Role of Postoperative Radiotherapy After Curative Resection and Adjuvant Chemotherapy for Patients With Pathological Stage N2 Non–Small-Cell Lung Cancer: A Propensity Score Matching Analysis

BackgroundThe objective of this study was to evaluate the role of postoperative radiotherapy (PORT) in the setting of adjuvant chemotherapy for pathological stage N2 (pN2) non–small-cell lung cancer (NSCLC).Materials and MethodsA retrospective review of 219 consecutive pN2 NSCLC patients who underwent curative surgery followed by adjuvant chemotherapy was performed. Forty-one patients additionally received PORT. Propensity scores for PORT receipt were individually calculated and used for matching to compare the outcome between patients who did (+) and did not (-) receive PORT. One hundred eleven patients in the PORT (-) group and 38 patients in PORT (+) group were matched. Clinical and pathologic characteristics were well-balanced.ResultsThe median follow-up duration was 48 months. In the matched patients, PORT resulted in a significantly lower crude locoregional relapse (43.2% vs. 23.7%; P = .032). Also, PORT was associated with improved locoregional control (LRC) rate (5-year LRC 63.7% vs. 48.6%; P = .036), but not distant metastasis-free survival, disease-free survival (DFS), and overall survival. An exploratory subgroup analysis suggested a potential DFS benefit of PORT in patients with multiple station mediastinal lymph node metastases (5-year DFS, 43.2% vs. 16.6%; P = .037) and squamous cell carcinoma histology (5-year DFS, 70.1% vs. 23.3%; P = .011).ConclusionsEven in the setting of adjuvant chemotherapy, PORT significantly increased LRC for patients with curatively resected pN2 NSCLC. Some subgroups appear to benefit from PORT in terms of DFS and LRC. Individualized strategies based on risk factors might be considered.     

The Value of Radiotherapy in Patients With Resectable Stage IIIA Non–Small-Cell Lung Cancer in the Era of Individualized Treatment: A Population-Based Analysis

IntroductionNo consensus has been achieved on the benefit of radiotherapy for resected stage IIIA NSCLC patients. The division of stage IIIA has changed significantly in 2017. This study aims to explore the effects of radiotherapy on the survival of patients with resectable stage IIIA NSCLC in the new era.Patients and MethodsPatients diagnosed with NSCLC between 2010 and 2018 were identified in the 8th edition TNM classification from the Surveillance, Epidemiology, and End Results database. A nomogram was developed by integrating all independent predictors for lung cancer-specific survival (LCSS). The Propensity Score Matching (PSM) and subgroup analysis were applied to mitigate potential bias. Survival analyses were conducted using the Kaplan Meier curves and Cox proportional hazards regression.ResultsA total of 2632 stage IIIA NSCLC patients were enrolled. The C-index of the nomogram for the prediction of LCSS was 0.636 (95% CI, 0.616-0.656). In the group of patients with N2 stage who featured more than 5 positive regional lymph nodes, compared with non-PORT, PORT did prolong postoperative survival time (50 vs. 31 months; P= .005). N2 patients with visceral pleural invasion (VPI), older (age >65), or had a larger tumor (size >3 cm) could also benefit from adjuvant radiotherapy.ConclusionTreatment protocol for stage IIIA NSCLC patients should be individualized. Based on our findings, N2 patients with more than 5 positive regional lymph nodes, VPI, larger tumor size (greater than 3 cm), and older (age above 65) could benefit from adjuvant radiotherapy. Further well-designed randomized trials are warranted.     

The Role of Postoperative Radiation Therapy for pN2 Non–small-cell Lung Cancer

BackgroundThe role for postoperative radiation therapy (PORT) for patients with non–small-cell lung cancer (NSCLC) with mediastinal lymph node (LN) involvement (pN2 disease) is controversial. We compared surgery alone with PORT among patients with pN2 NSCLC. We then performed subset analyses to better delineate patients that might benefit from PORT.Patients and MethodsWe conducted a propensity score (PS)-matched, inverse probability of treatment weighting (IPTW) Surveillance, Epidemiology, and End Results (SEER) analysis of patients with pN2 disease from 1989 to 2016 with surgery alone or PORT. Multiple imputation with chained equations was used for missing LN data.ResultsA total of 8631 patients were included in this analysis; 4579 underwent surgery alone, and 4052 underwent PORT. Following PS matching and IPTW, there was no difference in overall survival (OS) (hazard ratio [HR], 0.99; P = .76). However, PORT improved OS among a subset of patients with a LN positive to sampled ratio ≥ 50% (HR, 0.90; P = .01). Moreover, there was a trend towards improved OS among this subset, even with chemotherapy (HR, 0.91; P = .09).ConclusionPORT is not associated with an improvement or detriment in OS for all patients with pN2 NSCLC. However, patients with a positive to sampled LN ratio ≥ 50% may benefit, regardless of chemotherapy status. Nevertheless, PORT will remain the standard of care as we await the results of the ongoing LUNG ART trial.     

A randomized trial of TLR-2 agonist CADI-05 targeting desmocollin-3 for advanced non-small-cell lung cancer

BackgroundRandomized controlled trial to evaluate synergy between taxane plus platinum chemotherapy and CADI-05, a Toll like receptor-2 agonist targeting desmocollin-3 as a first-line therapy in advanced non-small-cell lung cancer (NSCLC).Patients and methodsPatients with advanced NSCLC (stage IIIB or IV) were randomized to cisplatin-paclitaxel (chemotherapy group, N= 112) or cisplatin-paclitaxel plus CADI-05 (chemoimmunotherapy group, N = 109). CADI-05 was administered a week before chemotherapy and on days 8 and 15 of each cycle and every month subsequently for 12 months or disease progression. Overall survival was compared using a log-rank test. Computed tomography was carried out at baseline, end of two cycles and four cycles. Response rate was evaluated using Response Evaluation Criteria in Solid Tumors criteria by an independent radiologist.ResultsAs per intention-to-treat analysis, no survival benefit was observed between two groups [208 versus 196 days; hazard ratio, 0.86; 95% confidence interval (CI) 0.63–1.19; P = 0.3804]. In a subgroup analysis, improvement in median survival by 127 days was observed in squamous NSCC with chemoimmunotherapy (hazard ratio, 0.55; 95% CI 0.32–0.95; P = 0.046). In patients receiving planned four cycles of chemotherapy, there was improved median overall survival by 66 days (299 versus 233 days; hazard ratio, 0.64; 95% CI 0.41 to 0.98; P = 0.04) in the chemoimmunotherapy group compared with the chemotherapy group. This was associated with the improved survival by 17.48% at the end of 1 year, in the chemoimmunotherapy group. Systemic adverse events were identical in both the groups.ConclusionThere was no survival benefit with the addition of CADI-05 to the combination of cisplatin-paclitaxel in patients with advanced NSCLC; however, the squamous cell subset did demonstrate a survival advantage.     

Role of Postoperative Radiotherapy in Pathologic Stage IIIA (N2) Non–Small Cell Lung Cancer in a Prospective Nationwide Oncology Outcomes Database

IntroductionThe role of postoperative radiotherapy (PORT) in the treatment of pathologic stage IIIA (N2) NSCLC remains controversial. We investigated practice patterns and outcomes for these patients in a prospectively maintained nationwide oncology outcomes database.MethodsPatients with known histologic features of pathologic stage IIIA (N2) NSCLC who underwent an operation with negative margins and received adjuvant multiagent chemotherapy from 2004 to 2013 were identified from the National Cancer Data Base and stratified by the use of PORT. Multivariable logistic regression modeling was used to examine factors associated with receiving PORT, and multivariable proportional hazards regression was used to examine the association of treatment and mortality, adjusting for demographic, socioeconomic and clinicopathologic factors. Landmark analysis and covariate balancing propensity score (CBPS) weighting were also explored to account for immortal time bias and nonrandomization.ResultsA total of 2691 patients were identified, with a median follow-up of 32.32 months. In multivariable analysis, improved overall survival was associated with multiple factors, including younger age, female sex, lower Charlson-Deyo comorbidity index, histologic type (with squamous cell being better than adenocarcinoma), smaller tumor size, lower pathologic T stage, surgical procedure (with pneumonectomy or lobectomy being better than sublobar resection), and receipt of PORT (all p < 0.05). Before landmark analysis, the hazard ratio (HR) showed an overall survival benefit for patients receiving PORT (adjusted HR = 0.83, 95% CI [confidence interval]: 0.72–0.95; p = 0.008). This benefit remained significant after CBPS weighting (HR = 0.81, 95% CI: 0.70–0.94, p = 0.005), almost significant after landmark analysis (adjusted HR = 0.84, 95% CI: 0.69–1.007, p = 0.059), and significant after landmark analysis with CBPS weighting (HR = 0.77, 95% CI: 0.63–0.94, p = 0.009). Median survival past landmark time was 27.43 months in the PORT group and 25.86 months in the non-PORT group. Factors significantly associated with receiving PORT were facility location, facility type, Charlson-Deyo comorbidity index, and grade (all p < 0.05).ConclusionsImproved survival is associated with receipt of PORT for patients with pathologic stage IIIA (N2) NSCLC treated with complete resection and multiagent chemotherapy.     

The role of postoperative radiotherapy (PORT) in pulmonary large cell neuroendocrine carcinoma (PLCNEC)

PurposeTo assess the long-term survivals and related prognostic indicators of patients with pulmonary large cell neuroendocrine carcinoma (PLCNEC), and determine the prognostic value of post-operative radiotherapy in PLCNEC.Materials and methodsPatients diagnosed with PLCNEC between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were included in our study. Cox proportional hazard model was used to evaluate the factors related to overall survival (OS). Propensity score matching analysis (PSM analysis) was used to balance the variables differences between postoperative radiotherapy (PORT) and non-PORT groups.ResultsA total of 701 postoperative cases were identified, with the median follow-up time of 23 months. The 3- and 5-year OS were 50.7%, and 41.2%, respectively. Multivariate analysis revealed that stage I (P < 0.001), age < 65 years old (P < 0.001), chemotherapy (P < 0.001) were independent favorable prognostic factors. There is no significant difference in survival between patients with or without postoperative radiotherapy (PORT) after PSM analysis (P = 0.489). No survival benefit in favor of PORT were displayed, even when subgroups were deeply analyzed.ConclusionsAge, stage, and chemotherapy were significantly associated with OS of patients with resected PLCNEC. However, PORT after resection did not improve long-term outcome of PLCNEC patients.     

乳腺癌腋窝淋巴结清扫术后阴性淋巴结数目的临床意义(英文)

Objective: The purpose of this study was to evaluate the impact of the negative lymph node (LN) count on the survival of the breast cancer patients in early stage after the axillary dissection. Methods: The breast cancer patients with T1-2N0-1M0 stage between January 2001 and December 2005 in Jiangsu Cancer Hospital, who underwent the axillary LNs dissection, were enrolled in this study. We analyzed the data of these patients including information of follow-up and postoperative pathological results. All patients were divided into two groups according to the axillary LN status and each group was divided into four subgroups according to the negative LN count. Cox regression analysis was performed to screen the pathological factor including the negative LN count on the survival and to compare the different negative LN count on the survival. Results: COX proportional hazard regression model showed that the survival of the breast cancer was significantly associated with the negative LN count. In T1-2N0 group, when the negative LN count was 3 or less, 4 to 5, 6 to 9 and 10 or more, the median survival time was (82.6 ± 4.1) months, (101.5 ± 1.3) months, (104.7 ± 1.0) months, and (110.5 ± 0.9) months respectively (P < 0.05). In T1-2N1 group, when the negative LN count was 6 or less, 7 to 8, 9 to 10 and 11 or more, the median survival time was (95.4 ± 1.9) months, (101.8 ± 1.1) months, (104.9 ± 1.0) months, and (106.5 ± 0.9) months respectively (P < 0.05). Conclusion: The negative LN count can reflect the adequacy of the axillary dissection. Increasing negative LN count is independently associated with improved survival in pT1-2N0M0 or pT1-2N1M0 staging breast cancer patients. The negative LN count should be considered for incorporation into staging for breast cancer with the axillary LN dissection.     

Survival impact of postoperative radiotherapy in patients with olfactory neuroblastoma: 513 cases from the SEER database

PuposeTo evaluate the impact of postoperative radiotherapy (PORT) on survival in olfactory neuroblastoma (ONB) patients with different tumor staging.Material and methodsPatients with ONB were selected in the Surveillance, Epidemiology and End Results (SEER) database from 2004–2016. Survival analyses were performed using Kaplan–Meier (K-M) method, Cox regression analysis, and competing risk model.ResultsA total of 513 patients were included in the study. Univariate and multivariate analysis results demonstrated that PORT was not an independent prognostic factor for overall survival (OS) of modified Kadish stage A and B patients (P = 0.699 and P = 0.248, respectively). Kadish stage C and D patients who underwent PORT had significantly better OS than those who did not undergo PORT (P = 0.03 and P < 0.0001). K-M curves revealed that the 5- and 10-year OS rates of patients who underwent PORT vs. non-PORT were 85.3% vs. 70.4% and 68.2% vs. 56.8% in stage C patients, respectively. For stage D patients, the 5-year OS rates were 70.7% and 42.6%, and 10-year OS rates were 53.4% and 29.5% in the PORT and non-PORT groups, respectively. The competitive risk model revealed that the 5-year cancer-specific cumulative mortality incidence decreased by 26.6% while the 10-year mortality incidence decreased by 41.4% in Kadish stage C patients who were treated using PORT; meanwhile, for Kadish stage D patients who were treated with PORT, the 5- and 10-year mortality incidences were reduced by 35.3% and 42.6%, respectively. Furthermore, we found that chemotherapy was not related to the prognosis of ONB patients (all P > 0.05).ConclusionOur results indicate that PORT improved survival outcomes of modified Kadish stage C and D ONB patients. However, PORT may not affect survival for modified Kadish stage A and B individuals. Chemotherapy was not recommended for ONB; therefore, further studies are warranted to determine its therapeutic significance.     

Postoperative Radiotherapy for Patients With Completely Resected Pathologic N2 Non–Small-Cell Lung Cancer: A Retrospective Analysis

BackgroundAdjuvant radiotherapy in non–small-cell lung cancer (NSCLC) is still controversial. The purpose of this retrospective study was to evaluate the role of postoperative radiotherapy (PORT) in terms of local control and survival in pathologic N2 NSCLC.Patients and MethodsFrom January 2003 to December 2008, 66 patients with pathologic N2 NSCLC received PORT. Mediastinal lymph node metastases were classified into single (12 patients) or multiple (54 patients) stations. All patients received conformal radiation therapy, with a median total dose of 50.4 Gy. Target volumes included the bronchial stump, ipsilateral hilum, all pathologically involved lymph node regions, and all the lymph nodes between 2 noncontiguous pathologic nodal stations. The pattern of failure was considered as locoregional or systemic, or a combination of both. Locoregional failure was defined as in field or out of field.ResultsMedian follow-up time was 34.9 months (range 3.5-62.8 months). Local control was 80% at 12 months, 77.2% at both 24 and 36 months, and 72.1% at 60 months. The pattern of failure was locoregional in 3 patients (1 out of field and 2 in field) and systemic in 25 patients, with 12 patients presenting both locoregional and distant disease. Overall survival at 12, 36, and 60 months was 77%, 44%, and 37%, respectively. Median survival time was 34 months. The number of pathologically involved lymph node stations was a prognostic factor for local control (P = .05), cancer-specific survival (CSS) (P = .04), and disease-free survival (DFS) (P = .04).ConclusionDespite the limitations of the present study, mainly represented by its retrospective nature, our data support the role of PORT in terms of locoregional control and overall survival benefit; the number of involved mediastinal lymph nodes represents a significant prognostic factor in patients with pathologic N2 NSCLC.     

The impact of surgery on the multidisciplinary treatment of bronchogenic small cell carcinoma

Recent results of studies on patients with SCLC treated by surgery with curative intent followed by adjuvant chemotherapy demonstrate a definite progress in comparison to non-surgical-treatment programs for patients with comparable stage of disease. Of 186 randomized patients enrolled for the multicenter cooperative ISC-Study I and II, 76 patients with stage pT_1-3N₀M₀ received surgery for cure followed by chemotherapy and selective radiotherapy to the brain. The projected 4 year crude survival rate by September 1991 was 57 %. In 27 of 43 patients with stage PT_1-3N₂M₀, the tumors were completely resected, resulting in a 4 year survival rate of 32%. The survival curve for both groups of patients shows a sharp bent at 27 months postoperatively, whereafter the survival curves take a plateau-like course.

These promising results were confirmed by several other groups. They are in favour of initial surgery for resectable tumors, followed by postoperative chemotherapy, while patients on preoperative chemotherapy followed by adjuvant surgery showed less favourable results.

     

Neoadjuvant Chemotherapy With Docetaxel-Cisplatin in Patients With Stage III N2 Non–Small-Cell Lung Cancer

IntroductionTo assess the efficacy and potential prognostic factors of patients with stage III N2 non–small-cell lung cancer (NSCLC) treated with neoadjuvant docetaxel-cisplatin (DP) chemotherapy followed by surgical resection.MethodsSixty-two patients with NSCLC treated with DP as neoadjuvant chemotherapy between November 2003 and December 2009 were identified and reviewed in this study. Tumor response, survival, and clinicopathologic data were collected retrospectively. The time to event was analyzed by fitting Cox proportional hazards models.ResultsFifty-eight (94%) of 62 patients eventually underwent surgical resection after DP. The overall clinical response rate to induction DP chemotherapy was 42%. Patients with squamous cell carcinoma (SCC) histology were more likely to response to the DP regimen than those with adenocarcinoma histology (68% vs. 33%, P = .006). With a median follow-up of 82.4 months among the 58 patients, there were 41 (71%) tumor relapses and 27 (47%) deaths. The median event-free survival was 27.5 months (95% CI, 22.3-32.7 months), and the median overall survival was 66.7 months (95% CI, 35.1-98.3 months). In multivariate analysis, when fitting the Cox proportional hazards model, SCC histology (hazard ratio [HR] 0.234 [95% CI, 0.098-0.560]; P = .001) and mediastinal downstaging to N0 (HR 0.451 [95% CI, 0.226-0.898]; P = .024) were independent predictors of better event-free survival.ConclusionsNeoadjuvant chemotherapy with the DP regimen is both active and well tolerated in patients with stage III N2 NSCLC. SCC histology predicted a better treatment response and survival outcome than adenocarcinoma histology in this patient group. Further investigation of combined-modality treatment is warranted to improve survival in the adenocarcinoma subset of stage III N2 NSCLC.     

Postoperative Radiotherapy for Locally Advanced NSCLC: Implications for Shifting to Conformal,High-Risk Fields

BackgroundTo examine the effect of radiotherapy field size on survival outcomes and patterns of recurrence in patients treated with postoperative radiotherapy (PORT) for non–small-cell lung cancer (NSCLC).MethodsWe retrospectively reviewed the records of 216 patients with T1-4 N1-2 NSCLC following surgery and PORT using whole mediastinum (WM) or high-risk (HR) nodal fields from 1998 to 2015. Survival rates were calculated using the Kaplan-Meier method. Univariate and multivariable analyses were conducted using Cox proportional hazards modeling for outcomes and logistic regression analysis for treatment toxicities.ResultsMedian follow-up was 28 months (interquartile range [IQR] 13-75 months) and 38 months (IQR 19-73 months) for WM (n = 131) and HR (n = 84) groups, respectively. Overall survival (OS) was not significantly different between groups (median OS: HR 49 vs. WM 32 months; P = .08). There was no difference in progression-free survival (PFS), freedom from locoregional recurrence (LRR), or freedom from distant metastasis (P > .2 for all). Field size was not associated with OS, PFS, or LRR (P > .40 for all). LRR rates were 20% for HR and 26% for WM groups (P = .30). There was no significant difference in patterns of initial site of LRR between groups (P > .1). WM fields (OR 3.73, P = .001) and concurrent chemotherapy (odds ratio 3.62, P = .001) were associated with grade ≥2 toxicity.ConclusionsLocoregional control and survival rates were similar between PORT groups; an improved toxicity profile was observed in the HR group. Results from an ongoing prospective randomized clinical trial will provide further insight into the consequences of HR PORT fields.     

Prognostic role of Twist, Slug, and Foxc2 expression in stage I non-small-cell lung cancer after curative resection

BackgroundLung cancer is the leading cause of cancer-related death in the world. Only about 60% of patients with stage I non–small-cell lung cancer (NSCLC) can be cured by surgery alone. Current clinical and molecular markers are inadequate prognosticators. We developed a 3-marker model that closely approximates survival probability of patients with stage I NSCLC.MethodsExpression of Twist, Slug, and Foxc2 was assessed by immunohistochemistry in tissue microarrays that contained paired tumor and peritumoral lung tissue from 137 patients who underwent surgical resection for stage I NSCLC. The prognostic value of Twist, Slug, and Foxc2, and the cumulative effects of the 3 markers on survival were evaluated.ResultsIncreased expression of Twist, Slug, and Foxc2 was observed in 38.0%, 18.2%, and 27.7% of primary tumors, respectively. Overexpression of Twist, Slug, and Foxc2 in stage I NSCLC was associated with a worse overall survival (P = .001, P = .002, P < .001, respectively) and correlated with a shorter recurrence-free survival (P < .001, P = .001, P < .001 respectively). The cumulative influence of these markers on outcome was analyzed; a combination of more than 2 positive markers was an independent predictor of recurrence-free and overall survival (P = .002 and P = .009, respectively).ConclusionsThe Twist/Slug/Foxc2 model is useful in predicting survival of stage I NSCLC and may be helpful in refining current treatment strategy.     

Correlation of DNA Repair Gene Polymorphisms With Clinical Outcome in Patients With Locally Advanced Non–Small-Cell Lung Cancer Receiving Induction Chemotherapy Followed by Surgery

ObjectiveThe aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-B non–small-cell lung cancer (NSCLC) treated with neoadjuvant gemcitabine/cisplatin/docetaxel followed by surgery.Materials and MethodsA total of 109 patients with stage IIIA and IIIB NSCLC were prospectively genotyped to examine a potential association between XPD 312 (aspartic acid [Asp]/asparagine [Asn]), XPD 751 (lysine [Lys]/glutamine [Gln]), and RRM1 (−37 C/A) polymorphisms with response and survival.ResultsThe median survival was 32.14 months for carriers of XPD 312 Asp/Asp and 12.04 months for those with the variant Asn allele (P = .05). In addition, event-free survival was longer for patients with the XPD 312 Asp/Asp genotype compared with patients with Asp/Asn or Asn/Asn (P = .03). A similar but nonsignificant trend was observed for the XPD 751 genotype. In a multivariate analysis, complete resection and age emerged as prognostic factors for overall survival; in patients with incomplete resection or exploratory thoracotomy, XPD 312 was the most significant prognostic factor (P = .03).ConclusionThe XPD 312 single nucleotide polymorphism is a prognostic factor for survival in patients with locally advanced NSCLC receiving induction chemotherapy followed by surgery. The Asn allele is associated with unfavorable outcome and could be used for better stratification of patients.     

Prognostic Impact of Mediastinal Lymph Node Dissection in Octogenarians With Lung Cancer: JACS1303

IntroductionThe prognostic significance of mediastinal lymph node dissection (MLND) in elderly patients with non–small cell lung cancer (NSCLC) remains unclear. This post hoc analysis of a nationwide multicenter cohort study (JACS1303) evaluated the prognostic significance of MLND in octogenarians with NSCLC.Materials and MethodsWe included 622 octogenarians with NSCLC who underwent lobectomy. The median follow-up duration was 41.1 months. We compared survival and perioperative outcomes between patients who did and did not undergo MLND.ResultsIn total, 414 (67%) patients underwent MLND (ND2 group), whereas 208 (33%) did not undergo MLND (ND0-1 group). The disease stage was more advanced in the ND2 group than in the ND0-1 group. Disease-free survival was slightly greater in the ND0-1 group with marginal significance (P= .079). In the matched cohort (N = 228), which mainly consisted of patients with clinical stage I disease (96%), there was no significant difference between the 2 groups regarding overall and disease-free survival (P= .908 and P = .916, respectively). Operative time and blood loss were significantly lower in the ND0-1 group than in the ND2 group in the entire cohort (P< .001 and P = .050, respectively) and in the matched cohort (P = .003 and P= .046, respectively).ConclusionBased on a nationwide prospective database, we found limited prognostic impact of MLND, suggesting that MLND can be omitted for octogenarians with early-stage NSCLC.     

Modern post-operative radiotherapy for stage III non-small cell lung cancer may improve local control and survival: A meta-analysis

Background

We hypothesized that modern postoperative radiotherapy (PORT) could decrease local recurrence (LR) and improve overall survival (OS) in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC).

Methods

To investigate the effect of modern PORT on LR and OS, we identified published phase III trials for PORT and stratified them according to use or non-use of linear accelerators. Non-individual patient data were used to model the potential benefit of modern PORT in stage IIIA-N2 NSCLC treated with induction chemotherapy and resection.

Results

Of the PORT phase III studies, eleven trials (2387 patients) were included for OS analysis and eight (1677 patients) for LR. PORT decreased LR, whether given with cobalt, cobalt and linear accelerators, or with linear accelerators only. An increase in OS was only seen when PORT was given with linear accelerators, along with the most significant effect on LR (relative risk for LR and OS 0.31 (p = 0.01) and 0.76 (p = 0.02) for PORT vs. controls, respectively).Four trials (357 patients) were suitable to assess LR rates in stage III NSCLC treated with surgery, in most cases after induction chemotherapy. LR as first relapse was 30% (105/357) after 5 years. In the modeling part, PORT with linear accelerators was estimated to reduce LR rates to 10% as first relapse and to increase the absolute 5-year OS by 13%.

Conclusions

This modeling study generates the hypothesis that modern PORT may increase both LR and OS in stage IIIA-N2 NSCLC even in patients being treated with induction chemotherapy and surgery.     

Adjuvant chemotherapy for elderly patients with stage I non-small-cell lung cancer ≥4 cm in size: an SEER–Medicare analysis

We have used population-based data from the SEER–Medicare registry to show that adjuvant chemotherapy is associated with improved survival among elderly patients with early-stage non-small-cell lung cancer ≥4 cm. These findings extend the results of a prior RCT to the growing population of older patients with cancer.BackgroundThe role of adjuvant chemotherapy for non-small-cell lung cancer (NSCLC) stage I patients with tumors size ≥4 cm is not well established in the elderly.Patients and methodsWe identified 3289 patients with stage I NSCLC (T2N0M0 and tumor size ≥4 cm) who underwent lobectomy from the Surveillance, Epidemiology and End Results (SEER)–Medicare linked database diagnosed from 1992 to 2009. Overall survival and rates of serious adverse events (defined as those requiring admission to hospital) were compared between patients treated with resection alone, platinum-based adjuvant chemotherapy, or postoperative radiation (PORT) with or without adjuvant chemotherapy. Propensity scores for receiving each treatment were calculated and survival analyses were conducted using inverse probability weights based on the propensity score.ResultsOverall, 84% patients were treated with resection alone, 9% received platinum-based adjuvant chemotherapy, and 7% underwent PORT with or without adjuvant chemotherapy. Adjusted analysis showed that adjuvant chemotherapy [hazard ratio (HR), 0.82; 95% confidence interval (CI) 0.68–0.98] was associated with improved survival compared with resection alone. Conversely, the use of PORT with or without adjuvant chemotherapy (HR 1.91; 95% CI 1.64–2.23) was associated with worse outcomes. Patients receiving adjuvant chemotherapy had more serious adverse events compared with those treated with resection alone, with neutropenia (odds ratio, 21.2; 95% CI 5.8–76.6) being most significant. No significant difference was observed in rates of fever, cytopenias, nausea, and renal dysfunction.ConclusionsPlatinum-based adjuvant chemotherapy is associated with reduced mortality and increased serious adverse events in elderly patients with stage I NSCLC and tumor size ≥4 cm.     

Nephroureterectomy and segmental ureterectomy in the treatment of invasive upper tract urothelial carcinoma: A population-based study of 2299 patients

PurposeThe TNM staging system represents the cornerstone for classifying patients with upper tract urothelial carcinoma (UTUC). We tested the prognostic impact of pT and pN stages on cancer-specific mortality (CSM) in a large population-based cohort of surgically treated patients with UTUC.MethodsOur analyses relied on 2299 patients treated with nephroureterectomy (NU) or segmental ureterectomy (SU) for UTUC within nine Surveillance, Epidemiology and End Results registries between 1988 and 2004. CSM rates after surgery were graphically explored using Kaplan–Meier plots. Univariable and multivariable Cox regression models tested the effect of pT and pN stages on CSM, after adjusting for tumour grade, age, gender, primary tumour location, type and year of surgery.ResultsFive years after surgery, the overall CSM-free survival rate was 77.6%. The 5-year CSM-free survival rates of pT₁N₀ (n = 739), pT₂N₀ (n = 422), pT₃N₀ (n = 691), pT₄N₀ (n = 190) and any T N_1–3 (n = 257) were, respectively, 93.5 versus 86.2 versus 64.5 versus 54.7 versus 35.0%. The 5-year CSM-free survival rates of pT_1–2N_1–3 (n = 41) and pT_3–4N_1–3 (n = 216) patients were, respectively, 68.9% and 28.7% (p = 0.006). In multivariable analyses, pT and pN stages (p < 0.001), as well as tumour grade (p < 0.001), achieved independent predictor status. Advanced age adversely affected CSM-free survival (p = 0.001). Conversely, tumour location, gender, year and type of surgery did not exert independent predictor status.ConclusionDurable cancer control can be expected in patients treated with NU or SU for organ-confined (pT_1–2) UTUC. Conversely, the presence of non-organ-confined (pT_3–4) disease and/or of nodal metastases (pN_1–3) exerts a profound detrimental effect on CSM-free survival.     

术后辅助3DRT改善pT2－3N0M0期食管癌患者长期生存

目的 评价3DRT (3DCRT、IMRT)在pT_2－3N₀M₀期胸段食管鳞癌根治术后辅助治疗中的临床价值。方法 分析2004—2011年本院入组pT_2－3N₀M₀期胸段食管鳞癌根治术后3DRT前瞻性非随机Ⅱ期临床研究的96例及同期全部单纯手术820例患者的复发、生存及放疗不良反应。Kaplan-Meier法计算生存率并Logrank检验,Cox模型预后多因素分析。结果 术后放疗组T₃期、肿瘤长度≥5 cm患者比例显著高于单纯手术组。术后放疗、单纯手术组5年样本数分别为35、270例。术后放疗、单纯手术组5年OS率分别为74.3%、59.9%(P=0.010),5年DFS率分别为71.0%、51.7%(P=0.002)。多因素分析显示术后放疗是影响OS、DFS的因素(P=0.030、0.004)。术后放疗组和单纯手术组总复发率、LRR率、远处转移率分别为22.9%和43.0%(P=0.000)、18.8%和35.2%(P=0.001)、11.5%和21.3%(P=0.024)。术后放疗组25例(26.0%)发生3级早晚期不良反应。结论 辅助3DRT较单纯手术降低了pT_2－3N₀M₀期胸段食管鳞癌术后复发率,提高了5年DFS、OS且不良反应反应可耐受,但还需前瞻性Ⅲ期随机研究证实。     

The Significance of Lymph Node Ratio and Total Lymph Nodes Examined in Determining the Indications of Adjuvant Radiation in pN2 Non–small Cell Lung Cancer

Introduction/BackgroundPast studies have shown mixed results of postoperative radiation (PORT) for pN2 NSCLC patients. We hypothesize that PORT can improve overall survival (OS) in pN2 NSCLC patients with high lymph node ratio (LNR).Materials/MethodsThe National Cancer Database was queried for non-metastatic pN2 NSCLC patients with R0 surgery and adjuvant chemotherapy from 2004 to 2016. Cox models were used to assess the impact of PORT and LNR on OS adjusted for patient characteristics and treatment information.ResultsAmong 4,050 patients, 1,728 (42.7%) had PORT. There was increased use of IMRT in the more recent period (53.8% in 2010-2016 vs 24.0% in 2004-2009). PORT was associated with better OS in the overall cohort. For patients with inadequate lymph node dissection (LND), PORT marginally improved OS (HR = 0.91, p = 0.058). Among patients with adequate LND, PORT did not improve OS for patients with LNR <15% (HR = 1.11, p = 0.21), or LNR 15-29% (HR = 1.03, p = 0.73), but it significantly improved OS for patients with LNR ≥30% (HR = 0.83, p = 0.006). In patients with LNR≥30%, IMRT significantly improved OS when compared to no PORT (HR = 0.75, p < 0.05) while 3D RT did not (HR = 0.89, p = 0.32).ConclusionsPORT was associated with better survival for pN2 NSCLC patients after R0 resection, adequate LND with high LNR, after accounting for multiple confounders. Among the whole cohort, most of the OS benefits of PORT were driven by patients with inadequate LND, high LNR or use of IMRT.