ALK immunohistochemistry positive, FISH negative NSCLC is infrequent, but associated with impaired survival following treatment with crizotinib.

OBJECTIVE: Metastasized non-small cell lung cancer (NSCLC) with an anaplastic lymphoma kinase (ALK) rearrangement is usually sensitive to a range of ALK-tyrosine kinase inhibitors. ALK-positive NSCLC have been identified in pivotal phase III trials with fluorescence in situ hybridization (ALK FISH+). These tumors are also expressing the fusion product (ALK immunohistochemistry (IHC)+). However, discrepant cases occur, including ALK IHC + FISH-. The aim of this study was to collect ALK IHC + cases and compare within this group response to crizotinib treatment of ALK FISH + cases with ALK FISH- cases. MATERIALS AND METHODS: In this European prospective multicenter research study patients with Stage IV ALK IHC + NSCLC treated with crizotinib were enrolled. Tumor slides were validated centrally for ALK IHC and ALK FISH. RESULTS: Registration of 3523 ALK IHC tests revealed a prevalence of 2.7% (n = 94) ALK IHC + cases. Local ALK FISH analysis resulted in 48 concordant (ALK IHC+/FISH+) and 16 discordant (ALK IHC+/FISH-) cases. Central validation revealed 37 concordant and 7 discordant cases, 5 of which had follow-up. Validation was hampered by limited amount of tissue in biopsy samples. The PFS at 1 year for ALK concordant and discordant was 58% and 20%, respectively (HR = 2.4; 95% CI: 0.78-7.3; p = 0.11). Overall survival was significantly better for concordant cases than discordant cases after central validation (HR=4.5; 95% CI= 1.2-15.9; p=0.010. CONCLUSION: ALK IHC + FISH- NSCLC is infrequent and associated with a worse outcome on personalized treatment. A suitable predictive testing strategy may be to screen first with IHC and then confirm with FISH instead of considering ALK IHC equivalent to ALK FISH according to the current guidelines.

Mindfulness-based stress reduction added to care as usual for lung cancer patients and/or their partners: A multicentre randomized controlled trial.

OBJECTIVE: Lung cancer patients report among the highest distress rates of all cancer patients. Partners report similar distress rates. The present study examined the effectiveness of additional mindfulness-based stress reduction (care as usual [CAU] + MBSR) versus solely CAU to reduce psychological distress in lung cancer patients and/or their partners. METHODS: We performed a multicentre, parallel-group, randomized controlled trial. Mindfulness-based stress reduction is an 8-week group-based intervention, including mindfulness practice and teachings on stress. Care as usual included anticancer treatment, medical consultations, and supportive care. The primary outcome was psychological distress. Secondary outcomes included quality of life, caregiver burden, relationship satisfaction, mindfulness skills, self-compassion, rumination, and posttraumatic stress symptoms. Outcomes were assessed at baseline, post-intervention, and 3-month follow-up. Linear mixed modeling was conducted on an intention-to-treat sample. Moderation (gender, disease stage, baseline distress, participation with/without partner) and mediation analyses were performed. RESULTS: A total of 31 patients and 21 partners were randomized to CAU + MBSR and 32 patients and 23 partners to CAU. After CAU + MBSR patients reported significantly less psychological distress (p = .008, d = .69) than after CAU. Baseline distress moderated outcome: those with more distress benefitted most from MBSR. Additionally, after CAU + MBSR patients showed more improvements in quality of life, mindfulness skills, self-compassion, and rumination than after CAU. In partners, no differences were found between groups. CONCLUSION: Our findings suggest that psychological distress in lung cancer patients can be effectively treated with MBSR. No effect was found in partners, possibly because they were more focused on patients' well-being rather than their own.

Can free DNA be detected in sputum of lung cancer patients?

SUMMARY: Free DNA is present in the serum of cancer patients in a higher concentration than that in non-cancer patients. Free DNA in sputum may originate from malignant or inflammatory diseases. The aim of the study was to examine the presence of free DNA in sputum and the relationship to lung cancer. The contribution of inflammatory cells was established as well. The amount of free and cellular DNA in sputum was determined using real-time beta-globin PCR in 28 lung cancer patients and 68 controls. Free DNA was present in sputum samples of the cancer patients and controls. We found no differences in DNA concentration in sputum of patients with and without lung cancer. For all patients combined the amount of free DNA was related to the amount of inflammation. Further, we found increased hypermethylation of RASSF1A in lung cancer patients compared to controls to show that tumour related DNA is present in sputum. In conclusion, free DNA can be detected in sputum of lung cancer patients. The amount of free DNA is related to the amount of inflammation, but not to the presence of lung cancer.

[Respiratory side-effects of drugs]. / Adembenemende bijwerkingen van medicamenten.

Three patients, men aged 65 and 49 and a woman of 38 years, presented with drug-induced interstitial pneumonitis due to nilutamide, bleomycin and nitrofurantoin usage respectively. The signs and symptoms of drug-induced interstitial pneumonitis occur from within several hours up to months or years after the start of treatment, and sometimes even after the cessation of treatment, and consist of a dry cough, dyspnoea, fever and crackles upon auscultation. The results of further investigations are atypical and consist of abnormalities on the X-ray or CT of the thorax and lymphocytosis in the bronchoalveolar lavage fluid. The mechanisms of damage usually include direct pulmonary toxicity and indirect inflammatory or immunological processes. In most patients, the pulmonary abnormalities disappear after cessation of the drug treatment. Sometimes the disease progresses to pulmonary fibrosis and respiratory failure despite treatment with corticosteroids.

[Unusual form of ileus, except in elderly patients?]. / Een ongebruikelijke vorm van dunnedarmileus, tenzij bij oudere patiënten?

Two women aged 88 and 92, recently admitted to hospital, were diagnosed with gallstone ileus. Over a longer period of time they had suffered intermittently from abdominal pain related to a migrating and impacting stone. This disease is mostly diagnosed correctly during exploratory laparotomy for persistent intestinal obstruction. CT scanning, however, is a new and helpful way to early diagnosis. Both women had successful surgery. Gallstone ileus is a disease of the elderly; its early diagnosis is important. CT can be very helpful in this respect.