Karin Holmskov Hansen

Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase–Positive Non–Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial

Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC. Patients and Methods Patients were stratified by brain metastases and best response to crizotinib. They were randomly assigned (1:1) to oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (180 mg once daily [with lead-in]; arm B). Investigator-assessed confirmed objective response rate (ORR) was the primary end point. Results Of 222 patients enrolled (arm A: n = 112, 109 treated; arm B: n = 110, 110 treated), 154 (69%) had baseline brain metastases and 164 of 222 (74%) had received prior chemotherapy. With 8.0-month median follow-up, investigator-assessed confirmed ORR was 45% (97.5% CI, 34% to 56%) in arm A and 54% (97.5% CI, 43% to 65%) in arm B. Investigator-assessed median progression-free survival was 9.2 months (95% CI, 7.4 to 15.6) and 12.9 months (95% CI, 11.1 to not reached) in arms A and B, respectively. Independent review committee-assessed intracranial ORR in patients with measurable brain metastases at baseline was 42% (11 of 26 patients) in arm A and 67% (12 of 18 patients) in arm B. Common treatment-emergent adverse events were nausea (arm A/B, 33%/40%), diarrhea (arm A/B, 19%/38%), headache (arm A/B, 28%/27%), and cough (arm A/B, 18%/34%), and were mainly grades 1 to 2. A subset of pulmonary adverse events with early onset (median onset: day 2) occurred in 14 of 219 treated patients (all grades, 6%; grade ≥ 3, 3%); none occurred after escalation to 180 mg in arm B. Seven of 14 patients were successfully retreated with brigatinib. Conclusion Brigatinib yielded substantial whole-body and intracranial responses as well as robust progression-free survival; 180 mg (with lead-in) showed consistently better efficacy than 90 mg, with acceptable safety.

The occurrence of hyponatremia in SCLC and the influence on prognosis: A retrospective study of 453 patients treated in a single institution in a 10-year period

Hyponatremia is often seen in SCLC, and is thought to be caused by the paraneoplastic syndrome SIADH. Variable results of the prognostic significance of low P-sodium (P-Na) have been reported. This study was performed to investigate the prognostic value of hyponatremia in SCLC. Data was obtained from files from 453 patients diagnosed with SCLC and treated at Odense University Hospital from 1995 to 2005 in which data on P-sodium was available. The standard chemotherapy was six cycles of carboplatin-etoposide. P-Na was <125 mEq/L in 47 patients (11%) and 126-135 mEq/L in 151 (33%), and 255 patients (56%) showed normal values. The median survival was 11.2 months in patients with normal P-Na, and 7.1 months in patients with subnormal values (p=0.0001). In a Cox multivariate analysis of the 402 patients treated with carboplatin-etoposide, hyponatremia was associated with poorer prognosis. Other independent prognostic factors included LDH, gender, age, performance status, stage, and low value of albumin. Treatment prior to year 2000 was of border line significance, while in-significant factors included hemoglobin level, WBC and alkaline phosphatase. In 61 patients with P-Na <130 mEq/L receiving two or more cycles of chemotherapy, only 15 of the 61 patients (25%) normalized the value of P-Na to 136 mEq/L or above at the time of the second cycle of chemotherapy. The patients who did not fully regain normal values of P-Na, had poorer survival compared with the patients who did in a univariate analysis (p=0.027), and in a Cox multivariate analysis. In conclusion, hyponatremia was a significant prognostic factor associated with poor prognosis and so was failure to normalize P-Na within the first two cycles of chemotherapy.

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.

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

Spinal cord lesions in decompression sickness

The frequency of diving accidents is increasinglone of rihich is the decompression sickness (DCS).It is caused. by N2-bubbles formed in the tissues during ascent-Dependent on the localisation of the N2-bubble the less harmful1 DCS I (skinand limb-bends) is distinguished from the more serious DCS I1 with CNS involvement(l).At least one third of all DCS cases show neurological deficits and remarkably about 80% of these are spinal lesions(2).We present 8 cases of spinal DCS.