Aija Knuuttila

Background: Significant progress has been made in the management of metastatic NSCLC (mNSCLC). Our study investigated characteristics, treatment patterns, and outcomes in this patient population and subgroups based on histology and PD-L1 status. Methods: We conducted a retrospective analysis of electronic health records of patients with mNSCLC 1/2019-8/2023 at HUS, Helsinki University Hospital, Finland. Patient characteristics, treatment, and outcomes were analyzed. Results: We identified 646 patients with mNSCLC, including those metastatic at diagnosis and whose cancer later progressed to metastatic, who received systemic therapy. Median age was 70 years (interquartile range [IQR]: 62–75). Squamous cell carcinoma (SqC) presented 19% of patients, adenocarcinoma 68%, and other non-SqC 13%. Amongst the non-SqC patients 53% were female, whereas only 32% of SqC patients were female. Treatment evolved considerably, with increased use of immuno-oncology (IO) and tyrosine kinase inhibitor (TKI) therapies. Median overall survival was 8 months (confidence interval [CI] 95%: 6–9) for those treated with chemotherapy alone, 12 months (CI 95%: 7–18) for those treated with IO therapy, 14 months (CI 95%: 11–15) for those treated with IO + chemotherapy, and 24 months (CI 95%: 16–38) for those treated with TKIs. Interpretation: Our study reports real-world management of patients with mNSCLC and evolving treatment patterns in clinical practice from the first years of IO treatment availability. As we continue to monitor more recent data, the proportion receiving chemotherapy alone is anticipated to continue decreasing. It is crucial to assess current outcomes in NSCLC to target resources correctly and improve prognosis.

While KRAS is the most frequently mutated oncogene in non-small cell lung cancer (NSCLC), KRAS-mutant tumors have long been considered difficult to treat and thus, an unmet need still remains. Partly due to the lack of targeted treatments, comprehensive real-world description of NSCLC patients with KRAS mutation is still largely missing in Finland. In this study, all adult patients diagnosed with locally advanced and unresectable or metastatic NSCLC from 1 January 2018 to 31 August 2020 at the Hospital District of Helsinki and Uusimaa were first identified in this retrospective registry-based real-world study. The final cohort included only patients tested with next generation sequencing (NGS) and was stratified by the KRAS mutation status. A total of 383 patients with locally advanced and unresectable or metastatic NSCLC and with NGS testing performed were identified. Patients with KRAS mutation (KRAS G12C n = 35, other KRAS n = 74) were younger than patients without KRAS mutations, were all previous or current smokers, and had more often metastatic disease at diagnosis. Also, these patients had poorer survival, with higher age, Charlson comorbidity index (CCI) being 5 or above, and KRAS G12C being the most significant risk factors associated with poorer survival. This suggests that the patients with KRAS mutation have a more aggressive disease and/or tumors with KRAS mutation are more difficult to treat, at least without effective targeted therapies.

Pemetrexed has emerged as standard chemotherapy for malignant pleural mesothelioma (MPM). MPMs at two Finnish University Hospitals during 7 years (2000-2006) were reviewed in order to evaluate the treatments, survival and prognostic factors. The results in two periods (before pemetrexed use in 2000-2002 and with pemetrexed in 2003-2006) were compared. Data were collected from the individual patient records retrospectively, and analysed. Altogether 197 patients were diagnosed with following histologies: 136 (69%) epithelioid, 19 (10%) sarcomatoid, 17 (9%) mixed, 25 (13%) not specified; 141 (72%) patients received treatment (five extrapleural pneumonectomy, 36 pleurectomy/decortication, 126 chemotherapy). Median survival was 12.9 months and the 1-, 2- and 3-year survivals were 51.8%, 21.8% and 12.1%, respectively. Univariate analysis showed no significant difference in survival between the patients diagnosed before or during the pemetrexed era (P = 0.124). The patients receiving pemetrexed or other chemotherapy had median survivals of 16.7 and 15.3 months, respectively. The independent prognostic factors for survival were histology and asbestos exposure. Non-epithelioid histology yielded 17 times higher risk of dying than epithelioid. Asbestos exposure doubled the risk of dying, but only in patients diagnosed in 2003-2006. Pemetrexed is beneficial for selected patients, but it has not changed the outcome of the whole MPM population as much as perhaps anticipated. Patient groups with various treatments or symptomatic care only reached survival results comparable to those reported in chemotherapy trials, thus emphasising the need for better subtyping of mesothelioma and individualising the treatment.

To evaluate MR imaging and CT in differentiating malignant pleural mesothelioma from other malignancies or benign pleural disease. Thirty-four patients (18 pleural mesotheliomas, 9 other malignancies, 7 benign pleural diseases) were examined using enhanced CT and MR. Two radiologists reviewed the CT and two others the MR images. Comparisons were made between the diagnostic groups and the imaging methods. The abnormalities commonly found in malignant disease, but significantly less frequently in benign pleural disease, were focal thickening and enhancement of interlobar fissures. In mesothelioma, enhancement of interlobar fissures, tumour invasion of the diaphragm, mediastinal soft tissue or chest wall, were significantly more often observed than in other malignancies and MR was the most sensitive method. In other malignancies, invasion of bony structures was a more common finding and was also better shown by MR. The contrast-enhanced T1 fat-suppressed (CET1fs) sequence detected these features better than other MR sequences. MR, especially the CET1fs sequence in three planes, gave more information than enhanced CT. Focal thickening and enhancement of interlobar fissures were early abnormalities indicating malignant pleural disease. MR could be clinically useful for differentiating mesothelioma from other pleural diseases.

We chose to treat malignant pleural mesothelioma with a combination of docetaxel and irinotecan (CPT-11), because there have been preliminary reports that CPT-11 is active against mesothelioma, and docetaxel and CPT-11 were the most active agents in our in vitro experiments in human mesothelioma cell lines. Fifteen previously untreated patients with pleural mesothelioma (IMIG Stage III-IV) were given docetaxel 60 mg/m2 followed by CPT-11 190 mg/m2 on day 1, repeated every 3 weeks. All the patients were evaluable for toxicity and 13 patients were evaluated for response. No objective responses (complete or partial) were achieved, but there were two minor responses (overall response rate 15%) each of a duration of 4 months. Three patients had stable disease (23%); median time to progression was 7 months. Median survival in all the patients was 8.5 months from the first chemotherapy cycle and 11 months from diagnosis. Toxicity was severe with seven of 15 patients suffering neutropenic fever and six of 15 patients grade 3-4 diarrhea. The trial was discontinued because of toxicity and lack of activity. We do not recommend the combination of docetaxel and CPT-11 using the schedule presented here for further investigation in malignant mesothelioma. However, CPT-11 and docetaxel, individually, still warrant further study in this disease, especially in combination with cisplatin.