Abstract
Background
The standard first-line systemic treatment for patients with non-oncogene addicted advanced nonsquamous non-small cell lung cancer (NSCLC) is immunotherapy with immune checkpoint ...inhibitors (ICI) and/or chemotherapy (ChT). Therapy after failing ICI +/− ChT remains an open question, and docetaxel plus nintedanib represent a valid second line option.
Patients and methods
A multicenter retrospective trial of real-life treatment patterns and outcomes of patients with advanced lung adenocarcinoma treated with docetaxel plus nintedanib after the failure of ICI and/or ChT was performed. Patients from 2 Slovenian and 1 Croatian oncological center treated between June 2014 and August 2022 were enrolled. We assessed objective response (ORR), disease control rate (DCR), median progression free survival (PFS), median overall survival (OS), and safety profile of treatment.
Results
There were 96 patients included in the analysis, with ORR of 18.8%, DCR of 57.3%, median PFS of 3.0 months (95% CI: 3.0–5.0 months), and a median OS of 8.0 months (95% CI: 7.0–10.0 months). The majority of patients (n = 47,49%) received docetaxel plus nintedanib as third-line therapy. The ORR for this subset of patients was 19.1%, with a DCR of 57.4%. The highest response rate was observed in patients who received second-line docetaxel plus nintedanib after first-line combination of ChT-ICI therapy (n = 24), with an ORR of 29.2% and DCR of 66.7% and median PFS of 4.0 months (95% CI: 3.0–8.0 months). Fifty-three patients (55.2%) experienced adverse events (AEs), most frequently gastrointestinal; diarrhea (n = 29, 30.2%), and increased liver enzyme levels (n = 17, 17.7%).
Conclusions
The combination of docetaxel and nintedanib can be considered an effective therapy option with an acceptable toxicity profile for patients with advanced NSCLC after the failure of ICI +/− ChT.
To determine the frequency of common symptoms in long COVID and their effect on the quality of life, and to determine the factors contributing to a more severe long COVID.
The study enrolled 266 ...patients who were either referred to long-COVID outpatient clinic or were inpatients undergoing rehabilitation. The data were collected between December 2020 and May 2021. We evaluated the symptoms experienced during acute and long COVID and comorbidities. Functional status was assessed with Post Covid Functional Status (PCFS).
The final sample consisted of 261 patients. After acute COVID-19 period (>4 weeks), almost 80% of patients had impaired functional status. Only 21.5% reported no functional impairment (0 on PCFS scale). A higher PCFS score was associated with female sex (P<0.001) and oxygen therapy requirement during acute disease (P=0.001). However, it was not associated with having a pre-existing lung disease (P=0.749). Disease severity did not pose a risk for developing a more severe long COVID.
Women were at greater risk for developing greater functional impairment in long COVID, although we have no explanation why. Malignant disease and hypertension also presented a risk factor for greater functional impairment. More studies are warranted to determine if patients with certain lung disease are more susceptible to long COVID.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The most commonly used topical hemostatic agents during flexible bronchoscopy (FB) are cold saline and adrenaline. Data on use of other agents such as tranexamic acid (TXA) for this purpose are ...limited.
Is TXA effective and safe in controlling iatrogenic bleeding during FB compared with adrenaline?
We conducted a cluster-randomized, double-blind, single-center trial in a tertiary teaching hospital. Patients were randomized in weekly clusters to receive up to three applications of TXA (100 mg, 2 mL) or adrenaline (0.2 mg, 2 mL, 1:10000) after hemostasis failure after three applications of cold saline (4 ° C, 5 mL). Crossover was allowed (for up to three further applications) before proceeding with other interventions. Bleeding severity was graded by the bronchoscopist using a visual analog scale (VAS; 1 = very mild, 10 = severe).
A total of 2,033 FBs were performed and 130 patients were randomized successfully to adrenaline (n = 65) or TXA (n = 65), whereas 12 patients had to be excluded for protocol violations (two patients from the adrenaline arm and 10 patients from TXA arm). Bleeding was stopped in 83.1% of patients (54/65) in both groups (P = 1). The severity of bleeding and number of applications needed for bleeding control were similar in both groups (adrenaline: mean VAS score, 4.9 ± 1.3 n = 1.8 ± 0.8; TXA: mean VAS score, 5.3 ± 1.4 n = 1.8 ± 0.8). Both adrenaline and TXA were more successful in controlling moderate bleeding (86.7% and 88.7%, respectively) than severe bleeding (40% and 58.3%, respectively; P = .008 and P = .012, respectively) and required more applications for severe bleeding (3.0 ± 0 and 2.4 ± 0.5, respectively) than moderate bleeding (1.7 ± 0.8 and 1.7 ± 0.8, respectively) control (P = .006 and P = .002, respectively). We observed no drug-related adverse events in either group.
We found no significant difference between adrenaline and TXA for controlling noncatastrophic iatrogenic endobronchial bleeding after cold saline failure, adding to the body of evidence that TXA can be used safely and effectively during FB.
ClinicalTrials.gov; No.: NCT04771923; URL: www.
gov.
We present unusual treatment outcome in a 59-year-old male diagnosed with metastatic lung adenocarcinoma with a very good response to ruxolitinib as monotherapy. In June 2017, this patient was ...diagnosed with myeloproliferative neoplasm – Janus-associated kinases 2 positive – and in December 2017 ruxolitinib therapy was started. At the same time, patient was diagnosed with lung adenocarcinoma in the left lower lobe with positive anaplastic lymphoma kinase mutation and with right lower lobe metastasis. Because of partial regression of tumor size noted on the computed tomography (CT) scans during tumor investigation, we did not apply any therapy for lung adenocarcinoma. A follow-up CT scan done in March 2018 showed further size reduction of tumor lesion in lower left lobe (91%), while follow-up CT scan done in June 2018 showed further size reduction of tumor lesion in lower right lobe (82%).
Aim To determine the frequency of common symptoms in long COVID and their effect on the quality of life, and to determine the factors contributing to a more severe long COVID. Methods The study ...enrolled 266 patients who were either referred to long-COVID outpatient clinic or were inpatients undergoing rehabilitation. The data were collected between December 2020 and May 2021. We evaluated the symptoms experienced during acute and long COVID and comorbidities. Functional status was assessed with Post Covid Functional Status (PCFS). Results The final sample consisted of 261 patients. After acute COVID-19 period (>4 weeks), almost 80% of patients had impaired functional status. Only 21.5% reported no functional impairment (0 on PCFS scale). A higher PCFS score was associated with female sex (P < 0.001) and oxygen therapy requirement during acute disease (P=0.001). However, it was not associated with having a pre-existing lung disease (P = 0.749). Disease severity did not pose a risk for developing a more severe long COVID. Conclusion Women were at greater risk for developing greater functional impairment in long COVID, although we have no explanation why. Malignant disease and hypertension also presented a risk factor for greater functional impairment. More studies are warranted to determine if patients with certain lung disease are more susceptible to long COVID.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
e21188
Background: Inflammatory cells have important effects on tumor development. Systemicinflammation markers can be used as prognostic factors. Numerous studiesshown that high pretreatment ...neutrophil-to-lymphocyte ratio (NLR) and/or platelet-to-lymphocyte ratio (PLR) levels are potential prognostic predictors for poor progression-free survival (PFS) and overall survival (OS) in NSCLC patients receiving immunotherapy. Methods: We performed a cohort study of patients with metastatic or recurrent NSCLC treated with nivolumab monotherapy in second‐line or further‐line treatment in Clinical hospital centre Zagreb. Pre-treatment NLR and PLR were calculated by division of neutrophils and platelets by lymphocytes measured in peripheral blood. Patients were categorized in two sub-groups according to their NLR and PLR values. In previous meta-analyses it was suggested that significant cut-off value of NLR is NLR < 5 and ≥5 and PLR < 160 and ≥160. We analysed PFS and OS. Results: Overall 105 patients diagnosed with NSCLC were treated with nivolumab. The patients were enrolled from March 2017 until October 2017 and were observed them for disease progression and death until June 1st 2020. Most of the patients were male (71; 67.6%) with median age 60.3 years (36-77). Our patients were selected on the basis of good performance status, so most of them had ECOG PS 0 and 1 (103; 98.1%). Therapy was applied mostly in the second and third line (67; 64%), but even up to seventh line (2; 1.9%). Median duration of therapy was 34.5 weeks (2-149), while median number of doses was 17 (1-69).The median PFS was 7.2 months (95% CI 4.53-9.86). Regardless of previous treatment the mOS was 16.1 months (95% CI 11.26-20.93).We observed median value of NLR 4.08 (IQR 2.44-5.84) and PLR 200 (IQR 127.49-284.72). Patients with low PLR had better overall survival compared to patients with low PLR (mOS 20.5 months vs 11.9 months; 95%CI 14.07-26.92 vs 7.35-16.44; p = 0.039). The same was not as clear in mPFS, tendency of better mPFS was toward low PLR, but it did not reach statistical difference (low PLR mPFS 9.1 months vs high PLR mPFS 6.1 months; p = 0.49).Patients with low NLR had significantly better overall survival compared to patients with high NLR (mOS low NLR 18.2 vs high NLR 10.1 months; 95%CI 13.07-23.32 vs 6.04-14.15; p = 0.014). Again, the statistical significance was not reached for progression-free survival (mPFS low NLR 8.3 months vs high NLR 5.8 months; 95%CI 4.81-11.78 vs 2.91-8.68; p = 0.214). Conclusions: Here, we demonstrated that the presence of indicators of systemic inflammation suchas high NLR and high PLR are associated with poor overall survival, but not withprogression-free survival in pre‐treated NSCLC patients who received nivolumabtreatment. The limitation of our study is the lack of a randomizedcontrol and small sample size. The main strength of our study is that it is real-worldeveryday clinical setting.
A 43-year-old woman, who was a non-smoker and who had been previously identified as having malignant pericardial effusion and a PET scan suggestive of a primary malignant tumour in the left upper ...lobe of the lung with mediastinal lymphadenopathy was referred to the emergency department at the University Hospital Centre Zagreb in December, 2012, because of progressive dyspnoea.
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