Synchronous Solitary Brain Metastasis Research Articles

Long-term Survival with 18-Fluorodeoxyglucose Positron Emission Tomography-directed Therapy in Non-small Cell Lung Cancer with Synchronous Solitary Brain Metastasis

AimsAt diagnosis, <1% of patients with non-small cell lung cancer (NSCLC) have synchronous solitary brain metastasis (SSBM). In prior cohorts without 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) staging, definitive treatment to intracranial and intrathoracic disease showed a 5-year overall survival (OS) of 11–21%. We investigated the long-term survival outcomes for patients with SSBM NSCLC, diagnosed in the FDG-PET/CT era and treated definitively with local therapies to both intracranial and intrathoracic sites of disease. Materials and methodsThis retrospective study assessed patients staged with FDG-PET/CT who received definitive lung and SSBM treatment from February 1999 to December 2017. A lung-molecular graded prognostic assessment (lung-molGPA) score was assigned for each patient using age, performance status score, and, where carried out, molecular status. Overall survival and progression-free survival (PFS) were calculated using Kaplan–Meier methods. Cox proportional hazard models determined OS and PFS prognostic factors. ResultsForty-nine patients newly diagnosed with NSCLC and SSBM had a median age of 63 years (range 34–76). The median follow-up of all patients was 3.9 years. Thirty-three patients (67%) had ≥T2 disease, 23 (47%) had ≥N2. At 2 years, 45% of first failures were intracranial only (95% confidence interval 30–59). At 3 and 5 years, OS was 45% (95% confidence interval 32–63) and 30% (95% confidence interval 18–51), respectively. In ≥N1 disease, 5-year OS was 34% (95% confidence interval 18–63). The 3- and 5-year PFS was 8% (95% confidence interval 3–22) and 0%, respectively. Higher lung-molGPA was associated with longer OS (hazard ratio 0.26, 95% confidence interval 0.11–0.61, P = 0.002). Higher lung-molGPA (hazard ratio 0.33, 95% confidence interval 0.15–0.71, P = 0.005) and lower N-stage (hazard ratio 1.56, 95% confidence interval 1.13–2.15, P = 0.007) were associated with longer PFS. ConclusionsDefinitive treatment of patients with NSCLC and SSBM staged with FDG-PET/CT can result in 5-year survivors, including those with ≥N1 disease.

ES21.02 Biological Disease Characterization of OMD

Tabled 1Variation in the characterization of OMDTrialOMD characteristicsOMD timingIyengar et al (2017)· ≤6 sites of extracranial disease (including primary) · ≤3 sites in liver or lung ·Up to 2 contiguous vertebral metastases considered a single siteAfter first-line therapy and without progressionGomez et al (2016)· ≤3 metastatic sites · Any N1-3 thoracic nodes considered a single site · Satellite lesions counted as separate sitesAfter first-line therapy and without progressionParikh et al (2014)· ≤5 metastatic sitesAfter first-line therapy and without progressionCheruvu et al (2011)· ≤8 metastatic sitesAt time of initial stagingKhan et al (2006)· 1-2 metastatic sites · Definitive (surgery and/or chemoradiation) treatment of thoracic diseaseAfter treatment of thoracic disease Open table in a new tab Recent years have seen a marked increase in interest in the concept of oligometastatic disease (OMD) in non-small cell lung cancer (NSCLC). Lacking a precise and consistent definition, OMD is generally considered to represent a relatively favorable clinical state, with more indolent biology, a limited number of disease sites, and potential for prolonged periods of disease control. Discussions of oligometastatic NSCLC area inexorably linked with management considerations, specifically the use of local therapies such as surgery and radiation therapy. There are numerous clinical and biological rationales to support such approaches: (1) disease progression most commonly occurs in original sites of gross disease1; (2) metastatic sites may propagate secondary metastases (parallel progression model)2; (3) solid tumors are composed of faster growing (sensitive) and slower growing (resistant) cell populations (Norton-Simon hypothesis)3; (4) resistance depends on spontaneous mutations and therefore increases with time (Goldie-Coldman hypothesis).4 Nevertheless, several questions regarding the characterization and optimal management of OMD remain (Table 1). Up to how many sites of disease constitute an oligometastatic state? Does a “site” of disease comprise a single lesion or neighboring tumors? Does the anatomic site matter? For instance, brain metastases have historically been considered a more favorable location for definitive treatment of OMD, and their emergence may reflect pharmacokinetic failure rather than molecular evolution.5,6 Additionally, there are likely meaningful clinical differences between OMD states depending on whether they are defined at diagnosis (de novo), after initial exposure to systemic therapy (induced), recurrence, or progression. OMD may also have a distinct biologic phenotype. The metastatic cascade includes loss of cellular adhesion, increased motility, primary tumor invasiveness, entry into and survival in the circulation, and entry into and colonization of distant organs.7 Tumor dormancy, regulated in part by interferon signaling, may impact the number, location, and timing of metastases.8 Expression of genes that positively regulate the cell cycle may determine whether cancer growth occurs as polymetastasis versus oligometastasis. Ideally, ongoing and future clinical trials will collect biospecimens for discovery and validation of OMD biomarkers, thereby enabling the identification of cases most likely to benefit from OMD treatment paradigms. 1. Rusthoven KE, Hammerman SF, Kavanagh BD, Birtwhistle MJ, Stares M, Camidge DR. Is there a role for consolidative stereotactic body radiation therapy following first-line systemic therapy for metastatic lung cancer? A patterns-of-failure analysis. Acta Oncol 2009;48:578-83. 2. Klein CA. Parallel progression of primary tumours and metastases. Nat Rev Cancer 2009;9:302-12. 3. Norton L, Simon R. Tumor size, sensitivity to therapy, and design of treatment schedules. Cancer Treat Rep 1977;61:1307-17. 4. Goldie JH, Coldman AJ. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 1979;63:1727-33. 5. Hu C, Chang EL, Hassenbusch SJ, 3rd, et al. Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis. Cancer 2006;106:1998-2004. 6. Grommes C, Oxnard GR, Kris MG, et al. "Pulsatile” high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer. Neuro Oncol 2011;13:1364-9. 7. Gupta GP, Massague J. Cancer metastasis: building a framework. Cell 2006;127:679-95. 8. Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nature reviews Immunology 2006;6:836-48. stereotactic radiation therapy, Oligometastatic, Non-Small Cell Lung Cancer

EP-1351 Long-term survival with FDG-PET directed therapy in NSCLC with synchronous solitary brain metastasis

EP-1351 Long-term survival with FDG-PET directed therapy in NSCLC with synchronous solitary brain metastasis

Outcomes of aggressive treatment in esophageal cancer patients with synchronous solitary brain metastasis.

The aim of the present study was to investigate the outcomes of esophageal cancer (EC) patients with isolated synchronous brain oligometastasis (oligo-BM) treated with chemoradiotherapy (CRT) of the primary site and localized treatment of the BM with surgery, radiotherapy (RT) or radiosurgery. Of 125 EC patients investigated, seven patients (6%) had solitary BM. Six patients were diagnosed prior to, and one patient was diagnosed during, treatment. All patients were treated with neoadjuvant chemotherapy and whole-brain RT (WBRT) for BM. All but one patient received definitive CRT with a median RT dose of 50.4 Gy using conventional fractionation RT. The median age at diagnosis was 59 years (range, 48-77 years). Six patients succumbed to mortality, and one continued to receive systemic chemotherapy at the last visit. The median survival time of the patients was 18.9 months (range, 10.0-27.2 months). Median time to progression after completion of the treatments was 8 months (range, 3-9 months). Two patients had progression of the primary tumor, and one patient had progression of the BM. The neurological status of three patients with BM who were identified during the staging work-up did not deteriorate as a consequence of WBRT. In conclusion, the present study has demonstrated that aggressive treatment of the primary tumor and oligo-BM in patients with EC may prolong the survival time.

Definitive Chemoradiation Therapy Following Surgical Resection or Radiosurgery Plus Whole-Brain Radiation Therapy in Non-Small Cell Lung Cancer Patients With Synchronous Solitary Brain Metastasis: A Curative Approach

The aim of this study was to evaluate the impact of definitive thoracic chemoradiation therapy following surgery or stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) on the outcomes of patients with non-small cell lung cancer (NSCLC) with synchronous solitary brain metastasis (SSBM). A total of 63 NSCLC patients with SSBM were retrospectively evaluated. Patients were staged using positron emission tomography-computed tomography in addition to conventional staging tools. Thoracic radiation therapy (TRT) with a total dose of 66 Gy in 2 Gy fractions was delivered along with 2 cycles of cisplatin-based chemotherapy following either surgery plus 30 Gy of WBRT (n=33) or SRS plus 30 Gy of WBRT (n=30) for BM. Overall, the treatment was well tolerated. All patients received planned TRT, and 57 patients (90.5%) were also able to receive 2 cycles of chemotherapy. At a median follow-up of 25.3 months (7.1-52.1 months), the median months of overall, locoregional progression-free, neurological progression-free, and progression-free survival were 28.6, 17.7, 26.4, and 14.6, respectively. Both univariate and multivariate analyses revealed that patients with a T1-T2 thoracic disease burden (P=.001), a nodal stage of N0-N1 (P=.003), and no weight loss (P=.008) exhibited superior survival. In the present series, surgical and radiosurgical treatments directed toward SSBM in NSCLC patients were equally effective. The similarities between the present survival outcomes and those reported in other studies for locally advanced NSCLC patients indicate the potentially curative role of definitive chemoradiation therapy for highly selected patients with SSBM.

Surgical treatment for non-small cell lung cancer patients with synchronous solitary brain metastasis

背景与目的非小细胞肺癌脑转移较多见，常用的治疗方法有放疗、化疗等，但预后不佳。本研究拟了解手术在非小细胞肺癌同步单发脑转移综合治疗中的作用。方法回顾性分析46例非小细胞肺癌同步单发脑转移患者的临床资料。所有患者接受肺部肿瘤切除，术后行全脑放疗及化疗。其中13例患者行脑转移瘤切除，33例患者行脑部立体定向放射治疗。结果本组患者总的中位生存期为16.8个月，1年、2年和3年生存率分别为76.1%、20.9%和4.7%。脑转移瘤手术组和立体定向治疗组的中位生存期分别为18.3个月和15. 8个月（P=0.091, 2）。结论手术切除肺部原发肿瘤及脑转移瘤对改善非小细胞肺癌单发脑转移患者的预后具有一定作用。脑转移瘤手术切除或立体定向治疗对患者的生存期未见有影响。

長期生存した同時性孤立性脳転移を有する直腸癌の1例

長期生存した同時性孤立性脳転移を有する直腸癌の1例

Five-year tumor-free survival after aggressive trimodality therapy for T3N0M1b non-small cell lung cancer with synchronous solitary brain metastasis

Several recent studies have demonstrated that some patients might benefit from aggressive therapy for thoracic stage I lung cancer and synchronous solitary brain metastasis. However, the indication for the patients with advanced T-stage is still unclear. We herein present a patient with synchronous solitary brain metastasis from non-small cell lung cancer who survived without recurrence for 5 years following surgery after chemotherapy, even though the primary tumor was T3N0 thoracic stage II. Aggressive treatment for both the primary site and brain metastasis may therefore be an effective treatment for locally advanced non-small cell lung cancer patients with synchronous solitary brain metastasis.

Management and Prognosis in Synchronous Solitary Resected Brain Metastasis from Non–Small-Cell Lung Cancer

Background Reports in the medical literature have described cases of extended survival of patients with non–small-cell lung cancer (NSCLC) with solitary metastatic disease who have received aggressive treatment both to the brain metastasis and to the local/regional disease. The objective of this research is to analyze prognostic factors that predict for outcome in this unique patient population. Patients and Methods A single-institution, retrospective chart review was performed on 35 patients with NSCLC and a synchronous solitary brain metastasis (SSBM) treated with craniotomy and whole-brain radiation therapy. Eight patients (22.9%) had chest surgery, 24 (68.6%) had chemotherapy, and 14 (40%) had thoracic radiation as part of their local management. Fourteen had stage I/II disease (42.9%), and 20 had stage III disease (57.1%). Mean age at diagnosis was 58.5 years. Eighteen patients (56.25%) had a brain metastasis < 3 cm, and 14 patients (43.75%) had a metastasis > 3 cm. Results Median survival was 7.8 months, and at last follow-up, 3 patients (8.6%) were alive and well, 6 patients (17.1%) were alive and with disease, 24 patients (68.6%) had died of disease, and 2 patients (5.7%) had died of other causes. Univariate analysis demonstrated that lung surgery ( P = .0033), primary lung treatment > 8 weeks after brain surgery ( P = .0128), and stage I/II disease ( P = .0467) were predictive of overall survival. Conclusion Survival remains poor for patients with NSCLC with an SSBM. However, patients with thoracic disease amenable to local resection should be considered for such therapy because a survival advantage could exist compared with patients with more locally advanced disease.

Aggressive Trimodality Therapy for T1N2M1 Nonsmall Cell Lung Cancer with Synchronous Solitary Brain Metastasis: Case Report and Rationale

Aggressive treatment, including resection of both metastasis and primary tumor, has been studied for non-small cell lung cancer patients with synchronous solitary brain metastasis. Involvement of mediastinal lymph nodes is considered a poor prognostic factor and a contraindication to surgical resection of the primary lung tumor after treatment for brain metastasis. Here we present the case of a patient who presented with a Stage IV T1N2M1 non-small cell lung cancer with synchronous solitary brain metastasis. He is alive and without evidence of disease two years after aggressive, multimodality treatment that included craniotomy, whole-brain radiation therapy, thoracic surgery, chemotherapy, and mediastinal radiation therapy.

The elderly with synchronous non-small cell lung cancer and solitary brain metastasis: Does palliative thoracic radiotherapy have a useful role?

We evaluated the prognosis associated with advanced age by comparing the clinical features of individuals 65 years of age and older to those of younger patients with single metastasis to the brain alone (SMBA) and simultaneous non-small cell lung cancer (NSCLC), and the potential role of palliative thoracic radiotherapy in this cohort of patients. Our 23-year experience included 72 consecutive (22 elderly and 50 non-elderly) people. Older patients predominantly presented with N0-N1 stage disease and coexisting illness. Univariate analysis showed that younger age (p=0.04) and operative removal of SMBA (p=0.01) were predictive of better survival. However, with multivariate analysis, resection of SMBA remained the sole predictor of prognosis. The application of NSCLC radiotherapy for palliation did not favorably alter outcome. In conclusion, elderly patients with simultaneous NSCLC and SMBA seem to fare less well than their younger counterparts. Moreover, the concurrent application of radiotherapy for palliation of the lung neoplasm was not prognostically advantageous.

Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis

Solitary brain metastases occur in about 50% of patients with brain metastases from nonsmall cell lung cancer (NSCLC). The standard of care is surgical resection of solitary brain metastases, or stereotactic radiosurgery (SRS) plus whole brain radiation therapy (WBRT). However, the optimal treatment for the primary site of newly diagnosed NSCLC with a solitary brain metastasis is not well defined. The goal was to distinguish which patients might benefit from aggressive treatment of their lung primary in patients whose solitary brain metastasis was treated with surgery or SRS. The cases of 84 newly diagnosed NSCLC patients presenting with a solitary brain metastasis and treated from December 1993 through June 2004 were retrospectively reviewed at The University of Texas M. D. Anderson Cancer Center. All patients had undergone either craniotomy (n = 53) or SRS (n = 31) for management of the solitary brain metastasis. Forty-four patients received treatment of their primary lung cancer using thoracic radiation therapy (median dose 45 Gy; n = 8), chemotherapy (n = 23), or both (n = 13). The median Karnofsky performance status score was 80 (range, 60-100). Excluding the presence of the brain metastasis, 12 patients had AJCC Stage I primary cancer, 27 had Stage II disease, and 45 had Stage III disease. The median follow-up was 9.7 months (range, 1-86 months). The 1-, 2-, 3-, and 5-year overall survival rates from time of lung cancer diagnosis were 49.8%, 16.3%, 12.7%, and 7.6%, respectively. The median survival times for patients by thoracic stage (I, II, and III) were 25.6, 9.5, and 9.9 months, respectively (P = .006). By applying American Joint Committee on Cancer staging to only the primary site, the thoracic Stage I patients in our study with solitary brain metastases had a more favorable outcome than would be expected and was comparable to Stage I NSCLC without brain metastases. Aggressive treatment to the lung may be justified for newly diagnosed thoracic Stage I NSCLC patients with a solitary brain metastasis, but not for locally advanced NSCLC patients with a solitary brain metastasis.

Management of solitary brain metastases

In response to a recently published letter regarding the ‘aggressive management of non-small cell lung cancer with synchronous solitary brain metastases’ [ 1 Vasudev N.S. Crosse B.A. Snee M. Joffe J.K. Aggressive management of non-small cell lung cancer with synchronous solitary brain metastasis. Clin Oncol (R Coll Radiol). 2004; 16: 158-159 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ], we would contend that the case for whole brain radiotherapy (WBRT) after surgical resection of a solitary metastasis is not yet resolved.

Lung cancer with synchronous solitary brain metastasis: palliative or radical treatment?

Carcinoma of the lung is the malignancy that most commonly metastasizes to the brain. It is not uncommon for patients to have brain metastasis at the time of initial presentation with non-small cell lung cancer (NSCLC). The optimum treatment for the patients presenting with NSCLC and synchronous solitary brain metastasis has been controversial but with clear evidence of benefit in selected patients when in receipt of radical treatment for both, the lung tumor and the cerebral metastasis. Nevertheless, this treatment is not always offered to patients who are potential candidates, despite the evidence in the literature. We undertook a review of literature to assess the benefit of aggressive therapy, and which patients would benefit from it, and what constitutes the most appropriate treatment. We conclude that, in selected patients, the potentially-curative dual resection of the primary tumour and the brain metastasis can achieve improvements in survival rate and quality-of-life. However, identification of reliable prognostic factors to select appropriate patients is needed. To date there is no clear evidence regarding what should be the radical treatment for cerebral metastasis (surgery, radiosurgery, total cranial radiotherapy following either of these…)