Pegfilgrastim-Induced Aortitis in a Patient with Small-Cell Lung Cancer Who Received Immunotherapy Combined with Chemotherapy

Introduction: Granulocyte colony-stimulating factor (G-CSF), including pegfilgrastim, increases the peripheral blood leukocyte count and is widely used in clinical practice in combination with cytotoxic chemotherapy. The most frequent side effects of G-CSF are pain and fever; aortitis, in contrast, is a rare and serious side effect. Case Presentation: A 73-year-old man with small-cell lung cancer was treated with a full dose of a combination of carboplatin/etoposide/durvalumab and pegfilgrastim. The patient developed fever and right ear pain 12 days after pegfilgrastim administration and was diagnosed with aortitis by contrast-enhanced computed tomography 5 days later. Because the patient had already been administered the immune checkpoint inhibitor and had a history of hepatitis B, the patient was followed up without corticosteroid administration, and the patient’s symptoms resolved spontaneously. Conclusion: In situations where immunosuppression should be avoided, we believe that follow-up without corticosteroids for G-CSF-induced aortitis is a promising option

Impact on prognosis of rebiopsy in advanced non-small cell lung cancer patients after epidermal growth factor receptor-tyrosine kinase inhibitor treatment: a systematic review

Abstract Background Osimertinib, the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has become the standard treatment in cases where rebiopsy reveals T790M mutation after the first-line EGFR-TKI treatment. However, the prognosis of patients after rebiopsy, the most important outcome for cancer patients, has not been described sufficiently. This systematic review aimed to clarify whether rebiopsy contributes to improved prognosis in the first- or second-generation EGFR-TKI refractory patients. Methods Using free word and control terms related to “non-small cell lung cancer” and “rebiopsy,” we searched studies from Medical Literature Analysis and Retrieval System Online via PubMed, Embase, Cochrane Central Register of Controlled Trials, and World Health Organization International Clinical Trials Registry Platform. We included cohort studies and case reports written in English and judged whether each study answers our research questions. Results Of the 144 studies included, only one reported the prognosis of patients with/without rebiopsy showing that in EGFR-TKI refractory non-small cell lung cancer patients, the post-progression survival (PPS) was significantly longer in patients who received rebiopsy and treatment based on a resistant mechanism (median PPS 24.2 months) than those who received rebiopsy and salvage regimen (median PPS 15.2 months, p = 0.002) and who did not receive rebiopsy (median PPS 9.7 months, p < 0.001). Most of the other studies reported the detection rate of T790M mutation or rebiopsy procedure. Conclusions Only a few previous studies have investigated the effectiveness of rebiopsy. Hence, further study is needed to determine the prognosis or adverse events of rebiopsy

Small cell lung cancer transformation during immunotherapy with nivolumab: A case report

We report a rare case of transformation of non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC), without epidermal growth factor receptor (EGFR) gene mutation, during immunotherapy treatment with nivolumab. A 75-year-old man was referred to our hospital following the observation of a 64 mm mass in a chest computed tomography (CT) scan. A transbronchial biopsy of the mass identified the pathological presence of poorly differentiated NSCLC, with no histological signs of SCLC. No mutations were identified in the EGFR gene. A clinical diagnosis of NSCLC (cT3N3M1a, stage IV) was made following a positron emission tomography (PET)–CT scan and enhanced brain magnetic resonance imaging. Docetaxel and bevacizumab were selected as the first-line chemotherapy regimen; however, after two cycles, the patient developed a gastrointestinal perforation, and discontinuation of cytotoxic chemotherapy was recommended. Owing to gradual disease progression, immunotherapy with nivolumab was selected as the second-line regimen. During the immunotherapy, the tumor continued to progress and some subcutaneous tumors emerged. Biopsy of a subcutaneous tumor revealed SCLC, with positive immunostaining for cluster of differentiation 56, synaptophysin, and thyroid transcription factor-1. Serum tumor markers of SCLC were also elevated. Based on these results, we concluded that in this case NSCLC had transformed to SCLC during immunotherapy with nivolumab

Organizing pneumonia secondary to pulmonary cryptococcosis in immunocompromised patient

Pulmonary cryptococcal infections are fungal infections that often occur in immunocompromised patients and present with a variety of radiographic patterns ranging from nodular to infiltrative shadows. In the present case, we experienced a rare case of organizing pneumonia due to cryptococcal infection in a 71-year-old woman with rheumatoid arthritis. Transbronchial lung biopsy showing fibrotic changes in the alveolar walls, small granulation lesions and cryptococcal organisms with positive Grocott staining. Serum cryptococcal antigen was also found to be positive. Based on these findings, we confirmed the diagnosis of secondary organizing pneumonia due to cryptococcal infection. Treatment with corticosteroids and antifungal drugs led to improvement of the cough and reduction of organizing pneumonia. In immunocompetent patients with organizing pneumonia, it is essential to perform bronchoscopic lung biopsies and serum antigen tests to search for the cause, whenever possible, as it may be due to an infection caused by Cryptococcus, as in the present case

Safety of flexible bronchoscopy and clinical course for elderly patients with suspected primary lung cancer

Abstract Background There have been several reports demonstrating the safety of flexible bronchoscopy (FB) in the elderly, but none have focused specifically on lung cancer, which is a frequent biopsy procedure. Methods In this study, we retrospectively evaluated the safety of FB and subsequent treatment in elderly patients with suspected primary lung cancer. Elderly patients were defined as 75 years of age or older. Results A total of 141 patients, 77 in the elderly group and 64 in the nonelderly group, were reviewed. The median age of the elderly group was 80 years. Transbronchial lung biopsy was performed in more than 80% of all patients. Primary lung cancer was diagnosed in 42 (54.4%) of the elderly group and 35 (54.7%) of the nonelderly group (p = 0.38). Approximately 70% of the elderly patients with a confirmed diagnosis were treated, while more than half of the undiagnosed elderly patients had best supportive care. Complications such as bleeding, pneumothorax, fever, and pneumonia were similar in the elderly and nonelderly groups. Conclusions This study suggests that flexible bronchoscopy can be performed as safely in the elderly as in the nonelderly. Furthermore, even elderly patients may have a greater chance of receiving treatment when a definitive diagnosis is achieved

Re-immunotherapy with nivolumab plus ipilimumab in advanced non-small cell lung cancer patients previously treated with anti-programmed death-1 and/or anti-programmed death ligand-1 antibodies

Abstract Background The role of re-immunotherapy in advanced non-small cell lung cancer (NSCLC) remains unclear. No studies have evaluated the re-immunotherapy regimen including anti-cytotoxic T-lymphocyte antigen-4 antibody for lung cancer treatment. This study aimed to investigate the efficacy and safety of re-immunotherapy with nivolumab plus ipilimumab in patients with advanced NSCLC previously treated with anti-programmed death-1 (PD-1) and/or anti-programmed death ligand-1 (PD-L1) antibodies. Methods We retrospectively reviewed patients with advanced or recurrent NSCLC who received immunotherapy with nivolumab plus ipilimumab (without concomitant cytotoxic chemotherapy) between November 2020 and November 2022 at the National Hospital Organization Kyoto Medical Center, Kyoto, Japan. Data were extracted from patients who had previously received immunotherapies with anti-PD-1 and/or anti-PD-L1 antibodies. Treatment responses and adverse events were evaluated. Results Of the 67 patients who received immunotherapy with nivolumab plus ipilimumab, 23 were included in final analysis. The objective response rate was 17%, and the disease control rate was 48% for nivolumab plus ipilimumab therapy. The highest grade of immune-related adverse events was grade 3, occurring in 11% of cases. Conclusion Re-immunotherapy with nivolumab plus ipilimumab after anti-PD-1 and/or anti-PD-L1 immunotherapy may be feasible and provide clinical benefit in selected patients. Further prospective studies are warranted to identify the patient population that may benefit from re-immunotherapy

Serial interferon-gamma release assay in lung cancer patients receiving immune checkpoint inhibitors: a prospective cohort study

Recent advancements in cancer immunotherapy using immune checkpoint inhibitors (ICIs) have received considerable attention. Although advantageous, ICI therapies cause unique immune-related adverse events (irAEs) in some patients. Moreover, infectious diseases, such as tuberculosis, have been recognized as emerging concerns during immunotherapy. We aimed to evaluate the interferon-gamma release assay (IGRA) conversion rate and active tuberculosis incidence during immunotherapy to elucidate the incidence of tuberculosis reactivation after ICI therapy induction. We prospectively assessed IGRA results in lung cancer patients who received ICI monotherapy before ICI treatment and at 6 and 12 months after ICI treatment. We also assessed computed tomography findings to determine the presence of active tuberculosis when positive IGRA results were obtained. The ICIs used were nivolumab, pembrolizumab, atezolizumab, and durvalumab. In all, 178 patients were prospectively recruited between March 2017 and March 2020. Of these, 123 completed serial IGRAs, of whom 18, 101, and 4, respectively, had positive, negative, and indeterminate IGRAs at baseline. Three and four patients, respectively, showed IGRA reversion and conversion during immunotherapy. One patient with a sustained, stable positive IGRA and one with IGRA conversion developed active pulmonary tuberculosis during immunotherapy. We found that 3.3% and 1.6% of the patients developed IGRA conversion and active tuberculosis, respectively. Of the four patients who developed IGRA conversion, one developed active pulmonary tuberculosis during immunotherapy. Another patient with sustained, stable positive IGRA developed active tuberculosis. Physicians should be alert to tuberculosis development during ICI therapy, and IGRA testing is a useful tool to assess the risk of developing active tuberculosis.</p

De Novo SCLC Transformation From KRAS G12C-Mutated Lung Adenocarcinoma With Excellent Response to Sotorasib: A Case Report

The transformation to SCLC is a known mechanism of resistance against molecularly targeted therapies. This study reports a patient with untreated lung adenocarcinoma, characterized by a KRAS G12C mutation, which transformed into SCLC before treatment. Both the adenocarcinoma and SCLC components were responsive to sotorasib