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1
Future Oncol
2020 Dec 8. doi: 10.2217/fon-2020-1100. Online ahead of print.
PD-L1 testing based on SP142 antibody in metastatic triple-negative breast cancer: summary of an expert round-table discussion
Vicente Peg 1, María Ángeles López-García 2, Laura Comerma 3, Gloria Peiró 4, Tomás García-Caballero 5, Ángel Concha López 6, Ana Suárez-Gauthier 7, Irune Ruiz 8, Federico Rojo 9
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PMID: 33289433 DOI: 10.2217/fon-2020-1100
Abstract
Triple-negative breast cancer (TNBC) is more aggressive than other breast cancer subtypes. TNBC is characterized by increased expression of Programmed Death-ligand 1 (PD-L1), a signal used by many tumors to escape the immune response. Expression of PD-L1 is a positive predictor of response to immunotherapy; therefore, it should be investigated in TNBC in order to select patients who may benefit from anti-PD-L1 therapies. While many PD-L1 assays are available, only the VENTANA platform with the anti-PD-L1 (SP142) antibody is licensed as a companion diagnostic device for selecting patients with metastatic/advanced TNBC who are candidates for treatment with atezolizumab. In this article, we provide a summary of an expert round-table discussion about PD-L1 testing, using the SP142 antibody in metastatic TNBC.
Keywords: PD-L1; antibody; breast cancer; diagnosis; immunohistochemistry; immunotherapy.
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2
Review Oncogene
2020 Dec 7. doi: 10.1038/s41388-020-01578-4. Online ahead of print.
Nerve fibers in the tumor microenvironment in neurotropic cancer-pancreatic cancer and cholangiocarcinoma
Xiuxiang Tan 1 2 3, Shivan Sivakumar 4 5, Jan Bednarsch 2, Georg Wiltberger 2, Jakob Nikolas Kather 6, Jan Niehues 6, Judith de Vos-Geelen 7, Liselot Valkenburg-van Iersel 7, Svetlana Kintsler 8, Anjali Roeth 2 3, Guangshan Hao 9, Sven Lang 2, Mariëlle E Coolsen 1, Marcel den Dulk 1 2, Merel R Aberle 3, Jarne Koolen 1, Nadine T Gaisa 8, Steven W M Olde Damink 1 2 3, Ulf P Neumann 1 2, Lara R Heij 10 11 12
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PMID: 33288884 DOI: 10.1038/s41388-020-01578-4
Abstract
Pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) are both deadly cancers and they share many biological features besides their close anatomical location. One of the main histological features is neurotropism, which results in frequent perineural invasion. The underlying mechanism of cancer cells favoring growth by and through the nerve fibers is not fully understood. In this review, we provide knowledge of these cancers with frequent perineural invasion. We discuss nerve fiber crosstalk with the main different components of the tumor microenvironment (TME), the immune cells, and the fibroblasts. Also, we discuss the crosstalk between the nerve fibers and the cancer. We highlight the shared signaling pathways of the mechanisms behind perineural invasion in PDAC and CCA. Hereby we have focussed on signaling neurotransmitters and neuropeptides which may be a target for future therapies. Furthermore, we have summarized retrospective results of the previous literature about nerve fibers in PDAC and CCA patients. We provide our point of view in the potential for nerve fibers to be used as powerful biomarker for prognosis, as a tool to stratify patients for therapy or as a target in a (combination) therapy. Taking the presence of nerves into account can potentially change the field of personalized care in these neurotropic cancers.
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3
Blood Adv
2020 Dec 8;4(23):6051-6063. doi: 10.1182/bloodadvances.2020003471.
Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations
Caroline Diorio 1 2, Kevin O McNerney 1 2, Michele Lambert 1 3, Michele Paessler 1 4, Elizabeth M Anderson 5, Sarah E Henrickson 1 6, Julie Chase 1 7, Emily J Liebling 7, Chakkapong Burudpakdee 1, Jessica H Lee 1, Frances B Balamuth 8, Allison M Blatz 9, Kathleen Chiotos 9 10, Julie C Fitzgerald 1 10, Therese M Giglia 11, Kandace Gollomp 1 3, Audrey R Odom John 9, Cristina Jasen 6, Tomas Leng 1 2, Whitney Petrosa 1, Laura A Vella 9, Char Witmer 3, Kathleen E Sullivan 1 6, Benjamin L Laskin 12, Scott E Hensley 5, Hamid Bassiri 1 9, Edward M Behrens 1 7, David T Teachey 1 2
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PMID: 33290544 DOI: 10.1182/bloodadvances.2020003471
Abstract
Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patients with acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 [COVID-19]; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range [IQR], 244-622 ng/mL), severe disease (median, 646 ng /mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P < .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C.
© 2020 by The American Society of Hematology.
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4
Review Cancers (Basel)
2020 Dec 3;12(12):E3616. doi: 10.3390/cancers12123616.
Update on the Management of Breast Cancer during Pregnancy
Francesca Poggio 1, Marco Tagliamento 2 3, Chiara Pirrone 2 3, Davide Soldato 2 3, Benedetta Conte 2 3, Chiara Molinelli 2 3, Maurizio Cosso 4, Piero Fregatti 5 6, Lucia Del Mastro 1 3, Matteo Lambertini 3 7
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PMID: 33287242 DOI: 10.3390/cancers12123616
Free article
Abstract
The diagnosis of breast cancer during pregnancy represents a challenging situation for the patient, her caregivers and physicians. Pregnancy adds complexity to oncological treatment planning, as many therapies can be potentially dangerous to the fetus. Therefore, a multidisciplinary approach is needed to offer a proper care for obtaining the best possible outcomes for the mother and the future child. Breast surgery is feasible throughout the pregnancy while radiotherapy should be postponed after delivery. Administration of chemotherapy is considered safe and can be given during the second and third trimesters, while it is contraindicated in the first trimester due to the high risk of fetal malformations. Endocrine therapy and targeted agents are not recommended during the whole pregnancy period; however, limited data are available on the use of the majority of new anticancer drugs in this context. The aim of the current review is to provide an update on the current state of art about the management of women diagnosed with breast cancer during pregnancy.
Keywords: breast cancer; chemotherapy; endocrine therapy; immunotherapy; pregnancy; pregnancy during breast cancer; radiotherapy; surgery; targeted therapy.
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5
Life (Basel)
2020 Dec 3;10(12):E325. doi: 10.3390/life10120325.
Any Role of PIK3CA and PTEN Biomarkers in the Prognosis in Oral Squamous Cell Carcinoma?
Anna Starzyńska 1, Paulina Adamska 1, Aleksandra Sejda 2, Monika Sakowicz-Burkiewicz 3, Łukasz Jan Adamski 1, Giulia Marvaso 4 5, Piotr Wychowański 6, Barbara Alicja Jereczek-Fossa 4 5
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PMID: 33287350 DOI: 10.3390/life10120325
Free article
Abstract
Oral squamous cell carcinoma (OSCC) accounts for 95% of the lesions in the oral cavity. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new therapies in OSCC is urgently needed. One objective of such treatment may be a signaling pathway of phosphatidylinositol 3-kinase. The study group included 92 patients treated for OSCC at the University Clinical Centre in Gdańsk, Poland. Study was performed on formalin-fixed paraffin-embedded samples from primary OSCC. Phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) and phosphatase and tensin homolog encoded on chromosome 10 (PTEN) protein expression was assessed by immunohistochemistry (IHC). PIK3CA gene copy number was analyzed using chromogenic and silver in situ hybridization where molecular probes are marked by chromogens and silver ions. PIK3CA IHC H-score ≥ 70 was found in 51.65% patients, and loss of PTEN protein was noticed in 31.46% cases. PIK3CA amplification was detected in 5 t umors. In the case of PTEN protein expression, there was an inverse correlation with the T stage of the primary tumor (r = -0.243) and positive correlation with a 5-year survival (r = 0.235). The number of copies of the PIK3CA gene was associated with the tumor grading (r = 0.208). The present study shows that loss of PTEN protein and the grading (p = 0.040), distant metastases (p = 0.033), smoking (p = 0.016), and alcohol abuse (p = 0.042) were prognostic factors for the survival of patients with OSCC. In contrast, the presence of amplification and OSCC on the floor of the mouth resulted in a nearly six-fold increase in the risk of shortening survival (p = 0.037). Our finding suggests a potential prognostic significance of PTEN loss and PIK3CA amplification in OSCC. Future studies are needed to confirm our results.
Keywords: PIK3CA amplification; PTEN loss; oral squamous cell carcinoma; phosphatidylinositol 3-kinase pathway.
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6
Review Clin Lymphoma Myeloma Leuk
2020 Oct 30;S2152-2650(20)30582-6. doi: 10.1016/j.clml.2020.10.015. Online ahead of print.
Primary Central Nervous System Lymphoma: Evolving Biologic Insights and Recent Therapeutic Advances
Dai Chihara 1, Kieron Dunleavy 2
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PMID: 33288483 DOI: 10.1016/j.clml.2020.10.015
Abstract
Primary central nervous system lymphoma (PCNSL) is a rare and clinically aggressive disease entity associated with poor survival. Though high-dose methotrexate-based immunochemotherapy approaches are effective at inducing responses, few patients experience long-term durable remissions. Recently, novel insights into the biology of this unique disease have been elucidated and have paved the way for the investigation of rational approaches such as Bruton tyrosine kinase inhibition and immunomodulation. Although these strategies can induce high response rates in PCNSL, remissions are short lived, with median progression-free survivals in the range of 6 months or less. Moving forward, understanding the mechanisms of treatment resistance with these and other novel agents is key to developing optimal combinatorial strategies. New approaches such as immune checkpoint inhibition and chimeric antigen receptor T-cell therapy are under investigation for PCNSL and thus far demonstrate activity in anecdotal clinical experiences. Future trials should focus on investigating novel rational combinations designed to optimally target the biology of PCNSL and simultaneously investigate mechanisms of resistance leading to treatment failure.
Keywords: Activated B-cell (ABC) subtype; BTK; BTK inhibitors; CAR T-cell therapy; Primary central nervous system lymphoma.
Copyright © 2020 Elsevier Inc. All rights reserved.
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7
Medicine (Baltimore)
2020 Dec 4;99(49):e23329. doi: 10.1097/MD.0000000000023329.
Correlation analysis and clinical significance of CA125, HE4, DDI, and FDP in type II epithelial ovarian cancer
Li Qiao 1, Xinhua Chen 1, Xuxia Xi 1, Xueqin Chen 1, Pengpeng Zhang 1, Hua Dong 1, Xiaohua Wu 2, Xiaojun Chen 2
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PMID: 33285710 PMCID: PMC7717762 DOI: 10.1097/MD.0000000000023329
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Abstract
Ovarian cancer is one of the common female malignant tumors. The early diagnosis and treatment of ovarian cancer has been a research hotspot. Therefore, we aimed to investigate the correlations between the levels of carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4), D-dimer (DDI), and fibrinogen degradation product (FDP) in patients with type II epithelial ovarian cancer.From January 2018 to January 2019, a total of 952 patients who underwent initial surgery for epithelial ovarian cancer were enrolled in this study. Peripheral venous blood was taken before operation, and the levels of CA125, HE4, DDI, and FDP were tested. The correlations between the levels of CA125, HE4, DDI, and FDP and other clinical indicators (such as presence or absence of chemotherapy, surgical conditions) were analyzed.The level of DDI or FDP was statistically associated with age, chemotherapy, Figo staging, surgical procedure, HE4 level, and CA125 level, respectively. Moreover, the Figo stag ing was statistically correlated with the levels of HE4 and CA125. Besides, we found the levels of CA125 and HE4 were positively correlated with the levels of DDI and FDP.The levels of CA125 and HE4 are the traditional detection indexes for patients with type II epithelial ovarian cancer, and these 2 indicators reflected the degree of disease and prognosis. The levels of DDI and FDP were closely related to the levels of CA125 and HE4 in type II epithelial ovarian cancer, and they also helped to assess the prognosis of epithelial ovarian cancer. Further larger-scale prospective cohort studies are warranted to determine these associations in the future.
Conflict of interest statement
There are no potential conflicts of interest to disclose.
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8
Brain Topogr
2020 Dec 8. doi: 10.1007/s10548-020-00813-1. Online ahead of print.
Brain Tissue Conductivity Measurements with MR-Electrical Properties Tomography: An In Vivo Study
Stefano Mandija 1 2, Petar I Petrov 3, Jord J T Vink 3, Sebastian F W Neggers 3, Cornelis A T van den Berg 4 5
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PMID: 33289858 DOI: 10.1007/s10548-020-00813-1
Abstract
First in vivo brain conductivity reconstructions using Helmholtz MR-Electrical Properties Tomography (MR-EPT) have been published. However, a large variation in the reconstructed conductivity values is reported and these values differ from ex vivo conductivity measurements. Given this lack of agreement, we performed an in vivo study on eight healthy subjects to provide reference in vivo brain conductivity values. MR-EPT reconstructions were performed at 3 T for eight healthy subjects. Mean conductivity and standard deviation values in the white matter, gray matter and cerebrospinal fluid (σWM, σGM, and σCSF) were computed for each subject before and after erosion of regions at tissue boundaries, which are affected by typical MR-EPT reconstruction errors. The obtained values were compared to the reported ex vivo literature values. To benchmark the accuracy of in vivo conductivity reconstructions, the same pipeline was applied to simulated data, which allow knowledge of ground truth conductivity. Provided sufficient boundary erosion, the in vivo σWM and σGM values obtained in this study agree for the first time with literature values measured ex vivo. This could not be verified for the CSF due to its limited spatial extension. Conductivity reconstructions from simulated data verified conductivity reconstructions from in vivo data and demonstrated the importance of discarding voxels at tissue boundaries. The presented σWM and σGM values can therefore be used for comparison in future studies employing different MR-EPT techniques.
Keywords: Brain; Conductivity; Electrical properties; MR-EPT.
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9
Review Cancers (Basel)
2020 Dec 3;12(12):E3622. doi: 10.3390/cancers12123622.
Epigenetics in Breast Cancer Therapy-New Strategies and Future Nanomedicine Perspectives
Verona Buocikova 1, Ivan Rios-Mondragon 2, Eleftherios Pilalis 3 4, Aristotelis Chatziioannou 3 4, Svetlana Miklikova 1, Michal Mego 5, Karlis Pajuste 6, Martins Rucins 6, Naouale El Yamani 7, Eleonora Marta Longhin 7, Arkadij Sobolev 6, Muriel Freixanet 8, Victor Puntes 8 9 10, Aiva Plotniece 6, Maria Dusinska 7, Mihaela Roxana Cimpan 2, Alena Gabelova 1, Bozena Smolkova 1
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PMID: 33287297 DOI: 10.3390/cancers12123622
Free article
Abstract
Epigenetic dysregulation has been recognized as a critical factor contributing to the development of resistance against standard chemotherapy and to breast cancer progression via epithelial-to-mesenchymal transition. Although the efficacy of the first-generation epigenetic drugs (epi-drugs) in solid tumor management has been disappointing, there is an increasing body of evidence showing that epigenome modulation, in synergy with other therapeutic approaches, could play an important role in cancer treatment, reversing acquired therapy resistance. However, the epigenetic therapy of solid malignancies is not straightforward. The emergence of nanotechnologies applied to medicine has brought new opportunities to advance the targeted delivery of epi-drugs while improving their stability and solubility, and minimizing off-target effects. Furthermore, the omics technologies, as powerful molecular epidemiology screening tools, enable new diagnostic and prognostic epigenetic biomarker identifi cation, allowing for patient stratification and tailored management. In combination with new-generation epi-drugs, nanomedicine can help to overcome low therapeutic efficacy in treatment-resistant tumors. This review provides an overview of ongoing clinical trials focusing on combination therapies employing epi-drugs for breast cancer treatment and summarizes the latest nano-based targeted delivery approaches for epi-drugs. Moreover, it highlights the current limitations and obstacles associated with applying these experimental strategies in the clinics.
Keywords: breast cancer; drug resistance; epi-drugs; epigenetics; nanomedicine; targeted delivery.
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10
Cancers (Basel)
2020 Dec 3;12(12):E3612. doi: 10.3390/cancers12123612.
Cancer Testis Antigens and Immunotherapy: Expression of PRAME Is Associated with Prognosis in Soft Tissue Sarcoma
Markus Albertsmeier 1, Annelore Altendorf-Hofmann 2, Lars H Lindner 3, Rolf D Issels 3, Eric Kampmann 3, Hans-Roland Dürr 4, Gabriele Schubert-Fritschle 5, Martin K Angele 1, Thomas Kirchner 6, Achim A Jungbluth 7, Thomas Knösel 6
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PMID: 33287125 DOI: 10.3390/cancers12123612
Free article
Abstract
(1) Background: PRAME, NY-ESO-1, and SSX2 are cancer testis antigens (CTAs), which are expressed in testicular germ cells with re-expression in numerous cancer types. Their ability to elicit humoral and cellular immune responses have rendered them promising targets for cancer immunotherapy, but they have never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: On a protein level, we examined PRAME, NY-ESO-1, and SSX2 expression in tumour tissues of 249 high-risk STS using immunohistochemistry. We correlated expression levels with clinicopathological parameters including tumour-infiltrating lymphocyte (TIL) counts, grading, and long-term survival. (3) Results: Expression of PRAME, NY-ESO-1, and SSX2 was observed in 25 (10%), 19 (8%), and 11 (4%) of 249 specimens with distinct patterns for histo-subtypes. Expression of PRAME was associated with shorter patient survival (p = 0.005) and higher grade (G2 vs. G3, p = 0.001), while NY-ESO-1 exp ression was correlated with more favourable survival (p = 0.037) and lower grade (G2 vs. G3, p = 0.029). Both PRAME and NY-ESO-1 expression were more frequent in STS with low TIL counts. In multivariate analysis, high PRAME and low SSX2 expression levels as well as metastatic disease and non-radical resections were independent predictors of shorter overall survival. (4) Conclusions: CTAs PRAME, NY-ESO-1, and SSX2 show distinct expression patterns in different STS subtypes. These results demonstrate their prognostic relevance and may guide future immunotherapeutic approaches in STS.
Keywords: NY-ESO-1; PRAME; SSX2; biomarker; cancer/testis antigens; human; immunohistochemistry; soft tissue sarcoma; tumour infiltrating lymphocytes.
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11
Cancer
2020 Dec 8. doi: 10.1002/cncr.33364. Online ahead of print.
Phase 2 study of copanlisib in combination with gemcitabine and cisplatin in advanced biliary tract cancers
Elaine S Tan 1, Biwei Cao 2, Jongphil Kim 2, Taymeyah E Al-Toubah 1, Rutika Mehta 1, Barbara A Centeno 3, Richard D Kim 1
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PMID: 33289918 DOI: 10.1002/cncr.33364
Abstract
Background: Biliary tract cancer (BTC) has a poor prognosis despite treatment with first-line gemcitabine and cisplatin. In BTC, PI3K/AKT pathway activation has been shown to increase resistance to chemotherapy, which may be overcome with PI3K inhibition. This phase 2 study evaluated the safety and efficacy of copanlisib, a PI3K inhibitor, with gemcitabine and cisplatin in advanced BTCs. The role of PTEN expression in outcomes was also explored.
Methods: Patients with advanced/unresectable BTC received gemcitabine, cisplatin, and copanlisib as their first-line treatment. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints were the response rate (RR), median overall survival (OS)/PFS, and safety profile. An assessment of PTEN expression by immunohistochemistry was also performed along with molecular profiling.
Results: Twenty-four patients received at least 1 dose of the study drug. The PFS rate at 6 months was 51%; the median OS was 13.7 months (95% CI, 6.8-18.0 months), and the median PFS was 6.2 months (95% CI, 2.9-10.1 months). Nineteen patients were evaluable for RR: 6 patients achieved a partial response (31.6%), and 11 (57.9%) had stable disease. The most common grade 3/4 adverse events were a decreased neutrophil count (45.83%), anemia (25%), increased lipase (25%), and hypertension (20.8%). Twenty patients had tissue evaluable for the PTEN status. The PFS for low (n = 9) and high PTEN expression (n = 11) was 8.5 and 4.6 months, respectively (P = .19). The median OS for low and high PTEN expression groups was 17.9 and 7.0 months, respectively (P = .19).
Conclusions: The addition of copanlisib to gemcitabine and cisplatin does not improve PFS at 6 months. However, future studies using PTEN as a potential biomarker should be considered.
Lay summary: The addition of copanlisib, a PI3K inhibitor, to standard chemotherapy for advanced biliary tract cancers was assessed for efficacy and safety. Twenty-four patients with advanced biliary tract cancer received treatment in this study. There was no difference in survival with the addition of copanlisib in comparison with standard chemotherapy. Copanlisib may be more effective and increase survival in patients with low PTEN expression levels. Further studies are needed to confirm this. No unexpected adverse events occurred.
Keywords: PI3K; cholangiocarcinoma; copanlisib; personalized medicine; targeted therapy.
© 2020 American Cancer Society.
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12
BMC Public Health
2020 Dec 7;20(1):1885. doi: 10.1186/s12889-020-09980-z.
Burnout among Portuguese healthcare workers during the COVID-19 pandemic
Ivone Duarte 1 2, Andreia Teixeira 1 2, Luísa Castro 1 2 3, Sílvia Marina 1 2, Carla Ribeiro 4, Cristina Jácome 1 2, Vera Martins 2, Inês Ribeiro-Vaz 1 2 5, Hugo Celso Pinheiro 6, Andreia Rodrigues Silva 7, Miguel Ricou 1 2, Bruno Sousa 8, Cristiana Alves 1, Andreia Oliveira 1, Paula Silva 9, Rui Nunes 1, Carla Serrão 10
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PMID: 33287794 DOI: 10.1186/s12889-020-09980-z
Free article
Abstract
Background: During COVID-19 pandemic, healthcare workers (HCWs) have had high workload and have been exposed to multiple psychosocial stressors. The aim of this study was to evaluate HCWs in terms of the relative contributions of socio-demographic and mental health variables on three burnout dimensions: personal, work-related, and client-related burnout.
Methods: A cross-sectional study was performed using an online questionnaire spread via social networks. A snowball technique supported by health care institutions and professional organizations was applied.
Results: A total of 2008 subjects completed the survey. Gender, parental status, marriage status, and salary reduction were found to be significant factors for personal burnout. Health problems and direct contact with infected people were significantly associated with more susceptibility to high personal and work-related burnout. Frontline working positions were associated with all three dimensions. Higher levels of stress and depression in HCWs were significantly associated with increased levels of all burnout dimensions. Higher levels of satisfaction with life and resilience were significantly associated with lower levels of all burnout dimensions.
Conclusions: All three burnout dimensions were associated with a specific set of covariates. Consideration of these three dimensions is important when designing future burnout prevention programs for HCWs.
Keywords: Burnout; Stress; COVID-19; Depression; Healthcare workers; Life satisfaction; Resilience.
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13
Med Phys
2020 Dec 8. doi: 10.1002/mp.14644. Online ahead of print.
Automated gross tumour volume contour generation for large-scale analysis of early stage lung cancer patients planned with 4D-CT
Angela Davey 1, Marcel van Herk 1 2, Corinne Faivre-Finn 1 3, Sean Brown 1 3, Alan McWilliam 1 2
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PMID: 33290579 DOI: 10.1002/mp.14644
Abstract
Purpose: Early stage lung cancer patients undergoing stereotactic ablative radiotherapy receive four-dimensional computed tomography (4D-CT) for treatment planning. Often, an internal gross target volume (iGTV), which approximates the motion envelope of a tumour over the breathing cycle, is delineated without defining a gross tumour volume (GTV). However, the GTV volume and shape are important parameters for prognostic and dose modelling, and there is interest in radiomic features extracted from the GTV and surrounding tissue. We demonstrate and validate a method to generate the GTV from an iGTV contour to aid retrospective analysis on routine data.
Method: It is possible to reconstruct the geometry of a tumour with knowledge of tumour motion and the motion envelope formed during respiration. To demonstrate this, tumour motion path was estimated with local rigid registration, and the iGTV positioned incrementally at stations along the reverse path. It is shown that tumour volume is the largest set common to the intersection of the iGTV at the different positions, so hence can be derived. This was implemented for 521 lung lesions on 4D-CT. Eleven patients with a GTV delineation performed by a radiation oncologist on a reference phase (50%) were used for validation. The generated GTV was compared to that delineated by expert using distance-to-agreement, volume, and distance between centres of mass. An overall success rate was determined by detecting registration inaccuracy and performing a quality check on the routine iGTV. For successfully generated contours, GTV volume was compared to iGTV volume in a prognostic model for overal l survival.
Results: For the validation dataset, distance-to-agreement mean (0.79-1.55mm) and standard deviation (0.68-1.51mm) was comparable to expected observer variation. Difference in volume was less than 5cm3 , and average difference in position was 1.21mm. Deviations in shape and position were mainly caused by delineation interpretation differences between iGTV and GTV as opposed to algorithm performance. For the complete dataset, an acceptable contour was generated for 94% of patients using statistical and visual assessment to detect failures. Generated GTV volumes improved prognostic model performance over iGTV volumes.
Conclusion: A method to generate a GTV from an iGTV and 4D-CT dataset was developed. This method facilitates data analysis of early stage lung cancer patients treated in the routine setting i.e. data mining, prognostic modelling, and radiomics. Generation failure detection removes the need for visual assessment of all contours, reducing a time-consuming aspect of big-data analysis. Favourable prognostic performance of generated GTV volumes over iGTV ones demonstrates opportunities to use this methodology for future study.
Keywords: 4D-CT; GTV; SABR; iGTV; lung cancer; swept volume; tumour motion.
This article is protected by copyright. All rights reserved.
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14
Am J Health Syst Pharm
2020 Dec 8;zxaa373. doi: 10.1093/ajhp/zxaa373. Online ahead of print.
Navigating uncharted waters: Developing a standardized approach for evaluating and implementing biosimilar products at a comprehensive cancer center
Mara N Villanueva 1, Jennifer E Davis 2, Stacey M Sobocinski 1
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PMID: 33289499 DOI: 10.1093/ajhp/zxaa373
Abstract
Purpose: The processes for formulary implementation and electronic health record (EHR) integration of biosimilar products at a comprehensive cancer center are described. Implications for research protocols are also discussed.
Summary: The existing literature focuses on practical considerations for formulary addition of biosimilar products, but there is a lack of guidance on how to implement the change, particularly within the EHR. Before building the ordering tools for biosimilars, the clinical and informatics teams should determine the role of biosimilars at the institution, identify drug-specific product characteristics that affect medication build, and characterize implications of future formulary changes or drug shortages. Leveraging an orderable record provides the ability to include logic that maps to multiple products and also allows for future implementation of changes within the medication record rather than requiring "swaps" at the treatment protocol level. The institutional review board should coordinate changes in affected research protocols and consent forms and work with principal investigators to amend protocols when necessary. Pharmacy leaders should develop processes to oversee inventory during the transition period and minimize the risk of errors.
Conclusion: The development of a standardized approach for evaluating and implementing biosimilar products improves efficiency and collaboration among the various team members responsible for the products' integration into existing workflows, including implications for clinical research. Implementing biosimilars for agents used to treat cancer will pose new challenges and require additional considerations. Partial implementation of biosimilars continues to pose multiple challenges in the provision of patient care.
Keywords: biological products; biosimilar pharmaceuticals; electronic health records; formulary; pharmacists.
Published by Oxford University Press on behalf of the American Society of Health-System Pharmacists 2020.
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15
Int Immunopharmacol
2020 Dec 3;90:107186. doi: 10.1016/j.intimp.2020.107186. Online ahead of print.
JAK2 expression is correlated with the molecular and clinical features of breast cancer as a favorable prognostic factor
Qiang Liu 1, Bolun Ai 1, Xiangyi Kong 1, Xiangyu Wang 1, Yihang Qi 1, Zhongzhao Wang 2, Yi Fang 3, Jing Wang 4
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PMID: 33290964 DOI: 10.1016/j.intimp.2020.107186
Abstract
Janus kinases are a family of non-receptor tyrosine kinases involved in autoimmune diseases and malignancies. In breast cancer, the immune related role of JAK2 remains unclear. We aimed to investigate its role at transcriptome level and its relationship with the clinical outcome of breast cancer. This study enrolled a total of 2994 breast cancer samples with transcriptome data, including 1090 samples from The Cancer Genome Atlas (TCGA) and 1904 from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). JAK2 expression was significantly upregulated in both PR positive group (P < 0.01) and HER2 negative group (P < 0.01), and was correlated with American Joint Committee on Cancer (AJCC) stage and tumor malignancies of breast cancer. Functional enrichment analysis revealed that genes correlated with JAK2 were mainly involved in essential functions associated with immune response. Intriguingly, we investigated the association between JAK2 and immune modulators in pa n-cancer, JAK2 expression was positively correlated with most of these immune modulators. In clinical aspect, higher expression of JAK2 was an independent indicator of favorable prognosis in breast cancer patients. The expression of JAK2 is tightly related to the pathology and molecular pathology of breast cancer, and synergistic with other checkpoint members thereby playing a specific role in regulating tumor immune microenvironment. To our knowledge, this is the largest and most comprehensive study characterizing the expression pattern of JAK2 and its special immune functions together with its prognostic values in breast cancer. These findings might shed novel sights for future research in cancer immunotherapy by targeting immune checkpoint molecules.
Keywords: Breast cancer; Cancer immunotherapy; Immune infiltrates; JAK2; Prognostic factor.
Copyright © 2020 Elsevier B.V. All rights reserved.
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16
Curr Med Chem
2020 Dec 7. doi: 10.2174/0929867328666201207202012. Online ahead of print.
Targeting the JAK/STAT Signaling Pathway for Breast Cancer
Fei Shao 1, Xiaonan Pang 1, Gyeong Hun Baeg 2
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PMID: 33290193 DOI: 10.2174/0929867328666201207202012
Abstract
Breast cancer is the most common malignant tumor in women worldwide. Traditional ways of treatment, includ-ing radiotherapy and endocrine therapy, for breast cancer have inevitable side effects. In recent decades, targeted therapies for breast cancer have rapidly advanced and shown a promising future. The JAK/STAT signaling pathway has been shown to play important roles in tumorigenesis, maintenance and metastasis of breast cancer. Hence, many small molecule inhibi-tors of JAK and STAT proteins have been developed. These inhibitors exhibit potent inhibitory effects on breast cancer in both cellular and animal models, and even some of them have already been in clinical trials. This review article discussed the JAK/STAT signal transduction pathway in the pathogenesis of breast cancer, and the potential for the application of JAK/STAT inhibitors in breast cancer treatment.
Keywords: Breast cancer; Inhibitors; JAK/STAT pathway; STAT3 dimerization; Targeted therapy; Therapeutics.
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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17
Trends Microbiol
2020 Nov 6;S0966-842X(20)30270-5. doi: 10.1016/j.tim.2020.10.008. Online ahead of print.
Joining European Scientific Forces to Face Pandemics
M Helena Vasconcelos 1, Stefano Alcaro 2, Virginia Arechavala-Gomeza 3, Jan Baumbach 4, Fernanda Borges 5, Tiziana A L Brevini 6, Javier De Las Rivas 7, Yvan Devaux 8, Pavel Hozak 9, Minna M Keinänen-Toivola 10, Giovanna Lattanzi 11, Thomas Mohr 12, Modra Murovska 13, Bhupesh K Prusty 14, Roy A Quinlan 15, Dolores Pérez-Sala 16, Carmen Scheibenbogen 17, Harald H H W Schmidt 18, Isabel Silveira 19, Paolo Tieri 20, Alexander Tolios 21, Chiara Riganti 22
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PMID: 33288385 PMCID: PMC7716745 DOI: 10.1016/j.tim.2020.10.008
Free PMC article
Abstract
Despite the international guidelines on the containment of the coronavirus disease 2019 (COVID-19) pandemic, the European scientific community was not sufficiently prepared to coordinate scientific efforts. To improve preparedness for future pandemics, we have initiated a network of nine European-funded Cooperation in Science and Technology (COST) Actions that can help facilitate inter-, multi-, and trans-disciplinary communication and collaboration.
Keywords: COST Actions; COVID-19; interdisciplinary network; pandemic.
Copyright © 2020 Elsevier Ltd. All rights reserved.
15 references1 figure
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18
Future Oncol
2020 Dec 8. doi: 10.2217/fon-2020-1071. Online ahead of print.
Proximal versus total gastrectomy for proximal gastric cancer: a Surveillance, Epidemiology, and End Results Program database analysis
Jianchang Wei 1, Ping Yang 1, Qing Huang 1, Zhuanpeng Chen 1, Tong Zhang 1, Feng He 1, He Hu 1, Junbin Zhong 1, Wanglin Li 1, Fang Wei 1, Qiang Wang 1, Jie Cao 1
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PMID: 33289395 DOI: 10.2217/fon-2020-1071
Abstract
Aims: To addresses whether surgical procedure (proximal gastrectomy [PG] vs total gastrectomy [TG]) influences survival outcomes. Methods: Patients were selected from Surveillance, Epidemiology and End Results Program (SEER) database. Survival curve was used to evaluate the differences in overall survival (OS) and cancer-specific survival (CSS). Results: No significant difference was detected in OS and CSS time between PG and TG groups. Also, no significant differences were observed in OS and CSS times between the two groups with respect to clinical stage, tumor stage, node stage, age, gender and tumor differentiation. Tumor differentiation, tumor size, tumor stage, node stage and age were independent prognostic factors in patients with proximal gastric cancer. Conclusions: TG was not necessary for proximal gastric cancer patients, and PG may be considered as an ideal surgery approach.
Keywords: proximal gastrectomy; proximal gastric cancer; total gastrectomy.
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19
Future Oncol
2020 Dec 8. doi: 10.2217/fon-2020-0907. Online ahead of print.
Carfilzomib in combination with daratumumab in the management of relapsed multiple myeloma
Cyrille Touzeau 1 2 3, Chloé Antier 1, Philippe Moreau 1 2 3
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PMID: 33289427 DOI: 10.2217/fon-2020-0907
Abstract
The therapeutic landscape of relapsed multiple myeloma (MM) is constantly evolving. To date, a large proportion of patients present with lenalidomide refractory disease at time of first or second relapse. In this context, few efficient options are currently available. Carfilzomib and daratumumab are approved in the relapse setting. Recently, Phase Ib and Phase III trials evaluated the triplet drug combination daratumumab-carfilzomib-dexamethasone in the relapse setting and demonstrated strong clinical efficacy, especially in lenalidomide refractory patients. Based on these results, this combination has been approved by the US FDA for relapsed MM patients. The present review discusses the safety and efficacy of daratumumab-carfilzomib-dexamethasone in MM.
Keywords: carfilzomib; daratumumab; lenalidomide; monoclonal antibody; myeloma; proteasome inhibitor.
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20
Jpn J Clin Oncol
2020 Dec 9;hyaa220. doi: 10.1093/jjco/hyaa220. Online ahead of print.
Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck
Susumu Okano 1, Akihiro Homma 2, Naomi Kiyota 3, Makoto Tahara 1, Nobuhiro Hanai 4, Takahiro Asakage 5, Kazuto Matsuura 6, Takenori Ogawa 7, Yuki Saito 8, Daisuke Sano 9, Takeshi Kodaira 10, Atsushi Motegi 11, Koichi Yasuda 12, Shunji Takahashi 13, Kaoru Tanaka 14, Takuma Onoe 15, Tomoya Yokota 16, Yoshinori Imamura 3, Yosuke Ariizumi 5, Tetsuo Akimoto 11, Ryuichi Hayashi 6
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PMID: 33290543 DOI: 10.1093/jjco/hyaa220
Abstract
In order to maximize the benefit of induction chemotherapy, practice based on a comprehensive interpretation of a large number of clinical trials, as in this review, is essential. The standard treatment for locally advanced squamous cell carcinoma of the head and neck is surgery or chemoradiation. However, induction chemotherapy followed by (chemo) radiotherapy may be used in some circumstances. Although many clinical trials of induction chemotherapy have been conducted, a rationale other than to preserve the larynx is still controversial. Selection of this modality should therefore be made with care. The current standard regimen for induction chemotherapy is docetaxel, cisplatin and 5-FU, but concerns remain about toxicity, cost and the duration of treatment. Regarding treatment after induction chemotherapy, it is also unclear whether radiation alone or chemoradiation is the better option. Furthermore, there is no answer as to what drugs should be used in combination with radiation therapy after induction chemotherapy. Several new induction chemotherapy treatment developments are currently underway, and future developments are expected. This review article summarizes the current position of induction chemotherapy for head and neck squamous cell carcinoma, based on the evidence produced to date, and discusses the future prospects for this treatment.
Keywords: chemotherapy; head and neck; induction; organ preservation; squamous cell carcinoma.
© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.
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