Tumor organoids offer new opportunities for translational cancer research, but unlike animal models, their broader use is hindered by the lack of clinically relevant imaging endpoints. Here, we ...present a positron-emission microscopy method for imaging clinical radiotracers in patient-derived tumor organoids with spatial resolution 100-fold better than clinical positron emission tomography (PET). Using this method, we quantify
F-fluorodeoxyglucose influx to show that patient-derived tumor organoids recapitulate the glycolytic activity of the tumor of origin, and thus, could be used to predict therapeutic response in vitro. Similarly, we measure sodium-iodine symporter activity using
Tc- pertechnetate and find that the iodine uptake pathway is functionally conserved in organoids derived from thyroid carcinomas. In conclusion, organoids can be imaged using clinical radiotracers, which opens new possibilities for identifying promising drug candidates and radiotracers, personalizing treatment regimens, and incorporating clinical imaging biomarkers in organoid-based co-clinical trials.
Atypical chronic myeloid leukemia,
negative (aCML) is a rare myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) with a high rate of transformation to acute myeloid leukemia, and poor ...survival. Until now, the diagnosis has been based on morphological grounds only, possibly making the real frequency of the disease underestimated. Only recently, new insights in the molecular biology of MDS/MPN syndromes have deepened our knowledge of aCML, enabling us to have a better molecular profile of the disease. The knowledge gleaned from next generation sequencing has complemented morphologic and laboratory WHO criteria for myeloid neoplasms and can provide greater specificity in distinguishing aCML from alternative MDS/MPN or MPNs. The most commonly mutated genes (>20%) in aCML are
,
,
,
, and
, and less frequently (< 10%)
,
,
,
, and
Several of these mutations affect the JAK-STAT, MAPK, and ROCK signaling pathways, which are targetable by inhibitors that are already in clinical use and may lead to a personalized treatment of aCML patients unfit for allogeneic transplant, which is currently the only curative option for fit patients. In this review, we present two emblematic clinical cases and address the new molecular findings in aCML and the available treatment options.
Background
This meta-analysis aims to investigate the role of complete mesocolic excision (CME) in the treatment of right-side colon cancer when compared with standard right-side hemicolectomy, ...focusing on oncological outcomes, mortality and morbidity rates.
Materials and methods
A systematic literature search was performed on MEDLINE and EMBASE archives, including studies on CME in right-side colon cancer. Primary outcomes were five-year disease-free survival and five-year overall survival. Secondary outcomes investigated were mortality and morbidity rates, intraoperative blood loss, anastomotic leakage, postoperative ileus, day of postoperative flatus, pulmonary infection, duration of hospital stay and number of lymph nodes harvested.
Results
Seventeen studies have been included in this meta-analysis for a total of 3918 patients. The five-year disease-free survival (DFS) and overall survival (OS) results improved in the CME group with respect to conventional right-side colectomy with an OR 1.88 (95% CI 1.02–3.45) and OR 2.77 (95% CI 1.33–5.74), respectively. The incidence of mortality and morbidity was comparable between the two groups. Moreover, conventional surgery time was faster than CME (MD 33.69 min, 95% CI 12.79–54.59), while no significant differences were reported in mean blood loss and hospital stay. Furthermore, the CME group showed a higher mean number of harvested lymph nodes (MD 7.08 lymph nodes 95% CI 4.90–9.27).
Conclusion
Complete mesocolic excision of the right-side colectomy improves oncological outcomes without increasing mortality and morbidity rates compared to standard right-side hemicolectomy. CME should therefore be routinely performed in the treatment of right-side colon cancer.
Purpose
Transarterial radioembolization (TARE) with yttrium-90 (
90
Y) microspheres is a liver-directed treatment for primary and secondary hepatic malignancies. Personalized dosimetry aims for ...maximum treatment effect and reduced toxicity. We aimed to compare pre-treatment voxel-based dosimetry from
99m
Tc macroaggregated albumin (MAA) SPECT/CT with post-treatment
90
Y PET/CT for absorbed dose values, and to evaluate image quality of
90
Y SiPM-based PET/CT.
Methods
Forty-two patients (28 men, 14 women, mean age: 67 ± 11 years) with advanced hepatic malignancies were prospectively enrolled. Twenty patients were treated with glass and 22 with resin microspheres. Radiation absorbed doses from planning
99m
Tc-MAA SPECT/CT and post-therapy
90
Y PET/CT were assessed.
90
Y PET/CT images were acquired for 20 min and reconstructed to produce 5-, 10-, 15-, and 20-min datasets, then evaluated using the 5-point Likert scale.
Results
The mean administered activity was 3.44 ± 1.5 GBq for glass and 1.62 ± 0.7 GBq for resin microspheres. The mean tumor absorbed doses calculated from
99m
Tc-MAA SPECT/CT and
90
Y PET/CT were 175.69 ± 113.76 Gy and 193.58 ± 111.09 Gy (
P
= 0.61), respectively for glass microspheres; they were 60.18 ± 42.20 Gy and 70.98 ± 49.65 Gy (
P
= 0.37), respectively for resin microspheres. The mean normal liver absorbed doses from
99m
Tc-MAA SPECT/CT and
90
Y PET/CT were 32.70 ± 22.25 Gy and 30.62 ± 20.09 Gy (
P
= 0.77), respectively for glass microspheres; they were 18.33 ± 11.08 Gy and 24.32 ± 15.58 Gy (
P
= 0.17), respectively for resin microspheres. Image quality of
90
Y PET/CT at 5-, 10-, 15-, and 20-min scan time showed a Likert score of 3.6 ± 0.54, 4.57 ± 0.58, 4.84 ± 0.37, and 4.9 ± 0.3, respectively.
Conclusions
99m
Tc-MAA SPECT/CT demonstrated great accuracy for treatment planning dosimetry. SiPM-based PET/CT scanner showed good image quality at 10-min scan time, acquired in one bed position. A PET/CT scan time of 5 min showed acceptable image quality and suffices for dosimetry and treatment verification. This allows for inclusion of
90
Y PET/CT in busy routine clinical workflows. Studies with larger patient cohorts are needed to confirm these findings.
The high-background glucose metabolism of normal gray matter on 18F-fluoro-2-D-deoxyglucose (FDG) positron emission tomography (PET) of the brain results in a low signal-to-background ratio, ...potentially increasing the possibility of missing important findings in patients with intracranial malignancies. To explore the strategy of using a deep learning classifier to aid in distinguishing normal versus abnormal findings on PET brain images, this study evaluated the performance of a two-dimensional convolutional neural network (2D-CNN) to classify FDG PET brain scans as normal (N) or abnormal (A). Methods: Two hundred eighty-nine brain FDG-PET scans (N;
n
= 150, A;
n
= 139) resulting in a total of 68,260 images were included. Nine individual 2D-CNN models with three different window settings for axial, coronal, and sagittal axes were trained and validated. The performance of these individual and ensemble models was evaluated and compared using a test dataset. Odds ratio, Akaike’s information criterion (AIC), and area under curve (AUC) on receiver-operative-characteristic curve, accuracy, and standard deviation (SD) were calculated. Results: An optimal window setting to classify normal and abnormal scans was different for each axis of the individual models. An ensembled model using different axes with an optimized window setting (window-triad) showed better performance than ensembled models using the same axis and different windows settings (axis-triad). Increase in odds ratio and decrease in SD were observed in both axis-triad and window-triad models compared with individual models, whereas improvements of AUC and AIC were seen in window-triad models. An overall model averaging the probabilities of all individual models showed the best accuracy of 82.0%. Conclusions: Data ensemble using different window settings and axes was effective to improve 2D-CNN performance parameters for the classification of brain FDG-PET scans. If prospectively validated with a larger cohort of patients, similar models could provide decision support in a clinical setting.
Summary Background & aims Parkinson's disease (PD) patients can benefit considerably from appropriate nutritional care, particularly from diet. However, there is limited evidence on the eating habits ...of PD patients and their relationship with the features of the disease. Methods We conducted a large case–control study. Consecutive PD patients ( N = 600) receiving systematic nutritional care and healthy controls ( N = 600) matched (1:1) for age, gender, education, physical activity level and residence were studied using a 66-item food frequency questionnaire. The relationship between dietary habits and the following features of PD were investigated in patients: body weight, energy balance, constipation, and levodopa therapy (dose) and its related motor complications. Results PD patients had lower BMI and reported higher food intake than controls. BMI was found to be inversely associated with disease duration and severity, and levodopa-related motor complications, whereas energy intake was positively associated with these variables. An increase in protein intake by 10 g over physiological requirements (0.8 g/kg/day) corresponded to a mean increase in levodopa dose of 0.7 mg/kg/day. Constipation was also associated with higher levodopa requirements. Finally, protein intake and its distribution throughout the day influenced levodopa-related motor complications. Conclusion The management of protein intake and the treatment of constipation should be considered to be an integral part of the care of PD patients. Attention should always be focused on energy intake also. This would result in the maintenance of nutritional status, the optimization of levodopa-therapy and the minimization of its related motor complications.
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in western countries, with an incidence of approximately 5.1/100,000 new cases per year. Some patients may never require ...treatment, whereas others relapse early after front line therapeutic approaches. Recent whole genome and whole exome sequencing studies have allowed a better understanding of CLL pathogenesis and the identification of genetic lesions with potential clinical relevance. Consistently, precision medicine plays a pivotal role in the treatment algorithm of CLL, since the integration of molecular biomarkers with the clinical features of the disease may guide treatment choices. Most CLL patients present at the time of diagnosis with an early stage disease and are managed with a watch and wait strategy. For CLL patients requiring therapy, the CLL treatment armamentarium includes both chemoimmunotherapy strategies and biological drugs. The efficacy of these treatment strategies relies upon specific molecular features of the disease.
disruption (including both
mutation and 17p deletion) is the strongest predictor of chemo-refractoriness, and the assessment of
status is the first and most important decisional node in the first line treatment algorithm. The presence of
disruption mandates treatment with biological drugs that inhibit the B cell receptor or, alternatively, the B-cell lymphoma 2 (BCL2) pathway and can, at least in part, circumvent the chemorefractoriness of
-disrupted patients. Beside
disruption, the mutational status of immunoglobulin heavy variable (IGHV) genes also helps clinicians to improve treatment tailoring. In fact, patients carrying mutated IGHV genes in the absence of
disruption experience a long-lasting and durable response to chemoimmunotherapy after fludarabine, cyclophosphamide, and rituximab (FCR) treatment with a survival superimposable to that of a matched general population. In contrast, patients with unmutated IGHV genes respond poorly to chemoimmunotherapy and deserve treatment with B cell receptor inhibitors. Minimal residual disease is also emerging as a relevant biomarker with potential clinical implications. Overall, precision medicine is now a mainstay in the management and treatment stratification of CLL. The identification of novel predictive biomarkers will allow further improvements in the treatment tailoring of this leukemia.
Purpose
While definitive long-term results are not yet available, the global safety and oncologic adequacy of laparoscopic surgery for right colectomy remain controversial. The aim of the study was ...to evaluate differences in safety of laparoscopic right colectomy, compared with open surgery, with particular attention to cancer patients.
Methods
A systematic review from 1991 to 2014 was performed searching the MEDLINE and EMBASE databases (PROSPERO Registration number: CRD42014015256). We included randomised and controlled clinical studies comparing laparoscopic and open resection for rectal cancer. Primary endpoints were 30 days mortality and overall morbidity. Then, a meta-analysis was conducted by a fixed-effect model, performing a sensitivity analysis by a random-effect model. Relative risk (RR) was used as an indicator of treatment effect; a RR less than 1.0 was in favour of laparoscopy. Publication bias was assessed by funnel plot, heterogeneity by the
I
2
test and subgroup analysis on oncologic patients.
Results
Twenty-seven studies, representing 3049 patients, met the inclusion criteria; only 2 were randomised for a total of 211 patients. Mortality was observed in 1.2 % of patients in the laparoscopic group and in 3.4 % of patients in the open group. The overall RR was 0.45 (95 % CI 0.21–0.93,
p
= 0.031). The raw incidence of overall complications was significantly lower in the laparoscopic group (16.8 %) compared to the open group (24.2 %). The overall RR was 0.81 (95 % CI 0.70–0.95,
p
= 0.007).
Conclusions
Based on the evidence of few randomised and mostly controlled series, mortality and morbidity were significantly lower after laparoscopy compared to open surgery.
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