Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV from the Canadian cohort of the observational BICSTaR study.

The BICSTaR (BICtegravir Single Tablet Regimen) study is investigating the effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with human immunodeficiency virus (HIV) treated in routine clinical practice. BICSTaR is an ongoing, prospective, observational cohort study across 14 countries. Treatment-naïve (TN) and treatment-experienced (TE) people with HIV (≥18 years of age) are being followed for 24 months. We present an analysis of the primary endpoint (HIV-1 RNA < 50 copies/mL; missing-equals-excluded [M = E]) at month 12 in the BICSTaR Canada cohort, including secondary (CD4 count, CD4/CD8 ratio, safety/tolerability) and exploratory (persistence, treatment satisfaction) endpoints. In total, 201 participants were enrolled in the BICSTaR Canada cohort. The analysis population included 170 participants (TN, n = 10; TE, n = 160), with data collected between November 2018 and September 2020. Of the participants, 88% were male, 72% were White, and 90% had ≥ 1 comorbid condition(s). Median (quartile [Q]1-Q3) age was 50 (39-58) years and baseline CD4 count was 391.5 (109.0-581.0) cells/µL in TN participants and 586.0 (400.0-747.0) cells/µL in TE participants. After 12 months of B/F/TAF treatment, HIV-1 RNA was < 50 copies/mL in 100% (9/9) of TN-active participants and 97% (140/145) of TE-active participants (M = E analysis). Median (Q1-Q3) CD4 cell count increased by +195 (125-307) cells/µL in TN participants and by + 30 (-50 to 123) cells/µL in TE participants. Persistence on B/F/TAF was high through month 12 with 10% (1/10) of TN and 7 % (11/160) of TE participants discontinuing B/F/TAF within 12 months of initiation of treatment. No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 7% (12/169) of participants, leading to B/F/TAF discontinuation in 4 of 169 participants. Improvements in treatment satisfaction were observed in TE participants. B/F/TAF demonstrated high levels of effectiveness, persistence, and treatment satisfaction, and was well tolerated through month 12 in people with HIV treated in routine clinical practice in Canada.

Minimal Extrathyroid Extension (mETE) as the Only Risk Factor in Patients with Papillary Thyroid Carcinoma (PC): Its Clinical Impact on Recurrence and Outcome during Long-Term Follow-Up.

Minimal extrathyroid extension (mETE) effect on papillary thyroid carcinoma (PC) prognosis is still debated even more so now that this factor has been removed in the 8th AJCC Edition, supporting the hypothesis that mETE is not associated with aggressive tumors. We retrospectively enrolled 91 PC patients (Group 1) submitted to total thyroidectomy and radioiodine ablation. At the time of the primary tumor surgery, mETE was ascertained in all patients with no other risk factors, such as multifocality, vascular invasion, neck and distant metastases, and aggressive histological variants. As controls, 205 consecutive matched PC patients (Group 2) without mETE and the aforementioned risk factors were enrolled. During the follow-up (average 8 years), 16/91 (17.58%) Group 1 patients and 15/205 (7.32%) Group 2 patients developed metastases (p = 0.0078). Cox regression analysis showed an increased risk of metastases in patients with mETE (HR: 2.58 (95% CI 1.28-5.22) p = 0.008). Disease-free survival (DFS) was significantly lower in patients with mETE than in controls (p = 0.0059). The present study seems to demonstrate that mETE can be associated with an aggressive PC and can be considered, even alone without other risk factors, an independent factor of unfavorable DFS. Thus, by excluding mETE in the 8th AJCC Edition, patient care and management could be compromised.

Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus.

BACKGROUND: Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear. METHODS: We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality. RESULTS: CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10-6.19] and 2.03 [95% CI 1.24-3.33], respectively). CD4 cell counts below 350 cells/µL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies. CONCLUSIONS: In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM.

Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV: Real-world insights from BICSTaR cohorts.

BACKGROUND: Real-world evidence is an essential component of evidence-based medicine. The aim of the BICSTaR (BICtegravir Single Tablet Regimen) study is to assess effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in antiretroviral treatment-naïve (TN) and treatment-experienced (TE) people with HIV. METHODS: BICSTaR is a prospective, observational cohort study. Participants (≥18 years) are being followed for 24 months. A pooled analysis is presented at 12 months, with the primary endpoint of effectiveness (HIV-1 RNA <50 copies/mL) and secondary endpoints of safety and tolerability (as per protocol). An exploration of patient-reported outcome measures using standardized questionnaires is included. RESULTS: Between June 2018 and May 2021, 1552 people with HIV were enrolled across 12 countries. The analysed population comprised 1509 individuals (279 TN, 1230 TE); most were white (76%), male (84%) and had one or more comorbid conditions (68%). Median age was 47 years. After 12 months of B/F/TAF treatment, HIV-1 RNA was <50 copies/mL in 94% (221/236) of TN participants and 97% (977/1008) of TE participants. Median CD4 cell count increased by 214 cells/µL (p < 0.001) in TN participants and 13 cells/µL (p = 0.014) in TE participants; median CD4/CD8 ratios increased by 0.30 and 0.03, respectively (both p < 0.001). Persistence was high at 12 months (TN, 97%; TE, 95%). No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 13% of participants through 12 months, leading to B/F/TAF discontinuation in 6%. CONCLUSIONS: The findings of this study provide robust real-world evidence to support the broad use of B/F/TAF in both TN and TE people with HIV.

Hashimoto's Thyroiditis and Papillary Thyroid Carcinoma: A Follow-Up Study in Patients with Absence of Aggressive Risk Factors at the Surgery of the Primary Tumor.

Hashimoto's thyroiditis (HT) is often associated with papillary thyroid carcinoma (PC); it is still a matter of controversy whether the behavior of carcinoma is more aggressive or not. During the follow-up, we retrospectively enrolled 97 patients with PC/HT after thyroidectomy without risk factors at the surgery of the primary tumor, such as multifocality/multicentricity, extrathyroid tumor extension, vascular invasion, neck and distant metastases, and aggressive histological variants. HT diagnosis was confirmed by histology and serum thyroid antibodies. Tumor size was ≤10 mm in 64 cases (microcarcinomas); 206 matched PC patients after thyroidectomy without HT and risk factors were enrolled as controls, totaling 122 microcarcinomas. During follow-up, metastases occurred in 15/97 (15.5%) PC/HT cases, eight microcarcinomas, and in 16/206 (7.8%) without HT, eight microcarcinomas (p = 0.04). Considering both PC/HT and PC patients without HT who developed metastases, univariate analysis showed an increased risk of metastases in patients with HT coexistence, OR: 2.17 (95% CI 1.03-4.60) p = 0.043. Disease-free survival (DFS) was significantly (p = 0.0253) shorter in PC/HT than in the controls. The present study seems to demonstrate that HT is not a cancer protective factor in PC patients given the less favorable outcomes and significantly shorter DFS. HT may also represent an independent recurrence predictor without other risk factors.

Performance Analysis of Six Semi-Automated Tumour Delineation Methods on [18F] Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in Patients with Head and Neck Cancer.

Background. Head and neck cancer (HNC) is the seventh most common neoplastic disorder at the global level. Contouring HNC lesions on [18F] Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scans plays a fundamental role for diagnosis, risk assessment, radiotherapy planning and post-treatment evaluation. However, manual contouring is a lengthy and tedious procedure which requires significant effort from the clinician. Methods. We evaluated the performance of six hand-crafted, training-free methods (four threshold-based, two algorithm-based) for the semi-automated delineation of HNC lesions on FDG PET/CT. This study was carried out on a single-centre population of n=103 subjects, and the standard of reference was manual segmentation generated by nuclear medicine specialists. Figures of merit were the Sørensen-Dice coefficient (DSC) and relative volume difference (RVD). Results. Median DSC ranged between 0.595 and 0.792, median RVD between -22.0% and 87.4%. Click and draw and Nestle's methods achieved the best segmentation accuracy (median DSC, respectively, 0.792 ± 0.178 and 0.762 ± 0.107; median RVD, respectively, -21.6% ± 1270.8% and -32.7% ± 40.0%) and outperformed the other methods by a significant margin. Nestle's method also resulted in a lower dispersion of the data, hence showing stronger inter-patient stability. The accuracy of the two best methods was in agreement with the most recent state-of-the art results. Conclusions. Semi-automated PET delineation methods show potential to assist clinicians in the segmentation of HNC lesions on FDG PET/CT images, although manual refinement may sometimes be needed to obtain clinically acceptable ROIs.

Role of Functional Neuroimaging with 123I-MIBG and 123I-FP-CIT in De Novo Parkinson's Disease: A Multicenter Study.

BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder, with incidence and prevalence rates of 8-18 per 100,000 people per year and 0.3-1%, respectively. As parkinsonian symptoms do not appear until approximately 50-60% of the nigral DA-releasing neurons have been lost, the impact of routine structural imaging findings is minimal at early stages, making Parkinson's disease an ideal condition for the application of functional imaging techniques. The aim of this multicenter study is to assess whether 123I-FP-CIT (DAT-SPECT), 123I-MIBG (mIBG-scintigraphy) or an association of both exams presents the highest diagnostic accuracy in de novo PD patients. METHODS: 288 consecutive patients with suspected diagnoses of Parkinson's disease or non- Parkinson's disease syndromes were analyzed in the present Italian multicenter retrospective study. All subjects were de novo, drug-naive patients and met the inclusion criteria of having undergone both DAT-SPECT and mIBG-scintigraphy within one month of each other. RESULTS: The univariate analysis including age and both mIBG-SPECT and DAT-SPECT parameters showed that the only significant values for predicting Parkinson's disease in our population were eH/M, lH/M, ESS and LSS obtained from mIBG-scintigraphy (p < 0.001). CONCLUSIONS: mIBG-scintigraphy shows higher diagnostic accuracy in de novo Parkinson's disease patients than DAT-SPECT, so given the superiority of the MIBG study, the combined use of both exams does not appear to be mandatory in the early phase of Parkinson's disease.

The DASciS Software for BSI Calculation as a Valuable Prognostic Tool in mCRPC Treated with 223RaCl2: A Multicenter Italian Study.

BACKGROUND/AIM: Radium-223 dichloride (223RaCl2) represents a therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) patients dealing with symptomatic bone metastases. The identification of baseline variables potentially affecting the life-prolonging role of 223RaCl2 is still ongoing. Bone scan index (BSI) defines the total load of bone metastatic disease detected on a bone scan (BS) and is expressed as a percentage value of the whole bone mass. The aim of this multicenter study was to assess the impact of baseline BSI on overall survival (OS) in mCRPC patients treated with 223RaCl2. For this purpose, the DASciS software developed by the Sapienza University of Rome for BSI calculation was shared between six Italian Nuclear Medicine Units. METHODS: 370 pre-treatment BS were analyzed through the DASciS software. Other clinical variables relevant to OS analysis were taken into account for the statistical analysis. RESULTS: Of a total of 370 patients, 326 subjects had died at the time of our retrospective analysis. The median OS time from the first cycle of 223RaCl2 to the date of death from any cause or last contact was 13 months (95%CI 12-14 months). The mean BSI value resulted in 2.98% ± 2.42. The center-adjusted univariate analysis showed that baseline BSI was significantly associated with OS as an independent risk factor (HR 1.137, 95%CI: 1.052-1.230, p = 0.001), meaning that patients with higher BSI values had worse OS. When adjusting for other measures on multivariate analysis, in addition to Gleason score and baseline values of Hb, tALP, and PSA, baseline BSI was confirmed to be a statistically significant parameter (HR 1.054, 95%CI: 1.040-1.068, p < 0.001). CONCLUSIONS: Baseline BSI significantly predicts OS in mCRPC treated with 223RaCl2. The DASciS software was revealed to be a valuable tool for BSI calculation, showing rapid processing time and requiring no more than a single demonstrative training for each participating center.

Evaluation of Bone Scan Index as a Prognostic Tool in Breast Cancer Patients with Bone Metastasis.

BACKGROUND: Bone metastatic involvement represents a leading cause of death in patients with advanced breast cancer (BC). At present, it is not clear whether the bone metastatic load might impact Overall Survival (OS) in patients with bone metastatic BC at diagnosis. For this purpose, we used the Bone Scan Index (BSI), which is a reproducible and quantitative expression of tumor load observed at bone scintigraphy. OBJECTIVE: The aim of this study was to associate BSI with OS in bone metastatic BC patients. METHODS: In this retrospective study, we enrolled BC patients with bone metastases at the scintigraphic bone scan performed for staging purposes. The BSI was calculated through the DASciS software, and statistical analysis was carried out. Other clinical variables relevant to OS analysis were taken into account. RESULTS: Of a total of 94 patients, 32% died. In most cases, the histotype was ductal infiltrating carcinoma. The median OS from diagnosis was 72 months (CI 95%: 62-NA). The univariate analysis with COX regression showed that only hormone therapy significantly correlates with OS (HR 0.417, CI 95%: 0.174-0.997, p < 0.049). As concerning BSI, the statistical analysis showed that it does not predict OS in BC patients (HR 0.960, 95% CI: 0.416-2.216, p < 0.924). CONCLUSION: Although the BSI significantly predicts OS in prostate cancer and in other tumors, we observed that the metastatic load of bone disease has not a key role in prognostic stratification in our population.

Qualitative and Semiquantitative Parameters of 18F-FDG-PET/CT as Predictors of Malignancy in Patients with Solitary Pulmonary Nodule.

This study aims to evaluate the reliability of qualitative and semiquantitative parameters of 18F-FDG PET-CT, and eventually a correlation between them, in predicting the risk of malignancy in patients with solitary pulmonary nodules (SPNs) before the diagnosis of lung cancer. A total of 146 patients were retrospectively studied according to their pre-test probability of malignancy (all patients were intermediate risk), based on radiological features and risk factors, and qualitative and semiquantitative parameters, such as SUVmax, SUVmean, TLG, and MTV, which were obtained from the FDG PET-CT scan of such patients before diagnosis. It has been observed that visual analysis correlates well with the risk of malignancy in patients with SPN; indeed, only 20% of SPNs in which FDG uptake was low or absent were found to be malignant at the cytopathological examination, while 45.45% of SPNs in which FDG uptake was moderate and 90.24% in which FDG uptake was intense were found to be malignant. The same trend was observed evaluating semiquantitative parameters, since increasing values of SUVmax, SUVmean, TLG, and MTV were observed in patients whose cytopathological examination of SPN showed the presence of lung cancer. In particular, in patients whose SPN was neoplastic, we observed a median (MAD) SUVmax of 7.89 (±2.24), median (MAD) SUVmean of 3.76 (±2.59), median (MAD) TLG of 16.36 (±15.87), and a median (MAD) MTV of 3.39 (±2.86). In contrast, in patients whose SPN was non-neoplastic, the SUVmax was 2.24 (±1.73), SUVmean 1.67 (±1.15), TLG 1.63 (±2.33), and MTV 1.20 (±1.20). Optimal cut-offs were drawn for semiquantitative parameters considered predictors of malignancy. Nodule size correlated significantly with FDG uptake intensity and with SUVmax. Finally, age and nodule size proved significant predictors of malignancy. In conclusion, considering the pre-test probability of malignancy, qualitative and semiquantitative parameters can be considered reliable tools in patients with SPN, since cut-offs for SUVmax, SUVmean, TLG, and MTV showed good sensitivity and specificity in predicting malignancy.

First-, Second-, and Third-Generation Radiolabeled Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Positron Emission Tomography: State of the Art, a Systematic Review.

Introduction: Lung cancer (LC) is a leading cause of death among men and women, with non-small cell LC (NSCLC) accounting for a substantial portion of the histopathological spectrum and epidermal growth factor receptor (EGFR) mutations being correlated with its manifestation and evolution. Positron emission tomography (PET)/computed tomography has been the most widely used instrument to assess and monitor LC in a noninvasive way, including EGFR-mutated NSCLC, and its course during therapy, indicating to the referring physician the response to ongoing treatment or the lack of it. This systematic review aims to evaluate the feasibility and safety of radiolabeled EGFR tyrosine kinase inhibitors (TKis) in PET in clinical practice. Materials and Methods: From 1999 to April 2022 a Medline search was conducted on four different databases such as PubMed, Cochrane Library, Scopus, and Web of Sciences. Clinical studies were assessed by Quality Assessment of Diagnostic accuracy Studies-2 (QUADAS-2) and preclinical studies were also reported in this review. Results: Nine clinical studies were QUADAS-2 assessed and risk-of-bias assessment, and it turned out acceptable as two out of eight studies had low risk of bias in all four domains for risk-of-bias assessment, and the other four studies had three low-risk domains. The overall assessment for applicability risks was low. Conclusions: Radiolabeled EGFR-TKis in PET are a valid tool in identifying patients who may benefit from TKi therapy and who may not as a means to start an effective treatment. Although the number of clinical studies conducted so far is meager, these new PET tracers are already proving to be very useful in clinical settings as patient prognosis can be better assessed.

A Comparative Follow-Up Study of Patients with Papillary Thyroid Carcinoma Associated or Not with Graves' Disease.

Whether papillary carcinoma (PC) behavior is more aggressive in Graves' disease (GD) patients than PC cases without GD is controversial. We retrospectively enrolled 33 thyroidectomized PC/GD patients during long-term follow-up, 23/33 without risk factors at surgery, and 18/33 microcarcinomas; 312 PC euthyroid-matched patients without risk factors served as controls. A total of 14/33 (42.4%) PC/GD patients, 4 with and 10 without risk factors at diagnosis, 6 with microcarcinoma, underwent metastases during follow-up. In controls, metastases in 21/312 (6.7%) were ascertained. Considering 10/23 PC/GD patients and 21/312 controls without risk factors who developed metastases, univariate analysis showed that there was an increased risk of metastasis appearance for PC/GD cases (p < 0.001). Disease-free survival (DFS) was significantly (p < 0.0001, log-rank test) shorter in PC/GD patients than in controls. Significantly more elevated aggressiveness in 6/18 PC/GD patients with microcarcinoma than in controls was also ascertained with shorter DFS. Thus, in the present study, PC/GD had aggressive behavior during follow-up also when carcinoma characteristics were favorable and some cases were microcarcinomas. GD and non-GD patient comparison in the cases without risk factors at diagnosis showed an increased risk to develop metastases in GD during follow-up, suggesting that GD alone might be a tumor aggressiveness predictive factor in these cases.

Breast-Specific Gamma Imaging: An Added Value in the Diagnosis of Breast Cancer, a Systematic Review.

PURPOSE: Breast cancer is the most common solid tumor and the second highest cause of death in the United States. Detection and diagnosis of breast tumors includes various imaging modalities, such as mammography (MMG), ultrasound (US), and contrast-enhancement MRI. Breast-specific gamma imaging (BSGI) is an emerging tool, whereas morphological imaging has the disadvantage of a higher absorbed dose. Our aim was to assess if this imaging method is a more valuable choice in detecting breast malignant lesions compared to morphological counterparts. METHODS: research on Medline from 1995 to June 2022 was conducted. Studies that compared at least one anatomical imaging modality with BSGI were screened and assessed through QUADAS2 for risk of bias and applicability concerns assessment. Sensitivity, specificity, positive and negative predictive value (PPV and NPV) were reported. RESULTS: A total of 15 studies compared BSGI with MMG, US, and MRI. BSGI sensitivity was similar to MRI, but specificity was higher. Specificity was always higher than MMG and US. BSGI had higher PPV and NPV. When used for the evaluation of a suspected breast lesion, the overall sensitivity was better than the examined overall sensitivity when BSGI was excluded. Risk of bias and applicability concerns domain showed mainly low risk of bias. CONCLUSION: BSGI is a valuable imaging modality with similar sensitivity to MRI but higher specificity, although at the cost of higher radiation burden.

Differential Diagnosis of Alzheimer Disease vs. Mild Cognitive Impairment Based on Left Temporal Lateral Lobe Hypomethabolism on 18F-FDG PET/CT and Automated Classifiers.

PURPOSE: We evaluate the ability of Artificial Intelligence with automatic classification methods applied to semi-quantitative data from brain 18F-FDG PET/CT to improve the differential diagnosis between Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI). PROCEDURES: We retrospectively analyzed a total of 150 consecutive patients who underwent diagnostic evaluation for suspected AD (n = 67) or MCI (n = 83). All patients received brain 18F-FDG PET/CT according to the international guidelines, and images were analyzed both Qualitatively (QL) and Quantitatively (QN), the latter by a fully automated post-processing software that produced a z score metabolic map of 25 anatomically different cortical regions. A subset of n = 122 cases with a confirmed diagnosis of AD (n = 53) or MDI (n = 69) by 18-24-month clinical follow-up was finally included in the study. Univariate analysis and three automated classification models (classification tree -ClT-, ridge classifier -RC- and linear Support Vector Machine -lSVM-) were considered to estimate the ability of the z scores to discriminate between AD and MCI cases in. RESULTS: The univariate analysis returned 14 areas where the z scores were significantly different between AD and MCI groups, and the classification accuracy ranged between 74.59% and 76.23%, with ClT and RC providing the best results. The best classification strategy consisted of one single split with a cut-off value of ≈ -2.0 on the z score from temporal lateral left area: cases below this threshold were classified as AD and those above the threshold as MCI. CONCLUSIONS: Our findings confirm the usefulness of brain 18F-FDG PET/CT QL and QN analyses in differentiating AD from MCI. Moreover, the combined use of automated classifications models can improve the diagnostic process since its use allows identification of a specific hypometabolic area involved in AD cases in respect to MCI. This data improves the traditional 18F-FDG PET/CT image interpretation and the diagnostic assessment of cognitive disorders.

Personalized Dosimetry in the Context of Radioiodine Therapy for Differentiated Thyroid Cancer.

The most frequent thyroid cancer is Differentiated Thyroid Cancer (DTC) representing more than 95% of cases. A suitable choice for the treatment of DTC is the systemic administration of 131-sodium or potassium iodide. It is an effective tool used for the irradiation of thyroid remnants, microscopic DTC, other nonresectable or incompletely resectable DTC, or all the cited purposes. Dosimetry represents a valid tool that permits a tailored therapy to be obtained, sparing healthy tissue and so minimizing potential damages to at-risk organs. Absorbed dose represents a reliable indicator of biological response due to its correlation to tissue irradiation effects. The present paper aims to focus attention on iodine therapy for DTC treatment and has developed due to the urgent need for standardization in procedures, since no unique approaches are available. This review aims to summarize new proposals for a dosimetry-based therapy and so explore new alternatives that could provide the possibility to achieve more tailored therapies, minimizing the possible side effects of radioiodine therapy for Differentiated Thyroid Cancer.

Patient-reported pain severity and health-related quality of life in patients with multiple myeloma in real world clinical practice.

BACKGROUND: The association between patient self-reported pain severity and health-related quality-of-life (HRQoL) is poorly understood. AIMS: This real-world study of symptomatic multiple myeloma (MM) patients sought to determine how pain severity from a single question asked during routine clinical consultation was associated with HRQoL. METHODS AND RESULTS: Point-in-time data on HRQoL of 330 patients with MM (median age 70 years) receiving anti-myeloma therapy in Germany and Italy from November 2017 through February 2018 were analyzed. HRQoL was assessed using validated questionnaires (Work Productivity and Activity Impairment [WPAI], European Organization for Research and Treatment of Cancer Quality of Life Questionnaire -C30 and -MY20). Physical pain severity was assessed during clinical consultation by a single question, asking patients to describe their pain as "no pain," "mild," "moderate," or "severe." Associations between patient-reported pain severity and HRQoL scores were assessed by analysis of variance or χ2 tests. Ninety-six of the 330 patients (29.1%) reported moderate to severe pain. Increase in pain severity, from "no" to "severe" pain, was associated with significantly decreased overall HRQoL (mean score 70.2 to 33.3); significant decreases in levels of physical (82.7 to 35.1), social (81.1 to 44.4), emotional (78.1 to 48.3), and role functioning (79.5 to 38.9); and increased levels of WPAI usual activity impairment (35.4 to 71.4), and fatigue burden (26.0 to 68.9) (all p < .001). CONCLUSION: Higher pain severity, based on a single self-report question, was associated with poorer HRQoL in patients with MM, thereby supporting the clinical relevance of directly asking patients to self-evaluate their pain severity.

Physical, emotional and social pain communication by patients diagnosed and living with multiple myeloma.

Aim: To describe physical, social and emotional aspects of pain self-reported by patients with multiple myeloma (MM), and patient-physician communication of physical pain. Materials & methods: We analyzed self-reported data from 330 adults receiving anti-MM therapy in Germany and Italy on health-related quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Core-30 Questionnaire version 3, -MY20) and bone pain symptoms. Results: Patients experienced clinically important physical (69%), emotional (58%) and social (22%) pain. Less than three-quarters of physicians' records matched patients' perception of bone pain (71.5%), with bone pain not recorded in 19.7% of patients experiencing it. Nearly half of physicians underestimated bone pain severity. Conclusion: Patients with MM experience physical, social and emotional pain. Discordance regarding bone pain symptoms and severity was observed, suggesting the need for improved communication.

Initiation of bone-targeted agents in patients with bone metastases and breast or castrate-resistant prostate cancer actively treated in routine clinical practice in Europe.

BACKGROUND: Guidelines recommend starting bone-targeted agents (BTA), such as zoledronic acid and denosumab, as soon as bone metastases (BMs) are definitively diagnosed in all patients with breast cancer (BC) or castration-resistant prostate cancer (CRPC) whether they are symptomatic or not. METHODS: Data were analyzed from 1364 patients with BC and 1161 patients with CRPC who had BMs and were receiving anti-cancer therapy in hospitals across six European countries (Belgium, France, Germany, Italy, Spain and the UK). The 731 physicians (medical oncologists or urologists) provided insights in the decision-making factors driving their management of bone health for these patients, and the patient medical records indicated how these decisions were reflected in routine clinical practice. RESULTS: Within three months of a BM diagnosis, 74% of BC and 51% of CRPC patients had initiated treatment with a BTA. Around 12% of BC and 23% of CRPC patients did not receive a BTA following BM diagnosis. Irrespective of the tumour type (BC or CRPC), most physicians prescribed either denosumab or zoledronic acid as first BTA therapy. Physicians reported bone pain as a major decision-making factor to initiate a BTA. The presence of bone complications at BM diagnosis and bone pain at BM diagnosis were found to be significant predictive factors for a BTA initiation, irrespective of tumour type. CONCLUSIONS: Despite European Society for Medical Oncology (ESMO) guidance on bone protection irrespective of symptomatic disease, not all patients with BMs received a BTA following a BM diagnosis. This suggests that clinical judgements and patients' communication of their pain to their physicians contributed to the decision to prescribe bone protection therapy in cancer patients.

Risk of infections and mortality in Danish patients with cancer diagnosed with bone metastases: a population-based cohort study.

OBJECTIVES: Risk of infections in patients with solid cancers and bone metastases (BM) and the subsequent impact on prognosis is unclear. We examined the risk of infections among patients with cancer diagnosed with BM and the subsequent impact of infections on mortality. DESIGN: Population-based cohort study. SETTING: Danish medical databases holding information on all hospital contacts in Denmark. PARTICIPANTS: Adult patients with solid cancers and BM between 1 January 1994 and 30 November 2013. OUTCOME MEASURES: In the risk analyses, the outcome was time to hospitalisation for common severe infections, pneumonia, sepsis and urinary tract infections. In the mortality analysis, we used Cox regression to compute HRs of death, modelling infection as time-varying exposure, stratifying for primary cancer type and adjusting for age, sex and comorbidities. RESULTS: Among 23 336 patients with cancer and BM, cumulative incidences of common severe infections were 4.6%, 14.0% and 20.0% during 1 month, 1 year and 10 years follow-up. The highest incidence was observed for pneumonia, followed by urinary tract infections and sepsis. Infection was a strong predictor of 1 month mortality (adjusted HR: 2.1 (95% CI 1.8 to 2.3)) and HRs increased after 1 and 10 years: 2.4 (95% CI 2.3 to 2.6) and 2.4 (95% CI 2.4 to 2.6). Sepsis and pneumonia were the strongest predictors of death. Results were consistent across cancer types. CONCLUSION: Patients with cancer and BM were at high risk of infections, which was associated with a more than twofold increased risk of death for up to 10 years of follow-up. The findings underscore the importance of preventing infections in patients with cancer and BM.