imaging following a positive MCED test. Further, these results provide preliminary support for the recommendation that patients who participate in MCED testing and receive a FP result can safely return to routine care after comprehensive anatomic and functional imaging and clinical evaluation reveal no suspicion of cancer.

Bone marrow biopsy can be omitted in the diagnostic workup of CNS lymphoma of DLBCL origin: a population-based retrospective study in the PET-CT era

Currently, bone marrow (BM) biopsy (BMB) is recommended in the initial staging of patients with the presumed primary central nervous system (CNS) lymphoma (PCNSL). However, the added value of BMB in the era of positron emission tomography (PET-CT) has been challenged in other lymphoma subtypes. We analyzed BM findings in patients with biopsy-proven CNS lymphoma and a negative PET-CT scan for disease outside CNS. A comprehensive Danish population-based registry search was performed to identify all patients with CNS lymphoma of diffuse large B cell lymphoma (DLBCL) histology with available BMB results and staging PET-CT without systemic lymphoma. A total of 300 patients fulfilled the inclusion criteria. Of them, 16% had a previous history of lymphoma, while 84% were diagnosed with PCNSL. None of the patients had DLBCL in the BM. A minority (8.3%) had discordant BMB findings, mainly low-grade histologies that did not influence treatment choice in any case. In conclusion, the risk of overlooking concordant BM infiltration in patients with CNS lymphoma of DLBCL histology and negative PET-CT scan is negligible. As we did not find any patient with DLBCL in the BMB, our results suggest that BMB can be safely omitted in the diagnostic workup in patients with CNS lymphoma and a negative PET-CT.

LBA38 BNT211-01: A phase I trial to evaluate safety and efficacy of CLDN6 CAR T cells and CLDN6-encoding mRNA vaccine-mediated in vivo expansion in patients with CLDN6-positive advanced solid tumours

BNT211 is a potential first-in-class therapeutic approach for claudin 6 (CLDN6)-positive solid tumors with two components: chimeric antigen receptor (CAR) T cells targeting the tumour-specific antigen CLDN6 and a CLDN6-encoding CAR T cell-Amplifying RNA Vaccine (CARVac) designed to expand adoptively transferred CAR T cells and improve their persistence. This is a first-in-human trial (NCT04503278) in patients (pts) with CLDN6-positive relapsed/refractory solid tumours, ECOG PS 0/1 and no further standard treatment options. Following lymphodepletion, the bifurcated 3+3 design comprises CLDN6 CAR T cell dose escalations for monotherapy and combined with CLDN6 CARVac, applied repeatedly after CAR T infusion with one intra-pt dose escalation (25→50 μg). Key primary endpoint is safety and tolerability. As of 15 Jun 2022, 22 pts had been treated, mainly with testicular (13) and ovarian (4) cancers. 7 pts were treated at dose level (DL) 1 (107 CAR T cells/pt; including 1 pt with <107 cells) and 13 pts at DL2 (108 CAR T cells/pt; including 1 pt with a 50% lymphodepletion regimen and 2 pts with no lymphodepletion). 2 pts had dose-limiting toxicities: 1/6 at DL2 monotherapy (pancytopenia), and 1/7 at DL2 + CARVac (hemophagocytic lymphohistiocytosis). Most treatment-emergent adverse events ≥G2 were related to lymphodepletion or asymptomatic transaminase/lipase elevations. Cytokine release syndrome (CRS) was ≤G2, except for 1 pt with no lymphodepletion who had G3 CRS (all resolved). 7/21 evaluable pts (per RECIST v1.1, 6 wks post-infusion) had PR, 8 had SD (6 with target lesion shrinkage) and 6 had PD (including 2 deaths before assessment); as 1 pt was infused with <107 cells they were non-evaluable. 5 pts with testicular cancer responded at 6 wks, with CAR T-cell persistence and further tumour shrinkage; 1 pt was investigator-assessed as CR after 18 wks (negative PET-CT and tumour-marker negative). CLDN6 CAR T cells ± CLDN6 CARVac had a manageable safety profile in this first-in-human trial, with encouraging signs of clinical activity in pts with limited treatment options.

PULMONARY MALT LYMPHOMA PRESENTING WITH EXTENSIVE CYSTIC LUNG DISEASE

TYPE: Case Report TOPIC: Signs and Symptoms of Chest Diseases INTRODUCTION: MALT (mucosa-associated lymphoid tissue) lymphoma is type of marginal zone non-Hodgkin lymphoma of B-cell origin that can rarely involve the lungs. We hereby present a case of pulmonary MALT lymphoma in a patient with Sjögren’s syndrome that presented with extensive cystic lung changes that was initially confused with lymphangioleiomyomatosis (LAM). CASE PRESENTATION: A 44-year-old former smoker female presented with worsening dyspnea on exertion and dry eyes and mouth. Chest CT had previously demonstrated numerous thin-walled cysts that had been present for several years. Due to worsening dyspnea and pulmonary cystic disease (image 1), she underwent a non-diagnostic VATS lung biopsy 3 years prior to consultation due to concern for LAM. Past medical history was notable for rheumatoid arthritis treated with adalimumab and leflunomide. Laboratory evaluation showed markedly elevated SSA and SSB antibody titers, which along with keratoconjuctivitis sicca and xerostomia was consistent with the diagnosis of Sjögren’s syndrome. The VATS lung biopsy was re-reviewed and showed atypical lymphoplasmacytic infiltrates with kappa light chain deposition, consistent with MALT lymphoma. Esophagogastroduodenoscopy and bone marrow biopsy were negative and staging PET-CT scan revealed no evidence of extrathoracic lymphoma. She was treated with weekly rituximab for 4 doses. DISCUSSION: Pulmonary MALT lymphoma is a rare disorder associated with autoimmune disorders, such as Sjögren’s syndrome. Extensive bilateral cysts are rare. Prognosis is typically good, although progression into high-grade B-cell lymphoma may occur. Treatment depends on symptoms and extent of disease. CONCLUSIONS: Pulmonary MALT lymphoma should be on the differential in patients presenting with bilateral extensive cystic disease. Image1: DISCLOSURE: Nothing to declare. KEYWORD: MALT Lymphoma

Survival benefit associated with postoperative PET–CT before adjuvant radiotherapy or chemoradiotherapy in patients with oral squamous cell carcinoma

The aim of this study was to analyse the impact of postoperative positron emission tomography–computed tomography (PET–CT) before adjuvant treatment in oral squamous cell carcinoma (OSCC) patients. Patients with OSCC requiring adjuvant treatment following surgery were divided retrospectively into two groups based on the implementation of PET–CT. The study endpoints were disease-specific survival (DSS) and overall survival (OS). A total of 123 patients underwent PET–CT examination; 28 had abnormal images, but only seven were confirmed to be pathologically positive. A total of 145 patients underwent computed tomography/magnetic resonance imaging (CT/MRI) examination; 20 had abnormal images, but only one was confirmed to be pathologically positive. The median OS time was 5.4 years in the PET–CT group and 4.3 years in the CT/MRI group, demonstrating a significant difference (P = 0.024). Findings were similar for the median DSS time. In patients with positive PET–CT results, the median DSS was 4.3 years and median OS was 3.5 years, and in those with negative PET–CT results, the median survival time could not be calculated as fewer than 50% of patients reached these endpoints; both differences were significant (P = 0.007 and P < 0.001). Although the false-positive rate of postoperative PET–CT is high, it improves the chance of survival through early and more frequent detection of recurrence.

Progression Free Survival (PFS) Analysis of Daratumumab (Dara), Cyclophosphamide, Thalidomide and Dexamethasone: A Quadruplet Intensified Treatment for Transplant Eligible Newly Diagnosed Multiple Myeloma (TE NDMM) Patients

Background: Newly drugs access for MM treatment still a challenge in some countries. One of the most available inductions for TE NDMM patients (pts) worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)-(CTd). Dara the first anti- CD38, had been combined with VCd, VTd and VRd and markedly increased the depth and duration of the response. We hypothesized that Dara and CTd combination could be safe and allow deeper activity as an alternative protocol.Aims: The aims of this analysis were to evaluate Progression Free Survival (PFS) of Dara-CTd treatment and minimal residual disease (MRD) after one year of Dara maintenance. Primary endpoint of the study was to evaluate the VGPR after two consolidation cycles post-autologous stem cell transplantation (ASCT).Methods: This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: TE NDMM, creatinine clearance > 30 ml/min, normal cardiac, renal and liver function and the Easter Cooperative Oncology Group (ECOG) performance status = 0 - 2. The protocol was Dara-CTd for up to four 28-day induction cycles: C-500mg oral (PO) on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, (d) at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose intravenous (IV) on days 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 - 4, followed by ASCT. All pts received up to four 28-day consolidation cycles that was started at D+30 after ASCT: Dara at 16mg/Kg and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara at 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. G-CSF was used for stem cell (SC) mobilization and plerixafor had been allowed whenever the pts need. The MRD was evaluated by next-generation flow (NGF) based and PET-CT was performed when the patient obtained NGF negativity or finished consolidation. PFS outcome was estimated using Kaplan-Meier method. All pts received antiviral, anti-pneumocystis and anti-thrombotic prophylaxis. Data cut-off was June 15, 2021.Results: The first pts was enrolled in November 2018. A total of 24 pts were included, the median age being 60 (range 37- 67 years), 23 (92%) were non-white, 5 (21%) had an R-ISS = 1, 12 (54%) had an R-ISS = 2 and 4 (16%), an R-ISS = 3. Six (25%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, all pts have completed induction, 20 have received transplant and 17 have completed D+90 post-transplant assessment. No SC mobilization failure was observed, and six (30%) pts needed plerixafor use. By ITT analysis after a median follow up of 20 months the PFS at 12 and 18 months was 86%. No PFS difference was observed between different subgroups.Regarding response rates, after the end of induction (cycle 4), 19 (90%) of the pts obtained > PR and 8 (38%) obtained >VGPR, including three MRD negativity by NGF. 17 pts have completed two consolidation cycles after transplant and 94% obtained > VGPR as best response, 13 (76%) obtained MRD negativity by NGF and 10 (58%) had negative PET-CT. Seven (41%) pts had both flow and PET-CT negativity. Six pts completed one year of maintenance and five of them (83%) still MRD negativity by NGF. Four pts died from infection, two of them related with covid infection (one before transplant and one during maintenance). Another case post-transplant, considered not related to the investigational agent and one after consolidation, related to the investigational agent. Two pts have discontinued treatment due to progression - 1 before ASCT e 1 during maintenance.The most common adverse events (AEs) grades 3 and 4 were neutropenia (n = 12), infusion reaction (n = 7), neuropathy (n = 6), lymphopenia (n = 4), infection (n = 3), hypertension (n = 1) and rash (n = 1).Summary/Conclusion: The Daratumumab - CTd protocol is an active regimen capable of producing deep and sustainable responses and improve the PFS of NDMM TE pts with a favorable safety profile. Clinical trial information: NCT03792620. DisclosuresDe Queiroz Crusoe: Janssen: Research Funding. Hungria: Sanofi: Honoraria, Other: Support for attending meetings/travel ; Takeda: Honoraria; Abbvie: Honoraria; Amgen, BMS, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings/travel .

DARATUMUMAB (DARA), CYCLOPHOSPHAMIDE, THALIDOMIDE AND DEXAMETHASONE: A QUADRUPLET INTENSIFIED TREATMENT FOR TRANSPLANT ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA (TE NDMM) PATIENTS

Newly drugs access for MM treatment still a challenge in some countries. One of the most availableinductions for TE NDMM patients (pts) worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)-(CTd). Dara the first anti- CD38, had been combined with VCd, VTd and VRd and markedly increased the depth andduration of the response. We hypothesized that the combination of Dara and CTd could be safe and allow deeper activityas an alternative protocol. The primary endpoint was to evaluate the VGPR after two consolidation cycles post-autologousstem cell transplantation (ASCT). Secondary endpoints were the overall response rate during alltreatment phases and minimal residual disease (MRD), based on the International Myeloma WorkingGroup (IMWG) criteria that includes the next-generation flow (NGF) by the EuroFlow®and PET-CTand the safety profile. This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: TENDMM, creatinine clearance > 30 mL/min, normal cardiac, renal and liver function and the EasterCooperative Oncology Group (ECOG) performance status = 0 - 2. The protocol was Dara-CTd for upto four 28-day induction cycles: C-500 mg oral (PO) on days 1,8 and 15, T at 100-200 mg PO on days1 to 28, (d) at 40 mg PO on days 1,8,15 and 22 and Dara at 16 mg/kg/dose intravenous (IV) on days1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 – 4, followed by ASCT. All ptsreceived up to four 28-day consolidation cycles that was started at D+30 after ASCT: Dara at 16 mg/kg and (d) at 40 mg every other week, associated with T at 100 mg PO on days 1 - 28. Dara at 16 mg/kg was used monthly as maintenance until progression or limiting toxicity. G-CSF was used forstem cell (SC) mobilization and plerixafor had been allowed whenever the pts need. All pts receivedantiviral, anti-pneumocystis and anti-thrombotic prophylaxis. The first pts was enrolled in November 2018. A total of 21 pts were included, the median age being 56 (range 37– 67 years), 19 (90%) were non-white, 3 (14%) had an R-ISS = 1, 12 (57%) had an R-ISS = 2 and 3 (14%), an R-ISS = 3. Five (24%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, all pts have completedinduction, 19 have received transplant and 17 have completed D+90 post-transplant assessment. No SC mobilizationfailure was observed, and five (26%) pts needed plerixafor use. In an intention to treatment analysis, after the end ofinduction (cycle 4), 19 (90%) of the pts obtained > PR and 8 (38%) obtained >VGPR, including three MRD negativity byNGF. 17 pts have completed two consolidation cycles after transplant and 94% obtained > VGPR as best response, 12(70%) obtained MRD negativity by NGF and nine (53%) had negative PET-CT. Seven (41%) pts had both flow and PETCTnegativity. Three pts died from infection, one before transplant because of Covid infection, on post-transplant, considered not related to the investigational agent, and another after consolidation, related to the investigational agent. The most common nonhematological adverse events (AEs) grades 3 and 4 before ASCT were neuropathy (n = 6), infusion reaction (n = 7), infection (n = 2), hypertension (n = 1) and rash (n = 1). This is the first study that combined Dara with CTd as induction for TE NDMM pts. This presentdata has shown that the association of Dara-CTd achieved the primary end point once > 90% of the pts achieved VGPRafter two consolidations cycles, and safety profile was acceptable. NCT03792620.

P-172: Daratumumab (Dara), Cyclophosphamide, Thalidomide and Dexamethasone: a quadruplet intensified treatment for transplant eligible newly diagnosed Multiple Myeloma (TE NDMM) patients final results

<h3>Background</h3> Newly drugs access for MM treatment still a challenge. One of the available inductions for TE NDMM patients (pts) worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)- (CTd). We hypothesized that the Daratumumab and CTd combo could be safe and allow deeper activity as an alternative protocol. Primary endpoint was to evaluate the VGPR after two consolidation cycles post-ASCT. Secondary endpoints were the ORR during all treatment phases and MRD, based on the IMWG criteria that includes the NGF by the EuroFlow® and PET-CT and the safety profile <h3>Method</h3> This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: TE NDMM, CrCl > 30 ml/min, normal cardiac, renal and liver function and the ECOG performance status=0 - 2. The protocol was Dara-CTd for up to four 28-day induction cycles: C-500mg PO on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, (d) at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose IV- QW during cycles 1 - 2 and every other week in cycles 3 – 4, followed by ASCT. All pts received up to four 28-day consolidation cycles that was started at D+30 after ASCT: Dara and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara was used monthly as maintenance until progression or limiting toxicity. G-CSF was used for stem cell (SC) mobilization and plerixafor if needed. All pts received anti(viral, pneumocystis and thrombotic) prophylaxis. <h3>Results</h3> A total of 21 pts were included, the median age being 56 (range 37 – 67 years), 19 (90%) were non-white, 3 (14%) had an R-ISS = 1, 12 (57%) had an R-ISS = 2 and 3 (14%), an R-ISS = 3. Five (24%) pts had HR [del17p, t(4;14) or t(14;16)]. To date, all pts have completed induction, 19 have received transplant and 17 have completed D+90 post-transplant assessment. No SC mobilization failure was observed, and five (26%) pts needed plerixafor use. In an ITT analysis, after the end of induction (cycle 4), 19 (90%) of the pts obtained > PR and 8 (38%) obtained >VGPR, including three MRD negativity by NGF. 17 pts have completed two consolidation cycles after transplant and 94% obtained > VGPR, 12 (70%) obtained MRD negativity by NGF and nine (53%) had negative PET-CT. Seven (41%) pts had both flow and PET-CT negativity. Three pts died from infection, one before transplant because of Covid, one on post-transplant, considered not related to the investigational agent, and another after consolidation, related to the investigational agent. The most common nonhematological AEs grades 3 and 4 before ASCT were neuropathy (n = 6), infusion reaction (n = 7), infection (n = 2), hypertension (n = 1) and rash (n = 1). <h3>Conclusion</h3> This is the first study that combined Dara with CTd as induction for TE NDMM pts. This present data has shown that the association of Dara-CTd achieved the primary end point once > 90% of the pts achieved VGPR after two consolidations cycles, and safety profile was acceptable. <h3>Clinical trial information</h3> NCT03792620.

PET-CT Does Not Impact on the Outcome of the Patients Affected By Multiple Myeloma after Autologous Transplantation: A Real Life Experience

BackgroundVarious imaging techniques are used for management of patients with multiple myeloma (MM) after Autologous Stem Cell Transplantation (ASCT). Between them, PET-CT is a whole-body, high-sensitive imaging tool used to discriminate bone involvement. About the prognostic role of PET-CT, the NCCN guidelines state that “PET-CT results after induction therapy and stem cell transplant help in predicting prognosis of patients with symptomatic MM”. Several previous studies demonstrated that the presence of at least 3 focal lesions with SUV>4.2 and extra-medullary disease was associated to shorter PFS and OS [Zamagni E, 2011]. With these premises, we decided to retrospectively assess if PET-CT precociously performed after ASCT (at 3-6 months) would be able to predict the quality of response or survival in our series of autotransplanted MM patients.Methods45 patients underwent to PET-CT after ASCT: two third of them received as induction the combination of bortezomib, thalidomide, and dexamethasone (VTD); another quarter received bortezomib, anthracycline, and dexamethasone (VAD); the remaining subjects were treated with bortezomib or thalidomide and dexamethasone (VD, TD).ResultsThe 67% of patients receiving VTD as induction achieved a response, with 69% of CR+VGPR versus the only 7% of optimal responses offered by the VAD regimen. At the end of the high-dose procedure, overall 62% of our patients were in CR o VGPR. The median OS was 58 months, and at 40 months the 45% of our patients was still progression-free. In order to avoid positive and negative falses, we calculated the specificity and the sensitivity of PET-CT: in our hands, PET-CT sensitivity resulted 60.7% and specificity 29.4%. For further details, see Table1.The PET-CT positivity did not significantly correlate with the clinical response assessed at the same time-points: indeed, in the subgroup of PET-CT-positive cases, the 26.7% showed a poor response, as expected. Nevertheless, unexpectedly, the 37.8% of positive cases achieved at least a VGPR. On the other hand, the 24.4% of cases with negative PET-CT were in good response, but, conversely, 11.1% of these PET-negative patients were in poor response (p=ns). Overall, the median OS was 17 months in PET-CT-positive patients versus not reached at 40 months in the negative subgroup; nevertheless, this difference was not statistically significant (p=0.29). Finally, we assessed if PET-CT status after ASCT could predict the OS length: in this setting, the median OS was 23 months for PET-CT-positive patients versus not reached at 40 months in the negative subgroup; even in this case, this difference was not statistically significant (p=0.28). The same analysis was performed in terms of PFS: overall, the median PFS was 18 months in PET-CT-positive patients versus 37 months in the negative subgroup; (p=0.55). Finally, we assessed if PET-CT status during follow-up could predict the PFS length: the median PFS of the entire series was 32 months for PET-CT-positive patients versus 60 months in the negative subgroup; once more, this difference was not statistically significant (p=0.15).ConclusionsIn conclusion, the status of PET-CT precociously performed after ASCT was not able to discriminate quality of response or survivals in our patients. This result does not confirm already published data; we argue that this discrepancy could depend on the adoption in our series of the newer and more effective regimens in respect of the VAD, previously adopted in the studies where a significant prognostic impact of PET-CT was demonstrated. Finally, another relevant aspect of our study is that it represents the output of a real-life experience. [Display omitted] DisclosuresGalimberti:Novartis: Speakers Bureau; Pfizer: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Incyte: Speakers Bureau.

Early PET-CT to Guide Escalated Therapy in Advance Stage Hodgkin Lymphoma

BackgroundNowadays treatment for advanced stage Hodgkin lymphoma (LH) remains controversial. ABVD therapy has been historically the standard of care, later on, more sustained dose / intensity regimens like BEACOPP have emerged and improved progression-free survival of patients through better initial control of the disease but without significant overall survival profit due to potentially increased immediate and delayed toxicity. More recently, PET directed strategy with escalation or de-escalation protocols based on the response to the early PET-CT have shown promising results in finding the best way to balance optimal control of the disease with lesser treatment related toxicity.We report here our experiment of treatment escalation in case of positive PET-CT after 2 cycles of ABVD (PET-CT 2) as first-line therapy patients with advanced Hodgkin lymphoma.MethodsBetween 2008 and 2016, 102 patients with Hodgkin lymphoma underwent PET-CT evaluation at diagnosis and after 2 cycles of treatment, 50 had advanced disease (Stage III or IV of Ann Arbor) among witch, 47 received ABVD, 2 BEACOPP and 1 VABEM as initial therapy. The metabolic responses were assessed according to the Deauville criteria.ResultsBefore initiating treatment, the prognosis of the patients was intermediate for 24 patients (48%) and unfavorable for 20 (40%), the median of age was 48 years (min-max: 19-85). Escalated treatment was needed for the 11 patients (22%) refractory to ABVD protocol. The median PFS was 66 months (47-85) and median overall survival (OS) was not achieved; OS at 60 months was 65%. We found no difference in survival between patients with negative PET-CT and those with positive PET-CT, who have benefited from an escalation of treatment.ConclusionThis study evaluated escalating first-line treatment ABVD for advanced stage Hodgkin lymphoma patients with positive PET-CT 2. This management aims to reduce the toxicity of intensive treatments when good control of the disease is asserted. One goal of our study is also to identify the higher risk patients for whom more intensive treatment could be used as first-line treatment. DisclosuresLeleu:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

FDG-PET Utilizing Deauville Scoring Is Superior to Conventional Imaging for Staging and Response Assessment in Pediatric and Adult Patients with Nodular Lymphocyte Predominant Hodgkin's Lymphoma

Introduction:Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma. Data are limited regarding FDG-PET-CT scan (PET-CT) use in NLPHL. We are reporting our experience with PET-CT utility in staging and response assessment of patients with NLPHL and compare this with conventional contrast enhanced CT scan (CT).Methods:Using prospectively collected lymphoma data base and Hospital Tumor Registry, all pediatrics and adult patients with NLPHL seen at our institution from 2003 to 2016 were captured. Patients who underwent pre-treatment CT and PET-CT, during the course of chemotherapy, at the end of planned treatment or for relapsed /refractory disease prior to have new treatment were included in this study. PET-CT response was assessed using both visual assessment method (mediastinal blood pool activity was used as a reference for normal uptake) and Deauville criteria. Both methods were compared (5-point Deauville Criteria; a score of 1-3 as negative-disease and 4-5 as positive-disease).ResultsWe identified 67 NLPHL who met the inclusion criteria. Median age at diagnosis was 27 years (6-56 years) and median follow-up was 30.7 months (5.95-157.4) with a male: female ratio of 4.1:1. Median SUV-max was 8.8 (2.0 to 18.8). In 30 pediatrics patients (age <21 years), median SUV-max was 8.7 (4.0 to 18.8).In the per-scan analysis, the sensitivity, specificity and positive predictive value of pre-treatment PET-CT was 100 %, 99% and 98% respectively. Among the total of 79 pre-therapeutic PET-CT, 948 sites were analyzed, 238 sites were true-positive (1 bone/3 bone marrow involvement, 4 parotids, 4 nasopharynx, 3 liver, 2 lungs, and 221 nodal involvement), 5 were false positive (4 were progressive transformation of germinal center and 1 was reactive lymph node) and 705 sites were true negative. In 5 patients, PET-CT revealed extra nodal disease that was subsequently confirmed on follow-up, but was not picked by CT. There was an agreement between the CT and the PET-CT staging in 68 scans (86%). The staging was changed in 11 (14%) patients; 8 (10%) were upstaged (7 nodal and 1 bone marrow) and 3 (4%) were down staged by PET-CT.A total of 33 bone marrow biopsies (BMBx) were performed and PET-CT confirmed all BMBx results (32 BMBx negative and PET-CT negative, 1 patient BMBx positive and PET-CT positive) showing 100% concordance and suggesting a positive PET-CT for bone or bone marrow is adequate to designate advanced stage. In 2 patients, pre-therapeutic PET-CT revealed bone marrow involvement that was unsuspected before the PET-CT examination.A total of 83 end of treatment PET-CT were carried out, 72 scans were negative (score 1-3) and 11 scans were positive (score 4-5). Treatment consisted of local treatment in the form of surgery/radiation in 7 patients, 2-4 cycles of ABVD +/- radiotherapy in 43 patients, and 6-8 cycles of ABVD +/- radiotherapy in 17 patients. Of the 238 previously involved sites, 204 became true negative, 31 remained true positive, and 3 sites had false negative results with no false positives, showing the negative predictive value of 98.6% with specificity of 100%. Deauville criteria correlated very well with visual assessment criteria. 83 post treatment CT scans showed that out of 238 previously involved sites, 180 became true negative, 24 sites were false positive with specificity of 88%. Two year progression free survival of the entire cohort was 83%.Twenty one patients with stage II, III and IV patients whom were planned to receive 6-8 cycles of chemotherapy underwent mid-treatment PET-CT that were assessed based on Deauville Criteria. 13 patients had negative-disease with none failed primary treatment. 8 had positive-disease; out of which 4 failed primary treatment (numbers are too small for statistics) (Table1).Conclusion:Our data suggest that baseline PET scan is far superior to CT staging. A negative pre-therapy PET-CT for bone/bone marrow is sufficient to omit BMBx. Mid-treatment PET-CT response may have a prognostic role. The validity of the Deauville Score for interpretation of the end of treatment response assessment scans in adult and pediatric patients has been confirmed by the present study. PET-CT has much better specificity for response assessment than CT. Deauville criteria are in concordance with visual assessment criteria and can be applied in real practice. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical utility of FDG PET-CT in stage 1 and advanced testicular seminoma.

5027 Background: Testicular seminoma is highly curable; however, treatments can cause long-term morbidity in survivors. Following chemotherapy for advanced seminoma, positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose together with computerised tomography (PET-CT) can identify patients with residual masses who do not need additional treatment. Its role in detecting recurrence during active surveillance, particularly in patients with small indeterminate masses, is unknown. We assessed the clinical utility of PET-CT in testicular seminoma undergoing active surveillance for stage 1 disease and following curative-intent treatment for advanced disease. Methods: An institutional database was interrogated to identify patients with testicular seminoma who underwent PET-CT between 2000-2020. Demographic, clinicopathological, PET-CT findings and outcome data were retrieved. The positive predictive value (PPV) of PET-CT for correctly identifying disease recurrence was calculated, with disease recurrence (true positive) defined as progressive radiological change, response to treatment or histological confirmation. Negative predictive value (NPV) was calculated for correctly identifying non-recurrence (true negative) at 24-months post PET-CT. Results: We identified 193 PET-CT in 181 stage 1 patients. Of these, 18 (10%) PET-CT were positive, with all correctly diagnosing recurrence, PPV 100%. Of the 138 negative PET-CT with at least 24 months follow up, 5 recurrences developed, NPV 96%. In the subset of PET-CT conducted for suspicion of recurrence in stage 1 patients (n = 71: abnormal imaging n = 65, elevated markers n = 4, other clinical suspicion n = 2), 16 (23%) PET-CT were positive, with all correctly diagnosing recurrence, PPV 100%. In this subset, the NPV is 93% at 24 months (3 recurrences in 44 negative PET-CT). We also identified 154 PET-CT in 77 post-treatment, advanced stage patients. Of these, 69 (45%) PET-CT were positive, with 51 correctly diagnosing recurrence, PPV 74%. Of the 66 negative PET-CT with at least 24 months follow up, 5 recurrences developed, NPV 92%. In the subset of PET-CT performed for suspicion of recurrence following treatment for advanced disease (n = 61: abnormal imaging n = 49, elevated markers n = 5, other clinical suspicion n = 7), 41 (67%) PET-CT were positive, with 36 correctly diagnosing recurrence, PPV 88%. In this subset, the NPV is 94% at 24 months (1 recurrence in 17 negative PET-CT). Conclusions: At our centre, PET-CT has a very high PPV for recurrence, particularly in stage 1 disease, and a very high NPV for non-recurrence in all disease settings. In the subset of PET-CT performed for suspicion of recurrence, PPV is &gt; 88% and NPV is &gt; 93%. The role of PET-CT should be considered in patients with suspicion of recurrence where it may prevent over-treatment in up to 70% patients in stage 1 or 30% in advanced disease.

Prognostic Value of 2-Deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography after Autologous Hematopoietic Stem Cell Transplantation in Lymphoma Using Deauville Scores.

Purpose In the present study, we mainly aimed to evaluate the prognostic value of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]F-FDG) positron emission tomography (PET)/computed tomography (CT) after autologous stem cell transplantation (ASCT) in lymphoma. Procedures. A total of 76 lymphoma patients who benefited from [18F]F-FDG PET-CT (within 3 months and 3–6 months) after ASCT in our institution between April 2010 and December 2019 were enrolled in this retrospective study. These abovementioned patients were divided into two groups based on the Deauville criteria. The Kaplan–Meier method was used in survival analysis, and the log-rank method was adopted in comparison. Prognostic factor analysis was performed by the Cox regression model. Results Positive post-ASCT [18F]F-FDG PET-CT was associated with lower progression-free survival (PFS) and overall survival (OS) (p = 0.001 and p = 0.022, respectively). Univariate analysis showed the post-ASCT PET-CT result was the only independent factor associated with PFS (p = 0.002). Both the number of previous treatments and post-ASCT PET-CT result had a different impact on OS (p = 0.040 and p = 0.028, respectively). Multivariate analysis showed the post-ASCT PET-CT result was the only independent factor associated with OS (p = 0.028). The results showed no significant change from the abovementioned results when DS < 3 was defined as the negative result. For patients who had a PET-CT scan within 3–6 months after ASCT, the negative PET-CT group had a better prognosis including PFS and OS (p = 0.009 and p = 0.025, respectively). However, among the patients receiving PET-CT within 3 months, the result was not statistically significant (p = 0.064 and p = 0.445, respectively). Conclusion Collectively, we found that the post-ASCT [18F]F-FDG PET-CT was a strong indicator for PFS and OS, and a time window of 3–6 months was appropriate for post-ASCT [18F]F-FDG PET-CT. Trial registration number: ChiCTR2100042745.

Stadification ganglionnaire lombo-aortique dans les cancers du col de stade supérieur ou égal à IB2: comparaison des performances du PETscan au 18FDG et du curage lombo-aortique à partir des données du registre des cancers gynécologiques de Côte d’Or de 2003 à 2016

IntroductionCurrent guidelines (ASCO, ESTRO, and ESGO) recommend para-aortic lymphadenectomy (PAL) for lymph node staging in patients with a negative initial PET-CT in locally advanced cervical cancer (LACC), with the aim to determine the radiation fields for radiochemotherapy. The main goal of this study was to compare overall survival (OS) in two groups, which differed according to the para-aortic lymph node staging technique used: imaging alone versus imaging and PAL. Secondary objectives were to determine recurrence-free survival (RFS), the proportion of false negatives on PET-CT, and surgery-related complications. MethodsWe conducted a retrospective, observational study on data from the Côte d’Or gynaecological cancer registry collected from 2003 to 2016, and compared two groups of LACC with different techniques for staging para-aortic lymph nodes: PET-CT alone (iN group) (n=99) and PET-CT associated with PAL (pN group) (n=35) for a total of 134 patients. ResultsOS (HR=1.04 (95% CI: 0.53-2.03); P=0.9) and RFS (HR=0.65 (95% CI: 0.29-1.45); P=0.29) were similar in both groups. There were 11.4% of false negatives in PET-CT, and 2.9% of patients who underwent PAL experienced complications. The staging method, iN or pN, had no impact on the time to the implementation of concomitant radiochemotherapy. ConclusionFor lymph node staging in LACC, PAL after a PET-CT as compared with PET-CT staging alone, had no significant impact on OS or RFS.

Diagnostic Laparoscopy Improves Staging of Malignant Pleural Mesothelioma With Routine Positron Emission Tomography Imaging

With a multimodal treatment strategy, cytoreductive surgery extends survival in malignant pleural mesothelioma. Improving the accuracy of staging can refine patient selection. Our objective was to determine whether diagnostic laparoscopy (DL) improves staging for patients with malignant pleural mesothelioma with the routine use of positron emission tomography (PET). We performed a retrospective review of our prospectively maintained database from February 2014 to May 2019. Inclusion criteria were patients who had disease in the chest that was deemed potentially resectable by radiographic criteria and who underwent DL as part of the staging evaluation before surgery. Of 187 patients (71% men, 80% epithelial) who underwent DL during staging, 76% proceeded to surgery; 22% were unresectable at exploratory thoracotomy and 78% underwent resection (pleurectomy and decortication, 68%; extrapleural pneumonectomy, 32%). Also, 89% had a PET computed tomography (CT), and 11% had a preoperative CT without PET. DL revealed peritoneal disease in 17%. Among patients with pathologically proven disease at DL, 77% had negative PET-CT imaging. Based on the pathologic findings at DL the sensitivity, specificity, positive predictive value, and negative predictive value of PET-CT were 23%, 78%, 17%, and 83%, respectively. The accuracy of PET-CT was 68%. PET-CT has low sensitivity and diagnostic accuracy to identify peritoneal disease in malignant pleural mesothelioma. DL as part of the preoperative staging defines an important subset of patients with bicavitary disease. We recommend DL as a component of staging before surgery.

Is Biopsy of Contralateral Hilar N3 Lymph Nodes With Negative PET-CT Scan Findings Necessary When Performing Endobronchial Ultrasound Staging?

Systematic endobronchial ultrasound (EBUS)-guided lung cancer staging starts with hilar N3 nodes, proceeding sequentially to mediastinal N3, N2, and N1 nodes, with sampling of all enlarged nodes (size,≥ 5mm) by EBUS. However, procedure time is limited by patient comfort when moderate sedation is used. It is unclear if EBUS staging should start with hilar N3 nodes or whether starting with mediastinal N3 nodes suffices. Knowing the probability of hilar N3 nodes with PET-CT scan negative findings harboring occult metastasis can inform this decision. What proportion of patients with hilar N3 nodes showing negative PET-CT scan findings have malignancy by EBUS? This retrospective observational, single-center cohort study included consecutive patients with clinical-radiographic T1-3, N0-3, M0 non-small cell lung cancer undergoing systematic EBUS staging with biopsy of hilar N3 nodes with negative PET-CT scan findings. The primary outcome was the proportion of patients with malignant hilar N3 nodes showing negative PET-CT scan findings. Based on expert opinion, a threshold probability of malignancy of less than 5%was considered sufficient to skip hilar N3 nodes. We used the binomial exact test to compare the observed proportion vsthreshold probability of 5%. Of 1,737 consecutive patients undergoing EBUS staging, 1,567 showed negative PET-CT scan findings of the hilar N3 nodes. These nodes were enlarged by EBUS and were sampled in 739 patients. Malignancy was found in the hilar N3 nodes of 5 of 739 patients (0.68%; 95%CI, 0.22%-1.57%). The proportion was significantly less than the threshold probability (P< .001). Patients with positive PET scan results of the mediastinal N3 nodes were at higher risk of having occult hilar N3 nodal metastasis (P= .003), found in 3 of 46 patients (6.5%; 95%CI, 1.4%-17.9%) with positive PET scan results of the mediastinal N3 nodes. When using moderate sedation, because time is limited, it is reasonable to start with the mediastinal N3 nodes if the hilar and mediastinal N3 nodes show negative PET scan results. Patients with positive PET scan findings of the mediastinal N3 nodes probably should undergo hilar N3 node sampling.

Solitary cerebral metastasis from undiagnosed prostate cancer. Potential role of multiparametric MRI prostate in pre-treatment diagnostic protocols

A 73-year-old man presented with a three-week history of weakness and loss of co-ordination of the left-hand side and weakness of left-hand grip. MRI brain revealed an enhancing lesion in the right parietal lobe, adjacent to the central sulcus, with surrounding oedema and a small satellite lesion in motor cortex. Body CT and FDGPET CT revealed no obvious primary neoplasm. The patient underwent craniotomy with resection of the lesion, subsequent histopathology confirmed a metastatic carcinoma of likely prostate cancer primary origin. The patient was on 5-ARI (Finasteride) for lower urinary tract symptoms that decrease serum PSA levels to half and had benign feeling prostate on digital rectal examination (DRE). Subsequent MRI prostate confirmed presence of a lesion with very high probability of prostate cancer. The patient’s serum Prostate Specific Antigen (PSA) level was 6.8 (13.6 corrected for Finastride) which is relatively low in the context of metastatic disease. Given the recent NICE guidelines of using pre-biopsy multiparametric MRI (mpMRI) for diagnosis of prostate cancer, we suggest that in patients with cerebral metastases of unknown primary, with negative body CT, FDG PET-CT, low PSA and negative DRE, mpMRI prostate should be included in diagnostic protocol in the selected group of men, to enable early diagnosis and performing more suitable and targeted treatment. Keywords: Brain metastasis; prostate cancer; multiparametric MRI; metastasis of unknown origin