Gunnar Hillerdal

Karolinska University Hospital, Tukholma, Stockholm, Sweden

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Publications (77)322.27 Total impact

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    Erik Folch · Gunnar Hillerdal

    Preview · Article · Sep 2015 · European Respiratory Journal
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    ABSTRACT: An increasing proportion of cancer patients are aged >65 years and many are aged >70 years. Treatment of the elderly with lung cancer has, therefore, become an important issue; so we performed a retrospective study of our patients to demonstrate how elderly patients with NSCLC are treated in real-life, clinical practice. All patients aged ≥70 years with NSCLC at our department were reviewed retrospectively. In total, 1059 patients (50.8% of all NSCLC patients). Of these patients, 243 (22.9%) received chemotherapy, 164 (70.4%) of whom were treated with a platinum doublet using carboplatin. Second- and third-line chemotherapy were given to 31.4% and 13.9% of patients, respectively. Median overall survival was 289 and 320 days for male and female patients, respectively. Patients with performance status (PS) 0 experienced significantly better survival than patients with PS1 or PS 2: 410, 314, and 204 days, respectively. Age was of less importance, with patients aged 70–79 years versus those aged ≥80 years. Treatment of elderly NSCLC patients with chemotherapy is feasible if they have a good PS and appears to prolong survival. In this study, we found no significant differences in survival either between age groups or genders.
    Full-text · Article · Aug 2015
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    ABSTRACT: To evaluate the feasibility and adherence to home delivery (HD) of pemetrexed maintenance treatment in patients with advanced non-squamous non-small cell lung cancer (nsqNSCLC). Exploratory, prospective, single-arm, Phase II study in advanced nsqNSCLC patients, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1 that did not progress after 4 first-line induction cycles of a platinum doublet. The first cycle of pemetrexed (500mg/m(2)) was hospital administered, further cycles were HD until progressive disease or discontinuation. Feasibility was assessed by the adherence rate to HD (probability of reversion to hospital administration or treatment discontinuation due to HD) as primary endpoint, and by health-related quality-of-life (HRQoL: EQ-5D, lung cancer symptom scale [LCSS]), satisfaction with HD, overall survival (OS), and safety. 52 patients (UK & Sweden) received a median of 4 (range 1-19) pemetrexed maintenance cycles. Adherence rate up to Cycle 6 was 98.0% (95% confidence interval [CI]: 86.4%, 99.7%). All but 2 patients remained on HD. 1 patient discontinued after Cycle 1 (patient decision), and 1 after Cycle 6 (non-compliance with oral dexamethasone). 87% (33/38) of the patients preferred home to hospital treatment and in 90% (28/31) of cases, physicians were satisfied with distant management of patients. During HD Cycles 2-4 mean change from baseline ranged from 3.0 to 7.7 for EQ-5D visual analog scale. The 6-month OS rate was 73% (95% CI: 58%, 83%). 1 patient had an HD-related adverse event (device-related infection, Grade 2) and 1 patient died after Cycle 1, before HD, due to a possibly drug-related atypical pneumonia. HD of pemetrexed maintenance treatment in patients with advanced nsqNSCLC was feasible, safe, and preferred by patients, while maintaining HRQoL. Physicians were satisfied with distant patient management. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · May 2015 · Lung Cancer
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    Eva Branden · Gunnar Hillerdal · Karl Kolbeck · Hirsh Koyi
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    ABSTRACT: The standard treatment for non-small cell lung cancer (NSCLC) stages IIIb and IV is a platinum compound combined with a third-generation cytotoxic agent. We decided to conduct a phase II study to assess whether the platinum compound could be replaced with pemetrexed with similar results and without an increase in side effects. Consecutive eligible patients were randomized to either the standard arm of gemcitabine plus carboplatin (GC) or the experimental arm of gemcitabine plus pemetrexed (GP). Fifty evaluable patients were enrolled in the GC arm, and 44 received GP. There were 10 partial responses in the GC arm and 16 in the GP arm. With GC, mean survival was 9 months compared with 15 months with GP. The side effects were similar in both groups. Pemetrexed can replace platinum compounds in the first-line treatment of stage IIIb and IV NSCLC without increasing the side effects. A trend toward better survival was observed in the patients receiving pemetrexed instead of a platinum compound, and this should be studied further. ©AlphaMed Press; the data published online to support this summary is the property of the authors.
    Full-text · Article · Mar 2015 · The Oncologist
  • Hirsh Koyi · Gunnar Hillerdal

    No preview · Article · Feb 2015 · Lakartidningen
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    ABSTRACT: Objectives First-line pemetrexed-cisplatin (Pem-Cis) induction therapy followed by Pem maintenance, and first-line bevacizumab- (Bev-) based therapy are treatment options for patients with advanced non-squamous NSCLC. This study explored efficacy and safety of first-line induction Pem-Cis + Bev followed by maintenance Pem + Bev. Materials and methods Patients with ECOG performance status (PS) 0-1 were scheduled to receive 4 cycles Pem 500 mg/m2, Cis 75 mg/m2, and Bev 7.5 mg/kg, given every 21 days. In absence of progressive disease (PD) and if ECOG-PS ≤1, patients could continue Pem + Bev maintenance until PD or unacceptable toxicity. All patients received vitamin supplementation as per Pem label. Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), response rate, and toxicity. Results 109 patients received induction therapy (median age 61yrs, ECOG-PS 0/1 54/46%, stage IIIB/IV 9/91%, adenocarcinoma 91%), 72 patients (66.1%) started maintenance therapy. Median (maximum) numbers of cycles were 4 (4) for Cis and 8 (34) for Pem + Bev. Overall, median PFS and OS were 6.9 (90%CI 5.7-8.3) and 14.7 (95%CI 11.5-19.7) months. For patients starting maintenance therapy, median (95%CI) PFS and OS were 9.4 (7.2-11.5) and 19.7 (14.9-25.9) months. Overall response and disease control rates were 42.2% and 67.9%, respectively. Two patients died from study-treatment related toxicity (gastrointestinal hemorrhage, aspiration pneumonia; both during induction therapy). Most common G3/4 toxicities were neutropenia (25.7%) and fatigue (14.7%); hypertension was less common (5.5%). Conclusion Patients with advanced NS-NSCLC eligible for Bev-treatment may derive clinical benefit at acceptable toxicity from the addition of Bev to both Pem-Cis induction and Pem maintenance therapy; however, this is not an approved combination regimen. Identifier: NCT01004250
    Full-text · Article · Oct 2014 · Lung Cancer
  • Gunnar Hillerdal · Stephanie Mindus
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    ABSTRACT: Background: Lung volume reduction surgery can improve lung function and working capacity in severe heterogeneous emphysema. Endobronchial lung volume reduction (ELVR) performed by one-way valves inserted via a flexible bronchoscope can result in a moderate but significant improvement in lung function and exercise tolerance, eliminating the surgical risks. Objectives: Most studies of this method have excluded patients with α1-antitrypsin (AAT) deficiency, but small series of cases with positive short-term outcome have been reported. The sustainability of results has been questioned and we here present our experience in AAT-deficient patients treated with ELVR followed up for up to 4 years. Methods: From August 2008 to January 2012, 15 patients were treated with ELVR. Inclusion criteria were homozygotic AAT deficiency, age <80 years, residual volume of 140% or more, forced expiratory volume in 1 s (FEV1) 15-45% of predicted, severe heterogeneous emphysema, symptoms severely restricting daily life, informed consent and absence of other serious diseases. Results: One patient coughed up valves after 2 months, 1 developed pneumothorax and had valve displacement and subsequent removal, and 1 improved from an FEV1 of 0.62 to 0.84 liters, but after 4 months developed repeated and severe pneumonia and the valves had to be removed. Thus, 12 patients remained and were followed up for at least 1 year. In these patients, FEV1 increased (mean: 54%), the quality of life was much improved, and 2 patients could be taken off oxygen therapy. During the 4-year follow-up, patients demonstrated no significant deterioration in lung function. Conclusion: In carefully selected AAT deficiency patients with severe emphysema, ELVR can be safely performed with encouraging long-lasting results. © 2014 S. Karger AG, Basel.
    No preview · Article · Sep 2014 · Respiration
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    ABSTRACT: Home-based care in oncology is mainly reserved for patients at the end of life. Regulations regarding home delivery of cytotoxics differ across Europe, with a notable lack of practice guidelines in most countries. This has led to a lack of data addressing the feasibility of home-based administration of cytotoxic chemotherapy. In advanced non-squamous non-small cell lung cancer, pemetrexed is approved as maintenance therapy after first-line chemotherapy. In this setting, patients have the potential to be treated long-term with maintenance therapy, which, in the absence of unacceptable toxicity, is continued until disease progression. The favourable safety profile of pemetrexed and the ease of its administration by 10-minute intravenous infusion every 3 weeks make this drug a suitable candidate for administration in a home setting. Literature and regulations relevant to the home-based delivery of cytotoxic therapy were reviewed, and a phase II feasibility study of home administration of pemetrexed maintenance therapy was designed. At least 50 patients with advanced non-squamous non-small cell lung cancer, Eastern Cooperative Oncology Group performance status 0--1 and no progressive disease after four cycles of platinum-based first-line therapy are required to allow investigation of the feasibility of home-based administration of pemetrexed maintenance therapy (500 mg/m2 every 3 weeks until progressive disease or unacceptable toxicity). Feasibility is being assessed as adherence to the home-based administration process (primary endpoint), patient safety, impact on patients' quality of life, patient and physician satisfaction with home care, and healthcare resource use and costs. Enrolment of patients from the UK and Sweden, where home-based care is relatively well developed, commenced in December 2011. This feasibility study addresses an important aspect of maintenance therapy, that is, patient comfort during protracted home-based chemotherapy. The study design requires unusual methodology and specific logistics to address outcomes relevant to the home-delivery approach. This article presents a study design that offers a novel and reproducible model for home-based chemotherapy, and provides an up-to-date overview of the literature regarding this type of treatment.Trial NCT01473563.
    Full-text · Article · Oct 2013 · Health and Quality of Life Outcomes
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    ABSTRACT: Diagnosis of malignant mesothelioma is challenging. The first available diagnostic material is often an effusion and biochemical analysis of soluble markers may provide additional diagnostic information. This study aimed to establish a predictive model using biomarkers from pleural effusions, to allow early and accurate diagnosis. Effusions were collected prospectively from 190 consecutive patients at a regional referral centre. Hyaluronan, N-ERC/mesothelin, C-ERC/mesothelin, osteopontin, syndecan-1, syndecan-2, and thioredoxin were measured using ELISA and HPLC. A predictive model was generated and validated using a second prospective set of 375 effusions collected consecutively at a different referral centre. Biochemical markers significantly associated with mesothelioma were hyaluronan (odds ratio, 95% CI: 8.82, 4.82-20.39), N-ERC/mesothelin (4.81, 3.19-7.93), CERC/mesothelin (3.58, 2.43-5.59) and syndecan-1 (1.34, 1.03-1.77). A two-step model using hyaluronan and N-ERC/mesothelin, and combining a threshold decision rule with logistic regression, yielded good discrimination with an area under the ROC curve of 0.99 (95% CI: 0.97-1.00) in the model generation dataset and 0.83 (0.74-0.91) in the validation dataset, respectively. A two-step model using hyaluronan and N-ERC/mesothelin predicts mesothelioma with high specificity. This method can be performed on the first available effusion and could be a useful adjunct to the morphological diagnosis of mesothelioma.
    Full-text · Article · Aug 2013 · PLoS ONE
  • Gunnar Hillerdal · Karl Kölbeck · Hans Jacobsson

    No preview · Article · Aug 2013 · Lakartidningen
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    Gunnar Hillerdal

    Preview · Article · Aug 2013 · European Respiratory Journal
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    ABSTRACT: The current paradigm is that untreated lung cancer is invariably and rapidly fatal, therefore the medical community normally dismisses the idea that a patient could live with such a disease for years without any therapy.Yet, evidence from lung cancer screening research and from recent clinical series suggests that, although rarely recognized in routine practice, slow-growing lung cancers do exist and are more common than previously thought.Current evidence is reviewed and clinical cases are illustrated to show that slow-growing lung cancer is a real clinical entity, and the reasons why management protocols developed in the screening setting may also be useful in clinical practice are discussed. Features suggesting that a lung cancer may be slow-growing are described and appraised, areas of uncertainty are examined, modern management options for early-stage disease are appraised, and the influence that all this knowledge might have on our clinical decision-making is weighed. Further research directed at developing appropriate guidelines for these peculiar but increasingly common patients is warranted.
    Preview · Article · May 2013 · European Respiratory Journal
  • Tom Treasure · Gunnar Hillerdal · Martin Utley

    No preview · Article · Sep 2011 · Thorax
  • Gunnar Hillerdal · Christer Sederholm · Kerstin Andersson
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    ABSTRACT: Sequential administration of chemotherapeutic drugs might have advantages: additive toxicity is avoided and the individual drugs can be given in full dosages. The Swedish group earlier found the combination of gemcitabine and carboplatin to be effective and with acceptable toxicity. The group therefore decided to add docetaxel in a sequential way in a randomized phase II study. Patients were randomized to either gemcitabine or carboplatin for six cycles or the same regimen for three cycles followed by weekly single agent docetaxel. The primary objective was time to progression (TTP). One hundred and twenty-three patients with performance status WHO 0-2 and with earlier un-treated non-small cell lung cancer with measurable stage IIIB disease, not amenable to curative treatment, or stage IV disease without known metastatic spread to the CNS, were enrolled. Hematological toxicity was more common in the GC group but clinically significant bleeding or leucopenic fever occurred only in a minority of patients. No complete responses were noted. Partial response (PR) was observed in 19.3% and 20.8% in the GC and GCD group, respectively. Progression-free survival was 5.6 and 4.8 months and overall survival time 10.6 and 10.1 months in the GC and GCD groups, respectively. Thus, sequential treatment with docetaxel after treatment with gemcitabine and carboplatin did not improve time to progression, response rates, or overall survival.
    No preview · Article · Feb 2011 · Lung cancer (Amsterdam, Netherlands)
  • Gunnar Hillerdal

    No preview · Article · Sep 2010 · Lakartidningen
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    ABSTRACT: The village of Karain, Turkey, has the world's highest prevalence rate of malignant mesothelioma (MM). Environmental exposure to erionite is thought to cause the disease. However, it has also been suggested that the disease is mainly genetic. Residents in Karain village were traced from 1990 to 2006. Mineral samples were obtained from stones used in construction of their houses and any fibers present were identified. All women who had moved to the village as brides were traced and their cause of death determined. MM was the cause of death in 52 of 322 villagers, representing 50.5% of all deaths. Only 2 of 8 types of stones used in construction contained erionite, and these stones had been used almost exclusively in the mid-sections of the village, where MM was common. In houses not containing erionite, no cases of MM were observed. Sixty-four women came as brides to Karain from villages where erionite or asbestos is not found. Of the 16 women who have died, 11 (69%) died from MM. The extreme risk of MM in Karain is due to indoor exposure to erionite. The effect of genetic factors on mesothelioma development cannot be evaluated in this study, but is likely to be minor.
    No preview · Article · Apr 2010 · Archives of Environmental and Occupational Health
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    Y Izzetin Baris · Gunnar Hillerdal
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    ABSTRACT: At least four of the sultans who ruled during the 19th century suffered from tuberculosis (TB), and probably many of the women and children in the harem too. Life there was crowded with low standards of hygiene, resulting in high mortality, especially among children. Infectious diseases were the main killers and TB was one of the many factors behind the decline and fall of the empire.
    Preview · Article · Sep 2009 · Journal of Medical Biography
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    ABSTRACT: Material from 117 consecutive patients with lung cancer was investigated with respect to serological markers for chronic Chlamydia pneumoniae infection. Specific C. pneumoniae IgA antibodies were found significantly more often in patients with lung cancer than in control groups with coronary heart disease and in healthy controls, even after adjustment for smoking. The results suggest that chronic C. pnmmoniae infection is common in patients with lung cancer.
    No preview · Article · Aug 2009 · Apmis
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    ABSTRACT: Malignant pleural mesothelioma has a poor prognosis and there is limited effect of treatment. The Nordic Mesothelioma groups decided in the year 2000 to investigate a combination of liposomized doxorubicin, carboplatin, and gemcitabine for this disease in a phase II study. From January 2001, to December 2003, 173 evaluable patients with biopsy-verified malignant mesothelioma were included. Two patients were lost to follow-up, but all the others were followed for at least 4 years or until death. Toxicity was fairly low. There were 56 responses (32.4%), of which 2 were complete; the median time to progression was 8.6 months, and the median overall survival was 13 months. Some patients had their responses 4 to 6 months after last treatment. For 116 patients with epitheloid subtype, median survival was 17 months. A subgroup of these patients with good performance status, early stage, and age 70 years or less, showed a median survival of 22 months. The treatment yields good results with a high number of responses and long survival, and a low toxicity. The long survival of the epitheloid subgroup with good prognostic factors is as good as or even better than some studies on "radical" surgery or multimodal treatment, underlining the need of randomized studies to evaluate such treatment options.
    No preview · Article · Dec 2008 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
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    ABSTRACT: To evaluate weekly induction chemotherapy followed by weekly concomitant chemoradiotherapy in a multicentre phase II study of patients with unresectable stage III non-small cell lung cancer (NSCLC; stage wet IIIB excluded). Eligible patients received three weekly cycles of paclitaxel 100 mg/m2 and carboplatin AUC2 followed by six weekly cycles of paclitaxel 60 mg/m2 and carboplatin AUC2 in combination with thoracic radiotherapy (2 Gy per fraction and day to a total dose of 60 Gy). Sixty-four patients (40 males and 24 females) with a median age of 63 years (range, 43-79 years) entered the study. T and N stage were distributed as follows: T1 2 patients (3.2%), T2 10 patients (15.6%), T3 15 patients (23.4%), T4 37 patients (57.8%); N0 10 patients (15.6%), N1 1 patient (1.6%), N2 26 patients (40.6%), N3 26 patients (40.6%), and N missing 1 patient (1.6%). Seven patients (10.9%) suffered from grade 3/4 oesophagitis. Grade 1/2 oesophagitis occurred in 36 patients (56.3%) and pneumonitis grade 1/2 occurred in 10 patients (15.6%). Sixty-three patients were evaluated on an intent-to-treat basis. The overall response rate was 74.6%. The median time to progression was 247 days and median overall survival was 461 days. According to subgroup analyses, no statistically significant differences were noted according to gender, age (<65 vs. > or =65 years), performance status, histology, or study centre. Induction chemotherapy followed by concurrent chemoradiotherapy with weekly cycles of paclitaxel and carboplatin is feasible and generates moderate toxicity. Efficacy is comparable to other recently published regimens. However, prognosis remains, in general, poor for this group of patients and further work to develop better therapy is required.
    Full-text · Article · Sep 2008 · Anticancer research

Publication Stats

1k Citations
322.27 Total Impact Points


  • 1995-2015
    • Karolinska University Hospital
      • Department of Respiratory Medicine and Allergy
      Tukholma, Stockholm, Sweden
  • 2013
    • Istituto Clinico Humanitas IRCCS
      • Department of Thoracic Surgery
      Rozzano, Lombardy, Italy
  • 2005-2007
    • Karolinska Institutet
      • Respiratory Medicine Unit
      Solna, Stockholm, Sweden
  • 1994-2002
    • Uppsala University Hospital
      • Department of Infectious Diseases
      Uppsala, Uppsala, Sweden
  • 1992
    • Akademiska Sjukhuset
      Uppsala, Uppsala, Sweden
  • 1981-1991
    • Uppsala University
      Uppsala, Uppsala, Sweden
  • 1990
    • National Veterinary Institute, Sweden
      Uppsala, Uppsala, Sweden