bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncologists’ perspectives on metastatic hormone sensitive prostate cancer management.
Authors: Heckman Patrick , Yan Donglin , Zhou Xitong , Myint Zin
Published: March 2023

84

Background: The treatment of metastatic hormone sensitive prostate cancer (mHSPC) has evolved over the past 7 years. Combination therapies with either [Androgen deprivation therapy (ADT) + Docetaxel] or [ADT + androgen receptor signaling inhibitors (ARSi) such as abiraterone acetate/enzalutamide/apalutamide] have demonstrated overall survival (OS) benefit compared to ADT + placebo in mHSPC. Recently two trials (ARASENS and PEACE-1) also demonstrate an OS benefit from the addition of docetaxel to ADT + ARSi (abiraterone acetate or darolutamide) compared to ADT + docetaxel. Given these recent advances there is not a clear consensus on how to best manage patients with mHSPC as there are no head-to-head trials. In this study, we assess oncologists’ treatment preferences as it pertains to this subset of patients. Methods: An 8-item online survey was sent on September 6th, 2022 to medical oncologists in the United States. We described five different case scenarios and three demographic questionnaires. Cases consisted of patients with mHSPC both de novo and primary progressive with low and high volumes. Treatment options included ADT monotherapy, ADT + ARSi (doublet), or ADT + ARSi + docetaxel (triplet therapy). Respondents reported their practice setting, location, and years of clinical experience. Data was collected and analyzed via REDCap. Results: Surveys were completed by (n=83) medical oncologists across the US. 14.5% of respondents were from Kentucky; 51.8% have been in practice < 10 years, 20.5% 10-20 years, and 27.7%> 20 years. For patients with de novo high volume disease, 85.5% (71) preferred treatment with triplet therapy. For the same patient population, 94.4% (51) of university-based providers preferred triplet therapy vs 68.9% (20) of those in a non-academic setting. Preferences differed regarding patients with primary progressive high-volume disease in which 59.8% (49) preferred a triplet regimen while 37.8% (31) preferred a doublet regimen. Of those choosing triplet therapy, 53.7% (29) were from an academic institution while 71.4% (20) practiced in a nonacademic setting. Of those choosing doublet therapy, 42.6% (23) were from an academic institution versus 28.6% (8) in a nonacademic setting. For patients with de novo or primary progressive low volume disease, 81.5% of respondents preferred doublet therapy without a notable difference between academic and non-academic responders. Conclusions: We find a consensus in management of patients with de novo high volume mHSPC (prefer triplet) and de novo or primary progressive low volume disease (prefer doublet) regardless of practice setting, location, or practice duration. However, for patients with primary progressive high-volume disease, a higher percentage of non-academic providers prefer triplet therapy compared to their university counterparts.
Physician preferences for nonmetastatic castration-resistant prostate cancer treatments: A discrete choice experiment among men in mainland China.
Authors: Fan Yu , Huang Shiyun , Xu Rui , He Zhisong
Published: March 2023

88

Background: A range of medication options are available for non-metastatic castration-resistant prostate cancer (nmCRPC), with varying efficacy and safety profiles. We used a discrete choice experiment (DCE) to explore how physicians make treatment decisions between adverse events (AEs) and survival gains in nmCRPC in mainland China. Methods: Physicians’ preferences for medication attributes were assessed through an online survey including 14 treatment choice questions, each comparing 2 hypothetical treatment profiles, which varied safety (fatigue, skin rash, cognitive problems, falls, and fractures) in terms of severity and frequency and efficacy (overall survival [OS] and time to pain progression [TPP]) in terms of duration of effect. Preference weights and importance scores for each attribute were estimated using random parameters logit models. The amount of survival gain physicians were willing to trade off for a reduction in specific AEs was also estimated. Results: In total, 80 physicians who had experience in treating nmCRPC patients were involved in this study. Physicians’ duration of clinical practice was about 18.4±7.39 years. In addition, 57.6% of participants were from regions with more developed economics, including North, East and South China. The results indicated that physician preferences were logically ordered, with higher efficacy and lower risks for AEs being favored over lower efficacy and higher risks for AEs. The most important attributes for treatment decision were OS (Relative importance, RI = 29.2%), serious fracture (RI = 24.4%), serious fall (RI =15.4%) and TPP (RI =10.6%). Comparing non-serious AEs including fatigue, skin rash and cognitive problems, physicians emphasized the risk reduction of fatigue the most. The trade-off analysis between OS and adverse events suggested that physicians were willing to trade 7.5 and 4.7 months of OS to reduce the risk of severe fracture from 8% to none, and the risk of serious fall from 8% to none. In an exploratory subgroup analysis, it was found that physicians with more than 15 years of clinical practice put more emphasis on overall survival, risk of serious fracture, and risk of serious fall compared to less experienced physicians (≤15 years). Physicians from regions with more developed economics tended to put more value on reduction of AEs as compared to physicians from the rest regions. Conclusions: OS is the most important attribute for physicians when treating nmCRPC patients. Physicians were willing to trade the duration of OS to reduce the risk of serious adverse events. These results emphasize the importance of carefully balancing therapies’ benefits and risks to ultimately optimize the overall quality of nmCRPC patients’ survival.
Atezolizumab (atezo) + platinum/gemcitabine (plt/gem) vs placebo + plt/gem for first-line (1L) treatment (tx) of locally advanced or metastatic urothelial carcinoma (mUC): Final OS from the randomized Phase 3 IMvigor130 study.
Authors: Galsky Matt D. , Arranz Arija Jose Angel , De Santis Maria , Davis Ian D. , Bamias Aristotelis , Kikuchi Eiji , Garcia del Muro Xavier , Park Se Hoon , De Giorgi Ugo , Alekseev Boris , Mencinger Marina , Izumi Kouji , Puente Javier , Li Jian-Ri , O'Donnell Peter H. , Bernhard Sandrine , Lee Chooi Peng , Bene-Tchaleu Fabiola , Mariathasan Sanjeev , Grande Enrique
Published: March 2023

LBA440

Background: The IMvigor130 primary analysis demonstrated statistically significant PFS benefit with 1L atezo + plt/gem (Arm A) vs placebo + plt/gem (Arm C) in pts with mUC (Galsky Lancet 2020). Interim data showed improved OS with Arm A vs C but did not cross the pre-specified threshold for significance (Galsky Lancet 2020; Galsky AACR 2021). In exploratory analyses, OS improved when atezo was combined with cisplatin (cis) vs carboplatin (carbo) regardless of PD-L1 status. Here, we report final OS data from Arms A and C. Methods: Pts were randomly assigned 1:1:1 to Arm A, B (atezo alone) or C. Arm A and C pts received cis or carbo per investigator (INV) choice. Co-primary endpoints were PFS per INV RECIST 1.1 and OS (Arm A vs C), and OS (Arm B vs C), tested hierarchically. Safety, ORR and DOR, disease control rate (DCR; confirmed CR, PR or [SD ≥ 6 mo]) and pre-specified exploratory OS data are also reported. Results: As of data cutoff Aug 31, 2022 (49 mo since last pt randomly assigned), in ITT pts, OS benefit was not statistically significant; in the cis subgroup, HR was 0.76 (95% CI 0.57, 1.01; Table). In ITT pts, DCR was 65% (290/447) in Arm A and 60% (239/397) in Arm C. 81% of safety-evaluable pts (370/454) in Arm A and 80% (312/389) in Arm C had a Gr 3/4 tx-related AE (TRAE). Gr 5 TRAEs occurred in 9 pts (2%) in Arm A and 4 (1%) in Arm C; Gr 3/4 AEs of special interest were seen in 41 pts (9%) in Arm A and 17 (4%) in Arm C. Conclusions: In this final analysis, improved OS with atezo + plt/gem vs placebo + plt/gem did not reach statistical significance in ITT pts with mUC. As seen with prior exploratory data, improved OS with atezo + plt/gem was greater when pts received cis vs carbo. No new safety signals were seen. Clinical trial information: NCT02807636 . [Table: see text]
Extreme bipolar androgen therapy with darolutamide and testosterone cypionate in patients with metastatic castration-resistant prostate cancer: ExBAT (LACOG 0620) trial.
Authors: Isaacsson Velho Pedro H , Girardi Daniel da Motta , Soares Andrey , Fontes Jardim Denis Leonardo , Maluf Fernando Cotait , Morbeck Igor Alexandre , Dias Mariane Fontes , Souza Vinicius Carrera , Silva Adriano Goncalves E , de Jesus Rafaela Gomes , Rebelatto Taiane Francieli , Bastos Diogo Assed
Published: March 2023

TPS276

Background: Prostate cancer has an intrinsic dependence on androgens and androgen receptor (AR) regulation. Suppression of gonadal androgen synthesis known as androgen deprivation therapy (ADT), either by orchiectomy or by pharmacological modulation, represents the treatment backbone of metastatic disease. Unfortunately, almost invariably, patients develop resistance to ADT, progressing to a state called castration-resistant prostate cancer (CRPC), defined as disease progression at serum testosterone levels in the castrate range. Bipolar Androgen Therapy (BAT), consisting of exogenous supraphysiological doses of testosterone followed by castrate levels, has shown clinical activity in multiple early phase clinical trials, in addition to improvement of quality of life (QoL) in CRPC patients. Alternated administration of BAT and novel AR-targeted therapies, a strategy entitled by our group as Extreme Bipolar Androgen Therapy (ExBAT), has never been tested in patients with CRPC. The objective of our study is to assess the ExBAT approach in metastatic CRPC. Methods: ExBAT (NCT04558866) is a phase 2, single-arm, multicenter trial assessing patients with mCRPC who progressed to abiraterone by PCWG3 criteria. Prior docetaxel for metastatic hormone-sensitive disease is allowed if ≥ 12 months elapsed from last dose of docetaxel. Included patients receive testosterone cypionate 400 mg IM on day 1 followed by darolutamide 1,200 mg/day orally for 4 weeks (starting on day 29 through day 56) on 63-day cycles. The primary endpoint is radiographic progression-free survival (rPFS) at 12 months. Secondary endpoints include PSA decline rates, overall survival, toxicity, quality of life, and predictive biomarkers of response/survival. Tumor assessments are performed every 9 weeks, for the first 2 cycles and every 18 weeks thereafter up to 12 months. Patients with disease progression with clinical benefit are allowed to continue treatment. Patients without disease progression after 12 months are allowed to receive study treatment on Extension Phase. The sample size of 47 patients (considering 5% drop-out) was calculated based on the primary endpoint using a two-sided 5% significance level Chi-square Test for One Proportion and achieves 80% power to detect the difference between a 50% rPFS at 12 months comparing with 30% in the historic control group. NCT04558866. From June2021 to September2022, 31 of planned 47 patients have been enrolled in 8 Brazilian centers. Results are not available at the time of submission. Clinical trial information: NCT04558866 .
A phase 1/2 study of REGN4336, a PSMAxCD3 bispecific antibody, alone and in combination with cemiplimab in patients with metastatic castration-resistant prostate cancer.
Authors: Kelly William Kevin , Hussain Arif , Saraiya Biren , Thanigaimani Pradeep , Sun Furong , Seebach Frank A. , Lowy Israel , Sandigursky Sabina , Miller Elizabeth
Published: March 2023

TPS284

Background: Prostate cancer is the leading cause of new cancer diagnoses and the second most common cause of cancer-related death in American men. Prognosis is especially poor for men with metastatic castration resistant prostate cancer (mCRPC). Prostate-specific membrane antigen (PSMA) is highly expressed on malignant prostate tissue but shows limited expression on normal tissue. As such, PSMA is an excellent research target for treatment of mCRPC. REGN4336 is a PSMAxCD3 bispecific antibody designed to facilitate T-cell–mediated killing of PSMA-expressing tumor cells. In preclinical models, REGN4336 demonstrated strong PSMA-dependent antitumor activity that was dose-dependent. Preclinical data also support clinical research into the combination of REGN4336 with cemiplimab (anti–programmed cell death-1) for treating mCRPC. Methods: This is an open-label, Phase 1/2, first-in-human, multicenter dose-escalation study with dose expansion evaluating safety, tolerability, pharmacokinetics (PK), and antitumor activity of REGN4336 administered subcutaneously alone and in combination with intravenous cemiplimab in patients with mCRPC (NCT05125016). Patients must have received at least two prior lines of systemic therapy approved for metastatic and/or castration-resistant disease including a second-generation anti-androgen therapy. In Module 1, REGN4336 as monotherapy is administered weekly but may be extended to once every 3 weeks following identification of the minimal pharmacologically active dose. In Module 2, REGN4336 will be administered in combination with cemiplimab (350 mg) once every 3 weeks after a 4-week REGN4336 monotherapy lead-in cycle. Study therapies are administered until disease progression, intolerable adverse events, withdrawal of consent, or a study withdrawal criterion is met. The primary objectives in dose escalation are to evaluate the safety, tolerability, PK, and recommended phase 2 dosing regimen (RP2DR) of REGN4336 alone and in-combination with cemiplimab. Expansion cohort(s) will be enrolled once RP2DRs have been determined. During the expansion phase, the primary objective is to assess clinical activity, as measured by objective response rate with REGN4336 alone or in combination with cemiplimab per modified Prostate Cancer Working Group 3 criteria. At selected sites, PSMA positron emission tomography/computed tomography scans will be performed at predefined timepoints on study. This study is currently open to enrollment. Clinical trial information: NCT03088540 .
SunRISe-4: TAR-200 plus cetrelimab or cetrelimab alone as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or refuse neoadjuvant platinum-based chemotherapy.
Authors: Psutka Sarah P. , Cutie Christopher , Bhanvadia Sumeet Kaur , Keegan Kirk A. , Crist Wendy , Tian Shaozhou Ken , Maffeo John , Raybold Bradley , Kashmer Marietta , Hasan Mohamad , Li Xiang , Beeharry Neil , Thomas Shibu , Tian Hui , Powles Thomas
Published: March 2023

TPS584

Background: Standard of care for patients (pts) with MIBC is radical cystectomy (RC) with neoadjuvant systemic platinum-based chemotherapy (PBC); however, systemic chemotherapy is associated with significant toxicity. TAR-200 is an intravesical drug delivery system that provides local continuous gemcitabine release within the bladder. SunRISe-4 (NCT04919512) is an open-label, multicenter, randomized phase 2 study designed to assess the efficacy and safety of neoadjuvant TAR-200 + systemic cetrelimab (CET [anti–programmed death-1 antibody]) vs neoadjuvant CET alone in pts with MIBC scheduled for RC who are ineligible for or refuse neoadjuvant PBC. Methods: Eligibility criteria: age ≥18 years, Eastern Cooperative Oncology Group performance status of 0 or 1, histologically confirmed cT2-T4a MIBC with absence of nodal or metastatic disease at screening, and residual intravesical tumor volume of ≤3 cm prior to randomization. Pts will be stratified by completeness of transurethral resection of bladder tumor (TURBT; visibly complete vs incomplete and ≤3 cm) and tumor stage (cT2 vs cT3-4a) at initial diagnosis. Pts (N≈160) will be randomized 5:3 to receive TAR-200 + CET (Cohort 1, n≈100) or CET alone (Cohort 2, n≈60). In Cohort 1, TAR-200 (225 mg gemcitabine) will be placed intravesically at the initial treatment visit; TAR-200 will be removed and replaced over a 12-week period. In both cohorts, CET will be serially dosed intravenously over the same timeframe. Primary disease assessments include axial imaging (at screening and Week 6), centralized review of TURBT (initial diagnostic TURBT or debulking TURBT for pts with lesions >3 cm after initial TURBT) as well as RC and nodal tissue specimens. After RC, all pts will have follow-up visits from Weeks 4 to 108 post RC (end of study). The primary outcome measure is the pathologic complete response rate at time of RC. Secondary outcome measures include safety, tolerability, and recurrence-free survival (per Response Evaluation Criteria in Solid Tumors 1.1 or histologic evidence). Exploratory outcome measures include patient-reported cancer-related quality of life (Functional Assessment of Cancer Therapy–Bladder questionnaire) and pathologic overall response rate at RC. Overall survival and time to symptomatic progression, pharmacokinetics, biomarker analysis, and immunogenicity will also be evaluated. As of September 12, 2022, 2 of 160 planned pts have been enrolled and randomized, and recruitment is ongoing at ≈95 sites. Clinical trial information: NCT04919512 .
A phase 2 basket study of tucatinib and trastuzumab in previously treated solid tumors with HER2 alterations: Urothelial cancer cohort (SGNTUC-019).
Authors: Yu Evan Y. , Jin Fan , Ramos Jorge , Tan Qianwen , Galsky Matt D.
Published: March 2023

TPS587

Background: Tucatinib, a highly selective human epidermal growth factor receptor 2 (HER2)-directed tyrosine kinase inhibitor approved in multiple regions for HER2-positive (HER2+) metastatic breast cancer, is being investigated as a novel therapy for metastatic colorectal cancer, gastric cancer, and other solid tumors. In xenograft models of HER2+ and HER2-mutated tumors, dual targeting of HER2 with tucatinib plus trastuzumab showed superior activity to either alone (Kulukian 2020; Peterson 2020). Despite development of several new therapies for metastatic urothelial cancer (UC), most patients are refractory to subsequent therapies and die from the disease, highlighting the need for additional therapeutic approaches. Given that 20%–30% of metastatic UCs have molecular alterations of the ErbB family, tucatinib plus trastuzumab warrants further evaluation. SGNTUC-019 (NCT04579380) is a multi-cohort, open-label, phase 2 study evaluating tucatinib plus trastuzumab in patients with previously treated solid tumors displaying HER2+ or HER2-mutated solid tumors, including a cohort with locally advanced or metastatic UC. Methods: Eligible patients in the UC cohort must have HER2+ locally advanced or metastatic disease, with progression during or after, or intolerance of, the most recent line of systemic therapy. Patients must have an ECOG PS ≤1; adequate hepatic, hematologic, renal, and cardiac function; and no prior exposure to HER2-directed therapy. HER2 alterations can be demonstrated by HER2 overexpression/amplification in tumor tissue by prior IHC/ISH or by HER2 amplification in prior or prescreening NGS assay of ctDNA or prior tissue NGS assay. The HER2 overexpression/amplification UC cohort will enroll 12 response-evaluable patients per RECIST 1.1. If ≥2 responses are observed, the cohort will be expanded to 30. The primary objective is antitumor activity, with confirmed ORR as the primary endpoint and DCR, duration of response, PFS, and OS as secondary efficacy endpoints. Confidence intervals (CIs) will be calculated for confirmed ORR and DCR. For time-to-event endpoints, median survival time will be estimated by the Kaplan-Meier method, and the associated 95% CI will be calculated using complementary log-log transformation. Safety endpoints will be assessed using descriptive statistics. Patients will receive tucatinib 300 mg orally twice daily and trastuzumab 8 mg/kg intravenously on Cycle 1 Day 1 and 6 mg/kg every 21 days from Cycle 2 Day 1. Disease assessments per RECIST 1.1 will occur every 6 weeks for 24 weeks, then every 12 weeks. Trough concentrations of tucatinib will be evaluated in Cycles 2–6, with peak concentration sampled in Cycle 3. Quality of life will be evaluated every second cycle using the EQ-5D-5L. Sites are currently enrolling within the US, EU, and Asia Pacific. Clinical trial information: NCT04579380 .
CaboCombo: A prospective international non-interventional study of first-line cabozantinib plus nivolumab for the treatment of patients with advanced renal cell carcinoma.
Authors: Barthelemy Philippe , Dutailly Pascale , Qvick Bryan , Perrot Valérie , Verzoni Elena
Published: March 2023

TPS740

Background: The combination of cabozantinib plus nivolumab (Cabo + Nivo) was approved in Europe in 2021 for the first-line (1L) treatment of patients with advanced renal cell carcinoma (aRCC) based on evidence from the phase 3 CheckMate 9ER trial. In the CheckMate 9ER trial (N = 651), Cabo + Nivo improved overall survival (hazard ratio [HR] 0.70 [95% confidence interval: 0.55–0.90]; p = 0.0043) and progression-free survival (HR 0.56 [95% CI: 0.46–0.68]; p ≤ 0.0001) versus sunitinib. There is clinical interest in the effectiveness and tolerability of Cabo + Nivo as used in routine cancer care. Methods: CaboCombo is a prospective, international, real-world non-interventional study to evaluate the effectiveness and tolerability of 1L Cabo + Nivo in adults (aged ≥ 18 years) with aRCC with a clear-cell component. In total 311 patients will be enrolled across 70 centers in countries where 1L Cabo + Nivo has marketing authorization and reimbursement. The decision to prescribe Cabo + Nivo will be made prior to, and independently from, the decision to enroll patients. The primary endpoint is real-world landmark overall survival assessed 18 months after Cabo + Nivo initiation. Secondary endpoints include: real-world treatment patterns; median progression-free survival; objective response rate; duration of response; disease control rate; time to response; treatment-emergent adverse events, and changes in disease-related symptoms and pain during the treatment period (assessed by the Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index – Disease Related Symptoms questionnaire, and the Numerical Pain Rating Scale). Patients will be enrolled over 24 months and followed for up to 42 months. The nature and timing of study visits and assessments will be as per usual care at each participating center; no additional diagnostic or monitoring procedures will be conducted. Treatment will continue until disease progression, unacceptable toxicity or withdrawal of participant consent. Two interim analyses will be conducted, the first a description of baseline characteristics when at least 50% of participants have been recruited. No changes in study design or conduct will be made based on the results of these analyses. Clinical trial information: NCT05361434 .
Correlation of the immune tumor microenvironment (I-TME) with gene expression profiles as prognostic and predictive factors in patients (pts) with metastatic renal carcinoma (mRCC) treated with immunotherapy (Meet-URO 18 I-TME study).
Authors: Catalano Fabio , Murianni Veronica , Rebuzzi Sara Elena , Galuppini Francesca , Buti Sebastiano , Brunelli Matteo , Maruzzo Marco , Dei Tos Angelo Paolo , Basso Umberto , Banna Giuseppe Lugi , Signori Alessio , Sbaraglia Marta , Damassi Alessandra , Cremante Malvina , Puglisi Silvia , Gandini Annalice , Rebuzzi Marta , Mosca Alessandra , Fornarini Giuseppe , Rescigno Pasquale
Published: March 2023

TPS753

Background: Several studies suggested that response to immunotherapy may be influenced by many factors, including peripheral blood biomarkers, the composition of I-TME and different molecular expression pathways. In mRCC patients, immunotherapy has become part of clinical practice, but the identification of patients most likely to respond to checkpoint inhibitors is still an unmet clinical need. Moreover, there are no validated and clinically applicable gene expression panels as prognostic and/or predictive response biomarkers. To date, three major groups of immune-related gene expression were identified in mRCC: the angiogenesis pathway, the T-effector pathway and the mixed pathway (doi: 10.1038/s41598-020-58804-y). Each group of gene expression seems to be responsible for a different type of immune response in the I-TME. However, a significant association with treatment response to immunotherapy has not yet been demonstrated. Methods: The Meet-URO 18 is a multicentric retrospective translational study aimed at identifying distinctive molecular patterns of the I-TME with a prognostic and predictive role in mRCC (primary objective). Pretreated mRCC patients receiving ≥2nd line nivolumab have been divided according to clinical benefit in responders (PFS ≥ 12 months) versus non-responders (PFS ≤ 3 months). Secondary objectives include the correlation between primary tumor and metastases to identify a potential inter-tumor heterogeneity and the correlation with survival and response outcomes. Histological samples of primary tumors and/or metastases have been collected for the transcriptomic analyses together with clinical data of patients from medical records. The transcriptomic characterization of the I-TME of the primary tumor and/or metastases will be performed using the analytical platform "nCounter" of NanoString®, which analyzes the expression of 71 genes involved in angiogenesis, immunomodulation mediated by T-effector response, mechanisms of tumor invasion and mechanisms of calcium channel flows. The gene-panel include a group of 66 genes previously demonstrated to be related in the immune-response in mRCC (doi: 10.1038/s41598-020-58804-y) and 5 housekeeping genes (RPS13, PPIA, RPL27, RP2, B-ACT).
Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: A 10-Year Follow-Up of TAM-01 Study
Authors: Lazzeroni Matteo , Puntoni Matteo , Guerrieri-Gonzaga Aliana , Serrano Davide , Boni Luca , Buttiron Webber Tania , Fava Marianna , Briata Irene M. , Giordano Livia , Digennaro Maria , Cortesi Laura , Falcini Fabio , Serra Patrizia , Avino Franca , Millo Francesco , Cagossi Katia , Gallerani Elisa , De Simone Alessia , Cariello Anna , Aprile Giuseppe , Renne Maria , Bonanni Bernardo , DeCensi Andrea
Published: March 2023

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

PURPOSE

Five-year data of the phase III trial TAM-01 showed that low-dose tamoxifen at 5 mg once daily administered for 3 years in women with intraepithelial neoplasia (IEN) reduced by 52% the recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS), without additional adverse events over placebo. Here, we present the 10-year results.

METHODS

We randomly assigned 500 women with breast IEN (atypical ductal hyperplasia, lobular carcinoma in situ [LCIS], or hormone-sensitive or unknown DCIS) to low-dose tamoxifen or placebo after surgery with or without irradiation. The primary end point was the incidence of invasive breast cancer or DCIS.

RESULTS

The TAM-01 population included 500 women (20% atypical ductal hyperplasia, 11% LCIS, and 69% DCIS). The mean (±SD) age at the start of treatment was 54 ± 9 years, and 58% of participants were postmenopausal. After a median follow-up of 9.7 years (IQR, 8.3-10.9 years), 66 breast cancers (15 in situ; 51 invasive) were diagnosed: 25 in the tamoxifen group and 41 in the placebo group (annual rate per 1,000 person-years, 11.3 with tamoxifen v 19.5 with placebo; hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.95; log-rank P = .03). Most recurrences were invasive (77%) and ipsilateral (59%). Regarding contralateral breast cancer incidence, there were six events in the tamoxifen arm and 16 in the placebo arm (HR, 0.36; 95% CI, 0.14 to 0.92; P = .025). The number needed to be treated to prevent one case of breast event with tamoxifen therapy was 22 in 5 years and 14 in 10 years. The benefit was seen across all patient subgroups. There was a significant 50% reduction of recurrence with tamoxifen in the DCIS cohort, which represents 70% of the overall population (HR, 0.50; 95% CI, 0.28 to 0.91; P = .02). No between-group difference in the incidence of serious adverse events was reported during the prolonged follow-up period.

CONCLUSION

Tamoxifen 5 mg once daily for 3 years significantly prevents recurrence from noninvasive breast cancer after 7 years from treatment cessation without long-term adverse events.
The Perioperative Frontal Relative Ratio of the Alpha Power of Electroencephalography for Predicting Postoperative Delirium After Highly Invasive Surgery: A Prospective Observational Study
Authors: Kinoshita Hirotaka , Saito Junichi , Kushikata Tetsuya , Oyama Tasuku , Takekawa Daiki , Hashiba Eiji , Sawa Teiji , Hirota Kazuyoshi
Published: March 2023

BACKGROUND:

We investigated the associations between postoperative delirium (POD) and both the relative ratio of the alpha (α)-power of electroencephalography (EEG) and inflammatory markers in a prospective, single-center observational study.

METHODS:

We enrolled 84 patients who underwent radical cancer surgeries with reconstruction for esophageal cancer, oral floor cancer, or pharyngeal cancer under total intravenous anesthesia. We collected the perioperative EEG data and the perioperative data of the inflammatory markers, including neutrophil gelatinase-associated lipocalin, presepsin, procalcitonin, C-reactive protein, and the neutrophil-lymphocyte ratio (NLR). The existence of POD was evaluated based on the Intensive Care Delirium Screening Checklist. We compared the time-dependent changes in the relative ratio of the EEG α-power and inflammatory markers between the patients with and without POD.

RESULTS:

Four of the 84 patients were excluded from the analysis. Of the remaining 80 patients, 25 developed POD and the other 55 did not. The relative ratio of the α-power at baseline was significantly lower in the POD group than the non-POD group (0.18 ± 0.08 vs 0.28 ± 0.11, P < .001). A time-dependent decline in the relative ratio of α-power in the EEG during surgery was observed in both groups. There were significant differences between the POD and non-POD groups in the baseline, 3-h, 6-h, and 9-h values of the relative ratio of α-power. The preoperative NLR of the POD group was significantly higher than that of the non-POD group (2.88 ± 1.04 vs 2.22 ± 1.00, P < .001), but other intraoperative inflammatory markers were comparable between the groups. Two multivariable logistic regression models demonstrated that the relative ratio of the α-power at baseline was significantly associated with POD.

CONCLUSIONS:

Intraoperative frontal relative ratios of the α-power of EEG were associated with POD in patients who underwent radical cancer surgery. Intraoperative EEG monitoring could be a simple and more useful tool for predicting the development of postoperative delirium than measuring perioperative acute inflammatory markers. A lower relative ratio of α-power might be an effective marker for vulnerability of brain and ultimately for the development of POD.
Feinting Repeats, Repeating Feints: The Developmental “Double Return” in Brahms and Sonata Theory Typology
Authors: Taylor Benedict
Published: March 2023

One of the most prominent characteristics of Johannes Brahms's approach to sonata form is the return to the tonic at the start of the second section (or “rotation”) for a restatement of the exposition's primary theme. Well-known examples include the finales of the First and Third Symphonies, the opening movements of the G-minor Piano Quartet and Fourth Symphony, and the Tragic Overture. This common basic principle can nevertheless underpin a variety of formal typologies. Ostensibly a three-part sonata form with developmental double return would be most likely labeled a sonata rondo (type 4 in Hepokoski and Darcy's sonata theory), while a two-part design is so typical of Brahms's practice that it has become known as a “Brahmsian deformation” (expanded type 1). Yet numerous cases exist in which neither reading above is permitted—most notably, three-part sonata forms with developmental double return used as opening movements. In these cases sonata theory is left classifying these designs as a conventional type 3 sonata with an expositional repeat feint. There are some serious problems, however, with this interpretation. First is the sheer number of pieces in which this double return occurs; in fact, after 1878 Brahms is more likely to “feign” a repeat than to provide one. Second, how the primary theme returns is hardly ever identical to its opening appearance and can rarely be confused with an exposition repeat (the op. 25 Quartet and Fourth Symphony are exceptions in this sense). Exploring these works, the author proposes a new subtype of the type 3 sonata to classify Brahms's mature practice, called “type 34.” Ultimately, though, these findings may lead to questions regarding the efficacy of a classically oriented typology confronted with late nineteenth-century practice.
Performance Spaces for Improvised and Notated Music
Authors: Andersen Drake
Published: March 2023

Abstract compositional spaces have long been used to illustrate structural relationships within and between musical works. However, despite robust scholarship employing spaces to depict the possibilities available to composers, space-based analytical methods have rarely been used to study the performance of music. Through case studies drawn from improvised and notated music, this article introduces the questions and methodologies by which analogous spaces for performance, which the author terms performance spaces, may be generated and analyzed. The author also considers the unique properties of hybrid spaces that combine the tools of discrete mathematics, such as graphs, with distance-based metrics.
POST HOC ANALYSIS ON THE INCIDENCE OF CONGENITAL HEART DISEASE IN BAKU-AZERBAIJAN CALCULATED BY A PROSPECTIVE EPIDEMIOLOGY STUDY
Authors: Petropoulos Andreas
Published: March 2023

Background: The incidence of Congenital Heart Disease (CHD)in Azerbaijan was firstly published following  a prospective study, using Echo-2D as a study method, in 2019.

Aim:  Of this post hoc analysis of the first ever prospective epidemiology study that calculated incidence and types of CHD in Baku, Azerbaijan, is to verify the forms of diseases that will have and early clinical impact on the patients and the health system of the country.

Population-method: From June 2016 to August 2018, 2570, term neonates were screened in 2 major state maternity hospitals in Baku. Their screening was randomized to equal females/males with not known previous obstetric alert regarding CHD. Scanning was done by two teams of pediatric cardiologists by using echo-2D. Each team was ‘blinded’ to the findings of each other. All scans were recorded, and a third senior physician reevaluated them.

Results: From 2570 term neonates of the general population, they detected 47 CHD’s. From them, 17 were critical and severe-CHD and 7/47(14.9%) were  of moderate complex. 17/47 (36.2%) were cyanotic and 30/47(63.8%) were non-cyanotic. The incidence of simple CHD was 25/47(53.2%). Analysis of the specific anatomy is presented in table1. The estimated incidence was 1.83%.  As this incidence has been among the highest reported a post hoc analysis has clarified and presented an important clinical rate of 1.48% after redacting minimal defects without any clinical significance, as minor PDA’s, ASD II, VSD’s. A post hoc calculation of BAov, revealed an anatomical BAov incidence of 1.65% and a functional BAov incidence of 1.4%.

Conclusions: This first-ever prospective epidemiology study in Azerbaijan involving a cohort equal to 1.65% of the annual living births of the country, estimated a high incidence of CHD. This is among the highest reported globally.  The amount of critical and severe CHD after the post hoc analysis increased from 46.8% to 55.3%. The incidence of cyanotic CHD after the post hoc analysis increased from 36.2% to 42.1%.  These high numbers are possibly related to an isolated population and conjugated marriage customs of the country. As this represented a state population health burden a post hoc analysis based on clinical important CHD minimized the calculated index nearby 20%.
General versus spinal anesthesia in percutaneous nephrolithotomy: A systematic review and meta-analysis
Authors: Indra Rachman Rinaldo , Birowo Ponco , Nurullah Ghifari , Cho Prof. Sung Yong , Atmoko Widi , Widyahening Indah Suci , Rasyid Nur
Published: March 2023

Background: Percutaneous nephrolithotomy (PCNL) is the preferred treatment for the removal of large kidney stones, sized >20 mm. However, there is still an ongoing debate concerning the best anesthesia for PCNL. This study aimed to compare the efficacy and safety between general and spinal anesthesia for PCNL.

Methods: A systematic review and meta-analysis study. A systematic, electronic literature search was performed in several databases, including PubMed, Scopus, and Google Scholar until July 1st, 2022. The quality of the articles was examined using Crombie's Items (for non-randomized controlled trials (RCTs)) and Jadad Scale (for RCTs). The outcomes assessed were operation time, fluoroscopy time, length of stay, stone-free rate, overall complication rate, specific postoperative complications, cost, pain score, and postoperative analgesic requirement. The article selection was reported based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We assessed four RCTs and eight retrospective studies. Meta-analysis of selected studies was performed using the Review Manager 5.3.

Results: General anesthesia resulted in fewer Clavien–Dindo grade II (OR: 0.68; 95% CI: 0.49 – 0.94; p=0.02), major complications (OR: 0.65; 95% CI: 0.45 – 0.94; p=0.02, and lower transfusion rates (OR: 0.70; 95% CI: 0.53 – 0.94; p=0.02). Whereas spinal anesthesia resulted in faster operation time (Mean Difference: -12.98; 95% CI: -20.56 – -5.41; p<0.001, fluoroscopy time (MD: -26.15; 95% CI: -42.79 – -9.50; p=0.002), reduced length of stay (MD: -0.47; 95% CI: -0.75 – 0.20; p<0.001), and lower postoperative analgesic requirement and cost. No significant difference in stone-free rate (OR: 1.08; 95% CI: 0.92 – 1.26; p=0.37). PCNL performed using either general anesthesia or spinal anesthesia is equally safe and effective.

Conclusions: Each method of anesthesia has its own advantages and disadvantages. The final choice between general and spinal anesthesia should be based on the patient's condition and surgical team preference.
Knowledge and Practice of Herbal Medicine on Oral Health among Dental Personnel in Malaysia
Authors: Tabnjh Abedelmalek , W Ahmad Wan Muhamad Amir , Hasan Ruhaya , bin Sinor Mohd Zulkarnain , de Abreu Mauro Henrique Nogueira Guimarães , Wong Ling Shing , Djearamane Sinouvassane , Selvaraj Siddharthan
Published: March 2023

Objective: To investigate the association between knowledge and practice of medical herbs related to oral heath among staffs at School of Dental Sciences, Universiti Sains Malaysia, Malaysia.

Methods: A cross-sectional study was conducted at the School of Dental Sciences, USM, on 100 lecturers, dental surgery assistants, nurses, administrative workers, and dental technicians. A set of knowledge and practice questionnaire was used in this study. Descriptive statistics, chi-square and correlation were used to analyze the data.

Results: The results showed that the dental staff's knowledge of oral herbal medicines was 32.8%. This indicates that they had a moderate level of knowledge. Almost three-quarters of the employees (73%) practiced at a low level (0-25%), while only 13.85% practiced at a moderate level. The findings revealed that there was no significant relationship between knowledge and practice scores and age or gender. The results, from the other hand, revealed a significant association between practice scores and the type of occupations among staff (P=0.04). The Correlation analyses shows a moderately positive relationship between knowledge and practice.

Conclusions: Dental staff had a moderate level of knowledge and a poor level of practice with regard to herbal medicines for oral health. There was a significant association between age and knowledge and there was a significant association between the knowledge and practice among the dental personnel
How academic sabbaticals are used and how they contribute to research – a small-scale study of the University of Cambridge using interviews and analysis of administrative data
Authors: Ioppolo Becky , Wooding Steven
Published: March 2023

Background: Academic sabbaticals are seen as an important aspect of academic life and require considerable resources, however, little research has been done into how they are used and whether their effects can be measured. We explored these issues at the University of Cambridge.

Methods: A mixed method approach including 24 interviews with academics, eight interviews with administrators; alongside analysis of administrative and publication data between 2010 and 2019.

Results: Academics underline the importance of sabbaticals in providing uninterrupted time for research that is used to think, explore new ideas, master new techniques, develop new collaborations, draw together previous work, set work in a wider context, and provide personal discretion in research direction. They also highlight sabbaticals’ contributions in allowing the beneficial effects of combining teaching and research, while mitigating some of the disadvantages. However, it is difficult to detect the effect of sabbaticals on publications using a time series approach.

Conclusions: Sabbaticals provide manifold contributions to academic research at the University of Cambridge; however, detecting and quantifying this contribution, and extending these findings requires wider and more detailed investigation.
Impact of obesity on periodontal condition - a systematic review of literature
Authors: Bartosik-Zielińska Diana , Bartosik Magdalena , Blicharz Monika , Blicharz Agnieszka , Swatko Tomasz
Published: March 2023

Introduction: In recent years, more and more of the population is overweight and obese. Adipose tissue is a metabolically active tissue that releases adipocytokines and inflammatory hormones. As a result of the excess amount of adipose tissue in the body, the risk of systemic diseases as well as diseases occurring in the oral cavity, including periodontitis, increases.
Aim of the study: A systematic review of the existing evidence on the association between overweight/obesity and periodontitis.
Materials and methods: The literature available in the PubMed database was perfomed, using the following keywords: obesity and periodontitis; obesity; periodontal disease; overweight; periodontitis.
Results: The results of the presented studies indicate a positive correlation between overweight and obesity and periodontitis. In many publications, the odds ratio for periodontitis increased with increasing BMI. In addition, a high WC rate is associated with an increased incidence of periodontitis. Pro-inflammatory mediators responsible for the development and advancement of periodontitis are produced, among others, by adipose tissue.
Conclusion: An increased amount of adipose tissue as a metabolically active tissue, secreting pro-inflammatory mediators, can significantly affect the development and periodontitis. Therefore, overweight and obese people with a high BMI and WC may have a higher risk of periodontitis.
HACIA EL PERFIL DEL AUXILIAR DE CONVERSACIÓN EN EL CONTEXTO EUROPEO: CARACTERÍSTICAS, ROLES Y FUNCIONES EN EL SIGLO XXI.
Authors: López Medina Beatriz , Otto Ana
Published: March 2023

En el contexto europeo, los auxiliares de conversación (LAs) han formado parte de las clases de lenguas extranjeras durante más de un siglo. Los LAs, considerados actualmente un valioso recurso para los estudiantes de idiomas, trabajan en contextos similares en todo el continente (colegios, universidades, escuelas de idiomas) y, en teoría, deberían desempeñar las mismas funciones en sus países de acogida. Sin embargo, en la práctica, las características principales y las funciones previstas pueden diferir según el país anfitrión. El objetivo de este estudio es doble: en primer lugar, comparar las funciones de los auxiliares de conversación entre cuatro países europeos (Francia, Italia, España y Austria). A tal efecto, se tomaron como referencia las guías publicadas en países anfitriones y dirigidas a los LAs. En segundo lugar, destacar las características que mejor identifican y definen a los auxiliares de conversación europeos. Para este análisis, se utilizó un estudio comparativo entre países siguiendo el enfoque de la Teoría Fundamentada con el software MAXQDA. Los resultados del análisis indican que los auxiliares de conversación proceden de diferentes entornos educativos y han recibido información básica sobre el país de acogida y sobre cuestiones pedagógicas y metodológicas. Se les considera principalmente embajadores de la lengua y la cultura de origen, y trabajan en asociación con un profesor mentor o supervisor que dirige la clase. Se espera que este trabajo contribuya a crear un perfil europeo del auxiliar de conversación en el siglo XXI, que resulte útil tanto para los auxiliares actuales como los de futuro y los responsables encargados de crear estas guías.
LAS PRESENTACIONES EN LOS CONGRESOS TWITTER: UN ANÁLISIS RETÓRICO Y SEMIÓTICO DE UN GÉNERO DIGITAL EMERGENTE.
Authors: Villares Rosana
Published: March 2023

Entre las responsabilidades de los investigadores se encuentra la comunicación y difusión del conocimiento científico. Sin embargo, esta tarea ha ido evolucionando con el tiempo y han surgido nuevas formas de comunicación digital. Este estudio explora las estrategias de comunicación de ciencia empleadas por los científicos en un género digital emergente, las presentaciones en los congresos Twitter. Un corpus de 55 presentaciones (300 tweets) se analizó empleando los marcos teóricos y metodológicos del análisis de género y de recursos semióticos. Los resultados muestran que los investigadores reutilizaron su conocimiento previo de otros géneros académicos orales en el nivel macro-estructural mientras que en el nivel micro-estructural se encontró un mayor dinamismo retórico. Con respecto a los recursos semióticos, la estrategia más empleada por los autores fue el uso de imágenes e hipervínculos. Las interrelaciones más comunes entre texto y otros recursos semióticos fueron las funciones de concurrencia y complementariedad. De esta forma, gracias a la combinación de recursos, los autores pudieron reforzar las ideas mencionadas en el texto y ofrecer información adicional para continuar explorando los temas de investigación. Este estudio contribuye a la investigación actual sobre comunicación científica a través de la descripción y análisis de los géneros digitales emergentes.
Acute onset of bullous skin rash and acute kidney injury after exposure to radiocontrast: Sweet's syndrome
Authors: Abdelnabi Mahmoud , Cavazos Annia , Pruneda Corley , Thongpiya Jerapas , Yingchoncharoen Pitchaporn , Sullivan Sierra , Davalos Jesus , Tarbox Michele
Published: March 2023

Sweet's syndrome or acute febrile neutrophilic dermatosis is characterized by an acute inflammatory skin eruption of oedematous and erythematous papules, plaques or nodules, accompanied by fever, and leucocytosis with possible extracutaneous involvement. Aetiologies include infections, inflammatory bowel disease, pregnancy or malignancy, or the syndrome may be drug-induced by many classes of medications or very rarely, radiocontrast exposure. Herein, the authors report a case of radiocontrast-induced bullous Sweet's syndrome and contrast-induced acute kidney injury in a woman in her 60s with a complex medical history.