Background Current literature lacks a comparison of lymph node metastases and non-pathological lymph nodes distribution in breast cancer patients. The aim of the current retrospective study was to generate a comprehensive atlas of the lymph node system. Methods 143 breast cancer patients underwent F-18-FDG-PET/CT (PET/CT) imaging for staging purposes and were diagnosed with regional lymph node metastases. Based on the PET/CT data set a total of 326 lymph node metastases and 1826 non-pathological lymph nodes were detected and contoured manually in the patient collective. Using rigid and deformable registration algorithms all structures were transferred to a template planning CT of a standard patient. Subsequently, a 3D-atlas of the distribution of lymph node metastases and non-pathological lymph nodes were generated and compared to each other. Results Both, lymph node metastases and non-pathological lymph nodes, accumulated in certain areas (“hot-spots”) within the lymphatic drainage system. However large differences regarding the distribution patterns were detected: lymph node metastases hot spots occurred in close proximity to the subclavian vein in level I-III, whereas the non-pathological lymph nodes accumulated mostly (within a wider range) in level I. In level II and III lymph node metastases exceeded clearly the areas in which non-pathological lymph nodes occurred. Conclusion Lymph node metastases and non-pathological lymph node distribution within the lymph node system differ clearly. Based on our results, an individual adjustment of the CTV in order to include visible lymph nodes in level II and III should be discussed.

Objective: The purpose of this study was to estimate the dose distribution from randomized trials (MA.20, EORTC 22922-10925 (EORTC), AMAROS and the Z0011 trial) on lymph node (LN) irradiation on a large LN atlas. Methods: 580 F-18-FDG-PET/CT positive LN metastases of 235 patients were transferred rigidly and non-rigidly to three "template CTs" (standard, obese and slender patient). Further, the LN clinical target volumes (CTVs) were contoured according to the ESTRO-guidelines. Treatment plans were designed (each for the left and right side) for all patients based on the study protocols of the MA.20, EORTC, AMAROS and Z0011 trial. Subsequently, the dose distribution in the ESTRO-CTVs and in the 580 LNs were assessed. Results: Our results reveal variable dose coverage (26.8 +/- 17.3 Gy-53.0 +/- 1.8 Gy) in the targeted LN areas (ESTRO-CTV and LN) in dependence of the treatment planning design and the patients' body shape. None of the treatment plan designs provided full dose coverage to the lymphatic drainage system. High tangent irradiation resulted in a similar dose distribution in L I and II compared to the AMAROS field design. Conclusion: Inclusion of the entire lymphatic system may not be necessary for all patients to reproduce the oncologic benefit shown in the randomized LN-irradiation trials. Inclusion of axillary level II and extension of the supraclavicular CTV can be considered in selected high-risk patients, based on dose recalculation of the MA.20 trial. Further, our results amplify earlier assumptions that irradiation may have accounted for the good results after SLND alone in the Z0011 trial. (C) 2019 Elsevier B.V. All rights reserved.

Objective Tangential field irradiation in breast cancer potentially treats residual tumor cells in the axilla after sentinel lymph node biopsy (SLNB). In recent years, hypofractionated radiotherapy has gained importance and currently represents the recommended standard in adjuvant breast cancer treatment for many patients. So far, the impact of hypofractionation on the effect of incidental lymph node irradiation has not be addressed. Materials and methods Biological effective dose (BED) and tumor control probability (TCP) were estimated for four different hypofractionated radiation schemes (42.50 Gy in 16 fractions [Fx]; 40.05 Gy in 15 Fx; 27 Gy in 5 Fx; and 26 in 5 Fx) and compared to conventional fractionation (50 Gy in 25 Fx). For calculation of BED and TCP, a previously published radiobiological model with an α/β ratio of 4 Gy was used. The theoretical BED and TCP for incidental irradiation between 0 and 100% of the prescribed dose were evaluated. Subsequently, we assessed BED and TCP in 431 axillary lymph node metastases. Results The extent of incidental lymph node irradiation and the fractionation scheme have a direct impact on BED and TCP. The estimated mean TCP in the axillary nodes ranged from 1.5 ± 6.4% to 57.5 ± 22.9%, depending on the patient’s anatomy and the fractionation scheme. Hypofractionation led to a significant reduction of mean TCP of lymph node metastases for all schedules. Conclusion Our data indicate that hypofractionation might affect the effectiveness of incidental radiotherapy in the axilla. This is particularly relevant for patients with positive sentinel lymph nodes who receive SLNB only.

The objective of this retrospective study was to assess the detection rate (DR), positive predictive value (PPV), and correct detection rate (CDR) of 18F-rhPSMA-7 PET/CT in biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy (RP) using composite validation. Methods:18F-rhPSMA-7 PET/CT scans of patients with BCR between July 2017 and June 2018 were retrospectively reviewed. All suspicious lesions were recorded. The reference standard was histopathology or combinations of histopathology, imaging, or prostate-specific antigen (PSA) follow up, defined as composite reference standard. DR was calculated as the proportion of PSMA PET-positive patients to all patients independent of the reference standard, whereas the CDR was the percentage of patients who had at least 1 true-positive PSMA PET lesion localized that corresponded with the reference standard. The PPV was defined as the proportion of patients who had true-positive to all positive findings. The correlation between DR and patient characteristics was evaluated. Results: A total of 532 patients with a median PSA level of 0.97 ng/mL (interquartile range: 0.41-2.46 ng/mL) were included. Of these, 162 patients had composite follow-up at a median duration of 5.6 mo (range: 1.1-14.2 mo). The proportion of patients who had no lesion visualized on PET/CT, localized disease, and any distant metastases (M1) were 20%, 43%, and 37%, respectively. PET DR among all patients was 80%. On a per-patient basis, the PPV of 18F-rhPSMA-7 PET/CT in the composite cohort was 88%, and the CDR was 70%. The PPV in the histopathology-proven cohort was 91%, and the CDR in this subgroup was 73%. In patients with PSA levels ≥ 1 ng/mL the DR and PPV were 90% and 91%, respectively, resulting in a CDR of 82%. In patients with PSA levels < 1 ng/mL, the DR and PPV were 69% and 85%, respectively, resulting in a CDR of 59%. There was a significant positive correlation between 18F-rhPSMA-7 PET/CT detection efficacy and stratified PSA levels (P = 0.005), as well as PSA nadir after prostatectomy (P < 0.001). Conclusion:18F-rhPSMA-7 PET/CT offers high PPV in BCR after RP. Its CDR is dependent on the prescan PSA value with excellent CDR in patients with PSA ≥ 1 ng/mL.

Abstract Acute myeloid leukemia (AML) is a malignant disease of the bone marrow, comprising various subtypes. We have investigated seven different AML cell lines that showed different sensitivities toward the inducer of apoptosis ABT-737, with IC50 concentrations ranging from 9.9 nM to 1.8 µM. Besides, the AML cell lines revealed distinct differences in 18F-FDG uptake ranging from 4.1 to 11.0%. Moreover, the Pearson coefficient (0.363) suggests a moderate correlation between 18F-FDG uptake and the IC50 values of ABT-737. Differentiation of the AML cell lines NB-4 and AML-193 with all-trans-retinoic-acid (ATRA) induced a significant increase in sensitivity towards ABT-737 along with a reduced uptake of 18F-FDG. Therefore, 18F-FDG uptake could be predictive on sensitivity to treatment with ABT-737. Furthermore, because differentiation treatment of AML cells using ATRA reduced 18F-FDG uptake and increased sensitivity towards ABT-737, a combined treatment regimen with ATRA and ABT-737 might be a promising therapeutic option in the future.

18F-labeled prostate-specific membrane antigen (PSMA) PET tracers are increasingly used in preference to 68Ga-PSMA-11 for restaging biochemical recurrence (BCR) of prostate cancer. They are associated with longer half-lives, larger-scale production, and lower positron range than their 68Ga-labeled counterparts. Here, we describe the efficacy of an 18F-labeled radiohybrid PSMA, rhPSMA-7, a novel theranostic PSMA-targeting agent for imaging BCR of prostate cancer. Methods: Datasets from 261 consecutive patients with noncastrate BCR after radical prostatectomy who underwent 18F-rhPSMA-7 PET/CT at our institution between June 2017 and March 2018 were reviewed retrospectively. All lesions suspected of being recurrent prostate cancer were recorded. The detection rate for sites of presumed recurrence was correlated with patients' prostate-specific antigen (PSA) level, primary Gleason score, and prior therapy (androgen deprivation therapy and external-beam radiation therapy). Results: The 261 patients had a median PSA level of 0.96 ng/mL (range, 0.01-400 ng/mL). The median injected activity of 18F-rhPSMA-7 was 336 MBq, with a median uptake time of 76 min. In total, 211 patients (81%) showed pathologic findings on 18F-rhPSMA-7 PET/CT. The detection rates were 71% (42/59), 86% (44/51), 86% (42/49), and 95% (76/80) at PSA levels of 0.2 to <0.5 ng/mL, 0.5 to <1 ng/mL, 1 to <2 ng/mL, and ≥2 ng/mL, respectively. In 32% patients (7/22) with a PSA of less than 0.2 ng/mL, suggestive lesions were present. 18F-rhPSMA-7 PET/CT revealed local recurrence in 43% of patients (113). Lymph node metastases were present in the pelvis in 42% of patients (110), in the retroperitoneum in 17% (45), and in a supradiaphragmatic location in 8.0% (21). Bone and visceral metastases were detected in 21% (54) and 3.8% (10), respectively. Detection efficacy was not influenced by prior external-beam radiation therapy (79.1% vs. 82.1%, P = 0.55), androgen deprivation therapy within the 6 mo preceding imaging (80.6% vs. 80.9%, P = 0.54), or primary Gleason score (77.9% for ≤7 vs. 82.6% for ≥8, P = 0.38). Conclusion:18F-rhPSMA-7 PET/CT offers high detection rates in early BCR after radical prostatectomy, especially among patients with low PSA values.