Profiling of serum metabolome of breast cancer: multi-cancer features discriminate between healthy women and patients with breast cancer.

Introduction: The progression of solid cancers is manifested at the systemic level as molecular changes in the metabolome of body fluids, an emerging source of cancer biomarkers. Methods: We analyzed quantitatively the serum metabolite profile using high-resolution mass spectrometry. Metabolic profiles were compared between breast cancer patients (n=112) and two groups of healthy women (from Poland and Norway; n=95 and n=112, respectively) with similar age distributions. Results: Despite differences between both cohorts of controls, a set of 43 metabolites and lipids uniformly discriminated against breast cancer patients and healthy women. Moreover, smaller groups of female patients with other types of solid cancers (colorectal, head and neck, and lung cancers) were analyzed, which revealed a set of 42 metabolites and lipids that uniformly differentiated all three cancer types from both cohorts of healthy women. A common part of both sets, which could be called a multi-cancer signature, contained 23 compounds, which included reduced levels of a few amino acids (alanine, aspartate, glutamine, histidine, phenylalanine, and leucine/isoleucine), lysophosphatidylcholines (exemplified by LPC(18:0)), and diglycerides. Interestingly, a reduced concentration of the most abundant cholesteryl ester (CE(18:2)) typical for other cancers was the least significant in the serum of breast cancer patients. Components present in a multi-cancer signature enabled the establishment of a well-performing breast cancer classifier, which predicted cancer with a very high precision in independent groups of women (AUC>0.95). Discussion: In conclusion, metabolites critical for discriminating breast cancer patients from controls included components of hypothetical multi-cancer signature, which indicated wider potential applicability of a general serum metabolome cancer biomarker.

The Real-World Evidence on the Fragility and Its Impact on the Choice of Treatment Regimen in Newly Diagnosed Patients with Multiple Myeloma over 75 Years of Age.

Fragility scales are intended to help in therapeutic decisions. Here, we asked if the fragility assessment in MM patients ≥ 75 years old qualified for treatment by the local physician correlates with the choice of treatment: a two- or three-drug regimens. Between 7/2018 and 12/2019, we prospectively enrolled 197 MM patients at the start of treatment from the 13 Polish Myeloma Group centers. The data to assess fragility were prospectively collected, but centrally assessed fragility was not disclosed to the local center. The activity of daily living (ADL) could be assessed in 192 (97.5%) and was independent in 158 (80.2%), moderately impaired in 23 (11.7%), and 11 (5.6%) in completely dependent. Patients with more than three comorbidities made up 26.9% (53 patients). Thus, according to the Palumbo calculator, 43 patients were in the intermediate fitness group (21.8%), and the rest belonged to the frailty group (153, 77.7%). Overall, 79.7% of patients (157) received three-drug regimens and 20.3% (40) received two-drug regimens. In each ECOG group, more than three out of four patients received three-drug regimens. According to the ADL scale, 82.3% of the independent 65.2% of moderately impaired, and 81.8% of the dependent received three-drug regimens. Out of 53 patients with at least four comorbidities, 71.7% received three-drug regimens, and the rest received two-drug regimens. Thirty-four patients from the intermediate fit group (79.0%), and 123 (79.9%) from the frail group received three-drug regimens. Early mortality occurred in 25 patients (12.7%). No one discontinued treatment due to toxicity. To conclude, MM patients over 75 are mainly treated with triple-drug regimens, not only in reduced doses, regardless of their frailty scores. However, the absence of prospective fragility assessment did not negatively affect early mortality and the number of treatment discontinuations, which brings into question the clinical utility of current fragility scales in everyday practice.

The Severity of Pain in Prostate Biopsy Depends on the Biopsy Sector.

BACKGROUND: The pain experienced by a patient during a prostate fusion biopsy is cumulative and can also be modulated by many factors. The aim of the study was to assess the association between the degree of pain intensity during prostate biopsy and the region of the biopted organ. MATERIALS AND METHODS: The study included a group of 143 patients who underwent prostate fusion biopsy under local analgesia followed by blockage of the periprostatic nerve. After a biopsy, the patients completed the original questionnaire about the pain experienced during the procedure. RESULTS: There was a statistically significant difference in pain score between cores taken in the apex (median 5 (IQR 2-5)), medium level (median 1 (IQR 1-2)), and prostate base (median 1 (IQR 1-3)) (p < 0.001). The malignancy scale ISUP ≥ 2 (p = 0.038) and lower PSA value (r = -0.17; p = 0.046) are associated with higher pain during procedure. Biopsy time was correlated with discomfort (r = 0.19; p = 0.04). Age (p = 0.65), lesion size (p = 0.29), PI-RADS score (p = 0.86), prostate volume (p = 0.22), and the number of cores (p = 0.56) did not correspond to the pain scale. CONCLUSIONS: The apex is the most sensitive sector of the prostate. ISUP ≥ 2 and patients with low PSA levels more often indicated higher values on the pain rating scale.

The influence of the operator's experience on the outcomes of fusion prostate biopsy.

Introduction: Magnetic resonance imgaing (MRI) targeted biopsy is the gold standard for prostate cancer (PCa) diagnosis. In this study, we examined the association between the operator's experience and the improvement in the precision of the MRI prostate biopsy procedure and the detection of PCa. Material and methods: We included consecutive patients who underwent prostate fusion biopsy. Data on biopsy duration, prostate-specific antigen (PSA) value, lesion size, number of samples taken, number of cores involved, and International Society of Urological Pathology (ISUP) grade were subjected to statistical analysis, with the study group divided into three consecutive time periods (tertiles). Results: There were statistically significant differences in biopsy duration between tertiles (p <0.001). The greatest difference in the involved/taken cores ratio occurred between the first and third tertile (p = 0.002). The difference between the first and second tertile was insignificant (p = 0.4), while the difference between the second and third tertile was statistically significant (p = 0.004). The differences between tertiles in Prostate Imaging and Reporting Data System v2.1 were also significant (p = 0.003). The PSA value (p = 0.036) was statistically significant, unlike prostate volume (p = 0.16), digital rectal examination (DRE) (p = 0.7), and ISUP grade (p = 0.7). There was no statistical difference between tested tertiles in the number of detected PCa ISUP ≥2 (Z = 0.191; p = 0.8). Conclusions: The abilities and precision of the operator increase with the increase in the number of procedures performed. The biopsy duration is shortened, and the detection of PCa during the procedure seems to improve with the operator's experience.

The role of thyroid sonographic malignancy risk features when the fine needle aspiration biopsy result is indeterminate.

INTRODUCTION: Although the role of the thyroid ultrasound is well established in the initial thyroid nodule work up, it is still equivocal whether the thyroid ultrasound pattern could have an impact on refining malignancy risk after an indeterminate cytopathology result. We aim to assess the possible supportive role of the thyroid nodule ultrasound malignancy risk features listed in the Polish guidelines when a biopsy result is indeterminate. MATERIAL AND METHODS: We retrospectively reviewed thyroid ultrasound scans from 175 adult patients with thyroid nodules and indeterminate cytopathology results, who underwent thyroid surgery. Sonographic malignancy risk features were reported in accordance with the guidelines of the Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma and included the following: solid structure, hypoechogenicity, microcalcifications, taller than wide shape, irregular margins, features of extrathyroidal expansion, suspicious cervical lymph nodes. RESULTS: The malignancy risk in relevant cytological categories, estimated on the basis of histological verification, was 10.9% for Bethesda III category, 12.1% for Bethesda IV, and 71.4% for Bethesda V. The predominant type of thyroid malignancy was papillary thyroid carcinoma (79%). Thyroid nodules sonographic malignancy risk features provided high specificity but low sensitivity in selected groups of indeterminate thyroid nodules. Microcalcifications was the only characteristic that solely had a clinically relevant positive likelihood ratio (> 10) to suggest malignancy in the analysed cohort, but it was not observed in thyroid nodules eventually verified as follicular thyroid carcinoma. An accumulation of more than one sonographic risk feature yielded significant increase in malignancy risk only in Bethesda V category thyroid nodules. CONCLUSIONS: The impact of sonographic malignancy risk features on refining post-biopsy probability of thyroid cancer in thyroid nodule with indeterminate cytopathology, may be inadequate to sort patients (without any doubt) between those who require thyroid surgery and those who only require surveillance. There is an urgent need to search for new tools in the diagnostics of indeterminate thyroid nodules and to standardize thyroid ultrasound reports.