Chemoradiotherapy for untreated Masaoka-Koga stage IVB thymic carcinoma: a single-center retrospective study.

BACKGROUND: Thymic carcinoma (TC) is a rare type of a malignant tumor. The optimal treatment for Masaoka-Koga stage IVB TC patients is controversial due to the rarity of the disease. Chemotherapy is still the preferred option, but the outcomes are unsatisfactory. Whether radiotherapy combined with chemotherapy could improve prognosis remains unclear. METHODS: Untreated stage IVB TC patients who have received first-line chemotherapy were included in the present study. The patients who have undergone surgery were excluded. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). RESULTS: Sixty-seven patients were included in the study. A total of 31 patients received chemoradiotherapy (ChemoRT cohort), and the remaining 36 patients only received chemotherapy (Chemo cohort). The median follow-up period was 40.3 months. The ORR for the ChemoRT and Chemo cohorts was 61.3 and 27.8%, respectively (P = 0.006). Furthermore, PFS (P = 0.003) and OS (P = 0.046) were significantly superior in the ChemoRT cohort. Radiotherapy maintained a significant favorable effect on PFS in multivariate analysis (P = 0.014), but the effect on OS was insignificant (P = 0.249). There was no advantage in PFS (P = 0.302) in the ChemoRT cohort in patients who received < 4 cycles of chemotherapy. In contrast, radiotherapy significantly improved PFS (P = 0.005) in patients who received ≥ 4 cycles of chemotherapy. CONCLUSIONS: Chemoradiotherapy used as the first-line treatment improved ORR and PFS in Masaoka-Koga stage IVB TC patients. Patients receiving more cycles of chemotherapy may have a better chance to benefit from chemoradiotherapy.

Host-Guest Encapsulation to Promote the Formation of a Multicomponent Trigonal-Prismatic Metallacage.

An inclusion complex of a trigonal-prismatic metallacage with two coronene guests was constructed by multicomponent coordination-driven self-assembly from a 90° platinum(II) acceptor [cis-Pt(PEt3)2(OTf)2], disodium terephthalate, and 2,4,6-tri(4-pyridyl)-1,3,5-triazine in the presence of excess coronene. This platinum(II)-based trigonal prism was found to be a highly matched host to simultaneously encapsulate two coronene molecules. The encapsulation of coronene can effectively promote the formation of a pure single-prismatic metallacage and can stabilize the self-assembled structure via strong π-π-stacking interactions between coronene and the metallacage.

Correction to: Timing of thoracic radiotherapy is more important than dose intensification in patients with limited-stage small cell lung cancer: a parallel comparison of two prospective studies.

Correction to: Strahlenther Onkol 2019 https://doi.org/10.1007/s00066-019-01539-1 The original version of this article unfortunately contained a mistake. The correct version of the funding information are given ….

Timing of thoracic radiotherapy is more important than dose intensification in patients with limited-stage small cell lung cancer: a parallel comparison of two prospective studies.

PURPOSE: The optimal radiotherapy dose/fraction for limited-stage small cell lung cancer (SCLC) is undefined. Our objectives were to compare efficacy between hyperfractionated thoracic radiotherapy (TRT; 1.5 Gy 2 times per day [bid] in 30 fractions) and hypofractionated TRT (2.5 Gy once per day [qd] in 22 fractions), and to explore prognostic factors influencing the prognosis, such as the timing of TRT. METHODS: Patients enrolled in two independent prospective studies were combined and analyzed. The primary endpoint was local/regional control (LRC). The prognosis was analyzed using the Cox proportional hazards regression model. RESULTS: Ninety-two and 96 patients were treated with hyperfractionated TRT and hypofractionated TRT, respectively. The 1­ and 2­year LRC rates of the two arms were 82.1 and 60.7%, and 84.9 and 68.8% (P = 0.27), respectively. The median overall survival (OS) times (months) were 28.3 (95% confidence interval, CI 16.4-40.1) and 22.0 (95% CI 16.4-27.5), while the 1­year, 3­year, and 5­year OS rates were 85.2, 40.8, and 27.1%, and 76.9, 34.3, and 26.8% (P = 0.37), respectively. Using a multivariate Cox regression study, time (days) from the initiation of chemotherapy to TRT (TCT) ≤43 was associated with improved LRC (hazard radio, HR 0.39, 95% CI 0.20-0.76; P = 0.005). Time (days) from the start of chemotherapy to the end of TRT (SER) ≤63 (HR 0.50, 95% CI 0.32-0.80; P = 0.003) and prophylactic cranial irradiation (HR 0.43; 95% CI 0.29-0.63; P = 0.000) were favorably related to OS. Grade 2/3 acute radiation esophagitis was observed in 37.0 and 17.7% of patients in the hyperfractionated and hypofractionated arms, respectively (P = 0.003). CONCLUSION: Both hyperfractionated and hypofractionated TRT schedules achieved good LRC and OS for patients with limited-stage SCLC in this study. Keeping TCT ≤43 and SER ≤63 resulted in a better prognosis. The incidence of acute esophagitis was significantly higher in the hyperfractionated arm.

Comparison of efficacy and safety of second- and third-generation TKIs for non-small-cell lung cancer with uncommon EGFR mutations.

BACKGROUND: The efficacy of definite for non-small-cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations has been preliminarily demonstrated. However, there is a paucity of data with which to compare the efficacy and safety of second- and third-generation TKIs in patients with NSCLC carrying uncommon EGFR mutations. METHODS: We compared the efficacy and safety of second- and third-generation TKIs in all NSCLC patients in whom next-generation sequencing confirmed uncommon EGFR mutations, including G719X, S768I, and L861Q. The parameters analyzed included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The rate of treatment-related adverse events (AEs) reflected the safety of these TKIs. RESULTS: Eighty-four NSCLC patients with uncommon EGFR mutations were enrolled between April 2016 and May 2022 at Zhejiang Cancer Hospital, including 63 treated with second-generation TKIs and 21 treated with third-generation TKIs. The ORR for all patients receiving TKIs was 47.6%, and the DCR was 86.9%. The median PFS for NSCLC patients with uncommon EGFR mutations receiving TKIs was 11.9 months and OS was 30.6 months. There was no significant difference in PFS after treatment with second- or third-generation TKIs (13.3 vs. 11.0 months, respectively, P = 0.910) or in OS (30.6 vs. 24.6 months, respectively P = 0.623). The third-generation TKIs showed no severe toxicity. CONCLUSIONS: The efficacy of second- and third-generation TKIs for NSCLC with uncommon EGFR mutations does not differ, and so can be used to treat NSCLC patients with these mutations.

The effect of EGFR-TKIs on survival in advanced non-small-cell lung cancer with EGFR mutations: A real-world study.

BACKGROUND: Few large-scale studies have been published using real-world data related to overall survival (OS) improvements in advanced epidermal growth factor receptor (EGFR)-mutant lung cancer patients; therefore, little is known regarding the characteristics of patients who could benefit most from EGFR-tyrosine kinase inhibitors (TKIs). Our study aimed to assess whether EGFR-TKI treatment confers survival benefits among advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations in the Chinese population. PATIENTS AND METHODS: A total of 6451 advanced NSCLC patients were diagnosed between January 1, 2013 and June 30, 2019 in Zhejiang Cancer Hospital. Ultimately, 2864 patients with a confirmed EGFR mutation genotype were enrolled in our study. OS was measured from the time of diagnosis of advanced NSCLC until death or last follow-up. RESULTS: Median follow-up for OS of advanced EGFR-mutant NSCLC patients was 28.33 months in our study. Patients who received EGFR-TKIs demonstrated better survival compared to those without EGFR-TKI treatment (mOS: 29.77 vs. 22.97 months, p < 0.0001). A total of 451 patients switched to third-generation EGFR-TKI treatment and obtained a significantly better survival than those who adopted first-line third-generation EGFR-TKIs or those who did not receive third-generation EGFR-TKIs after disease progression with first- or second-generation EGFR-TKI treatment (mOS: 38.0 vs. 32.5 vs. 28.3 months, p < 0.0001). As for EGFR genotypes, patients with exon 19 deletion showed better OS, followed by those with L858R mutation (32.4 vs. 24.83 months, p = 0.0013). NGS versus PCR testing showed no statistical differences with respect to survival outcomes (mOS: 27.5 vs. 27.47 months, p = 0.6745). CONCLUSION: Advanced EGFR-mutant patients treated with EGFR-TKIs obtained absolute superior survival in the Chinese population.

Derived Neutrophil-Lymphocyte Ratio and C-Reactive Protein as Prognostic Factors for Early-Stage Non-Small Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy.

Objectives: To explore the relationship between peripheral blood inflammation parameters and overall survival (OS) and progression-free survival (PFS) of early-stage non-small cell lung cancer patients who underwent stereotactic body radiotherapy (SBRT). Patients and methods: In this study, eligible patients treated with SBRT from 2013 to 2018, and both serum complete blood count and blood biochemical results were available prior to (within 60 days) radiotherapy were included. Results: A review of hospital registries identified 148 patients, and the 5-year OS and PFS of the entire cohort were 69.8% and 65.6%, respectively, with the median follow-up time was 52.8 months. Multivariable analysis showed that derived neutrophil-lymphocyte ratio (dNLR) ≥1.4 and C-reactive protein (CRP) ≥2.9 were statistically and independently associated with worse OS (HR = 4.62, 95% CI 1.89-11.27, p = 0.001; HR = 2.92, 95% CI 1.49-5.70, p = 0.002, respectively). The 5-year OS for patients with dNLR below and equal to or above the 1.4 were 85.3% and 62.9% (p = 0.002), respectively, and 76.7% for the low CRP group versus 58.5% for the high CRP group (p = 0.030). Higher serum level of post-treatment CRP also independent parameters for inferior PFS (HR = 4.83, 95% CI 1.28-18.25, p = 0.020). Conclusions: Our results demonstrate that dNLR and CRP are associated with the outcomes of early-stage NSCLC patients treated with SBRT, which may assist in selecting optimal nursing care and therapeutic scheme for every individual.

Comparison of stereotactic body radiation therapy versus surgery for multiple primary lung cancers after prior radical resection: A multicenter retrospective study.

Background: Patients who previously underwent surgical resection of initial primary lung cancer are at a high risk of developing multiple primary lung cancers (MPLCs). The purpose of this study was to compare the efficacy and safety between stereotactic body radiation therapy (SBRT) and surgery for MPLCs patients after prior radical resection for the first lung cancers. Methods: In this multicenter retrospective study, eligible MPLC patients with tumor diameter of 5.0 cm or less at N0M0 who underwent SBRT or reoperation between January 2013 and August 2020 were enrolled. The primary endpoint was the 3-year locoregional recurrence and treatment-related toxicity. Kaplan-Meier method was used to calculate survival rates. The χ2 test was adapted to assess the difference of categorical variables between the two subgroup patients. Results: A total of 203 (73 in the SBRT group and 130 in the surgery group) patients from three academic cancer centers were evaluated with a median follow-up of 38.3 months. The cumulative 1-, 2-, and 3-year incidences of locoregional recurrence were 5.6 %, 7.0 % and 13.1 % in the SBRT group versus 3.2 %, 4.8 % and 7.4 % in the surgery group, respectively [hazard ratio (HR), 1.97; 95 % confidence interval (CI), 0.74-5.24; P = 0.14]. The cancer-specific survival rates were 95.9 %, 94.5 % and 88.1 % versus 96.9 %, 94.6 % and 93.8 % in the SBRT and surgery groups respectively (HR, 1.72; 95 % CI, 0.67-4.44; P = 0.23). In the SBRT group, two patients (2.7 %) suffered from grade 3 radiation pneumonitis, while in the surgery group, grade 3 complications occurred in four (3.1 %) patients, and four cases were expired due to pneumonia or pulmonary heart disease within 90 days after surgery. Conclusions: SBRT is an effective therapeutic option with limited toxicity compared to surgery for patients with MPLCs after prior radical surgical resection, and it could be considered as an alternative treatment for those patients.

Comparison of Efficacy and Safety of Platinum-Based Chemotherapy as First-Line Therapy between B3 Thymoma and Thymic Carcinoma.

BACKGROUND: B3 type thymoma is defined as a well-differentiated thymic carcinoma and is similar to a thymic carcinoma. However, the differences between them are not well defined. In addition, the data to compare the efficacy and safety of platinum-based chemotherapy as first-line therapy between B3 thymoma and thymic carcinoma are lacking. METHODS: The efficacy and safety of platinum-based chemotherapy as first-line therapy was retrospectively compared between a group of 36 patients with type B3 thymoma and a group of 127 patients with thymic carcinoma treated between January 2009 and March 2022 at the Zhejiang Cancer Hospital. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events were analyzed. RESULTS: The ORRs for B3 thymoma and thymic carcinoma were 36.1% and 28.3%, respectively (p = 0.370). Among all patients, the difference in PFS between B3 thymoma and thymic carcinoma was not significant (11.3 vs. 10.1 months, p = 0.118). The squamous carcinoma subgroup did not exhibit any differences in PFS compared to B3 thymoma (11.7 vs. 11.3 months, p = 0.161). The result for the non-squamous carcinoma subgroup was similar (6.5 vs. 11.3 months, p = 0.128). Furthermore, the OS values for B3 thymoma and thymic carcinoma were not significantly different (58.3 vs. 35.1 months, p = 0.067). However, there were differences in OS between B3 thymoma and non-squamous carcinoma (58.3 vs. 30.6 months, p = 0.031). CONCLUSIONS: B3 thymoma and especially squamous carcinoma patients may be treated using a similar therapy scheme as that utilized for thymic carcinoma.

Definitive local therapy for extracranial single-organ oligorecurrent non-small-cell lung cancer: A single institutional retrospective study.

Oligometastatic non-small-cell lung cancer (NSCLC) is potentially curable. Oligo-recurrence occurs with oligometastatic disease characterized by well-controlled primary lesion. The purpose of the present study was to explore the value of definitive local therapy (DLT) for extracranial single-organ oligorecurrent NSCLC. A total of 81 patients with NSCLC who had extracranial single-organ oligorecurrence after receiving radical treatment at the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2017 were analyzed. The primary endpoint was progression-free survival (PFS), and the secondary endpoint was overall survival (OS). The median follow-up time of the 81 patients was 65.8 months. A total of 39 patients received DLT. A large proportion of patients who did not accept DLTs received specific tyrosine kinase inhibitors (TKIs). The results of multivariate analysis showed that DLT and specific TKI therapy were favorable prognostic factors significantly related to PFS. Further analysis showed that for patients without specific TKI therapy, DLT significantly improved PFS and the 5-year PFS rate. The 5-year OS rate also improved, but the improvement was not significant. For extracranial single-organ oligorecurrent NSCLC, PFS was significantly superior in patients receiving DLT. Among them, for the subgroup of patients who did not receive specific TKI therapy, DLT is expected to improve long-term prognostic outcomes.

Comparison of the outcomes of sublobar resection and stereotactic body radiotherapy for stage T1-2N0M0 non-small cell lung cancer with tumor size ≤ 5 cm: a propensity score matching analysis.

BACKGROUND: Surgery and stereotactic body radiotherapy (SBRT) are both suitable treatment options for early stage Non-small cell lung cancer (NSCLC), which accounts for the majority of lung cancer. This study compared the outcomes of sublobar resection (SLR) and SBRT in patients with stage T1-2N0M0 NSCLC with tumor size ≤5 cm. METHODS: Patients with T1-2N0M0 lung cancer who underwent SLR or SBRT between January, 2012 and December, 2016 were included in this retrospective study. The survival outcomes and toxicity of the SLR and SBRT cohorts were compared using Kaplan-Meier survival plots. In a second exploratory analysis, propensity score matching (PSM) was applied to reduce selection bias between the two groups of patients. RESULTS: A total of 121 SLR and 109 SBRT cases were included. The average follow-up was 49.4 months. Prior to PSM, the 5-year overall survival (OS) and cancer-specific survival (CSS) rates in the SLR group (82.8% and 89.0%, respectively) were superior to those in the SBRT group (67.0% and 75.3%; P=0.001 and P=0.013, respectively). There were no statistically significant differences in the five-year locoregional control and disease-free survival (DFS) rates between the groups. PSM identified 40 patients from each treatment group who shared similar characteristics. At 5 years, the OS rates in the SLR and SBRT groups were comparable (79.9% vs. 66.5%, respectively; P=0.154). After PSM, the rates of CSS, locoregional control, and DFS were also similar between the groups (P=0.458, 0.369, and 0.698, respectively). In the SBRT group, one patient developed grade 3 radioactive pneumonitis. No grade >3 toxicities or treatment-related deaths occurred in either group. CONCLUSIONS: SBRT may be an alternative option to SLR for patients who cannot tolerate lobectomy because of medical comorbidities and has a similar level of effectiveness.

[Prognostic Analysis of NSCLC Based on the Tumor-associated Macrophages, Tumor Neo-vessels and PD-L1 Expression in Tumor Microenvironment].

BACKGROUND: Tumor microenvironment is a complex and dynamic community, which plays a crucial role in tumor progression via the co-evolution of cancer cells and tumor stroma. Among them, tumor-associated macrophages (TAMs) and tumor neo-vessels are two key components in the tumor microenvironment during cancer invasion. In addition, programmed cell death ligand 1/programmed cell death ligand 1 (PD-1/PD-L1) also plays an important role in tumorigenesis and development, and the clinical strategies to block PD-1/PD-L1 pathway could have great benefits for cancer patients. This study was aimed at analyzing the quantitative expression and prognostic significance of TAMs, tumor neo-vessels and PD-L1 in tumor microenvironment and exploring the relations between the expression of above components with the patients' prognosis of non-small cell lung cancer (NSCLC). METHODS: Clinico-pathological data and surgical specimens of 92 patients with NSCLC were collected, and immunohistochemistry was used to stain the expression of TAMs, tumor neo-vessels and PD-L1 on tumor tissue and peri-tumor tissues. The inverted microscopy was used to take pictures and Image-pro Plus 6.0 software was used for quantitative analysis. The clinicopathological characteristics and overall survival (OS) were analyzed. RESULTS: The median OS of 92 NSCLC cases was 22.5 month. The expression of TAMs, tumor neo-vessels and PD-L1 in tumor tissue and peri-tumor tissues were not statistically significant (P>0.05). According to the cutoff of above key three components in tumor microenvironment, all the cases could be classified into high, middle and low expression groups. The survival analysis demonstrated that the OS in high expression group of TAMs (P=0.016) and PD-L1 (P=0.002) was shorter than the other two groups, respectively, with statistical significance. The OS in high tumor neo vessels group was shorter than the other two groups. However, there was no statistical significance between these three group (P=0.626). Combined with above the three components, all the cases could be classified into low, middle and high density groups. The survival analysis demonstrated that the median OS of combined high density group was shorter than the other two groups (P=0.001). Multivariate analysis by Cox regression indicated that pathological type, TAMs and PD-L1 expression were the independent prognostic factors. CONCLUSIONS: The key components of TAMs and PD-L1 in tumor microenvironment are closely related to the prognosis of NSCLC patients.

Comparison Of Long Term Results Between Matched Chemoradiotherapy And Surgery For Limited Stage Small Cell Lung Cancer.

PURPOSE: To compare the efficacy of chemoradiotherapy or surgery for limited-stage small cell lung cancer (SCLC). PATIENTS AND METHODS: A retrospective analysis was performed on 138 patients with limited-stage SCLC who received surgery (69 patients) or chemoradiotherapy (69 patients) between January 2000 and September 2016 in Zhejiang Cancer Hospital. Patients of the chemoradiotherapy group were selected by using "pair-matched case-control" methodology from a cohort of 503 patients who received chemoradiotherapy. RESULTS: The major prognostic factors, including T, N stage, treatment duration, age, gender, and whether or not they received prophylactic cranial irradiation were well balanced between two groups. The median overall survival (OS) time and 5-year OS rate were 37.1 months and 45.0% in the surgical group vs 45.0 months and 45.0% in the chemoradiotherapy group (P=0.846). The median progression-free survival (PFS) time and 5-year PFS rate were 27.1 months and 37.8% vs 36.2 months and 40.0%, respectively, in the two groups (P=0.610). The 5-year OS rate (62.3% vs 40.1%, P=0.038) and 5-year PFS rate (80.1% vs 40.1%, P=0.048) in the surgical group were significantly higher than those of the chemoradiotherapy group in patients with stage I disease. The 5-year OS rate (41.2% vs 50.6%, P=0.946) and 5-year PFS rate (64.7% vs 42.1%, P=0.280) of surgery for stage II SCLC were comparable to chemoradiotherapy. As for stage III SCLC, compared with the surgical group, the chemoradiotherapy group had a better 5-year OS trend (25.1% vs 47.6%, P=0.220), but the difference did not reach statistical significance. CONCLUSION: Surgery could confer survival benefits in patients with p-stage I disease, but not in patients with p-stage II and III disease.