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  1. Book ; Thesis: Prognostic factors in soft tissue sarcoma

    Engellau, Jacob

    tissue microarray for immunostaining, the importance of whole-tumor sections and time-dependence

    (Acta orthopaedica Scandinavica : Supplementum ; 314)

    2004  

    Author's details Jacob Engellau
    Series title Acta orthopaedica Scandinavica : Supplementum ; 314
    Acta orthopaedica Scandinavica
    Acta orthopaedica Scandinavica ; Supplementum
    Collection Acta orthopaedica Scandinavica
    Acta orthopaedica Scandinavica ; Supplementum
    Language English
    Size 52 S. : Ill., graph. Darst.
    Publisher Taylor & Francis
    Publishing place S.l.
    Publishing country Sweden
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Lund, Univ., Diss., 2004
    HBZ-ID HT014241899
    Database Catalogue ZB MED Medicine, Health

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    Uk I Zs 99 -Suppl.314- verfügbar in Königswinter Königswinter

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  2. Article ; Online: The influence of "bad news" and "neutral/good news" on patients' perception of physician empathy during oncology consultations.

    Tranberg, Mattias / Ekedahl, Henrik / Fürst, Carl Johan / Engellau, Jacob

    Cancer medicine

    2024  

    Abstract: Objectives: Being met with empathy increases information sharing, treatment coherence, and helps patients to recover faster. However, we do not know how the content of the conversation about disease progression, new treatments, or other issues ... ...

    Abstract Objectives: Being met with empathy increases information sharing, treatment coherence, and helps patients to recover faster. However, we do not know how the content of the conversation about disease progression, new treatments, or other issues concerning serious illness affects patients' perceptions of the physician's empathy, and thus, the quality of the conversation. This study aimed to test the hypothesis that patients will rate their physician lower following a "bad news" consultation using the consultation and relational empathy (CARE) measure.
    Methods: A total of 186 outpatients from the Department of Oncology were recruited for this study. After meeting with a patient, the physician filled out a form, placing the patient in either the "bad news" group, or the "neutral/good news" group along with information about the patient and the consultation. The patient was given the CARE measure after the visit.
    Results: The patients who had received bad news rated their physicians a significantly lower score on the CARE measure, even though the effect size was small, than those who had neutral/good news. On average, bad news consultations were 11 min longer.
    Conclusions: Physicians need to be aware of the patients' need to be known and understood, in addition to having skills to attend to emotional cues and concerns, since the current study's finding could be a sign either of the content being projected onto the physician or that the physician is focused on the message rather than on the patient.
    Language English
    Publishing date 2024-01-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2659751-2
    ISSN 2045-7634 ; 2045-7634
    ISSN (online) 2045-7634
    ISSN 2045-7634
    DOI 10.1002/cam4.6903
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  3. Article ; Online: Patterns of Communication About Serious Illness in the Years, Months, and Days before Death.

    Tranberg, Mattias / Jacobsen, Juliet / Fürst, Carl Johan / Engellau, Jacob / Schelin, Maria E C

    Palliative medicine reports

    2022  Volume 3, Issue 1, Page(s) 116–122

    Abstract: Background: Communication with patients and families about serious illness impacts quality of life and helps facilitate decision-making.: Objective: To elucidate the pattern of communication about serious illness for patients who have died in an ... ...

    Abstract Background: Communication with patients and families about serious illness impacts quality of life and helps facilitate decision-making.
    Objective: To elucidate the pattern of communication about serious illness for patients who have died in an inpatient setting.
    Design: Three hundred patients from the Swedish Registry of Palliative Care 2015-2017 were randomly selected for manual chart review.
    Setting: Patients who died in a palliative care, oncology, or internal medicine unit in Sweden were selected.
    Measurements: We report on the frequency of conversations at three time points, 6 months or longer before death ("Years"), 15 days-6 months before death ("Months"), and 0-14 days before death ("Days"). We also report the timing of the conversation about dying.
    Results: A total of 249 patients were included after exclusions; they had an average of 2.1 conversations (range 1-6). The first conversation took place a median of 53 days before death and the last conversation took place a median of 9 days before death. Separate conversations with the next of kin took place a median of two days before death. We could verify a conversation about dying in only 156/249 (63%) medical records.
    Conclusions: Communication about serious illness between clinicians, patients, and families occurs iteratively over a period before death. Measuring the quality of communication about serious illness using a years, months, and days framework may help ensure that patients and families have sufficient information for medical and personal decision making.
    Language English
    Publishing date 2022-08-04
    Publishing country United States
    Document type Journal Article
    ISSN 2689-2820
    ISSN (online) 2689-2820
    DOI 10.1089/pmr.2022.0024
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  4. Article ; Online: Complications after proton radiotherapy in children, focusing on severe late complications. A complete Swedish cohort 2008-2019.

    Martinsson, Ulla / Svärd, Anna-Maja / Witt Nyström, Petra / Embring, Anna / Asklid, Anna / Agrup, Måns / Haugen, Hedda / Fröjd, Charlotta / Engellau, Jacob / Nilsson, Martin P / Isacsson, Ulf / Kristensen, Ingrid / Blomstrand, Malin

    Acta oncologica (Stockholm, Sweden)

    2023  Volume 62, Issue 10, Page(s) 1348–1356

    Abstract: Background: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), ... ...

    Abstract Background: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), following proton RT delivered to a complete Swedish cohort of paediatric patients aged <18 years treated 2008-2019.
    Material and methods: Data was downloaded from a national registry. Complications with a possible causation with RT are reported. Proton treatments until July 2015 was performed with a fixed horizontal 172 MeV beam (The Svedberg Laboratory (TSL), Uppsala) in a sitting position and thereafter with gantry-based pencil-beam scanning technique (Skandion Clinic, Uppsala) in a supine position.
    Results: 219 courses of proton RT (77 at TSL and 142 at Skandion) were delivered to 212 patients (mean age 9.2 years) with various tumour types (CNS tumours 58%, sarcomas 26%, germ cell tumours 7%). Twenty-five patients had severe acute complications (skin, mucous membrane, pharynx/oesophagus, larynx, upper gastrointestinal canal, lower gastrointestinal canal, eyes, ears). Fifteen patients had severe late complications; with increased proportion over time: 4% at 1-year follow-up (FU), 5% at 3-year, 11% at 5-year. Organs affected were skin (1 patient), subcutaneous tissue (4), salivary glands (1), upper GI (1), bone (7), joints (2), CNS (2), PNS (1), eyes (1) and ears (5). Twenty-one of the 28 patients with 10-year FU had at least one late complication grades 1-4 and fourteen of them had more than one (2-5 each).
    Conclusion: The most important result of our study is the relatively low proportion of severe late complications, comparable with other proton studies on various tumours. Furthermore, the numbers of late complications are lower than our own data set on a mixed population of photon and proton treated paediatric patients, assuring the safety of using proton therapy also in the clinical practice.
    MeSH term(s) Humans ; Child ; Protons ; Radiotherapy Dosage ; Sweden ; Proton Therapy/methods ; Soft Tissue Neoplasms
    Chemical Substances Protons
    Language English
    Publishing date 2023-11-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 896449-x
    ISSN 1651-226X ; 0349-652X ; 0284-186X ; 1100-1704
    ISSN (online) 1651-226X
    ISSN 0349-652X ; 0284-186X ; 1100-1704
    DOI 10.1080/0284186X.2023.2260946
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  5. Article: Prognostic factors in soft tissue sarcoma. Tissue microarray for immunostaining, the importance of whole-tumor sections and time-dependence.

    Engellau, Jacob

    Acta orthopaedica Scandinavica. Supplementum

    2004  Volume 75, Issue 314, Page(s) 2 p preceding table of contents–52, backcover

    Abstract: In adult soft tissue sarcoma (STS) of the extremities and trunk wall, improved prognostic factors are needed to identify patients at high-risk for metastasis. Various factors are included in the many prognostic systems currently in use and the prognostic ...

    Abstract In adult soft tissue sarcoma (STS) of the extremities and trunk wall, improved prognostic factors are needed to identify patients at high-risk for metastasis. Various factors are included in the many prognostic systems currently in use and the prognostic value of immunohistochemical (IHC) expression of biological markers is unclear. The tissue-preserving, high throughput tissue microarray (TMA) technique for analysis of immunohistochemical expression of biological markers was validated for Ki-67, and was found to yield results comparable to conventional staining methods. TMA was used to study the IHC expression of multiple markers (Ki-67, p53, cyclin A, bcl-2, beta-catenin, CD44, and Pgp) in 218 malignant fibrous histiocytomas (MFH) and in 140 mixed STS. In the MFH series, tumor size and Ki-67, as the only IHC marker, provided independent prognostic information. In the mixed STS series whole-tumor sections were used and TMA was performed in the peripheral tumor growth zone. Whole-tumor sections facilitated assessment of the strong independent prognostic factors for metastasis vascular invasion, hazard ratio (HR) 3.5, tumor necrosis (HR 2.8), and tumor growth pattern (HR 3.2), and the latter also correlated with local recurrence (LR). In comparison, histological malignancy grade, tumor size, and depth were not of independent prognostic value. When TMA was performed from the peripheral tumor growth zone, the IHC expression of Ki-67 (HR 1.9), beta-catenin (HR 2.7), CD44 (HR 2.1) and Pgp (HR 2.4) were independent prognostic factors. Finally, prognostic factors were found to be time-dependent, and most had lost their prognostic value after 2 years, whereas LR was a strong prognostic factor for metastasis whenever it occurred.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prognosis ; Sarcoma/chemistry ; Sarcoma/mortality ; Sarcoma/pathology ; Time Factors ; Tissue Array Analysis/methods
    Language English
    Publishing date 2004-12
    Publishing country Sweden
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 0300-8827 ; 0001-6470
    ISSN 0300-8827 ; 0001-6470
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  6. Article ; Online: Sustained and controlled delivery of doxorubicin from an in-situ setting biphasic hydroxyapatite carrier for local treatment of a highly proliferative human osteosarcoma.

    Liu, Yang / Raina, Deepak Bushan / Sebastian, Sujeesh / Nagesh, Harshitha / Isaksson, Hanna / Engellau, Jacob / Lidgren, Lars / Tägil, Magnus

    Acta biomaterialia

    2021  Volume 131, Page(s) 555–571

    Abstract: Doxorubicin (DOX) is a cornerstone drug in the treatment of osteosarcoma. However, achieving sufficient concentration in the tumor tissue after systemic administration with few side effects has been a challenge. Even with the most advanced nanotechnology ...

    Abstract Doxorubicin (DOX) is a cornerstone drug in the treatment of osteosarcoma. However, achieving sufficient concentration in the tumor tissue after systemic administration with few side effects has been a challenge. Even with the most advanced nanotechnology approaches, less than 5% of the total administered drug gets delivered to the target site. Alternatives to increase the local concentration of DOX within the tumor using improved drug delivery methods are needed. In this study, we evaluate a clinically approved calcium sulfate/hydroxyapatite (CaS/HA) carrier, both in-vitro and in-vivo, for local, sustained and controlled delivery of DOX to improve osteosarcoma treatment. In-vitro drug release studies indicated that nearly 28% and 36% of the loaded drug was released over a period of 4-weeks at physiological pH (7.4) and acidic pH (5), respectively. About 63% of the drug had been released after 4-weeks in-vivo. The efficacy of the released drug from the CaS/HA material was verified on two human osteosarcoma cell lines MG-63 and 143B. It was demonstrated that the released drug fractions functioned the same way as the free drug without impacting its efficacy. Finally, the carrier system with DOX was assessed using two clinically relevant human osteosarcoma xenograft models. Compared to no treatment or the clinical standard of care with systemic DOX administration, the delivery of DOX using a CaS/HA biomaterial could significantly hinder tumor progression by inhibiting angiogenesis and cell proliferation. Our results indicate that a clinically approved CaS/HA biomaterial containing cytostatics could potentially be used for the local treatment of osteosarcoma. STATEMENT OF SIGNIFICANCE: The triad of doxorubicin (DOX), methotrexate and cisplatin has routinely been used for the treatment of osteosarcoma. These drugs dramatically improved the prognosis, but 45-55% of the patients respond poorly to the treatment with low 5-year survival. In the present study, we repurpose the cornerstone drug DOX by embedding it in a calcium sulfate/hydroxyapatite (CaS/HA) biomaterial, ensuring a spatio-temporal drug release and a hypothetically higher and longer lasting intra-tumoral concentration of DOX. This delivery system could dramatically hinder the progression of a highly aggressive osteosarcoma compared to systemic administration, by inhibiting angiogenesis and cell proliferation. Our data show an efficient method for supplementary osteosarcoma treatment with possible rapid translational potential due to clinically approved constituents.
    MeSH term(s) Bone Neoplasms/drug therapy ; Cell Line, Tumor ; Doxorubicin/pharmacology ; Doxorubicin/therapeutic use ; Drug Delivery Systems ; Durapatite/therapeutic use ; Humans ; Osteosarcoma/drug therapy
    Chemical Substances Doxorubicin (80168379AG) ; Durapatite (91D9GV0Z28)
    Language English
    Publishing date 2021-07-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2173841-5
    ISSN 1878-7568 ; 1742-7061
    ISSN (online) 1878-7568
    ISSN 1742-7061
    DOI 10.1016/j.actbio.2021.07.016
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  7. Article ; Online: Organ sparing total marrow irradiation compared to total body irradiation prior to allogeneic stem cell transplantation.

    Haraldsson, André / Wichert, Stina / Engström, Per E / Lenhoff, Stig / Turkiewicz, Dominik / Warsi, Sarah / Engelholm, Silke / Bäck, Sven / Engellau, Jacob

    European journal of haematology

    2021  Volume 107, Issue 4, Page(s) 393–407

    Abstract: Objectives: Total body irradiation (TBI) is commonly used prior to hematopoietic stem cell transplantation (HSCT) in myeloablative conditioning regimens. However, TBI may be replaced by total marrow irradiation (TMI) at centres with access to Helical ... ...

    Abstract Objectives: Total body irradiation (TBI) is commonly used prior to hematopoietic stem cell transplantation (HSCT) in myeloablative conditioning regimens. However, TBI may be replaced by total marrow irradiation (TMI) at centres with access to Helical TomoTherapy, a modality that has the advantage of delivering intensity-modulated radiotherapy to long targets such as the entire bone marrow compartment. Toxicity after organ sparing TMI prior to HSCT has not previously been reported compared to TBI or with regard to engraftment data.
    Methods: We conducted a prospective observational study on 37 patients that received organ sparing TMI prior to HSCT and compared this cohort to retrospective data on 33 patients that received TBI prior to HSCT.
    Results: The 1-year graft-versus-host disease-free, relapse-free survival (GRFS) was 67.5% for all patients treated with TMI and 80.5% for patients with matched unrelated donor and treated with TMI, which was a significant difference from historical data on TBI patients with a hazard ratio of 0.45 (P = .03) and 0.24 (P < .01). Engraftment with a platelet count over 20 [K/µL] and 50 [K/µL] was significantly shorter for the TMI group, and neutrophil recovery was satisfactory in both treatment cohorts. There was generally a low occurrence of other treatment-related toxicities.
    Conclusions: Despite small cohorts, some significant differences were found; TMI as part of the myeloablative conditioning yields a high 1-year GRFS, fast and robust engraftment, and low occurrence of acute toxicity.
    MeSH term(s) Adolescent ; Adult ; Bone Marrow/drug effects ; Bone Marrow/pathology ; Bone Marrow/radiation effects ; Child ; Child, Preschool ; Female ; Graft Survival/physiology ; Graft vs Host Disease/diagnosis ; Graft vs Host Disease/immunology ; Graft vs Host Disease/pathology ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Male ; Middle Aged ; Myeloablative Agonists/therapeutic use ; Myelodysplastic Syndromes/mortality ; Myelodysplastic Syndromes/pathology ; Myelodysplastic Syndromes/therapy ; Myeloproliferative Disorders/mortality ; Myeloproliferative Disorders/pathology ; Myeloproliferative Disorders/therapy ; Prospective Studies ; Radiotherapy, Intensity-Modulated/methods ; Radiotherapy, Intensity-Modulated/mortality ; Survival Analysis ; Transplantation Conditioning/methods ; Transplantation, Homologous ; Whole-Body Irradiation/methods ; Whole-Body Irradiation/mortality
    Chemical Substances Myeloablative Agonists
    Language English
    Publishing date 2021-06-24
    Publishing country England
    Document type Comparative Study ; Journal Article ; Observational Study
    ZDB-ID 392482-8
    ISSN 1600-0609 ; 0902-4441
    ISSN (online) 1600-0609
    ISSN 0902-4441
    DOI 10.1111/ejh.13675
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    Zs.A 323: Show issues Location:
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  8. Article ; Online: Implementing safe and robust Total Marrow Irradiation using Helical Tomotherapy - A practical guide.

    Haraldsson, André / Engellau, Jacob / Lenhoff, Stig / Engelholm, Silke / Bäck, Sven / Engström, Per E

    Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)

    2019  Volume 60, Page(s) 162–167

    Abstract: Total Marrow Irradiation (TMI) with Helical Tomotherapy is a radiotherapy treatment technique that targets bone marrow and sanctuary sites prior to stem cell or bone marrow transplantation (SCT/BMT). TMI is a complex procedure that involves several ... ...

    Abstract Total Marrow Irradiation (TMI) with Helical Tomotherapy is a radiotherapy treatment technique that targets bone marrow and sanctuary sites prior to stem cell or bone marrow transplantation (SCT/BMT). TMI is a complex procedure that involves several critical steps that all need to be carefully addressed for a successful implementation, such as dose homogeneity in field junctions, choice of target margins, integrity of treatment and back-up planning. In this work we present our solution for a robust and reproducible workflow throughout the treatment chain and data for twenty-three patients treated to date.
    Material & methods: Patients were immobilized in a whole body vacuum cushion and thermoplastic mask. CT-scanning and treatment were performed in two parts with field matching at the upper thigh. Target consisted of marrow containing bone and sanctuary sites. Lungs, kidneys, bowel, heart and liver were defined as organs at risk (OAR). A fast surface scanning system was used to position parts of the body not covered by the imaging system (MVCT) as well as to reduce treatment time.
    Results: All patients completed their treatment and could proceed with SCT/BMT. Doses to OARs were significantly reduced and target dose homogeneity was improved compared to TBI. Robustness tests performed on field matching and patient positioning support that the field junction technique is adequate. Replacing MVCT with optical surface scanning reduced the treatment time by 25 min per fraction.
    Conclusion: The methodology presented here has shown to provide a safe, robust and reproducible treatment for Total Marrow Irradiation using Tomotherapy.
    MeSH term(s) Adolescent ; Adult ; Bone Marrow/radiation effects ; Child ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/therapy ; Organs at Risk ; Patient Care Team ; Patient Positioning/instrumentation ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated/instrumentation ; Radiotherapy, Intensity-Modulated/methods ; Stem Cell Transplantation ; Time Factors ; Tomography, X-Ray Computed ; Young Adult
    Language English
    Publishing date 2019-04-06
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 1122650-x
    ISSN 1724-191X ; 1120-1797
    ISSN (online) 1724-191X
    ISSN 1120-1797
    DOI 10.1016/j.ejmp.2019.03.032
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  9. Article: High Recurrence Rate of Myxofibrosarcoma: The Effect of Radiotherapy Is Not Clear.

    Teurneau, Hjalmar / Engellau, Jacob / Ghanei, Iman / Vult von Steyern, Fredrik / Styring, Emelie

    Sarcoma

    2019  Volume 2019, Page(s) 8517371

    Abstract: Background: Myxofibrosarcoma (MFS) is one of the more common types of soft-tissue sarcoma (STS) in patients over 60 years of age. Local recurrence (LR) rates have been reported to be higher compared to other STS types.: Patients and methods: Using a ... ...

    Abstract Background: Myxofibrosarcoma (MFS) is one of the more common types of soft-tissue sarcoma (STS) in patients over 60 years of age. Local recurrence (LR) rates have been reported to be higher compared to other STS types.
    Patients and methods: Using a population-based series from the southern Sweden health care region, 56 consecutive patients with MFS and localized disease at diagnosis were analyzed with respect to LR and distant metastases after surgery ± adjuvant treatment.
    Results: The overall local recurrence (
    Conclusions: The rate of LR for patients with myxofibrosarcoma was high. The impact of RT on local tumor control was unclear. The surgical margin was important for both local and distant tumor control. Large tumor size was a risk factor for distant metastasis.
    Language English
    Publishing date 2019-10-01
    Publishing country Egypt
    Document type Journal Article
    ZDB-ID 1338527-6
    ISSN 1357-714X
    ISSN 1357-714X
    DOI 10.1155/2019/8517371
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    Zs.A 5073: Show issues Location:
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  10. Article ; Online: Bone mineral: A trojan horse for bone cancers. Efficient mitochondria targeted delivery and tumor eradication with nano hydroxyapatite containing doxorubicin.

    Liu, Yang / Nadeem, Aftab / Sebastian, Sujeesh / Olsson, Martin A / Wai, Sun N / Styring, Emelie / Engellau, Jacob / Isaksson, Hanna / Tägil, Magnus / Lidgren, Lars / Raina, Deepak Bushan

    Materials today. Bio

    2022  Volume 14, Page(s) 100227

    Abstract: Efficient systemic pharmacological treatment of solid tumors is hampered by inadequate tumor concentration of cytostatics necessitating development of smart local drug delivery systems. To overcome this, we demonstrate that doxorubicin (DOX), a ... ...

    Abstract Efficient systemic pharmacological treatment of solid tumors is hampered by inadequate tumor concentration of cytostatics necessitating development of smart local drug delivery systems. To overcome this, we demonstrate that doxorubicin (DOX), a cornerstone drug used for osteosarcoma treatment, shows reversible accretion to hydroxyapatite (HA) of both nano (nHA) and micro (mHA) size. nHA particles functionalized with DOX get engulfed in the lysosome of osteosarcoma cells where the acidic microenvironment causes a disruption of the binding between DOX and HA. The released DOX then accumulates in the mitochondria causing cell starvation, reduced migration and apoptosis. The HA+DOX delivery system was also tested in-vivo on osteosarcoma bearing mice. Locally delivered DOX via the HA particles had a stronger tumor eradication effect compared to the controls as seen by PET-CT and immunohistochemical staining of proliferation and apoptosis markers. These results indicate that in addition to systemic chemotherapy, an adjuvant nHA could be used as a carrier for intracellular delivery of DOX for prevention of tumor recurrence after surgical resection in an osteosarcoma. Furthermore, we demonstrate that nHA particles are pivotal in this approach but a combination of nHA with mHA could increase the safety associated with particulate nanomaterials while maintaining similar therapeutic potential.
    Language English
    Publishing date 2022-02-26
    Publishing country England
    Document type Journal Article
    ISSN 2590-0064
    ISSN (online) 2590-0064
    DOI 10.1016/j.mtbio.2022.100227
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