Analyses of the local control of pulmonary Oligometastases after stereotactic body radiotherapy and the impact of local control on survival.

BACKGROUND: Successful local therapy for oligometastases may lead to longer survival. The purpose of this multicentre retrospective study was to investigate factors affecting the local control (LC) of pulmonary oligometastases treated by stereotactic body radiotherapy (SBRT) and to investigate the impact of LC on survival. METHODS: The inclusion criteria included 1 to 5 metastases, the primary lesion and other extrathoracic metastases were controlled before SBRT, and the biological effective dose (BED10) of the SBRT was 75 Gy or more. The Cox proportional hazards model was used for analyses. RESULTS: Data of 1378 patients with 1547 tumours from 68 institutions were analysed. The median follow-up period was 24.2 months. The one-year, 3-year and 5-year LC rates were 92.1, 81.3 and 78.6%, respectively, and the 1-year, 3-year and 5-year overall survival rates were 90.1, 60.3 and 45.5%, respectively. Multivariate analysis for LC showed that increased maximum tumour diameter (p = 0.011), type A dose calculation algorithm (p = 0.005), shorter overall treatment time of SBRT (p = 0.035) and colorectal primary origin (p < 0.001 excluding oesophagus origin) were significantly associated with a lower LC rate. In the survival analysis, local failure (p < 0.001), worse performance status (1 vs. 0, p = 0.013; 2-3 vs. 0, p < 0.001), oesophageal primary origin (vs. colorectal origin, p = 0.038), squamous cell carcinoma (vs. adenocarcinoma, p = 0.006) and increased maximum tumour diameter (p < 0.001) showed significant relationships with shorter survival. CONCLUSIONS: Several factors of oligometastases and SBRT affected LC. LC of pulmonary oligometastases by SBRT showed a significant survival benefit compared to patients with local failure.

Factors related to primary cancer death and non-primary cancer death in patients treated with stereotactic body radiotherapy for pulmonary oligometastases.

Cancer-specific death (CSD) and non-cancer-specific death (non-CSD) after stereotactic body radiotherapy (SBRT) for pulmonary oligometastases have not been studied in detail. The aim of this study was to determine the cumulative incidences of CSD and non-CSD and to reveal prognostic factors. Data from a large survey of SBRT for pulmonary oligometastases were used for analyses, and patients with unknown cause of death were excluded from current analyses. CSD was primary cancer death and non-CSD was non-primary cancer death including a series of cancer treatment-related deaths. Cumulative incidences were calculated using the Kaplan-Meier method and a stratified Cox regression model was used for multivariate analyses (MVA). Fifty-two patients with an unknown death were excluded and a total of 1326 patients was selected. CSD and non-CSD occurred in 375 and 109 patients, respectively. The median OS period was 53.2 months and the cumulative incidences of 1-, 3-, and 5-year CSD vs. non-CSD rates were 6.5% vs. 2.3%, 29.5% vs. 8.6%, and 41.2% vs. 11.0%, respectively. In MVA, the incidence of CSD was related to performance status (1 vs. 0; p < 0.001, 2-3 vs. 0; p = 0.011), oligometastatic state (sync-oligometastases vs. oligo-recurrence, p = 0.026) and maximum tumor diameter (p = 0.009), and the incidence of non-CSD was related to age (p = 0.001), sex (p = 0.030), performance status (2-3 vs. 0; p = 0.002), and irradiated tumor-located lung lobe (left lower lobe vs. other lobes, p = 0.036). CSD was main cause of death, but non-CSD was not rare after SBRT. Prognostic factors for CSD and non-CSD were different, and an understanding of the factors would help in treatment.

Analyses of local control and survival after stereotactic body radiotherapy for pulmonary oligometastases from colorectal adenocarcinoma.

This study is a subset analysis of a retrospective multicenter study performed in Japan and its purpose was to investigate the effectiveness of stereotactic body radiotherapy (SBRT) for pulmonary oligometastases from colorectal cancer. Local control (LC), freedom from further metastases, relapse-free survival and overall survival (OS) after SBRT were retrospectively analyzed. The Kaplan-Meier method was used to estimate lifetime data and the log-rank test was performed as univariate analyses. The Cox proportional hazards model was applied in multivariate analyses. Data for 330 patients with 371 tumors were used for analyses. The median follow-up period was 25.0 months. The 3-year LC, freedom from further metastases, relapse-free survival and OS rates were 64.9, 34.9, 24.9 and 63.4%, respectively. The results of multivariate analyses showed that a higher LC rate was associated with no history of local therapy for oligometastases (P = 0.01), SBRT without concurrent chemotherapy (P < 0.01), type B calculation algorithm (P < 0.01) and higher biological effective radiation doses (≥115 Gy, P = 0.04). A longer OS was associated with no history of local therapy for oligometastases (P = 0.04), a more recent period of SBRT (2010-15, P = 0.02), tumor located in the upper or middle lobe (P < 0.01) and higher biological effective radiation doses (≥115 Gy, P = 0.01). In conclusion, OS after SBRT was good, but LC rate was relatively low. The use of high biological effective radiation doses can improve both LC and OS outcomes.

Pulmonary Oligometastases Treated by Stereotactic Body Radiation Therapy: A Nationwide Survey of 1,378 Patients.

AIM: This study was performed to confirm the superior overall survival (OS) after pulmonary oligo-recurrence compared to pulmonary sync-oligometastases in a large nationwide study. PATIENTS AND METHODS: Patients that met the following criteria were included: 1 to 5 lung-only metastases at the beginning of stereotactic body radiation therapy (SBRT) was performed between January 2004 and June 2015, and the biological effective dose (BED) of SBRT was 75 Gy or more. The parameters included in the analyses were age, gender, ECOG PS, primary lesion, pathology, oligoetastatic state, SBRT date, chemotherapy before SBRT, chemotherapy concurrent SBRT, chemotherapy after SBRT, maximum tumor diameter, number of metastases, field coplanarity, dose prescription, BED10, OTT of SBRT. RESULTS: In total, 1,378 patients with 1,547 tumors were enrolled. Oligo-recurrence occurred in 1,016 patients, sync-oligometastases in 118, and unclassified oligometastases in 121. The three-year OS was 64.0% for oligo-recurrence and 47.5% for sync-oligometastasis (p<0.001). In the multivariate analysis, the hazard ratio (HR) for sync-oligometastases versus oligo-recurrence was 1.601 (p=0.014). Adverse events of Grade 5 were occurred in 3 patients. CONCLUSION: This is the first nationwide to indicate that the OS of patients with pulmonary oligo-recurrence is better than that of patients with sync-oligometastases.

Serious gastric perforation after second stereotactic body radiotherapy for peripheral lung cancer that recurred after initial stereotactic body radiotherapy: a case report.

BACKGROUND: In recent reports, re-irradiation with stereotactic body radiotherapy for lung tumors in patients previously treated with thoracic radiation therapy resulted in several serious toxicities. Serious non-lung toxicities were observed mostly in patients with central tumors, but we experienced a case of fatal gastric perforation after a second stereotactic body radiotherapy in a patient with a peripheral lung tumor. CASE PRESENTATION: An 83-year-old Asian man was diagnosed with T2N0M0 lung cancer in the form of squamous cell carcinoma in the lower lobe of his left lung. He was treated with stereotactic body radiotherapy of 40 Gy in 4 fractions and the tumor decreased in size in partial response. The local tumor recurred 8 months after the first stereotactic body radiotherapy, and he was re-irradiated with a second stereotactic body radiotherapy of 50 Gy in 4 fractions. A Sengstaken-Blakemore tube was inserted below his diaphragm by laparoscopic surgery before the second stereotactic body radiotherapy in order to reduce the stomach dose by keeping his stomach apart from the tumor. Two months after the second stereotactic body radiotherapy, he developed fatal gastric perforation and gastropleural fistula penetrating his diaphragm. CONCLUSIONS: To the best of our knowledge, this is the first report about a gastric perforation after stereotactic body radiotherapy for lung tumors and it warns of serious complication of stereotactic body radiotherapy in not only centrally located but also peripherally located tumors like in this case.

Significant antitumor response of disseminated glioblastoma to bevacizumab resulting in long-term clinical remission in a patient with encephalocraniocutaneous lipomatosis: A case report.

The prognosis of recurrent and disseminated glioblastoma is very poor. Bevacizumab is an effective established therapy for recurrent glioblastoma following treatment with radiotherapy plus temozolomide. However, the efficacy of bevacizumab is limited to prolonging progression-free survival, without significant prolongation of the overall survival. We herein report a case of glioblastoma in a 32-year-old female patient with encephalocraniocutaneous lipomatosis (ECCL) that had disseminated following surgical resection and subsequent treatment with temozolomide and radiation therapy. The disseminated tumors disappeared completely after five courses of bevacizumab therapy. Surprisingly, the patient has remained in clinical remission for >2.5 years after dissemination by continuing this therapy. To the best of our knowledge, this is the first case of long-time clinical remission following glioblastoma dissemination and treatment with bevacizumab. In the present case, bevacizumab exerted an atypically strong antitumor effect against disseminated glioblastoma after multidisciplinary treatments had already been applied. Moreover, this is the first report of ECCL associated with a malignant brain tumor.

Stereotactic body radiotherapy for metachronous multisite oligo-recurrence: a long-surviving case with sequential oligo-recurrence in four different organs treated using locally radical radiotherapy and a review of the literature.

Stereotactic body radiotherapy (SBRT) for oligometastases represents a recent trend in radiation oncology. While abundant data are available regarding the use of SBRT for the treatment of lung or liver oligometastases from various retrospective series and prospective trials, relatively little information has been accumulated for the treatment of oligometastases at sites other than the lungs and liver, particularly for sequential oligometastases in multiple organs. Oligometastases with primary lesions controlled is called "oligo-recurrence." We describe herein the case of a lung cancer patient who developed repeated oligo-recurrence at multiple sites that were each controlled by radical radiotherapy and achieved long-term survival and discuss the merits of locally aggressive radiotherapy for this type of disease condition with reviewing the literature. Although further investigation should be undertaken to clarify the benefits, objectives, and methods of SBRT for the treatment of oligometastases, we believe utilization of SBRT may be worthwhile for patients with remote metastases who hope for treatment to acquire better local control and possible longer survival.