cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.24185309
title: ctDNA-guided adjuvant treatment after radical-intent treatment of metastatic spread from colorectal cancer—the first interim results from the OPTIMISE study

description: Patients with detectable ctDNA after radical-intent treatment of metastatic spread from colorectal cancer (mCRC) have a very high risk of recurrence, which may be prevented with intensified adjuvant chemotherapy (aCTh). In the OPTIMISE study, we investigate ctDNA-guided aCTh after radical-intent treatment of mCRC. Here we present results from the preplanned interim analysis. The study is an open-label 1:1 randomized clinical trial comparing ctDNA-guided aCTh against standard of care (SOC), with a run-in phase investigating feasibility measures. Key inclusion criteria; radical-intent treatment for mCRC and clinically eligible for triple-agent chemotherapy. Patients underwent a PET-CT scan before randomization. ctDNA analyses of plasma samples were done by ddPCR, detecting CRC-specific mutations and methylation of the <i>NPY</i> gene. In the ctDNA-guided arm, ctDNA positivity led to an escalation strategy with triple-agent chemotherapy, and conversely ctDNA negativity led to a de-escalation strategy by shared-decision making. Patients randomized to the standard arm were treated according to SOC. Feasibility measures for the run-in phase were; the inclusion of 30 patients over 12 months in two Danish hospitals, compliance with randomization &gt;80%, rate of PET-CT-positive findings &lt;20%, and eligibility for triple-agent chemotherapy &gt;80%. Thirty-two patients were included. The rate of PET-CT-positive cases was 22% (<i>n</i> = 7/32). Ninety-seven percent of the patients were randomized. Fourteen patients were randomly assigned to SOC and sixteen to ctDNA-guided adjuvant treatment and follow-up. All analyses of baseline plasma samples in the ctDNA-guided arm passed the quality control, and 19% were ctDNA positive. The median time to result was three working days. All ctDNA-positive patients were eligible for triple-agent chemotherapy. The study was proven to be feasible and continues in the planned large-scale phase II trial. Results from the OPTIMISE study will potentially optimize the adjuvant treatment of patients undergoing radical-intent treatment of mCRC, thereby improving survival and reducing chemotherapy-related toxicity.
DOI: 10.6084/m9.figshare.24185309.v1
title: ctDNA-guided adjuvant treatment after radical-intent treatment of metastatic spread from colorectal cancer—the first interim results from the OPTIMISE study

description: Patients with detectable ctDNA after radical-intent treatment of metastatic spread from colorectal cancer (mCRC) have a very high risk of recurrence, which may be prevented with intensified adjuvant chemotherapy (aCTh). In the OPTIMISE study, we investigate ctDNA-guided aCTh after radical-intent treatment of mCRC. Here we present results from the preplanned interim analysis. The study is an open-label 1:1 randomized clinical trial comparing ctDNA-guided aCTh against standard of care (SOC), with a run-in phase investigating feasibility measures. Key inclusion criteria; radical-intent treatment for mCRC and clinically eligible for triple-agent chemotherapy. Patients underwent a PET-CT scan before randomization. ctDNA analyses of plasma samples were done by ddPCR, detecting CRC-specific mutations and methylation of the <i>NPY</i> gene. In the ctDNA-guided arm, ctDNA positivity led to an escalation strategy with triple-agent chemotherapy, and conversely ctDNA negativity led to a de-escalation strategy by shared-decision making. Patients randomized to the standard arm were treated according to SOC. Feasibility measures for the run-in phase were; the inclusion of 30 patients over 12 months in two Danish hospitals, compliance with randomization &gt;80%, rate of PET-CT-positive findings &lt;20%, and eligibility for triple-agent chemotherapy &gt;80%. Thirty-two patients were included. The rate of PET-CT-positive cases was 22% (<i>n</i> = 7/32). Ninety-seven percent of the patients were randomized. Fourteen patients were randomly assigned to SOC and sixteen to ctDNA-guided adjuvant treatment and follow-up. All analyses of baseline plasma samples in the ctDNA-guided arm passed the quality control, and 19% were ctDNA positive. The median time to result was three working days. All ctDNA-positive patients were eligible for triple-agent chemotherapy. The study was proven to be feasible and continues in the planned large-scale phase II trial. Results from the OPTIMISE study will potentially optimize the adjuvant treatment of patients undergoing radical-intent treatment of mCRC, thereby improving survival and reducing chemotherapy-related toxicity.
DOI: 10.6084/m9.figshare.24163016
title: Time trends in systemic treatment for patients with metastatic prostate cancer: a national cohort study

description: Several new systemic treatments for primary metastatic prostate cancer patients (mPCa) were introduced in the last decade for both hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). However, little is known about the introduction of these treatments in clinical practice. In this national cohort study, we described users and non-users of systemic treatment beyond androgen deprivation therapy (ADT). We also explored whether there was a shift in treatment patterns after the introduction of Docetaxel for mHSPC patients. All patients registered in the Cancer Registry of Norway with mPCa diagnosed in 2010-18 were included. Data on systemic therapy (Docetaxel, Abiraterone, Enzalutamide, Cabazitaxel, and Radium-223) were provided from the Norwegian Prescription Database, the Norwegian Patient Registry, and the Norwegian Control and Payment of Health Reimbursement Database. Descriptive results about patient and disease characteristics were presented using frequencies and proportions, means and standard deviations, or medians and interquartile ranges. Of the 2770 patients included in this study, 48% received systemic treatment beyond ADT. The proportion of patients receiving systemic treatment increased during the study period. Systemic treatment users were younger, in better general condition, and had more aggressive tumors than non-users. A treatment shift was observed after 2015, with 48% of patients receiving systemic treatment (mainly Docetaxel) in the mHSPC phase compared to 4% of those diagnosed 2010-14. No significant treatment differences were observed across health regions. An increasing proportion of patients received systemic treatment during the period 2010–18. However, less than 50% of patients in our study received systemic treatment. In accordance with updated guidelines, Docetaxel was introduced after 2015 with an increasing proportion of patients receiving systemic treatment as mHSPC. Further studies should address the disease course and treatment given to patients who do not receive systemic treatment.
DOI: 10.6084/m9.figshare.24163016.v1
title: Time trends in systemic treatment for patients with metastatic prostate cancer: a national cohort study

description: Several new systemic treatments for primary metastatic prostate cancer patients (mPCa) were introduced in the last decade for both hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). However, little is known about the introduction of these treatments in clinical practice. In this national cohort study, we described users and non-users of systemic treatment beyond androgen deprivation therapy (ADT). We also explored whether there was a shift in treatment patterns after the introduction of Docetaxel for mHSPC patients. All patients registered in the Cancer Registry of Norway with mPCa diagnosed in 2010-18 were included. Data on systemic therapy (Docetaxel, Abiraterone, Enzalutamide, Cabazitaxel, and Radium-223) were provided from the Norwegian Prescription Database, the Norwegian Patient Registry, and the Norwegian Control and Payment of Health Reimbursement Database. Descriptive results about patient and disease characteristics were presented using frequencies and proportions, means and standard deviations, or medians and interquartile ranges. Of the 2770 patients included in this study, 48% received systemic treatment beyond ADT. The proportion of patients receiving systemic treatment increased during the study period. Systemic treatment users were younger, in better general condition, and had more aggressive tumors than non-users. A treatment shift was observed after 2015, with 48% of patients receiving systemic treatment (mainly Docetaxel) in the mHSPC phase compared to 4% of those diagnosed 2010-14. No significant treatment differences were observed across health regions. An increasing proportion of patients received systemic treatment during the period 2010–18. However, less than 50% of patients in our study received systemic treatment. In accordance with updated guidelines, Docetaxel was introduced after 2015 with an increasing proportion of patients receiving systemic treatment as mHSPC. Further studies should address the disease course and treatment given to patients who do not receive systemic treatment.
DOI: 10.6084/m9.figshare.24574201
title: Testosterone replacement therapy is not associated with increased prostate cancer incidence, prostate cancer-specific, or cardiovascular disease-specific mortality in Finnish men

description: Concerns have been expressed over the safety of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH). Previous studies have shown controversial results regarding the association of TRT with the risk of cardiovascular events or prostate cancer (PCa) incidence, aggressiveness, and mortality. This study explores the overall risk of PCa and risk by tumor grade and stage, as well as mortality from PCa and cardiovascular disease (CVD), among men treated with TRT compared to men without LOH and TRT use. The study included 78,615 men of age 55–67 years at baseline from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). Follow-up started at randomization and ended at death, emigration, or a common closing date January 1st, 2017. Cox proportional hazards regression model with time-dependent variables and adjustment for age, trial arm, use of other medications, and Charlson comorbidity index was used. Comprehensive information on TRT purchases during 1995–2015 was obtained from the Finnish National Prescription Database. PCa cases were identified from the Finnish Cancer Registry and causes of death obtained from Statistics Finland. Over the course of 18 years of follow-up, 2919 men were on TRT, and 285 PCa cases were diagnosed among them. TRT users did not exhibit a higher incidence or mortality rate of PCa compared to non-users. On the contrary, men using TRT had lower PCa mortality than non-users (HR = 0.52; 95% CI 0.3–0.91). Additionally, TRT users had slightly lower CVD and all-cause mortality compared to non-users (HR = 0.87; 95% CI 0.75–1.01 and HR = 0.93; 95% CI 0.87–1.0, respectively). No time- or dose-dependency of TRT use was evident in any of the analyses. Men using TRT were not associated to increased risk for PCa and did not experience increased PCa- or CVD-specific mortality compared to non-users. Further studies considering blood testosterone levels are warranted.
DOI: 10.6084/m9.figshare.24574201.v1
title: Testosterone replacement therapy is not associated with increased prostate cancer incidence, prostate cancer-specific, or cardiovascular disease-specific mortality in Finnish men

description: Concerns have been expressed over the safety of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH). Previous studies have shown controversial results regarding the association of TRT with the risk of cardiovascular events or prostate cancer (PCa) incidence, aggressiveness, and mortality. This study explores the overall risk of PCa and risk by tumor grade and stage, as well as mortality from PCa and cardiovascular disease (CVD), among men treated with TRT compared to men without LOH and TRT use. The study included 78,615 men of age 55–67 years at baseline from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). Follow-up started at randomization and ended at death, emigration, or a common closing date January 1st, 2017. Cox proportional hazards regression model with time-dependent variables and adjustment for age, trial arm, use of other medications, and Charlson comorbidity index was used. Comprehensive information on TRT purchases during 1995–2015 was obtained from the Finnish National Prescription Database. PCa cases were identified from the Finnish Cancer Registry and causes of death obtained from Statistics Finland. Over the course of 18 years of follow-up, 2919 men were on TRT, and 285 PCa cases were diagnosed among them. TRT users did not exhibit a higher incidence or mortality rate of PCa compared to non-users. On the contrary, men using TRT had lower PCa mortality than non-users (HR = 0.52; 95% CI 0.3–0.91). Additionally, TRT users had slightly lower CVD and all-cause mortality compared to non-users (HR = 0.87; 95% CI 0.75–1.01 and HR = 0.93; 95% CI 0.87–1.0, respectively). No time- or dose-dependency of TRT use was evident in any of the analyses. Men using TRT were not associated to increased risk for PCa and did not experience increased PCa- or CVD-specific mortality compared to non-users. Further studies considering blood testosterone levels are warranted.
DOI: 10.6084/m9.figshare.24198055
title: The impact of implementing current treatment modalities and female sex on gastric cancer outcomes, 2000–2016: a longitudinal nationwide cohort study

description: The implementation of current treatment modalities and their impact on nationwide gastric cancer outcomes remain poorly understood. Biological differences between females and males could impact survival. We aimed to analyze rates of gastric surgery, chemotherapy, and radiotherapy as well as changes in overall survival among gastric cancer patients diagnosed between 2000–2008 and 2009–2016, respectively, in Finland. Data on gastric cancer patients were collected from national registries. Cox regression analysis and the Kaplan–Meier method were used to analyze differences in survival. We identified 9223 histologically confirmed gastric cancer patients. The rate of gastric surgery decreased from 44% (<i>n</i> = 2282) to 34% (<i>n</i> = 1368; <i>p</i> &lt; 0.001). The proportion of gastric surgery patients who underwent preoperative oncological treatment increased from 0.5% (<i>n</i> = 12) to 16.2% (<i>n</i> = 222) between the calendar periods (<i>p</i> &lt; 0.001) and stood at 30% in 2016. The median overall survival (OS) improved from 30 months [95% confidence interval (CI) 28–33] to 38 months (95%CI 33–42; <i>p</i> = 0.006) and the period 2009–2016 independently associated with a lower risk of death [hazard ratio (HR) 0.78, 95%CI 0.70–0.87] among patients who underwent gastric surgery. Females exhibited a lower risk of death (HR 0.88, 95%CI 0.81–0.97) among patients who underwent gastric surgery. Preoperative oncological treatment was gradually introduced into clinical practice and OS among gastric surgery patients improved. Moreover, female surgical patients exhibited a better survival than male patients.
DOI: 10.6084/m9.figshare.24198055.v1
title: The impact of implementing current treatment modalities and female sex on gastric cancer outcomes, 2000–2016: a longitudinal nationwide cohort study

description: The implementation of current treatment modalities and their impact on nationwide gastric cancer outcomes remain poorly understood. Biological differences between females and males could impact survival. We aimed to analyze rates of gastric surgery, chemotherapy, and radiotherapy as well as changes in overall survival among gastric cancer patients diagnosed between 2000–2008 and 2009–2016, respectively, in Finland. Data on gastric cancer patients were collected from national registries. Cox regression analysis and the Kaplan–Meier method were used to analyze differences in survival. We identified 9223 histologically confirmed gastric cancer patients. The rate of gastric surgery decreased from 44% (<i>n</i> = 2282) to 34% (<i>n</i> = 1368; <i>p</i> &lt; 0.001). The proportion of gastric surgery patients who underwent preoperative oncological treatment increased from 0.5% (<i>n</i> = 12) to 16.2% (<i>n</i> = 222) between the calendar periods (<i>p</i> &lt; 0.001) and stood at 30% in 2016. The median overall survival (OS) improved from 30 months [95% confidence interval (CI) 28–33] to 38 months (95%CI 33–42; <i>p</i> = 0.006) and the period 2009–2016 independently associated with a lower risk of death [hazard ratio (HR) 0.78, 95%CI 0.70–0.87] among patients who underwent gastric surgery. Females exhibited a lower risk of death (HR 0.88, 95%CI 0.81–0.97) among patients who underwent gastric surgery. Preoperative oncological treatment was gradually introduced into clinical practice and OS among gastric surgery patients improved. Moreover, female surgical patients exhibited a better survival than male patients.
DOI: 10.6084/m9.figshare.24461185
title: Clinical implication of genetic intratumor heterogeneity for targeted therapy in head and neck cancer

description: Genomic profiling is increasingly used both in therapeutic decision-making and as inclusion criteria for trials testing targeted therapies. However, the mutational landscape may vary across different areas of a tumor and intratumor heterogeneity will challenge treatments or clinical decisions based on single tumor biopsies. The purpose of this study was to assess the clinical relevance of genetic intratumor heterogeneity in head and neck squamous cell carcinomas (HNSCC) using the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT). This prospective study included 33 whole tumor specimens from 28 patients with primary or recurrent HNSCC referred for surgery. Three tumor blocks were selected from central, semi-peripheral, and peripheral positions, mimicking biopsies in three different locations. Genetic analysis of somatic copy number alterations (SCNAs) was performed on the three biopsies using Oncoscan, focusing on 45 preselected HNSCC genes of interest. Clinical relevance was assessed using the ESCAT score to investigate whether and how treatment decisions would change based on the three biopsies from the same tumor. The SCNAs identified among 45 preselected genes within the three tumor biopsies derived from the same tumor revealed distinct variations. The detected discrepancies could potentially influence treatment approaches or clinical decisions in 36% of the patients if only one tumor biopsy was used. Recurrent tumors exhibited significantly higher variation in SCNAs than primary tumors (<i>p</i> = .024). No significant correlation between tumor size and heterogeneity (<i>p</i> = .7) was observed. In 36% of patients diagnosed with HNSCC, clinically significant intratumor heterogeneity was observed which may have implications for patient management. This finding substantiates the need for future studies that specifically investigate the clinical implications associated with intratumor heterogeneity.
DOI: 10.6084/m9.figshare.24461185.v1
title: Clinical implication of genetic intratumor heterogeneity for targeted therapy in head and neck cancer

description: Genomic profiling is increasingly used both in therapeutic decision-making and as inclusion criteria for trials testing targeted therapies. However, the mutational landscape may vary across different areas of a tumor and intratumor heterogeneity will challenge treatments or clinical decisions based on single tumor biopsies. The purpose of this study was to assess the clinical relevance of genetic intratumor heterogeneity in head and neck squamous cell carcinomas (HNSCC) using the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT). This prospective study included 33 whole tumor specimens from 28 patients with primary or recurrent HNSCC referred for surgery. Three tumor blocks were selected from central, semi-peripheral, and peripheral positions, mimicking biopsies in three different locations. Genetic analysis of somatic copy number alterations (SCNAs) was performed on the three biopsies using Oncoscan, focusing on 45 preselected HNSCC genes of interest. Clinical relevance was assessed using the ESCAT score to investigate whether and how treatment decisions would change based on the three biopsies from the same tumor. The SCNAs identified among 45 preselected genes within the three tumor biopsies derived from the same tumor revealed distinct variations. The detected discrepancies could potentially influence treatment approaches or clinical decisions in 36% of the patients if only one tumor biopsy was used. Recurrent tumors exhibited significantly higher variation in SCNAs than primary tumors (<i>p</i> = .024). No significant correlation between tumor size and heterogeneity (<i>p</i> = .7) was observed. In 36% of patients diagnosed with HNSCC, clinically significant intratumor heterogeneity was observed which may have implications for patient management. This finding substantiates the need for future studies that specifically investigate the clinical implications associated with intratumor heterogeneity.
DOI: 10.6084/m9.figshare.25451299
title: Laboratory Data.xlsx

description: This dataset includes the original data of SWIR and laboratory data in the manuscript of Ju et al., submitted to EPSL.
DOI: 10.6084/m9.figshare.25451299.v1
title: Laboratory Data.xlsx

description: Tianwen-1 mission is China’s first Martian exploration mission, and the Zhurong rover has successfully landed in southern Utopia Planitia. The MarSCoDe onboard the Zhurong rover can obtain mineralogical information on the Martian surface materials by using SWIR spectra. However, the exact types of hydrated phases are not clear in the existing literature. Thus we combined the SWIR spectra and laboratory database of binary mixtures to further constrain mineral types and their contents. Our results reveal that allophane may be the source of hydration features in the SWIR spectra of the Tianwen-1 landing site. This is of great significance to the geological interpretation and process of the landing site.
DOI: 10.18167/dvn1/l9sqvo
title: Replication Data for: “Phosphorus sorption and availability in an andosol after a decade of organic or mineral fertilizer applications: importance of pH and organic carbon modifications in soil as compared to phosphorus accumulation"

description: Dataset of the paper entitled Phosphorus sorption and availability in an andosol after a decade of organic or mineral fertilizer applications: importance of pH and organic carbon modifications in soil as compared to phosphorus accumulation. We conducted a 10-years-old field experiment on an andosol and compared fields that had been amended with mineral or organic (dairy slurry and manure compost) fertilizers against a non-fertilized control. Water and Olsen extractions and inorganic phosphorus sorption experiments were realized on soils sampled after 6 and 10 years of trial. We also realized an artificial and ex situ alkalization of the control soil to isolate the effect of pH on the sorption capacity of inorganic phosphorus.