RESUMO
Introduction The gold standard treatment of stage I non-small cell lung cancer (NSCLC) is surgical resection. For medically inoperable patients, stereotactic body radiation therapy (SBRT) can provide comparable local control (LC) and overall survival (OS). The objectives of this study are to determine the three-year LC and OS for SBRT compared to early-stage NSCLC patients treated with alternative radiation modalities at our institution. Materials and methods This retrospective study included a total of 139 consecutive patients who were diagnosed with stage I (T1-2 N0 M0) NSCLC and treated with radiation therapy at our institution between 2015 and 2020. Patient demographics and clinical data were obtained from chart reviews. Treatment subgroups were: SBRT (48Gy/4 or 60Gy/8), hypofractionation (60Gy/15), conventional fractionation (60Gy/30 or 50Gy/20), and palliative radiation (20Gy/5, 30Gy/10, or 40Gy/15). Kaplan-Meier curves were plotted for LC and OS. We also performed Cox's proportional hazard regression analysis. Results The median patient age was 74 (range 52-91). The numbers of patients in each treatment subgroup were: SBRT (44), hypofractionation (78), conventional fractionation (8), and palliative (9). Differences in age, gender, and histopathological cell type between subgroups were not statistically significant. Metastatic progression was the most common outcome amongst treatment failures, followed by local recurrence and regional spread. Median post-treatment follow-up in months for each subgroup was: SBRT (20.2), hypofractionated (20.7), conventional fractionation (13.9), and palliative (14.4). Post-treatment three-year LC was found to be significantly better with SBRT (94%) versus hypofractionation (71%), conventional fractionation (80%), and palliative (71%). OS at three years were SBRT (67%), hypofractionation (59%), conventional fractionation (66%), and palliative (44%). As a whole, 72% (100/139) of patients had biopsy-proven NSCLC. Analysis showed biopsy status had no statistical significance with regards to LC or OS. Every 20 years of age had a 3.2x risk of death (95% CI: 1.425-7.268). Concerning the treatment modalities, there were significant differences for the hazard of death compared to SBRT: hypofractionation had 2.58x increased risk while palliative had 5.83x increased risk. The proportion of patients who experienced post-treatment radiation pneumonitis or dermatitis were: SBRT (7%, 2%), hypofractionation (8%, 3%), conventional fractionation (13%, 25%), and palliative (0%, 0%), respectively. No patients who experienced grade III or higher toxicities were observed as defined by Common Terminology Criteria for Adverse Events (CTCAE). Conclusion Our experience confirms SBRT can provide durable three-year local control with a comparable rate of post-treatment complications versus other radiation modalities for early-stage NSCLC. SBRT appears to be non-inferior to hypofractionation with regards to three-year LC.
RESUMO
Reaction of 2,6-dicyanopyridine with 2 equiv. of 2-(propylthio)benzenamine in the presence of lithium bis(trimethylsilyl)amide, followed by ring-closing oxidation with N-chlorosuccinimide affords the novel tridentate ligand, 2,6-bis-(1',2',4'-benzothiadiazinyl)pyridine (LH2). Electrochemical studies on the free ligand LH2 reveal a single well-defined 2e- oxidation process with E1/2 = +0.90 V. EPR studies of the in situ chemical oxidation of LH2 reveal the generation of a benzotriazinyl radical. Reactions of ligand LH2 with a range of divalent transition metal salts in either MeOH or MeCN in a 2 : 1 ratio at ambient temperatures afforded mononuclear complexes with general formula [M(LH2)2][X]2 (M = Mn, X = CF3SO3 (1); Fe, X = CF3SO3 (2); Fe, X = BF4 (3); Co, X = Cl (4); Ni, X = Cl (5); Zn, X = CF3SO3 (6)) and the 1 : 1 complex [Cu(LH2)(NO3)2] (7). In all cases the LH2 ligand binds in a tridentate N,N',N'' chelate fashion via benzothiadiazinyl NBTDA and pyridyl Npy atoms. The low spin FeII complexes (2 and 3) were implemented for NMR and UV-Vis solution studies of ligand reactivity as well as cyclic voltammetry which reveal two 1e-oxidation waves. The metal complexes 1-6 are discussed and reveal a range of geometries between octahedral and trigonal prismatic with the greatest deviation from octahedral symmetry apparent for ions with no crystal field stabilisation energy, i.e. d10 ZnII and high spin d5 MnII ions.
