Immunotherapy is the most promising method in the treatment of lung cancer, especially in connection with the rapidly growing development of monoclonal antibodies aimed at inhibiting immune checkpoints: anti-CTLA-4, anti-PD-1, anti-PD-L1. Classic immuno-mediated adverse events that occur with this method of treatment can affect several organs, including the lungs. Pneumonitis is a potentially life-threatening complication and often requires rapid treatment with high doses of corticosteroids and antibacterial drugs. We present the case of a 67-year-old patient with primary multiple malignant tumors of the larynx and left lung after combined treatment and incomplete treatment with Nivolumab, complicated by immuno-mediated pneumonitis. This report highlights the importance of treating patients with contraindications to chemotherapy when specific antitumor treatment is required, as well as timely detection of a rare but dangerous adverse event: immuno-mediated pneumonitis that occurs during treatment with immune checkpoint inhibitors. Thus, knowing the frequency of adverse events when using PD-1 and PD-L1 inhibitors, as well as the possible presence of comorbidities in patients, will make it easier for doctors to make informed decisions in the treatment of patients, and understanding the interaction of the tumor and the immune system will help determine the best predictors of response and further improve the results of treatment of patients with NSCLC.
The abscopal effect was described more than 50 years ago and is a phenomenon in which radiation therapy promotes the regression of metastatic foci remote from the site of radiation. For decades, this effect has been described as a rare, unexplained phenomenon in patients receiving radiation therapy. Today, the abscopal effect is still an exceptional phenomenon: the mechanism underlying it is still not fully understood. It is believed that the abscopal effect is most likely associated with systemic immune responses that occur under the influence of radiation therapy.We present the case of a 63-year-old patient with advanced peripheral cancer of the upper lobe of the left lung, disease progression in the form of metastatic brain lesions and regression of tumor foci in the lungs after radiation therapy to the brain, while the patient did not receive additional treatment in the form of immunotherapy.The article examines the history of the abscopal effect, an attempt is made to understand the mechanisms of its occurrence, which can help to further improve the results of treatment of patients with NSCLC using radiation therapy and modern approaches to complex cancer treatment.
Introduction. The addition of durvalumab after chemoradiation therapy in unresectable stage III non-small-cell lung cancer (NSLC) is a new standard of care.Aim. Study the features and outcomes of durvalumab maintenance treatment after chemoradiotherapy in patients with unresectable stage III NSCLC in the real-world clinical practice in Russia.Materials and methods. 50 patients with unresectable III stage NSCLC after concurrent or sequential chemoradiotherapy (CRT) were enrolled in this observational retrospective study. Median follow up time at primary analysis was 12.4 months.Results. A mean age of the patients in the study was 61.2 years (58.4-64.1; 95% CI). Most of the patients had received sequential CRT (76%, n = 38). Median time of durvalumab start from the end of CRT varied from 22 to 50 days (overall - 35 days). Estimated median PFS and OS were 10.86 months (7.78-14.01, 95% CI) and 26 months (20.19-31.81, 95% CI), respectively. There was a trend toward increased PFS in patients with smoking history: 12 months (9.79-14.2; 95% CI) versus 4,9 months (0.0-12.47; 95% CI), p = 0.2. Half of the patients without smoking history (5/10) had targetable mutations (EGFR ex 19, ALK, ROS1, cMET). Most common reported adverse events of special interest were pneumonitis grade 1-2 (36%, n = 18), leading permanent treatment discontinuation to in 6% of patients (n = 3). There were no reported cases of grade 3-4 adverse events.Conclusions. Real-world characteristic of patients in our study were different from PACIFIC trial. Sequential CRT is the most frequent treatment option in locally advanced unresectable NSCLC in Russia. Estimated PFS was shorter than in PACIFIC, but there were less cases of pneumonitis.
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer type and arises from keratinocytes. Most cSCC progress from a UV-induced precancerous lesion termed actinic keratosis (AK). Despite various efforts to characterize these lesions molecularly, the etiology of AK and its progression to cSCC remain only partially understood. Here we have used Infinium MethylationEPIC BeadChips to interrogate the DNA methylation status of about 850.000 CpGs in epidermis samples from healthy skin, AK and cSCC. Importantly, we found that the premalignant AK samples displayed classical features of cancer methylomes and were highly similar to cSCC methylomes. Further analysis identified typical features of stem cell methylomes, such as a reduced DNA methylation age, non-CpG methylation and stem cell-related keratin and enhancer methylation patterns. Interestingly, this signature was detected only in one half of the AK and cSCC samples, while the other half showed keratin and enhancer methylation patterns that were more closely related to the control epidermis. These findings suggest the existence of two distinct subclasses of AK and cSCC that originate from distinct keratinocyte differentiation stages. Citation Format: Manuel Rodríguez Paredes, Felix Bormann, Günter Raddatz, Julian Gutekunst, Carlota Lucena-Porcel, Florian Köhler, Elisabeth Wurzer, Katrin Schmidt, Joachim Röwert-Huber, Evgeniya Denisova, Lars Feuerbach, Esther Herpel, Ingo Nindl, Thomas G. Hofmann, Marc Winnefeld, Frank Lyko. Methylation profiling identifies two subclasses of cutaneous squamous cell carcinoma related to distinct cell types of origin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5333.
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