Immune checkpoint inhibitors (ICIs) are a newly developed component of cancer care that expands the treatment possibilities for patients. Their use has been associated with several immune-related adverse events, including ICI-induced sarcoidosis-like reactions. This article reviews the data concerning ICI-induced sarcoidosis-like reactions currently available in the medical literature. These reactions have been reported in three classes of ICIs: anti-cytotoxic T-lymphocyte associated protein 4 antibodies, programmed death 1 inhibitors and programmed death ligand 1 inhibitors. These reactions are indistinguishable from sarcoidosis with a similar histology, pattern of organ involvement, and pattern of clinical manifestations. The most common locations to observe granulomatous inflammation from these reactions is in intrathoracic locations (the lung and/or mediastinal lymph nodes) and the skin. The median time between initiation of an ICI and the development of a sarcoidosis-like reaction averaged 14 weeks. Clinicians have opted to use corticosteroids and/or discontinue the ICI, or take no action when these reactions have developed. Regardless of whether the clinician performed an intervention or not, these reactions have uniformly improved or resolved after ICI-treatment, which provides additional temporal evidence supporting the presence of a sarcoidosis-like reaction as opposed to sarcoidosis. There is even evidence that the development of an ICI-induced sarcoidosis-like reaction suggests that the ICI is effective as an anti-tumor agent and should be continued. As is the case for sarcoidosis, sarcoidosis-like reactions do not mandate antisarcoidosis therapy, especially if the condition is asymptomatic. When treatment of sarcoidosis-like reaction is required, it may be prudent to continue ICI therapy and add antisarcoidosis therapy because standard antisarcoidosis regimens seem to be effective. Further research into the mechanisms involved in the development of ICI-induced sarcoidosis-like reactions may give insights into the immunopathogenesis of sarcoidosis.

BACKGROUND: Despite the established causal relationship between tobacco smoking and cancer, many cancer patients continue to smoke after diagnosis. This partly reflects ignorance of the beneficial effects of smoking cessation, even after diagnosis. The aim of this study was to demonstrate the effects of continuing or quitting smoking in patients with diagnosed cancer. METHODS: The study was based on a review of medical databases (PubMed Central, MEDLINE, Cochrane Library) in the last 30 y. All articles included in the present analysis were in English. RESULTS: In subjects with early-stage lung cancer, continued smoking after diagnosis is associated with an increased risk of all-cause mortality and decreased survival. Research has demonstrated significant differences in actuarial overall survival favoring the non-smoking group among subjects with lung cancer. In subjects with oral cancer, smoking cessation or reduction leads to a significant reduction in mortality. There is also evidence that tobacco smoking aggravates and prolongs radiotherapyinduced complications. Of particular importance is evidence that continued smoking is associated with adverse effects during anti-cancer treatment. Smoking promotes tumor progression and increases resistance to chemotherapy due to nicotine-induced resistance to apoptosis by modulating mitochondrial signaling. Continued smoking is also related to inferior outcomes of treatment with novel targeted therapies such as erlotinib. Smoking in subjects with gastric and lung cancer is also associated with an increased risk of developing second primary tumors. Quitting smoking after lung cancer diagnosis is associated with a better performance status, whereas persistent smokers have worse overall quality of life. Subjects who continue to smoke despite being diagnosed with cancer report more severe pain than subjects who have never smoked and greater pain-related functional impairment. CONCLUSIONS: Continued smoking after cancer diagnosis is related to reduced treatment efficacy and reduced survival, increased risk for second primary malignancies, and deterioration of quality of life.

The aim of this study was to investigate several bone markers in Non-Small Cell Lung (NSCLC) and Small Cell Lung (SCLC) patients experiencing or not secondary bony disease. Fasting serum levels of bone formation, bone resorption, and osteoclastogenesis markers were determined in 22 NSCLC patients with bone metastases, 18 without bone metastasis, and 28 SCLC patients. A total of 29 healthy volunteers were also included in the study. Decreased osteocalcin (OC) serum levels and increased osteopontin and ligand of the receptor of nuclear factor kB (RANKL) serum levels were detected in NCSLC patients with bone metastases while increased C-terminal cross-linking telopeptide of type I collagen and increased RANKL/OPG (osteoprotegerin) ratio were detected in SCLC patients. Increased serum levels of OPG were observed in all lung cancer patients. OPG may be actively involved in the development of lung cancer metastasis. Furthermore, OC, OPN, and RANKL in NSCLC and CTX and RANKL in SCLC patients may also have a broader role in the pathogenesis and spread of lung cancer. They also provide useful information in identifying the group of patients that may benefit from a more rigorous treatment.

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Background: Docetaxel (DT) is an extensively used taxane, frequently associated with hypersensitivity reactions. The aim of this study was to record the epidemiological and clinical features of hypersensitivity to DT in non-small cell lung cancer patients in order to obtain useful information concerning the management of these patients. We also developed a desensitization protocol and evaluated its clinical application. Methods: We retrospectively reviewed records of 620 non-small cell lung cancer patients treated with DT-containing regimens in the adjuvant, first-, second- or next-line setting. Data from 102 patients who had exhibited hypersensitivity reactions were analyzed according to the Common Toxicity Criteria for Adverse Events version 3.0. Five patients were chosen for the desensitization protocol. We applied the standard protocol for parenteral desensitization to β-lactam antibiotics, and DT treatment was carried out with a series of 10-fold dilutions in sufficient volume to administer the total dose. Results: One hundred and two patients (16.5%) were recorded as having hypersensitivity to DT. Reactions were observed after approximately 2.5 ± 1.0 cycles. Only 14 patients (14/620, 2%) developed grade 3–4 hypersensitivity. Reactions were more likely in patients during second- or third-line chemotherapy, but no other correlation (age, gender, atopic status) was observed. Five patients completed a parenteral desensitization protocol and continued their treatment uneventfully. Conclusions: Hypersensitivity reactions to DT respond quickly to discontinuation along with appropriate supportive care. Premedication and increased infusion time may allow readministration. The desensitization protocol that we developed provides a reliable alternative to permanent discontinuation of DT.