Efficacy and safety of apatinib combined with whole-brain radiation therapy with a simultaneous integrated boost for brain metastases from non-small cell lung cancer: a multicenter retrospective study

BackgroundBrain metastases (BMs) develop in 20–65% of non-small cell lung cancer (NSCLC) patients and are associated with a poor prognosis. Apatinib, a tyrosine kinase inhibitor (TKI) that selectively inhibits the vascular endothelial growth factor receptor 2, is safe and significantly prolongs the survival of chemotherapy-refractory gastric cancer patients. This retrospective study evaluated the safety and efficacy of apatinib combined with concurrent brain radiotherapy in NSCLC patients with BMs.MethodsThis trial enrolled patients with non-recurrent BM from histologically-confirmed NSCLC without any limits regarding the BM size/quantity. Eligibility criteria were patients 18–75 years old with measurable BM from histologically-confirmed NSCLC (including both newly-diagnosed and previously treated NSCLC) and expected survival time greater than 3 months. Oral apatinib (500 or 250 mg/day) was started within 1 week prior to commencing whole brain radiotherapy with simultaneous integrated boost (WBRT-SIB) and continued until one week after radiotherapy completion. In addition to toxicities, analyzed outcomes included intracranial overall response rate (iORR), intracranial disease control rate (iDCR), intracranial progression free survival (iPFS), and overall survival (OS).ResultsFrom July 2016 to January 2020, 16 patients were enrolled in this retrospective study. After 3 months of brain radiotherapy, the iORR was 75%, the iDCR was 100%, and the brain edema index (EI) was significantly reduced compared to that before brain radiation therapy (4.2 vs. 1.9; P=0.02). The median iPFS was 16.5 months [95% confidence interval (CI): 15.1–37.4 months]. The median OS was 26 months (95% CI: 17.0–54.0 months). Most of the patients tolerated apatinib well, but 7 patients had side effects, most commonly grade 1 or 2. Only 2 patients experienced grade 3 adverse events (hypertension and oral mucositis), and no grade 4 or 5 toxicities were observed.ConclusionsApatinib combined with WBRT-SIB appears to be safe and effective in treating BMs in NSCLC patients.     

A propensity-matched analysis of stereotactic body radiotherapy and sublobar resection for stage I non-small cell lung cancer in patients at high risk for lobectomy: the results in a Chinese population

BackgroundTo investigate the comparative effectiveness of stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) in patients with stage I non-small cell lung cancer (NSCLC) considered to be high-risk lobectomy patients.MethodsFrom January 2012 to December 2015, patients who underwent SBRT or SLR for clinical stage I NSCLC were examined retrospectively. Propensity score matching (PSM) was performed to reduce selection bias in SBRT and SLR patients.ResultsData from 86 SBRT and 79 SLR patients was collected. Median follow-up periods of the SBRT and SLR groups were 32 and 37 months, respectively. Patients treated with SBRT exhibited significantly higher age, higher likelihood of being male, larger tumor diameter, lower forced expiratory volume in 1 second (FEV1), and poorer performance status compared with SLR patients. There were no significant differences between SBRT and SLR patients for 3-year overall survival (OS) (80.3% and 82.3%, P=0.405), cause-specific survival (CSS) (81.3% and 83.4%, P=0.383), and local control (LC) (89.7% and 86.0%, P=0.501). Forty-nine patients were identified from each group after performing PSM. After patients were matched for age, gender, performance status, tumor characteristics and pulmonary function, no significant differences were observed in 3-year OS (85.4% and 73.3%, P=0.649), CSS (87.2% and 74.9%, P=0.637) and LC (95.6% and 82.1%, P=0.055). Prevalence of significant adverse events (grade 3 or worse) was 0% and 10.2% in the matched SBRT and SLR groups (P=0.056), respectively.ConclusionsDisease control and survival in the SBRT patients was equivalent to that seen in SLR patients with stage I NSCLC considered high-risk lobectomy candidates. SBRT could therefore be an alternative option to SLR in treating patients with a high operative risk.     

Trends and costs of stereotactic body radiation therapy in metastatic non-small cell lung cancer

BackgroundThe purpose of this study is to describe stereotactic body radiation therapy (SBRT) use, outcomes, hospitalizations and costs compared to patients receiving chemotherapy among patients with metastatic non-small cell lung cancer (NSCLC).MethodsUsing the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified patients aged ≥66 with metastatic NSCLC treated with SBRT as first-line treatment between 2004 and 2014. Multivariable logistic regression identified covariates associated with SBRT. Overall survival (OS) between SBRT and chemotherapy was compared using the Kaplan-Meier estimator and Cox proportional hazards regression. To compare hospitalizations and associated costs, we matched patients treated with SBRT to those with comparable prognostic factors receiving chemotherapy.ResultsWe identified 215 patients with metastatic NSCLC who received SBRT and 12,486 patients who received chemotherapy as first-line treatment. SBRT use increased from 0.5% to 3% and was associated with older age, female sex, poor disability status, and lower T- and N-stage. OS increased with SBRT, female sex, higher income and decreased with higher Charlson Comorbidity Score ≥2, poor disability status, higher T-stage and higher N-stage. Among a matched sample, SBRT patients underwent fewer hospitalizations vs. chemotherapy patients (73% vs. 81%, P=0.02). Among those hospitalized, SBRT patients incurred higher hospitalization costs ($33,063 vs. $23,865, P<0.001) but costs per month of survival were similar.ConclusionsSBRT is increasing among Medicare patients with metastatic NSCLC. Our findings suggest that SBRT may play a role in management of select metastatic NSCLC patients in addition to standard-of-care chemotherapy.     

The impact of pathologic staging of the hilar/mediastinal nodes on outcomes in patients with early-stage NSCLC receiving stereotactic body radiotherapy

BackgroundThe importance of invasive mediastinal nodal staging in early-stage non-small cell lung cancer (NSCLC) in the PET/CT era is dependent on tumor factors that increase risk of nodal metastasis. At our institution, patients undergo biopsy via either CT-guidance (without nodal staging) or navigational bronchoscopy with endobronchial ultrasound transbronchial needle aspiration for nodal staging. This study aims to compare outcomes after stereotactic body radiotherapy (SBRT) stratified by receipt of invasive mediastinal nodal staging.MethodsIn this retrospective study, records of all consecutive patients undergoing SBRT for early-stage NSCLC between 2010 and 2017 were analyzed. The association between time-to event outcomes (recurrence and survival) were evaluated with covariates of interest including tumor size, location, histology, smoking history, prior lung cancer history, radiation dose and receipt of nodal staging. Both univariable and multivariable analyses were used to examine these comparisons.ResultsOverall, 158 patients were treated with SBRT. One hundred forty-nine out of one hundred fifty-eight patients (94%) underwent PET/CT staging, and all patients underwent tumor-directed biopsy. Seventy-nine patients underwent navigational bronchoscopy with nodal staging and 79 patients underwent CT-guided biopsy without nodal staging. Receipt of nodal staging was not associated with tumor size (P=0.35), yet was associated with central tumor location (P<0.001). There was no statistically significant association between receipt of nodal staging and time-to-event recurrence or survival outcomes; for example 3-year overall survival (OS) was 65% vs. 67% (P=0.65) and 3-year freedom from nodal failure was 84% vs. 69% (P=0.1) for those with and without nodal staging, respectively.ConclusionsSimilar recurrence and survival outcomes were observed after SBRT regardless of receipt of invasive mediastinal nodal staging. Further prospective evaluation can help identify which patients might derive greatest benefit from invasive staging of the mediastinum in the PET/CT era.     

Dynamic nomogram for long-term survival in patients with non-small cell lung cancer after pneumonectomy

BackgroundThe study aims to identify prognostic factors of overall survival (OS) in patients who had pneumonectomy, in order to develop a practical dynamic nomogram model.MethodsA total of 2,255 patients with non-small cell lung cancer (NSCLC) who underwent pneumonectomy were identified from 2010–2015 in the Surveillance, Epidemiology, and End Results (SEER) database. The cohort was divided into a training (2011–2015) and a validation [2010] cohort. A nomogram and a risk classification system were constructed from the independent survival factors in multivariable analysis. The predictive accuracy of the nomogram was measured through internal and external validation.ResultsIndependent prognostic factors associated with OS were gender, age, pathology, tumor size, N stage, chemotherapy, and radiotherapy. The C-index of the nomogram for OS was 0.675 (95% CI: 0.655–0.694). Similarly, the AUC of the model was 0.733, 0.709, and 0.701 for the 1-, 3-, and 5-year OS, respectively. The calibration curves for survival demonstrated good agreement. Significant statistical differences were found in the OS of patients within different risk groups. An online calculation tool was established for clinical use.ConclusionsThis novel nomogram was able to provide a reliable prognosis for survival in patients with NSCLC undergoing pneumonectomy.     

Outcomes of surgically managed primary lung sarcomas: a National Cancer Database analysis

BackgroundPrimary lung sarcoma (PLS) represents a rare form of lung cancer with outcomes that are poorly defined by small datasets. We sought to characterize clinical and pathological characteristics and associated survival within the surgically managed subgroup of these unusual pulmonary malignancies.MethodsWe performed a retrospective analysis of the National Cancer Database (NCDB), which was queried for cases of surgically managed PLS diagnosed between 2004–2014. Adjusted mortality was evaluated in a multivariable Cox proportional hazards model and compared to surgically manage non-small cell lung cancer (NSCLC) patients from the same time period.ResultsA total of 695 patients with surgically managed PLS were identified with 37 different histologic subtypes. The mean age of diagnosis was 57.7 years (range, 18–90 years). A majority of patients underwent surgical resection alone (64.3%) with an estimated 5-year overall survival (OS) of 51%. The multivariable Cox model identified increasing age, Charlson-Deyo score ≥2, high tumor grade, tumor size >5 cm, positive margins, and positive lymph nodes to be associated with higher risk for mortality (P<0.05). Compared to 101,428 surgically managed patients with adenocarcinoma, PLS patients were younger with fewer comorbidities but had larger tumors, higher grade tumors, and were more likely node negative (P<0.001). Surgery with adjuvant chemotherapy was associated with worse survival than surgery alone (HR 1.41, 95% CI: 1.05–1.88). The extent of parenchymal resection (lobar vs. sublobar) was not predictive for survival. Five-year OS was lower for patients with PLS (44%) than adenocarcinoma (53.6%, P<0.001).ConclusionsThe survival of surgically managed PLS is reasonable and impacted by tumor attributes and the completeness of surgical resection. Further study to define the role of multimodal therapy is indicated.     

Prognostic value of selected platelet parameters of patients operated for non-small cell lung cancer

BackgroundPlatelets play a vital role in the neoplastic process. Platelet parameters are hence an important source of information concerning ongoing neoplastic disease. The aim of the study is to assess the impact of selected platelet parameters on the survival of patients with non-small cell lung cancer (NSCLC).MethodsThe study included 532 (174 female and 358 male) patients aged 36–84 years (mean age 63.6 years) operated on due to NSCLC, staged IA–IIIA. Before the operation, all patients received a blood morphology test. The following parameters were subjected to statistical analysis: platelet count, mean platelet volume (MPV) parameter, platelet distribution width (PDW) parameter, platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation (SII) index. These findings were compared with the clinical data of the patients, and the probability of overall survival was analyzed.ResultsThe univariate analysis revealed a correspondence between PDW, MPV, PLR and SII index and patient survival. The multivariate analysis including patient clinical data found the following factors to have negative prognostic value for patients operated on due to NSCLC: male sex, advancement stage of neoplastic disease and Charlson Comorbidity Index (CCI) above 4, and PLR >144.ConclusionsPDW value, PLR and SII index are independent prognostic factors. In the multi-factor model, male sex, the advancement stage of the neoplastic disease, CCI above 4 and PLR lower than 144 had the greatest prognostic value.     

Implications of pneumonitis after chemoradiation and durvalumab for locally advanced non-small cell lung cancer

BackgroundConsolidation durvalumab improved overall survival (OS) in locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy (CRT) in the PACIFIC trial; however, pneumonitis was increased with durvalumab. We sought to examine real-world outcomes with the PACIFIC paradigm, especially factors associated with pneumonitis, using a multi-institutional review.MethodsPatients with LA-NSCLC treated with CRT followed by durvalumab from January 2017–February 2019 were identified at 2 institutions. We characterized demographics, tumor factors, radiotherapy, and duration of durvalumab. We examined pneumonitis outcomes including re-challenge success, with secondary endpoints of progression-free survival (PFS) and OS.ResultsThirty-four patients were included with median follow-up of 12 months (range, 3 to 20 months); 94% had stage III disease. The cumulative grade >2 pneumonitis rate was 26.5% with 2 patients developing grade 3 pneumonitis and no grade 4/5 events. Median time to pneumonitis after RT was 2.4 months (range, 0 to 4.9 months). Pneumonitis management included median prednisone dose of 60 mg for median taper of 6 weeks with durvalumab held for median of 4.5 weeks (range, 2 to 8 weeks); 70% of pneumonitis patients received durvalumab re-challenge, with pneumonitis recurring in 14% of patients. 3-month and 6-month pneumonitis-free-survival were 76.9% and 73.6%, respectively; 9- and 12-month OS were 96% (75.1–99.8%), 86.6% (63.5–95.5%), respectively; 9- and 12-month PFS were 68% (47.5–82.5%), 48.7% (25.3–68.3%). Pneumonitis development did not significantly impact PFS or OS (P>0.05).ConclusionsAmong LA-NSCLC patients treated with CRT followed by consolidation durvalumab, more than 25% developed symptomatic pneumonitis. In this small case series, pneumonitis did not appear to negatively impact survival, and durvalumab re-challenge appeared feasible after pneumonitis treatment with steroids.     

Preoperative coronary artery calcifications in veterans predict higher all-cause mortality in early-stage lung cancer: a cohort study

BackgroundLung cancer patients often have comorbidities that may impact survival. This observational cohort study examines whether coronary artery calcifications (CAC) impact all-cause mortality in patients with resected stage I non-small cell lung cancer (NSCLC).MethodsVeterans with stage I NSCLC who underwent resection at a single institution between 2005 and 2018 were selected from a prospectively collected database. Radiologists blinded to patient outcomes graded CAC severity (mild, moderate, or severe) in preoperative CT scans using a visual estimation scoring system. Inter-rater reliability was calculated using the kappa statistic. All-cause mortality was the primary outcome. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to compare time-to-death by varying CAC.ResultsThe Veteran patients (n=195) were predominantly older (median age of 67) male (98%) smokers (96%). The majority (68%) were pathologic stage IA. Overall, 12% of patients had no CAC, 27% mild, 26% moderate, and 36% severe CAC. Median unadjusted survival was 8.8 years for patients with absent or mild CAC versus 6.3 years for moderate and 5.9 years for severe CAC (P=0.01). The adjusted hazard ratio for moderate CAC was 1.44 (95% CI, 0.85–2.46) and for severe CAC was 1.73 (95% CI, 1.03–2.88; P for trend <0.05).ConclusionsThe presence of severe CAC on preoperative imaging significantly impacted the all-cause survival of patients undergoing resection for stage I NSCLC. This impact on mortality should be taken into consideration by multidisciplinary teams when making treatment plans for patients with early-stage disease.     

Tumor size as a predictor for prognosis of patients with surgical IIIA-N2 non-small cell lung cancer after surgery

BackgroundThe 8^th edition of the American Joint Committee on Cancer staging system for lung cancer made major revisions to T staging, especially the size division of stage II/III patients. However, the value of tumor size in the postoperative prognosis of IIIA–N2 non-small cell lung cancer (NSCLC) is seldom mentioned, and survival data of such patients should be re-evaluated according to the 8^th edition staging system.MethodsPatients with IIIA-N2 NSCLC after surgery were identified in the Surveillance, Epidemiology, and End Results database (n=4,128). All patients were stratified according to tumor size, 5-year overall survival (OS) was then compared. Cox regression analysis was used to determine the value of size to discriminate patients with prognostic differences and establish a predictive nomogram system. Patients with IIIA-N2 NSCLC from our own institute (n=583) were used to validate the results.ResultsThe prognosis of patients with tumor sizes of 0–2, 2–4 and 4–5 cm differed greatly from each other in the training cohort, with 5-year OS rates of 53.7%, 43.9% and 36.9% respectively (P<0.001), in the validation cohort, the rates were 54.1%, 38.4% and 33.8% respectively. Tumor size >2 cm was considered an independent risk factor compared to the ≤2 cm group in the Cox regression analysis: 2–4 cm (HR =1.25, 1.12–1.39; P<0.001), 4–5 cm (HR =1.51, 1.32–1.39; P<0.001), the validation cohort showed the same trend. The concordance index of the training set was 0.634 (0.622–0.646), while that of the validation set was 0.716 (0.686–0.746). The calibration plot showed optimal consistency between the nomogram predicted survival and observed survival.ConclusionsTumors with different sizes showed significant postoperative survival differences among patients with IIIA-N2 NSCLC. Tumor size should be considered when making surgery decisions in such patients, with tumor size ≤2 cm showing considerably better prognosis.     

Efficacy and safety of pemetrexed maintenance chemotherapy for advanced non-small cell lung cancer in a real-world setting

BackgroundPemetrexed maintenance therapy offers a survival benefit in patients with nonprogressive advanced nonsquamous non-small cell lung cancer (NSCLC) with good tolerability. This study was designed to analyze the efficacy and safety of pemetrexed maintenance chemotherapy in advanced nonsquamous NSCLC patients in a real-world setting.MethodsThe response rate (RR) and adverse events in 71 nonsquamous NSCLC patients treated with pemetrexed-based chemotherapy were observed until disease progression or unacceptable toxicities. Measures of survival were analyzed during follow-up.ResultsOf 69 efficacy-evaluable patients, the objective response rate (ORR) was 46.4% and the disease control rate (DCR) was 98.6%. ORR showed no significant difference between patients who received pemetrexed as first-line therapy and those who received pemetrexed as second-line or higher treatment. The median treatment cycle for all patients was 8. The median progression-free survival (PFS) was 9.5 months (m) and median overall survival (OS) was 30.5 m. The univariate and multivariate analyses showed that the number of chemotherapy cycles was an independent factor for PFS. The most common adverse reactions were grade 1 to 2 hematologic toxicities, gastrointestinal reactions, and liver enzyme abnormalities. Only 1 patient experienced a grade 3 gastrointestinal event.ConclusionsPemetrexed maintenance chemotherapy can improve PFS in patients with advanced nonsquamous NSCLC with good tolerability.     

Older patients more likely to die from cancer-related diseases than younger with stage IA non-small cell lung cancer: a SEER database analysis

BackgroundVarious reports showed some conflicting data on survival at different ages. This study aimed to investigate the main cause of death in older patients with lung cancer and to perform a comparison with younger patients in order to observe the differences between these two cohorts.MethodsOutcomes of patients with stage IA non-small cell lung cancer (NSCLC) ≤3 cm who underwent lobectomy without induction therapy in the Surveillance, Epidemiology, and End Results-18 (SEER-18; January 2004 to December 2016) database were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis.ResultsA total of 16,672 eligible NSCLC cases were found in the SEER database. The number of patients aged ≤60, 61–70, and ≥71 years was 3,930, 6,391, and 6,351, respectively. Among these patient groups, 527 (13.4%), 1,018 (15.9%), and 1,235 (19.4%) died of lung cancer during follow-up, while 357 (9.1%), 964 (15.1%) and 1,579 (25.2%) died of non-lung cancer diseases, respectively. The overall survival (OS) and lung cancer-specific survival (LCSS) rates of younger patients showed a significant survival advantage over older patients. After propensity-score matching (PSM) of patients aged ≤60 and ≥71 years using a ratio of 1:1, we found that 403 (12.9%) and 584 (18.7%) patients in the ≤60 and ≥71 years age groups died of lung cancer, respectively. The OS and LCSS rates of younger patients still exhibited a significant survival advantage over older patients.ConclusionsOlder patients with stage IA NSCLC have a worse prognosis compared with younger patients. Also, cancer-related causes were more frequent in older patients than non-cancer-related causes.     

The impact of an N1 lymph node examination in patients with early-stage non-small cell lung cancer: a retrospective cohort study

BackgroundThe examination of lymph nodes (LNs) is critical for accurate node staging in patients with non-small cell lung cancer (NSCLC), but a consensus on the examinations of hilar and intrapulmonary (N1 station) LNs has not been reached. This study aimed to evaluate the role of LN dissection and pathological examination of N1 LN stations and their effects on survival in patients with stage IA-IIA NSCLC.MethodsData from patients pathologically staged as IA-IIA who underwent radical surgery and confirmed as lacking LN metastases from January 2008 to March 2018 were retrospectively reviewed. The Kaplan-Meier method was used to determine the overall survival (OS) and disease-free survival (DFS). After propensity score matching (PSM), a Cox model was used to determine the prognostic factors.ResultsOf the 1,935 patients investigated, the median number of N1 stations examined was 3. Patients with at least 2 N1 stations examined had apparently better OS (P=0.002) and DFS (P=0.001). All patients were divided into patients with 0–1 N1 station examined and patients with 2–5 N1 stations examined. After PSM, the number of N1 stations examined was an independent prognostic factor for DFS (P=0.004). Patients with 2–5 N1 stations examined experienced prolonged DFS (P=0.010). Patients in group 12 experienced prolonged OS (P=0.021) and DFS (P=0.026). Patients in group 13 or 14 experienced prolonged OS (P=0.028).ConclusionsA larger extent of N1 station examination was associated with prolonged DFS in patients with stage IA-IIA NSCLC after lobectomy. The dissection and examination of at least 2 N1 stations included LNs from the lobar and segmental drainage fields.     

Analysis of the prognostic role and biological characteristics of circulating tumor cell-associated white blood cell clusters in non-small cell lung cancer

BackgroundRecently, circulating tumor-cell-associated white blood cell (CTC-WBC) clusters have been reported to have prognostic value in some cancers. The prognostic role of CTC-WBC clusters in lung cancer has not yet been elucidated. Very little information is available about the biological characteristics of CTC-WBC clusters.MethodsA total of 82 patients with non-small cell lung cancer (NSCLC) were included in this study, and 61 patients with advanced-stage disease were closely followed-up. All patients had blood drawn prior to treatment. Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) platform was used to isolate and identify CTCs and CTC-WBC clusters. Kaplan-Meier survival analysis and Cox regression analysis were applied to assess patient progression-free survival (PFS). Further, qualitative and quantitative analyses the size and ploidy characteristics of CTC-WBC clusters.ResultsFirstly, CTC‐WBC clusters appeared more in the advanced (stage III and IV) stage (P=0.043) than in the early stage. Furthermore, the multivariable analysis (Cox proportional hazards model) revealed that the high‐CTC (≥7/6 mL) group and CTC‐WBC clusters (≥1/6 mL) positive group both had significantly worse PFS, with a hazard ratio (HR) of 2.89 [95% confidence interval (CI): 1.36–6.17, P=0.006] and 2.18 (95% CI: 1.07–4.43, P=0.031), respectively. In the conjoint analysis, compared to patients with <7 CTCs/6 mL without CTC-WBC clusters, patients with ≥7 CTCs/6 mL with CTC-WBC clusters had the highest risk of progression (HR =7.13, 95% CI: 2.51–20.23, P<0.001). In addition, the presence of ≥3-cell CTC-WBC clusters in patients may indicate a shorter PFS (P<0.05) and a higher risk of progression (HR =2.90, 95% CI: 1.06–7.89, P=0.037). Furthermore, compared with the characteristics of the total CTCs, almost all of the CTCs that could recruit WBCs were large cells (≥5 µm) and exhibited polyploidy (≥ tetraploid) (both P<0.01).ConclusionsThe presence of CTC-WBC clusters was an independent prognostic factor for advanced NSCLC. The joint analysis of CTCs and CTC-WBC clusters could provide additional prognostic value to the enumeration of CTCs alone. Besides, most of the CTCs in CTC‐WBC clusters were large polyploid cells.     

Stereotactic body radiation therapy (SBRT) for patients with stage I non-small cell lung cancer is applicable to more tumors than sublobar resection

BackgroundVirtually all patients with medically inoperable stage I non-small cell lung cancer (NSCLC) can receive stereotactic body radiation therapy. However, the percentage of such patients in whom sublobar resection is technically feasible is unknown. This discrepancy can confound clinical trial eligibility and designs comparing stereotactic body radiation therapy vs. sublobar resection.MethodsA total of 137 patients treated with stereotactic body radiation therapy for lung lesions (3/2013–11/2017) underwent retrospective review. Diagnostic CT chest and PET/CT images, stereotactic body radiation therapy dates, and demographic data were collected on 100 of 137 patients. Two experienced board-certified thoracic surgeons independently reviewed anonymized patients’ pre-stereotactic body radiation therapy diagnostic imaging and completed a custom survey about the technical feasibility of sublobar resection for each patient. Interrater agreement was measured using Cohen’s kappa coefficient by bootstrap methodology. Summary statistics were performed for baseline demographics and tumor characteristics.ResultsOf the 100 patients, 57% were female, with median age of 75 years (range, 52–95 years) and Karnofsky Performance Status of 80 (range, 40–100). Most patients (61%) had Stage IA1, T1a tumors. For interrater agreement analysis, one patient was removed from each cohort due to inability to locate tumor on images, leaving 98 patients analyzed. Comparing Surgeon #1 vs. Surgeon #2, 64 (65.3%) vs. 69 (70.3%) of tumors were thought eligible for sublobar resection, respectively (κ=0.414).ConclusionsStereotactic body radiation therapy for stage I NSCLC is applicable to more tumors than sublobar resection, with ~30–35% of stereotactic body radiation therapy patients unable to undergo sublobar resection assessed by pretreatment diagnostic imaging based on technical grounds. This study illustrates that clinical trials comparing stereotactic body radiation therapy vs. sublobar resection are limited to only a subpopulation of patients with stage I NSCLC.     

Risk factors and survival analysis of arrhythmia following lung cancer surgery: a retrospective study

BackgroundSurgical treatment of lung cancer is one of the important treatments for early-stage non-small cell lung cancer (NSCLC). However, arrhythmia, especially atrial fibrillation (AF) and supraventricular arrhythmia, are quite common among patients after surgical treatment of lung cancer. The impact of postoperative arrhythmia (PA) on survival is rarely reported. Our aim was to evaluate the risk factors of PA and its impact on overall survival (OS) after lung cancer surgery.MethodsA total of 344 patients diagnosed with NSCLC who underwent lung cancer surgery were enrolled in this study. These patients were divided into two groups based on the occurrence of PA. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors of PA. The Kaplan-Meier method was applied to show the OS differences between the two groups.ResultsThe incidence of PA was 16% (55/344). Among these 55 patients, 20 had AF, 30 had sinus tachycardia, and 5 had premature beats. A total of 332 patients underwent lung cancer radical resection. Operation type (P<0.001), preoperative abnormal ECG (P=0.032), transfusion (P=0.016), postoperative serum potassium concentration (P=0.001) and clinical stage (P<0.05) were risk factors for PA. PA (HR 2.083, 95% CI, 1.334–3.253; P=0.001), age (HR 1.543, 95% CI, 1.063–2.239; P=0.025) and mediastinal lymph node metastasis (HR 2.655, 95% CI, 1.809–3.897; P<0.001) were independent prognostic risk factors for OS by multivariate cox analysis.ConclusionsWe identified PA as an independent prognostic risk factor to predict poor OS in patients who underwent lung cancer surgery and had risk factors for PA. We therefore provides guidance for PA in improving the prognosis of lung cancer patients.     

The role of postoperative radiotherapy for thymomas: a multicentric retrospective evaluation from three Italian centers and review of the literature

BackgroundThymoma is a rare mediastinal neoplasia. Surgery is the backbone of the treatment, but the role of postoperative radiotherapy (PORT) remains controversial. We aimed to obtain data on survival and safety in patients treated with PORT in three different Italian institutions.MethodsWe retrospectively analyzed 183 consecutive patients who underwent surgery from 1981 to 2015. According to the Masaoka-Koga staging system, 39.3%, 32.7%, 18.6% and 9.8% patients were in stage I, II, III and IV of disease, respectively. PORT was indicated in 114 patients (62.3%), while 69 subjects underwent surgery alone. Complete resection was obtained in 68 patients who underwent PORT. Adverse events (AEs) were graded according to CTCAE v4.0. We analyzed the recent literature to describe the current reports on PORT for resected thymoma.ResultsMean follow-up was 130 months (range, 3–417 months). Overall survival (OS) at 1-, 5- and 10-year from surgery was 98.3%, 90.2% and 69.7% respectively. One-, 5- and 10-year disease specific survival (DSS) was 98.9%, 92.3% and 89.8% respectively. Disease free survival (DFS) at 1, 5 and 10 years from surgery was 96.7%, 88.3% and 82.8% respectively. Univariate analysis showed that complete resection, cell histology A-AB-B1 and stages I–II were significant predictors of better DSS and DFS. Multivariate analysis showed that sex, R0 margins and WHO histology was independent prognostic factors. Among patients treated with PORT, a trend towards better OS was evident with Masaoka stage I–II (P=0.09). Patients with R0 margins treated with PORT showed better OS and DSS (P=0.05). No differences in DSS for performance status (P=0.70), WHO histology (P=0.19), paraneoplastic syndrome (P=0.23) and surgical procedure (P=0.53) were evident. Patients treated with PORT had a higher level of acute AEs compared to surgery alone, but none of these was graded ≥3.ConclusionsOur results confirmed that patients with incompletely resected thymoma had the worst OS and DSS. High grade acute toxicity was not different between PORT and surgery alone. Other trials reported a significant benefit in OS, DSS and DFS in stage IIb–IV thymoma treated with PORT.     

Thoracic stereotactic body radiation therapy plus first-line tyrosine kinase inhibitors for patients with epidermal growth factor receptor-mutant polymetastatic non-small-cell lung cancer: A propensity-matched retrospective study

The role of thoracic stereotactic body radiation therapy (SBRT) in addition to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant polymetastatic non-small-cell lung cancer (NSCLC) has not been well established. This retrospective study aimed to evaluate the efficacy and safety of EGFR-TKIs with thoracic SBRT for the treatment of this patient group.Polymetastatic NSCLC was defined as having >5 metastatic lesions. Patients with polymetastatic NSCLC harboring positive EGFR mutations after initial TKI therapy for at least 8 weeks were eligible for SBRT between August 2016and August 2019. Eligible patients were treated with thoracic SBRT, and TKIs were administered for the duration of SBRT and continued after SBRT until they were considered ineffective. The control group was treated with TKI monotherapy. Propensity score matching (ratio of 1:4) was used to account for differences in baseline characteristics. Progression-free survival (PFS), overall survival, and treatment safety were evaluated.In total, 136 patients were included in the study population. Among them, 120 patients received TKIs alone, and 16 patients received TKIs with thoracic SBRT. The baseline characteristics did not significantly differ between the two cohorts after propensity score matching. The median PFS was 17.8 months in the thoracic SBRT group and 10.8 months in the control group (P = .033). In the multivariate analysis, a Cox regression model showed that thoracic SBRT was an independent statistically significant positive predictor of improved survival, with a hazard ratio of 0.54 (P = .046). We recorded no severe toxic effects or grade 4 to 5 toxicities.Real-world data demonstrate that thoracic SBRT significantly extends PFS in EGFR-mutant polymetastatic NSCLC patients with tolerable toxicity. Given these results, randomized studies are warranted.     

Differential outcomes of residual disease in surgically-resected non-small cell lung cancer and the importance of guideline-concordant adjuvant therapy

BackgroundPositive mediastinal lymph nodes, a marker for systemic disease, and positive margins, a marker for local disease, following resection of non-small cell lung cancer (NSCLC) are forms of residual disease. The objective of this study is to compare survival of patients with residual disease and to study the effect of receipt of guideline vs. non-guideline concordant care.MethodsThe National Cancer Database (NCDB) was used to identify patients who underwent treatment naïve surgical resection with clinical stage T1-3N0-1M0 NSCLC between 2006–2016 and had pN2 disease, positive surgical margins, or both. Concordant care was determined based on form of chemotherapy and radiation, dosage, volume, modality, and duration. Kaplan-Meier survival curves and log-rank tests were used to compare five-year survival. Multivariable analysis using Cox proportional hazards modeling identified factors that contributed to worse overall survival.ResultsThere were 8,189 patients included: pN2 (5,416), positive margins (2,386), and both (387). Five-year survival rates for all patients were pN2 (35.8%), positive margins (33.9%), and both (22.9%) (P<0.0001). On multivariable analysis, positive margins were an independent predictor of better survival relative to pN2 disease (HR =0.729, CI: 0.676, 0.787, P<0.0001). Receipt of non-guideline concordant treatment was an independent predictor of worse survival compared to receipt of guideline-concordant treatment (HR =1.61, CI: 1.504, 1.725, P<0.0001).ConclusionsIn upfront surgical patients, guideline-concordant treatment in the setting of residual disease is associated with better overall survival compared with non-guideline concordant treatment. Pathologic N2 disease is associated with a lower survival rate than positive resection margins, possibly reflecting the systemic nature of pN2 disease.     

支气管动脉灌注化疗联合三维适形调强放疗治疗中央型非小细胞肺癌的临床研究

目的评价支气管动脉灌注化疗联合三维适形放疗治疗中央型非小细胞肺癌的临床价值。方法 73例不能手术切除的中央型非小细胞肺癌患者分成2组,研究组:36例(鳞癌27例,腺癌9例)采用支气管动脉灌注化疗联合三维适形放疗方案,对照组:37例(鳞癌27例,腺癌10例)采用静脉化疗联合普通放疗方案。观察2组方案的有效率、临床收益率(CBR)、不良反应和生存期。结果两组近期有效率(CR+PR)分别为83.33%和62.16%(P=0.043),临床收益率分别为91.67%和72.97%(P=0.037),中位生存期分别为20.8个月和13.3个月,1、2年生存率分别为80.55%、63.86%和59.46%、40.54%(P<0.05)。结论支气管动脉灌注化疗联合三维适形放疗较静脉化疗联合普通放疗治疗中央型非小细胞肺癌可明显提高近期有效率、临床收益率和患者的1、2年生存率。