Introduction:
Lung cancer is the leading cause of cancer death worldwide. In Canada, in 2021 alone, an estimated 21,000 patients have died from this disease. Non-small cell lung cancer (NSCLC) constitutes 85% of all lung cancer cases diagnosed. Over the past 30 years, treatment of unresected locally advanced (LA)-NSCLC evolved from treatment with chest radiotherapy (RT) alone to the current standard of care (SOC) of concurrent chemo-radiation (cCRT), followed by consolidative immunotherapy. Modern RT has influenced the survival of LA-NSCLC patients. In this work we analyzed data from provincial and local institutional databases to evaluate whether, i) the use of modern imaging with 18F-deoxyglucose (FDG)-positron emission tomography (PET), ii) dose of chest RT to tumors and iii) unintentional irradiation of normal tissues during treatment for lung cancer, influence outcomes of patients managed with RT.
Methodology:
Ontario provincial databases were searched through the Institute of Clinical Evaluative Sciences (IC/ES) for stage III NSCLC patients diagnosed between 2007 and 2017. Surgical patients were excluded, and all patients that received RT with or without chemotherapy were selected. Patients were divided into groups of different RT doses (<40Gy, 40-55.9Gy, and ≥56Gy) and whether they underwent diagnostic FDG-PET. For the next study phase (the institutional level), we retrospectively identified and reviewed LA-NSCLC patients treated at local health integration network area 4 (LHIN4) cancer centres (Juravinski and Walker Family Cancer Centres) from 2009 to 2019. We selected patients treated in that period with chest RT > 40Gy with or without chemotherapy. Patients’ data were reviewed individually for disease characteristics, staging investigations, RT treatment parameters and survival outcomes. Dosimetric analysis was performed on both groups of patients (RT alone group and cCRT group).
Results:
The provincial analysis included 5,577 stage III patients who had received chest RT without surgery between January 2007 and March 2017. Within this group, 39.8% (2,225) received RT alone, 47.4% (2,645) received concurrent chemo-radiotherapy (cCRT), and 12.6% (707) received sequential chemo-radiotherapy (sCRT). Median overall survival (OS) with RT alone in three dose groups <40Gy, 40-55.9Gy, ≥ 56Gy was 7.2, 8.5 and 13.3 months compared to 16.5, 15.8 and 22 months for cCRT patients. Higher RT dose and PET utilization were independently associated with improved survival in multivariate analysis.
At the institutional analysis, 84 patients were treated with RT alone, 184 with cCRT and patients with sequential CRT were excluded. In the RT alone group, the median, 1- and 3-year overall survival were 18.1 months, 64.4% and 24.3%, respectively. In comparison, the median, 1- and 3-year survival outcomes in the cCRT group were 36.3 months, 82.5%, and 50.4%, respectively. Additionally, 79.8% of patients in the radiation alone group and 95.1% in cCRT group had PET staging. In univariate analysis, the RT dose prescribed to the tumor and RT dose delivered to the heart were significantly associated with survival, while multivariate analysis only showed the significant association between RT dose to heart and overall survival.
Conclusions:
Our population-based analysis confirmed that radiation monotherapy remains a widely used treatment modality in LA-NSCLC. Higher RT doses and utilization of FDG-PET imaging are associated with improved survival in patients with unresected LA-NSCLC managed with RT. The institutional analysis suggests that in well-staged patients with LA-NSCLC, chest RT of ≥40Gy is associated with improved survival outcomes that compare favorably with historical results of definitive RT alone treatment. Further, survival of patients staged well with FDG-PET and treated with SOC cCRT was higher than historical reports. Importantly, in this study we found that RT dose delivered to the heart associates negatively with patient survival. These findings can help improve clinical decision-making in the management of unresected LA-NSCLC and can serve as basis for future clinical trials. / Thesis / Master of Science (MSc) / Lung cancer is the leading cause of cancer death in Canada and worldwide. These tumors are present as two main histological types, small cell and non-small cell lung cancer, the latter of which consists the majority of the cases diagnosed. Although treatments with surgery or radiotherapy provide reasonable outcomes in lung cancer cases detected early, a high proportion of patients present with localized but advanced disease that is inoperable. Over the last three decades, treatment of locally advanced non-small cell lung cancer has evolved from radiation alone to chemoradiation and immunotherapy. These developments have increased the survival of these patients. In this thesis, we tried to dissect the elements that play roles in the survival of locally advanced non-small cell lung cancer patients. To do this, we evaluated such patients at two levels. First, at the provincial level, we evaluated the type of treatments, and we explored the association of metabolic imaging with positron emission tomography (PET) and the use of high-dose chest radiotherapy with patient survival. Second, at the institutional level, we assessed patients’ outcomes with a more detailed approach. We analyzed the type of treatment along with a detailed dosimetric analysis. The results of our analysis suggest that the use of PET scans and curative radiotherapy is associated with improved survival. On the other hand, the unintentional treatment of the heart with increasing doses of radiotherapy, taking place during chest radiation for lung cancer, is associated with poor outcomes. These results provide a basis for further investigation to improve outcomes of radiotherapy in this disease.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/28426 |
| Date | January 2022 |
| Creators | Gouran-savadkoohi, Mohammad |
| Contributors | Tsakiridis, Theodoros, Health Sciences |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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