cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.12962063.v1
title: Voluntary wheel running can lead to modulation of immune checkpoint molecule expression

description: Exercise and physical activity (PA) are associated with reduced tumor growth and enhanced intra-tumoral immune cell infiltration in mice. We aimed to investigate the role of PA achieved by voluntary wheel running in promoting the immunogenic profile across several murine tumor models, and to explore the potential of checkpoint blockade and PA in the form of voluntary wheel running as combination therapy. The experiments were performed with C57BL/6 mice bearing subcutaneous tumors while having access to running wheels in their cages, where key immunoregulatory molecules expressed in the tumor tissue were measured by qPCR. Furthermore, we tested the hypothesis that wheel running combined with PD-L1 -or PD-1 inhibitor treatment could lead to an additive effect on tumor growth in mice bearing B16 melanoma tumors. Wheel running increased immune checkpoint expression (PD-1, PD-L1, PD-L2, CD28, B7.1 and B7.2) in B16 tumor-bearing mice, while induction of only PD-L2 was found in E0771 breast cancer and Lewis Lung Cancer. In studies combining voluntary wheel running with PD-1 -and PD-L1 inhibitors we found significant effects of wheel running on attenuating B16 melanoma tumor growth, in line with previous studies. We did, however, not find an additive effect of combining either of the two immunotherapeutic treatments with access to running wheels. B16 tumors displayed upregulated expression of immune regulatory molecules and decreased tumor growth in response to PA. However, combining PA with PD-1 or PD-L1 blockade did not lead to a further augmented inhibition of tumor growth.
DOI: 10.6084/m9.figshare.12850955
title: Tumor infiltrating lymphocyte grade in Merkel cell carcinoma: relationships with clinical factors and independent prognostic value

description: Surrogate markers of the host immune response are not currently included in AJCC staging for Merkel cell carcinoma (MCC), and have not been consistently associated with clinical outcomes. We performed an analysis of a large national database to investigate tumor infiltrating lymphocyte (TIL) grade as an independent predictor of overall survival (OS) for patients with MCC and to characterize the relationship between TIL grade and other clinical prognostic factors. The NCDB was queried for patients with resected, non-metastatic MCC with known TIL grade (absent, non-brisk and brisk). Multivariable Cox regression modeling was performed to define TIL grade as a predictor of OS adjusting for other relevant clinical factors. Multinomial, multivariable logistic regression was performed to characterize the relationship between TIL grade and other clinical prognostic factors. Multiple imputation was performed to account for missing data bias. Both brisk (HR 0.55, CI 0.36–0.83) and non-brisk (HR 0.77, CI 0.60–0.98) were associated with decreased adjusted hazard of death relative to absent TIL grade. Adverse clinical factors such as 1–3 positive lymph nodes, lymphovascular invasion (LVI) and immunosuppression were associated with increased likelihood of non-brisk TIL relative to absent TIL grade (<i>p</i> values p Histopathologic TIL grade was independently predictive for OS in this large national cohort. Significant differences in the likelihood of non-brisk or brisk TIL relative to absent grade were present with regards to LVI, ECS and immune status. TIL grade may be a useful prognostic factor to consider in addition to more granular characterization of TIL morphology and immunophenotype.
DOI: 10.6084/m9.figshare.12850955.v1
title: Tumor infiltrating lymphocyte grade in Merkel cell carcinoma: relationships with clinical factors and independent prognostic value

description: Surrogate markers of the host immune response are not currently included in AJCC staging for Merkel cell carcinoma (MCC), and have not been consistently associated with clinical outcomes. We performed an analysis of a large national database to investigate tumor infiltrating lymphocyte (TIL) grade as an independent predictor of overall survival (OS) for patients with MCC and to characterize the relationship between TIL grade and other clinical prognostic factors. The NCDB was queried for patients with resected, non-metastatic MCC with known TIL grade (absent, non-brisk and brisk). Multivariable Cox regression modeling was performed to define TIL grade as a predictor of OS adjusting for other relevant clinical factors. Multinomial, multivariable logistic regression was performed to characterize the relationship between TIL grade and other clinical prognostic factors. Multiple imputation was performed to account for missing data bias. Both brisk (HR 0.55, CI 0.36–0.83) and non-brisk (HR 0.77, CI 0.60–0.98) were associated with decreased adjusted hazard of death relative to absent TIL grade. Adverse clinical factors such as 1–3 positive lymph nodes, lymphovascular invasion (LVI) and immunosuppression were associated with increased likelihood of non-brisk TIL relative to absent TIL grade (<i>p</i> values p Histopathologic TIL grade was independently predictive for OS in this large national cohort. Significant differences in the likelihood of non-brisk or brisk TIL relative to absent grade were present with regards to LVI, ECS and immune status. TIL grade may be a useful prognostic factor to consider in addition to more granular characterization of TIL morphology and immunophenotype.
DOI: 10.6084/m9.figshare.12962063
title: Voluntary wheel running can lead to modulation of immune checkpoint molecule expression

description: Exercise and physical activity (PA) are associated with reduced tumor growth and enhanced intra-tumoral immune cell infiltration in mice. We aimed to investigate the role of PA achieved by voluntary wheel running in promoting the immunogenic profile across several murine tumor models, and to explore the potential of checkpoint blockade and PA in the form of voluntary wheel running as combination therapy. The experiments were performed with C57BL/6 mice bearing subcutaneous tumors while having access to running wheels in their cages, where key immunoregulatory molecules expressed in the tumor tissue were measured by qPCR. Furthermore, we tested the hypothesis that wheel running combined with PD-L1 -or PD-1 inhibitor treatment could lead to an additive effect on tumor growth in mice bearing B16 melanoma tumors. Wheel running increased immune checkpoint expression (PD-1, PD-L1, PD-L2, CD28, B7.1 and B7.2) in B16 tumor-bearing mice, while induction of only PD-L2 was found in E0771 breast cancer and Lewis Lung Cancer. In studies combining voluntary wheel running with PD-1 -and PD-L1 inhibitors we found significant effects of wheel running on attenuating B16 melanoma tumor growth, in line with previous studies. We did, however, not find an additive effect of combining either of the two immunotherapeutic treatments with access to running wheels. B16 tumors displayed upregulated expression of immune regulatory molecules and decreased tumor growth in response to PA. However, combining PA with PD-1 or PD-L1 blockade did not lead to a further augmented inhibition of tumor growth.
DOI: 10.6084/m9.figshare.12850958
title: Extranodal NK/T-cell lymphoma, nasal type, with extranasal presentation – a case report and a review of the literature

description: Extranodal NK/T-cell lymphoma (ENKTCL), nasal type is a very rare and aggressive non-Hodgkin lymphoma. Most commonly it occurs in the upper aerodigestive tract. But, it can also manifest at locations such as the skin, soft tissue, gastrointestinal tract (GI), lungs, testis, etc. These locations are designated as extranasal ENKTCL. The patients with the latter have often more adverse clinical features and poorer survival rate compared with nasal sites. We present a case of an 83-year-old patient with a primary ENKTCL, nasal type, with extranasal presentation in the right upper eyelid. Materials for the literature review was obtained by a comprehensive search on PubMed, which yielded 82 eligible cases with extranasal ENKTCL. Sixty-eight cases (83 %) were localized as primary ENKTCL in the lungs (17), central nervous system (CNS) (14), testis (11), GI-tract (7), skin (6), orbit and intraocular tissue (4), pancreas (2), adrenal gland (2), breast (1), etc. 14 cases (17 %) presented as extended or disseminated diseases involving exclusively organs outside the upper aerodigestive tract. There was no systematic pattern of organ involvement in the extended/disseminated ENKTCL. 63 % of the patient with localized extranasal ENKTCL and about 50% of patients with extended/disseminated disease were reported to have died of the disease. Treatment strategies varied with no preferred option. Among the used treatment options were chemotherapy, radiotherapy, surgery, stem cell transplantation alone or in different combinations. ENKTCL is a highly aggressive disease which may present in extranasal areas. Although the tumors respond to both chemotherapy and radiotherapy, durable complete remissions are very rare.
DOI: 10.6084/m9.figshare.13110191
title: Treatment-related leukopenia in anal cancer patients associated with worse outcome: results of a retrospective cohort study

description: Treatment-related leukopenia in anal cancer patients associated with worse outcome: results of a retrospective cohort study
DOI: 10.6084/m9.figshare.13110191.v1
title: Treatment-related leukopenia in anal cancer patients associated with worse outcome: results of a retrospective cohort study

description: Treatment-related leukopenia in anal cancer patients associated with worse outcome: results of a retrospective cohort study
DOI: 10.6084/m9.figshare.12850979
title: Feasibility and clinical impact of routine molecular testing of gastrointestinal cancers at a tertiary centre with a multi-gene, tumor-agnostic, next generation sequencing panel

description: High-throughput sequencing technologies are increasingly used in research but limited data are available on the feasibility and value of these when routinely adopted in clinical practice. We analyzed all consecutive cancer patients for whom genomic testing by a 48-gene next-generation sequencing (NGS) panel (Truseq Amplicon Cancer Panel, Illumina) was requested as part of standard care in one of the largest Belgian cancer networks between 2014 and 2019. Feasibility of NGS was assessed in all study patients, while the impact of NGS on the decision making was analyzed in the group of gastrointestinal cancer patients. Tumor samples from 1064 patients with varying tumor types were tested, the number of NGS requests increasing over time (<i>p</i> p ≤ .0002). Non-surgical sampling procedure (OR 7.97, <i>p</i> p = .0006) and more recent year of testing (OR 1.79, <i>p</i> = .0258) were independently associated with NGS failure. Excluding well-known actionable or clinically relevant mutations which are recommended by international guidelines and commonly tested by targeted sequencing, 57/279 (20.4%) assessable gastrointestinal cancer patients were found to have tumors harboring at least one actionable altered gene according to the OncoKB database. NGS results, however, had a direct impact on management decisions by the treating physician in only 3 cases (1.1%). Our findings confirm that NGS is feasible in the clinical setting with acceptably low failure rates and rapid turnaround time. In gastrointestinal cancers, however, NGS-based multiple-gene testing adds very little to standard targeted sequencing, and in routine practice the clinical impact of NGS panels including genes which are not routinely recommended by international guidelines remains limited.
DOI: 10.6084/m9.figshare.12850958.v1
title: Extranodal NK/T-cell lymphoma, nasal type, with extranasal presentation – a case report and a review of the literature

description: Extranodal NK/T-cell lymphoma (ENKTCL), nasal type is a very rare and aggressive non-Hodgkin lymphoma. Most commonly it occurs in the upper aerodigestive tract. But, it can also manifest at locations such as the skin, soft tissue, gastrointestinal tract (GI), lungs, testis, etc. These locations are designated as extranasal ENKTCL. The patients with the latter have often more adverse clinical features and poorer survival rate compared with nasal sites. We present a case of an 83-year-old patient with a primary ENKTCL, nasal type, with extranasal presentation in the right upper eyelid. Materials for the literature review was obtained by a comprehensive search on PubMed, which yielded 82 eligible cases with extranasal ENKTCL. Sixty-eight cases (83 %) were localized as primary ENKTCL in the lungs (17), central nervous system (CNS) (14), testis (11), GI-tract (7), skin (6), orbit and intraocular tissue (4), pancreas (2), adrenal gland (2), breast (1), etc. 14 cases (17 %) presented as extended or disseminated diseases involving exclusively organs outside the upper aerodigestive tract. There was no systematic pattern of organ involvement in the extended/disseminated ENKTCL. 63 % of the patient with localized extranasal ENKTCL and about 50% of patients with extended/disseminated disease were reported to have died of the disease. Treatment strategies varied with no preferred option. Among the used treatment options were chemotherapy, radiotherapy, surgery, stem cell transplantation alone or in different combinations. ENKTCL is a highly aggressive disease which may present in extranasal areas. Although the tumors respond to both chemotherapy and radiotherapy, durable complete remissions are very rare.
DOI: 10.6084/m9.figshare.12850979.v1
title: Feasibility and clinical impact of routine molecular testing of gastrointestinal cancers at a tertiary centre with a multi-gene, tumor-agnostic, next generation sequencing panel

description: High-throughput sequencing technologies are increasingly used in research but limited data are available on the feasibility and value of these when routinely adopted in clinical practice. We analyzed all consecutive cancer patients for whom genomic testing by a 48-gene next-generation sequencing (NGS) panel (Truseq Amplicon Cancer Panel, Illumina) was requested as part of standard care in one of the largest Belgian cancer networks between 2014 and 2019. Feasibility of NGS was assessed in all study patients, while the impact of NGS on the decision making was analyzed in the group of gastrointestinal cancer patients. Tumor samples from 1064 patients with varying tumor types were tested, the number of NGS requests increasing over time (<i>p</i> p ≤ .0002). Non-surgical sampling procedure (OR 7.97, <i>p</i> p = .0006) and more recent year of testing (OR 1.79, <i>p</i> = .0258) were independently associated with NGS failure. Excluding well-known actionable or clinically relevant mutations which are recommended by international guidelines and commonly tested by targeted sequencing, 57/279 (20.4%) assessable gastrointestinal cancer patients were found to have tumors harboring at least one actionable altered gene according to the OncoKB database. NGS results, however, had a direct impact on management decisions by the treating physician in only 3 cases (1.1%). Our findings confirm that NGS is feasible in the clinical setting with acceptably low failure rates and rapid turnaround time. In gastrointestinal cancers, however, NGS-based multiple-gene testing adds very little to standard targeted sequencing, and in routine practice the clinical impact of NGS panels including genes which are not routinely recommended by international guidelines remains limited.
DOI: 10.6084/m9.figshare.13079735
title: An easily adaptable validated risk score predicts cancer-specific survival in stage II colon cancer

description: An easily adaptable validated risk score predicts cancer-specific survival in stage II colon cancer
DOI: 10.6084/m9.figshare.13079735.v1
title: An easily adaptable validated risk score predicts cancer-specific survival in stage II colon cancer

description: An easily adaptable validated risk score predicts cancer-specific survival in stage II colon cancer
DOI: 10.6084/m9.figshare.12948537
title: Natural language processing for automated quantification of bone metastases reported in free-text bone scintigraphy reports

description: The widespread use of electronic patient-generated health data has led to unprecedented opportunities for automated extraction of clinical features from free-text medical notes. However, processing this rich resource of data for clinical and research purposes, depends on labor-intensive and potentially error-prone manual review. The aim of this study was to develop a natural language processing (NLP) algorithm for binary classification (single metastasis versus two or more metastases) in bone scintigraphy reports of patients undergoing surgery for bone metastases. Bone scintigraphy reports of patients undergoing surgery for bone metastases were labeled each by three independent reviewers using a binary classification (single metastasis versus two or more metastases) to establish a ground truth. A stratified 80:20 split was used to develop and test an extreme-gradient boosting supervised machine learning NLP algorithm. A total of 704 free-text bone scintigraphy reports from 704 patients were included in this study and 617 (88%) had multiple bone metastases. In the independent test set (<i>n</i> = 141) not used for model development, the NLP algorithm achieved an 0.97 AUC-ROC (95% confidence interval [CI], 0.92–0.99) for classification of multiple bone metastases and an 0.99 AUC-PRC (95% CI, 0.99–0.99). At a threshold of 0.90, NLP algorithm correctly identified multiple bone metastases in 117 of the 124 who had multiple bone metastases in the testing cohort (sensitivity 0.94) and yielded 3 false positives (specificity 0.82). At the same threshold, the NLP algorithm had a positive predictive value of 0.97 and F1-score of 0.96. NLP has the potential to automate clinical data extraction from free text radiology notes in orthopedics, thereby optimizing the speed, accuracy, and consistency of clinical chart review. Pending external validation, the NLP algorithm developed in this study may be implemented as a means to aid researchers in tackling large amounts of data.
DOI: 10.6084/m9.figshare.12948537.v1
title: Natural language processing for automated quantification of bone metastases reported in free-text bone scintigraphy reports

description: The widespread use of electronic patient-generated health data has led to unprecedented opportunities for automated extraction of clinical features from free-text medical notes. However, processing this rich resource of data for clinical and research purposes, depends on labor-intensive and potentially error-prone manual review. The aim of this study was to develop a natural language processing (NLP) algorithm for binary classification (single metastasis versus two or more metastases) in bone scintigraphy reports of patients undergoing surgery for bone metastases. Bone scintigraphy reports of patients undergoing surgery for bone metastases were labeled each by three independent reviewers using a binary classification (single metastasis versus two or more metastases) to establish a ground truth. A stratified 80:20 split was used to develop and test an extreme-gradient boosting supervised machine learning NLP algorithm. A total of 704 free-text bone scintigraphy reports from 704 patients were included in this study and 617 (88%) had multiple bone metastases. In the independent test set (<i>n</i> = 141) not used for model development, the NLP algorithm achieved an 0.97 AUC-ROC (95% confidence interval [CI], 0.92–0.99) for classification of multiple bone metastases and an 0.99 AUC-PRC (95% CI, 0.99–0.99). At a threshold of 0.90, NLP algorithm correctly identified multiple bone metastases in 117 of the 124 who had multiple bone metastases in the testing cohort (sensitivity 0.94) and yielded 3 false positives (specificity 0.82). At the same threshold, the NLP algorithm had a positive predictive value of 0.97 and F1-score of 0.96. NLP has the potential to automate clinical data extraction from free text radiology notes in orthopedics, thereby optimizing the speed, accuracy, and consistency of clinical chart review. Pending external validation, the NLP algorithm developed in this study may be implemented as a means to aid researchers in tackling large amounts of data.
DOI: 10.6084/m9.figshare.12850967.v1
title: Adipose tissue density on CT as a prognostic factor in patients with cancer: a systematic review

description: Predicting oncologic outcomes is essential for optimizing the treatment for patients with cancer. This review examines the feasibility of using Computed Tomography (CT) images of fat density as a prognostic factor in patients with cancer. A systematic literature search was performed in PubMed, Embase and Cochrane up to March 2020. All studies that mentioned using subcutaneous or visceral adipose tissue (SAT and VAT, respectively) CT characteristics as a prognostic factor for patients with cancer were included. The primary endpoints were any disease-related outcomes in patients with cancer. After screening 1043 studies, ten studies reporting a total of 23 – ten for SAT and thirteen for VAT – comparisons on survival, tumor recurrence and postsurgical infection were included. All ten studies included different types of malignancy: six localized, two metastatic disease, and two both. Five different anatomic landmarks were used to uniformly measure fat density on CT: lumbar (L)4 (<i>n</i> = 4), L3 (<i>n</i> = 2), L4-L5 intervertebral space (<i>n</i> = 2), L5-S1 intervertebral space (<i>n</i> = 1), and the abdomen (<i>n</i> = 1). Overall, six of ten SAT comparisons (60%) and six of thirteen VAT comparisons (46%) reported a significant (<i>p</i> This review may support the feasibility of using SAT or VAT on CT as a prognostic tool for patients with cancer in predicting adverse outcomes such as survival and tumor recurrence. Future research should standardize radiologic protocol in prospective homogeneous series of patients on each cancer diagnosis group in order to establish accurate parameters to help physicians use CT scan defined characteristics in clinical practice.
DOI: 10.6084/m9.figshare.12948525
title: The role of chemotherapy in patients with small cell lung cancer and poor performance status

description: There are limited data on the role of chemotherapy in patients with small cell lung cancer (SCLC) and poor performance status (PS). This was a retrospective analysis of a prospective observational study in patients with SCLC and PS 3 or 4. We recorded the initial therapy, symptom improvement, response rate, overall survival (OS), and the impact of various factors on OS. From June 2010 to August 2019, we enrolled 234 patients; 185 (79%) with PS 3 and 49 (21%) PS 4. Initial therapy was best supportive care (BSC) in 49 patients (21%), standard full dose chemotherapy in 31 (13%), and attenuated chemotherapy in 154 (66%). In 89% patients treated with attenuated chemotherapy, symptom-relief occurred at a median of 3 days (IQR, 1–7). Grade 3 and higher toxicities developed in 60% patients treated with initial attenuated chemotherapy, commonly hyponatremia in 39%, neutropenia in 16%, anemia in 11%, and infection in 10%. Grade 3 and higher toxicities as a result of standard chemotherapy occurred in 89% patients treated with upfront standard full dose chemotherapy compared to 69% of patients who received initial attenuated chemotherapy with subsequent treatment escalation. Overall, there were 6 (2.6%) toxic deaths. The response rate to chemotherapy was 77%. The median OS of the patients who received any chemotherapy was significantly longer at 6 months (95% CI, 4.8–7.2) compared to 1 month (95% CI, 0.4–1.6 months) in patients who were managed with BSC, <i>p</i> Chemotherapy prolongs survival in patients with SCLC and poor PS. Administering an initial attenuated chemotherapy regimen followed by standard full-dose chemotherapy when the PS improves may lower toxicity and improve tolerance.