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INTRODUCTION AND OBJECTIVES:Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is overexpressed by prostate cancer (PCa) cells and can be targeted using the novel PET radiotr...

INTRODUCTION AND OBJECTIVES:99mTc-MIP-1404 (1404) is a small molecule SPECT imaging agent that binds to prostate-specific membrane antigen (PSMA) allowing for the detection of prostate cancer (PCa)...

TPS187 Background: PSMA is a transmembrane glycoprotein overexpressed in prostate cancer (PC) and further upregulated in castrate resistant disease. 1095 is a novel PSMA-targeted small molecule radioligand therapeutic that binds to the extracellular domain of PSMA selectively with high affinity, internalized, and delivers a targeted lethal radiation dose to PC cells. 18F-DCFPyL is a novel PSMA-targeted PET imaging agent that has shown robust diagnostic performance for detecting recurrent and metastatic PC. In the ARROW study, pts must demonstrate 18F-DCFPyL avidity prior to 1095 treatment. Methods: ARROW is an open-label, randomized (2:1) trial of enza plus 1095 or enza alone in pts with progressive mCRPC who previously received abi. ~120 pts (80: 1095 + enza; 40: enza alone) will be treated at multiple sites in the US and Canada. Eligible male pts must have metastatic disease documented by bone scan or soft tissue lesions measurable per RECIST 1.1 on CT/MRI, be PSMA-avid as determined by 18F-DCFPyL PET/CT, have evidence of biochemical or radiographic progression on abi, and be ineligible for or refuse to receive chemotherapy. Pts will receive enza (prescribed per approved labeling) with or without 1095 (100 mCi dose, followed by up to 3 additional doses administered at least 8 weeks apart, as determined by dosimetry evaluation and occurrence of dose-limiting events). The primary objective is to determine the efficacy of 1095 plus enza compared to enza alone, based on PSA response (confirmed PSA decline ≥50%) rate according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Additional objectives include objective response rate based on PCWG3-modified RECIST 1.1, progression-free survival (PFS) defined as the first occurrence of radiographic progression (PCWG3-modified RECIST 1.1), unequivocal clinical progression, or death from any cause, duration of response, overall survival, and the safety and tolerability of 1095 radioligand therapy. Due to the COVID-19 pandemic, enrollment was halted in April 2020 but is reopening in October 2020. Clinical trial information: NCT03939689.

32 Background: Conventional imaging and bone scintigraphy are suboptimal modalities for identifying PCa. PSMA-based imaging is highly promising for PCa detection. 18F-DCFPyL is a novel PSMA-targeted radiopharmaceutical for positron emission tomography (PET) that may be useful in staging of PCa. The diagnostic performance, detection rate, and potential impact of 18F-DCFPyL on staging of pts with high- risk PCa have been previously reported. Here we report on the impact of 18F-DCFPyL on staging of pts with PCa recurrence or metastases on conventional imaging. Methods: 18F-DCFPyL-PET/CT was evaluated in 117 men with radiologic evidence of local recurrence or metastatic disease on baseline anatomical imaging (CT, MRI) or whole-body bone scintigraphy and in whom at least one lesion was deemed amenable to biopsy. A single dose of 9 mCi (333 MBq) of 18F-DCFPyL was administered via intravenous injection, followed by PET/CT acquisition 1 to 2 hours thereafter. Based on TNM staging: prostatic (T), pelvic LN (N), extra-pelvic LN (M1a), bone (M1b) and other visceral organs/soft tissue (M1c), 18F-DCFPyL-PET/CT detection rates including lesion counts were systematically analyzed. Three central, blinded, and independent readers evaluated the 18F-DCFPyL scans. Results: In this study, 82 (70%) patients had baseline radiographic M1 stage disease (14 patients with M1a, 50 patients with M1b, 18 patients with M1c) and 33 (28%) patients were M0 stage at baseline by central conventional imaging review; two patients were unevaluable. 18F-DCFPyL-PET/CT up-staged 58% (19/33) of pts from M0 to M1, of whom 91% (10/11) who underwent an extra-pelvic biopsy were confirmed to have M1 disease by pathology, including 9 patients with M1b and 1 patient with M1a. Of the patients who were staged M1 at baseline, 18F-DCFPyL-PET/CT upstaged 16% (10/64; M1a to M1b or M1c: n = 4; M1b to M1c: n = 6) of pts to a higher M1 sub-stage and down-staged 22% (18/82) to M0. Conclusions: 18F-DCFPyL-PET/CT identified M1 disease in the majority of patients examined who otherwise had locoregional disease. These data suggest that 18F-DCFPyL-PET/CT may be a useful tool in properly staging men with both metastatic and nonmetastatic relapsed disease, which could lead to superior treatment paradigms than currently exist using conventional imaging. Clinical trial information: NCT02981368.

In patients with differentiated thyroid carcinoma scheduled to receive doses of I for diagnostic or therapeutic purposes, we compared patients prepared with thyroid hormone withdrawal (THW) versus recombinant human thyroid stimulating hormone (rh-TSH) to evaluate the incidence of cancelled procedures because of inadequate thyroid stimulation.Thyroid cancer patients after thyroidectomy who were scheduled for diagnostic or therapeutic I procedures between January 2012 and June 2015 were retrospectively reviewed. Patients were divided based on preparation modality (THW vs rh-TSH), and the incidence of cancelled procedures was compared.Charts from 761 patients were reviewed, 292 THW and 569 rh-TSH. A total of 10 patients (3.4%) in the THW group had cancelled procedures because of insufficient thyroid stimulation (TSH20 mU/L). If a TSH threshold of 30 mU/L were used, 57 patients (17.1%) would have been cancelled. Comparing the groups with chi-squared analysis for both TSH thresholds yielded significantly more cancellations in the THW group (P0.001).Our study has shown that THW in preparation for I procedures leads to significantly more cancellations because of insufficient thyroid stimulation as compared with rh-TSH, which led to no cancellations. The added cost and inconvenience to this cancer population should therefore be considered when selecting a preparation modality.Retrospective cohort-Level III.

TPS5596 Background: PSMA is a transmembrane glycoprotein expressed in normal human prostate epithelium at low levels, but highly upregulated in metastatic prostate cancer (PC). 18F-DCFPyL is a novel PSMA-targeted PET imaging agent that has shown highly promising diagnostic performance for detection of metastatic disease, with potential to identify disease amenable to theranostic targeting. 1095 is a novel PSMA-targeted small molecule that binds to the extracellular domain of PSMA selectively with high affinity. The complex is internalized, allowing the beta emitter, I-131, to kill PC cells. Methods: ARROW is an open-label, randomized (2:1) trial of enza plus 1095 or enza alone in pts with progressive mCRPC who previously received abi. ~120 pts (80: 1095 + enza; 40: enza alone) will be treated at ~40 sites in the US and Canada. Eligible male pts must be at least 18 yo with metastatic disease documented by bone scan or soft tissue lesions measurable per RECIST 1.1 on CT/MRI, be PSMA-avid as determined by 18F-DCFPyL PET/CT, have evidence of biochemical or radiographic progression on abi, and be ineligible for or refuse to receive chemotherapy. Pts will receive enza (prescribed per approved labeling) with or without 1095 (100 mCi dose, followed by up to 3 additional dose(s) administered at least 8 weeks apart, as determined by dosimetry evaluation and occurrence of dose-limiting events). The primary objective is to determine the efficacy of 1095 plus enza compared to enza alone, based on PSA response (confirmed PSA decline ≥50%) rate according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Additional objectives include objective response rate based on PCWG3-modified RECIST 1.1, progression-free survival (PFS) defined as the first occurrence of radiographic progression (PCWG3-modified RECIST 1.1), unequivocal clinical progression, or death from any cause, duration of response, overall survival, and the safety and tolerability of 1095 radioligand therapy. Clinical trial information: NCT03939689 .

4514 Background: Ramucirumab (Ram) as monotherapy or plus paclitaxel is a proven second-line option for advanced gastroesophageal adenocarcinoma (GEA). More and more patients (pts) are pretreated with docetaxel in the perioperative or first-line setting. These pts may benefit more from another, non-cross resistant chemotherapy backbone regimen. This trial evaluates the addition of Ram to FOLFIRI as second line treatment. Methods: This is a multicenter, randomized, investigator initiated, phase II trial. Pts with GEA who have progressed after treatment with a fluoropyrimidine/platinum-containing regimen were randomized 2:1 to either FOLFIRI plus Ram every two weeks (Arm A) or paclitaxel (days 1, 8, 15 of a 28-day cycle) plus Ram every two weeks (Arm B). Major endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and toxicity. Results: 111 pts (median age 61 years, 65% of pts had prior docetaxel therapy) were enrolled and 110 analyzed within intention to treat population (ITT, Arm A, 72; Arm B, 38). In the ITT, there was no significant difference in median OS (A, 6.8 vs. B, 7.6 months, HR 0.94, p = 0.77) and median PFS (A, 4.6 vs. B, 3.6 months, HR 0.72, p = 0.12). For pts with prior docetaxel use (71/110), median PFS was A, 4.3 vs. B, 2.0 months, HR 0.49, p = 0.008 and median OS was A, 7.5 vs. B, 6.4 months, HR 0.71, p = 0.25. In 101 pts with tumor assessment and included in the response analysis, ORR and DCR was 23% and 65% in Arm A and 11% and 60% in Arm B, respectively. 67 pts assessable for response were pre-treated with docetaxel. In these pts, ORR was 24% in Arm A and 9% in Arm B. Disease control rate (DCR) was 67% and 41% for Arm A and B respectively. Both therapies were similarly tolerable, final safety results will be shown. Conclusions: The RAMIRIS trial demonstrated feasibility of the combination of FOLFIRI and Ram. With a response rate of 24% and a median PFS of 4.3 months, docetaxel pre-treated pts seemed to derive pronounced benefit from FOLFIRI-Ram, providing a rationale for a phase III trial, which is currently ongoing. Clinical trial information: NCT03081143 .

9 Background: Current imaging modalities are suboptimal for the initial staging of men at risk of harboring occult metastatic prostate cancer (PCa). PSMA-based imaging is considered highly promising for PCa detection. 18F-DCFPyL is a novel PSMA-targeted radiopharmaceutical for positron emission tomography (PET) that may be useful in staging of pts with high risk PCa. The diagnostic performance of 18F-DCFPyL regarding regional and distant metastases has been previously reported. Here we report on detection rates and the resulting impact 18F-DCFPyL may have on staging of pts with high risk PCa. Methods: 18F-DCFPyL PET/CT was evaluated in 252 men with high-risk PCa who were planned for radical prostatectomy with lymphadenectomy (RP-PLND). 9 mCi (333 MBq) of 18F-DCFPyL was administered 1-2 hours prior to PET/CT. Based on TNM staging, 18F-DCFPyL PET/CT detection rates including lesion counts were systematically analyzed: prostatic (T), pelvic LN (N), extra-pelvic LN (M1a), bone (M1b) & other visceral organs/soft tissue (M1c). Three central, blinded, and independent readers evaluated the 18F-DCFPyL scans. Results: At study entry, 97% and 99% of all evaluable pts had no known nodal or metastatic disease, respectively, based on standard cross-sectional imaging. Of these, 18F-DCFPyL PET/CT staged 37 (14.7%) pts with N1 disease and 27 (10.7%) pts with M1 disease (1 [0.4%] M1a, 23 [9.1%] M1b, and 3 [1.2%] M1c). In total, 56 (22%) of patients were upstaged to N1 or M1 disease by 18F-DCFPyL. The positive predictive value of 18F-DCFPyL based on histopathologic validation for pelvic LNs was 86.7% (95% CI: 70, 95). Only one patient in Cohort A underwent a biopsy of their 18F-DCFPyL detected M1 finding; histopathology confirmed the metastatic lesion in the spine to be a true positive. Conclusions: A total of 22% of pts with high-risk PCa planned for RP-PLND had regional or distant metastatic lesions detected on 18F-DCFPyL PET/CT. These results suggest the potential utility of 18F-DCFPyL PET/CT in the staging of men with newly diagnosed high risk PCa to develop optimized treatment paradigms. Clinical trial information: NCT02981368.

TPS260 Background: PSMA is a transmembrane glycoprotein expressed in normal human prostate epithelium at low levels, but highly upregulated in metastatic prostate cancer (PC). 18F-DCFPyL is a novel PSMA-targeted PET imaging agent that has shown highly promising diagnostic performance for detection of metastatic disease, with potential to identify disease amenable to theranostic targeting. 1095 is a novel PSMA-targeted small molecule that binds to the extracellular domain of PSMA selectively with high affinity. The complex is internalized, allowing the beta emitter, I-131, to kill PC cells. Methods: ARROW is an open-label, randomized (2:1) trial of enza plus 1095 or enza alone in pts with progressive mCRPC who previously received abi. ~120 pts (80: 1095 + enza; 40: enza alone) will be treated at ~40 sites in the US and Canada. Eligible male pts must be at least 18 yo with metastatic disease documented by bone scan or soft tissue lesions measurable per RECIST 1.1 on CT/MRI, be PSMA-avid as determined by 18F-DCFPyL PET/CT, have evidence of biochemical or radiographic progression on abi, and be ineligible for or refuse to receive chemotherapy. Pts will receive enza (prescribed per approved labeling) with or without 1095 (100 mCi dose, followed by up to 3 additional dose(s) administered at least 8 weeks apart, as determined by dosimetry evaluation and occurrence of dose-limiting events). The primary objective is to determine the efficacy of 1095 plus enza compared to enza alone, based on PSA response (confirmed PSA decline ≥50%) rate according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Additional objectives include objective response rate based on PCWG3-modified RECIST 1.1, progression-free survival (PFS) defined as the first occurrence of radiographic progression (PCWG3-modified RECIST 1.1), unequivocal clinical progression, or death from any cause, duration of response, overall survival, and the safety and tolerability of 1095 radioligand therapy. Clinical trial information: NCT03939689.

A 69-year-old man with biochemical recurrence after radical prostatectomy underwent 6 months of androgen deprivation therapy. Upon discontinuation of androgen deprivation therapy, serum prostate-specific antigen rose again to 0.69 ng/mL, and F-DCFPyL PET/CT was performed to identify the site of recurrence. However, only an intense focus of uptake in the spleen could be found. Subsequent contrast-enhanced MRI findings were pathognomonic for splenic hemangioma.

Introduction: We sought to evaluate the diagnostic performance of 18F-fluorocholine positron emission tomography-computed tomography (18F-FCH PET/CT) for initial staging of patients with high-risk prostate cancer. Secondary objectives were to compare the value of 18F-FCH PET/CT to conventional imaging modalities and to evaluate its clinical impact. Methods: We conducted a retrospective study of 76 patients who underwent 18F-FCH PET/CT for initial staging of high-risk prostate cancer. Using pre-established validation criteria, sensitivity and specificity were determined for metastatic disease. Results were compared to findings on magnetic resonance imaging (MRI), computed tomography (CT), and bone scan (BS) when available. Results: Twenty-two (29%) PET/CT scans were positive, 49 (64%) negative, and five (7%) equivocal for nodal or metastatic disease. Of the positive scans, 17 showed regional lymph node involvement, 12 distant nodes, five bone metastases, and three lung metastases. Overall per-patient sensitivity, specificity, positive and negative predictive values for metastatic disease were 65%, 100%, 100%, and 78%, respectively. Sensitivity, specificity, and positive and negative predictive values were 64%, 100%, 100%, and 80%, respectively, for nodal involvement and 86%, 100%, 100%, and 98%, respectively, for bone and other metastases. Conventional imaging was negative for the lesion(s) found on PET/CT in five patients. PET/CT changed the clinical management in nine patients (12%). Conclusions: Although 18F-FCH PET/CT offers some benefits over conventional imaging and demonstrates a high specificity, it remains limited by its sensitivity in the context of high-risk prostate cancer staging. PET with novel urea-based small molecule prostate-specific membrane antigen (PSMA) inhibitors may overcome some of these limitations. However, the interpretation of the study result is limited by the lack of available histological gold standard, the inclusion of several patients who received androgen-deprivation therapy (ADT) prior to PET/CT, our retrospective design, and a relatively small sample size.

A 60-year-old female with no significant medical history presented with hematuria. A computed tomography (CT) scan revealed extensive lymphadenopathy with hypodensities in the liver and spleen, and she was referred for anTıbbi anamnezinde özellik olmayan 60 yaşında bir kadın hematüri ile başvurdu. Bilgisayarlı tomografide (BT) yaygın lenfadenopatiyle birlikte karaciğer ve dalakta hipodens alanlar saptanması üzerine primeri bilinmeyen malignite değerlendirilmesi amacıyla 18F-fluorodeoksiglukoz (18F-FDG) pozitron emisyon tomografisi/BT (PET/BT) için yönlendirildi. PET/BT’de 18F-FDG tutan yaygın lenfadenopatiler ve ölçülemeyecek kadar fazla yoğun 18F-FDG tutan akciğer, karaciğer ve dalak nodülleri saptandı, malignite açısından şüpheli bulundu. PET-kılavuzluğunda posterior superior spina iliacadan yapılan kemik iliği biyopsisinde sarkoidoz ile uyumlu non-kazeifiye granülomlar saptandı. Hasta konservatif olarak takip edildi ve 9 yıllık takip süresinde klinik sorun oluşmadı.

Radioactive iodine (RAI) treatment of differentiated thyroid cancer has been used in clinical practice for almost 60 years and is generally accepted to be a safe and efficacious treatment. Severe toxicity in the form of radiation pneumonitis, sometimes progressing to fibrosis, and bone marrow suppression are reported but remain rare. We present a case of severe myelosuppression requiring hospitalization and transfusion support in an otherwise well, young female patient who had received 175 mCi I-131 for low-volume micronodular lung disease one month prior, with a cumulative lifetime administered activity of 575 mCi. The most important risk factors for myelosuppression following RAI are the activity received, the amount of functioning thyroid tissue present, and the lifetime cumulative activity received.Radyoaktif iyot (RAİ) diferansiye tiroid kanseri tedavisinde yaklaşık 60 yıldır klinik uygulamada kullanılmaktadır ve genellikle güvenli ve etkili bir tedavi olarak kabul edilir. Fibrozise ilerleyebilen radyasyon pnömonisi ve kemik iliği süpresyonu gibi ciddi yan etkiler bildirilmiştir ancak nadiren rastlanır. Bu makalede bir ay önce düşük volümlü mikronodüler akciğer hastalığı için 175 mCi I-131 tedavisi, hayat boyu uygulanan kümülatif aktivite 575 mCi, aldıktan sonra ciddi miyelosüpresyon nedeniyle hastane yatışı ve transfüzyon desteği ihtiyacı olan genç bir kadın hasta sunulmaktadır. RAİ sonrası miyelosüpresyon için en önemli risk faktörleri alınan aktivite miktarı, mevcut fonksiyonel tiroid dokusu ve alınan hayat boyu kümülatif aktivite miktarıdır.

A 58-year-old man with Gleason 4+3 prostate cancer was initially treated by radical prostatectomy followed by salvage radiotherapy to the prostate bed for postoperative biochemical failure. One year later, F-fluorocholine PET/CT detected a pelvic lymph node recurrence, which was treated with radiation therapy and 6 months of androgen deprivation. PSA started to rise again 18 months later, but F-fluciclovine PET/CT failed to demonstrate the site of recurrence at a PSA of 0.63 ng/mL. However, Ga-PSMA PET/CT revealed a single positive 4-mm perirectal lymph node (PSA 0.80 ng/mL at time of scan), in retrospect anatomically apparent but negative on F-fluciclovine PET/CT.

A 67-year-old female patient with no prior history of benign thyroid disease was diagnosed with primary thyroid lymphoma and was staged with18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). She was treated with chemotherapy and external beam radiation therapy, and a follow-up PET/CT showed significant reduction in the size of the thyroid lymphoma with persistent intense 18F-FDG uptake, which was interpreted as partial response to therapy. However, two subsequent PET/CT studies showed no change in the persistent intense 18F-FDG uptake in the thyroid and a biopsy confirmed the presence of thyroiditis with no evidence of residual lymphoma. Follow-up PET/CTs performed over the subsequent three years showed stable intensely 18F-FDG avid thyroiditis with no evidence of lymphoma recurrence. We present the imaging characteristics of a long term radiation treatment induced thyroiditis mimicking 18F-FDG avid residual disease on PET/CT.

A 65-year-old male patient with a one year history of liver transplantation was referred for an 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) to rule out post transplant lymphoproliferative disease. Multiple foci of intense abnormal 18F-FDG uptake were seen in the transplanted liver which were concerning for malignancy. Explantation of the liver approximately 1 month following the PET/CT revealed multiple inflammatory and ischemic changes including large bile duct necrosis, acute cholangitis, bile duct obstruction changes and periportal fibrosis, with no evidence of malignancy. We present the 18F-FDG PET/CT image findings of this case.

Background and aims With the debate over extent of lymphadenectomy in endometrial cancer, sentinel lymph node (SLN) mapping may provide a focused approach to evaluate the most relevant lymph nodes (LN) while minimizing the complications. We evaluated SLN mapping using filtered technetium 99 , indocyanine green (ICG), and blue dye. Methods Prospective evaluation of 100 patients who underwent SLN mapping by using submucosal and deep stromal cervical injections of technetium 99 , ICG, and blue dye as part of the staging for endometrial cancer. Results 286 SLNs were mapped (2.9 per patient) in 92% of patients. The bilateral detection rate was 76%. ICG had a significantly higher SLN detection rate than blue dye in both overall (87% vs 71%, respectively; p=0.005) and bilateral (65% vs 43%, respectively; p=0.002) detection, but similar SLN detection rates compared to technetium 99 in both overall (87% vs 88%, respectively; p=0.83) and bilateral (65% vs 71%, respectively; p=0.36) detection. In eight cases, the SLN was in the para-aortic area and in 14 cases in the pre-sacral, hypogastric vein, or parametrial area. In nine cases, the SLN was positive for metastasis, and in seven cases the SLN was the only positive node. One SLN was falsely negative. No complications or anaphylactic reactions occurred. Conclusion Intra-operative SLN mapping using cervical injection is feasible in patients with endometrial cancer and yields adequate detection rates. It allows mapping of SLNs in areas (pre-sacral, hypogastric vein, parametrial) not routinely sampled. Given the poorer performance of blue dye, surgeons may omit its use if a combination of ICG and technetium 99 is used.

A 72-year-old man with prostate cancer (stage T3b, Gleason score 7) treated by radical prostatectomy was found to have biochemical failure (prostate-specific antigen 8.5 ng/mL) and a suspicious growing nodularity at the left prostate bed on MRI. F-fluorocholine PET/CT failed to demonstrate any site of uptake suggestive of malignancy. A bone scan did exclude bone metastases. Ga-PSMA PET/CT revealed various positive lymph nodes in the supraclavicular, mediastinal, and hilar regions. This was confirmed on F-DCFPyl PET/CT, with the addition of a suspicious right axillary lymph node. Mediastinal biopsy confirmed metastatic prostate cancer.

IMPORTANCE: Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. OBJECTIVE: To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. DESIGN, SETTING, AND PARTICIPANTS: The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. INTERVENTIONS: Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. MAIN OUTCOMES AND MEASURES: The primary end point was overall survival. RESULTS: In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P

A 60 year old woman who presented with multiple small subcutaneous nodules in the upper back and arms, was referred for an [18F] fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) after histological evaluation revealed metastatic leiomyosarcoma of unknown origin. The PET/CT showed multiple 18F-FDG-avid subcutaneous nodules, bone lesions, as well as a large left renal mass, which was biopsied to confirm a primary renal leiomyosarcoma arising from the renal parenchyma. A post therapy PET/CT showed overall progression of disease. The use of 18F-FDG PET/CT in the staging and evaluation of response to therapy of a renal leiomyosarcoma has not been previously described in the literature.

A 73-year-old woman undergoing hormone therapy for previously treated localized breast cancer presented at oncology follow-up 4 years after mastectomy/radiation therapy with weight loss, night sweats, and abdominal pain. Contrast computed tomography (CT) abdomen revealed a soft-tissue mass posterior to the pancreas, several enlarged retroperitoneal lymph nodes, and a dilated portal vein. On 18F-fluorodeoxyglucose positron emission tomography/CT, metabolic activity extended along the portal vein, outlining most of the liver venous system. This “tree-like” appearance was diagnostic of recent portal vein thrombosis by vascular compression from the retroperitoneal mass. Biopsy of the mass later confirmed undifferentiated adenocarcinoma without breast cancer marker expression.

A 44-year-old woman was found to have new diffuse lung uptake on a follow-up whole-body I scan 1 year after being treated with surgery and radioactive iodine for papillary thyroid cancer. However, subsequent CT thorax and thyroglobulin levels were both unremarkable. Shortly after, she presented with respiratory symptoms, exhibiting end-expiratory wheezing on auscultation. Metacholine challenge test confirmed asthma. Symptoms improved under inhaled corticosteroids and beta-2 agonists. Resolution of lung uptake was confirmed on a second I imaging 6 months later.

4023 Background: Ramucirumab as monotherapy and in combination with paclitaxel is a proven second-line option for advanced gastroesophageal adenocarcinoma (GEA). More and more patients (pts) are pretreated with docetaxel in the perioperative or first-line setting. For those pts, the benefit of a combination of ramucirumab and paclitaxel is unclear, and physicians would choose an irinotecan-based regimen as second line treatment. This provides a rationale for the evaluation of FOLFIRI + ramucirumab. Methods: This is a multicenter, randomized, investigator initiated, phase II trial, planned to include 111 pts with advanced GEA to receive 2:1 either FOLFIRI plus ramucirumab every two weeks (Arm A) or paclitaxel (days 1, 8, 15 of a 28-day cycle) plus ramucirumab every two weeks (Arm B). Primary endpoint is 6-months OS rate. This abstract displays interim results of safety and overall objective response (ORR) in docetaxel pre-treated group from up to 65 randomized pts. The results were needed to decide on conducting a subsequent phase III study. Results: 58 (A, 36; B, 22) pts were included in the safety analysis and 50 pts with tumor assessment in the response analysis. Main ≥ grade 3 adverse events were respectively in arms A/B: neutropenia (20%/22%), fatigue (6%/0%), diarrhea (8%/3%), and related SAEs (14% v 23%). Twenty-nine of 50 pts (58%) were pre-treated with docetaxel. In these pts, ORR was 30% in Arm A (5/17) and 8% (1/12) in Arm B. Disease control rate (DCR) was 65% and 50% for Arm A and B respectively. Conclusions: The interim safety analysis of the RAMIRIS trial has demonstrated feasibility of the combination of FOLFIRI and ramucirumab. Docetaxel pre-treated pts had higher ORR and DCR when ramucirumab is combined with FOLFIRI, instead of paclitaxel. EudraCT: 2015-005171-24. Clinical trial information: NCT03081143.

We evaluated the feasibility and tolerability of triple- versus double-drug chemotherapy in elderly patients with oesophagogastric cancer.Patients aged 65 years or older with locally advanced or metastatic oesophagogastric cancer were stratified and randomised to infusional 5-FU, leucovorin and oxaliplatin without (FLO) or with docetaxel 50 mg/m(2) (FLOT) every 2 weeks. The study is registered at ClinicalTrials.gov, identifier NCT00737373.One hundred and forty three (FLO, 71; FLOT, 72) patients with a median age of 70 years were enrolled. The triple combination was associated with more treatment-related National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3/4 adverse events (FLOT, 81.9%; FLO, 38.6%; P.001) and more patients experiencing a ≥10-points deterioration of European Organization for Research and Treatment of Cancer Quality of Life (EORTC QoL) global health status scores (FLOT, 47.5%; FLO 20.5%; p=.011). The triple combination was associated with more alopecia (P.001), neutropenia (P.001), leukopenia (P.001), diarrhoea (P=.006) and nausea (P=.029).). No differences were observed in treatment duration and discontinuation due to toxicity, cumulative doses or toxic deaths between arms. The triple combination improved response rates and progression-free survival in the locally advanced subgroup and in the subgroup of patients aged between 65 and 70 years but not in the metastatic group or in patients aged 70 years and older.The triple-drug chemotherapy was feasible in elderly patients with oesophagogastric cancer. However, toxicity was significantly increased and QoL deteriorated in a relevant proportion of patients.The study was partially funded by Sanofi-Aventis.

The clinical course of sarcomas is difficult to predict on the basis of current clinical and pathologic prognostic criteria and further advancements for diagnosis, tumor–nodes–metastasis staging, grading and prognosis are actively being sought. This article discusses fluorodeoxyglucose (FDG) PET/CT as a marker for grading sarcomas and briefly touches on other roles of FDG PET/CT in the diagnosis and management of this disease. Incidence, risk factors, demographics, staging and grading systems are reviewed. Limitations of the major grading systems are discussed, with a focus on interobserver variability. Next, a summary of evidence to suggest that FDG PET/CT can be used for grading sarcomas is presented. Sarcoma grade is strongly associated with SUVmax; however, FDG PET/CT cannot entirely supplant histologic grading and the former should be used alone only when histopathology is not available. Certain limitations are touched upon in the metabolic grading of these tumors and finally, the future perspective ...

Systemic lupus erythematosus (SLE) is associated with a variety of inflammatory processes that can affect the lymph nodes, brain, kidneys, and spleen. We present two patients with SLE in whom SLE-associated conditions complicated interpretation of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging of the lymph nodes and the spleen. The imaging findings mimicked lymphoma, but histopathological evaluation showed benign processes including reactive follicular hyperplasia in the lymph nodes, Kikuchi-Fujimoto disease in perisplenic lymph nodes, and inflammatory changes and lymphoid hyperplasia in the spleen.

A 67 year old woman with a 10 year history of rheumatoid arthritis (RA) treated with methotrexate and prednisone, presented with a 2 year history of worsening multiple cutaneous plaques of variable appearance. Two distinct skin lesions were biopsied to reveal a composite cutaneous lymphoma, possibly caused by long term methotrexate therapy. An [18F] fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was performed to stage the malignancy, and was later repeated to evaluate response to chemotherapy, which guided subsequent management. We present the PET/CT imaging findings of this very rare iatrogenic (methotrexate induced) immunodeficiency-associated lymphoproliferative disorder.

Our society is characterized by increasing diversity. Immigrants greatly contribute to this diversification. Currently, one fifth of the population in Germany is considered to be of immigrant origin. Healthcare needs of immigrants are often not sufficiently taken into account by healthcare institutions. This may result in many barriers encountered by immigrants in the healthcare system, which may affect the utilization and quality of care. These barriers are particularly pronounced in nursing and palliative care. Current strategies aiming to reduce these barriers are limited as they often only focus on culture and religion, thereby neglecting the role of other diversity dimensions, such as sex and socioeconomic status. Diversity management is able to overcome these shortcomings by implementing conditions in healthcare institutions which promote awareness and openness towards the diversity of healthcare clients. This can improve the quality of care and can contribute to patient-oriented healthcare.

Disseminated histoplasmosis is an opportunistic infection encountered in immunocompromised patients such as those with human immunodeficiency virus infection/acquired immune deficiency syndrome. Involvement of the central nervous system (CNS) can occur in 5-20% of cases of disseminated histoplasmosis, and CNS histoplasmosis can be very difficult to diagnose via conventional imaging modalities such as CT or MRI. The role of 18F-fludeoxyglucose positron emission tomography/CT scan in the diagnosis of CNS histoplasmosis has not been established. A 66-year-old female presented with dizziness and unsteady gait and was diagnosed with human immunodeficiency virus infection and CNS histoplasmosis. In this report, we present the MRI and 18F-fludeoxyglucose positron emission tomography/CT image findings.

Fibrous dysplasia accounts for approximately 7% of benign bone tumours and is a developmental disorder of unknown aetiology. Malignant transformation has been reported in 0.4% of all cases of fibrous dysplasia, and the use of 18F-fludeoxyglucose positron emission tomography/CT scan in the evaluation of malignant transformation has not yet been established. A 72-year-old male with a long-standing history of polyostotic fibrous dysplasia presented with chest and back pain and was evaluated with a 99mTc-methylene diphosphonate bone scan as well as an 18F-fludeoxyglucose positron emission tomography/CT scan to define the extent of bone involvement and assess for possible malignant transformation. We present the imaging findings as well as the long-term follow-up of this case.

A 32year-old female presenting with right lower quadrant pain was found to have caecal varices. Extensive work-up revealed underlying protein C deficiency.

Low grade lymphoma may transform into a more aggressive lymphoma and this transformation is usually associated with a poor outcome. A 65year old man presented with two metabolically active splenic lesions on a staging [18F] fluoro-2-deoxy-d-glucose (

A wide variety of malignant renal and urinary bladder diseases can be detected on (18)F-FDG PET/CT. Although the PET/CT findings are often nonspecific, the aim of this atlas was to demonstrate that the spectrum of renal and urinary bladder malignancy that can be evaluated with PET/CT is much broader than current medical literature would suggest. PET/CT readers and oncologists should be aware of the variety of urological tumor types that can be detected on PET/CT and some of the patterns of (18)F-FDG uptake that can be observed in these cases.

A 74-year-old man with newly diagnosed prostate cancer underwent Ga-PSMA PET/CT, which demonstrated intense uptake in and adjacent the L2 vertebral body. Subsequent MRI of the lumbar spine showed an aggressive L2 hemangioma with adjacent soft tissue extension. There was congruence of the intraosseous and extraosseous components of the hemangioma and the PSMA PET uptake. This is a rare but important potential pitfall in Ga-PSMA PET/CT-a soft tissue lesion with intense tracer uptake related not to a nodal metastasis of prostate cancer but to extraosseous extension of an aggressive vertebral body hemangioma.

TPS5092Background: Accurate localization of sites of disease is essential for delivering optimal care to patients with prostate cancer. This is especially true for patients who may have distant dis...

In asymptomatic infertility patients, no significant relationship was found between the presence of antisperm antibodies (ASA) in serum and in semen samples (IgG and/or IgA ASA), differentiated with the mixed antiglobulin reaction (MAR), and the microbial colonization of ejaculates covering a broad spectrum of microorganisms. Likewise, there was no significant association of ASA with microbial findings in patients' female partners, who also presented without symptoms of genital tract infection and were screened at the same time. Furthermore, ASA in semen (IgG and IgA) were not significantly related to several potential markers of subclinical male sexual gland infection or inflammation (leukocytes, PMN elastase, albumin, C3c) evaluated in aliquots of the same ejaculates used for immunological testing.

Purpose This study was designed to compare fluorouracil, leucovorin, and oxaliplatin with fluorouracil, leucovorin, and cisplatin in patients with advanced gastric cancer. Patients and Methods Patients with previously untreated advanced adenocarcinoma of the stomach or esophagogastric junction were randomly assigned to receive either fluorouracil 2,600 mg/m2 via 24-hour infusion, leucovorin 200 mg/m2, and oxaliplatin 85 mg/m2 (FLO) every 2 weeks or fluorouracil 2,000 mg/m2 via 24-hour infusion, leucovorin 200 mg/m2 weekly, and cisplatin 50 mg/m2 every 2 weeks (FLP). The primary end point was progression-free survival (PFS). Results Two hundred twenty patients (median age, 64 years; metastatic, 94%) were randomly assigned. FLO was associated with significantly less (any grade) anemia (54% v 72%), nausea (53% v 70%), vomiting (31% v 52%), alopecia (22% v 39%), fatigue (19% v 34%), renal toxicity (11% v 34%), thromboembolic events (0.9% v 7.8%), and serious adverse events related to the treatment (9% v 19%). FLP was associated with significantly less peripheral neuropathy (22% v 63%). There was a trend toward improved median PFS with FLO versus FLP (5.8 v 3.9 months, respectively; P = .077) and no significant difference in median overall survival (10.7 v 8.8 months, respectively). However, in patients older than 65 years (n = 94), treatment with FLO resulted in significantly superior response rates (41.3% v 16.7%; P = .012), time to treatment failure (5.4 v 2.3 months; P < .001), and PFS (6.0 v 3.1 month; P = .029) and an improved OS (13.9 v 7.2 months) as compared with FLP, respectively. Conclusion FLO reduced toxicity as compared with FLP. In older adult patients, FLO also seemed to be associated with improved efficacy.

Background: Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma, but has not yet been evaluated in the context of resectable patients. Here we report findings from the phase 2 part of the phase 2/3 FLOT4 trial, which compared histopathological regression in patients treated with a docetaxel-based triplet chemotherapy versus an anthracycline-based triplet chemotherapy before surgical resection.Methods: In this randomised, open-label, phase 2/3 study, eligible participants were recruited from 28 German oncology centres. Patients with resectable gastric or gastro-oesophageal junction cancer who had clinical stage cT2 or higher, nodal positive (cN+) disease, or both were randomly assigned (1:1) to either three preoperative and three postoperative 3-week cycles of intravenous epirubicin 50 mg/m2on day 1, intravenous cisplatin 60 mg/m2on day 1, and either fluorouracil 200 mg/m2as continuous intravenous infusion or capecitabine 1250 mg/m2orally (two doses of 625 mg/m2per day) on days 1 to 21 (ECF/ECX group) or four preoperative and four postoperative 2-week cycles of docetaxel 50 mg/m2, intravenous oxaliplatin 85 mg/m2, intravenous leucovorin 200 mg/m2, and fluorouracil 2600 mg/m2as a 24 h infusion, all on day 1 (FLOT group). Randomisation was done centrally with an interactive web-response system based on a sequence generated with blocks (block size 2) stratified by Eastern Cooperative Oncology Group performance status, location of primary tumour, age, and nodal status. No masking was done. Central assessment of pathological regression was done according to the Becker criteria. The primary endpoint was pathological complete regression (tumour regression grade TRG1a) and was analysed in the modified intention-to-treat population, defined as all patients who were randomly assigned to treatment excluding patients who had surgery but did not provide resection specimens for central evaluation. The study (including the phase 3 part) has completed enrolment, but follow-up is ongoing and this is an interim analysis. The trial is registered with ClinicalTrials.gov, number NCT01216644. Findings: Between Aug 18, 2010, and Aug 10, 2012, 300 patients (152 patients in the ECF/ECX group; 148 patients in the FLOT group) were enrolled into the phase 2 part of the study, 265 of whom (137 in the ECF/ECX group; 128 in the FLOT group) were assessable on a modified intention-to-treat basis. 119 (93%) of 128 patients in the FLOT group and 126 (92%) of 137 patients in the ECF/ECX group were given all planned preoperative cycles of treatment. FLOT was associated with significantly higher proportions of patients achieving pathological complete regression than was ECF/ECX (20 [16%; 95% CI 10-23] of 128 patients vs eight [6%; 3-11] of 137 patients; p=0·02). 44 (40%) of 111 patients in the ECF/ECX group and 30 (25%) of 119 patients in the FLOT group had at least one serious adverse event involving a perioperative medical or surgical complication. The most common non-surgical grade 3-4 adverse events were neutropenia (52 [38%] of 137 patients in the ECF/ECX group vs 67 [52%] of 128 patients in the FLOT group), leucopenia (28 [20%] vs 36 [28%]), nausea (23 [17%] vs 12 [9%]), infection (16 [12%] vs 15 [12%]), fatigue (19 [14%] vs 11 [9%]), and vomiting (13 [10%] vs four [3%]). Interpretation: Perioperative FLOT was active and feasible to administer, and might represent an option for patients with locally advanced, resectable gastric or gastro-eosophageal junction adenocarcinoma.

Sarcomas are relatively rare primary malignan­ cies that originate from the embryonic meso­ derm and are responsible for less than 1% of adult cancers, but comprise approximately 6% of childhood malignancies [1]. Despite aggres­ sive therapy, including surgery, adjuvant chemo­ therapy and radiotherapy, sarcoma patients’ prognosis remains guarded and overall survival has not improved substantially over the past few decades; 40% of patients with high­grade lesions will die from metastatic disease [1]. At initial histopathologic diagnosis, sarcoma grading is a fundamental step in patient evalua­ tion and plays a prominent role in overall stag­ ing. As recognized by WHO, there are two principle grading systems – the National Cancer Institute and the French Federation of Cancer Centers Sarcoma Group (FNCLCC) [2]. The more widely­used FNCLCC grade is based on three parameters: tumor differentiation, mitotic activity and necrosis. Each of these parameters receives a score: differentiation (1–3), mitotic activity (1–3) and necrosis (0–2). The sum of the scores generates a grade: grade 1 is a score of 2–3, grade 2 is 4–5 and grade 3 is 6–8. Sarcomas are extremely heterogeneous tumors, which often contain high­grade components, in addition to lower­grade areas. Frequently, sarcomas show intraturmoral necrosis, further complicating histopathological assessment. As a result of this heterogeneity, difficulty arises in accurately grading sarcomas as the assessment becomes dependent on which part of the sarcoma was biopsied and/or selected for histologic exam­ ination by the pathologist. Significant patholo­ gist interobserver variability exists when deter­ mining the histological sarcoma type, presence of necrosis and quantifying mitotic activity [3]. Given the importance of accurately determining tumor grade – and subsequently prognosis and

We report the case of a 65-year-old woman with a history of adenoid cystic carcinoma (ACC) of the breast. Fifteen years after mastectomy, the patient underwent a right upper lobectomy for a lung mass, and biopsy indicated ACC metastasis. Ten years after lobectomy, an F-FDG PET/CT was performed for restaging to rule out further metastases. We observed intense FDG uptake in enlarged polylobulated kidneys, which was biopsy proven as ACC metastasis.

Introduction: We sought to determine predictive factors (patient and prostate- specific antigen [PSA] characteristics) for 18F-fluoromethylcholine positron emission tomography-computed tomography (18F-FCH PET/ CT) positivity in the context of biochemical recurrence after local treatment of prostate cancer (PCa) with curative intent.Methods: This is a retrospective study including 60 18F-FCH PET/ CT scans of patients with biochemical recurrence after initial radical prostatectomy (RP), external beam radiation therapy (EBRT), or focal high-intensity focused ultrasound (HIFU) with curative intent. The results were compared to findings on magnetic resonance imaging (MRI), computed tomography (CT), bone scan (BS), and histological analysis when available. Univariate analysis was performed to correlate results with patient characteristics.Results: Thirty-eight (63.3%) scans were positive, 17 (28.3%) negative, and 5 (8.3%) equivocal. Of the positive scans, 16 demonstrated local recurrence, 12 regional/distant lymph nodes, five bone metastasis, and five local and distant recurrences. Among the 22 PET/CTs showing metastasis, conventional imaging was performed in 16 patients (72.7%). Of these, it demonstrated the lesion(s) found on PET/CT in eight patients (50.0%), was negative in seven (43.8%), and equivocal in one (6.3%). The trigger PSA (p=0.04), prostate-specific antigen velocity (PSAV) (p=0.03), and prostate-specific antigen doubling time (PSADT) (p=0.046) were significantly different when comparing positive and negative scans. Patients with positive scans were more likely to have received EBRT initially (odds ratio [OR] 11.0, 95% confidence interval [CI] 2.2‒55.3). A trigger PSA of 2.6 ng/mL had a sensitivity of 84% and specificity of 65% for a positive scan. PET/CT changed the clinical management plan in 17 patients (28.3%).Conclusions: 18F-FCH PET/CT demonstrates a high detection rate for local and distant recurrences after localized PCa treatment. A trigger PSA above 2.6 ng/mL seems optimal for appropriate patient selection.

4 Background: There is a need for effective treatments in the second- or further line setting in advanced gastric cancer, especially for new agents. In the current trial we evaluated paclitaxel with RAD001 (everolimus) in patients with gastric carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen. Methods: This is a randomized, double-blind, multi-center phase III study. Patients with gastric carcinoma or adenocarcinoma of the esophagogastric junction which has progressed after treatment with a fluoropyrimidine/platinum-containing regimen were randomly assigned to receive Paclitaxel (80 mg/m2) on day 1, 8 and 15 plus placebo (arm A) or RAD001 (10mg daily, arm B) d1-d28, repeated every 28 days as 2nd, 3rd or 4thline therapy. Primary end point was overall survival (OS), secondary endpoints were best overall response, disease control rate, progression free survival (PFS) and toxicity. Results: 300 patients (median age: 62 years; median lines prior therapy: 2) were randomly assigned (Arm A, 150, Arm B, 150). Response rate (complete and partial response) was 8.0% (95%CI: 4.2%-13.6%) in the paclitaxel/RAD001 arm and 7.3% (95% CI: 3.7%-12.7%) in the paclitaxel/placebo arm (p = 0.4).There was no significant difference in median PFS (placebo, 2.07 vs. RAD001, 2.2 months, HR 0.88, p = 0.3) and median OS (placebo, 5.1 vs. RAD001, 6.1 months, HR 0.92, p = 0.48). Combination of paclitaxel and RAD001 was tolerable, but the placebo arm was associated with significantly less (any grade) mucositis (15.8% vs. 37.2%), fever (10.3% vs 20.7%), leukopenia (11.6% vs. 21.4%), neutropenia (13.0% vs. 27.6%) and thrombocytopenia (2.1% vs 14.5%). Conclusions: The addition of RAD001 to paclitaxel/RAD001 did not significantly improve outcomes in pretreated metastatic gastric or esophagogastric junction adenocarcinoma. Additional biomarker studies are planned to look for subgroups that may have a benefit. Clinical trial information: NCT01248403.

A 69-year-old woman presented with a spontaneous right subtrochanteric hip fracture. Pan-imaging following orthopedic repair failed to identify a primary malignancy to explain the presumed pathologic basis for this fracture. The patient then underwent bone scintigraphy and SPECT/CT which showed mild uptake in multifocal endosteal thickening of the lateral left femoral diaphysis, diagnostic of bisphosphonate-associated femoral shaft stress fractures, but no evidence of metastatic bone disease. Atypical bisphosphonate-associated subtrochanteric and femoral shaft stress fractures have a fairly specific appearance on bone scintigraphy, and nuclear medicine physicians should be aware of this relatively infrequent emerging pathology.