bluuebunny/crossref_metadata_2025 huggingface dataset:
The inflationary effect of the budget deficit: does financial sector development matter?
Authors: Aragaw Abebe
Published: June 2024

This study aims to examine the budget deficit–inflation relationship, considering financial sector development and broad money supply as moderating and mediating variables. For this purpose, a panel data set ranging from polled mean group, mean group, and dynamic fixed effect estimation techniques are employed. Hence, the pooled mean group estimation result reveals that the budget deficit is inflationary. In addition, GDP per capita, the effective exchange rate, financial sector development, regulatory quality, and the interaction term of the budget deficit and financial sector development are significant determinants of inflation. The study further examines the role of the broad money supply as a mediating variable in the budget deficit–inflation relationship. The structural equation model results and the mediation effect tests confirmed a partial mediation effect of the broad money supply on the budget deficit–inflation relationship. Based on the findings, it is recommended to strengthen regulatory quality, reduce broad money supply, and improve financial sector development. By doing so, we can create a more stable and efficient economy that benefits everyone in the long run.
Effect of social and behavioral change interventions on minimum dietary diversity among pregnant women and associated socio-economic inequality in Rajasthan, India
Authors: Sharma Anshita , Chanda Srei , Porwal Akash , Wadhwa Namita , Santhanam Divya , Ranjan Raghwesh , Shah Hemang , Adyanthaya Shachi , Meena Ramavatar
Published: June 2024

Background

Maternal dietary diversity is a key to improving the birth and child health outcomes. Besides socio-economic factors, the nutrition specific program- Social and Behavioural Change Communication (SBCC) interventions aimed to improve maternal dietary diversity has varied levels of impact on the socio-economic groups in poor resource setups.

Objective

To measure the factors associated with the minimum dietary diversity (MDD) among pregnant women in selected districts of Rajasthan with special emphasis on the SBCC components. Additionally, it measures the socio-economic gaps in the behaviour of consumption of diversified diet during pregnancy.

Methods

Data from a cross sectional survey of 6848 pregnant women, who have received a continuous SBCC counselling and registered under a state introduced conditional cash transfer program, during May to June, 2023, in five intervention districts -Banswara, Baran, Dunagrpur, Pratapgarh and Udaipur in Rajasthan was used. A 24 h recall based food consumption behaviour has been gathered to measure the MDD of pregnant women. Study has used descriptive statistics, multivariate regressions, and multivariate decomposition analysis to address the research objectives.

Results

Study finds that only 55.2% of pregnant women are consuming diverse diet in the study duration with mean dietary diversity score is 4.8 (+/- 1.5). Logistic regression finds that SBCC components such as frontline workers (aOR = 1.3, CI: 1.1–1.4), community motivators (aOR = 1.9, CI: 1.7–2.1), and participation in MCHND (aOR = 1.0, CI: 0.9-1.2) have significant and higher likelihood on consumption of MDD food on previous day. A higher education and belonging from richer wealth quintile also show higher association for consumption of MDD. Multivariate decomposition shows, among richest and poorest wealth categories there is 19% point difference (58% difference due to coefficient vs. 42% difference due to composition) in MDD consumption. This is positively contributed by the caste and educational categories of women.

Conclusion

Despite a predominant vegetarian diet consuming population, better maternal dietary diversity was observed among those exposed to higher dose of SBCC intervention package. Educational status and caste of the respondent were significantly associated with minimum dietary diversity and contributed to the socio-economic inequality highlighting the importance of tailored and sustained SBCC interventions.
The relationship between body composition and left ventricular performance in women with breast, lymphoma, or sarcoma cancer
Authors: Mabudian Leila , Reding Kerry , D’Agostino Ralph B. , Heiston Emily M. , Bellissimo Moriah P. , Olson Kristine , Ntim William O. , Klepin Heidi D. , Dressler Emily V. , Moore Tonya , Jordan Jennifer H. , O’Connell Nathaniel S. , Ladd Amy , Weaver Kathryn E. , Ky Bonnie , Wagner Lynne I. , Hackney Mary Helen , Lesser Glenn J. , Hundley W Gregory ,   The UPBEAT Study Team
Published: June 2024

Background

To understand how body composition in those with elevated body mass index impacts left ventricular function decline during cancer treatment, we determined the association between baseline body mass index (BMI), intra-abdominal adipose tissue (IAT) and subcutaneous adipose tissue (SAT) with baseline to 3-month left ventricular ejection fraction (LVEF) change among women receiving potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or sarcoma.

Methods

Women underwent potentially cardiotoxic chemotherapy, such as doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab, for treatment of breast cancer, lymphoma, or sarcoma. We obtained magnetic resonance images (MRIs) of body composition and cardiac function prior to treatment, and then a repeat MRI for cardiac function assessment at three months into treatment. Analyses and assessment of abdominal adipose tissue volumes and LVEF outcomes were conducted by independent reviewers blinded to all patient identifiers. A general linear model was created to examine associations between adipose tissue depots, BMI, and 3-month LVEF change.

Results

Women (n = 210) aged 56 ± 11 years with breast cancer, lymphoma, and sarcoma were enrolled (n = 195, 14, 1 respectively). Baseline BMI, IAT, and SAT fat were independently associated with 3-month LVEF declines (p = 0.001 to 0.025 for all). After adjusting for baseline cardiovascular disease risk factors, BMI, IAT, and SAT, BMI remained the only variable associated with 3-month LVEF decline (p = 0.047).

Conclusions

These results suggest that factors other than abdominal adipose tissue or traditional cardiovascular risk factors may contribute to 3-month declines in LVEF among women with elevated BMI receiving potentially cardiotoxic chemotherapy. Further investigation should be conducted on psychosocial stress, physical activity, sleep, or diet.

Trial registration

DETECTIV_NCT01719562, WF99112, & WF97415—NCT02791581.
The achievement of pre-operative expectations in patients undergoing knee arthroplasty: a cohort study evaluating unique patient goals
Authors: Karunaratne Sascha , Harris Ian Andrew , Horsley Mark , Trevena Lyndal , Solomon Michael
Published: June 2024

Background

Total knee arthroplasty (TKA) is a common procedure employed to treat end-stage osteoarthritis. While TKA is generally believed to have acceptable outcomes, many patients report pain or functional deficits not in line with their expectation following the procedure. It has been postulated that patient’s pre-operative expectations regarding post-operative treatment outcomes play a significant role in satisfaction. It is therefore important to assess if the outcomes of surgery truly align with patient’s individual expectations. Thus, the purpose of this study was to determine the degree to which patient expectations of TKA are achieved and the contribution of TKA to achieving patient goals one year after surgery.

Methods

A consecutive sample of 110 patients booked for total knee arthroplasty were asked to identify their most important goals to inform the Direct Questioning of Objectives Index (DQO Index, range 0 to 1) and identify their surgical goals and grade their expectation that a knee arthroplasty would achieve each goal on an 11-point scale. One year after surgery, the DQO Index was repeated to assess their current ability to achieve each pre-operative goal, and asked to estimate the contribution of their knee arthroplasty in achieving each goal. Mean differences between baseline and one year follow-up were calculated regarding the DQO Index and expected achievement of pre-operative goals.

Results

According to the DQO Index at one year, patients improved from a poor quality of life pre-operatively (mean ± standard deviation: 0.20 ± 0.18) to moderately high quality of life (mean ± standard deviation: 0.71 ± 0.21) reflecting a large improvement in ability to achieve each goal. Although achievement improved, for each goal, the patient estimates of the extent to which the knee arthroplasty had contributed to achieving the goal was lower than their initial expectation provided pre-operatively (mean difference range: 0.6 to 1.9 on an 11-point scale).

Conclusion

Patients undergoing TKA have high expectations that their surgery will address their primary goals. Despite surgery largely achieving these goals (improved pain and function), the extent to which the goals were achieved was lower than patients had expected pre-operatively.
Diagnosis and treatment of Parkinson´s disease (guideline of the German Society for Neurology)
Authors: Höglinger Günter ,   German Parkinson’s Guidelines Committee, Bähr Mathias , Becktepe Jos , Berg Daniela , Brockmann Kathrin , Buhmann Carsten , Ceballos-Baumann Andrés , Claßen Joseph , Deuschl Cornelius , Deuschl Günther , Dodel Richard , Ebersbach Georg , Eggers Carsten , van Eimeren Thilo , Fanciulli Alessandra , Fimm Bruno , Folkerts Ann-Kristin , Gausepohl Madeleine , Hasan Alkomiet , Hermann Wiebke , Hilker-Roggendorf Rüdiger , Höglinger Günter , Höllerhage Matthias , Hopfner Franziska , Jost Wolfgang , Kalbe Elke , Kassubek Jan , Klebe Stephan , Klein Christine , Klietz Martin , Koeglsperger Thomas , Kühn Andrea , Krack Paul , Krismer Florian , Kuhlenbäumer Gregor , Levin Johannes , Liepelt-Scarfone Inga , Lingor Paul , Loewenbrück Kai , Löhle Matthias , Lorenzl Stefan , Maaß Sylvia , Maetzler Walter , Menzel Regina , Meyer Philipp T , Mollenhauer Brit , Neumann Manuela , Odin Per , Outeiro Tiago , Pötter-Nerger Monika , Reese René , Reetz Kathrin , Rieß Olaf , Ruf Viktoria , Schneider Anja , Schrader Christoph , Schnitzler Alfons , Seppi Klaus , Sixel-Döring Friederike , Storch Alexander , Tönges Lars , Trenkwalder Claudia , Walter Uwe , Wächter Tobias , Warnecke Tobias , Wegner Florian , Winkler Christian , Witt Karsten , Woitalla Dirk , Zeuner Kirsten , Trenkwalder Claudia
Published: June 2024

Introduction

The aim of this German national guideline is to optimize the clinical care of patients with Parkinson's disease (PD) in terms of diagnostics, drug and surgical treatment and care.

Summary or definition of the topic

This guidance was prepared for the German Society of Neurology (DGN) in collaboration with the Austrian Society of Neurology (ÖGN) and the Swiss Neurological Society (SNG) for German-speaking countries. The guidelines for the diagnosis and treatment of PD have been revised by a national expert group and the guideline commission of the DGN at S2k level. The main objective of these guidelines is to optimize the clinical care of PD patients regarding diagnosis, including early detection, technical diagnostic examinations, and pharmacological as well as invasive treatment options.

Recommendations

The updated PD diagnosis and treatment guidelines are emphasizing optimized clinical care. Key revisions include preferring the name "Parkinson's disease" over previous terms and adopting International Parkinson and Movement Disorder Society (MDS) diagnostic criteria. Recommendations cover genetic and imaging diagnostics, initial pharmacotherapy considering efficacy and patient factors, and tailored pharmacological combinations for complications. Guidelines extend to managing cognitive, affective, psychotic, and autonomic symptoms, along with non-oral therapies like pump therapy and deep brain stimulation. Special situations like akinetic crisis, driving ability, and care concepts are addressed, ensuring comprehensive management for PD patients at various stages and conditions.

Conclusions

This guidance reflects the state of the art at the beginning of 2024.
Prevalence and predictors of depression, anxiety, and stress among refugees in Egypt
Authors: El-Ghitany Engy M. , Ashour Ayat , Elrewany Ehab , Farghaly Azza G. , Shata Zeinab
Published: June 2024

Background

Many Refugees show multiple distressing psychological and mental health problems associated with stressful and adverse conditions in host countries. Even though Egypt is one of the top five destination countries hosting refugees and asylum-seekers in the MENA region, there is a lack of studies investigating mental health problems among refugees in Egypt. This study aimed to assess the prevalence and predictors of depression, anxiety, and stress symptoms among refugees living in Egypt.

Methods

A total of 398 refugees aged 18 and above were interviewed from migrants’/refugees' community centers in Giza, Alexandria, Dakahlia, and Damietta governorates. A predesigned structured interview questionnaire was used to collect socio-demographic and migration-related variables. The Arabic Version of Depression Anxiety Stress Scales (DASS-21) was used to assess the presence and severity of the three negative emotional states.

Results

Nearly two-thirds of the participants were Syrian (66.4%). The majority resided in Alexandria and Giza governorates (75.9%), were females (73.4%), and were married (71.1%). The most reported migration difficulty was housing (41.5%). Anxiety symptoms were reported among 63.3% (95% CI: 58.59%- 68.05%) of sampled refugees, followed by depression (61.3%, 95% CI: 56.52%-66.10%), and stress symptoms (51.5%, 95% CI: 46.56%-56.36%). Results of regression analysis showed that; female gender predicted anxiety (aOR 2.419, 95% CI: 1.485–3.941, p < 0.001) and stress (aOR 2.053, 95% CI: 1.197–3.519, p = 0.009), while younger age groups (18–25 yr. and 26–50 yr.) compared to the older age group (51 yr. and older) predicted depression (aOR 4.529, 95% CI: 1.696–12.097, p = 0.003 and aOR 2.177, 95% CI: 1.270- 3.733, p = 0.005, respectively) and stress (aOR 4.334, 95% CI: 1.556–12.074, p = 0.005 and aOR 1.808, 95% CI: 1.023–3.193, p = 0.041, respectively). Residence in Alexandria, housing, and employment difficulties predicted anxiety (aOR 2.354, 95% CI: 1.420–3.902, p < 0.001, aOR 1.726, 95% CI: 1.073–2.778, p = 0.025, and aOR 3.044, 95% CI: 1.248–7.425, p = 0.014, respectively), depression (aOR 1.949, 95% CI: 1.163–3.266, p = 0.011, aOR 1.666, 95% CI: 1.036–2.681, p = 0.035, and aOR 3.216, 95% CI: 1.321–7.828, p = 0.010, respectively), and stress (aOR 2.450, 95% CI: 1.431–4.195, p < 0.001, aOR 1.911, 95% CI: 1.187–3.078, p = 0.008, and aOR 4.482, 95% CI: 1.867–10.760, p < 0.001, respectively).

Conclusion

Mental health problems are prevalent among the refugee population in Egypt that are compounded by the difficult post-migration socio-economic situation. Multisectoral attention towards refugees’ mental health is urgently needed.
Ultrasound-guided foam sclerotherapy versus four-layer compression only for treatment of chronic venous ulcers
Authors: Issa Ahmed Sayed Ibrahim , Ibrahim Riham , Ayad Michael Samuel , Nagy Momen , Zaher Azza M. Abdel , Yassin Ahmed M.
Published: June 2024

Background

Chronic venous ulcers are prevalent, its incidence (1%) in the general population. Venous ulcers are quite a challenge for physicians to treat. Among the numerous pathological causes, venous hypertension remains the leading cause. This study aims to compare the safety, efficacy, short-term complications, factors affecting wound healing as well as pathological outcomes of ultrasound-guided foam sclerotherapy (UGFS) in conjunction with the four-layer compression bandage in the management of chronic venous ulcers.

Methods

Retrospective analysis of a hundred patients with chronic venous ulcers treated between December 2018 and December 2021. Two groups were studied: the control group, which received conventional compression, and the study group, which underwent injection sclerotherapy and conventional compression. Punch skin biopsies were taken from both groups before and after treatment to compare the histological effects of the two methods.

Results

Complete healing was achieved in 100% of the patients, with a shorter healing time in the study group (34.82 ± 4.7). Additionally, the degree of inflammation was significantly decreased but there was a higher local complication rate in the study group.

Conclusions

UGFS in conjunction with the compression bandage showed superior clinical and pathological results but, risk of complication was increased.
Role of diaphragmatic ultrasound in predicting weaning success from mechanical ventilation in pediatric intensive care unit
Authors: Eskander Amir Maurice , Abd-Elhameed Abeer Maghawry , Osman Noha Mohamed , Magdy Sondos Mohamed , ElKess George Ezzat
Published: June 2024

Background

Weaning off mechanical ventilation (MV) is a critical step in pediatric ICU; however, it lacks standardized criteria. Diaphragmatic ultrasound parameters like diaphragm thickening fraction (DTF), diaphragmatic excursion (DE) and time to peak inspiratory amplitude (TPIA) can be used to assess diaphragmatic muscle strength and to predict weaning success.

Aim of study

Is to assess the validity of diaphragmatic ultrasonography as a predictor of weaning outcome from mechanical ventilation in pediatric age group.

Methods

Prospective cohort study including 30 pediatric patients aged 0–18 years on mechanical ventilation. Ultrasound measurements of diaphragmatic thickening fraction, diaphragmatic excursion and time to peak inspiratory amplitude were taken during the spontaneous breathing trial (SBT) and compared between successful and failed weaning groups.

Results

Out of the included 30 patients (50% male), 19 patients (63.3%) were successfully weaned. Mechanical ventilation duration was significantly longer in the failed weaning group (P = 0.017). There was significant difference between both groups regarding right DE (P = 0.032) and left DE (P = 0.022) with cutoff values of > 4.1 mm and > 5.5 mm with AUC (Area under curve) of 0.737 and 0.831, respectively. There was no statistically significant difference between both groups regarding DTF or TPIA.

Conclusion

We have found that DE is a predictor of weaning success, while DTF and diaphragmatic TPIA had no correlation with weaning outcome.
From parental responsibility towards mutual understanding: reimagining the employment of epigenetic knowledge
Authors: Moormann Emma
Published: June 2024

This paper is interested in normative translations of findings in intergenerational epigenetics. Particularly, what role can and should epigenetic knowledge play in our normative thinking about parenthood and relationships such as those between individual parents and broader society or between parents and their children? How should epigeneticists engage in science communication to ensure that knowledge of intergenerational epigenetic effects is useful rather than harmful to parents and children? Much of the existing literature on the ethical aspects of epigenetics points out worrisome tendencies of epigenetic knowledge inspiring policies and discourses that lead to blaming and stigmatization of individual parents and women in particular. While such warnings are important, they are not the only shape ethical discussion of intergenerational epigenetics can take. Firstly, this paper claims that it is also worthwhile and necessary to imagine potential positive effects of epigenetic knowledge on parents and their children. It will be argued that an approach that focuses on empowerment of individual parents and children rather than general responsibility distributions fits will with a nonideal approach to normative theory that takes into account the unequal distributions of social, economic and material resources among parents. The second part of this paper explores whether narrative identity is a useful concept to imagine such a positive framework for the employment of epigenetic knowledge. It argues that integration of epigenetic knowledge in a shared narrative identity may benefit mutual understanding and self-knowledge, and perhaps also have an empowering effect on parents, children and families. After discussing the risks of (1) attaching too much weight to etiology and (2) any epigenetics discourse playing into ‘bionormativity’, the paper concludes that epigenetic knowledge can and should be used in a framework that goes beyond deterministic etiologies but embraces the complexities and interrelatedness of all factors influencing the health of future generations.
Consensus-Based Guidelines for Acute Myeloid Leukemia Management in Gulf Cooperation Council Countries: Addressing Unmet Regional Needs and the Changing AML Landscape
Authors: Al-Khabori Murtadha K. , Alhuraiji Ahmad , Alam Arif R. , Khan Faraz A. , El Omri Halima , Osman Hani Y. , AaL Yaseen Hasan M. , Al Bulushi Mahdiya Pir , Pandita Ramesh K. , Marashi Mahmoud M.
Published: June 2024

PURPOSE

AML is a heterogeneous hematologic malignancy. Region-specific recommendations for AML management can enhance patient outcomes. This article aimed to develop recommendations for the Gulf Cooperation Council (GCC) countries.

METHODS

Ten AML panel members from Kuwait, Oman, Qatar, and the United Arab Emirates (KOQU) participated in a modified two-round Delphi process. The panel first identified the unmet regional needs and finalized a list of core variables. Next, they voted on iterative statements drawn from international recommendations and provided feedback via a questionnaire. Consensus voting ≤70% was discussed, and additional clinical decision making statements were suggested. At round closure, a consensus vote took place on revised statements.

RESULTS

The panel reached ≥97.8% consensus on AML management. The panel agreed to use international risk stratification categories for personalized treatment of AML. The presence of ≥10% blasts for recurrent genetic abnormalities was required for a diagnosis of AML. Key consensus was reached for different treatment stages. The panel noted that older patients pose a challenge because of poor cytogenetics and genetic anomalies and require different treatment approaches. The panel recommended venetoclax-hypomethylating agents; fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor; and targeted therapy for AML relapsed/refractory disease. Supportive care is considered on the basis of prevailing organisms and drug resistance.

CONCLUSION

The GCC KOQU's consensus-based recommendations for managing AML include an evidence-based and region-specific framework.
Impact of exposure on outcomes with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer.
Authors: Petrylak Daniel P. , Chia Yen Lin , Yu Evan Y. , Powles Thomas , Flaig Thomas W. , Loriot Yohann , O'Donnell Peter H. , Heath Elisabeth I. , Kojima Takahiro , Park Se Hoon , Sonpavde Guru P. , Picus Joel , Matsubara Nobuaki , Obara Wataru , Chudasama Vaishali , Poondru Srinivasu , Harrison Michael , Kim Eric , Brancato Sam Joseph , Rosenberg Jonathan E.
Published: June 2024

4503

Background: Enfortumab vedotin (EV) is approved in combination with pembrolizumab and as a monotherapy for locally advanced or metastatic urothelial cancer (la/mUC). EV, alone and in combination with pembrolizumab, has demonstrated an OS benefit and a generally manageable safety profile in patients (pts) with previously treated or untreated la/mUC. Dose modifications, including reductions and interruptions, are recommended to manage EV-related AEs. This analysis evaluates the association between EV plasma exposure, which is impacted by dose modifications, and safety and efficacy outcomes. Methods: Characterization of dose- and exposure-response for efficacy and exposure-response for safety outcomes included pts in EV-101 (EV monotherapy 0.75, 1.0, and 1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle [3Q4W]), EV-201, and EV-301 (EV monotherapy 1.25 mg/kg 3Q4W). Time-averaged exposure up to an event of interest, Cavg, was computed using a population PK model. PK assessment included multiple samples in first 2 cycles, and pre-dose samples in subsequent cycles. Results: Dose modifications were common, including dose reductions to 1.0 mg/kg (EV-201 42.1%; EV-301 35.1%) and 0.75 mg/kg (EV-201 13.6%; EV-301 11.1%). EV showed consistent improvement in median PFS and OS vs chemotherapy across all exposure quartiles in EV-301 inclusive of dose modifications (Table). Greater initial EV exposure in the first 2 cycles was associated with a higher ORR and was consistent with dose-response (0.75 mg/kg 21.4% [sample size {n} = 14]; 1.0 mg/kg 18.5% [n = 27]; 1.25 mg/kg 40-51.1% across studies [n = 613]). Lower EV exposure was associated with lower risk of EV-related Grade ≥3 rash or skin reactions, Grade ≥2 peripheral neuropathy, and Grade ≥3 hyperglycemia (P<0.0001 for all). Conclusions: EV improved PFS and OS outcomes vs chemotherapy in pts with la/mUC across all exposure quartiles. The starting dose of 1.25 mg/kg 3Q4W resulted in EV exposure that maximized likelihood of response. Recommended dose modifications are effective for managing EV-related AEs and should be used as clinically indicated. Clinical trial information: NCT02091999 , NCT03219333 , and NCT03474107 . [Table: see text]
Partitioned overall survival: Comprehensive analysis of survival states over 4 years in CheckMate 9ER comparing first-line nivolumab plus cabozantinib versus sunitinib in advanced renal cell carcinoma (aRCC).
Authors: Mantia Charlene , Jegede Opeyemi , Viray Hollis , Atkins Michael B. , Rosenblatt Lisa , Yin Xin , McDermott David F. , Regan Meredith M.
Published: June 2024

4507

Background: Immunotherapy regimens can be associated with prolonged disease control after treatment discontinuation without the need for further anticancer therapy. An integrated, comprehensive partitioned survival analysis describes how patients spend overall survival (OS) time, on/off treatment, with/without toxicity. Previous analysis of first-line (1L) nivolumab (NIVO) + ipilimumab (IPI) for aRCC in CheckMate 214 showed treatment-free survival (TFS) twice as long vs sunitinib (SUN). TFS and survival states for immune checkpoint inhibitor plus tyrosine kinase inhibitor (TKI) combination are of interest. Methods: Overall, 651 patients (pts) with aRCC were randomized to receive 1L NIVO + cabozantinib (CABO) or SUN in the CheckMate 9ER trial; treatment continued until progression or intolerance, NIVO for at most 24 months. Minimum follow-up was 4 years. We partitioned area under the Kaplan–Meier (KM) OS curve into 3 survival states, defined from randomization: time on 1L protocol therapy, TFS, and survival after subsequent systemic therapy (second line [2L]) initiation. TFS and protocol therapy were subdivided as mean times with/without reported grade 2+ treatment-related adverse events (TRAEs). Areas under and between KM curves were estimated by 48-month restricted mean times to event. Bootstrapped 95% CIs for between-group differences are reported. Results: At 4 years post randomization, KM estimates of OS were 49.2% vs 40.2% of pts assigned to NIVO+CABO vs SUN, respectively; 17.6% vs 4.7% of pts were surviving treatment-free, and 15.8% vs 8.2% were continuing on 1L protocol therapy. Over the 48-month period since randomization (Table), the mean TFS (95% CI) was 2.4 (0.8–3.9) months longer after treatment with NIVO+CABO than SUN. At least half of TFS was spent with toxicity in both treatment groups, resulting in difference in mean TFS (95% CI) without toxicity of 0.7 (−0.4 to 1.8) month. The NIVO+CABO group spent a mean (95% CI) of 8.5 (6.2–10.8) months more survival time on 1L protocol therapy, whereas the SUN group spent a mean (95% CI) of 6.5 (4.4–8.6) months more survival time after 2L therapy initiation. Conclusions: Over the 4-year period since initiation of 1L therapy for aRCC, the longer OS achieved with NIVO+CABO was accompanied by 1.5 times longer mean time surviving treatment-free before 2L therapy compared with SUN, a smaller difference than seen for NIVO + IPI vs SUN. [Table: see text]
A multi-institution analysis of outcomes with first-line systemic therapy for 99 patients with metastatic chromophobe renal cell carcinoma.
Authors: Doshi Sahil D. , Dizman Nazli , Knezevic Andrea , Touma Amina , Alaghehbandan Reza , Ged Yasser , Ornstein Moshe Chaim , Hahn Andrew Warren , Msaouel Pavlos , Voss Martin H
Published: June 2024

4512

Background: Chromophobe renal cell carcinoma (ChRCC) represents ~5-10% of all RCCs. Given its rarity, there is limited clinical trial data to guide systemic therapy for metastatic disease. Phase 2 trials have demonstrated that targeted agents inhibiting vascular endothelial growth factor receptor and mammalian target of rapamycin have similar efficacy in ChRCC compared to conventional RCC. However, immune checkpoint inhibitor (IO) containing regimens appear less efficacious compared to other RCC subtypes. Importantly, these efforts have all enrolled < 30 ChRCC patients, and larger scale studies are needed. Methods: We conducted a retrospective study of patients with metastatic ChRCC seen at 3 academic centers. Baseline characteristics and treatment outcomes were obtained from EHR review. Patients were categorized into 4 treatment categories: 1) IO + targeted therapy doublets (e.g., lenvatinib plus pembrolizumab) 2) Pure IO monotherapy and doublets (e.g., ipilimumab plus nivolumab) 3) targeted therapy doublets (e.g., lenvatinib plus everolimus) and 4) targeted monotherapy (e.g., sunitinib). We calculated time to treatment failure (TTF) of first-line systemic therapy and overall survival (OS) by the Kaplan-Meier method. Median time-to-event was reported for each treatment category and categories compared with the log-rank test. Results: Ninety-nine patients with metastatic ChRCC treated with first-line systemic therapy were included; 62% were male, 44% had sarcomatoid features, and 33% had IMDC favorable risk. Outcomes with TTF and OS are summarized in the table below. Median TTF and 18-month OS rates were 5 months and 58% for the targeted monotherapy group, 15 months and 80% for the IO/targeted doublet group, 17 months and 65% for the targeted doublet group, and 7 months and 83% for the pure IO group. Treatment with any doublet containing a targeted agent compared to targeted monotherapy yielded a superior median TTF (15 vs 5 months, HR 0.48; 95% CI: 0.29, 0.80; p=0.005) and OS (56 vs 23 months, HR 0.56; 95% CI: 0.30, 1.04; p=0.07). Most treatment (64%) was discontinued due to progression; 25% due to toxicity. 11 patients had ongoing treatment at time of analysis. Conclusions: In this observational analysis, patients with targeted doublet regimens had a higher median TTF and OS compared to those receiving monotherapies. We continue to build on this dataset and plan to conduct progression free survival analysis. [Table: see text]
Avelumab (A) as neoadjuvant therapy in patients (pts) with muscle-invasive urothelial carcinoma (MIUC): Survival data of AURA trial, Oncodistinct 004.
Authors: Blanc Jeremy , Carnot Aurélien , Barthelemy Philippe , Casert Vinciane , Staudacher Lionel , Van den Brande Jan , Sautois Brieuc , Vanhaudenarde Vincent , Seront Emmanuel , Debien Veronique , Ameye Lieveke , Kotecki Nuria , Fantoni Jean Christophe , Tricard Thibault , Roumeguere Thierry Andre , Awada Ahmad , Martinez Chanza Nieves
Published: June 2024

4516

Background: Immunotherapy in the perioperative setting of MIUC appears promising. The AURA trial (NCT03674424) investigated the addition of avelumab to neoadjuvant dose-dense MVAC (ddMVAC) or cisplatin-gemcitabine (CG) respectively, followed by surgery in the cisplatin-eligible cohort. The primary endpoint was previously reported with high pathological complete response (pCR) rates with each cisplatin-based regimen. In the cisplatin-ineligible cohort, pts were randomized to neoadjuvant A alone or in combination with paclitaxel-gemcitabine (PG) followed by surgery. Avelumab monotherapy showed encouraging pCR but the addition of PG did not provide any benefit. Here, we report the survival data from cisplatin-eligible and ineligible cohorts of the AURA trial. Methods: In the cisplatin-eligible cohort, 79 pts were randomly assigned to the ddMVAC-A (n=39) or CG-A (n=40) groups. In the cisplatin-ineligible cohort, 58 pts were randomly assigned to the PG-A (n=29) or A (n=29) groups. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method at 12 months and 36 months for the overall cohort and by subgroups. Results: Median follow-up was 33 months and 45 deaths were reported. In the cisplatin-eligible cohort, 12-month DFS was 92% (95% CI, 83-96%) and 36-month DFS was 72% (95% CI, 57-83%). For ddMVAC-A group: 97% and 77%, respectively. For CG-A group: 86% and 68%. Overall, 12-month OS was 89% (95% CI, 80-95%) and 36-month OS was 73% (95% CI, 61-83%). For ddMVAC-A: 95% and 87%. For CG-A: 84% and 61%. Among the ypT0N0 pts, no events were registered within 12 months of follow-up showing a DFS rate of 100% for both arms. At 36 months no events were reported for pts treated with ddMVAC-A and two for CG-A showing DFS rates of 100% and 78% respectively. In the cisplatin-ineligible cohort, 12-month DFS was 60% (95% CI, 46-72%) and 12-month OS was 71% (95% CI, 57-81%). For PG-A: 52% and 67%. For A: 68% and 75%. Among the ypT0N0 pts, no DFS events occurred within 12 months. Data for 36-month are not yet mature. Overall, the main cause of death was disease progression (73%). Conclusions: The addition of neoadjuvant avelumab to cisplatin-based chemotherapy results in a high DFS and OS at 12 and 36 months respectively, especially in pts with complete response to neoadjuvant treatment. Combination with ddMVAC regimen offers robust activity. Cisplatin-ineligible pts had lower survival outcomes with no benefit of PG addition. Clinical trial information: NCT03674424 . [Table: see text]
Association of machine learning (ML)–derived histological features with transcriptomic molecular subtypes in advanced renal cell carcinoma (RCC).
Authors: Beig Niha , Nofallah Shima , McDermott David F. , Motzer Robert J. , Powles Thomas , Rini Brian I. , Koeppen Hartmut , Banchereau Romain , Markey Miles , Finberg Isaac , Singh Geetika , Yu Limin , Egger Robert , Parmar Chintan , Conway Jake , Hennek Stephanie , Ruderman Daniel , Vilchez Samuel , Huseni Mahrukh A , Giltnane Jennifer Margaret
Published: June 2024

4519

Background: Metastatic RCC (mRCC) is a molecularly heterogeneous disease. Transcriptomic analysis in the Phase 3 IMmotion 151 (Im151) trial identified 7 molecular subtypes that showed differential outcomes to Atezolizumab+Bevacizumab (A+B) vs Sunitinib (S) treatment (Motzer, Cancer Cell 2020). Here, we present histological correlates of these subtypes as identified in whole slide images (WSI) of hematoxylin and eosin (H&E) stained tumors. Methods: ML models identified 922 H&E derived, human interpretable histological features (ML HIFs) in RCC associated with tumor and stromal (including vessels, immune cells, fibroblasts) cell and tissue morphologies, and nucleus shape. These ML HIFs were then extracted from WSI in 2 mRCC trials – Im151 (n=797) and IMmotion150 (Im150, n=203). Previously described 7 molecular subtypes were combined into 4 subgroups (Angiogenic [comprised of Angiogenic/Stromal and Angiogenic], Complement/OmegaOxidation, T-effector, and Proliferative [comprised of Proliferative and Stromal Proliferative]) for computational power. Due to low prevalence, snoRNA subset was excluded. Univariate analysis with FDR correction was applied to identify positively associated ML HIFs in each of the 4 subgroups in the Im151 WSI and then validated in Im150 subgroups. Representative ML HIFs that showed uniquely higher abundance in each molecular subgroup in both studies were dichotomized by tertiles as ‘high’ or ‘low/intermediate’ and associated with progression free survival (PFS) to fit Cox proportional hazard models in Im151 study. Results: 169 ML HIFs were differentially enriched across 3 molecular subgroups in both Im151 and Im150 data sets. Angiogenic subgroup had higher prevalence of 40 ML HIFs associated with density of endothelial cells in cancer epithelium. T-effector subtype showed higher abundance of 64 ML HIFs associated with immune cell presence in stroma. Proliferative subgroup showed higher prevalence of 40 ML HIFs associated with nuclear morphologies. No ML HIFs were uniquely associated with the Complement/OmegaOxidation subgroup. Consistent with transcriptional findings in Im151, ML HIFs that were enriched in T-effector and Proliferative subgroups showed improved PFS benefit to A+B vs S (Table). Conclusions: We identified unique histological features of RCC tumors that correlate with previously defined molecular subtypes. Our results suggest that clinically relevant RCC subtypes may be extracted directly from H&E-stained WSI and may complement gene expression based patient stratification and selection strategies. [Table: see text]
Clinical utility of transcriptomic signatures to identify androgen receptor and neuroendocrine signaling in prostate cancer.
Authors: Chen Yu-Wei , Xiu Joanne , Poorman Kelsey Anne , Ryan Charles J. , Gilg Brady , Oberley Matthew James , Sledge George W. , Beltran Himisha , McKay Rana R.
Published: June 2024

5015

Background: Neuroendocrine prostate cancer (NEPC) is a relatively androgen receptor (AR)-independent and aggressive variant of PC that can arise from adenocarcinoma with varied degrees of adenocarcinoma and high-grade neuroendocrine histologic features seen during its progression. This study evaluated the clinical and molecular features of histologic subtypes of prostate tumors (adenocarcinoma, NEPC, mixed adeno-NE) based on previously validated AR signaling and NEPC transcriptomic signatures of PC. Methods: Whole exome (WES) and whole transcriptome sequencing (WTS) were performed on PC tumors. Molecular subsets were defined by AR signaling signature [AR score positive (+) vs negative (-)] and NEPC gene signature [NE score positive (+) vs negative (-)]. The prevalence of key molecular alterations (RB1, TP53, PTEN, AR, FANC, SLFN11 expression) were investigated. Genes encoding cell surface antigens with potential therapeutic implications were described across signature groups. Overall survival (OS) was obtained from claims data and analyzed with Kaplan-Meier estimator. Results: A total of 4,476 prostate tumors were analyzed in this study including: 3,623 prostate adenocarcinoma, 56 NEPC, and 25 tumors with mixed adeno-NE. Tissue from 2,641 (67%) tumors were collected from prostate and 1,326 (33%) were metastatic tumors [lymph node (14%), bone (9%), liver (7%), lung (2%), CNS (2%)]. The four AR/NEPC signature-defined subtypes were AR+/NE+ (N=649, 14%), AR+/NE- (N=1614, 36%), AR-/NE+ (N=875, 20%), and AR-/NE- (N=1358, 30%). AR+/NE- was most common in prostate (39%), LN (42%) and lung metastasis (35%); AR-/NE+ was most common in bone (34%) and liver metastasis (43%); AR-/NE- was most common in CNS metastasis. The most common gene alterations in each molecular subtype are defined in Table. AR-/NE+ tumors had the lowest mRNA expression of FOLH1(PSMA), STEAP1, TACSTD2 (Trop-2), CD276 (B7-H3), and PSCA among the four groups. DLL3 expression was higher among NE+ subtypes. FOLH1 and PSCA expression were higher among NE- subtypes. The median OS (months) was longer in NE- than NE+ subtypes [AR+/NE- (78.3), AR-/NE- (78.7) vs AR+/NE+ (70.7), AR-/NE+ (69.1)]. In the platinum-treated subgroup (N=146), the median OS was numerically longer among tumors with SLFN11 overexpression (17.6 vs 12.0) although this was not statistically significant (p-value: 0.99). Conclusions: Molecularly distinct subtypes of PC can be further characterized by AR signaling signature, NEPC gene expression signature, and co-occurring molecular alterations. The phase II biomarker-driven PREDICT trial will integrate the above signatures/molecular alterations to allocate treatment regimens in metastatic castration-resistant PC. [Table: see text]
PHAROS, a real-world multi-country European study on patients with high-risk localised and locally advanced prostate cancer receiving radical treatment.
Authors: Eiber Matthias , Aebersold Daniel M. , Valcarcel diaz Alfonso , Wetterauer Christian , Bach Michael , Camarrone Flavio , Herkommer Kathleen , Li Honghao , Campos Fernando Lopez , Mathieu Thomas , Olivier Jonathan , Pissart Geneviève , Robinson Paul , Shelan Mohamed , Stitou Hind , Thiriez Céline , Touzot Maxime , Villers Arnauld
Published: June 2024

5027

Background: Primary radical therapy with curative intent is standard of care for patients diagnosed with high risk (HR) localised (LPC) and locally advanced prostate cancer (LAPC). However, many patients relapse and detailed epidemiological data on natural history, routine management, and clinical outcomes in this setting are sparse. We aimed to explore real world data (RWD) to gain insights into the understanding of the disease pathway. Methods: PHAROS is a retrospective, observational study conducted in five academic centres across four European countries from 1989 to 2022 (France, Germany, Switzerland, Spain). All patients with HR LPC and LAPC, according to EAU guidelines, and treated by primary radical prostatectomy (RP) or radiotherapy (RT) (alone or with ADT) were eligible. Data were structured and analysed to describe the patient characteristics at the time of radical therapy, subsequent treatment patterns and clinical events including biochemical recurrence (BCR), event-free survival (EFS) [defined by loco-regional relapse, BCR, metastasis or death] and overall survival (OS) that were estimated by Kaplan-Meier method. Results: The table summarizes baseline characteristics and intermediate endpoints for a total of 2303 patients, mostly diagnosed between 2005 and 2020, with a mean follow-up of 6.8 years. RP patients were younger and more likely to be node-positive (N+) as compared to RT patients. EFS at 5 years was 48 % [0.43-0.54] in the RP cohort (N=1539), and 74% [0.66-0.81] in the RT cohort (N=764). At 5 years after radical treatment, 21% of the RP cohort developed distant metastases and rates were higher (30%) in centres with routine access to PSMA PET. The rate was lower (12%) in the RT cohort potentially because of extended hormonal treatment. The principal reported treatment after the first BCR in the RP cohort was salvage RT ±ADT and ADT for the RT cohort. Only 249 and 311 deaths were observed in the RP and RT cohort with an estimated 10-year OS of 73 % [0.66-0.80] and 69% [0.57-0.80], respectively. Conclusions: In this large RWD cohort of HR LPC & LAPC, initial results suggest that a significant proportion of patients fail after primary curative treatment within 5 years, indicating an unmet medical need to improve outcomes. Further analysis of the PHAROS dataset will bring better understanding of the real-world patient pathway in this setting and the role of intermediate endpoints. [Table: see text]
Association between body mass index and physical activity among prostate cancer survivors.
Authors: Haiderbhai Shabbir , Sahmoun Abe Eric
Published: June 2024

5029

Background: Prostate cancer (PCa) has become a chronic disease due to advances in treatment and earlier detection. Therefore, factors that modify survival post‐diagnosis are important. Obesity is associated with increased PCa recurrence and mortality. Thus, interventions that reduce obesity, e.g., physical activity (PA) may prolong survival. We assessed the association between body mass index (BMI) and PA among prostate cancer survivors as well as other modifiable predictors of PA. Methods: We conducted a cross-sectional analysis of data from the 2018-22 Behavioral Risk Factor Surveillance System, an ongoing national population-based telephone survey conducted in the U.S. The outcome variable is PA after PCa diagnosis. We classified BMI (exposure) using standard cut points defined by the WHO. Multivariable weighted logistic regression was used to examine the association between BMI and PA adjusting for confounders. All significance tests were two-sided and p-value < 0.05 was significant. The data were analyzed accounting for the complex sample survey design. Results: Of the 4,944 prostate cancer respondents, 78% were 65 years or older and 69% were White. 23% were obese class I and 11% were obese class II & III. Obese class I and obese class II & III respondents were significantly less likely to report PA (OR=0.48; 95% CI: 0.28-0.84 and OR=0.37; 95% CI: 0.20-0.67; respectively). Men who received a summary of their cancer treatment were significantly more likely to report PA (OR=1.53; 95% CI: 1.03-2.28). Current smokers were less likely to report PA (OR=0.50; 95% CI: 0.26-0.96). Conclusions: Obese men and current smokers were less likely to report PA. Men who received a summary of their cancer treatment were more likely to report PA. Healthcare providers should talk to their patients about the benefit of exercising and refer patients to available exercise programs. Key words: Prostate Cancer Survivorship; Body Mass Index; BRFSS; Quality of Care, Healthy Behaviors.
Utilization patterns and outcomes of radiotherapy for patients with germ cell tumor relapsing with brain metastases, with a focus on stereotactic radiosurgery.
Authors: Gui Chengcheng , Funt Samuel A , Yu Yao , Zinovoy Melissa , Chen Linda , Yamada Yoshiya , Pike Luke R. G. , Feldman Darren R. , Imber Brandon S.
Published: June 2024

5032

Background: Brain metastases (BM) from germ cell tumors (GCT) are a poor-prognostic feature. Nonetheless, many patients (pts) relapsing with BM achieve long-term disease control. Radiotherapy (RT) is a key component of GCT BM management, alongside salvage chemotherapy (CT), but minimal data are available to guide its use. Outcomes of stereotactic radiosurgery (SRS) alone, without whole brain RT (WBRT), are seldom reported. We describe treatment patterns and outcomes of pts with GCT who received RT for BM relapse. Methods: Male pts with extracranial GCT who received RT for BM relapse between 2005 and 2023 were included. Four subgroups were defined based on incorporation of RT into the broader BM treatment strategy: RT without concurrent salvage CT (Group 1), RT with salvage conventional-dose CT (CDCT) (Group 2), RT with high-dose CT (HDCT) (Group 3), and salvage RT for progressing BM initially treated with CT alone (Group 4). RT approach included WBRT and SRS. Primary outcomes were overall survival (OS) and intracranial progression (IP) from RT completion. Local progression (LP) after SRS was also assessed. Associations with outcomes were modeled with Cox regression and competing risk regression, accounting for death. Results: Sixty pts were included. Median age at BM diagnosis was 28 years. Median follow-up among those alive was 87 months. At 3 years after RT, OS was 39%, and IP was 44%. Groups 1, 2, 3, and 4 included 20, 17, 13, and 10 pts, respectively. Groups were not significantly associated with other baseline features, including RT approach. Outcomes by Group are reported (Table). OS was not significantly different in any Group. There was a trend for worse IP in Group 4, compared with all other groups (HR 2.2, 95% CI 0.99-5.1, p = 0.05). WBRT and SRS alone were used in 32 and 27 pts, respectively. RT approach was not significantly associated with other baseline features. Outcomes by RT approach are reported (Table). OS and IP were not significantly different. Among 53 BM treated with SRS, LP was 8% at 3 years. Among 27 pts treated with SRS, ≥ 2 BM (13 pts) predicted increased risk of death (HR 4.9, 95% CI 1.5-16, p = 0.01) and IP (HR 3.6, 95% CI 1.2-11, p = 0.02). This was not observed after WBRT. Conclusions: We found heterogeneous patterns of RT use for BM relapse: RT alone, RT with CDCT, RT with HDCT, and salvage RT after initial CT alone. Long-term survival and intracranial control are achievable with each strategy and with both WBRT and SRS. This analysis includes the largest reported series of GCT BM treated with SRS; local control after SRS is excellent, but caution is advised for pts with multiple BM, given elevated risk of IP and death. [Table: see text]