Adding Radiotherapy to Adjuvant Chemotherapy Does Not Improve Survival of Patients With N2 Lung Cancer

Drake, Justin; Portnoy, David C.; Tauer, Kurt W.; Weksler, Benny

doi:10.1016/j.athoracsur.2018.04.074

Cited by 17 publications

(9 citation statements)

References 29 publications

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“…A post hoc analysis of the Adjuvant Navelbine International Trialist Association (ANITA) trial supported the use of adjuvant chemoradiation [3], but meta-analyses and randomized trials have failed to demonstrate a benefit of adding radiation to adjuvant chemotherapy [4,5]. Our work using a propensity-matched cohort from the National Cancer Database did not demonstrate any benefit of adding radiation therapy in patients with clinical N0 disease found to have N2 disease at operation [6].…”

Section: Reply To the Editormentioning

confidence: 74%

PORT in Properly Selected Patients With Completely Resected Non-Small Cell Lung Cancer Should Not Be Quickly Dismissed

Shaikh

Cerfolio

et al. 2019

The Annals of Thoracic Surgery

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We read with interest the study published in The Annals of Thoracic Surgery titled, "Adding Radiation to Adjuvant Chemotherapy Does Not Improve Survival of Patients With N2 Lung Cancer" by Drake and colleagues [1]. Although we commend Drake and colleagues [1], we would like to address several reasons that the conclusions contradict the retrospective Adjuvant Navelbine International Trialist Association (ANITA) trial results [2], as well as another rigorous National Cancer Data Base study finding a benefit to postoperative radiation therapy (PORT) [3].Drake and colleagues [1] sampled roughly 3,000 N2 patients after including only clinically node-negative (cN0) patients. By doing so they excluded thousands of patients who were coded as clinically node negative ("cX") but who were coded pathologically as N2 in the database. Many patients without a clinical node stage who were found to be N2 at resection were excluded.Furthermore, in this study the interquartile range for radiation dose was 4,500 to 5,400 cGy, which suggests that the bottom quartile (n ¼ 220) received less than 4,500 cGy, a dose that may have not been associated with curative intent. Similarly, some patients may have received greater than 6,000 cGy in the postoperative setting, which is not clinically practiced in patients with negative margins.It is not addressed whether standard of care multiagent chemotherapy was included and whether radiation was administered concurrently or sequentially. Chemotherapy is usually not given concurrently because of toxicity. There is a National Cancer Data Base analysis revealing a survival disadvantage to concurrent chemotherapy with PORT [4].Drake and colleagues [1] also do not detail the extent of resection between groups. It is therefore unclear whether the extent of resection was balanced. Studies have demonstrated a survival disadvantage to PORT after pneumonectomy.In summary, readers interpret study results cautiously when there are unclear data within the methods.

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Section: Reply To the Editormentioning

confidence: 74%

PORT in Properly Selected Patients With Completely Resected Non-Small Cell Lung Cancer Should Not Be Quickly Dismissed

Shaikh

Cerfolio

et al. 2019

The Annals of Thoracic Surgery

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“…A recent randomized Phase II trial by Sun et al found no survival benefit for adjuvant concurrent chemoradiotherapy compared with adjuvant platinum-based chemotherapy alone (20). This finding has been supported by previous retrospective studies as well that suggest that there are no overall survival benefits to addition of adjuvant radiotherapy versus adjuvant chemotherapy alone (10,13,21). The findings of Sun et al must be interpreted cautiously, however, as sequential radiotherapy administered after adjuvant chemotherapy, rather than concurrent chemoradiotherapy, is more frequently performed (8,22,23).…”

Section: Discussionmentioning

confidence: 89%

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

Lieu¹,

Li²,

David³

et al. 2021

J Thorac Dis

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Background: Positive 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. Methods: The 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. Results: There were 8,189 patients included: pN2 (5,416), positive margins (2,386), and both (387). Fiveyear 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). Conclusions: In 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.

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“…However, some clinical trials revealed that PORT could only improve the local control of stage IIIA/N2 NSCLC, but failed to bring DFS or OS benefit ( 7 - 8 ). The phase III RCT, NCT00880971, enrolled 364 completely resected stage IIIA/N2 NSCLC patients from 2009 to 2017 ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

“…PORT could improve the local control, 5-years survival rate, and OS time ( 5 - 6 ). Unfortunately, some other studies found that PORT failed to bring disease-free survival (DFS) or OS benefit ( 7 - 8 ). The randomized controlled trials (RCTs) showed that PORT could only increase local recurrence-free rate ( 9 - 10 ).…”

Section: Introductionmentioning

confidence: 99%

The Prognostic Role of PORT and EGFR Mutation Status in Completely Resected Stage IIIA/N2 Non-Small Cell Lung Cancer Patients with Postoperative Chemotherapy

Yang

Wang

et al. 2021

Pathol. Oncol. Res.

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Background: The treatment choice for completely resected stage IIIA/N2 non-small cell lung cancer (NSCLC) patients is still controversial now. Our study aims to identify potential prognostic factors in stage IIIA/N2 NSCLC patients with complete surgical resection and postoperative chemotherapy.Methods: In this study, we screened the stage IIIA/N2 NSCLC patients diagnosed in the Affiliated Cancer Hospital of Zhengzhou University from 2015 to 2019. Completely resected patients with postoperative chemotherapy (PCT) were enrolled. The univariate and multivariate COX proportional hazards regression analyses were used to identify the prognostic factors. The Kaplan-Meier survival curve was used to compare the disease-free survival (DFS) and overall survival (OS) in the subgroup analyses.Results: 180 patients were collected, including 142 patients with PCT treatment alone and 38 patients with postoperative radiotherapy (PORT) treatment. The median DFS was 17.8 months (95% CI: 16.5–19.1 months) and the median OS was 50.6 months (47.4–53.9 months) in all the patients. The median DFS of the PORT group was significantly longer than the PCT group (38.7 vs 16.7 months, p < 0.001). Epidermal growth factor receptor (EGFR) mutation-positive patients had a worse DFS compared with EGFR mutation-negative patients (16.8 vs 18.0 months, p = 0.032). Possible prognostic factors were evaluated through univariate COX regression analysis. The further multivariate COX regression analysis showed that patients with PORT (HR: 0.318, 95% CI: 0.185–0.547, p < 0.001), EGFR mutation-negative (HR: 0.678, 95% CI: 0.492–0.990, p = 0.044), T1 (HR: 0.661, 95% CI: 0.472–0.925, p = 0.016), and lobectomy (HR: 0.423, 95% CI: 0.191–0.935, p = 0.034), had better DFS. The only independent prognostic factor of OS was the type of surgery (p = 0.013).Conclusion: PORT might improve the DFS of stage IIIA/N2 NSCLC patients with complete surgical resection and PCT, but it cannot increase OS. Besides, EGFR mutation status, T stage, and type of surgery are possible independent prognostic factors for DFS, and type of surgery is associated with OS. These factors remain to be clarified in further studies.

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Adding Radiotherapy to Adjuvant Chemotherapy Does Not Improve Survival of Patients With N2 Lung Cancer

Cited by 17 publications

References 29 publications

PORT in Properly Selected Patients With Completely Resected Non-Small Cell Lung Cancer Should Not Be Quickly Dismissed

PORT in Properly Selected Patients With Completely Resected Non-Small Cell Lung Cancer Should Not Be Quickly Dismissed

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

The Prognostic Role of PORT and EGFR Mutation Status in Completely Resected Stage IIIA/N2 Non-Small Cell Lung Cancer Patients with Postoperative Chemotherapy

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