Efficacy and Toxicity of Different Chemotherapy Protocols for Concurrent Chemoradiation in Non-Small Cell Lung Cancer—A Secondary Analysis of the PET Plan Trial

(1) Background: The optimal chemotherapy (CHT) regimen for concurrent chemoradiation (cCRT) is not well defined. In this secondary analysis of the international randomized PET-Plan trial, we evaluate the efficacy of different CHT. (2) Methods: Patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume definition and received isotoxically dose-escalated cCRT using cisplatin 80 mg/m2 (day 1, 22) and vinorelbin 15 mg/m2 (day 1, 8, 22, 29) (P1) or cisplatin 20 mg/m2 (day 1–5, 29–33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P2) or carboplatin AUC1 (day 1–5, 29–33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P3) or other CHT at the treating physician’s discretion. (3) Results: Between 05/2009 and 11/2016, 205 patients were randomized and 172 included in the per-protocol analysis. Patients treated in P1 or P2 had a better overall survival (OS) compared to P3 (p = 0.015, p = 0.01, respectively). Patients treated with carboplatin had a worse OS compared to cisplatin (HR 1.78, p = 0.03), but the difference did not remain significant after adjusting for age, ECOG, cardiac function creatinine and completeness of CHT. (4) Conclusions: Carboplatin doublets show no significant difference compared to cisplatin, after adjusting for possibly relevant factors, probably due to existing selection bias

The Ocean Sampling Day Consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

Visualisation of Respiratory Tumour Motion and Co-Moving Isodose Lines in the Context of Respiratory Gating, IMRT and Flattening-Filter-Free Beams

<div><p>Respiratory motion during percutaneous radiotherapy can be considered based on respiration-correlated computed tomography (4DCT). However, most treatment planning systems perform the dose calculation based on a single primary CT data set, even though cine mode displays may allow for a visualisation of the complete breathing cycle. This might create the mistaken impression that the dose distribution were independent of tumour motion. We present a movie visualisation technique with the aim to direct attention to the fact that the dose distribution migrates to some degree with the tumour and discuss consequences for gated treatment, IMRT plans and flattening-filter-free beams. This is a feasibility test for a visualisation of tumour and isodose motion. Ten respiratory phases are distinguished on the CT, and the dose distribution from a stationary IMRT plan is calculated on each phase, to be integrated into a movie of tumour and dose motion during breathing. For one example patient out of the sample of five lesions, the plan is compared with a gated treatment plan with respect to tumour coverage and lung sparing. The interplay-effect for small segments in the IMRT plan is estimated. While the high dose rate, together with the cone-shaped beam profile, makes the use of flattening-filter-free beams more problematic for conformal and IMRT treatment, it can be the option of choice if gated treatment is preferred. The different effects of respiratory motion, dose build-up and beam properties (segments and flatness) for gated vs. un-gated treatment can best be considered if planning is performed on the full 4DCT data set, which may be an incentive for future developments of treatment planning systems.</p></div

The Impact of Diffusion-Weighted MRI on the Definition of Gross Tumor Volume in Radiotherapy of Non-Small-Cell Lung Cancer.

OBJECTIVE:The study was designed to evaluate diffusion-weighted magnetic resonance imaging (DWI) vs. PET-CT of the thorax in the determination of gross tumor volume (GTV) in radiotherapy planning of non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS:Eligible patients with NSCLC who were supposed to receive definitive radio(chemo)therapy were prospectively recruited. For MRI, a respiratory gated T2-weighted sequence in axial orientation and non-gated DWI (b = 0, 800, 1,400 and apparent diffusion coefficient map [ADC]) were acquired on a 1.5 Tesla scanner. Primary tumors were delineated on FDG-PET/CT (stGTV) and DWI images (dwGTV). The definition of stGTV was based on the CT and visually adapted to the FDG-PET component if indicated (e.g., in atelectasis). For DWI, dwGTV was visually determined and adjusted for anatomical plausibility on T2w sequences. Beside a statistical comparison of stGTV and dwGTB, spatial agreement was determined with the "Hausdorff-Distance" (HD) and the "Dice Similarity Coefficient" (DSC). RESULTS:Fifteen patients (one patient with two synchronous NSCLC) were evaluated. For 16 primary tumors with UICC stages I (n = 4), II (n = 3), IIIA (n = 2) and IIIB (n = 7) mean values for dwGTV were significantly larger than those of stGTV (76.6 ± 84.5 ml vs. 66.6 ± 75.2 ml, p<0.01). The correlation of stGTV and dwGTV was highly significant (r = 0.995, p<0.001). Yet, some considerable volume deviations between these two methods were observed (median 27.5%, range 0.4-52.1%). An acceptable agreement between dwGTV and stGTV regarding the spatial extent of primary tumors was found (average HD: 2.25 ± 0.7 mm; DC 0.68 ± 0.09). CONCLUSION:The overall level of agreement between PET-CT and MRI based GTV definition is acceptable. Tumor volumes may differ considerably in single cases. DWI-derived GTVs are significantly, yet modestly, larger than their PET-CT based counterparts. Prospective studies to assess the safety and efficacy of DWI-based radiotherapy planning in NSCLC are warranted

PTV and tumour motion characteristics.

<p>PTV and tumour motion characteristics.</p

Example for a field segment with low monitor units (18 MU) located at the edge of the PTV.

<p>The segment is so small that the tumour may move completely outside in the respiratory phase (at the most cranial position). Due to the short irradiation time, this segment might hence miss the tumour. If this effect becomes significant for a number of fields, the dose distribution shown in Movie 2 is no longer valid, since it is based on the assumption that all respiratory phases will experience the same beam/segment configuration. More realistically, the low-MU segments will only be experienced by some respiratory phases. If the “wrong” phases are associated with the segments, the dose associated with these segments will not contribute to the PTV dose, but still increase the dose to organs at risk.</p

Baseline Demographic and Patient Characteristics.

<p><i>Abbreviations:</i> 1) NSCLC = non-small cell lung cancer; 2) thereof one patient with two lung lesions.</p

Magnetic resonance lymphography at 9.4 T using a gadolinium-based nanoparticle in rats: investigations in healthy animals and in a hindlimb lymphedema model

OBJECTIVES: Magnetic resonance lymphography (MRL) in small animals is a promising but challenging tool in preclinical lymphatic research. In this study, we compared the gadolinium (Gd)-based nanoparticle AGuIX with Gd-DOTA for interstitial MRL in healthy rats and in a chronic rat hindlimb lymphedema model. MATERIALS AND METHODS: A comparative study with AGuIX and Gd-DOTA for interstitial MRL was performed in healthy Lewis rats (n = 6). For this purpose, 75 μL of 3 mM AGuIX (containing 30 mM Gd-DOTA side residues) and 75 μL 30 mM Gd-DOTA were injected simultaneously in the right and left hindlimbs. Repetitive high-resolution, 3-dimensional time-of-flight gradient recalled echo MRL sequences were acquired over a period of 90 minutes using a 9.4 T animal scanner. Gadofosveset-enhanced MR angiography and surgical dissection after methylene blue injection served as supportive imaging techniques. In a subsequent proof-of-principle study, AGuIX-based MRL was investigated in a hindlimb model of chronic lymphedema (n = 4). Lymphedema of the right hindlimbs was induced by means of popliteal and inguinal lymphadenectomy and irradiation with 20 Gy. The nonoperated left hindlimbs served as intraindividual controls. Six, 10, and 14 weeks after lymphadenectomy, MRL investigations were performed to objectify lymphatic reorganization. Finally, skin samples of the lymphedematous and the contralateral control hindlimbs were analyzed by means of histology and immunohistochemistry. RESULTS: AGuIX-based MRL resulted in high-resolution anatomical depiction of the rodent hindlimb lymphatic system. Signal-to-noise ratio and contrast-to-noise ratio of the popliteal lymph node were increased directly after injection and remained significantly elevated for up to 90 minutes after application. AGuIX provided significantly higher and prolonged signal intensity enhancement as compared with Gd-DOTA. Furthermore, AGuIX-based MRL demonstrated lymphatic regeneration in the histopathologically verified chronic lymphedema model. Collateral lymphatic vessels were detectable 6 weeks after lymphadenectomy. CONCLUSIONS: This study demonstrates that AGuIX is a suitable contrast agent for preclinical interstitial MRL in rodents. AGuIX yields anatomical imaging of lymphatic vessels with diameters greater than 200 μm. Moreover, it resides in the lymphatic system for a prolonged time. AGuIX may therefore facilitate high-resolution MRL-based analyses of the lymphatic system in rodents