cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.25934/pr00006809.0
title: Available IPD datapackage for study 'A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study To Evaluate The Efficacy And Safety Of Three Fixed Doses (100 Mg, 200 Mg, Or 400 Mg) Of DVS-233 SR In Adult Outpatients With Major Depressive Disorder'

description: To compare the antidepressant efficacy and safety of subjects receiving DVS-233 SR versus subjects receiving placebo.
DOI: 10.6084/m9.figshare.15172873
title: Effects from physical exercise on reduced cancer-related fatigue: a systematic review of systematic reviews and meta-analysis

description: Cancer-related fatigue is one of the most prevalent and distressing symptoms among cancer patients, resulting in a great cancer research challenge. Numerous systematic reviews of physical training interventions have been conducted to find the most effective approach. However, evidence remains fragmented, and in which cancer population physical training is more effective than other populations is still unclear. Thus, this study critically appraised systematic reviews and meta-analyses on physical training to reduce adults’ cancer-related fatigue. A systematic review of systematic reviews and meta-analysis (PROSPERO: CRD42020189049), assessing the efficacy of exercise training for reducing cancer-related fatigue in adults, was conducted in PubMed, CINAHL, Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects, and Pedro. The selected studies (standardized mean difference, SMD; 95%CI), was quantitatively pooled using a random-effects model. Heterogeneity was tested using chi-squared (<i>Q</i>) and <i>I</i>-square statistics (<i>I</i><sup>2</sup>). Of 1438 identified articles, 11 met the inclusion criteria, and ten were meta-analyzed. The results yielded a positive effect of physical training on fatigue in all cancer populations, SMD = −0.33 (−0.43, −0.23). Subgroup analysis based on tumor localization showed a slightly higher physical training effect on fatigue in adults with breast cancer, SMD = −0.36 (−0.57, −0.15), and prostate cancer SMD = −0.34 (−0.45, −.0.22). Our analysis demonstrated some potential improvement in cancer-related fatigue in adult patients undergoing physical training during and after cancer treatments, particularly in patients with breast or prostate cancer.
DOI: 10.6084/m9.figshare.15172873.v1
title: Effects from physical exercise on reduced cancer-related fatigue: a systematic review of systematic reviews and meta-analysis

description: Cancer-related fatigue is one of the most prevalent and distressing symptoms among cancer patients, resulting in a great cancer research challenge. Numerous systematic reviews of physical training interventions have been conducted to find the most effective approach. However, evidence remains fragmented, and in which cancer population physical training is more effective than other populations is still unclear. Thus, this study critically appraised systematic reviews and meta-analyses on physical training to reduce adults’ cancer-related fatigue. A systematic review of systematic reviews and meta-analysis (PROSPERO: CRD42020189049), assessing the efficacy of exercise training for reducing cancer-related fatigue in adults, was conducted in PubMed, CINAHL, Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects, and Pedro. The selected studies (standardized mean difference, SMD; 95%CI), was quantitatively pooled using a random-effects model. Heterogeneity was tested using chi-squared (<i>Q</i>) and <i>I</i>-square statistics (<i>I</i><sup>2</sup>). Of 1438 identified articles, 11 met the inclusion criteria, and ten were meta-analyzed. The results yielded a positive effect of physical training on fatigue in all cancer populations, SMD = −0.33 (−0.43, −0.23). Subgroup analysis based on tumor localization showed a slightly higher physical training effect on fatigue in adults with breast cancer, SMD = −0.36 (−0.57, −0.15), and prostate cancer SMD = −0.34 (−0.45, −.0.22). Our analysis demonstrated some potential improvement in cancer-related fatigue in adult patients undergoing physical training during and after cancer treatments, particularly in patients with breast or prostate cancer.
DOI: 10.6084/m9.figshare.16636144
title: Time on treatment with abiraterone and enzalutamide in the Patient-overview Prostate Cancer in The National Prostate Cancer Register of Sweden

description: There are little and inconsistent data from clinical practice on time on treatment with the androgen receptor-targeted drugs (ART) abiraterone and enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC). We assessed time on treatment with ART and investigated predictors of time on treatment. Time on treatment with ART in men with mCRPC in the patient-overview prostate cancer (PPC), a subregister of the National Prostate Cancer Register (NPCR) of Sweden, was assessed by use of Kaplan–Meier plots and Cox regression. To assess the representativity of PPC for time on treatment, a comparison was made with all men in NPCR who had a filling for ART in the Prescribed Drug Registry. 2038 men in PPC received ART between 2015 and 2019. Median time on treatment in chemo-naïve men was 10.8 (95% confidence interval 9.1–13.1) months for abiraterone and 14.1 (13.5–15.5) for enzalutamide. After the use of docetaxel, time on treatment was 8.2 (6.5–12.4) months for abiraterone and 11.1 (9.8–12.6) for enzalutamide. Predictors of a long time on treatment with ART were long duration of ADT prior to ART, low serum levels of PSA at start of ART, absence of visceral metastasis, good performance status, and no prior use of docetaxel. PPC captured 2522/6337 (40%) of all men in NPCR who had filled a prescription for ART. Based on fillings in the Prescribed Drug Registry, men in PPC had a slightly longer median time on treatment with ART compared to all men in NPCR, 9.6 (9.1–10.3) vs. 8.6 (6.3–9.1) months. Time on treatment in clinical practice was similar or shorter than that in published RCTs, due to older age, poorer performance status and more comorbidities.
DOI: 10.6084/m9.figshare.16636144.v1
title: Time on treatment with abiraterone and enzalutamide in the Patient-overview Prostate Cancer in The National Prostate Cancer Register of Sweden

description: There are little and inconsistent data from clinical practice on time on treatment with the androgen receptor-targeted drugs (ART) abiraterone and enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC). We assessed time on treatment with ART and investigated predictors of time on treatment. Time on treatment with ART in men with mCRPC in the patient-overview prostate cancer (PPC), a subregister of the National Prostate Cancer Register (NPCR) of Sweden, was assessed by use of Kaplan–Meier plots and Cox regression. To assess the representativity of PPC for time on treatment, a comparison was made with all men in NPCR who had a filling for ART in the Prescribed Drug Registry. 2038 men in PPC received ART between 2015 and 2019. Median time on treatment in chemo-naïve men was 10.8 (95% confidence interval 9.1–13.1) months for abiraterone and 14.1 (13.5–15.5) for enzalutamide. After the use of docetaxel, time on treatment was 8.2 (6.5–12.4) months for abiraterone and 11.1 (9.8–12.6) for enzalutamide. Predictors of a long time on treatment with ART were long duration of ADT prior to ART, low serum levels of PSA at start of ART, absence of visceral metastasis, good performance status, and no prior use of docetaxel. PPC captured 2522/6337 (40%) of all men in NPCR who had filled a prescription for ART. Based on fillings in the Prescribed Drug Registry, men in PPC had a slightly longer median time on treatment with ART compared to all men in NPCR, 9.6 (9.1–10.3) vs. 8.6 (6.3–9.1) months. Time on treatment in clinical practice was similar or shorter than that in published RCTs, due to older age, poorer performance status and more comorbidities.
DOI: 10.6084/m9.figshare.16657334
title: The impact of sarcopenia on the efficacy and safety of immune checkpoint inhibitors in patients with solid tumours

description: Evidence suggests that sarcopenia is a significant predictive factor of worst outcomes and treatment-associated toxicities in patients with metastatic solid tumours. The aim of this study was to explore the relationship between low muscle mass and clinical outcomes and immune-related severe toxicities (IrST) in patients treated with immune checkpoint inhibitors (ICIs). A retrospective cohort of 261 consecutive metastatic solid tumour patients treated with ICIs were included in our study. Low muscle mass was defined as skeletal muscle index &lt;41 cm<sup>2</sup>/m<sup>2</sup> for females and &lt;43 cm<sup>2</sup>/m<sup>2</sup> for males if body mass index (BMI) &lt;25 kg/m<sup>2</sup> or &lt;53 cm<sup>2</sup>/m<sup>2</sup> if BMI ≥ 25 kg/m<sup>2</sup>. Severe toxicities (ST), including grade III-IV toxicities and side effects leading to treatment interruption, were recorded. The majority of patients (<i>n</i> = 179; 69%) included in this study had metastatic lung cancer. The prevalence of low muscle mass was 47%. The median progression-free survival (PFS) was 32.2 weeks for low muscle mass patients and 24.3 weeks for non-low muscle mass patients (adjusted HR, 0.80; 95% CI, 0.60–1.055; <i>p</i> = 0.11). For low muscle mass and non-low muscle mass lung cancer patients, median PFS was 24.0 weeks and 18.8 weeks (adjusted HR, 0.70; 95% CI, 0.50–0.98; <i>p</i> = 0.04) and median overall survival was 50.7 weeks and 41.1 weeks (adjusted HR, 0.77; 95% CI, 0.54–1.10, <i>p</i> = 0.15) respectively. Immune-related severe toxicities occurred in 3.3% and 9.4% of low muscle mass and non-low muscle mass patients respectively (adjusted OR, 0.69; 95% CI: 0.31–1.49; <i>p</i> = 0.35). No difference in outcomes and safety was observed for low muscle mass and non-low muscle mass patients treated with ICIs.
DOI: 10.6084/m9.figshare.16657334.v1
title: The impact of sarcopenia on the efficacy and safety of immune checkpoint inhibitors in patients with solid tumours

description: Evidence suggests that sarcopenia is a significant predictive factor of worst outcomes and treatment-associated toxicities in patients with metastatic solid tumours. The aim of this study was to explore the relationship between low muscle mass and clinical outcomes and immune-related severe toxicities (IrST) in patients treated with immune checkpoint inhibitors (ICIs). A retrospective cohort of 261 consecutive metastatic solid tumour patients treated with ICIs were included in our study. Low muscle mass was defined as skeletal muscle index &lt;41 cm<sup>2</sup>/m<sup>2</sup> for females and &lt;43 cm<sup>2</sup>/m<sup>2</sup> for males if body mass index (BMI) &lt;25 kg/m<sup>2</sup> or &lt;53 cm<sup>2</sup>/m<sup>2</sup> if BMI ≥ 25 kg/m<sup>2</sup>. Severe toxicities (ST), including grade III-IV toxicities and side effects leading to treatment interruption, were recorded. The majority of patients (<i>n</i> = 179; 69%) included in this study had metastatic lung cancer. The prevalence of low muscle mass was 47%. The median progression-free survival (PFS) was 32.2 weeks for low muscle mass patients and 24.3 weeks for non-low muscle mass patients (adjusted HR, 0.80; 95% CI, 0.60–1.055; <i>p</i> = 0.11). For low muscle mass and non-low muscle mass lung cancer patients, median PFS was 24.0 weeks and 18.8 weeks (adjusted HR, 0.70; 95% CI, 0.50–0.98; <i>p</i> = 0.04) and median overall survival was 50.7 weeks and 41.1 weeks (adjusted HR, 0.77; 95% CI, 0.54–1.10, <i>p</i> = 0.15) respectively. Immune-related severe toxicities occurred in 3.3% and 9.4% of low muscle mass and non-low muscle mass patients respectively (adjusted OR, 0.69; 95% CI: 0.31–1.49; <i>p</i> = 0.35). No difference in outcomes and safety was observed for low muscle mass and non-low muscle mass patients treated with ICIs.
DOI: 10.6084/m9.figshare.16752592
title: Predicting response to neoadjuvant chemotherapy in patients with oesophageal adenocarcinoma

description: Neoadjuvant chemotherapy is often used prior to surgical resection for oesophageal adenocarcinoma but remains ineffective in a high proportion of patients. The histological Mandard tumour regression grade is used to determine chemoresponse but is not available at the time of treatment decision-making. The aim of this cohort study was to identify factors that predict chemotherapy response prior to surgery. A prospectively collected database of patients undergoing surgical resection for oesophageal adenocarcinoma from a high-volume UK institution was used. Patients were subcategorised using pathological tumour response into ‘responders’ (Mandard grade 1–3) and ‘non-responders’ (Mandard grade 4 and 5). Multivariable logistic regression analysis was performed to calculate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for responder status adjusting for a variety of parameters. Receiver operating characteristic (ROC) curves were calculated. Among 315 patients included, 102 (32%) were responders and 213 (68%) non-responders. A decrease in radiological tumour volume (OR 1.92 95%CI 1.02–3.62; <i>p</i> = 0.05), a ‘partial response’ RECIST score (OR 7.16 95%CI 1.49–34.36; <i>p</i> = 0.01), a clinically improved dysphagia score (OR 2.79 95%CI 1.05–7.04; <i>p</i> = 0.04) and lymphovascular invasion (OR 0.06 95%CI 0.02–0.13; <i>p</i> = 0.000) influenced responder status. ROC curve analysis for responder status utilising all available parameters had an area under the curve (AUC) of 0.86. This study has highlighted the potential for using pre-defined factors to identify those patients who have responded to neoadjuvant chemotherapy, prior to surgical resection, potentially facilitating a more individualised therapeutic approach.
DOI: 10.6084/m9.figshare.16752592.v1
title: Predicting response to neoadjuvant chemotherapy in patients with oesophageal adenocarcinoma

description: Neoadjuvant chemotherapy is often used prior to surgical resection for oesophageal adenocarcinoma but remains ineffective in a high proportion of patients. The histological Mandard tumour regression grade is used to determine chemoresponse but is not available at the time of treatment decision-making. The aim of this cohort study was to identify factors that predict chemotherapy response prior to surgery. A prospectively collected database of patients undergoing surgical resection for oesophageal adenocarcinoma from a high-volume UK institution was used. Patients were subcategorised using pathological tumour response into ‘responders’ (Mandard grade 1–3) and ‘non-responders’ (Mandard grade 4 and 5). Multivariable logistic regression analysis was performed to calculate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for responder status adjusting for a variety of parameters. Receiver operating characteristic (ROC) curves were calculated. Among 315 patients included, 102 (32%) were responders and 213 (68%) non-responders. A decrease in radiological tumour volume (OR 1.92 95%CI 1.02–3.62; <i>p</i> = 0.05), a ‘partial response’ RECIST score (OR 7.16 95%CI 1.49–34.36; <i>p</i> = 0.01), a clinically improved dysphagia score (OR 2.79 95%CI 1.05–7.04; <i>p</i> = 0.04) and lymphovascular invasion (OR 0.06 95%CI 0.02–0.13; <i>p</i> = 0.000) influenced responder status. ROC curve analysis for responder status utilising all available parameters had an area under the curve (AUC) of 0.86. This study has highlighted the potential for using pre-defined factors to identify those patients who have responded to neoadjuvant chemotherapy, prior to surgical resection, potentially facilitating a more individualised therapeutic approach.
DOI: 10.6084/m9.figshare.17134209
title: Genomic landscape of treatment refractory metastatic colorectal cancer

description: Metastatic colorectal cancer (mCRC) is a complex and heterogeneous disease with few standard and targeted treatment options. Next-generation sequencing of tumor tissue was performed to identify cancer driver mutations to discover possible personalized treatment options, as targeted treatment possibilities are limited for this patient population. Results of genomic sequencing in patients with treatment-refractory mCRC are described in this retrospective analysis. Clinico-pathological characteristics and genomic sequence results of consecutive patients with refractory mCRC, referred to the Experimental Cancer Therapy Unit (ECTU) at Department of Oncology, Herlev & Gentofte Hospital in the period from 1 October 2015 to 14 December 2018 were reviewed in this retrospective analysis. Tumor tissue from the patients was analyzed by next-generation sequencing using the Oncomine Comprehensive primer panel to detect actionable variants of cancer driver mutations and microsatellite instability status. From August 2018 tumor mutational burden was also analyzed. A total of 80 patients with treatment-refractory mCRC and in a fairly good performance were referred to the ECTU during this period. Genomic sequencing of tumor tissue was performed for all 80 patients and a cancer driver mutation was identified in 90% (<i>n</i> = 72) of the patients. A total of 31.3% (<i>n</i> = 25) of the patients received therapy either as targetable therapy outside an available trial (<i>n</i> = 2), FDA approved therapy (<i>n</i> = 2), or treatment in phase 1 or 2 trials, independent of the genomic signature 26.3% (<i>n</i> = 21). Most mCRC patients refractory to standard anti-neoplastic therapies, presented with a cancer driver mutation, however, only a few of these mutations gave rise to matched therapies as only 2.5% of the patients from this period received targeted therapy.
DOI: 10.6084/m9.figshare.17134209.v1
title: Genomic landscape of treatment refractory metastatic colorectal cancer

description: Metastatic colorectal cancer (mCRC) is a complex and heterogeneous disease with few standard and targeted treatment options. Next-generation sequencing of tumor tissue was performed to identify cancer driver mutations to discover possible personalized treatment options, as targeted treatment possibilities are limited for this patient population. Results of genomic sequencing in patients with treatment-refractory mCRC are described in this retrospective analysis. Clinico-pathological characteristics and genomic sequence results of consecutive patients with refractory mCRC, referred to the Experimental Cancer Therapy Unit (ECTU) at Department of Oncology, Herlev & Gentofte Hospital in the period from 1 October 2015 to 14 December 2018 were reviewed in this retrospective analysis. Tumor tissue from the patients was analyzed by next-generation sequencing using the Oncomine Comprehensive primer panel to detect actionable variants of cancer driver mutations and microsatellite instability status. From August 2018 tumor mutational burden was also analyzed. A total of 80 patients with treatment-refractory mCRC and in a fairly good performance were referred to the ECTU during this period. Genomic sequencing of tumor tissue was performed for all 80 patients and a cancer driver mutation was identified in 90% (<i>n</i> = 72) of the patients. A total of 31.3% (<i>n</i> = 25) of the patients received therapy either as targetable therapy outside an available trial (<i>n</i> = 2), FDA approved therapy (<i>n</i> = 2), or treatment in phase 1 or 2 trials, independent of the genomic signature 26.3% (<i>n</i> = 21). Most mCRC patients refractory to standard anti-neoplastic therapies, presented with a cancer driver mutation, however, only a few of these mutations gave rise to matched therapies as only 2.5% of the patients from this period received targeted therapy.
DOI: 10.6084/m9.figshare.16574508
title: Intracranial effect of osimertinib in relapsed <i>EGFR</i>-mutated T790M-positive and -negative non-small cell lung cancer patients: results from a phase II study

description: Osimertinib is effective for relapsed T790M-positive patients with brain metastases. The high brain permeability suggests that also such patients without T790M could benefit. Therefore, we evaluated the effect of osimertinib on brain metastases in both T790M-positive and -negative patients. The TREM-study was an investigator-initiated phase II, single-arm, multi-institutional clinical trial conducted in Northern Europe. Patients with resistance to prior EGFR-TKIs received osimertinib until radiological progression, unacceptable toxicity or death. Baseline brain scans were performed in patients with known or suspected brain metastases and repeated every 8–12 weeks. We assessed intracranial efficacy in patients with baseline brain metastases. Brain metastases were detected in 48/199 patients at baseline. Of these, 63% were T790M-positive, 27% -negative and 10% had unknown T790M-status. The majority (73%) of the patients had received prior whole brain radiotherapy and additionally 8% had received stereotactic radiosurgery (SRS). Brain scans were available for review for 42 patients. The intracranial progression free survival was 39.7 versus 3.5 months for T790M + and T790M- patients, respectively (<i>p</i> &lt; 0.001). The overall intracranial disease control rate (iDCR) was 81%, and for T790M + and T790M- patients the DCR was 89% versus 55%, respectively. The estimated risk of CNS progression was 0.8% at 6 months and 6% at 12 months for T790M-positive patients, and 14% and 17% at 6 and 12 months, respectively, for the T790M-negative. This subgroup analysis confirms CNS efficacy of osimertinib in patients with the T790M resistance mutation, while other treatment options should be considered for EGFR-TKI relapsed T790M-negative patients with brain metastases.
DOI: 10.6084/m9.figshare.16574508.v1
title: Intracranial effect of osimertinib in relapsed <i>EGFR</i>-mutated T790M-positive and -negative non-small cell lung cancer patients: results from a phase II study

description: Osimertinib is effective for relapsed T790M-positive patients with brain metastases. The high brain permeability suggests that also such patients without T790M could benefit. Therefore, we evaluated the effect of osimertinib on brain metastases in both T790M-positive and -negative patients. The TREM-study was an investigator-initiated phase II, single-arm, multi-institutional clinical trial conducted in Northern Europe. Patients with resistance to prior EGFR-TKIs received osimertinib until radiological progression, unacceptable toxicity or death. Baseline brain scans were performed in patients with known or suspected brain metastases and repeated every 8–12 weeks. We assessed intracranial efficacy in patients with baseline brain metastases. Brain metastases were detected in 48/199 patients at baseline. Of these, 63% were T790M-positive, 27% -negative and 10% had unknown T790M-status. The majority (73%) of the patients had received prior whole brain radiotherapy and additionally 8% had received stereotactic radiosurgery (SRS). Brain scans were available for review for 42 patients. The intracranial progression free survival was 39.7 versus 3.5 months for T790M + and T790M- patients, respectively (<i>p</i> &lt; 0.001). The overall intracranial disease control rate (iDCR) was 81%, and for T790M + and T790M- patients the DCR was 89% versus 55%, respectively. The estimated risk of CNS progression was 0.8% at 6 months and 6% at 12 months for T790M-positive patients, and 14% and 17% at 6 and 12 months, respectively, for the T790M-negative. This subgroup analysis confirms CNS efficacy of osimertinib in patients with the T790M resistance mutation, while other treatment options should be considered for EGFR-TKI relapsed T790M-negative patients with brain metastases.