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Background: The cumulative, health system‐wide survival benefit of immune checkpoint inhibitors (ICIs) is unclear, particularly among real‐world patients with limited life expectancies and among subgroups poorly represented on clinical trials. We sought to determine the health system‐wide survival impact of ICIs. Methods: We identified all patients receiving PD‐1/PD‐L1 or CTLA‐4 inhibitors from 2010 to 2023 in the national Veterans Health Administration (VHA) system (ICI cohort) and all patients who received non‐ICI systemic therapy in the years before ICI approval (historical control). ICI and historical control cohorts were matched on multiple cancer‐related prognostic factors, comorbidities, and demographics. The effect of ICI on overall survival was quantified with Cox regression incorporating matching weights. Cumulative life‐years gained system‐wide were calculated from the difference in adjusted 5‐year restricted mean survival times. Results: There were 27,322 patients in the ICI cohort and 69,801 patients in the historical control cohort. Among ICI patients, the most common cancer types were NSCLC (46%) and melanoma (10%). ICI demonstrated a large OS benefit in most cancer types with heterogeneity across cancer types (NSCLC: adjusted HR [aHR] 0.56, 95% confidence interval [CI] 0.54–0.58, p < 0.001; urothelial: aHR 0.91, 95% CI 0.83–1.01, p = 0.066). The relative benefit of ICI was stable across patient age, comorbidity, and self‐reported race subgroups. Across VHA, 15,859 life‐years gained were attributable to ICI within 5‐years of treatment, with NSCLC contributing the most life‐years gained. Conclusion: We demonstrated substantial increase in survival due to ICIs across a national health system, including in patient subgroups poorly represented on clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: Cancer is a leading cause of global childhood mortality, affecting 400,000 children annually. While treatable with modern therapies, children living in low‐ and middle‐income countries (LMICs) have limited access to care and lower survival rates. Hospital‐based cancer registries (HBCRs) collect detailed patient information to critically evaluate and evolve care. The St. Jude Global Childhood Cancer Analytics Resource and Epidemiological Surveillance System (SJCARES) is a cloud‐based HBCR network facilitating quality data collection of pediatric cancer. Wide variation in the success of implementation has warranted further research into the implementation approach, to create a sustainable and adaptable HBCR in LMICs. Methods: Seven of 89 sites using the SJCARES registry were selected, stratified by global region and stage of implementation. Semi‐structured interviews were conducted with key groups (clinicians, administrators, data clerks) using an interview guide developed from the Consolidation Framework for Implementation Research (CFIR). Interviews were conducted via a video‐telephone software program and transcribed by a transcription service. Transcripts were thematically coded using rapid qualitative analysis. Results: A total of 18 participants (11 clinicians, 4 administrators, 3 data clerks) were interviewed. Several barrier themes were identified, including: difficulty integrating the registry into existing workflow; lack of resources; lack of government or administrative support; and damaged, misplaced, or illegible medical records. Facilitator themes were identified, including: internal support for the registry; clear and extensive training; and dedicated support staff. Conclusion: Interviewed participants identified key barriers and facilitators to the implementation of the SJCARES registry across multiple phases. We plan to use these results to develop targeted implementation strategies including a readiness assessment tool to help guide more successful implementation of the SJCARES registry and other HBCRs in LMICs. [ABSTRACT FROM AUTHOR]

Background: Advancements in cancer treatment and survivorship rely on participation in research and access to health records. Methods: This study explored preferences for data access and sharing in 14 workshops with 42 community members, most of whom were a cancer survivor or carer. Various scenarios for data access and sharing were presented and discussed, with participants' preferences summarized using descriptive statistics. Reasons underlying these preferences were identified through a thematic analysis of workshop transcripts. Results: Most participants indicated a willingness for researchers to use their self‐report data and current health records for a specific research project (86%). Many were also willing for their self‐report data and current (62%) or all future (44%) health records to be shared with other researchers for use in other studies if made aware of this. Willingness to consent to data access and sharing data in cancer research was influenced by: (i) the potential for data sharing to advance medical discoveries and benefit people impacted by cancer in the future, (ii) transparency around researchers' credibility and their intentions for data sharing, (iii) level of ownership and control over data sharing, and (iv) protocols for privacy and confidentiality in data sharing. Conclusions: Based on these themes, we present practical strategies for optimizing data access and sharing in cancer research. [ABSTRACT FROM AUTHOR]

Background: Selecting pembrolizumab monotherapy (MONO) or pembrolizumab plus platinum‐based chemotherapy (COMB) for patients with nonsmall cell lung cancer (NSCLC) and high programmed death‐ligand 1 (PD‐L1) expression is an important issue in clinical practice. We previously conducted a retrospective multicenter observational study of patients with NSCLC and high PD‐L1 expression who received MONO or COMB as a first‐line treatment. Here, we report updated data and evaluate the long‐term outcomes. Methods: We performed a retrospective multicenter study of 298 patients with NSCLC and high PD‐L1 expression who received MONO or COMB as first‐line treatment between December 2018 and January 2020. We reviewed the medical records and assessed the clinical efficacy and toxicity using a prolonged data cutoff. Results: In total, 164 (median age: 74 years) and 134 (median age: 68 years) patients received MONO and COMB, respectively; patients who received COMB were younger and had better performance statuses (0–1). At the prolonged data cutoff, the median follow‐up was 20.2 (range: 0.1–41.4) months. The median progression‐free survivals were 7.5 and 13.1 months, and overall survivals (OSs) were 17.2 and 33.7 months for MONO and COMB, respectively. Treatment discontinuation rates were 21.9% and 20.1% for the MONO and COMB, respectively. With prolonged follow‐up, although COMB demonstrated an OS benefit and higher objective response rate than MONO, in the propensity score matching analysis COMB didn't demonstrate a significant benefit compared to the MONO. Conclusions: COMB may be effective as a first‐line treatment for NSCLC with high PD‐L1 expression in a selected subset of patients. [ABSTRACT FROM AUTHOR]

Purpose: High‐quality communication is essential to patient‐centered care. Existing communication models and research tends to focus on what is said verbally with little attention to nonverbal aspects of communication. In sensitive and emotionally intensive healthcare encounters, such as in cancer care, provider and patient nonverbal behavior may be particularly important for communicating with empathy. Therefore, the aim of this study was to develop a conceptual model of communication that accounts for nonverbal behavior. Methods: We followed a systematic grounded theory design that involved semi‐structured interviews with 23 providers, including nurse practitioners, physicians, surgeons, and physician's assistants. Using constant comparative analysis, we analyzed transcripts and developed a grounded theory model of communication accounting for nonverbal behavior. Results: The major themes included building rapport, gauging how patients will take bad news, ensuring patients' understanding of their conditions, staying honest but hopeful, centering but guiding patient through cancer care, conveying empathy while managing heightened emotions, and ensuring patient understanding. Throughout the process, providers synthesize both verbal and nonverbal information and apply what they learn to future encounters. Conclusions: The results extend existing models of patient‐centered communication and invite communication intervention and research that incorporates nonverbal behavior. The model contributes an understanding of the full process of communication in clinical encounters. [ABSTRACT FROM AUTHOR]

Background: Avelumab first‐line (1 L) maintenance is a standard of care for advanced urothelial carcinoma (aUC) based on the JAVELIN Bladder 100 phase 3 trial, which showed that avelumab 1 L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression‐free survival (PFS) vs BSC alone in patients who were progression free after receiving 1 L platinum‐containing chemotherapy. Here, we comprehensively screened JAVELIN Bladder 100 trial datasets to identify prognostic factors that define subpopulations of patients with longer or shorter OS irrespective of treatment, and predictive factors that select patients who could obtain a greater OS benefit from avelumab 1 L maintenance treatment. Methods: We performed machine learning analyses to screen a large set of baseline covariates, including patient demographics, disease characteristics, laboratory values, molecular biomarkers, and patient‐reported outcomes. Covariates were identified from previously reported analyses and established prognostic and predictive markers. Variables selected from random survival forest models were processed further in univariate Cox models with treatment interaction and visually inspected using correlation analysis and Kaplan–Meier curves. Results were summarized in a multivariable Cox model. Results: Prognostic baseline covariates associated with OS included in the final model were assignment to avelumab 1 L maintenance treatment, Eastern Cooperative Oncology Group performance status, site of metastasis, sum of longest target lesion diameters, levels of C‐reactive protein and alkaline phosphatase in blood, lymphocyte proportion in intratumoral stroma, tumor mutational burden, and tumor CD8+ T‐cell infiltration. Potential predictive factors included site of metastasis, tumor mutation burden, and tumor CD8+ T‐cell infiltration. An analysis in patients with PD‐L1+ tumors had similar findings to those in the overall population. Conclusions: Machine learning analyses of data from the JAVELIN Bladder 100 trial identified potential prognostic and predictive factors for avelumab 1 L maintenance treatment in patients with aUC, which warrant further evaluation in other clinical datasets. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess the frequency of potential germline pathogenic variants that may contribute to risk of development of adult granulosa cell tumors (AGCT) given the paucity of germline testing guidelines for these patients. Methods: This was a retrospective cross‐sectional study analyzing comprehensive genomic profiling (CGP) results of AGCT with the FOXL2 p.C134W mutation submitted to Foundation Medicine between 2012 and 2022. Cases with a potential germline pathogenic variant were identified by filtering single nucleotide variants and short indels by variant allele frequency (VAF) and presence in ClinVar for select cancer susceptibility genes. Odds ratios for AGCT risk were calculated compared to a healthy population. Results: Prior to analysis, 595 patients were screened and 516 with a somatic FOXL2 p.C134W mutation were included. Potential germline pathogenic variants in a DNA repair‐related gene (ATM, BRCA1, BRCA2, CHEK2, PALB2, PMS2, RAD51C, or RAD51D) were found in 6.6% of FOXL2‐mutated AGCT. Potential germline pathogenic CHEK2 variants were found in 3.5% (18/516) of AGCT patients, a rate that was 2.8‐fold higher than Genome Aggregation Database non‐cancer subjects (95% CI 1.8–4.6, p < 0.001). The founder variants p.I157T (38.9%, 7/18) and p.T367fs*15 (c.1100delC; 27.8%, 5/18) were most commonly observed. CHEK2 VAF indicated frequent loss of the wildtype copy of the gene. Conclusions: These results support ongoing utilization of genomic tumor profiling and confirmatory germline testing for potential germline pathogenic variants. Further prospective investigation into the biology of germline variants in this population is warranted. [ABSTRACT FROM AUTHOR]

ABSTRACT Background The cumulative, health system‐wide survival benefit of immune checkpoint inhibitors (ICIs) is unclear, particularly among real‐world patients with limited life expectancies and among subgroups poorly represented on clinical trials. We sought to determine the health system‐wide survival impact of ICIs. Methods We identified all patients receiving PD‐1/PD‐L1 or CTLA‐4 inhibitors from 2010 to 2023 in the national Veterans Health Administration (VHA) system (ICI cohort) and all patients who received non‐ICI systemic therapy in the years before ICI approval (historical control). ICI and historical control cohorts were matched on multiple cancer‐related prognostic factors, comorbidities, and demographics. The effect of ICI on overall survival was quantified with Cox regression incorporating matching weights. Cumulative life‐years gained system‐wide were calculated from the difference in adjusted 5‐year restricted mean survival times. Results There were 27,322 patients in the ICI cohort and 69,801 patients in the historical control cohort. Among ICI patients, the most common cancer types were NSCLC (46%) and melanoma (10%). ICI demonstrated a large OS benefit in most cancer types with heterogeneity across cancer types (NSCLC: adjusted HR [aHR] 0.56, 95% confidence interval [CI] 0.54–0.58, p

Abstract Purpose Cancer is a leading cause of global childhood mortality, affecting 400,000 children annually. While treatable with modern therapies, children living in low‐ and middle‐income countries (LMICs) have limited access to care and lower survival rates. Hospital‐based cancer registries (HBCRs) collect detailed patient information to critically evaluate and evolve care. The St. Jude Global Childhood Cancer Analytics Resource and Epidemiological Surveillance System (SJCARES) is a cloud‐based HBCR network facilitating quality data collection of pediatric cancer. Wide variation in the success of implementation has warranted further research into the implementation approach, to create a sustainable and adaptable HBCR in LMICs. Methods Seven of 89 sites using the SJCARES registry were selected, stratified by global region and stage of implementation. Semi‐structured interviews were conducted with key groups (clinicians, administrators, data clerks) using an interview guide developed from the Consolidation Framework for Implementation Research (CFIR). Interviews were conducted via a video‐telephone software program and transcribed by a transcription service. Transcripts were thematically coded using rapid qualitative analysis. Results A total of 18 participants (11 clinicians, 4 administrators, 3 data clerks) were interviewed. Several barrier themes were identified, including: difficulty integrating the registry into existing workflow; lack of resources; lack of government or administrative support; and damaged, misplaced, or illegible medical records. Facilitator themes were identified, including: internal support for the registry; clear and extensive training; and dedicated support staff. Conclusion Interviewed participants identified key barriers and facilitators to the implementation of the SJCARES registry across multiple phases. We plan to use these results to develop targeted implementation strategies including a readiness assessment tool to help guide more successful implementation of the SJCARES registry and other HBCRs in LMICs.

Background: First‐line nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit versus chemotherapy in previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate 648 trial, leading to approvals of both nivolumab‐containing regimens in many countries. We report longer‐term follow‐up data. Methods: This open‐label, phase III trial (NCT03143153) enrolled adults with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. Primary endpoints were OS and progression‐free survival (PFS) by blinded independent central review. Hierarchical testing was performed first in patients with tumor cell programmed death ligand 1 (PD‐L1) expression of ≥1% and then in the overall population. Results: A total of 970 patients were randomly assigned. After 29 months of minimum follow‐up, nivolumab plus chemotherapy continued to demonstrate improvement in OS versus chemotherapy (hazard ratio [HR] = 0.59 [95% CI: 0.46–0.76]) in patients with tumor cell PD‐L1 expression of ≥1% and in the overall population (HR = 0.78 [95% CI: 0.65–0.93]) and with nivolumab plus ipilimumab versus chemotherapy (HR = 0.62 [95% CI: 0.48–0.80]) in patients with tumor cell PD‐L1 expression of ≥1% and in the overall population (HR = 0.77 [95% CI: 0.65–0.92]). In patients with tumor cell PD‐L1 expression of ≥1%, nivolumab plus chemotherapy demonstrated PFS benefit versus chemotherapy (HR = 0.67 [95% CI: 0.51–0.89]); PFS benefit was not observed with nivolumab plus ipilimumab versus chemotherapy (HR = 1.04 [95% CI: 0.79–1.36]). Among all treated patients (n = 936), Grade 3–4 treatment‐related adverse events were reported in 151 (49%, nivolumab plus chemotherapy), 105 (32%, nivolumab plus ipilimumab), and 110 (36%, chemotherapy) patients. Conclusions: Nivolumab plus chemotherapy and nivolumab plus ipilimumab continued to demonstrate clinically meaningful OS benefit versus chemotherapy with no new safety signals identified with longer follow‐up, further supporting use as first‐line standard treatment options for patients with advanced ESCC. [ABSTRACT FROM AUTHOR]

Abstract Background Advancements in cancer treatment and survivorship rely on participation in research and access to health records. Methods This study explored preferences for data access and sharing in 14 workshops with 42 community members, most of whom were a cancer survivor or carer. Various scenarios for data access and sharing were presented and discussed, with participants' preferences summarized using descriptive statistics. Reasons underlying these preferences were identified through a thematic analysis of workshop transcripts. Results Most participants indicated a willingness for researchers to use their self‐report data and current health records for a specific research project (86%). Many were also willing for their self‐report data and current (62%) or all future (44%) health records to be shared with other researchers for use in other studies if made aware of this. Willingness to consent to data access and sharing data in cancer research was influenced by: (i) the potential for data sharing to advance medical discoveries and benefit people impacted by cancer in the future, (ii) transparency around researchers' credibility and their intentions for data sharing, (iii) level of ownership and control over data sharing, and (iv) protocols for privacy and confidentiality in data sharing. Conclusions Based on these themes, we present practical strategies for optimizing data access and sharing in cancer research.

Abstract Purpose High‐quality communication is essential to patient‐centered care. Existing communication models and research tends to focus on what is said verbally with little attention to nonverbal aspects of communication. In sensitive and emotionally intensive healthcare encounters, such as in cancer care, provider and patient nonverbal behavior may be particularly important for communicating with empathy. Therefore, the aim of this study was to develop a conceptual model of communication that accounts for nonverbal behavior. Methods We followed a systematic grounded theory design that involved semi‐structured interviews with 23 providers, including nurse practitioners, physicians, surgeons, and physician's assistants. Using constant comparative analysis, we analyzed transcripts and developed a grounded theory model of communication accounting for nonverbal behavior. Results The major themes included building rapport, gauging how patients will take bad news, ensuring patients' understanding of their conditions, staying honest but hopeful, centering but guiding patient through cancer care, conveying empathy while managing heightened emotions, and ensuring patient understanding. Throughout the process, providers synthesize both verbal and nonverbal information and apply what they learn to future encounters. Conclusions The results extend existing models of patient‐centered communication and invite communication intervention and research that incorporates nonverbal behavior. The model contributes an understanding of the full process of communication in clinical encounters.

Abstract Background Selecting pembrolizumab monotherapy (MONO) or pembrolizumab plus platinum‐based chemotherapy (COMB) for patients with nonsmall cell lung cancer (NSCLC) and high programmed death‐ligand 1 (PD‐L1) expression is an important issue in clinical practice. We previously conducted a retrospective multicenter observational study of patients with NSCLC and high PD‐L1 expression who received MONO or COMB as a first‐line treatment. Here, we report updated data and evaluate the long‐term outcomes. Methods We performed a retrospective multicenter study of 298 patients with NSCLC and high PD‐L1 expression who received MONO or COMB as first‐line treatment between December 2018 and January 2020. We reviewed the medical records and assessed the clinical efficacy and toxicity using a prolonged data cutoff. Results In total, 164 (median age: 74 years) and 134 (median age: 68 years) patients received MONO and COMB, respectively; patients who received COMB were younger and had better performance statuses (0–1). At the prolonged data cutoff, the median follow‐up was 20.2 (range: 0.1–41.4) months. The median progression‐free survivals were 7.5 and 13.1 months, and overall survivals (OSs) were 17.2 and 33.7 months for MONO and COMB, respectively. Treatment discontinuation rates were 21.9% and 20.1% for the MONO and COMB, respectively. With prolonged follow‐up, although COMB demonstrated an OS benefit and higher objective response rate than MONO, in the propensity score matching analysis COMB didn't demonstrate a significant benefit compared to the MONO. Conclusions COMB may be effective as a first‐line treatment for NSCLC with high PD‐L1 expression in a selected subset of patients.

Abstract Objective The objective of this study was to assess the frequency of potential germline pathogenic variants that may contribute to risk of development of adult granulosa cell tumors (AGCT) given the paucity of germline testing guidelines for these patients. Methods This was a retrospective cross‐sectional study analyzing comprehensive genomic profiling (CGP) results of AGCT with the FOXL2 p.C134W mutation submitted to Foundation Medicine between 2012 and 2022. Cases with a potential germline pathogenic variant were identified by filtering single nucleotide variants and short indels by variant allele frequency (VAF) and presence in ClinVar for select cancer susceptibility genes. Odds ratios for AGCT risk were calculated compared to a healthy population. Results Prior to analysis, 595 patients were screened and 516 with a somatic FOXL2 p.C134W mutation were included. Potential germline pathogenic variants in a DNA repair‐related gene (ATM, BRCA1, BRCA2, CHEK2, PALB2, PMS2, RAD51C, or RAD51D) were found in 6.6% of FOXL2‐mutated AGCT. Potential germline pathogenic CHEK2 variants were found in 3.5% (18/516) of AGCT patients, a rate that was 2.8‐fold higher than Genome Aggregation Database non‐cancer subjects (95% CI 1.8–4.6, p

Abstract Background Avelumab first‐line (1 L) maintenance is a standard of care for advanced urothelial carcinoma (aUC) based on the JAVELIN Bladder 100 phase 3 trial, which showed that avelumab 1 L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression‐free survival (PFS) vs BSC alone in patients who were progression free after receiving 1 L platinum‐containing chemotherapy. Here, we comprehensively screened JAVELIN Bladder 100 trial datasets to identify prognostic factors that define subpopulations of patients with longer or shorter OS irrespective of treatment, and predictive factors that select patients who could obtain a greater OS benefit from avelumab 1 L maintenance treatment. Methods We performed machine learning analyses to screen a large set of baseline covariates, including patient demographics, disease characteristics, laboratory values, molecular biomarkers, and patient‐reported outcomes. Covariates were identified from previously reported analyses and established prognostic and predictive markers. Variables selected from random survival forest models were processed further in univariate Cox models with treatment interaction and visually inspected using correlation analysis and Kaplan–Meier curves. Results were summarized in a multivariable Cox model. Results Prognostic baseline covariates associated with OS included in the final model were assignment to avelumab 1 L maintenance treatment, Eastern Cooperative Oncology Group performance status, site of metastasis, sum of longest target lesion diameters, levels of C‐reactive protein and alkaline phosphatase in blood, lymphocyte proportion in intratumoral stroma, tumor mutational burden, and tumor CD8+ T‐cell infiltration. Potential predictive factors included site of metastasis, tumor mutation burden, and tumor CD8+ T‐cell infiltration. An analysis in patients with PD‐L1+ tumors had similar findings to those in the overall population. Conclusions Machine learning analyses of data from the JAVELIN Bladder 100 trial identified potential prognostic and predictive factors for avelumab 1 L maintenance treatment in patients with aUC, which warrant further evaluation in other clinical datasets.

Background: Mannitol is exclusively recommended in the National Comprehensive Cancer Network guidelines for diuresis in cisplatin (CDDP)‐based chemotherapy. The utility of furosemide, a widely used and convenient diuretic, thus requires clarification. Methods: This is a prospective, single‐centered, open‐label, noninferiority phase II study. Patients with thoracic malignancies who planned to receive CDDP‐based chemotherapy were randomly assigned to receive either mannitol (arm A) or furosemide (arm B). The primary end point was set as the proportion of patients who experienced any grade of "creatinine (Cr) increased" based on the upper limit of the normal range (ULN) during the first cycle as assessed by Common Terminology Criteria for Adverse Events Version 4.0. Secondary end points were Cr increased based on the baseline value during the first cycle, Cr increased after the completion of CDDP, and the proportion of patients with phlebitis. Results: Between April 2018 and March 2022, 115 patients were enrolled and 106 were analyzed. Any grade of Cr increased based on the ULN during the first cycle was 17.3% (arm A) and 24.1% (arm B), respectively (p = 0.34). Therefore, the primary end point was not met. After completion of chemotherapy, any grade of Cr increased was observed in 23.1% (arm A) and 31.5% (arm B), respectively. However, the actual serum Cr level and Cr clearance during the courses were not different between the arms. Phlebitis occurred more frequently in arm A (28.8%) than arm B (16.7%). Conclusions: Mannitol should remain the standard diuresis in CDDP‐based chemotherapy assessed by conventional CTCAE grading, but furosemide can be room for consideration when assessed by actual serum Cr level and Cr clearance. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the associations between the use of statins concurrent with androgen deprivation therapy (ADT) and the risks of mortality in Asian patients diagnosed with prostate cancer (PCa). Methods: Adult patients (≥18 years old) diagnosed with PCa who were receiving any form of ADT and were being treated at public hospitals in Hong Kong from December 1999 to March 2021 were retrospectively identified, with follow-up conducted until September 2021. Patients who had received medical castration for <180days without subsequent bilateral orchidectomy, those who had used statins concurrently with ADT for <180days, and those with missing baseline total cholesterol levels were excluded. Statin users were defined as individuals who had used statins for ≥180days concurrent with ADT, while non-users were those who had not used any statins. PCa-related mortality was the primary outcome, while all-cause mortality served as the secondary outcome. Inverse probability treatment weighting was employed to balance the covariates.Results: A total of 4920 patients were included, consisting of 2578 statin users and 2342 non-users (mean age 76.1±8.2 years). Over a mean follow-up period of 4.2±3.3 years, it was observed that statin users had significantly lower risks of both PCa-related mortality (weighted hazard ratio [wHR] 0.56 [95% confidence interval (CI) 0.48, 0.65], p<0.001) and all-cause mortality (wHR 0.57 [95% CI 0.51, 0.63], p<0.001), regardless of the type of ADT used. Notably, these associations were more pronounced among patients with less advanced PCa, as indicated by the absence of androgen receptor antagonist or chemotherapy usage (p value for interaction <0.001 for both outcomes). Conclusion(s): The use of statins concurrent with ADT was associated with reduced mortality risks among Asian patients with PCa. These findings suggest the need for additional research to explore the potential role of statins in the treatment of PCa patients. [ABSTRACT FROM AUTHOR]

Abstract Background First‐line nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit versus chemotherapy in previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate 648 trial, leading to approvals of both nivolumab‐containing regimens in many countries. We report longer‐term follow‐up data. Methods This open‐label, phase III trial (NCT03143153) enrolled adults with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. Primary endpoints were OS and progression‐free survival (PFS) by blinded independent central review. Hierarchical testing was performed first in patients with tumor cell programmed death ligand 1 (PD‐L1) expression of ≥1% and then in the overall population. Results A total of 970 patients were randomly assigned. After 29 months of minimum follow‐up, nivolumab plus chemotherapy continued to demonstrate improvement in OS versus chemotherapy (hazard ratio [HR] = 0.59 [95% CI: 0.46–0.76]) in patients with tumor cell PD‐L1 expression of ≥1% and in the overall population (HR = 0.78 [95% CI: 0.65–0.93]) and with nivolumab plus ipilimumab versus chemotherapy (HR = 0.62 [95% CI: 0.48–0.80]) in patients with tumor cell PD‐L1 expression of ≥1% and in the overall population (HR = 0.77 [95% CI: 0.65–0.92]). In patients with tumor cell PD‐L1 expression of ≥1%, nivolumab plus chemotherapy demonstrated PFS benefit versus chemotherapy (HR = 0.67 [95% CI: 0.51–0.89]); PFS benefit was not observed with nivolumab plus ipilimumab versus chemotherapy (HR = 1.04 [95% CI: 0.79–1.36]). Among all treated patients (n = 936), Grade 3–4 treatment‐related adverse events were reported in 151 (49%, nivolumab plus chemotherapy), 105 (32%, nivolumab plus ipilimumab), and 110 (36%, chemotherapy) patients. Conclusions Nivolumab plus chemotherapy and nivolumab plus ipilimumab continued to demonstrate clinically meaningful OS benefit versus chemotherapy with no new safety signals identified with longer follow‐up, further supporting use as first‐line standard treatment options for patients with advanced ESCC.

Abstract Background Personalized treatment for non‐small cell lung cancer (NSCLC) has advanced rapidly, and elucidating the genetic changes that trigger this disease is crucial for appropriate treatment selection. Both slow‐pull and aspiration methods of endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) are accepted methods for collecting samples suitable for next‐generation sequencing (NGS) to examine driver gene mutations and translocations in NSCLC. Here, we aimed to determine which of these two methods is superior for obtaining higher‐quality samples from patients with NSCLC. Methods Seventy‐one patients diagnosed with NSCLC via EBUS‐TBNA using the slow‐pull or aspiration (20‐mL negative pressure) methods between July 2019 and September 2022 were included. A total of 203 tissue samples from the 71 patients were fixed in formalin, embedded in paraffin, and mounted on slides. The presence of tissue cores, degree of blood contamination, and number of tumor cells were compared between the groups. The success rate of NGS, using Oncomine Dx Target Test Multi‐CDx, was also compared between the groups. Results The slow‐pull method was associated with a higher yield of tissue cores, lower degree of blood contamination, and higher number of tumor cells than the aspiration method. The success rate of the NGS was also significantly higher for the slow‐pull group (95%) than for the aspiration group (68%). Conclusion Overall, these findings suggest that the slow‐pull method is a superior technique for EBUS‐TBNA to obtain high‐quality tissue samples for NGS. The slow‐pull method may contribute to the identification of driver gene mutations and translocations and facilitate personalized treatment of NSCLC.

Abstract Background Sexual orientation and gender identity (SOGI) data collection in community oncology practices is critical to identify and address cancer inequities, but less than 20% of NCI Community Oncology Research Program (NCORP)‐affiliated practices regularly collect SOGI data despite widespread recommendations. We evaluated multilevel barriers and facilitators for SOGI data collection at NCORP practices. Methods We conducted 14 semi‐structured interviews at seven purposefully sampled NCORP oncology practices. We interviewed one clinician (oncologist, advanced practice provider) and one clinic staff member per practice. Thematic analysis informed by the Consolidated Framework for Implementation Research (CFIR) was conducted to identify barriers and facilitators. Results Thematic saturation occurred after interviews at six practices and was confirmed with interviews at an additional practice. Participants highlighted multilevel barriers including low levels of understanding, information technology infrastructure, and perceived low relative priority. Not understanding the role of SOGI data in oncology care contributed to cis‐heteronormative culture. At the clinic level, this culture coincided with a lack of processes and policies for collecting SOGI from all patients. At the care team level, perceived irrelevance to oncology care was related to discomfort asking SOGI, fear of patient discomfort, and limited awareness of SOGI in electronic health records. Suggested solutions included: normalizing asking SOGI questions, giving patients privacy to complete SOGI, and clarifying clinical relevance. Conclusions SOGI data collection barriers stemmed from perceptions that SOGI disclosure does not influence care quality. Oncology teams may benefit from training on culturally sensitive SOGI collection, education on SOGI data relevance to oncology practices, and support for implementing SOGI data collection policies.

BackgroundCDK12 inactivation leading to increased neoantigen burden has been hypothesized to sensitize tumors to immune checkpoint inhibition. Pan-cancer data regarding the frequency of CDK12 alterations are limited. We aimed to characterize CDK12 alterations across all cancer types through real-world clinical-grade sequencing.MethodsThis was a single-center retrospective analysis of 4994 cancer patients who underwent tissue or blood genomic profiling, including CDK12 assessment, conducted as part of routine care from December 2012 to January 2020. Prevalence, clinical characteristics, and treatment outcomes of patients with tumors with pathogenic CDK12 alterations were described.ResultsIn all, 39 (0.78%, n = 39/4994) patients had pathogenic CDK12 alterations. Among CDK12-altered tumors, the most common organ site was prostate (n = 9, 23.1%) followed by colorectal (n = 5, 12.8%). Adenocarcinoma was the most common histology (n = 26, 66.7%). Median follow-up from time of diagnosis was 4.02 years. Median overall survival from time of metastasis was 4.43 years (95% CI: 3.11-5.74). Ten patients with CDK12-altered tumors received at least one immune checkpoint inhibitor-containing regimen. The majority of patients (n = 6/10, 60%) experienced an objective response. Progression-free survival for patients who had metastatic disease and received a checkpoint inhibitor-containing regimen was 1.16 years (95% CI: 0.32-2.00).ConclusionCDK12 alterations are rare events across hematologic and solid tumor malignancies. They represent a clinically distinct molecular cancer subtype which may have increased responsiveness to checkpoint inhibition. Prospective studies are warranted to investigate checkpoint inhibition in CDK12-altered tumors.

Filanesib is a first-in-class kinesin spindle protein inhibitor which demonstrated safety and encouraging activity in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma in a preliminary analysis of dose-escalation phase results. This multicenter study included first a dose-escalation phase to determine maximum tolerated dose of two schedules of filanesib, bortezomib, and dexamethasone and a subsequent dose-expansion phase using the maximum tolerated doses. In the dose-expansion phase, 28 patients were evaluable for safety and efficacy. The most common grade ≥3 adverse events were neutropenia (21%) and anemia (18%), which were noncumulative and reversible, and hypertension (18%). The overall response rate was 43% with median duration of response not yet reached (range, 2.8-23.7+ months) with median follow-up of 6.3 months. A post hoc analysis incorporated 29 dose-escalation phase patients who received therapeutic filanesib doses, with an overall response rate of 39% and median duration of response of 18.0 months among the 57 total patients with median progression-free survival of 8.5 months. Notably, the PFS of high risk patients was comparable at 8.5 months, driven by the patients with 1q21 gain, characterized by increased MCL-1 expression, with a PFS of 9.1 months versus 3.5 months for the remainder of high risk patients. Patients with t(11;14) also had an encouraging PFS of 15.0 months. The combination of filanesib, bortezomib, and dexamethasone continues to show safety and encouraging activity in relapsed/refractory multiple myeloma, particularly in those patients with 1q21 gain and t(11;14).

Abstract Objective This study sought to investigate interactive participation and content of a moderated discussion forum within a web‐based psychoeducational intervention aimed at alleviating sexual dysfunction and fertility distress in young adults diagnosed with cancer. Methods The study is part of the Fex‐Can Young Adult randomized controlled trial (RCT), in which young adults with self‐reported sexual dysfunction or fertility distress were invited to participate. This study focuses on RCT participants that were randomized into the intervention condition. Sociodemographics and clinical characteristics of intervention participants and level of activity in the intervention were analyzed with descriptive statistics and compared between subgroups (“high” and “low” activity participants). Inductive qualitative thematic analysis was used to analyze the posts in the discussion forum. Results Of 135 intervention participants, 24% met the criteria for high activity participation. There were no statistically significant differences found in terms of clinical and sociodemographic characteristics between high and low activity participants. Ninety‐one participants (67%) accessed the discussion forum, and 19 (14%) posted at least once. Posters shared intimate details of their experiences of sexuality and fertility following cancer. The thematic analysis of posts resulted in four themes: fertility fears, perceptions of the changed body, missing out on life, and importance of support and information. Conclusions While a smaller proportion of participants posted in the discussion forum, a majority spent time reading posts (lurkers). Participants posting in the forum shared experiences of intimate relationships, body image, parenthood concerns, and support needs. The discussion forum was used by a majority of intervention participants, and provided appreciated support for those who posted in the forum. We therefore recommend similar interventions to include this opportunity for interaction and communication.

Abstract Objective This population‐based study examined the association between baseline uric acid (UA) and prostate cancer (PCa)‐related mortality amongst PCa patients receiving androgen deprivation therapy (ADT). Methods Adults with PCa who received ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with missing baseline UA were excluded. Patients were followed up until September 2021. The outcome was PCa‐related mortality. Results Altogether, 4126 patients (median follow‐up 3.1[interquartile range 1.4–6.0] years) were included. A J‐shaped association was observed between baseline UA level and PCa‐related mortality risk, with a direct association in those with mean(0.401 mmol/L) or above‐mean baseline UA levels (hazard ratio (HR) per standard deviation‐increase 1.35 [95% confidence interval 1.21,1.51], p

Abstract Background There is an unmet clinical need for minimally invasive diagnostic tests to improve the detection of grade group (GG) ≥3 prostate cancer relative to prostate antigen‐specific risk calculators. We determined the accuracy of the blood‐based extracellular vesicle (EV) biomarker assay (EV Fingerprint test) at the point of a prostate biopsy decision to predict GG ≥3 from GG ≤2 and avoid unnecessary biopsies. Methods This study analyzed 415 men referred to urology clinics and scheduled for a prostate biopsy, were recruited to the APCaRI 01 prospective cohort study. The EV machine learning analysis platform was used to generate predictive EV models from microflow data. Logistic regression was then used to analyze the combined EV models and patient clinical data and generate the patients' risk score for GG ≥3 prostate cancer. Results The EV‐Fingerprint test was evaluated using the area under the curve (AUC) in discrimination of GG ≥3 from GG ≤2 and benign disease on initial biopsy. EV‐Fingerprint identified GG ≥3 cancer patients with high accuracy (0.81 AUC) at 95% sensitivity and 97% negative predictive value. Using a 7.85% probability cutoff, 95% of men with GG ≥3 would have been recommended a biopsy while avoiding 144 unnecessary biopsies (35%) and missing four GG ≥3 cancers (5%). Conversely, a 5% cutoff would have avoided 31 unnecessary biopsies (7%), missing no GG ≥3 cancers (0%). Conclusions EV‐Fingerprint accurately predicted GG ≥3 prostate cancer and would have significantly reduced unnecessary prostate biopsies.

Abstract Background Pediatric Early Warning Systems (PEWS) assist early detection of clinical deterioration in hospitalized children with cancer. Relevant to successful PEWS implementation, the “stages of change” model characterizes stakeholder support for PEWS based on willingness and effort to adopt the new practice. Methods At five resource‐limited pediatric oncology centers in Latin America, semi‐structured interviews were conducted with 71 hospital staff involved in PEWS implementation. Purposive sampling was used to select centers requiring variable time to complete PEWS implementation, with low‐barrier centers (3–4 months) and high‐barrier centers (10–11 months). Interviews were conducted in Spanish, professionally transcribed, and translated into English. Thematic content analysis explored “stage of change” with constant comparative analysis across stakeholder types and study sites. Results Participants identified six interventions (training, incentives, participation, evidence, persuasion, and modeling) and two policies (environmental planning and mandates) as effective strategies used by implementation leaders to promote stakeholder progression through stages of change. Key approaches involved presentation of evidence demonstrating PEWS effectiveness, persuasion and incentives addressing specific stakeholder interests, enthusiastic individuals serving as models for others, and policies enforced by hospital directors facilitating habitual PEWS use. Effective engagement targeted hospital directors during early implementation phases to provide programmatic legitimacy for clinical staff. Conclusion This study identifies strategies to promote adoption and maintained use of PEWS, highlighting the importance of tailoring implementation strategies to the motivations of each stakeholder type. These findings can guide efforts to implement PEWS and other evidence‐based practices that improve childhood cancer outcomes in resource‐limited hospitals.

Abstract Background Sunitinib is a multi‐target tyrosine kinase inhibitor (TKI) that inhibits VEGF receptor 1, 2, 3 (VEGFRs), platelet‐derived growth factor receptor (PDGFR), colony‐stimulating factor receptor (CSFR), and the stem cell factor receptor c‐KIT. Temsirolimus inhibits mammalian target of rapamycin (mTOR) through binding to intracellular protein FKBP‐12. Both agents are approved for the treatment of metastatic renal cell carcinoma (mRCC), have different anticancer mechanisms, and non‐overlapping toxicities. These attributes form the scientific rationale for sequential combination of these agents. The primary objective of the study was to investigate the efficacy of alternating sunitinib and temsirolimus therapy on progression‐free survival (PFS) in mRCC. Methods We undertook a phase II, multi‐center, single cohort, open‐label study in patients with mRCC. Patients were treated with alternating dosing of 4 weeks of sunitinib 50 mg PO daily, followed by 2 weeks rest, then 4 weeks of temsirolimus 25 mg IV weekly, followed by 2 weeks rest (12 weeks total per cycle). The primary endpoint was PFS. Secondary endpoints included clinical response rate and characterization of the toxicity profile of this combination therapy. Results Nineteen patients were enrolled into the study. The median observed PFS (n = 13 evaluable for PFS) was 8.8 months (95% CI 6.8–25.2 months). Best responses achieved were five partial response, nine stable disease, and three disease progression according to RECIST 1.1 guidelines (two non‐evaluable). The most commonly observed toxicities were fatigue, platelet count decrease, creatinine increased, diarrhea, oral mucositis, edema, anemia, rash, hypophosphatemia, dysgeusia, and palmar‐plantar erythrodysesthesia syndrome. Conclusion Alternating sunitinib and temsirolimus did not improve the PFS in patients with mRCC.

Abstract Purpose To assess the effectiveness and safety of acupuncture for the prevention of chemotherapy‐induced nausea and vomiting (CINV), with a specific intention on exploring sources of between‐study variation in treatment effects. Methods MEDLINE, EMBASE, Cochrane CENTRAL, CINAHL, Chinese Biomedical Literature Database, VIP Chinese Science and Technology Periodicals Database, China National Knowledge Infrastructure, and Wanfang were searched to identify randomized controlled trials (RCTs) that compared acupuncture to sham acupuncture or usual care (UC). The main outcome is complete control (no vomiting episodes and/or no more than mild nausea) of CINV. GRADE approach was used to rate the certainty of evidence. Results Thirty‐eight RCTs with a total of 2503 patients were evaluated. Acupuncture in addition to UC may increase the complete control of acute vomiting (RR, 1.13; 95% CI, 1.02 to 1.25; 10 studies) and delayed vomiting (RR, 1.47; 95% CI, 1.07 to 2.00; 10 studies) when compared with UC only. No effects were found for all other review outcomes. The certainty of evidence was generally low or very low. None of the predefined moderators changed the overall findings, but in an exploratory moderator analysis we found that an adequate reporting of planned rescue antiemetics might decrease the effect size of complete control of acute vomiting (p = 0.035). Conclusion Acupuncture in addition to usual care may increase the complete control of chemotherapy‐induced acute vomiting and delayed vomiting but the certainty of evidence was very low. Well‐designed RCTs with larger sample sizes, standardized treatment regimens, and core outcome measures are needed.

Abstract Background The COVID‐19 pandemic altered healthcare systems globally, causing delays in care delivery and increased anxiety among patients and families. This study examined how hospital stakeholders and clinicians perceived the global impact of the COVID‐19 pandemic on children with cancer and their families. Methods This secondary analysis examined data from a qualitative study consisting of 19 focus groups conducted in 8 languages throughout 16 countries. A codebook was developed with novel codes derived inductively from transcript review. In‐depth analysis focused on the impact of the COVID‐19 pandemic on children with cancer and their families. Results Eight themes describing the impact of the pandemic on patients and their families were identified and classified into three domains: contributing factors (COVID‐19 Policies, Cancer Treatment Modifications, COVID‐19 Symptoms, Beliefs), patient‐related impacts (Quality of Care, Psychosocial impacts, Treatment Reluctance), and the central transformer (Communication). Participants described the ability of communication to transform the effect of contributing factors on patient‐related impacts. The valence of impacts depended on the quality and quantity of communication among clinicians and between clinicians and patients and families. Conclusions Communication served as the central factor impacting whether the COVID‐19 pandemic positively or negatively affected children with cancer and families. These findings emphasize the key role communication plays in delivering patient‐centered care and can guide future development of communication‐centered interventions globally.

Abstract Background Mannitol is exclusively recommended in the National Comprehensive Cancer Network guidelines for diuresis in cisplatin (CDDP)‐based chemotherapy. The utility of furosemide, a widely used and convenient diuretic, thus requires clarification. Methods This is a prospective, single‐centered, open‐label, noninferiority phase II study. Patients with thoracic malignancies who planned to receive CDDP‐based chemotherapy were randomly assigned to receive either mannitol (arm A) or furosemide (arm B). The primary end point was set as the proportion of patients who experienced any grade of “creatinine (Cr) increased” based on the upper limit of the normal range (ULN) during the first cycle as assessed by Common Terminology Criteria for Adverse Events Version 4.0. Secondary end points were Cr increased based on the baseline value during the first cycle, Cr increased after the completion of CDDP, and the proportion of patients with phlebitis. Results Between April 2018 and March 2022, 115 patients were enrolled and 106 were analyzed. Any grade of Cr increased based on the ULN during the first cycle was 17.3% (arm A) and 24.1% (arm B), respectively (p = 0.34). Therefore, the primary end point was not met. After completion of chemotherapy, any grade of Cr increased was observed in 23.1% (arm A) and 31.5% (arm B), respectively. However, the actual serum Cr level and Cr clearance during the courses were not different between the arms. Phlebitis occurred more frequently in arm A (28.8%) than arm B (16.7%). Conclusions Mannitol should remain the standard diuresis in CDDP‐based chemotherapy assessed by conventional CTCAE grading, but furosemide can be room for consideration when assessed by actual serum Cr level and Cr clearance.

Background: Personalized treatment for non‐small cell lung cancer (NSCLC) has advanced rapidly, and elucidating the genetic changes that trigger this disease is crucial for appropriate treatment selection. Both slow‐pull and aspiration methods of endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) are accepted methods for collecting samples suitable for next‐generation sequencing (NGS) to examine driver gene mutations and translocations in NSCLC. Here, we aimed to determine which of these two methods is superior for obtaining higher‐quality samples from patients with NSCLC. Methods: Seventy‐one patients diagnosed with NSCLC via EBUS‐TBNA using the slow‐pull or aspiration (20‐mL negative pressure) methods between July 2019 and September 2022 were included. A total of 203 tissue samples from the 71 patients were fixed in formalin, embedded in paraffin, and mounted on slides. The presence of tissue cores, degree of blood contamination, and number of tumor cells were compared between the groups. The success rate of NGS, using Oncomine Dx Target Test Multi‐CDx, was also compared between the groups. Results: The slow‐pull method was associated with a higher yield of tissue cores, lower degree of blood contamination, and higher number of tumor cells than the aspiration method. The success rate of the NGS was also significantly higher for the slow‐pull group (95%) than for the aspiration group (68%). Conclusion: Overall, these findings suggest that the slow‐pull method is a superior technique for EBUS‐TBNA to obtain high‐quality tissue samples for NGS. The slow‐pull method may contribute to the identification of driver gene mutations and translocations and facilitate personalized treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Background: Sexual orientation and gender identity (SOGI) data collection in community oncology practices is critical to identify and address cancer inequities, but less than 20% of NCI Community Oncology Research Program (NCORP)‐affiliated practices regularly collect SOGI data despite widespread recommendations. We evaluated multilevel barriers and facilitators for SOGI data collection at NCORP practices. Methods: We conducted 14 semi‐structured interviews at seven purposefully sampled NCORP oncology practices. We interviewed one clinician (oncologist, advanced practice provider) and one clinic staff member per practice. Thematic analysis informed by the Consolidated Framework for Implementation Research (CFIR) was conducted to identify barriers and facilitators. Results: Thematic saturation occurred after interviews at six practices and was confirmed with interviews at an additional practice. Participants highlighted multilevel barriers including low levels of understanding, information technology infrastructure, and perceived low relative priority. Not understanding the role of SOGI data in oncology care contributed to cis‐heteronormative culture. At the clinic level, this culture coincided with a lack of processes and policies for collecting SOGI from all patients. At the care team level, perceived irrelevance to oncology care was related to discomfort asking SOGI, fear of patient discomfort, and limited awareness of SOGI in electronic health records. Suggested solutions included: normalizing asking SOGI questions, giving patients privacy to complete SOGI, and clarifying clinical relevance. Conclusions: SOGI data collection barriers stemmed from perceptions that SOGI disclosure does not influence care quality. Oncology teams may benefit from training on culturally sensitive SOGI collection, education on SOGI data relevance to oncology practices, and support for implementing SOGI data collection policies. [ABSTRACT FROM AUTHOR]

Abstract Background There are no previous reports on the main causes of death in biliary tract cancer (BTC) patients. This study aimed to evaluate the main causes of death and survival rates in patients with BTC. Methods We retrospectively evaluated 143 patients who were diagnosed with unresectable BTC between August 2010 and March 2020. We classified the main causes of death based on laboratory data, imaging studies, and medical records. The main causes of death evaluated included liver failure, cholangitis, cachexia, other causes associated with tumor progression, and complications. We also analyzed survival rates for each main cause of death. Results After excluding patients who were lost to follow‐up, living patients, and patients who had no records of laboratory data within 30 days before the date of death, 108 patients were analyzed. The main cause of death was cholangitis in 33 (30.6%), cachexia in 22 (20.4%), liver failure in 10 (9.3%), other causes associated with tumor progression in 18 (16.7%), and complications in 25 (23.2%) patients. Median overall survival (OS) was 334.0 days in the chemotherapy group and 75.0 days in the best supportive care (BSC) group. Survival analyzed according to the main cause of death was significantly different between the chemotherapy and BSC groups; OS for cachexia, cholangitis, liver failure, other causes associated with tumor progression, and complications, respectively, were 453.0, 499.0, 567.0, 205.0, and 327.5 days (p = 0.003) in the chemotherapy group and 219.0, 69.0, 34.0, 93.0, and 56.0 days (p = 0.001) in the BSC group. Conclusion The main causes of death in patients with advanced BTC are cholangitis, cachexia, liver failure, other causes associated with tumor progression, and complications. Other causes associated with tumor progression in the chemotherapy group, and liver failure in the BSC group as the main causes of death shortened the survival of BTC patients.

Abstract Background Patients with alveolar rhabdomyosarcoma (ARMS) have inferior outcomes compared to patients with embryonal rhabdomyosarcoma (ERMS) and more effective chemotherapy options are needed for these patients. Vinorelbine is a semisynthetic vinca alkaloid that has clinical activity in relapsed rhabdomyosarcoma (RMS) when used alone or in combination with cyclophosphamide. Aims The goal of our study was to evaluate whether RMS histology subtype influences response rate to vinorelbine alone or in combination. Materials & Methods Five Phase 2 trials that enrolled RMS patients were included in the meta‐analysis. Two studies evaluated vinorelbine alone, two studies evaluated vinorelbine in combination with low dose oral cyclophosphamide, and one study evaluated vinorelbine and intravenous cyclophosphamide in combination with temsirolimus or bevacizumab. All RMS patients had relapsed or refractory disease and had received at least one prior therapy. Response was reported according to RECIST1.1 and was defined as a complete or partial response. Response data was obtained from published results or from trial principal investigator. RMS NOS patients were grouped with ERMS patients for this analysis. Summary estimates comparing differences between ARMS and ERMS response rates were generated using a random‐effects model to account for heterogeneity among the studies. Results One hundred fifty‐six enrolled patients evaluable for response were included in the meta‐analysis, 85 ARMS, 64 ERMS and 7 RMS‐NOS. The combined effect generated from the random‐effects model demonstrated a 41% increase (p = 0.001, 95% CI; 0.21–0.60) in response to vinorelbine as a single agent or in combination in patients with ARMS compared to patients with ERMS. There was no significant difference in the rate of progressive disease between patients with ARMS compared to ERMS (p = 0.1, 95%CI; −0.26–0.02). Discussion Vinorelbine is an active agent for the treatment of relapsed or refractory RMS and a meta‐analysis of Phase 2 studies shows that radiographic responses in patients with ARMS were significantly higher than ERMS or RMS‐NOS. Conclusion These data support further investigation of vinorelbine in newly diagnosed patients with RMS particularly those with alveolar histology.

Abstract Pembrolizumab plus chemotherapy improved progression‐free survival (PFS) and overall survival (OS) compared with placebo plus chemotherapy in patients with previously untreated locally recurrent inoperable or metastatic triple‐negative breast cancer with tumor programmed cell death ligand 1 (PD‐L1) combined positive score (CPS) ≥10 in the global, phase 3, randomized controlled trial KEYNOTE‐355. We report results for patients enrolled in Japan. Patients were randomized 2:1 to pembrolizumab 200 mg or placebo Q3W for 35 cycles plus chemotherapy (nab‐paclitaxel, paclitaxel, or gemcitabine–carboplatin). Primary endpoints were PFS per RECIST version 1.1 by blinded independent central review and OS in patients with PD‐L1 CPS ≥10, PD‐L1 CPS ≥1, and the intention‐to‐treat (ITT) population. No alpha was assigned to this exploratory analysis. Eighty‐seven patients were randomized in Japan (pembrolizumab plus chemotherapy, n = 61; placebo plus chemotherapy, n = 26), 66 (76%) had PD‐L1 CPS ≥1, and 28 (32%) had PD‐L1 CPS ≥10. Median time from randomization to data cutoff (June 15, 2021) was 44.7 (range, 37.2–52.9) months in the ITT population. Hazard ratios (HRs; 95% CI) for OS were 0.36 (0.14–0.89), 0.52 (0.30–0.91), and 0.46 (0.28–0.77) in the PD‐L1 CPS ≥10, PD‐L1 CPS ≥1, and ITT populations, respectively. HRs (95% CI) for PFS were 0.52 (0.20–1.34), 0.61 (0.35–1.06), and 0.64 (0.39–1.05). Grade 3 or 4 treatment‐related adverse events occurred in 85% of patients in each group (no grade 5 events). Consistent with the global population, pembrolizumab plus chemotherapy tended to show improvements in OS and PFS with manageable toxicity versus placebo plus chemotherapy in Japanese patients and supports this combination in this setting.

Abstract Background While immune checkpoint inhibitors (ICIs) are associated with elevated cardiovascular risks, evidence of any association between ICIs and myocardial infarction (MI) was scarce, especially in Asians. Methods Using prospectively collected population‐based data, this self‐controlled case series included patients prescribed an ICI between 1/1/2014 and 31/12/2020 in Hong Kong who had MI within January 1, 2013 to December 31, 2021. Incidence rate ratios (IRRs) for MI during and after ICI exposure were estimated, compared to the year before ICI initiation. Results Of 3684 identified ICI users, 24 had MI during the study period. MI incidence increased significantly in the first 90 days of exposure (IRR 3.59 [95% confidence interval: 1.31–9.83], p = 0.013), but not days 91–180 (p = 0.148) or ≥181 (p = 0.591) of exposure, nor postexposure (p = 0.923). Sensitivity analyses excluding patients with MI‐related death and incorporating extended exposure periods produced consistent results separately. Conclusions ICIs were associated with increased MI incidence in Asian Chinese patients during the first 90 days of use, but not later.

Abstract Background Cancer can impact the psychological well‐being of both patients and their informal caregivers. We investigated the joint trajectories of psychological distress among Singaporean advanced cancer patients–caregiver dyads. We also examined predictors of trajectory group membership. Methods This study utilised data from 299 patients with advanced solid cancer and their caregivers over 33 months (12 times points). Group‐based trajectory modelling was used to examine the joint trajectories of patient anxiety, patient depression, caregiver anxiety and caregiver depression scores using the Hospital Anxiety and Depression Scale. Results Four joint trajectory groups were found: (1) Patient–caregiver low distress (27%), (2) patient–caregiver increasing distress (28.5%), (3) patient low‐ caregiver borderline distress (25%), (4) patient‐caregiver high distress (19.5%). Dyads where the patient is below 50 years of age were more likely to be in Group 4. Dyads where caregiver–patient emotional closeness was low were more likely to be in Groups 2 or 4 where dyads reported increasing/high distress. Dyads that reported financial inadequacy were more likely to be in Groups 2, 3 and 4, while dyads with caregivers who were employed were more likely to be in group 3. Conclusions A substantial proportion of patients and caregivers reported anxiety and/or depression that lasted or increased throughout the study duration. We found significant heterogeneity in how dyads experienced psychological distress, suggesting that efforts should consider dyadic differences when providing psychological support. Particular focus should be placed on identifying dyads that are at risk and who require additional support.

Abstract Background A strong relationship has been observed between comorbidities and the risk of severe/fatal COVID‐19 manifestations, but no score is available to evaluate their association in cancer patients. To make up for this lacuna, we aimed to develop a comorbidity score for cancer patients, based on the Lombardy Region healthcare databases. Methods We used hospital discharge records to identify patients with a new diagnosis of solid cancer between February and December 2019; 61 comorbidities were retrieved within 2 years before cancer diagnosis. This cohort was split into training and validation sets. In the training set, we used a LASSO‐logistic model to identify comorbidities associated with the risk of developing a severe/fatal form of COVID‐19 during the first pandemic wave (March–May 2020). We used a logistic model to estimate comorbidity score weights and then we divided the score into five classes (=5). In the validation set, we assessed score performance by areas under the receiver operating characteristic curve (AUC) and calibration plots. We repeated the process on second pandemic wave (October–December 2020) data. Results We identified 55,425 patients with an incident solid cancer. We selected 21 comorbidities as independent predictors. The first four score classes showed similar probability of experiencing the outcome (0.2% to 0.5%), while the last showed a probability equal to 5.8%. The score performed well in both the first and second pandemic waves: AUC 0.85 and 0.82, respectively. Our results were robust for major cancer sites too (i.e., colorectal, lung, female breast, and prostate). Conclusions We developed a high performance comorbidity score for cancer patients and COVID‐19. Being based on administrative databases, this score will be useful for adjusting for comorbidity confounding in epidemiological studies on COVID‐19 and cancer impact.

Abstract Background In high‐income countries, hope facilitates parental coping and builds the clinical relationship between families of children with cancer and their clinicians. However, the manifestation of hope in low‐ and middle‐income countries (LMICs) remains poorly understood. Our study explores Guatemalan parents' experiences with hope during the pediatric oncology diagnostic process and aims to identify discrete actions clinicians take to support hope. Methods This qualitative study utilized audio‐recordings of the diagnostic process and an additional semi‐structured interview for 20 families of children with cancer at Unidad Nacional de Oncología Pediátrica in Guatemala. Spanish audio‐recordings were translated into English, transcribed, and coded using a priori and novel codes. Thematic content analysis using constant comparative methods explored parents' hopes and concerns. Results At diagnosis, Guatemalan parents expressed both hopes and concerns related to the entire cancer continuum. Throughout the diagnostic process, hope grew as concerns were alleviated. Clinicians supported hope by creating a supportive environment, providing information, affirming religious beliefs, and empowering parents. These strategies helped parents shift their focus from fear and uncertainty toward hope for their child's future. Parents expressed that establishing hope improved mood, promoted acceptance, and enabled them to care for themselves and their children. Conclusion These results confirm the relevance of supporting hope in pediatric oncology settings in LMICs and suggest that culture informs hope‐related needs. Supporting hope is critical across cultures and can be integrated into clinical conversation using the four processes identified by our results.

Abstract Background Black breast and ovarian cancer patients are underrepresented in clinical cancer trials disproportionate to the prevalence of these cancers in Black females. Historically, lower enrollment has been attributed to individualized factors, including medical mistrust, but more recently structural factors, including systemic racism, have received additional scrutiny. We interviewed Black women with a personal or family history of breast and ovarian cancer to understand their views and experiences related to research participation. Methods Qualitative interviews were conducted via telephone or video conference and transcribed verbatim. Transcripts were qualitatively analyzed for iterative themes related to the offer and participation in cancer clinical trials and research studies, impact on cancer care, and recommendations to increase enrollment of Black patients. Results Sixty‐one Black women completed an interview. Participants expressed that Black women are underrepresented in cancer research, and that this negatively impacted their own care. Many cited past historical abuses, including the Tuskegee syphilis trial, as a potential factor for lower enrollment but suggested that lower enrollment was better understood in the context of the entirety of their healthcare experiences, including present‐day examples of patient mistreatment or dismissal. Participants suggested that proactive community engagement, transparency, and increased representation of Black research team members were strategies likely to foster trust and bolster research participation. Conclusion(s) Medical mistrust is only a partial factor in the lower participation of Black patients in cancer research. Researchers should implement the strategies identified by our participants to promote diverse enrollment and ensure that Black patients are included in future therapeutic advances.

Abstract Background Survivorship care plans (SCPs) communicate cancer‐related information from oncology providers to patients and primary care providers. SCPs may limit overuse testing by specifying necessary follow‐up care. From a randomized, controlled trial of SCP delivery, we examined whether cancer‐related tests not specified in SCPs, but conducted after SCP receipt, were appropriate or consistent with overuse. Methods Survivors of breast, colorectal, or prostate cancer treated at urban‐academic or rural‐community health systems were randomized to one of three SCP delivery arms. Tests during 18 months after SCP receipt were classified as consistent with overuse if they were (1) not included in SCPs and (2) on a guideline‐based predetermined list of “not recommended surveillance.” After chart abstraction, physicians performed review and adjudication of potential overuse. Descriptive analyses were conducted of tests consistent with overuse. Negative binomial regression models determined if testing consistent with overuse differed across study arms. Results Among 316 patients (137 breast, 67 colorectal, 112 prostate), 140 individual tests were identified as potential overuse. Upon review, 98 were deemed to be consistent with overuse: 78 tumor markers and 20 imaging tests. The majority of overuse testing was breast cancer‐related (95%). Across sites, 27 patients (9%) received ≥1 test consistent with overuse; most were breast cancer patients (22/27). Exploratory analyses of overuse test frequency by study arm showed no significant difference. Conclusions This analysis identified practice patterns consistent with overuse of surveillance testing and can inform efforts to improve guideline‐concordant care. Future interventions may include individual practice patterns and provider education.

Objective: This population‐based study examined the association between baseline uric acid (UA) and prostate cancer (PCa)‐related mortality amongst PCa patients receiving androgen deprivation therapy (ADT). Methods: Adults with PCa who received ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with missing baseline UA were excluded. Patients were followed up until September 2021. The outcome was PCa‐related mortality. Results: Altogether, 4126 patients (median follow‐up 3.1[interquartile range 1.4–6.0] years) were included. A J‐shaped association was observed between baseline UA level and PCa‐related mortality risk, with a direct association in those with mean(0.401 mmol/L) or above‐mean baseline UA levels (hazard ratio (HR) per standard deviation‐increase 1.35 [95% confidence interval 1.21,1.51], p < 0.001), and an inverse association in those with below‐mean baseline UA levels (HR 0.78[0.67,0.92], p = 0.003). The former remained significant on competing risk regression, but not the latter. Conclusions: A J‐shaped relationship between baseline UA level and PCa‐related mortality risk was identified. This study was mainly limited by potential unmeasured and residual confounders. Further validation studies are warranted. [ABSTRACT FROM AUTHOR]

Objective: This study sought to investigate interactive participation and content of a moderated discussion forum within a web‐based psychoeducational intervention aimed at alleviating sexual dysfunction and fertility distress in young adults diagnosed with cancer. Methods: The study is part of the Fex‐Can Young Adult randomized controlled trial (RCT), in which young adults with self‐reported sexual dysfunction or fertility distress were invited to participate. This study focuses on RCT participants that were randomized into the intervention condition. Sociodemographics and clinical characteristics of intervention participants and level of activity in the intervention were analyzed with descriptive statistics and compared between subgroups ("high" and "low" activity participants). Inductive qualitative thematic analysis was used to analyze the posts in the discussion forum. Results: Of 135 intervention participants, 24% met the criteria for high activity participation. There were no statistically significant differences found in terms of clinical and sociodemographic characteristics between high and low activity participants. Ninety‐one participants (67%) accessed the discussion forum, and 19 (14%) posted at least once. Posters shared intimate details of their experiences of sexuality and fertility following cancer. The thematic analysis of posts resulted in four themes: fertility fears, perceptions of the changed body, missing out on life, and importance of support and information. Conclusions: While a smaller proportion of participants posted in the discussion forum, a majority spent time reading posts (lurkers). Participants posting in the forum shared experiences of intimate relationships, body image, parenthood concerns, and support needs. The discussion forum was used by a majority of intervention participants, and provided appreciated support for those who posted in the forum. We therefore recommend similar interventions to include this opportunity for interaction and communication. [ABSTRACT FROM AUTHOR]

Background: There is an unmet clinical need for minimally invasive diagnostic tests to improve the detection of grade group (GG) ≥3 prostate cancer relative to prostate antigen‐specific risk calculators. We determined the accuracy of the blood‐based extracellular vesicle (EV) biomarker assay (EV Fingerprint test) at the point of a prostate biopsy decision to predict GG ≥3 from GG ≤2 and avoid unnecessary biopsies. Methods: This study analyzed 415 men referred to urology clinics and scheduled for a prostate biopsy, were recruited to the APCaRI 01 prospective cohort study. The EV machine learning analysis platform was used to generate predictive EV models from microflow data. Logistic regression was then used to analyze the combined EV models and patient clinical data and generate the patients' risk score for GG ≥3 prostate cancer. Results: The EV‐Fingerprint test was evaluated using the area under the curve (AUC) in discrimination of GG ≥3 from GG ≤2 and benign disease on initial biopsy. EV‐Fingerprint identified GG ≥3 cancer patients with high accuracy (0.81 AUC) at 95% sensitivity and 97% negative predictive value. Using a 7.85% probability cutoff, 95% of men with GG ≥3 would have been recommended a biopsy while avoiding 144 unnecessary biopsies (35%) and missing four GG ≥3 cancers (5%). Conversely, a 5% cutoff would have avoided 31 unnecessary biopsies (7%), missing no GG ≥3 cancers (0%). Conclusions: EV‐Fingerprint accurately predicted GG ≥3 prostate cancer and would have significantly reduced unnecessary prostate biopsies. [ABSTRACT FROM AUTHOR]

Background: Pediatric Early Warning Systems (PEWS) assist early detection of clinical deterioration in hospitalized children with cancer. Relevant to successful PEWS implementation, the "stages of change" model characterizes stakeholder support for PEWS based on willingness and effort to adopt the new practice. Methods: At five resource‐limited pediatric oncology centers in Latin America, semi‐structured interviews were conducted with 71 hospital staff involved in PEWS implementation. Purposive sampling was used to select centers requiring variable time to complete PEWS implementation, with low‐barrier centers (3–4 months) and high‐barrier centers (10–11 months). Interviews were conducted in Spanish, professionally transcribed, and translated into English. Thematic content analysis explored "stage of change" with constant comparative analysis across stakeholder types and study sites. Results: Participants identified six interventions (training, incentives, participation, evidence, persuasion, and modeling) and two policies (environmental planning and mandates) as effective strategies used by implementation leaders to promote stakeholder progression through stages of change. Key approaches involved presentation of evidence demonstrating PEWS effectiveness, persuasion and incentives addressing specific stakeholder interests, enthusiastic individuals serving as models for others, and policies enforced by hospital directors facilitating habitual PEWS use. Effective engagement targeted hospital directors during early implementation phases to provide programmatic legitimacy for clinical staff. Conclusion: This study identifies strategies to promote adoption and maintained use of PEWS, highlighting the importance of tailoring implementation strategies to the motivations of each stakeholder type. These findings can guide efforts to implement PEWS and other evidence‐based practices that improve childhood cancer outcomes in resource‐limited hospitals. [ABSTRACT FROM AUTHOR]

Background: Sunitinib is a multi‐target tyrosine kinase inhibitor (TKI) that inhibits VEGF receptor 1, 2, 3 (VEGFRs), platelet‐derived growth factor receptor (PDGFR), colony‐stimulating factor receptor (CSFR), and the stem cell factor receptor c‐KIT. Temsirolimus inhibits mammalian target of rapamycin (mTOR) through binding to intracellular protein FKBP‐12. Both agents are approved for the treatment of metastatic renal cell carcinoma (mRCC), have different anticancer mechanisms, and non‐overlapping toxicities. These attributes form the scientific rationale for sequential combination of these agents. The primary objective of the study was to investigate the efficacy of alternating sunitinib and temsirolimus therapy on progression‐free survival (PFS) in mRCC. Methods: We undertook a phase II, multi‐center, single cohort, open‐label study in patients with mRCC. Patients were treated with alternating dosing of 4 weeks of sunitinib 50 mg PO daily, followed by 2 weeks rest, then 4 weeks of temsirolimus 25 mg IV weekly, followed by 2 weeks rest (12 weeks total per cycle). The primary endpoint was PFS. Secondary endpoints included clinical response rate and characterization of the toxicity profile of this combination therapy. Results: Nineteen patients were enrolled into the study. The median observed PFS (n = 13 evaluable for PFS) was 8.8 months (95% CI 6.8–25.2 months). Best responses achieved were five partial response, nine stable disease, and three disease progression according to RECIST 1.1 guidelines (two non‐evaluable). The most commonly observed toxicities were fatigue, platelet count decrease, creatinine increased, diarrhea, oral mucositis, edema, anemia, rash, hypophosphatemia, dysgeusia, and palmar‐plantar erythrodysesthesia syndrome. Conclusion: Alternating sunitinib and temsirolimus did not improve the PFS in patients with mRCC. [ABSTRACT FROM AUTHOR]

Purpose: To assess the effectiveness and safety of acupuncture for the prevention of chemotherapy‐induced nausea and vomiting (CINV), with a specific intention on exploring sources of between‐study variation in treatment effects. Methods: MEDLINE, EMBASE, Cochrane CENTRAL, CINAHL, Chinese Biomedical Literature Database, VIP Chinese Science and Technology Periodicals Database, China National Knowledge Infrastructure, and Wanfang were searched to identify randomized controlled trials (RCTs) that compared acupuncture to sham acupuncture or usual care (UC). The main outcome is complete control (no vomiting episodes and/or no more than mild nausea) of CINV. GRADE approach was used to rate the certainty of evidence. Results: Thirty‐eight RCTs with a total of 2503 patients were evaluated. Acupuncture in addition to UC may increase the complete control of acute vomiting (RR, 1.13; 95% CI, 1.02 to 1.25; 10 studies) and delayed vomiting (RR, 1.47; 95% CI, 1.07 to 2.00; 10 studies) when compared with UC only. No effects were found for all other review outcomes. The certainty of evidence was generally low or very low. None of the predefined moderators changed the overall findings, but in an exploratory moderator analysis we found that an adequate reporting of planned rescue antiemetics might decrease the effect size of complete control of acute vomiting (p = 0.035). Conclusion: Acupuncture in addition to usual care may increase the complete control of chemotherapy‐induced acute vomiting and delayed vomiting but the certainty of evidence was very low. Well‐designed RCTs with larger sample sizes, standardized treatment regimens, and core outcome measures are needed. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic altered healthcare systems globally, causing delays in care delivery and increased anxiety among patients and families. This study examined how hospital stakeholders and clinicians perceived the global impact of the COVID‐19 pandemic on children with cancer and their families. Methods: This secondary analysis examined data from a qualitative study consisting of 19 focus groups conducted in 8 languages throughout 16 countries. A codebook was developed with novel codes derived inductively from transcript review. In‐depth analysis focused on the impact of the COVID‐19 pandemic on children with cancer and their families. Results: Eight themes describing the impact of the pandemic on patients and their families were identified and classified into three domains: contributing factors (COVID‐19 Policies, Cancer Treatment Modifications, COVID‐19 Symptoms, Beliefs), patient‐related impacts (Quality of Care, Psychosocial impacts, Treatment Reluctance), and the central transformer (Communication). Participants described the ability of communication to transform the effect of contributing factors on patient‐related impacts. The valence of impacts depended on the quality and quantity of communication among clinicians and between clinicians and patients and families. Conclusions: Communication served as the central factor impacting whether the COVID‐19 pandemic positively or negatively affected children with cancer and families. These findings emphasize the key role communication plays in delivering patient‐centered care and can guide future development of communication‐centered interventions globally. [ABSTRACT FROM AUTHOR]

BackgroundHospitalized pediatric hematology-oncology (PHO) patients are at high risk for critical illness, especially in resource-limited settings. Unfortunately, there are no established quality indicators to guide institutional improvement for these patients. The objective of this study was to identify quality indicators to include in PROACTIVE (PediatRic Oncology cApaCity assessment Tool for IntensiVe carE), an assessment tool to evaluate the capacity and quality of pediatric critical care services offered to PHO patients.MethodsA comprehensive literature review identified relevant indicators in the areas of structure, performance, and outcomes. An international focus group sorted potential indicators using the framework of domains and subdomains. A modified, three-round Delphi was conducted among 36 international experts with diverse experience in PHO and critical care in high-resource and resource-limited settings. Quality indicators were ranked on relevance and actionability via electronically distributed surveys.ResultsPROACTIVE contains 119 indicators among eight domains and 22 subdomains, with high-median importance (≥7) in both relevance and actionability, and ≥80% evaluator agreement. The top five indicators were: (a) A designated PICU area; (b) Availability of a pediatric intensivist; (c) A PHO physician as part of the primary team caring for critically ill PHO patients; (d) Trained nursing staff in pediatric critical care; and (e) Timely PICU transfer of hospitalized PHO patients requiring escalation of care.ConclusionsPROACTIVE is a consensus-derived tool to assess the capacity and quality of pediatric onco-critical care in resource-limited settings. Future endeavors include validation of PROACTIVE by correlating the proposed indicators to clinical outcomes and its implementation to identify service delivery gaps amenable to improvement.

Abstract Background Developments in medical technology are resulting in continuous decreases in the cancer mortality rate of patients with gallbladder cancer, while non‐cancer deaths in cancer patients are becoming more common. The main cause of this is cardiovascular mortality (CVM). The purpose of this study was to determine the CVM risk in patients with primary gallbladder cancer (PGC). Methods We extracted information on patients in the SEER database who were diagnosed with PGC from 2004 to 2015, compared CVM in patients with PGC with the general United States population, and calculated standardized mortality rates (SMRs) and the absolute excess risk. A competing risks model was used to identify and analyze the independent risk factors for cardiovascular death in patients with PGC. Results This study included 5925 patients, 247 of whom died from cardiovascular disease. The SMR of cardiovascular death in patients with PGC was 15.84 (95% confidence interval: 15.83–15.85), and the SMR was slightly lower in male than female patients. The competing risks analysis indicated that age, marital status, cancer cell differentiation, chemotherapy status, and year of diagnosis were risk factors for cardiovascular death in patients with PGC. Conclusions The CVM risk is considerably higher in patients with PGC than in the general population. It is therefore very necessary to apply cardioprotective interventions to patients with PGC.