Frailty, psychological well-being, and social isolation in older adults with cognitive impairment during the SARS-CoV-2 pandemic: data from the GeroCovid initiative.

BACKGROUND: The containment measures linked to the COVID-19 pandemic negatively affected the phyco-physical well-being of the population, especially older adults with neurocognitive disorders (NCDs). This study aims to evaluate whether the frailty of NCD patients was associated with different changes in multiple health domains, in particular in relation to loneliness and social isolation, pre- and post-lockdown. MATERIALS AND METHODS: Patients were recruited from 10 Italian Centers for Cognitive Disorders and Dementia. Data were collected in the pre-pandemic period (T0), during the pandemic lockdown (T1), and 6-9 months post-lockdown (T2). The UCLA Loneliness Scale-3, Activities of Daily Living (ADL), Instrumental ADL (IADL), Mini-Mental State Examination, and Neuropsychiatric Inventory (NPI) were administered. Caregivers' burden was also tested. Patients were categorized as non-frail, pre-frail, and frail according to the Fatigue, Resistance, Ambulation, Illness, and Loss of Weight scale. RESULTS: The sample included 165 subjects (61.9% women, mean age 79.5 ± 4.9 years). In the whole sample, the ADL, IADL, and NPI scores significantly declined between T0 and T2. There were no significative variations in functional and cognitive domains between the frail groups. During lockdown we recorded higher Depression Anxiety Stress Scales and Perceived Stress Scale scores in frail people. In multivariable logistic regression, frailty was associated with an increase in social isolation, and a loss of IADL. CONCLUSIONS: We observed a global deterioration in functional and neuro-psychiatric domains irrespective of the degree of frailty. Frailty was associated with the worsening of social isolation during lockdown. Frail patients and their caregivers seemed to experience more anxiety and stress disorders during SARS-CoV-2 pandemic.

The dosimetric impact of axillary nodes contouring variability in breast cancer radiotherapy: An AIRO multi-institutional study.

AIM: To quantify the dosimetric impact of contouring variability of axillary lymph nodes (L2, L3, L4) in breast cancer (BC) locoregional radiotherapy (RT). MATERIALS AND METHODS: 18 RT centres were asked to plan a locoregional treatment on their own planning target volume (single centre, SC-PTV) which was created by applying their institutional margins to the clinical target volume of the axillary nodes of three BC patients (P1, P2, P3) previously delineated (SC-CTV). The gold standard CTVs (GS-CTVs) of P1, P2 and P3 were developed by BC experts' consensus and validated with STAPLE algorithm. For each participating centre, the GS-PTV of each patient was created by applying the same margins as those used for the SC-CTV to SC-PTV expansion and replaced the SC-PTV in the treatment plan. Datasets were imported into MIM v6.1.7 [MIM Software Inc.], where dose-volume histograms (DVHs) were extracted and differences were analysed. RESULTS: 17/18 centres used intensity-modulated RT (IMRT). The CTV to PTV margins ranged from 0 to 10 mm (median 5 mm). No correlation was observed between GS-CTV coverage by 95% isodose and GS-PTV margins width. Doses delivered to 98% (D98) and 95% (D95) of GS-CTVs were significantly lower than those delivered to the SC-CTVs. No significant difference between SC-CTV and GS-CTV was observed in maximum dose (D2), always under 110%. Mean dose ≥99% of the SC-CTVs and GS-CTVs was satisfied in 84% and 50%, respectively. In less than one half of plans, GS-CTV V95% was above 90%. Breaking down the GS-CTV into the three nodal levels (L2, L3 and L4), L4 had the lowest probability to be covered by the 95% isodose. CONCLUSIONS: Overall, GS-CTV resulted worse coverage, especially for L4. IMRT was largely used and CTV-to-PTV margins did not compensate for contouring issues. The results highlighted the need for delineation training and standardization.

Geometric contour variation in clinical target volume of axillary lymph nodes in breast cancer radiotherapy: an AIRO multi-institutional study.

OBJECTIVES: To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV). METHODS: The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them. RESULTS: Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by -29.25% and -27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements. CONCLUSIONS: Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address. ADVANCES IN KNOWLEDGE: The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.

4D CT analysis of organs at risk (OARs) in stereotactic radiotherapy.

Internal organs at risk volumes (IRV) represent the propagation of organs at risk (OARs) in 4DCT. Sixty consecutive patients that underwent 4DCT for thoracic stereotactic radiotherapy were analyzed and IRVs for heart, trachea, esophagus, bronchial tree, great vessels, and spinal cord were calculated. IRVs were then tested for the respect of dose constraints. IRVs were significantly bigger than standard OARs (p-value <0.001 for all the IRVs). IRVs that did not respect the dose constraints were, respectively, 7/60 (11.7%) for Heart IRV, 6/60 (10%) for Esophagus IRV, 11/60 (18.3%) for Trachea IRV, 16/60 (26.6%) for Bronchial Tree and 0/60 (0%) for great vessel and spinal cord IRV. In the subset of central targets, the percentage of plans that can be unacceptable taking into consideration OARs motion reaches 42%. The correlation of IRVs with clinical parameters and toxicity deserves future investigations in prospective trials.

Delta-radiomics increases multicentre reproducibility: a phantom study.

Texture analysis (TA) can provide quantitative features from medical imaging that can be correlated to clinical endpoints. The challenges relevant to robustness of radiomics features have been analyzed by many researchers, as it seems to be influenced by acquisition and reconstruction protocols. Delta-texture analysis (D-TA), conversely, consist in the analysis of TA feature variations at different acquisition times, usually before and after a therapy. Aim of this study was to investigate the influence of different CT scanners and acquisition parameters in the robustness of TA and D-TA. We scanned a commercial phantom (CIRS model 467, Gammex, Middleton, WI, USA), that is used for the calibration of electron density, two times by varying the disposition of plugs, using three different scanners. After the segmentation, we extracted TA features with LifeX and calculated TA features and D-TA features, defined as the variation of each TA parameters extracted from the same position by varying the plugs with the formula (Y-X)/X. The robustness of TA and D-TA features were then tested with intraclass coefficient correlation (ICC) analysis. The reliability of TA parameters across different scans, with different acquisition parameters and ROI positions has shown poor reliability in 12/37 and moderate reliability in the remaining 25/37, with no parameters showing good reliability. The reliability of D-TA, conversely, showed poor reliability in 10/37 parameters, moderate reliability in 10/37 parameters, and good reliability in 17/37 parameters. The comparison between TA and D-TA ICCs showed a significant difference for the whole group of parameters (p:0.004) and for the subclasses of GLCM parameters (p:0.033), whereas for the other subclasses of matrices (GLRLM, NGLDM, GLZLM, Histogram), the difference was not significant. D-TA features seem to be more robust than TA features. These findings reinforce the potentiality for using D-TA features for early assessment of treatment response and for developing tailored therapies. More work is needed in a clinical setting to confirm the results of the present study.

Sequential PET/CT with [18F]-FDG Predicts Pathological Tumor Response to Preoperative Short Course Radiotherapy with Delayed Surgery in Patients with Locally Advanced Rectal Cancer Using Logistic Regression Analysis.

Previous studies indicate that FDG PET/CT may predict pathological response in patients undergoing neoadjuvant chemo-radiotherapy for locally advanced rectal cancer (LARC). Aim of the current study is evaluate if pathological response can be similarly predicted in LARC patients after short course radiation therapy alone. METHODS: Thirty-three patients with cT2-3, N0-2, M0 rectal adenocarcinoma treated with hypo fractionated short course neoadjuvant RT (5x5 Gy) with delayed surgery (SCRTDS) were prospectively studied. All patients underwent 3 PET/CT studies at baseline, 10 days from RT end (early), and 53 days from RT end (delayed). Maximal standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and total lesion glycolysis (TLG) of the primary tumor were measured and recorded at each PET/CT study. We use logistic regression analysis to aggregate different measures of metabolic response to predict the pathological response in the course of SCRTDS. RESULTS: We provide straightforward formulas to classify response and estimate the probability of being a major responder (TRG1-2) or a complete responder (TRG1) for each individual. The formulas are based on the level of TLG at the early PET and on the overall proportional reduction of TLG between baseline and delayed PET studies. CONCLUSIONS: This study demonstrates that in the course of SCRTDS it is possible to estimate the probabilities of pathological tumor responses on the basis of PET/CT with FDG. Our formulas make it possible to assess the risks associated to LARC borne by a patient in the course of SCRTDS. These risk assessments can be balanced against other health risks associated with further treatments and can therefore be used to make informed therapy adjustments during SCRTDS.

Non small-cell lung cancer with metastasis to thigh muscle and mandible: two case reports.

INTRODUCTION: Lung cancer is the leading cause of cancer-related death in Europe and the US. Isolated metastases to skeletal muscle and the mandible are very uncommon. CASE PRESENTATION: This report presents two cases. Case 1 concerns a 45-year-old Caucasian woman affected by muscle metastasis of the right thigh from non-small-cell lung cancer. Case 2 concerns a 61-year-old Caucasian man affected by mandible metastasis from non-small-cell lung cancer. Both metastases were detected by diagnostic imaging studies. Both patients were treated with radiation therapy with palliative and antalgic intent. CONCLUSION: Radiation therapy was effective and well tolerated in both cases. Both our patients are alive, with follow-up of 18 months and five months, respectively.

A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells.

Organisms exposed to ionizing radiation are mainly damaged by free radicals, which are generated by the radiolysis of water contained in the cells. Recently a significant reduction of tissue injury from irradiation damage was demonstrated by using MnSOD-plasmid/liposome treatments in the protection of murine lung. In this study we show that a new active recombinant human MnSOD (rMnSOD), easily administered in vivo, not only exerts the same radioprotective effect on normal cells and organisms as any MnSOD, but it is also radiosensitizing for tumor cells. In addition, we show how healthy animals, exposed to lethal doses of ionizing radiation and daily injections with rMnSOD, were protected from radiodamage and were still alive 30 days after the irradiation, while animals treated with only PBS solution, in the absence of rMnSOD, died after 7-8 days from the radiotreatments. The molecular analysis of all irradiated tissues revealed that the antiapoptotic AVEN gene appeared activated only in the animals treated in the presence of rMnSOD. The data suggest that rMnSOD deserves to be considered as a pharmaceutical tool for making radiotherapy more selective on cancer cells and to prevent and/or cure the accidental damage derived from exposure to ionizing radiation.