Browsing by Subject "NSCLC"

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  • Borenius, Kristian (Helsingin yliopisto, 2021)
    Lung cancer caused the most cancer related deaths world-wide in 2018 and despite extensive research the prognosis of a lung cancer patient remains generally poor. Lung cancer is divided into different histological subtypes the two main types being non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Currently lung cancer is diagnosed with radiological imaging and tissue biopsies. Generally, curative treatment can be achieved only by surgical treatment of early-stage NSCLC. Only 20–25% of NSCLC are eligible for curative intent surgery. Furthermore, 30–55% of these patients have a fatal recurrence of lung cancer. Cell-free DNA (cfDNA) has gained interest in the field of oncology. Generally, cfDNA refers to all the DNA in the body that is free from cellular confinement. Circulating tumor DNA (ctDNA) is cfDNA that originates from cancer cells. It has potential to be a minimally invasive method used in various parts of cancer management including early detection, diagnosis, treatment, monitoring the response for treatment and identification of drug resistance. While the use of cfDNA still lacks clinical trials to be widely used in a clinical setting, it is highly possible that cfDNA analysis establishes a central role in the future in the oncological field.
  • Paajanen, Juuso; Ilonen, Ilkka; Lauri, Helena; Järvinen, Tommi; Sutinen, Eva; Ollila, Hely; Rouvinen, Eeva; Lemström, Karl; Räsänen, Jari; Ritvos, Olli; Koli, Katri; Myllärniemi, Marjukka (2020)
    Activin A has previously been associated with cancer cachexia and in vitro resistance to platinum-based chemotherapy. We studied circulating activin A concentrations as well as activin B and their antagonists' follistatin/follistatin-like 3 in presurgical patients with non-small-cell lung cancer and malignant pleural mesothelioma. We found that circulating activing A levels were elevated in malignant pleural mesothelioma and associated with cancer cachexia and poor response to platinum-based chemotherapy. Circulating activing A separated non-small-cell lung cancer from benign lung lesion. Background: Previous preclinical studies have shown that activin A is overexpressed in malignant pleural mesothelioma (MPM), associates with cancer cachexia, and is observed in in vitro resistance to platinum-based chemotherapy. We evaluated circulating activin levels and their endogenous antagonists' follistatin/follistatin-like 3 in intrathoracic tumors. Materials and Methods: Patients suspected of thoracic malignancy were recruited prior to surgery. Serum samples were collected from 21 patients with MPM, 59 patients with non-small-cell lung cancer (NSCLC), and 22 patients with benign lung lesions. Circulating activin/follistatin levels were measured using enzymelinked immunosorbent assay and compared with clinicopathologic parameters. Results: Circulating activin A levels were elevated in patients with MPM when compared with patients with NSCLC or benign lung lesion samples (P <.0001). Also, follistatin and follistatin-like 3 levels were the highest in MPM, although with less difference compared with activin A. Receiver operating characteristic analysis for activin A for separating NSCLC from benign lung lesion showed an area under the curve of 0.856 (95% confidence interval, 0.77-0.94). Activin A levels were higher in patients with cachexia (P <.001). In patients with MPM, activin A levels correlated positively with computed tomographybased baseline tumor size (R = 0.549; P = .010) and the change in tumor size after chemotherapy (R = 0.743; P = .0006). Patients with partial response or stable disease had lower circulating activin A levels than the ones with progressive disease (P = .028). Conclusion: Activin A serum level could be used as a biomarker in differentiating malignant and benign lung tumors. Circulating activin A levels were elevated in MPM and associates with cancer cachexia and reduced chemotherapy response. (C) 2019 The Author(s). Published by Elsevier Inc.
  • Rauma, Ville; Salo, Jarmo; Sintonen, Harri; Räsänen, Jari Veli; Ilonen, Ilkka (2016)
    Background: This study presents a retrospective evaluation of patient, disease, and treatment features predicting long-term survival and health-related quality of life (HRQoL) among patients who underwent surgery for non-small cell lung cancer (NSCLC). Methods: Between January 2000 and June 2009, 586 patients underwent surgery at the Helsinki University Hospital. The 276 patients still alive in June 2011 received two validated quality of life questionnaires (QLQ): the generic 15D and the cancer-specific EORTC QLQ-C30 + QLQ-LC13. We used binary and linear regression analysis modeling to identify patient, disease, and treatment characteristics that predicted survival and long-term HRQoL. Results: When taking into account patient, disease, and treatment characteristics, long-term survival was quite predictable (69.5% correct), but no long-term HRQoL (R-2 between 0.041 and 0.119). Advanced age at the time of surgery, male gender, comorbidity (measured with the Charlson comorbidity index), clinical and pathological stages II-IV, and postoperative infectious complications predicted a lower survival rate. Features associated with poorer long-term HRQoL (measured with the 15D) were comorbidity, postoperative complications, and the use of the video-assisted thoracoscopic surgery (VATS) technique. Conclusions: Long-term HRQoL is only moderately predictable, while prediction of long-term survival is more reliable. Lower HRQoL is associated with comorbidities, complications, use of the VATS technique, and reduced pulmonary function, while adjuvant therapy is associated with higher HRQoL.
  • Ali, Abir Salwa; Langer, Seppo W.; Federspiel, Birgitte; Hjortland, Geir Olav; Gronbaek, Henning; Ladekarl, Morten; Welin, Staffan; Vestermark, Lene Weber; Arola, Johanna; Osterlund, Pia; Knigge, Ulrich; Sorbye, Halfdan; Micke, Patrick; Grimelius, Lars; Gronberg, Malin; Janson, Eva Tiensuu (2020)
    Gastroenteropancreatic neuroendocrine neoplasms grade 3 (GEP-NENs G3) are rare tumors. These highly aggressive neoplasms are traditionally treated with platinum-based chemotherapy in combination with etoposide. Immune checkpoint proteins such as programmed cell death ligand (PD-L1) may have a role in different cancers allowing them escape the immune system and hence, progress. We aimed to investigate the immunohistochemical expression of PD-L1 in GEP-NEN G3 and evaluate its correlation to clinical parameters. In a cohort of 136 patients, 14 (10%) expressed PD-L1 immunoreactivity; four (3%) patients in the tumor cells and 10 (7%) had immunoreactive immune cells. PD-L1 expression did not correlate to clinical parameters, progression-free survival or overall survival. We conclude that PD-L1 expression is present only in a subset of GEP-NEN G3 patients. Further studies are needed to fully understand the role of PD-L1 in patients with GEP-NEN G3, including the future possibility for treatment with immune checkpoint inhibitors.
  • Andersson, Saana; Ilonen, Ilkka; Järvinen, Tommi; Rauma, Ville; Räsänen, Jari; Salo, Jarmo (2018)
    The role of positive lymph node location in non-small-cell lung cancer (NSCLC) patients and effects on survival was assessed. A total of 88 operated patients with unsuspected N2 disease or station 10 lymph nodes were included. No difference was found in survival between inferior positive mediastinal N2 node patients compared to multilevel N2 disease patients. The survival of patients with positive hilar disease was similar to the inferior mediastinal positive N2 group. Background: The role of surgery in the treatment of non-small-cell lung cancer that has spread to ipsilateral mediastinal or hilar lymph nodes (LNs) is controversial. We examined whether the location of LNs positive for non-small-cell lung cancer in mediastinum or hilum influences the survival of these patients. Patients and Methods: We reviewed data from 881 patients and analyzed those with unsuspected N2 disease or hilar (station 10) LNs. The patients were stratified into the following groups: group A, positive hilar Naruke 10; group B, superior mediastinal and aortic nodes (Naruke 1, 2, 3, 4, 5, and 6); group C, inferior mediastinal nodes (Naruke 7, 8, and 9), and multilevel group D (2 or more positive N2 levels). Results: A total of 69 pN2 and 19 pN1 patients were included. Progression-free survival (PFS) was statistically significant better in group B versus group C (P = .044) and group B versus group D (P = .0086). The overall survival (OS) of group A did not differ from that of group C. A statistically significant better OS was found between groups B and D (P= .051). Conclusion: Inferior positive mediastinal N2 node patients seem to have an OS and PFS as poor as multilevel N2 disease patients. The OS and PFS of patients with positive hilar disease are similar to those in the inferior mediastinal positive N2 group. Superior positive mediastinal N2 node patients have better OS and PFS than the inferior mediastinal positive N2 group. (C) 2018 Elsevier Inc. All rights reserved.
  • Rauma, Ville; Andersson, Saana; Robinson, Eric M.; Rasanen, Jari; Sintonen, Harri; Salo, Jarmo A.; Ilonen, Ilkka K. (2019)
    Very long-term health-related quality of life (HRQoL) is an important end point in operated early stage non-small-cell lung cancer with good prognosis. The results for very long-term HRQoL after minimally invasive video-assisted thoracoscopic surgery (VATS) has not been evaluated and compared to thoracotomy. Surprisingly, inferior overall HRQoL was evident for patients operated with VATS, independent of preoperative factors including age, comorbidities, and pulmonary function tests. Background: As a result of routine low-dose computed tomographic screening, lung cancer is more frequently diagnosed at earlier, operable stages of disease. In treating local non-small-cell lung cancer, video-assisted thoracoscopic surgery (VATS), a minimally invasive surgical approach, has replaced thoracotomy as the standard of care. While short-term quality-of-life outcomes favor the use of VATS, the impact of VATS on long-term health-related quality of life (HRQoL) is unknown. Patients and Methods: We studied patients who underwent lobectomy for the treatment of non-small-cell lung cancer from January 2006 to January 2013 at a single institution (n = 456). Patients who underwent segmentectomy (n = 27), who received neoadjuvant therapy (n = 13), or who were found to have clinical stage > T2 or > NO disease (n = 45) were excluded from analysis. At time of HRQoL assessment, 199 patients were eligible for study and were mailed the generic HRQoL instrument 15D. Results: A total of 180 patients (90.5%) replied; 92 respondents underwent VATS while 88 underwent open thoracotomy. The VATS group more often had adenocarcinoma (P = .006), and lymph node stations were sampled to a lesser extent (P = .004); additionally, hospital length of stay was shorter among patients undergoing VATS (P = .001). No other clinical or pathologic differences were observed between the 2 groups. Surprisingly, patients who underwent VATS scored significantly lower on HRQoL on the dimensions of breathing, speaking, usual activities, mental function, and vitality, and they reported a lower total 15D score, which reflects overall quality of life (P <.05). Conclusion: In contrast to earlier short-term reports, long-term quality-of-life measures are worse among patients who underwent VATS compared to thoracotomy. (C) 2019 Elsevier Inc. All rights reserved.