Ge Shen

Incidence and relapse risk of intracranial metastases within the perihippocampal region in 314 patients with breast cancer

PURPOSE The safe prerequisite of hippocampal-sparing whole brain radiotherapy (HS-WBRT) for patients with breast cancer is unclear. This study investigated the risk and relapse of perihippocampal (PH) metastases in breast cancer. METHODS Consecutive breast cancer patients with brain metastasis (BM) were reviewed. Metastases and hippocampi were contoured in cranial magnetic resonance imaging (MRI). The closest distance from metastasis to hippocampus was calculated. Clinical and radiographic variables were correlated with PH (in or within 5mm around the hippocampus) metastasis. The risk of post-treatment PH recurrence was estimated. RESULTS Three hundred and fourteen patients with 1678 metastases exhibited a median breast cancer-specific overall survival (OS) and OS after BM (BMOS) of 75.4 and 14.3 months, respectively. Hippocampal metastases were identified in 1.2% of metastases and 4.1% of patients. PH lesions comprised 3.5% of lesions in 11.1% of patients. The number and aggregated volume of BM were associated with PH disease probability (univariate). Only the number of BM significantly correlated with PH disease in the multivariate analysis. The patients with PH lesions exhibited more non-oligometastatic disease, increased tumor volume, and poor BMOS. One hundred and eleven patients without original PH lesions developed intracranial progression post-treatment. The risks of PH metastasis recurrence were 4.6% for WBRT and 6.8% for sub-therapeutic irradiation in the PH region. The increase in the absolute risk of PH recurrence with hippocampal-sparing irradiation was approximately 2%. CONCLUSIONS These novel findings indicate that BM from breast cancer exhibits low risks of metastases and relapse within the hippocampal avoidance region. Non-oligometastatic disease is associated with PH metastasis. Thus, HS-WBRT is considered safe and suitable for breast cancer.

Abscopal regression following SABR for non-small-cell-lung cancer: A case report

ABSTRACT Out-of-field tumor response, which is also called abscopal effect, bystander effect, or non-target effect, can be regarded as localized irradiation induced systemic antitumorigenic effects, indicating shrinkage of a tumor distant from the irradiated site. Although abscopal effect has been documented in several tumor types, it is a very rare phenomenon which is clinically reported in non-small-cell-lung carcinoma (NSCLC). Herein, we present a rare case of patient with NSCLC with 2 lesions in the upper lobe of left lung who, after receiving stereotactic ablative radiation therapy (SABR) to one of the tumors, had an apparent spontaneous regression of the other mass in the lung, suggestive of a radiation-induced abscopal effect.

Double CT imaging can measure the respiratory movement of small pulmonary tumors during stereotactic ablative radiotherapy

PURPOSE The purpose of this study was to investigate the application of double CT imaging to measuring the respiratory movement of small pulmonary tumors during stereotactic ablative radiotherapy (SABR). METHODS A total of 122 small pulmonary tumors were measured in 45 patients. CT scans were conducted twice in all 122 tumors, once at the end of quiet inhalation and once at the end of exhalation. CT scans were conducted three times including at the end of quiet inhalation, at the end of exhalation and at free breathing in 36 tumors of 17 patients. The displacement of the tumor center in three directions was measured. RESULTS The 3D motion of 122 tumors was 10.10±7.16 mm. On average, the tumors moved 1.96±2.03 mm (rang, 0-9 mm) in the X direction, 5.19±4.69 mm (rang, 0-19 mm) in the Y direction, and 7.38±6.48 mm (rang, 0-26 mm) in the Z direction. The 3D motion of tumors in the lower lung (13.00±7.64 mm) was significantly greater than that in the upper lung (7.15±5.14 mm), P<0.01. The 3D motion of the lower left lung was 16.35±7.31 mm, which was significantly greater than that of the lower right lung (11.40±7.04 mm), P<0.05. Movement in the anterior lung in the Y direction was significantly larger than in the posterior lung. The motion was 7.49±5.43 mm and 4.04±3.82 mm respectively, P<0.01. CONCLUSIONS Double CT imaging provides accurate data for determining the outline of each target area during stereotactic ablative radiotherapy plane. The location of small pulmonary tumor foci was significantly affected by respiratory and cardiac motion.

PD-1 mRNA expression in peripheral blood cells and its modulation characteristics in cancer patients

Immune checkpoint inhibitors that block the PD-1/PD-L1 signaling pathway have been used to treat a wide variety of cancers. Although results have been promising, significant inter-individual and inter-tumor variability has been observed. It is believed that better clinical outcome could be achieved if the treatment was individually designed based on the functional status of the PD-1/PD-L1 signaling and the cellular immunity. In this study, we analyzed the mRNA expression of PD-1 and other immunomodulatory genes in peripheral blood from cancer patients, and immunomodulatory gene expression during radiotherapy and immunomodulation therapy with cytokines. Our results show that the PD-1 mRNA expression is significantly increased in peripheral blood in cancer patients. Anti-cancer treatments can significantly modulate the PD-1 expression, but this is largely dependent on the initial immune status. Moreover, the PD-1 expression on peripheral lymphocytes can be immunoactivation-derived. These results suggest that the regulation and expression pattern of PD-1/PD-L1 signal is complicated which will influence the effect of blockade of the PD-1/PD-L1 signaling pathway for cancer treatment. Through combined analysis of PD-1, CTLA-4, and other immune markers in peripheral blood, we may accurately evaluate the functional status of PD-1/PD-L1 signaling and cellular immunity, thereby providing clues for guiding anti-PD-1 or anti-PD-L1 treatment.Immune checkpoint inhibitors that block the PD-1/PD-L1 signaling pathway have been used to treat a wide variety of cancers. Although results have been promising, significant inter-individual and inter-tumor variability has been observed. It is believed that better clinical outcome could be achieved if the treatment was individually designed based on the functional status of the PD-1/PD-L1 signaling and the cellular immunity. In this study, we analyzed the mRNA expression of PD-1 and other immunomodulatory genes in peripheral blood from cancer patients, and immunomodulatory gene expression during radiotherapy and immunomodulation therapy with cytokines. Our results show that the PD-1 mRNA expression is significantly increased in peripheral blood in cancer patients. Anti-cancer treatments can significantly modulate the PD-1 expression, but this is largely dependent on the initial immune status. Moreover, the PD-1 expression on peripheral lymphocytes can be immunoactivation-derived. These results suggest that the regulation and expression pattern of PD-1/PD-L1 signal is complicated which will influence the effect of blockade of the PD-1/PD-L1 signaling pathway for cancer treatment. Through combined analysis of PD-1, CTLA-4, and other immune markers in peripheral blood, we may accurately evaluate the functional status of PD-1/PD-L1 signaling and cellular immunity, thereby providing clues for guiding anti-PD-1 or anti-PD-L1 treatment.

Relief Effect of Bevacizumab on Severe Edema Induced by Re-irradiation in Brain Tumor Patients.

IntroductIon Brain edema is a serious clinical event and could cause various neurological symptoms such as dizziness and headache. Drugs frequently used to relieve brain edema include steroid, dehydrant (e.g., mannitol), and diuretics. But the effects of these drugs were limited in patients with severe edema. Bevacizumab has been applied in the treatment of cerebral radiation necrosis.[1] Case studies have reported on the application of bevacizumab in the treatment of severe brain edema.[2] In the present study, we describe significant effects of bevacizumab on severe brain edema in patients with re‐irradiation.

Stereotactic body radiation therapy for centrally‑located lung tumors

The application of high-dose irradiation to centrally-located lung tumors is generally considered to be of high risk in causing bronchial injury. The aim of the present retrospective study was to investigate the safety and efficacy of stereotactic body radiation therapy (SBRT) for patients with centrally-located lung tumors. In total, 28 patients who underwent SBRT for lung tumors within 2 cm of a major bronchus were retrospectively analyzed. The median total dose prescribed was 45 Gy (range, 36.3–52.5 Gy), the median fraction was 12 (range, 10–15) and the median dose per fraction was 3.6 Gy (range, 3–5 Gy). The median follow-up period for the surviving patients was 14 months (range, 10–41 months). The local control rate of SBRT was 100%, with a complete response (CR) rate of 32.1% (9/28); a partial response (PR) rate of 50% (14/28) and a stable disease (SD) rate of 17.9% (5/28). In total, 15 patients survived and 13 patients succumbed; 11 patients succumbed to tumor progression, one to congestive heart failure and one to a brain hemorrhage. The main side-effects included grade 2 esophagitis (17.9%; 5/28) atelectasis (10.7%; 3/28) and grade 2 late radiation pneumonitis (7.1%; 2/28). Severe late toxicity (≥ grade 3) was not observed in any patient. SBRT is an effective and safe therapy for centrally-located lung tumors.

Predictive value of peripheral regulatory T cells in non-small cell lung cancer patients undergoing radiotherapy

Background Studies increasingly focus on the impact of radiotherapy on immunity; however, the role of peripheral cellular immunity prior to radiotherapy in cancer patients remains largely unknown. In this study, we investigated the predictive roles of lymphocyte subsets on tumor progression in non-small cell lung cancer (NSCLC) patients undergoing radiotherapy, and their expression in NSCLC patients at first relapse. Methods We enrolled 70 NSCLC patients and 14 age- and sex-matched healthy donors and tested the lymphocyte subsets in their peripheral blood by flow cytometry. Among them, 40 newly diagnosed patients received radiotherapy and were enrolled to investigate the predictive value of lymphocyte subsets on tumor progression after radiotherapy by uni- and multivariate analyses; 30 patients at first relapse were included to evaluate the differences of lymphocyte subsets between them and first diagnosed patients and healthy volunteers. Results Increased proportions of regulatory T cells, CD8+ T cells, and CD8+CD28- T cells and decreased CD4+ T cells and CD4/CD8 ratios were observed in NSCLC patients at first relapse compared to newly diagnosed patients. In the 40 first diagnosed patients undergoing radiotherapy, uni- and multivariate analyses showed that increased level of regulatory T cells correlated with poor progression-free survival (hazard ratio = 2.55 and 3.76, P = 0.022 and 0.010, respectively). Conclusions Peripheral regulatory T cells were increased and independently predict tumor progression in NSCLC patients undergoing radiotherapy, suggesting the promising combination of radiotherapy and immunotherapy.

A nomogram for predicting survival in patients with breast cancer brain metastasis

Brain metastasis (BM) is common in patients with breast cancer. Predicting patient survival is critical for the clinical management of breast cancer brain metastasis (BCBM). The present study was designed to develop and evaluate a prognostic model for patients with newly diagnosed BCBM. Based on the clinical data of patients with BCBM treated in the Affiliated Hospital of Academy of Military Medical Sciences (Beijing, China) between 2002 and 2014, a nomogram was developed to predict survival using proportional hazards regression analysis. The model was validated internally by bootstrapping, and the concordance index (c-index) was calculated. A calibration curve and c-index were used to evaluate discriminatory and predictive ability, in order to compare the nomogram with widely used models, including recursive partitioning analysis (RPA), graded prognostic assessment (GPA) and breast-graded prognostic assessment (Breast-GPA). A total of 411 patients with BCBM were included in the development of this predictive model. The median overall survival time was 14.1 months. Statistically significant predictors for patient survival included biological subtype, Karnofsky performance score, leptomeningeal metastasis, extracranial metastasis, the number of brain metastases and disease-free survival. A nomogram for predicting 1- and 2-year overall survival rates was constructed, which exhibited good accuracy in predicting overall survival with a concordance index of 0.735. This model outperformed RPA, GPA and Breast-GPA, based on the comparisons of the c-indexes. The nomogram constructed based on a multiple factor analysis was able to more accurately predict the individual survival probability of patients with BCBM, compared with existing models.

Brain metastasis reirradiation in patients with advanced breast cancer

The outcome of recurrent brain metastasis is dismal. This study aims to assess the clinical outcomes and toxicity of reirradiation as a salvage treatment for progressive brain metastasis in patients with advanced breast cancer. Between July 2005 and September 2014, the medical records of 56 patients with brain metastasis from breast cancer were retrospectively reviewed. Of these patients, 39 received whole-brain radiotherapy (WBRT) followed by stereotactic radiosurgery (SRS) reirradiation (Group 1), and 17 received SRS followed by WBRT reirradiation (Group 2). Overall survival (OS) and brain progression-free survival rates/times were calculated using the Kaplan–Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Change in neurologic function was also assessed. The median OS was 10.8 months (range, 1.3–56.8 months). In Group 1, the median PFS time (PFS-1) was 6.5 months and the OS time was 11.4 months. Multivariate analysis revealed that longer OS was significantly associated with a high Karnofsky performance score (KPS) (P = 0.004), controlled extracranial metastasis (P = 0.001) and a good response to reirradiation (P = 0.034). In Group 2, the median PFS time (PFS-2) after reirradiation was 8.5 months and the OS time was 10.8 months. Multivariate analysis revealed that longer OS was significantly associated with a high KPS (P = 0.018). The majority of the patients had improved or stable neurological function. Reirradiation is an effective and a safe treatment for patients with brain metastases from breast cancer. It might delay the progression of intracranial disease and improve neurological function. A suitable patient selection for reirradiation was suggested.

Efficacy of repeated low-dose bevacizumab treatment with long-dosing interval for radiation-induced brain necrosis: a case report.

ABSTRACT A 40-year-old Chinese female patient, with radiation-induced brain necrosis after radiosurgery, was treated 6 times with a single dose of 200 mg (3.27 mg/kg) bevacizumab each time, and with an interval of 12–16 weeks between each treatment. Neurological symptoms such as dizziness, fatigue, and headache disappeared after each administration of bevacizumab. The results suggest that repeated bevacizumab treatment using a low-dose and long-dosing interval may significantly alleviate radiation necrosis and its symptoms.