Prophylactic Cranial Irradiation in Locally Advanced Non–Small-Cell Lung Cancer After Multimodality Treatment: Long-Term Follow-Up and Investigations of Late Neuropsychologic Effects

Stuschke, Martin; Eberhardt, Wilfried Ernst Erich; Pöttgen, Christoph; Stamatis, Georgios; Wilke, H.; Stüben, Georg; Stöblen, F.; Wilhelm, Hans; Menker, H.; Teschler, Helmut; Müller, R.-D.; Budach, Volker; Seeber, S.; Sack, H.

doi:10.1200/jco.1999.17.9.2700

Cited by 179 publications

(130 citation statements)

References 39 publications

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“…[1][2][3] This is the first site of recurrence in 15% to 40% of these patients, and autopsy studies have demonstrated that a substantial proportion of those who die of intrathoracic or extracranial disease progression from NSCLC also have synchronous brain metastasis. [3][4][5][6] Several authors have therefore suggested that with improvements in overall survival and localregional control from effective multimodality regimens incorporat-ing chemotherapy with radiation and/or surgery the incidence and relative importance of brain metastases among patients with locally advanced NSCLC has visibly increased.…”

Section: Discussionmentioning

confidence: 99%

“…Additional analysis reveled that 34% of patients recurred in the brain as the first site of failure, which was associated with a 4-fold increase in death. Stuschke et al 1 compared the outcomes of 47 patients treated with PCI to 28 patients who did not receive PCI after neoadjuvant chemotherapy followed by chemoradiotherapy and surgery. The authors found that PCI significantly reduced the rate of brain metastases as the first site of recurrence from 30% to 8% at 4 years and that of overall brain recurrence from 54% to 13%.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6] Patients who achieve a pCR after neoadjuvant chemotherapy or chemoradiotherapy for locally advanced NSCLC have a risk of death from brain metastases that exceeds potential mortality due to extracranial disease progression. Similar to others, we found that this risk was more elevated in patients with nonsquamous cell types compared with those with squamous histology.…”

Section: Discussionmentioning

confidence: 99%

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Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall‐cell lung cancer

Chen

Jahan

Jablons

et al. 2007

Cancer

127

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BACKGROUND. The incidence and pattern of brain metastases was analyzed among patients who achieved a pathological complete response (pCR) after neoadjuvant chemotherapy or chemoradiotherapy for locally advanced nonsmall‐cell lung cancer (NSCLC). METHODS. Between 1990 and 2004, 211 patients were treated with neoadjuvant therapy before surgical resection for stage III NSCLC. The clinical course of 51 patients who demonstrated a pCR were reviewed. The neoadjuvant regimen consisted of either chemotherapy (29 patients) or chemoradiotherapy (22 patients). Histology was 45% adenocarcinoma, 41% squamous cell, and 14% large cell carcinoma. No patient received prophylactic cranial irradiation (PCI). RESULTS. Overall survival at 1, 3, and 5 years was 82%, 63%, and 42%, respectively. The most common site of initial recurrence was the brain. Twenty‐two (43%) patients developed brain metastasis as the site of first failure, which represented 71% of all isolated recurrences. Ultimately, 28 (55%) patients developed brain metastases at some point during their clinical course. The 5‐year estimates of brain metastasis‐free survival for patients with squamous and nonsquamous cancers were 57% and 34%, respectively (P = .02). Median survival from the time of brain metastasis was 10 and 5 months for those with isolated and nonisolated recurrences, respectively. CONCLUSION. Patients with a pCR after multimodality therapy for locally advanced NSCLC are at excessively high risk for the subsequent development of brain metastases. Implications for management strategies including PCI and stereotactic radiosurgery (SRS) are discussed. Cancer 2007. © 2007 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall‐cell lung cancer

Chen

Jahan

Jablons

et al. 2007

Cancer

127

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“…One of the major problems with the use of combined modality treatment for locally advanced NSCLC is the high risk of brain metastasis (Stuschke et al, 1999;Thomas et al, 1999). A substantial proportion of patients undergoing successful R0 resection suffer from brain-only relapse.…”

Section: Specific Diseases Stage III N2 Diseasementioning

confidence: 99%

“…A substantial proportion of patients undergoing successful R0 resection suffer from brain-only relapse. A non-randomised observational study suggested that prophylactic cranial irradiation (PCI) might reduce the risk of brain metastasis in these patients (Stuschke et al, 1999). Whether or not PCI would benefit optimally treated patients with locally advanced NCLC is now under investigation in randomised trials.…”

Section: Specific Diseases Stage III N2 Diseasementioning

confidence: 99%

How to evaluate the risk/benefit of trimodality therapy in locally advanced non-small-cell lung cancer

Kunitoh¹,

Suzuki²

2007

Br J Cancer

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The trimodality approach represented by concurrent chemoradiotherapy followed by surgical resection is a highly effective, but potentially toxic therapy for locally advanced non-small-cell lung cancer (NSCLC). In this review, we discuss the current status of this therapy in patients with mediastinal node-positive (N2) stage III NSCLC or superior sulcus tumor, and present an overview of the principles for optimisation of the risk/benefit. Numerous clinical questions remain, and enrolment of patients into well-designed clinical trials should be encouraged.

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Prophylactic Cranial Irradiation vs Observation in Patients With Locally Advanced Non–Small Cell Lung Cancer

Sun

Wong

et al. 2019

JAMA Oncol

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IMPORTANCE Brain metastasis (BM) rates are high in locally advanced non-small cell lung cancer (LA-NSCLC), approaching rates seen in small cell lung cancer, where prophylactic cranial irradiation (PCI) is standard of care. Although PCI decreases the incidence of BM in LA-NSCLC, a survival advantage has not yet been shown. OBJECTIVE To determine if PCI improves survival in LA-NSCLC. DESIGN, SETTING, AND PARTICIPANTS Radiation Therapy Oncology Group (RTOG) 0214 was a randomized phase 3 clinical trial in stage III NSCLC stratified by stage (IIIA vs IIIB), histologic characteristics (nonsquamous vs squamous) and therapy (no surgery vs surgery). The study took place at 291 institutions in the United States, Canada, and internationally. Of 356 patients with stage III NSCLC entered onto this study, 16 were ineligible; therefore, 340 patients were randomized. INTERVENTION FOR CLINICAL TRIALS Observation vs PCI. MAIN OUTCOMES AND MEASURESThe primary outcome was overall survival (OS). The secondary end points were disease-free survival (DFS) and incidence of BM. RESULTSOf the 340 total participants, mean (SD) age was 61 years; 213 of the participants were men and 127 were women. The median follow-up time was 2.1 years for all patients, and 9.2 years for living patients. The OS for PCI was not significantly better than observation (hazard ratio [HR], 0.82; 95% CI, 0.63-1.06; P = .12; 5-and 10-year rates, 24.7% and 17.6% vs 26.0% and 13.3%, respectively), while the DFS (HR, 0.76; 95% CI, 0.59-0.97; P = .03; 5-and 10-year rates, 19.0% and 12.6% vs 16.1% and 7.5% for PCI vs observation) and BM (HR, 0.43; 95% CI, 0.24-0.77; P = .003; 5-and 10-year rates, 16.7% vs 28.3% for PCI vs observation) were significantly different. Patients in the PCI arm were 57% less likely to develop BM than those in the observation arm. Younger patients (<60 years) and patients with nonsquamous disease developed more BM. On multivariable analysis, PCI was associated with decreased BM and improved DFS, but not improved OS. Multivariable analysis within the nonsurgical arm suggests that PCI effectively prolongs OS, DFS, and BM. CONCLUSIONS AND RELEVANCEIn patients with stage III LA-NSCLC without progression of disease after therapy, PCI decreased the 5-and 10-year rate of BM and improved 5-and 10-year DFS, but did not improve OS. Although this study did not meet its primary end point, the long-term results reveal many important findings that will benefit future trials. Identifying the appropriate patient population and a safe intervention is critical.TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00048997

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Prophylactic Cranial Irradiation in Locally Advanced Non–Small-Cell Lung Cancer After Multimodality Treatment: Long-Term Follow-Up and Investigations of Late Neuropsychologic Effects

Cited by 179 publications

References 39 publications

Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall‐cell lung cancer

Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall‐cell lung cancer

How to evaluate the risk/benefit of trimodality therapy in locally advanced non-small-cell lung cancer

Prophylactic Cranial Irradiation vs Observation in Patients With Locally Advanced Non–Small Cell Lung Cancer

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