Treatment outcome for patients with primary nonsmall-cell lung cancer and synchronous brain metastasis

The purpose of this study was to evaluate the outcome of treatment for patients with newly diagnosed nonsmall-cell lung cancer (NSCLC) with an isolated, single, synchronous brain metastasis. A retrospective review was performed evaluating any patient diagnosed between 1982 and 1996 at the Cleveland Clinic Foundation with NSCLC metastatic only to the brain. Patients with multiple brain metastases or with systemic metastases to any other organ were excluded. Survival was measured from the date of the first treatment for malignancy. All hospital records were thoroughly reviewed in a retrospective manner. Thirty-three patients were identified who met the study criteria. Twelve patients had primary disease limited to the lung and hilar nodes, and 21 had more advanced primary disease with involvement of the mediastinum. Treatment of the chest was considered aggressive in 13 patients and palliative in 15. The primary tumor was observed in 5 patients. The management of the brain metastasis was as follows: 21 patients underwent surgical resection and postoperative whole brain radiotherapy (WBRT), 5 underwent stereotactic radiosurgery (SRS) and WBRT, 3 had resection alone, 2 had SRS alone, and 2 underwent WBRT alone. The median overall and disease-free survival for all patients was 6.9 months and 3.3 months, respectively. Overall survival was markedly improved with the addition of WBRT (P = 0.002) and with the aggressive management of the primary tumor (P = 0.005). A total of 9 patients experienced CNS failure, including both patients receiving WBRT alone. CNS failures were divided as follows: 3 local, 5 distant, and 1 local and distant. Two of the 4 patients with a local failure were salvaged, and ultimate local control of the original brain metastasis was achieved in 93.6% of cases. Survival remains poor for patients with Stage IV NSCLC even when metastatic disease is limited to a single site within the brain; however, aggressive therapy of both the lung primary and the brain metastasis may provide a survival advantage. Excellent local control of single brain metastases was achieved with a combination of WBRT with either surgical resection or SRS.     

Long-term survival in patients with synchronous, solitary brain metastasis from non-small-cell lung cancer treated with radiosurgery

PURPOSE: To report the outcome of patients with synchronous, solitary brain metastasis from non-small-cell lung cancer (NSCLC) treated with gamma knife stereotactic radiosurgery (GKSRS). PATIENTS AND METHODS: Forty-two patients diagnosed with synchronous, solitary brain metastasis from NSCLC were treated with GKSRS between 1993 and 2006. The median Karnofsky performance status (KPS) was 90. Patients had thoracic Stage I-III disease (American Joint Committee on Cancer 2002 guidelines). Definitive thoracic therapy was delivered to 26/42 (62%) patients; 9 patients underwent chemotherapy and radiation, 12 patients had surgical resection, and 5 patients underwent preoperative chemoradiation and surgical resection. RESULTS: The median overall survival (OS) was 18 months. The 1-, 2-, and 5-year actuarial OS rates were 71.3%, 34.1%, and 21%, respectively. For patients who underwent definitive thoracic therapy, the median OS was 26.4 months compared with 13.1 months for those who had nondefinitive therapy, and the 5-year actuarial OS was 34.6% vs. 0% (p < 0.0001). Median OS was significantly longer for patients with a KPS >or=90 vs. KPS < 90 (27.8 months vs. 13.1 months, p < 0.0001). The prognostic factors significant on multivariate analysis were definitive thoracic therapy (p = 0.020) and KPS (p = 0.001). CONCLUSIONS: This is one of the largest series of patients diagnosed with synchronous, solitary brain metastasis from NSCLC treated with GKSRS. Definitive thoracic therapy and KPS significantly impacted OS. The 5-year OS of 21% demonstrates the potential for long-term survival in patients treated with GKSRS; therefore, patients with good KPS should be considered for definitive thoracic therapy.     

Time for reappraisal of extracranial treatment options?

BACKGROUND.

The optimal treatment of the primary tumor in patients with brain metastases (BM) from newly diagnosed nonsmall cell lung cancer (NSCLC) remains unclear. The authors aimed to identify patient groups with synchronous BM for whom radical treatment of the primary site may be appropriate.

METHODS.

The medical records of 167 patients treated at our center between November 2000 and June 2009 for newly diagnosed NSCLC and synchronous BM were reviewed. All patients underwent surgery/radiosurgery (n = 86) or whole‐brain radiotherapy (WBRT; n = 81) for BM. Univariate and multivariate analyses assessed prognostic factors significant for overall survival (OS).

RESULTS.

Median OS of patients undergoing surgery/radiosurgery for BM was 12.1 months. Those undergoing “radical” thoracic treatment (n = 24) had a longer median OS (28.4 months) than those undergoing chemotherapy (n = 74; 12.1 months) or supportive therapy (n = 69; 5.6 months, P < .01). Patients with stage I thoracic disease (n = 23) had a longer median OS (18.5 months) than those with stage III (n = 43; 9.4 months) or with intra/extra‐thoracic metastases other than BM (stage IV; n = 20; 2.7 months, P < .01). Median OS of WBRT patients was 3.7 months. One patient underwent radical thoracic treatment. Patients undergoing chemotherapy (n = 42) had a longer median OS (5.7 months) than patients undergoing supportive therapy only (n = 38; 1.6 months, P < .01). Performance status and age were also associated with OS.

CONCLUSIONS.

Radical thoracic treatments may be justified in selected patients <65‐years‐old, eligible to undergo surgery/radiosurgery for synchronous BM from NSCLC, even when stage III thoracic disease is present. Cancer 2011. © 2010 American Cancer Society     

Gamma knife stereotactic radiosurgery for synchronous versus metachronous solitary brain metastases from non-small cell lung cancer

A retrospective study was conducted analyzing the clinical outcome and various prognostic factors in patients treated with gamma knife stereotactic radiosurgery (GK-SRS) for solitary brain metastasis from non-small cell lung carcinoma (NSCLC). A total of 72 patients from June of 1992 to January of 1999 were treated. All patients received GK-SRS to a median dose of 18Gy, with 45 patients receiving additional whole-brain radiation therapy. No one had evidence of extra-cranial metastasis at the time of diagnosis of brain metastases. The median follow-up was 15.7 months for the entire population and 99.5 months for those who were alive at the last follow-up. Univariate and multivariate analyses were used to test the impact of various prognostic factors on survival. The median and 5-year actuarial survivals for the entire cohort were 15.7 months and 10.4%, respectively. The presence of a metachronous versus a synchronous brain metastasis was the only factor significant in the univariate (P=0.045) and multivariate (P=0.002) analyses. Patients with metachronous solitary brain metastases had a significant median survival advantage compared to those with synchronous metastases (33.3 months versus 8.6 months, P=0.001). However, there was no statistically significant difference in median survival from the time of metastasis when treated with GK-SRS in these groups (12.5 months versus 8.4 months, P=0.50). The addition of WBRT did not improve overall survival (12.0 months versus 7.7 months, P=0.73). The 5-year actuarial survival for the metachronous and synchronous groups were 13.2 and 8.1%, respectively. In conclusion, patients presenting with a solitary metachronous brain metastasis from NSCLC achieved longer survivals than those with a synchronous metastasis. The tail in the survival curves demonstrates that a prolonged survival may be attained in patients with solitary metastases from NSCLC. This study adds to the growing body of literature that supports the use of SRS in the management of this patient population.     

Fractionated stereotactic body radiation therapy in the treatment of primary, recurrent, and metastatic lung tumors: the role of positron emission tomography/computed tomography-based treatment planning

PURPOSE: The aim of this study was to assess the outcomes of patients treated with stereotactic body radiation therapy (SBRT) in patients with primary, recurrent, or metastatic lung lesions, with a focus on positron emission tomography (PET)/computed tomography (CT)-based management. PATIENTS AND METHODS: Fifty-one patients with primary stage I non-small-cell lung cancer (NSCLC; n = 26), recurrent lung cancer after definitive treatment (n = 12), or solitary lung metastases (n = 13) were treated with SBRT between 2005 and 2007. Patients were treated with the CyberKnife Robotic Radiosurgery System with Synchrony respiratory tracking. A dose of 60 Gy was delivered in 3 fractions. All patients had CT or PET/CT performed at approximately 3-month intervals after treatment. RESULTS: The median follow-up was 12 months. Local control at median follow-up was 85% in patients with stage I NSCLC, 92% in patients with recurrent lung cancer, and 62% in the patients with solitary lung metastasis. Analysis of the 28 patients with pre- and post-treatment PET/CT scans demonstrated that those with stable disease (n = 4) had a mean standardized uptake value (SUV) decrease of 28%, partial responders (n = 11) had a decrease of 48%, and patients with a complete response (n = 11) had a decrease of 94%. Patients with progressive disease (n = 2) had an SUV decrease of only 0.4%. Only 2 patients (7%) who had reduced fluorodeoxyglucose avidity later progressed locally. No correlations were found between pretreatment SUV and tumor response, disease progression, or survival. Overall 1-year survival rates were 81%, 67%, and 85% among the patients with primary NSCLC, recurrent lung cancer, and solitary lung metastases, respectively. CONCLUSION: Stereotactic body radiation therapy with CyberKnife is an effective treatment for patients with medically inoperable recurrent or metastatic lung cancer. Positron emission tomography/CT is valuable in staging, planning, and evaluating treatment response and might predict long-term outcome.     

Surgery versus stereotactic radiosurgery for single synchronous brain metastasis from non-small cell lung cancer

Objective: The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery (SRS) for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer.Methods: Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years (range, 32(85 years). At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients (21.4%), lobectomies in 30 (71.4%), and wedge resection in 3 (7.2%). 48 patients (90.5%) underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS.Results: There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients (28.3%) had no evidence of lymph node metastases (N0), 20 patients (37.7%) had hilar metastases (N1), and 18 patients (34%) had mediastinal metastases (N2). The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant (P>0.05). In lymph node negative patients (N0), the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases (N1(2). The difference was significant (P<0.01). For adenocarcinomas, the 5-year survival rate was 5%. The correspondent data for squamous cell lung cancers was 3%. The difference was not significant (P>0.05).Conclusion: Although the overall survival rate for patients who have brain metastases from NSCLC is poor, surgical resection or radiosurgery may be beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.     

Adrenalectomy for solitary adrenal metastases from non-small cell lung cancer

BACKGROUND: The treatment of patients with adrenal metastases from lung cancer (non-small cell lung cancer, NSCLC) remains controversial. Several studies of adrenalectomy in cases of isolated adrenal metastases from NSCLC suggest that these patients could have improved survival. Our aim is to define the history of patients after resection of solitary metastases to the adrenal gland and to identify characteristics of patients who achieved prolonged survival. METHODS: Between January 1997 and July 2000, 11 patients underwent curative resection for metastatic NSCLC of the adrenal gland in our institution. In all patients who were accepted for curative adrenalectomy, the primary NSCLC had been treated by complete resection. RESULTS: Eleven patients (seven men and four women) with unilateral adrenal metastases of NSCLC entered the study. Median age was 59 years (range 47-67 years). There was no perioperative death. The overall median survival after metastasectomy was 12.6 months (CI: 9.2-16.1 months). Patients with curative resection and metachronous disease (n=6) had a median survival of 30.9 months and tended to do better than patients with synchronous adrenal metastases (n=5) (median survival: 10.3 months). CONCLUSIONS: We conclude that adrenalectomy for clinically solitary, resectable metastases can be performed safely. It appears reasonable that such selected patients should be considered surgical candidates.     

Treatment outcome for patients with primary NSCLC and synchronous solitary metastasis

Introduction

Non-small cell lung cancer (NSCLC) patients with synchronous solitary metastasis were generally considered as stage IV and believed to be incurable. Recently, growing evidence has indicated that surgical treatment may provide these patients with a survival benefit. The aim of this study was to retrospectively analyze the effectiveness of different treatments for primary tumors and solitary metastases.

Materials and methods

Patients older than 18 years with histologically confirmed stage IV NSCLC and a confirmed synchronous solitary metastasis that diagnosed within 2 months of primary NSCLC. Patients with uncontrolled massive pleural effusion were excluded. Between February 2002 and October 2010, 213 patients were considered eligible and enrolled in this cohort.

Results

The median survival time (MST) for the 213 patients was 12.6 months. Forty-five patients received primary pulmonary tumor surgery in the entire cohort. The MSTs of patients who received primary tumor resection and those who did not were 31.8 and 11.4 months (p < 0.01). The MST of the patients with solitary brain metastasis was 12.3 months. Forty-one patients who received brain surgical treatment or SRS had a MST of 15.4 months and others who only received WBRT had a MST of 11.5 months (p = 0.002). Gender, the stage of the primary tumor, PS and whether the primary tumor was removed all affected prognosis independently.

Conclusions

Aggressive local and metastasis treatments could lead to better clinical outcomes and thus provide an option for clinicians in the future management of patients with NSCLC and synchronous solitary metastasis.     

Validation of the Disease-Specific GPA for Patients With 1 to 3 Synchronous Brain Metastases in Newly Diagnosed NSCLC

Background

The disease-specific graded prognostic assessment (DS-GPA) for brain metastases is a powerful prognostic tool but has not been validated for patients with synchronous brain metastases (SBM) in newly diagnosed non–small-cell lung cancer (NSCLC).

Pulmonary resection in patients with nonsmall-cell lung cancer treated with gamma-knife radiosurgery for synchronous brain metastases

BACKGROUND: The aim of the current study was to determine whether a pulmonary resection and gamma-knife radiosurgery (GKRS) protocol is superior to GKRS alone in selected patients with stage IV nonsmall-cell lung cancer (NSCLC). METHODS: The authors performed a retrospective case-control study of 232 consecutive patients with newly diagnosed NSCLC from January 1998 to December 2005 and screened them to identify a study cohort in which all patients had thoracic stage I or II, Karnofsky performance status >or= 70, no extracranial metastases, and 1-3 synchronous brain metastases of less than 3 cm, and were treated with GKRS (n=31). The study cohort was divided into 2 groups, those with and without concomitant pulmonary resection. RESULTS: Sixteen patients with pulmonary resection were assigned to the treatment group and 15 without pulmonary resection were assigned to the control group. Median follow-up was 27.3 months (range, 4.4 months to 90.9 months). Mean survivals for the treatment group and the control group were 64.9 and 18.1 months, respectively (P< .001). There was a statistically significant association between pulmonary resection and better survival (OR=78.408). One-year and 5-year local brain tumor control rates were 97.1% and 93.5%, respectively. CONCLUSIONS: The pulmonary resection and GKRS protocol could prolong survival in patients with thoracic stage I or II NSCLC, no extracranial metastases, and a limited number of small synchronous brain metastases.     

A randomized phase III trial of stereotactic radiosurgery (SRS) versus observation for patients with asymptomatic cerebral oligo-metastases in non-small-cell lung cancer

In this study, we undertook a randomized phase III trial of 105 NSCLC patients with oligo (one to four) -brain metastases. Patients were randomly assigned (1:1) to receive either stereotactic radiosurgery (SRS) followed by chemotherapy or upfront chemotherapy alone. The results demonstrated that SRS followed by chemotherapy did not improve overall survival compared with upfront chemotherapy only.BackgroundIt is unclear whether treating brain metastasis before starting systemic chemotherapy can improve survival compared with upfront chemotherapy in non-small-cell lung cancer (NSCLC) with asymptomatic cerebral oligo-metastases.Patients and methodsWe undertook a randomized, controlled trial of 105 patients with one to four brain metastases, admitted to Samsung Medical Center between 2008 and 2013. Patients were randomly assigned to receive stereotactic radiosurgery (SRS) (49 patients) followed by chemotherapy or upfront chemotherapy (49 patients). The primary end point was overall survival (OS) and secondary end points included central nervous system (CNS) progression-free survival, progression to symptomatic brain metastasis and brain functional outcome.ResultsThe median age was 58 years (range, 29–85) with ECOG 0–1 performance status, and 40% of patients were never smokers. Most patients had adenocarcinoma, and about half of patients had only one brain metastasis, while the rest had multiple cerebral metastases. The median OS time was 14.6 months [95% confidence interval (CI), 9.2–20.0] in the SRS group and 15.3 months (95% CI, 7.2–23.4) for the upfront chemotherapy group (P = 0.418). There was no significant difference in time to CNS disease progression [median, 9.4 months (SRS) versus 6.6 months (upfront chemotherapy),P = 0.248]. Symptomatic progression of brain metastases was observed more frequently in the upfront chemotherapy group (26.5%) than the SRS group (18.4%) but without statistical significance.ConclusionsAlthough this study included smaller sample size than initially anticipated due to early termination, SRS followed by chemotherapy did not improve OS in oligo-brain metastases NSCLC patients compared with upfront chemotherapy. Further study with large number of patients should be needed to confirm the use of upfront chemotherapy alone in this subgroup of patients.Clinical trials numberNCT01301560.     

Stereotactic radiosurgery for brain metastases: Comparison of lung carcinoma vs. non-lung tumors

In the medical literature, stereotactic radiosurgery (SRS) for brain metastases results in rates of local control of 65 to 85%. To define patient selection criteria, we measured the survival in a population with a high proportion of non-small cell lung carcinoma (NCS lung) metastases that occurred soon after primary diagnosis. Between 9/89 and 10/93 30 adults (21 M, 9 F) had SRS for metastatic NSC lung carcinoma (14 patients) vs. non-lung carcinomas (16 patients having breast (3), renal (3), melanoma (3), GI (2, thyroid (1) or carcinoma of unknown origin (4)). The metastases were solitary for 22 patients and multiple for 8 patients. Average ages (y) (± SD) were 58.6 ± 10.4 for NSC lung patients and 53.4 ± 12.5 (p=0.32) for non-lung patients. The average interval (months) from diagnosis of the primary to metastasis was 23.8 ± 41.4 for all patients. This interval was shorter for NSC lung patients: 3.1 ± 6.0 vs. 48.0 ± 51.7 (p < 0.001) for non-lung patients. Twenty seven patients had conventional radiotherapy (XRT) before (24 patients) or after (3 patients) SRS. Doses (cGy) were 3303 ± 841 for 13 NSC lung patients and 4256 ± 992 for 14 non-lung patients (p = 0.034). The median time from primary diagnosis to SRS was shorter for the NSC lung patients (11 mo) compared to the non-lung patients (35 mo). SRS was given for recurrence of metastases after XRT for 11/14 NSC lung patients and 13/16 non-lung patients. The doses (cGy) of SRS were 1579 ± 484 vs. 1682 ± 476 (p=0.45) for the NSC lung and non-lung groups, respectively. After SRS a decrease in metastasis diameter was observed in 10 of 14 NSC lung patients vs. 12 of 16 non-lung patients (p=0.85 Chi-square). Twenty-seven of the 30 patients have died. For all patients, the median survival after diagnosis of the primary and after radiosurgery was 31.3 and 8.4 months, respectively. The median survival (95% CI) from primary diagnosis was 24.3 months (13.2–27.3) for NSC lung patients and 46.5 months (39.2–65.5) for non-lung patients (p=0.005 logrank test). The median survival (95% CI) after SRS was 7.9 months (3.0–14.3) for the NSC lung patients and 8.4 (2.9–11.9) months for the non-lung patients (p=0.98 logrank test). Within the two groups, no difference in survival was observed for patients who had SRS sooner (< 1 yr for NSC lung; < 3 yr for non-lung) after primary diagnosis: 9.3 vs. 6.5 mo for NSC lung (p = 0.21) and 10.5 vs. 7.2 mo for non-lung (p=0.87). In this series, the shortened intervals from primary diagnosis to SRS for NSC lung metastases was associated with post-SRS survivorship that was equivalent to the more favorable non-lung group.     

A pathology-based substrate for target definition in radiosurgery of brain metastases

PURPOSE: To investigate the need of a margin other than for accuracy reasons in stereotactic radiosurgery (SRS) of brain metastases by means of histopathology. METHODS AND MATERIALS: Evaluation of 45 patients from two pathology departments having had brain metastases and an autopsy of the brain. Growth patterns were reviewed with a focus on infiltration beyond the metastases boundary and made visible with immunohistochemical staining: the metastasis itself with tumor-specific markers, surrounding normal brain tissue with a glial marker, and a possible capsule with a soft tissue marker. Measurements were corrected by a tissue-shrinkage correction factor taken from literature. Outcomes parameters for infiltration were mean and maximum depths of infiltration and number of measured infiltration sites. RESULTS: In 48 of 76 metastases, an infiltration was present. The largest group of metastases was lung cancer. Small-cell lung cancer (SCLC) and melanoma showed a maximum depth of infiltration of > or =1 mm, and other histologies <1 mm. For non-small-cell lung cancer (NSCLC), melanoma, and sarcoma, the highest number of infiltrative sites were observed (median, 2; range, 1-8). SCLC showed significantly larger infiltrative growth, compared with other diagnostic groups. In NSCLC, the highest percentage of infiltration was present (70%). CONCLUSIONS: Infiltrative growth beyond the border of the brain metastasis was demonstrated in 63% of the cases evaluated. Infiltrative growth, therefore, has an impact in defining the clinical target volume for SRS of brain metastases, and a margin of approximately 1 mm should be added to the visible lesion.     

Number of metastatic sites is a strong predictor of survival in patients with nonsmall cell lung cancer with or without brain metastases

BACKGROUND:

The staging system for non–small cell lung cancer (NSCLC) does not consider tumor burden or number of metastatic sites, although oligometastases are more favorable.

METHODS:

Using log‐rank testing, the authors analyzed overall survival (OS) in 1284 patients newly presenting with metastatic NSCLC by number of metastatic organ sites and the presence of brain metastases.

RESULTS:

OS for patients without brain metastases was found to be correlated with the number of metastatic sites (P = .0009). Brain metastases conferred an inferior OS (median of 7 months vs 9 months; 95% confidence interval, 7‐8 months vs 8‐10 months [P = .00,002]). To evaluate the influence of tumor burden on OS, the authors considered subsets of patients in whom the brain (n = 135) or lung (n = 137) was the solitary metastatic organ site. In patients with brain metastases, OS was found to be correlated inversely with the volume of all metastases or the largest lesion (hazards ratio, 1.04 or 1.03, respectively; P = .01). For patients with lung metastases, OS was better for those with a maximum tumor size below the median of 40 mm (P = .0004).

CONCLUSIONS:

Staging of NSCLC and clinical trial patient stratification should include quantitation of tumor burden. The prognostic impact of brain metastases is small and partly dependent on tumor volume, which indicates the need for aggressive therapy for patients with NSCLC brain metastasis and their inclusion in clinical trials. Cancer 2009. © 2009 American Cancer Society.     

Non-small cell lung cancer and silent brain metastasis. Survival and prognostic factors

The detection of silent brain metastasis is becoming increasingly common in patients with non-small cell lung cancer (NSCLC). The aim of this study was to evaluate clinical course, prognostic significance, and treatment efficacy in patients with asymptomatic brain metastasis. A retrospective study of patients with cytologically and histologically diagnosed NSCLC and brain metastasis detected by cranial computed tomography or magnetic resonance imaging was performed. We compared 12 neurologically asymptomatic patients to 69 symptomatic patients and analyzed overall survival, clinical course, and prognostic factors (age, sex, performance status, histologic type, TNM stage, number and size of brain metastases, clinical neurologic status, and treatment of primary tumor and brain metastasis). The strongest favorable prognostic factor was active treatment of both the primary tumor (surgery, chemotherapy and/or thoracic radiotherapy) and brain metastasis (neurosurgery and/or whole brain radiotherapy). Neurologically asymptomatic patients had significantly longer survival times than did symptomatic patients (median survival of 7.5 and 4 months, respectively). Control of clinical neurologic status during follow-up was achieved in a greater proportion of asymptomatic patients (80%) than symptomatic patients (40%). We conclude that it is important to detect brain metastasis in patients with NSCLC before neurologic signs or symptoms develop, as early detection improves prognosis and provides patients with the opportunity of receiving timely and more effective treatment.     

High rate of detection of unsuspected distant metastases by pet in apparent stage III non-small-cell lung cancer: implications for radical radiation therapy

PURPOSE: Most radical radiotherapy (RT) candidates with non-small-cell lung cancer (NSCLC) have Stage III disease and ultimately die with distant metastases. We tested the hypothesis that positron emission tomography (PET) using 18-F fluorodeoxyglucose (FDG) would detect more unsuspected metastases in apparent Stage III disease than in Stages I-II. METHODS AND MATERIALS: Staging FDG-PET was performed for 167 NSCLC patients, with Stage I-III by conventional workup, who were candidates for curative therapy with surgery (n = 8), radical chemo/RT or RT (n = 156), or preoperative chemo/RT (n = 3). Each patient was allocated a conventional "pre-PET stage" and a "post-PET stage" that relied on PET when discordance with conventional staging occurred. RESULTS: Stage distribution pre-PET was n = 39 (Stage I), n = 28 (Stage II), and n = 100 (Stage III). In 32 patients (19%), PET detected distant metastasis, most commonly abdominal with 17 cases (adrenal, n = 7; liver, n = 4; other, n = 6). Other sites included lung (n = 10) and bone (n = 6). PET-detected metastasis increased with increasing pre-PET stage from I (7.5%) through II (18%) to III (24%, p = 0.016), and, in particular, was significantly higher in Stage III (p = 0.039). Biopsy confirmation was not routine, but progression occurred at PET-detected metastatic sites or other metastatic sites in all but 3 of the 32 patients by last review. CONCLUSION: PET staging is recommended for radical RT candidates with NSCLC. The highest yield of unexpected distant metastases is observed in Stage III.     

Stereotactic radiosurgical treatment of brain metastases in older patients

BACKGROUND: This study was designed to evaluate the therapeutic effect of stereotactic radiosurgery (SRS) in patients aged > or =75 years who presented with brain metastasis. METHODS: The authors analyzed the data from 44 consecutive patients treated with SRS for > or =1 brain metastasis. The median age at the time of treatment for brain metastases was 79.3 years (range, 75 years-86 years), and the median Karnofsky performance status was 80 (range, 50-100). At the time of SRS, 31 patients were treated for a single metastasis, and the remaining 13 patients were treated for > or =2 lesions (n = 74 lesions). The median tumor volume was 1.2 cm(3) (range, 0.007 cm(3)-22.5 cm(3)). The median maximal and marginal doses were 36 grays (Gy) (range, 18.8 Gy-48.2 Gy) and 20 Gy (range, 10 Gy-24 Gy), respectively. RESULTS: Median survival was 7.3 +/- 1.65 months (range, 1.6 months-38.9 months) from the time of diagnosis of brain metastasis. Median survival of the patients with a single brain metastasis (10.1 +/- 1.92 months) was longer than that of the patients with > or =2 metastases (6.6 +/- 1.28 months) (P <.02). A single lesion was found to be an independent favorable prognostic factor (P +/- = +/- .017; odds ratio, 2.385 [95% confidence interval, 1.167-4.874]) in univariate and multivariate analysis. Patients with nonsmall cell lung cancer fared worse than patients with other tumor types (survival of 6.5 +/- 0.70 months vs 10.1 +/- 2.33 months [P<.05]). CONCLUSIONS: SRS for patients aged > or =75 years with brain metastases is an effective and safe treatment modality that appears to improve survival, with outcomes that compare favorably with those reported for younger patients in an appropriately selected population.     

Salvage Surgical Resection after Linac-Based Stereotactic Radiosurgery for Newly Diagnosed Brain Metastasis

Background: This study aimed to assess the clinical outcomes of salvage surgical resection (SSR) after stereotactic radiosurgery and fractionated stereotactic radiotherapy (SRS/fSRT) for newly diagnosed brain metastasis. Methods: Between November 2009 and May 2020, 318 consecutive patients with 1114 brain metastases were treated with SRS/fSRT for newly diagnosed brain metastasis at our hospital. During this study period, 21 of 318 patients (6.6%) and 21 of 1114 brain metastases (1.9%) went on to receive SSR after SRS/fSRT. Three patients underwent multiple surgical resections. Twenty-one consecutive patients underwent twenty-four SSRs. Results: The median time from initial SRS/fSRT to SSR was 14 months (range: 2–96 months). The median follow-up after SSR was 17 months (range: 2–78 months). The range of tumor volume at initial SRS/fSRT was 0.12–21.46 cm³ (median: 1.02 cm³). Histopathological diagnosis after SSR was recurrence in 15 cases, and radiation necrosis (RN) or cyst formation in 6 cases. The time from SRS/fSRT to SSR was shorter in the recurrence than in the RNs and cyst formation, but these differences did not reach statistical significance (p = 0.067). The median survival time from SSR and from initial SRS/fSRT was 17 and 74 months, respectively. The cases with recurrence had a shorter survival time from initial SRS/fSRT than those without recurrence (p = 0.061). Conclusions: The patients treated with SRS/fSRT for brain metastasis need long-term follow-up. SSR is a safe and effective treatment for the recurrence, RN, and cyst formation after SRS/fSRT for brain metastasis.     

Brain metastases and non-small cell lung cancer. Prognostic factors and correlation with survival after irradiation

A total of 250 patients with brain metastases from non-small cell lung cancer (NSCLC) were treated with irradiation of their brain metastases. The median overall survival was 3.1 (95% CI: 2.7-3.5) months. 32/250 patients presenting with solitary brain metastasis underwent surgical resection. Their 1-year survival rate of 58% was significantly better than 89/250 patients with a solitary lesion but without surgery (14%, P=0.001). Patients with an absent or controlled primary tumor (101/250, 40.5%) had a 1-year survival rate of 26% as opposed to 11% for patients presenting with an active primary tumor (P=0.051). Patients presenting with metastases to the brain only showed a significant survival advantage over patients with extracranial metastases (1-year survival of 21% vs 6%, P=0.001). Karnofsky performance score, neurofunction status and response to steroids were also identified as prognostic factors. The total dose whole brain irradiation (WBI) was prognostic of significance with a 1-year survival of 35% for 30 Gy and boost, 23.5% for 30 Gy and 4% for the patients irradiated to a dose of 20 Gy WBI (P=0.001). When patients were grouped into the RTOG RPA (Recursive partitioning analysis) classes, patients within class I (73/250) had a 1-year survival of 28.5%, patients in class II (145/250) a survival of 14% at 1 year and patients into class III only a 6% 1-year survival rate. In a multivariate analysis, surgical resection, neurofunction class, metastatic extent and WBI dose remained significant prognostic factors. Although survival remains poor, there needs to be a continued interest in these patients, probably by participating in clinical trials.     

晚期小细胞肺癌和非小细胞肺癌不同转移部位预后意义的比较

  目的  明确不同转移部位对小细胞肺癌（small cell lung cancer,SCLC）和非小细胞肺癌（non-small cell lung cancer,NSCLC）预后影响的差异。  方法  回顾性分析天津医科大学肿瘤医院2012年1月至2017年12月确诊为晚期SCLC 266例和2015年1月至2017年12月确诊为晚期NSCLC 275例,总计541例患者病例资料。主要观察指标为总生存期（overall survival,OS）。  结果  在SCLC中,与多器官转移者相比,单器官转移者的预后更好（P=0.000 4）;在NSCLC中,单器官与多器官转移者之间未见到明显的生存差异（P=0.451）。在SCLC单器官转移者中,脑转移的预后相对最好,骨转移的预后相对较差,肝转移的预后最差,三者的中位生存时间（median survival time,MST）分别为14.5、11.5和10.3个月;在NSCLC单器官转移者中,肺内转移的预后最佳,肝和肾上腺转移者的预后较差,三者的MST分别为未达到、7.6和7.3个月。在SCLC多器官转移者中,有骨（P=0.046）、肝（P=0.019）转移者预后较差;而有无脑（P=0.995）、肺（P=0.847）、肾上腺（P=0.255）转移对患者的预后无显著性影响;在NSCLC多器官转移的患者中,有脑（P=0.054）、肾上腺转移（P=0.006）的患者预后较差;有肺（P=0.008）转移的患者预后较好;而有无骨（P=0.091）、肝（P=0.300）转移对患者的预后无显著性影响。  结论  不同转移部位对SCLC和NSCLC预后的影响存在差异。