Instrumental Evaluation of the Effects of Vertebral Consolidation Surgery on Trunk Muscle Activations and Co-Activations in Patients with Multiple Myeloma: Preliminary Results.

Multiple myeloma (MM) patients complain of pain and stiffness limiting motility. To determine if patients can benefit from vertebroplasty, we assessed muscle activation and co-activation before and after surgery. Five patients with MM and five healthy controls performed sitting-to-standing and lifting tasks. Patients performed the task before and one month after surgery. Surface electromyography (sEMG) was recorded bilaterally over the erector spinae longissimus and rectus abdominis superior muscles to evaluate the trunk muscle activation and co-activation and their mean, maximum, and full width at half maximum were evaluated. Statistical analyses were performed to compare MM patients before and after the surgery, MM and healthy controls and to investigate any correlations between the muscle's parameters and the severity of pain in patients. The results reveal increased activations and co-activations after vertebroplasty as well as in comparison with healthy controls suggesting how MM patients try to control the trunk before and after vertebroplasty surgery. The findings confirm the beneficial effects of vertebral consolidation on the pain experienced by the patient, despite an overall increase in trunk muscle activation and co-activation. Therefore, it is important to provide patients with rehabilitation treatment early after surgery to facilitate the CNS to correctly stabilize the spine without overloading it with excessive co-activations.

Mammographic calcifications undergoing percutaneous biopsy: outcome in women with and without a personal history of breast cancer.

PURPOSE: To compare the positive predictive values (PPVs) of BI-RADS categories used to assess pure mammographic calcifications in women with and without a previous history of breast cancer (PHBC). MATERIALS AND METHODS: In this retrospective study, all consecutive pure mammographic calcifications (n = 320) undergoing a stereotactic biopsy between 2016 and 2018 were identified. Mammograms were evaluated in consensus by two radiologists according to BI-RADS and blinded to patient history and pathology results. Final pathologic results were used as the standard of reference. PPV of BI-RADS categories were compared between the two groups. Data were evaluated using standard statistics, Mann-Whitney U tests and Chi-square tests. RESULTS: Two hundred sixty-eight patients (274 lesions, median age 54 years, inter-quartile range, 50-65 years) with a PHBC (n = 46) and without a PHBC (n = 222) were included. Overall PPVs were the following: BI-RADS 2, 0% (0 of 56); BI-RADS 3, 9.1% (1 of 11); BI-RADS 4a, 16.2% (6 of 37); BI-RADS 4b, 37.5% (48 of 128); BI-RADS 4c, 47.3% (18 of 38) and BI-RADS 5, 100% (4 of 4). The PPV of BI-RADS categories was similar in patients with and without a PHBC (P = .715). Calcifications were more often malignant in patients with a PHBC older than 10 years (47.3%, 9 of 19) compared to 1-2 years (25%, 1 of 4), 2-5 years (20%, 2 of 10) and 5-10 years (0%, of 13) from the first breast cancer (P = .005). CONCLUSION: PPV of mammographic calcifications is similar in women with or without PHBC when BI-RADS classification is strictly applied. A higher risk of malignancy was observed in patients with a PHBC longer than 10 years.

Assessing Trifecta Achievement after Percutaneous Cryoablation of Small Renal Masses: Results from a Multi-Institutional Collaboration.

Background and Objectives: To assess efficacy and safety of Percutaneous Cryoablation (PCA) of small renal masses (SRMs) using Trifecta outcomes in a large cohort of patients who were not eligible for surgery. Materials and methods: All PCAs performed in four different centers between September 2009 and September 2019 were retrospectively evaluated. Patients were divided in two different groups depending on masses dimensional criteria: Group-A: diameter ≤ 25 mm and Group-B: diameter > 25 mm. Complications rates were reported and classified according to the Clavien−Dindo system. The estimate glomerular filtration rate (eGFR) was calculated before PCA and during follow-up schedule. Every patient received a Contrast Enhanced Ultrasound (CEUS) evaluation on the first postoperative day. Radiological follow-up was taken at 3, 6, and 12 months for the first year, then yearly. Radiological recurrence was defined as a contrast enhancement persistence and was reported in the study. Finally, Trifecta outcome, which included complications, RFS, and preservation of eGFR class, was calculated for every procedure at a median follow-up of 32 months. Results: The median age of the patients was 74 years. Group-A included 200 procedures while Group-B included 140. Seventy-eight patients were eligible for Trifecta evaluation. Trifecta was achieved in 69.6% of procedures in Group-A, 40.6% in Group-B (p = 0.02). We observed an increased rate of complication in Group-B (13.0% vs. 28.6; p < 0.001). However, 97.5% were

Electron Density and Biologically Effective Dose (BED) Radiomics-Based Machine Learning Models to Predict Late Radiation-Induced Subcutaneous Fibrosis.

Purpose: to predict the occurrence of late subcutaneous radiation induced fibrosis (RIF) after partial breast irradiation (PBI) for breast carcinoma by using machine learning (ML) models and radiomic features from 3D Biologically Effective Dose (3D-BED) and Relative Electron Density (3D-RED). Methods: 165 patients underwent external PBI following a hypo-fractionation protocol consisting of 40 Gy/10 fractions, 35 Gy/7 fractions, and 28 Gy/4 fractions, for 73, 60, and 32 patients, respectively. Physicians evaluated toxicity at regular intervals by the Common Terminology Adverse Events (CTAE) version 4.0. RIF was assessed every 3 months after the completion of radiation course and scored prospectively. RIF was experienced by 41 (24.8%) patients after average 5 years of follow up. The Hounsfield Units (HU) of the CT-images were converted into relative electron density (3D-RED) and Dose maps into Biologically Effective Dose (3D-BED), respectively. Shape, first-order and textural features of 3D-RED and 3D-BED were calculated in the planning target volume (PTV) and breast. Clinical and demographic variables were also considered (954 features in total). Imbalance of the dataset was addressed by data augmentation using ADASYN technique. A subset of non-redundant features that best predict the data was identified by sequential feature selection. Support Vector Machines (SVM), ensemble machine learning (EML) using various aggregation algorithms and Naive Bayes (NB) classifiers were trained on patient dataset to predict RIF occurrence. Models were assessed using sensitivity and specificity of the ML classifiers and the area under the receiver operator characteristic curve (AUC) of the score functions in repeated 5-fold cross validation on the augmented dataset. Results: The SVM model with seven features was preferred for RIF prediction and scored sensitivity 0.83 (95% CI 0.80-0.86), specificity 0.75 (95% CI 0.71-0.77) and AUC of the score function 0.86 (0.85-0.88) on cross-validation. The selected features included cluster shade and Run Length Non-uniformity of breast 3D-BED, kurtosis and cluster shade from PTV 3D-RED, and 10th percentile of PTV 3D-BED. Conclusion: Textures extracted from 3D-BED and 3D-RED in the breast and PTV can predict late RIF and may help better select patient candidates to exclusive PBI.

Atypical ductal hyperplasia: breast DCE-MRI can be used to reduce unnecessary open surgical excision.

PURPOSE: To evaluate the diagnostic performance of dynamic contrast-enhanced (DCE)-MRI in predicting malignancy after percutaneous biopsy diagnosis of atypical ductal hyperplasia (ADH). METHODS AND MATERIALS: In this retrospective study, 68 lesions (66 women) with percutaneous biopsy diagnosis of ADH and pre-operative breast DCE-MRI performed between January 2016 and December 2017 were included. Two radiologists reviewed in consensus mammography, ultrasound, and MR images. The final diagnosis after surgical excision was used as standard of reference. Clinical and imaging features were compared in patients with and without upgrade to malignancy after surgery. The diagnostic performance of DCE-MRI in predicting malignant upgrade was evaluated. RESULTS: A 9-gauge vacuum-assisted biopsy was performed in 40 (58.8%) cases and a 14-gauge core needle biopsy in 28 (41.2%) cases. Upgrade to malignancy was observed in 17/68 (25%) lesions, including 4/17 (23.5%) cases of invasive cancer and 13/17 (76.5%) cases of ductal carcinoma in situ (DCIS). In 16/17 (94.1%) malignant and 20/51 (39.2%) benign lesions, a suspicious enhancement could be recognized in DCE-MRI. The malignant lesion without suspicious enhancement was a low-grade DCIS (4 mm size). Sensitivity, specificity, positive predictive value, and negative predictive value of DCE-MRI on predicting malignancy were respectively 94.1%, 60.7%, 44.4%, and 96.8%. No other clinical or imaging features were significantly different in patients with and without upgrade to malignancy. CONCLUSION: After a percutaneous biopsy diagnosis of ADH, malignancy can be ruled out in most of the cases, if no suspicious enhancement is present in the biopsy area at DCE-MRI. Breast DCE-MRI may be used to avoid surgery in more than half of the patients with final benign diagnosis. KEY POINTS: • Breast DCE-MRI can safely rule out malignancy if no suspicious enhancement is present in the biopsy area after a percutaneous biopsy diagnosis of ADH. • All cases of upgrade to high-grade DCIS and invasive cancers can be identified at breast DCE-MRI after a percutaneous biopsy diagnosis of ADH. • Breast DCE-MRI may be used to avoid surgery in more than half of the patients with final benign diagnosis.

Probe-based confocal laser endomicroscopy (pCLE) is a suitable method for extrapulmonary high grade neuroendocrine rectal carcinoma (HGNEC) evaluation.

The potential role of the probe-based confocal laser endomicroscopy (pCLE) has been analyzed in different pathologic conditions of the gastrointestinal tract. Here, we analyzed a case of extrapulmonary high grade neuroendocrine rectal carcinoma (HGNEC) using, for the first time, the pCLE system. A 72-year old man was diagnosed with an 8 cm diameter rectal HGNEC by standard colonoscopy integrated with the pCLE system. The diagnosis of neuroendocrine carcinoma was confirmed by immunohistochemical analyses. By using the pCLE system, we well defined and resolved vascular structures and mucosal architecture. An altered mucosal pattern and vascular defects, peculiar for HGNEC, were observed at high magnification, allowing the identification of a pattern which was quite different from that observed in poorly differentiated adenocarcinomas (PDA) where tissues appear darker, very irregular, even if glandular structures can still be recognized. This underlines the usefulness of pCLE in discriminating HGNECs from PDAs. In conclusion, pCLE could represent a valid and helpful method for in vivo HGNEC diagnosis, allowing prompt and careful management of the patient.

Therapeutic decision based on molecular detection of resistance mechanism in an ALK-rearranged lung cancer patient: a case report.

Background: The use of tyrosine kinase inhibitors (TKIs) of ALK is the therapy of choice for ALK-fusion patients. Unfortunately, all patients under this kind of treatment eventually develop acquired resistance through several well-known mechanisms, such as acquisition of a secondary mutation within the kinase domain, activation of a bypass signaling pathway, or a histological change like small-cell lung cancer transformation. At the time of progression, a tissue re-biopsy may give important molecular and morphological information regarding the mechanisms driving resistance to ALK TKIs. However, this procedure is not always feasible and it may not reflect the tumor heterogeneity, and therefore gives incomplete information. To overcome these drawbacks, the analysis of circulating tumor DNA (ctDNA) isolated from plasma, the so-called liquid biopsy, is emerging as a noninvasive and useful tool for detecting resistance mutations. Secondary resistance mutations are common in second-generation TKIs resistant patients and among these, Gly1202Arg (p.G1202R) emerged as the most frequent mutation. Case presentation: We have treated an ALK-positive lung adenocarcinoma patient with a sequential strategy of ALK TKIs. Patient follow-up was performed combining clinical, radiological, and molecular profiling. ctDNA was isolated from plasma and by means of ultra-deep next generation sequencing; we searched for secondary ALK resistance mutations on exons 21-25. ALK mutation Gly1202Arg (G1202R) was detected. We have documented consistency between plasma levels of G1202R mutation and radiological progression or improvement. Conclusion: Liquid biopsy appears to be a promising tool to anticipate progression and to drive the therapeutic strategy based upon ALK resistance mutations.

Multiparametric magnetic resonance imaging versus Partin tables and the Memorial Sloan-Kettering cancer center nomogram in risk stratification of patients with prostate cancer referred to external beam radiation therapy.

PURPOSE: To evaluate the agreement between multiparametric Magnetic Resonance Imaging (mpMRI), Partin tables (PT) and the Memorial Sloan Kettering Cancer Center nomogram (MSKCCn) in assessing risk category in prostate cancer (PCa) patients referred to External Beam Radiotherapy (EBRT). MATERIALS AND METHODS: In this bicentric study, we prospectively enrolled 80 PCa patients who underwent pre-EBRT mpMRI on a 3.0T magnet with a multiparametric protocol including high-resolution, multiplanar T2-weighted sequences, diffusion-weighted imaging and dynamic contrast-enhanced imaging. National comprehensive cancer network risk categories were assessed using prostate-specific-antigen level, Gleason score and the T-stage as defined by mpMRI or nomograms. Cohen's kappa statistic was used to calculate the agreement between mpMRI and nomograms in assessing the T-stage (organ-confined (OC) vs. non-organ-confined (nOC) disease) and risk category (≤ low risk vs. intermediate risk vs. ≥ high risk). RESULTS: mpMRI showed poor agreement with PT and MSKCCn in assessing nOC versus OC (k = 0.16 for both), translating into an mpMRI-induced reclassification of PT- and MSKCCn-related risk category in 36.3% (k = 0.43) and 41.3% (k = 0.31) of cases, respectively, with most changes occurring towards intermediate risk category. CONCLUSIONS: mpMRI showed low agreement with nomograms as a tool to stratify PCa risk, leading to significant risk reclassification. Assuming that mpMRI is a more reliable surrogate standard of reference for pathology, this technique should refine or replace nomograms in risk classification before EBRT.

Primary extragenital endometrial stromal sarcoma of the lung: first reported case and review of literature.

BACKGROUND: Endometrial stromal sarcomas arising in extrauterine and extraovarian sites, in the absence of a primary uterine lesion are quite rare, especially in the absence of endometriosis. They usually present as an abdominal or pelvic mass lesion. CASE PRESENTATION: In 2007, a 45-year-old woman underwent total hysterectomy for in situ squamous cell carcinoma of the cervix. In 2014, an upper left pulmonary lobectomy was performed for a mass, which was provisionally diagnosed as primary carcinosarcoma of the lung. A second histological revision of the lung surgical specimen was performed in the Pathology Unit of our Institute. After extensive immunohistochemical analyses, the preferred diagnosis was spindle-cell sarcoma, consistent with high-grade extragenital endometrial stromal sarcoma (EESS). A review of all slides of the hysterectomy specimen confirms the original diagnosis: no evidence of stromal tumor was found. Afterwards, the patient developed multiple and metachronous pulmonary lesions and a scapular soft tissue mass, which showed the same morphophenotypic features of the first lung mass. The patient was treated with antiblastic therapy, surgical resection and radioablation, when appropriate. To date, the patient has no signs or symptoms. CONCLUSIONS: The authors present the first case of primary EESS arising in the lung with no association with endometriosis published to date. Detailed clinical history and follow-up are also described. Moreover, extensive literature review is reported, along with differential diagnoses, immunohistochemical and molecular findings, pathogenetic hypotheses and treatment options. The knowledge of EESS potential extrauterine location and of its peculiar morphophenotypic aspects are required for a correct diagnosis, and for choosing the most suitable treatment.

Activity of crizotinib over choroidal metastases in non-small-cell lung cancer (NSCLC)-ALK rearranged: a case report.

BACKGROUND: Adenocarcinoma of the lung with EML4-ALK translocation is a rare subtype of Non Small-Cell Lung Cancer (NSCLC) that has recently shown to benefit from treatment with crizotinib. Despite the concerns about the efficacy of crizotinib over cerebral metastases, some reports have described its activity, although always after local treatment with radiotherapy. Recently it has been reported activity of crizotinib over choroidal metastases, again after radiotherapy. CASE PRESENTATION: Herein we report a case of activity of crizotinib over choroidal metastases not previously treated with radiotherapy. CONCLUSION: We suggest crizotinib may be active over choroidal metastases in a patient harboring ALK translocation with no need of radiotherapy.

Oxaliplapin and capecitabine (XELOX) based chemotherapy in the treatment of metastatic colorectal cancer: the right choice in elderly patients.

PURPOSE: Elderly patients with metastatic colorectal cancer (mCRC) differ from the general population and are underrepresented in clinical trials. We, retrospectively, analyzed the safety and efficacy of XELOX regimen in the treatment of elderly patients affected by mCRC. PATIENTS AND METHODS: One-hundred-eleven consecutive patients, aged 70 years or older, were enrolled in the study. RESULTS: All patients were evaluated for safety and efficacy (male/female, 63/48). Median age was 75 years (range 71-85 years). Median Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 0 (range 0-2). Metastatic sites distribution is as follows: liver (44.1%), lung (13.5%), liver plus lung (12.6%) and other (29.7%). A total of 584 cycles were administered (median 6 cycles/patient, range 2-10). Median follow-up time was 14.5 months (range 1-41 months). In an intent-to-treat analysis, objective responses and stable disease were recorded in 41 (40.4%) and 29 (26.6%) patients, respectively. The median response duration was 5.9 months (range 0.5-28.8). The median progression free-survival (PFS) was 7.5 months (range 1-26 months). The median overall survival (OS) was 15 months (range 1-64 months). The grade 3 toxicities were: neutropenia (8.1%), diarrhea and neurotoxicity (5.4% respectively). Most adverse events were mild to moderate; the most common was acute sensory neuropathy (57.6%). CONCLUSION: XELOX is a highly effective first-line treatment for mCRC elderly patients. Response rates, PFS and OS are similar to those observed with fluorouracil/leucovorin/oxaliplatin combinations. XELOX is a convenient regimen, likely to be preferred by both patient and healthcare providers.