Charlotte Kristiansen

Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme: A randomized phase II study

Abstract Background. Surgery followed by radiotherapy and concomitant and adjuvant temozolomide is standard therapy in newly diagnosed glioblastoma multiforme (GBM). Bevacizumab combined with irinotecan produces impressive response rates in recurrent GBM. In a randomized phase II study, we investigated the efficacy of neoadjuvant bevacizumab combined with irinotecan (Bev-Iri) versus bevacizumab combined with temozolomide (Bev-Tem) before, during and after radiotherapy in newly diagnosed GBM. Material and methods. After surgery, patients were randomized to Bev-Iri or Bev-Tem for eight weeks, followed by standard radiotherapy (60 Gy/30 fractions) and concomitant Bev-Iri or Bev-Tem followed by adjuvant Bev-Iri or Bev-Tem for another eight weeks. Bev-Iri: Bevacizumab and irinotecan were given every 14 days before, during and after radiotherapy. Bev-Tem: Bevacizumab was given as in Bev-Iri and temozolomide was given for five days every four weeks before and after radiotherapy and once daily during radiotherapy. The primary endpoint was response after neoadjuvant chemotherapy and a pre-specified response rate of 30% or more was considered of interest for future studies. Secondary endpoints were progression-free survival (PFS) and toxicity. Results. The response rate was 32% (95% CI 17–51%) for Bev-Tem (n = 32) and 23% (95% CI 9–44%) for Bev-Iri (n = 31) (p = 0.56). Median PFS was 7.7 and 7.3 months for Bev-Tem and Bev-Iri, respectively. Hematological toxicity was more frequent with Bev-Tem including one death from febrile neutropenia whereas non-hematological toxicity was manageable. Conclusions. Only the Bev-Tem arm met the pre-specified level of activity of interest. Our results did not indicate any benefit from Bev-Iri in first-line therapy as opposed to Bev-Tem in terms of response and PFS.

Trends in lung cancer in elderly in Denmark, 1980–2012

Abstract Background Lung cancer is an increasing problem in the older patient population due to the improvement in life expectation of the Western population. In this study we examine trends in lung cancer incidence and mortality in Denmark from 1980 to 2012 with special focus on the elderly. Material and methods Lung cancer was defined as ICD-10 codes C33-34. Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence, and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. Results In 2012, about 50% of lung cancers were diagnosed among persons aged 70 years or more. For men and women older than 75 years the incidence rates have been increasing and for those aged 80–84 years, the rates have doubled since 1980. Due to the poor survival, similar trends were seen in mortality rates. Over the period, the one-year relative survival rates almost doubled in patients aged 70 years or more, but still only 25% of the patients aged 80–89 years survived their lung cancer for one year. Conclusion The incidence of lung cancer is closely linked to the pattern of tobacco smoking with the differences between gender and age groups reflecting smoking behavior in birth cohorts. Elderly patients with lung cancer are a heterogeneous group in whom treatment should be offered according to comorbidity and a geriatric assessment.

Treatment and treatment considerations in a patient with advanced breast cancer and acute intermittent porphyria.

The porphyrias represent a collection of seven disorders due to genetic defects, each resulting from a partial deficiency of a specific enzyme in the haem biosynthesis pathway [1], this leads to overproduction syndromes with the formation of toxic haem precursors. Haem is synthesised in every human cell and about 85% are made in erythroid cells, where the majority are used for haemoglobin formation. Most of the remainder is produced in the liver, where 80% is used for the creation of different cytochromes. The porphyrias can be divided into two subgroups / hepatic or erythropoietic / according to the organ in which accumulation of porphyrins and their precursors mainly appears. The three most important entities are an acute porphyric attack and acute and chronic skin symptoms. The prevalence of porphyrias varies from 0.5 to 10 per 100 000 in different populations. The hepatic porphyrias (acute intermittent porphyria, variegate porphyria and hereditary coproporphyria) can induce acute attacks, where porphyrin precursors are excreted massively from the liver because of induction of haem biosynthesis [2]. An acute attack begins with minor behavioural changes such as anxiety, restlessness, and insomnia and proceeds rapidly to symptoms of autonomic and sensomotoric neuropathy. Abdominal pain / usually followed by vomiting and constipation / is common and severe, mimicking acute abdominal crisis. Pain in the back or in the extremities is frequently present. Hypertension and tachycardia are associated with the activity of the disease. About 75% of acute attacks have identifiable precipitants, e.g. porphyrinogenic drugs, infections, malignancies, alcohol, tobacco, illicit drug use, fasting, pre-menstrual stress. One of the possible mechanisms by which drugs can precipitate acute attacks is by induction of the cytochrome P450mediated oxidation leading to depletion of liver haem concentrations and thus induction of the haem biosynthesis pathway [2]. Measurements of urinary porphobilinogen must be undertaken during an acute attack, porphobilinogen and 5-aminolaevulinic acid. They are porphyrin precursors and will always be increased under an acute attack. To confirm the diagnosis of an acute attack, porphobilinogen has to be measured by a quantitative test and it is usually markedly increased and to a lesser extent 5-aminolaevulinic acid [1]. The majority of patients with acute intermittent porphyria will have a slightly increased urinary porphobilinogen during the symptomless phase. Treatment is administration of haem, which is infused daily for three to four consecutive days. There are limited information on cytotoxic chemotherapy and the porphyrias [3 /5]. We here describe and discuss an attempt to avoid potentially porphyrinogenic drugs but at the same time give an optimal antineoplastic and palliative treatment to a patient with dissiminated breast cancer. At age 42 years, a woman with acute intermittent porphyria since the age of 31 was diagnosed with cancer of her right breast. She was treated with metoprolol because of hypertension associated with porphyria, but was apart from the disease mentioned

Impact of comprehensive geriatric assessment on quality of life, overall survival, and unplanned admission in patients with non-small cell lung cancer treated with stereotactic body radiotherapy

OBJECTIVES Overall survival ﴾OS﴿ for patients with localized non-small cell lung cancer ﴾NSCLC﴿ treated with stereotactic body radiotherapy ﴾SBRT﴿ is poorer than for patients undergoing surgery. Patients who undergo SBRT are often ineligible for surgery due to significant comorbidities that can impact their mortality. A comprehensive geriatric assessment (CGA) that identifies and treats aging related comorbidities could improve OS and quality of life (QoL). This randomized study investigated if a CGA added to SBRT impacts QoL, survival, and unplanned admissions. MATERIALS AND METHODS From January 2015 to June 2016, 51 patients diagnosed with T1-2N0M0 NSCLC treated with SBRT were enrolled. The patients were randomized 1:1 to receive SBRT +/- CGA. EuroQoL Group 5D (EQ-5D) health index and visual analogue scale (VAS) scores were assessed at start of SBRT, at five weeks, and every third month for a year after SBRT. RESULTS There were 26 and 25 patients randomized to receive ± CGA, respectively. The repeated measures one-way analysis of variance (ANOVA) test of the EQ-5D health index and VAS scores did not show statistically significant differences between groups. For the EQ-5D VAS scores at twelve months follow-up there was a small difference between the groups although not statistically significant. Even though more patients deceased in the no-CGA group, no statistically significant difference in survival rates and unplanned admission rate was observed between groups. CONCLUSION In patients with localized NSCLC treated with SBRT, a CGA did not impact the overall QoL, the prevalence/length of unplanned admissions, or survival. There was an indication of small differences in QoL and survival in the data, but such differences can only be validated in larger studies.

Recall radiation myelitis after stereotactic radiation and dabrafenib in metastatic melanoma

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Epidermal growth factor receptor mutations in synchronous recurrent lung cancer in an 82-year-old woman. A case story

Five years later, in November 2010, a fluorodeoxyglucose positron emission tomography scan (PET-CT) showed recurrent lung cancer at both resected sites with two nodules on the right side and one nodule on the left side. A biopsy from the right tumour was diagnosed with adenocarcinoma. The tissue specimen was tested for EGFR mutation by polymerase chain reaction and a mutation was identified in exon 21 (p.L858R). The patient was not fit for repeated bilateral lung resection and was referred to the Department of Oncology. TKI treatment with erlotinib was initiated in a dose of 150 mg daily, but subsequent reduced to 50 mg due to side effects. A CT-scan performed two months later showed regression of the two tumours in the right lung and stable disease for the left tumour. The tumour specimens from 2005 were submitted to EGFR mutation analysis. An identical mutation was found in the right-sided cancer while no EGFR mutation was detected in the left lung. No biopsy from the left lung at recurrence in 2010 was obtained. PET-CT scan performed five months later showed almost complete regression of the right side tumours and no change in the FDG-positive tumour on the left side (Figure 1). The stage was now reclassified as synchronous local relapses of two different cancers and radical radiation therapy (RT) of the tumour at the left site was applied with a dose of 66 Gy in 33 fractions concurrently with continued erlotinib treatment of the right-sided tumours. At follow-up five months after start of RT, a CT-scan showed continued response of the EGFR-mutated tumour on the right side and complete response of the radiated tumour on the left side. We here report a case in which EGFR mutation analysis provided important information regarding treatment which was changed from palliative to curative intended treatment by changing the stage from disseminated disease of one cancer to two primary Epidermal growth factor receptor mutations in synchronous recurrent lung cancer in an 82-year-old woman. A case story