Haematotoxicity during peptide receptor radionuclide therapy: Baseline parameters differences and effect on patient's therapy course.

BACKGROUND: Mainly severe (CTCAE grade 3-4) haematotoxicity during peptide receptor radionuclide therapy (PRRT) is reported in literature due to major clinical impact, however moderate (CTCAE grade 2) haematotoxicity is common and could affect therapy management. The aim of this study was to evaluate the haematotoxicity course during PRRT and to compare baseline parameters between haematotoxicity grades. METHODS: In this retrospective study, 100 patients with a neuroendocrine tumour treated with PRRT were included. Patients were treated with an aimed number of four cycles with 7.4 GBq [177Lu]Lu-DOTA-TATE administered every 10 weeks. Haematological assessment was performed at baseline and frequently up to 10 weeks after the fourth cycle. The lowest haematological value was graded according to CTCAE v5.0, and patients were classified using the highest observed grade. Differences in baseline parameters, including [68Ga]Ga-DOTA-TATE positive tumour volume, were evaluated between CTCAE grades. RESULTS: Four cycles were completed by 86/100 of patients, 4/100 patients discontinued due to haematotoxicity, and 10/100 patients due to progressive disease. The treatment course was adjusted due to haematotoxicity in 24/100 patients, including postponed next cycle (n = 17), reduced administered activity (n = 13), and both adjustments (n = 10). The most observed haematotoxicity grade was grade 0-1 in 54/100 patients, grade 2 in 38/100 and grade 3-4 in 8/100. Significant differences in baseline leucocyte, neutrophil and platelet counts were observed between grade 0-1 and grade 2. However, the correlation between baseline and lowest observed values was poor to moderate. No differences between haematotoxicity grades and baseline parameters or somatostatin receptor positive tumour volume was observed. CONCLUSIONS: The incidence of severe haematotoxicity was low with extensive screening and monitoring. The vast majority of patients (96/100) was not restricted in treatment continuation by haematotoxicity; therefore, our selection criteria appeared appropriate for safe PRRT treatment. Baseline parameters showed limited correlation with the degree of decline in haematological values.

A head-to-head comparison between two commercial software packages for hybrid dosimetry after peptide receptor radionuclide therapy.

BACKGROUND: Dosimetry after peptide receptor radionuclide therapy (PRRT) is increasing; however, comparing or pooling of dosimetric results can be challenging since different approaches are used. The aim of this study was to perform a head-to-head comparison of post-PRRT curve fitting and dosimetry obtained from two commercial software Hybrid Viewer Dosimetry and PLANET Dose. METHODS: Post-therapy imaging included planar scintigraphy at 0.5, 4, 24 and 72 h post-injection of [177Lu]Lu-DOTA-TATE for kinetics and SPECT/CT at 24 h for quantification. On planar imaging, 2 cm regions-of-interest were positioned within the inferior pole of the kidneys and kidney cortex was segmented on low-dose CT. On both planar and SPECT/CT, 2 cm spheres were positioned in the proximal humerus (red marrow equivalent) and in the region with the highest uptake in tumour lesions. TACs were estimated with mono- and bi-exponential fits in both software systems, after which tissue absorbed (kidney, red marrow, tumour) and biological effective doses (kidney) were calculated. Agreement-ICC, Spearman correlation and Bland-Altman plots were used to compare results. RESULTS: Mono-exponential fits showed the most comparable correlation between the measured and fitted data between both software. The ICC between absorbed dose outcomes was > 0.7 in tumour lesions and kidneys, but negative for the red marrow. Spearman correlation was > 0.9 for mono-exponential fits in kidneys and tumour lesions, and -0.7 in red marrow. Bi-exponential fits resulted in lower correlations and agreement values. Concordance between both software packages concerning the number of PRRT cycles with 7.4 GBq was observed based on a biological effective dose limit of 27 Gy to the kidneys. CONCLUSION: [177Lu]Lu-DOTA-TATE dosimetry results of two software packages were comparable in the same dataset, despite the limited number of imaging time-points. However, these results should be verified in a larger cohort before pooling of clinical data, as the obtained results will depend on acquisition protocol, timing and lesions definition.

Tumor heterogeneity on (18)F-FDG-PET/CT for response monitoring in non-small cell lung cancer treated with erlotinib.

Response monitoring using fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography (FDG-PET/CT) textural features has potential in targeted treatment with erlotinib in non-small cell lung cancer (NSCLC) patients. Patients with substantial decrease of metabolic activity during erlotinib treatment will probably benefit from continued treatment. However, various aspects of the method (quantification tools, cut-off values, etc.) need to be standardized before the software becomes widely available in a similar manner as standardized uptake value (SUV) measurements. Heterogeneity on FDG-PET/CT opened an additional window for innovation but simultaneously a new challenge for molecular hybrid imaging.

Pleural pressure swing and lung expansion after malignant pleural effusion drainage: the benefits of high-temporal resolution pleural manometry.

BACKGROUND: Malignant pleural effusion is a common complication in end-stage cancer patients and can cause severe dyspnea. Therapeutic thoracentesis is often limited to 1 to 1.5 L. Pleural manometry can be used to recognize a not-expanded lung. METHODS: Interval pleural pressure measurements with a high temporal resolution were performed after each removal of 200 mL of fluid to observe pleural pressure swings. Pleural elastance was defined as the difference in pleural pressure divided by the change in volume. Chest x-rays were performed to evaluate lung expansion, reexpansion pulmonary edema, and fluid residue. RESULTS: Thirty-four procedures in 30 patients were eligible for analysis. Four patients had incomplete lung expansion after drainage. No reexpansion pulmonary edema was observed. Pleural pressure swing after 200 mL drainage was higher when the lung did not expand. Pleural elastance after removal of 500 mL was higher in the not-expanded subgroup. CONCLUSIONS: We demonstrated that a high pleural pressure swing after removal of only 200 mL was related to incomplete lung expansion. We confirmed the association between pleural elastance and lung expansion.

Potential value of color-coded dynamic breast-specific gamma-imaging; comparing (99m)Tc-(V)-DMSA, (99m)Tc-MIBI, and (99m)Tc-HDP in a mouse mammary tumor model.

Using a mouse mammary tumor model based on orthotopic transplantation of luciferase-expressing mouse ILC cells (KEP1-Luc cells), we evaluated the diagnostic value of three clinically applied tracers: (99m)Tc-(V)-DMSA, (99m)Tc-MIBI, and (99m)Tc-HDP. Uptake of the tracers is compared using static and dynamic imaging procedures. We found that dynamic imaging in combination with pixel-by-pixel color coding has an added value over (high resolution) static imaging procedures. Such dynamic imaging procedures could enhance the potential of breast-specific gamma-imaging.

Influence of breathing resistance of heat and moisture exchangers on tracheal climate and breathing pattern in laryngectomized individuals.

BACKGROUND: The aim of this study was to determine the influence of breathing resistance of heat and moisture exchangers (HMEs) on endotracheal climate and breathing pattern. METHODS: Endotracheal temperature and humidity and tidal volumes were measured in 11 laryngectomized patients with a regularly used HME with "standard" breathing resistance (Provox Normal HME; R-HME), a low breathing-resistance HME (Provox HiFlow HME; L-HME), and without HME. RESULTS: Both R-HME and L-HME increased end-inspiratory humidity (+5.8 and 4.7 mgH(2)O/L, respectively), decreased end-inspiratory temperature (-1.6 and -1.0 degrees C, respectively), and prolonged the exhalation breath length to approximately 0.5 seconds. The R-HME significantly enlarged tidal volumes (0.07 L; p < .05). CONCLUSIONS: Both HMEs significantly improve tracheal climate. The R-HME has better moistening properties and a small but significant positive effect on tidal volume. Therefore, if the higher resistance is tolerated, the R-HME is the preferred pulmonary rehabilitation device. The L-HME is indicated if lower breathing resistance is required.

Application of PET/CT in the development of novel anticancer drugs.

Combined positron emission tomography/computed tomography (PET/CT) is a relatively new imaging modality, combining the functional images of PET with the anatomical information of CT. Since its commercial introduction about 5 years ago, PET/CT has become an important tool in oncology. Currently, the technique is used for primary staging and restaging of cancer patients, as well as for surgery and radiation therapy planning. The abilities of PET/CT to measure early treatment response as well as drug distribution within the body make this technique very useful in the development of novel anticancer drugs. In this paper, the recent literature on the current role of PET/CT in drug development is reviewed.

Mitochondrial PO2 measured by delayed fluorescence of endogenous protoporphyrin IX.

Molecular oxygen is the primary oxidant in biological systems. The ultimate destination of oxygen in vivo is the mitochondria where it is used in oxidative phosphorylation. The ability of this process to produce an amount of high-energy phosphates adequate to sustain life highly depends on the available amount of oxygen. Despite a vast array of techniques to measure oxygen, major (patho)physiological questions remain unanswered because of the unavailability of quantitative techniques to measure mitochondrial oxygen in situ. Here we demonstrate that mitochondrial PO(2) can be directly measured in living cells by harnessing the delayed fluorescence of endogenous protoporphyrin IX (PpIX), thereby providing a technique with the potential for a wide variety of applications. We applied this technique to different cell lines (V-79 Chinese hamster lung fibroblasts, HeLa cells and IMR 32-K1 neuroblastoma cells) and present the first direct measurements of the oxygen gradient between the mitochondria and the extracellular volume.