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Nilsson, R. Jonas A.
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Publications (10 of 35) Show all publications
Rosell, R., Codony-Servat, J., González, J., Santarpia, M., Jain, A., Shivamallu, C., . . . González-Cao, M. (2024). KRAS G12C-mutant driven non-small cell lung cancer (NSCLC). Critical reviews in oncology/hematology, 195, Article ID 104228.
Open this publication in new window or tab >>KRAS G12C-mutant driven non-small cell lung cancer (NSCLC)
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2024 (English)In: Critical reviews in oncology/hematology, ISSN 1040-8428, E-ISSN 1879-0461, Vol. 195, article id 104228Article, review/survey (Refereed) Published
Abstract [en]

KRAS G12C mutations in non-small cell lung cancer (NSCLC) partially respond to KRAS G12C covalent inhibitors. However, early adaptive resistance occurs due to rewiring of signaling pathways, activating receptor tyrosine kinases, primarily EGFR, but also MET and ligands. Evidence indicates that treatment with KRAS G12C inhibitors (sotorasib) triggers the MRAS:SHOC2:PP1C trimeric complex. Activation of MRAS occurs from alterations in the Scribble and Hippo-dependent pathways, leading to YAP activation. Other mechanisms that involve STAT3 signaling are intertwined with the activation of MRAS. The high-resolution MRAS:SHOC2:PP1C crystallization structure allows in silico analysis for drug development. Activation of MRAS:SHOC2:PP1C is primarily Scribble-driven and downregulated by HUWE1. The reactivation of the MRAS complex is carried out by valosin containing protein (VCP). Exploring these pathways as therapeutic targets and their impact on different chemotherapeutic agents (carboplatin, paclitaxel) is crucial. Comutations in STK11/LKB1 often co-occur with KRAS G12C, jeopardizing the effect of immune checkpoint (anti-PD1/PDL1) inhibitors.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
AQP5, HUWE1, Immunotherapy, KRAS G12C, MRAS, NSCLC, RGS3, SHOC2, STK11/LKB1, VCP
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-221544 (URN)10.1016/j.critrevonc.2023.104228 (DOI)38072173 (PubMedID)2-s2.0-85185266160 (Scopus ID)
Available from: 2024-03-13 Created: 2024-03-13 Last updated: 2024-03-13Bibliographically approved
Källman, M., Bergström, S., Carlsson, T., Järås, J., Holgersson, G., Nordberg, J. H., . . . Bergqvist, M. (2023). Use of CAM among cancer patients: results of a regional survey in Sweden. BMC Complementary Medicine and Therapies, 23(1), Article ID 51.
Open this publication in new window or tab >>Use of CAM among cancer patients: results of a regional survey in Sweden
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2023 (English)In: BMC Complementary Medicine and Therapies, E-ISSN 2662-7671, Vol. 23, no 1, article id 51Article in journal (Refereed) Published
Abstract [en]

Background: The use of complementary and alternative medicine (CAM) by patients is widespread. However, there is a lack of knowledge regarding the extent and details of patient CAM use in Sweden, especially in rural Sweden. The aim of this study was to estimate the extent and characteristics of CAM use among cancer patients in Region Gävleborg. Methods: A total of 631 questionnaires were distributed to which 376 responses were registered, yielding a response rate of 59.6%. Questionnaires were distributed to oncology patients at their first visit for curative treatment at the Department of Oncology, Gävle Hospital. Palliative patients were recruited at their first visit and during enrollment in palliative outpatient care in their own homes. The characteristics of the respondents were presented with standard descriptive statistics. A multivariable logistic model was fitted to calculate odds ratios (ORs) and identify potential predictors (Age, Gender, Education, Diagnosis) of CAM use post-cancer diagnosis. Results: 54% of all participants reported lifetime CAM use, 34% reported CAM use post-diagnosis. The most common CAM methods used after diagnosis are vitamins, health food preparations, herbal teas, prayer and dietary methods. The most common source of information reported is family and friends. Almost 70% of those who used CAM after their diagnosis stated that they did not discuss their use with healthcare professionals. Most patients reported that they would like some CAM modalities to be offered within conventional care regardless of their own CAM use. Conclusions: The use of CAM is common among patients with cancer in the region of Gävleborg, and previous studies show a similar use in Sweden in general. Based on the widespread use of CAM and patient interest in discussing CAM use with healthcare professionals, greater attention and focus should be placed on creating a basis for this dialogue. If we, as healthcare professionals, are to emphasise our commitment to providing patient-centred care, we must acknowledge that patients use CAM and are seeking a dialogue about CAM use in their care.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023
Keywords
CAM, Cancer, Complementary and alternative medicine, Europe, Oncology, Sweden
National Category
Nursing Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-205348 (URN)10.1186/s12906-023-03876-2 (DOI)000934516700001 ()36797715 (PubMedID)2-s2.0-85148258849 (Scopus ID)
Funder
Umeå UniversityRegion GavleborgCancerforskningsfonden i Norrland
Available from: 2023-04-03 Created: 2023-04-03 Last updated: 2023-09-26Bibliographically approved
Thysell, E., Köhn, L., Semenas, J., Järemo, H., Freyhult, E., Lundholm, M., . . . Wikström, P. (2022). Clinical and biological relevance of the transcriptomic-based prostate cancer metastasis subtypes MetA-C. Molecular Oncology (4)
Open this publication in new window or tab >>Clinical and biological relevance of the transcriptomic-based prostate cancer metastasis subtypes MetA-C
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2022 (English)In: Molecular Oncology, ISSN 1574-7891, E-ISSN 1878-0261, no 4Article in journal (Refereed) Published
Abstract [en]

To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes, and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n=17), short-term castrated (n=21) or castration resistant (n=65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples was also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single-nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen-receptor-targeting treatments.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
MetA-C, Metastasis, Prognosis, Prostate cancer, Subtypes, Transcriptomic
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-190463 (URN)10.1002/1878-0261.13158 (DOI)000734478400001 ()34889043 (PubMedID)2-s2.0-85121666619 (Scopus ID)
Available from: 2021-12-16 Created: 2021-12-16 Last updated: 2023-10-23Bibliographically approved
In ’t Veld, S. G. .., Arkani, M., Post, E., Antunes-Ferreira, M., D'Ambrosi, S., Vessies, D. C. .., . . . Wurdinger, T. (2022). Detection and localization of early- and late-stage cancers using platelet RNA. Cancer Cell, 40(9), 999-1009.e6
Open this publication in new window or tab >>Detection and localization of early- and late-stage cancers using platelet RNA
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2022 (English)In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 40, no 9, p. 999-1009.e6Article in journal (Refereed) Published
Abstract [en]

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
blood, blood platelets, cancer, early detection, liquid biopsy, RNA, TEP
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-199458 (URN)10.1016/j.ccell.2022.08.006 (DOI)000888756000014 ()36055228 (PubMedID)2-s2.0-85137385164 (Scopus ID)
Funder
EU, Horizon 2020
Available from: 2022-09-27 Created: 2022-09-27 Last updated: 2023-09-05Bibliographically approved
Sol, N., 't Veld, S. G. J., Vancura, A., Tjerkstra, M., Leurs, C., Rustenburg, F., . . . Wurdinger, T. (2020). Tumor-Educated Platelet RNA for the Detection and (Pseudo)progression Monitoring of Glioblastoma. Cell Reports Medicine, 1(7), Article ID 100101.
Open this publication in new window or tab >>Tumor-Educated Platelet RNA for the Detection and (Pseudo)progression Monitoring of Glioblastoma
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2020 (English)In: Cell Reports Medicine, E-ISSN 2666-3791 , Vol. 1, no 7, article id 100101Article in journal (Refereed) Published
Abstract [en]

Tumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined by swarm intelligence, to detect and monitor glioblastoma. We assessed specificity by comparing the spliced RNA profile of TEPs from glioblastoma patients with multiple sclerosis and brain metastasis patients (validation series, n = 157; accuracy, 80%; AUC, 0.81 [95% CI, 0.74-0.89; p < 0.001]). Second, analysis of patients with glioblastoma versus asymptomatic healthy controls in an independent validation series (n = 347) provided a detection accuracy of 95% and AUC of 0.97 (95% CI, 0.95-0.99; p < 0.001). Finally, we developed the digitalSWARM algorithm to improve monitoring of glioblastoma progression and demonstrate that the TEP tumor scores of individual glioblastoma patients represent tumor behavior and could be used to distinguish false positive progression from true progression (validation series, n = 20; accuracy, 85%; AUC, 0.86 [95% CI, 0.70-1.00; p < 0.012]). In conclusion, TEPs have potential as a minimally invasive biosource for blood-based diagnostics and monitoring of glioblastoma patients.

Place, publisher, year, edition, pages
Elsevier, 2020
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-187436 (URN)10.1016/j.xcrm.2020.100101 (DOI)000642315000001 ()33103128 (PubMedID)2-s2.0-85096622064 (Scopus ID)
Funder
Cancerforskningsfonden i NorrlandNIH (National Institute of Health)Swedish Research Council
Available from: 2021-09-10 Created: 2021-09-10 Last updated: 2023-08-25Bibliographically approved
Tjon-Kon-Fat, L.-A., Sol, N., Wurdinger, T. & Nilsson, R. J. (2018). Platelet RNA in Cancer Diagnostics. Seminars in Thrombosis and Hemostasis, 44(2), 135-141
Open this publication in new window or tab >>Platelet RNA in Cancer Diagnostics
2018 (English)In: Seminars in Thrombosis and Hemostasis, ISSN 0094-6176, E-ISSN 1098-9064, Vol. 44, no 2, p. 135-141Article in journal (Refereed) Published
Abstract [en]

Platelets are involved in several steps of cancer metastasis. During this process, platelets are exposed to the tumor and its environment, thereby exchanging biomolecules with the tumor cells and resulting in tumor-mediated education of the platelets and a change in their RNA profile. Analysis of platelet RNA profiles or direct measurement of tumor-derived biomarkers within platelets can provide information on ongoing cancer-related processes in the individual (e.g., whether the patient has cancer, the tumor type, and possibly identify oncogenic alterations driving the disease for treatment selection). The close interaction with the disease process and the ability to respond to systemic alterations make platelets an interesting biosource for implementation in precision medicine.

Place, publisher, year, edition, pages
THIEME MEDICAL PUBL INC, 2018
Keywords
platelets, biomarkers, liquid biopsy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-145772 (URN)10.1055/s-0037-1606182 (DOI)000426118100007 ()28905353 (PubMedID)2-s2.0-85029755219 (Scopus ID)
Available from: 2018-06-18 Created: 2018-06-18 Last updated: 2018-06-18Bibliographically approved
Tjon-Kon-Fat, L.-A., Lundholm, M., Schröder, M., Wurdinger, T., Thellenberg-Karlsson, C., Widmark, A., . . . Nilsson, R. J. (2018). Platelets harbor prostate cancer biomarkers and the ability to predict therapeutic response to abiraterone in castration resistant patients. The Prostate, 78(1), 48-53
Open this publication in new window or tab >>Platelets harbor prostate cancer biomarkers and the ability to predict therapeutic response to abiraterone in castration resistant patients
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2018 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, no 1, p. 48-53Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Novel therapies for castration resistant prostate cancer (CRPC) have been introduced in the clinic with possibilities for individualized treatment plans. Best practice of those expensive drugs requires predictive biomarker monitoring. This study used circulating biomarker analysis to follow cancer-derived transcripts implicated in therapy resistance.

METHOD: The isolated platelet population of blood samples and digital-PCR were used to identify selected biomarker transcripts in patients with CRPC prior chemo- or androgen synthesis inhibiting therapy.

RESULTS: Fifty patients received either docetaxel (n = 24) or abiraterone (n = 26) therapy, with therapy response rates of 54% and 48%, respectively. Transcripts for the PC-associated biomarkers kallikrein-related peptidase-2 and -3 (KLK2, KLK3), folate hydrolase 1 (FOLH1), and neuropeptide-Y (NPY) were uniquely present within the platelet fraction of cancer patients and not detected in healthy controls (n = 15). In the abiraterone treated cohort, the biomarkers provided information on therapy outcome, demonstrating an association between detectable biomarkers and short progression free survival (PFS) (FOLH1, P < 0.01; KLK3, P < 0.05; and NPY, P < 0.05). Patients with biomarker-negative platelets had the best outcome, while FOLH1 (P < 0.05) and NPY (P = 0.05) biomarkers provided independent predictive information in a multivariate analysis regarding PFS. KLK2 (P < 0.01), KLK3 (P < 0.001), and FOLH1 (P < 0.05) biomarkers were associated with short overall survival (OS). Combining three biomarkers in a panel (KLK3, FOLH1, and NPY) made it possible to separate long-term responders from short-term responders with 87% sensitivity and 82% specificity.

CONCLUSION: Analyzing tumor-derived biomarkers in platelets of CRPC patients enabled prediction of the outcome after abiraterone therapy with higher accuracy than baseline serum PSA or PSA response.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2018
Keywords
biomarkers, liquid biopsy, personalized medicine, platelet, prostate cancer, therapy stratification
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-142384 (URN)10.1002/pros.23443 (DOI)000417131400007 ()29094381 (PubMedID)2-s2.0-85037377941 (Scopus ID)
Available from: 2017-11-29 Created: 2017-11-29 Last updated: 2023-03-24Bibliographically approved
Köhn, L., Johansson, M., Grankvist, K. & Nilsson, J. (2017). Liquid biopsies in lung cancer: time to implement research technologies in routine care?. Annals of Translational Medicine, 5(13), Article ID 278.
Open this publication in new window or tab >>Liquid biopsies in lung cancer: time to implement research technologies in routine care?
2017 (English)In: Annals of Translational Medicine, ISSN 2305-5839, E-ISSN 2305-5847, Vol. 5, no 13, article id 278Article, review/survey (Refereed) Published
Abstract [en]

Lung cancer is the leading cause of cancer mortality. A substantial progress in the understanding of lung cancer biology has resulted in several promising targeted therapies for advanced disease. Druggable targets today include point mutations such as EGFR, BRAF and re-arrangements in genes such as ALK and ROS1. Liquid biopsies collecting e.g., circulating tumor DNA (ctDNA) reflects overall tumor information and is not biased by analyzing of only a small fraction of the tumor and is always accessible in contrast to the lung cancer tissue. Technological advances in detection of low frequency mutation variants in ctDNA have made it the dominating liquid biopsy platform in terms of utility and sensitivity. Circulating DNA or RNA may possible be used to define populations with higher risk of developing lung cancer, thus reducing screening cohorts and increasing the positive predictive value of screening. Blood based-tests may also aid to identify genetic alterations several weeks prior to radiologically verified recurrence and may be of great value in the follow-up of lung cancer patients. Besides being an alternative to invasive biopsies in selected cases, liquid biopsies offer a unique possibility to monitor treatment response following medical treatment as well as treatment response and resistance development after targeted therapy, giving a possibility to modify the treatment after the genetic profile of the tumor. Ideally, genetic alterations found in ctDNA could be tracked in real-time discriminating between fast-growing life-threatening tumors from more indolent slow growing tumors or premalignant growth that are of no concern for the wellbeing of the patient. This review focuses on future perspectives of liquid biopsies in lung cancer care for different clinical settings and present current technological platforms for further discussion of possible strategies for implementation of liquid biopsies in lung cancer.

Place, publisher, year, edition, pages
AME Publishing Company, 2017
Keywords
cell-free DNA, liquid biopsy, lung cancer, next-generation sequencing, personalized medicine
National Category
Cancer and Oncology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-139154 (URN)10.21037/atm.2017.04.12 (DOI)000408647900011 ()28758104 (PubMedID)2-s2.0-85024840457 (Scopus ID)
Available from: 2017-09-11 Created: 2017-09-11 Last updated: 2023-03-24Bibliographically approved
Best, M. G., Sol, N., 't Veld, S. G. J., Vancura, A., Muller, M., Niemeijer, A.-L. N., . . . Wurdinger, T. (2017). Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets. Cancer Cell, 32(2), 238-252
Open this publication in new window or tab >>Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets
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2017 (English)In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 32, no 2, p. 238-252Article in journal (Refereed) Published
Abstract [en]

Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.

Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-142881 (URN)10.1016/j.ccell.2017.07.004 (DOI)000407932500010 ()28810146 (PubMedID)2-s2.0-85027221443 (Scopus ID)
Available from: 2017-12-13 Created: 2017-12-13 Last updated: 2023-03-24Bibliographically approved
Holgersson, G., Bergqvist, M., Nilsson, R. J., Thureson, M., Harmenberg, J. & Bergstrom, S. (2017). The prognostic value of pre-treatment leukocytosis in patients with previously treated, stage IIIB/IV non-small cell lung cancer treated with the IGF-1R pathway modulator AXL1717 or docetaxel: a retrospective analysis of a phase II trial. Asian Pacific Journal of Cancer Prevention, 18(6), 1555-1560
Open this publication in new window or tab >>The prognostic value of pre-treatment leukocytosis in patients with previously treated, stage IIIB/IV non-small cell lung cancer treated with the IGF-1R pathway modulator AXL1717 or docetaxel: a retrospective analysis of a phase II trial
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2017 (English)In: Asian Pacific Journal of Cancer Prevention, ISSN 1513-7368, Vol. 18, no 6, p. 1555-1560Article in journal (Refereed) Published
Abstract [en]

Background: The aim of the present study was to investigate any prognostic value of pre-treatment anemia, leukocytosis and thrombocytosis in patients with advanced pretreated NSCLC.

Methods: A randomized, multicenter phase II study comparing the IGF-1R modulator AXL with standard docetaxel in the treatment of previously treated stage IIIB or IV NSCLC patients was conducted in 2011-2013. Clinical and laboratory data were collected, including serum values for hemoglobin (Hgb), white blood cells (WBC) and platelets (Plt) at baseline. These hematological parameters were studied in relation to overall survival using Kaplan-Meier product-limit estimates and multivariate Cox proportional hazards regression models.

Results: The median overall survival for all patients was 8.9 months. Patients with leukocytosis (WBC > 9 x 109/L) had a significantly shorter median overall survival (4.2 months) as compared with those with a WBC ≤ 9 x 109/L at baseline (12.3 months) with a corresponding of HR 2.10 (95% CI: 1.29-3.43). Patients with anemia (Hgb < 110 g/L) had a non-significant (p = 0.097) shorter median overall survival (6.1 months) as compared with their counterparts with Hgb ≤ 110 g/L at baseline (9.4 months). As for thrombocytosis (Plt > 350 x 109/L), there was no statistically significant impact on overall survival. Leukocytosis retained its prognostic significance in a multivariate model where other clinical factors such as age, sex and WHO performance status were taken into consideration (HR: 1.83, 95% CI: 1.06-3.13, p = 0.029).

Conclusion: Pre-treatment leukocytosis is a strong and independent prognostic marker for shorter overall survival in previously treated stage IIIB or IV NSCLC patients receiving docetaxel or AXL1717. Combined use of pre-treatment leukocytosis assessments together with established prognostic factors such as performance status could be of help when making treatment decisions in this clinical setting.

Keywords
Anemia, Leukocytosis, NSCLC, Second-line, Thrombocytosis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-200196 (URN)10.22034/APJCP.2017.18.6.1555 (DOI)28669167 (PubMedID)2-s2.0-85021393565 (Scopus ID)
Available from: 2022-10-13 Created: 2022-10-13 Last updated: 2022-10-13Bibliographically approved
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