The impact of whole brain radiation therapy on overall survival in patients with extensive stage small cell lung cancer with brain metastases / 中华放射肿瘤学杂志

Objective:To evaluate whether whole brain radiation therapy(WBRT) could benefit small cell lung cancer (SCLC) patients with brain metastases.Methods:Clinical data of 245 patients who were diagnosed with extensive stage SCLC with brain metastases admitted to our hospital from 2010 to 2020 were retrospectively analyzed. Among them, 168 patients received WRBT (WBRT group, radiation dose: 30Gy in 10 fractions), and 77 patients did not receive WBRT (non-WBRT group). All patients received 4-6 cycles of chemotherapy, and the chemotherapy regimen included cisplatin (or carboplatin) plus etoposide. One hundred and fifteen patients received thoracic radiotherapy. The endpoint was overall survival after brain metastases(BM-OS). Chi-square test was used to compare categorical data, and stabilized inverse probability of treatment weighting(sIPTW) was used to match the factors between WBRT and no-WBRT groups. Survival analysis was estimated by Kaplan-Meier method, and the log-rank test was used to compare survival curves between two groups. Results:The median BM-OS for the whole group of patients was 9.1 months, and 10.6 months and 6.7 months in the WBRT and non-WBRT groups, respectively( P=0.003). After balanced influencing factors with stabilized sIPTW, significant difference still existed in BM-OS between two groups( P=0.02). In 118 patients with synchronous brain metastases, the median BM-OS in two groups were 13.0 months and 9.6 months( P=0.007); and in 127 patients with metachronous brain metastases, the median BM-OS were 8.0 months and 4.1 months( P=0.003). In 50 patients without extracranial metastases, the median BM-OS were 13.3 months and 10.9 months( P=0.259)in two groups; while in 195 patients with extracranial metastases, the median BM-OS were 9.5 months and 5.9 months( P=0.009)in two groups. Conclusions:WBRT could prolong the OS in extensive stage SCLC patients with brain metastases.

Progress on radiotherapy of primary central nervous system lymphoma / 中华放射肿瘤学杂志

Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin′s lymphoma that occurs in the brain, spinal cord, meninges or eyes. Diffuse large B-cell lymphoma accounts for the vast majority, of which non-GCB subtype is more common. The median survival time of untreated patients is only 3 months. Surgical removal of the tumor alone has no obvious survival benefit. Early single use of whole brain radiation therapy (WBRT) yields a high remission rate, but the duration is short, and delayed neurotoxicity is an important complication, especially for elderly patients. Subsequent studies found that high-dose methotrexate-based chemotherapy combined with WBRT significantly improved the prognosis of this disease. However, combination therapy increases the risk of neurotoxicity, and this strategy has been questioned. In recent years, reduced-dose WBRT and autologous hematopoietic stem cell transplantation have gradually replaced the previous standard-dose WBRT. This article reviews the progress on the radiotherapy for PCNSL.

Effect of whole-brain radiotherapy and TKIs on suvival of patients with brain metastases from non-small cell lung cancer stratified by EGFR mutation status / 中国肿瘤临床

Objective: To compare overall survival (OS) and intracranial progression-free survival (iPFS) effects of whole-brain radiotherapy (WBRT) and tyrosine kinase inhibitors (TKIs) in NSCLC patients with brain metastases (BM) stratified by EGFR mutation status (mutant, wild-type). Methods: We performed a retrospective analysis of 215 NSCLC BM patients diagnosed in January 2013 to January 2015 with known EGFR status and followed up to December 1, 2016. Stratified Kaplan-Meier curves and multivariate Cox models were used to evaluate the effects of WBRT (defined as≥30 Gy, "W") and TKIs (after BM, "T") on OS and iPFS independently and jointly. Two-sided P>0.20 was considered non-significant (ns). Results: In patients with BM, the mean age was 58 years, 52% were female, and 93% had adenocarcinoma. Those with EGFR mutations (114 patients) had "W" (35 patients) and "T" (87 patients) with adjusted hazard ratios (HRs) (P) of 1.135 (ns) and 0.202 (P<0.001) for OS, respectively, and 1.122 (ns) and 0.275 (P<0.001) for iPFS, respectively. "W+T" (22 patients), "T only" (65 patients), "W only"(13 patients), and "neither" (14 patients) had OS-median survival time (MST) of 14.1, 15.3, 7.1, and 4.3 months, respectively; their iPFS-MST were 14.1, 13.4, 6.8, and 4.5 months, respectively. Their adjusted HRs (P) were 0.196 (P=0.003), 0.114 (P<0.001), 0.434 (ns), 1.000 (ref) for OS, respectively, and 0.272 (P=0.012), 0.200 (P<0.001), 0.622 (ns), 1.000 (ref) for iPFS, respectively. Compared with "T only," "W+T" was not associated with better survival and "W only" had adjusted HRs (P) of 3.804 (P=0.025) for OS and 3.114 (P=0.032) for iPFS. The EGFR wild-type (101 patients) used "W" in 43 patients with OS-MST of 11.3 (7.1) and iPFS of 11.2 (4.8) months; the adjusted HRs (P) of "W"were 0.539 (P=0.105) for OS and 0.485 (P=0.048) for iPFS. Conclusions: In EGFR-mutant NSCLC BM patients, TKIs are associated with improved survival, whether, WBRT alone or combined are not. In cases of EGFR wild-type, WBRT confers the improved the iPFS.

The role of whole brain radiation therapy in treatment of primary central nervous system lymphoma: necessary or not / 中华放射肿瘤学杂志

Primary central nervous system lymphoma (PCNSL) is a type of extranodal non-Hodgkin lymphoma.Whole brain radiation therapy (WBRT) combined with high-dose methotrexate is the standard treatment.Although PCNSL patients are sensitive to radiation therapy,the duration of response is relatively short and it is likely to provoke delayed neurotoxicity,especially in the elderly patients.Reduced-dose WBRT and autologous stem cell transplantation (ASCT) can lower the risk of neutotoxicity,whereas the clinical efficacy remains to be validated.For the elderly patients with PCNSL,application of WBRT in the first-line treatment should be cautiously considered.

Progress in the treatment of non-small cell lung cancer with brain metastases / 中国肿瘤临床

Lung cancer is a malignant tumor,leading to the highest morbidity and mortality worldwide.Non-small cell lung cancer (NSCLC)accounts for approximately 80% of all lung cancer types.Out of all the patients with advanced NSCLC,more than 40% develop brain metastasis,and lung cancer associated with brain metastasis indicates poor prognosis.Traditional treatment options,such as ra-diotherapy,chemotherapy and surgery,have an extremely limited role in improvement of prognosis of such patients.In recent years, with the development of stereotactic radiotherapy and targeted therapy,particularly chemotherapy combined with targeted therapy, radiotherapy combined with targeted therapy and other types of therapies,NSCLC patients with brain metastases could benefit from these therapies with an improved quality of life and prolonged median overall survival. However, the ideal treatment regimen for NSCLC patients with brain metastases remains controversial.Recent advances in NSCLC with brain metastases will be described elabo-rately in this paper,to provide a theoretical basis for selecting a reasonable treatment plan for non-small lung cancer patients with brain metastasis.

Role of Recursive Partitioning Analysis and Graded Prognostic Assessment on Identifying Non-Small Cell Lung Cancer Patients with Brain Metastases Who May Benefit from Postradiation Systemic Therapy / 中华医学杂志(英文版)

<p><b>Background</b>The role of postradiation systemic therapy in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) was controversial. Thus, we explored the role of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG-RPA) and graded prognostic assessment (GPA) in identifying population who may benefit from postradiation systemic therapy.</p><p><b>Methods</b>The clinical data of NSCLC patients with documented BM from August 2007 to April 2015 of two hospitals were studied retrospectively. Cox regression was used for multivariate analysis. Survival of patients with or without postradiation systemic therapy was compared in subgroups stratified according to RTOG-RPA or GPA.</p><p><b>Results</b>Of 216 included patients, 67.1% received stereotactic radiosurgery (SRS), 24.1% received whole-brain radiation therapy (WBRT), and 8.8% received both. After radiotherapy, systemic therapy was administered in 58.3% of patients. Multivariate analysis found that postradiation systemic therapy (yes vs. no) (hazard ratio [HR] = 0.361, 95% confidence interval [CI] = 0.202-0.648, P = 0.001), radiation technique (SRS vs. WBRT) (HR = 0.462, 95% CI = 0.238-0.849, P = 0.022), extracranial metastasis (yes vs. no) (HR = 3.970, 95% CI = 1.757-8.970, P = 0.001), and Karnofsky performance status (<70 vs. ≥70) (HR = 5.338, 95% CI = 2.829-10.072, P < 0.001) were independent factors for survival. Further analysis found that subsequent tyrosine kinase inhibitor (TKI) therapy could significantly reduce the risk of mortality of patients in RTOG-RPA Class II (HR = 0.411, 95% CI = 0.183-0.923, P = 0.031) or with a GPA score of 1.5-2.5 (HR = 0.420, 95% CI = 0.182-0.968, P = 0.042). However, none of the subgroups stratified according to RTOG-RPA or GPA benefited from the additional conventional chemotherapy.</p><p><b>Conclusion</b>RTOG-RPA and GPA may be useful to identify beneficial populations in NSCLC patients with BM if TKIs were chosen as postradiation systemic therapy.</p>

Advances in treatment of radiation of non-small-cell lung cancer in the 15th World Conference on Lung Cancer / 肿瘤研究与临床

The 15th World Conference on Lung Cancer (WCLC) received about 210 abstracts on radiotherapy.These abstracts covered many realms,including the efficacy,safety,evaluation methods and dose fractionation study of stereotactic body radiotherapy (SBRT) on early stage non-small-cell lung cancer (NSCLC); control studies of high and standard radiation dose,different chemotherapy regimens and whether combined cetuximab in concurrent radiochemotherapy on locally advanced NSCLC clinical significance of postoperative 3D-conformal radiotherapy (3D-CRT) for patients with p Ⅲ A-N2 NSCLC after complete resection; the efficacy and safety of TKIs in combination with whole brain radiation therapy (WBRT) in NSCLC patients with multiple brain metastases,as well as the influence of EGFR mutation status on the curative effect.Besides,there are many reports about radiotherapy protection,toxicity,efficacy,prognosis and life quality assessment.

Multiple Gamma Knife Radiosurgery for Multiple Metachronous Brain Metastases Associated with Lung Cancer : Survival Time

OBJECTIVE: We compared the survival time between patients with multiple gamma knife radiosurgery (GKRS) and patients with a single GKRS plus whole brain radiation therapy (WBRT), in patients with multiple metachronous brain metastases from lung cancer. METHODS: From May 2006 to July 2010, we analyzed 31 patients out of 112 patients who showed multiple metachronous brain metastases. 20 out of 31 patients underwent multiple GKRS (group A) and 11 patients underwent a single GKRS plus WBRT (group B). We compared the survival time between group A and B. Kaplan-Meier method and Cox proportional hazards were used to analyze relationship between survival and 1) the number of lesions in each patient, 2) the average volume of lesions in each patient, 3) the number of repeated GKRS, and 4) the interval of development of new lesions, respectively. RESULTS: Median survival time was 18 months (range 6-50 months) in group A and 6 months (range 3-18 months) in group B. Only the average volume of individual lesion (over 10 cc) was negatively related with survival time according to Kaplan-Meier method. Cox-proportional hazard ratio of each variable was 1.1559 for the number of lesions, 1.0005 for the average volume of lesions, 0.0894 for the numbers of repeated GKRS, and 0.5970 for the interval of development of new lesions. CONCLUSION: This study showed extended survival time in group A compared with group B. Our result supports that multiple GKRS is of value in extending the survival time in patients with multiple metachronous brain metastases, and that the number of the lesions and the frequency of development of new lesions are not an obstacle in treating patients with GKRS.

Incidence and Risk Factors for Leptomeningeal Carcinomatosis in Breast Cancer Patients with Parenchymal Brain Metastases

OBJECTIVE: The objective of study is to evaluate the incidence of leptomeningeal carcinomatosis (LMC) in breast cancer patients with parenchymal brain metastases (PBM) and clinical risk factors for the development of LMC. METHODS: We retrospectively analyzed 27 patients who had undergone surgical resection (SR) and 156 patients with whole brain radiation therapy (WBRT) as an initial treatment for their PBM from breast cancer in our institution and compared the difference of incidence of LMC according to clinical factors. The diagnosis of LMC was made by cerebrospinal fluid cytology and/or magnetic resonance imaging. RESULTS: A total of 27 patients (14%) in the study population developed LMC at a median of 6.0 months (range, 1.0-50). Ten of 27 patients (37%) developed LMC after SR, whereas 17 of 156 (11%) patients who received WBRT were diagnosed with LMC after the index procedure. The incidence of LMC was significantly higher in the SR group compared with the WBRT group and the hazard ratio was 2.95 (95% confidence interval; 1.33-6.54, p<0.01). Three additional factors were identified in the multivariable analysis : the younger age group (<40 years old), the progressing systemic disease showed significantly increased incidence of LMC, whereas the adjuvant chemotherapy reduce the incidence. CONCLUSION: There is an increased risk of LMC after SR for PBM from breast cancer compared with WBRT. The young age (<40) and systemic burden of cancer in terms of progressing systemic disease without adjuvant chemotherapy could be additional risk factors for the development of LMC.

A Case of Complete Remission of Choriocarcinoma with Brain Metastases Treated with Multicycle High-dose MTX/EMA-CO, Intrathecal MTX and Whole Brain RT / 대한산부인과학회잡지

Patients of choriocarcinoma with brain metastases are considered to have a very poor prognosis due to chemo-refractoriness and recurrence. So, selection and individualization of patients then followed by multimodality therapy are very important. We present a case of a patient who experienced twice of craniotomies due to intracranial hemorrhage and an emergent explorative laparotomy due to intestinal perforation of the metastatic sites of choriocarcinoma. She was treated with 12 cycles of high-dose MTX/EMA-CO, intrathecal MTX and WBRT. Eventually she has obtained a complete remission that ongoing for 2 years. So, we report this case with a brief review of the literatures.

Clinical Features and Prognosis of Lung Cancer with Brain Metastasis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Brain metastasis is estimated to occur in 20~40% of solid tumor patients and the most common primary tumor is lung cancer. Even though the prognosis of brain metastasis is grave and the 1-year survival rate is only 15%, symptom palliations are made with whole brain radiation therapy. We retrospectively evaluated the clinical features and prognostic factors of lung cancer with brain metastasis. MATERIALS AND METHODS: From January 1987 to October 1999, 50 lung cancer patients with brain metastasis underwent whole brain radiation therapy. We reviewed the improvement in neurologic symptoms and survival according to the following parameters; performance status, histological type, presence of brain metastasis at the initial diagnosis of lung cancer, presence of extracranial metastasis, multiplicity of brain lesion, presence of primary lung symptom and treatment modalities. RESULTS: The most frequent symptom with brain metastasis was a headache (50%). Palliation of the headache and other symptoms was achieved in 81% of the patients. Median overall survival after brain metastasis was 21 weeks and the 1 year survival rate was 15%. Patients without extracranial metastasis had a longer median survival than those with, 38 weeks versus 15 weeks, respectively (p=0.01). CONCLUSION: In lung cancer with brain metastasis, neurologic symptoms can be palliated with whole brain radiation therapy, and in this study among such patients, absence of extracranial metastasis can be a good prognostic factor.