scholarly journals RT-01 Treatment results of salvage gamma knife and bevacizumab (AVAgamma therapy) for recurrent glioblastoma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii11-ii11
Author(s):  
Kenichi Sato ◽  
Taku Asanome ◽  
Yuuki Ishida ◽  
Hironori Sugio ◽  
Yoshimaru Ozaki ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Initial Treatment ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Treatment Results ◽  
Free Survival ◽  
Life Prognosis ◽  
Irradiation Volume ◽  
The Mean ◽  
Extended Discussion

Abstract Purpose: We report the treatment results of AVAgamma therapy combining gamma knife (GK) and bevacizumab for recurrent glioblastoma. Subjects: From August 2013 to April 2020, 44 patients (88 lesions) with recurrent glioblastoma treated with AVAgamma therapy as salvage therapy at the time of relapse after initial treatment. The average age is 61.5 years, with 26 men and 18 women. The tumor volume is 150 ml or less, and KPS is 40% or more as the indication of AVAgamma therapy. When the irradiation volume of GK is 15 ml or less, a single irradiation with a boundary dose of 20 to 26 Gy was performed, and when the irradiation volume was 15 ml or more, a single irradiation boundary dose was divided into two divided irradiations of 12 to 15 Gy. The mean therapeutic borderline dose was 24 Gy. Bevacizumab was administered 10 mg / kg or 15 mg / kg 1 to 10 times after GK. Methods: Median progression-free survival (mPFS), 6-month progression-free survival (PFS-6m), 6-month survival (OS-6m), median survival (mOS) from treatment with AVAgamma Considered mOS from initial treatment. Results: The mPFS from AVAgamma therapy was 5 months, PFS-6m was 37%, OS-6m was 79%, and mOS was 9 months. The mOS from initial treatment were 25 months. In relapsing glioma RPA classification, NABTT CNC class 5 mOS is 5.6 months, class 6 mOS is 6.4 months, but mOS from AVAgamma therapy is 9 months in class 5, 9 months in class 6. The survival time has been extended. Discussion: By AVAgamma therapy, it was thought that recurrent lesions were locally controlled and life prognosis was prolonged. Conclusion: AVAgamma therapy is thought to prolong the survival of recurrent glioblastoma and play an important role as salvage treatment.

scholarly journals RT-01 TREATMENT RESULTS OF SALVAGE GAMMA KNIFE STEREOTACTIC RADIOSURGERY AND BEVACIZUMAB (AVAGAMMA THERAPY) FOR RECURRENT GLIOBLASTOMA

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii21-ii21
Author(s):  
Kenichi Sato ◽  
Masami Takanashi ◽  
Yoshimaru Ozaki ◽  
Taku Asanome ◽  
Hironori Sugio ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Initial Treatment ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Treatment Results ◽  
Free Survival ◽  
Life Prognosis ◽  
Irradiation Volume ◽  
The Mean ◽  
Gamma Knife Stereotactic Radiosurgery

Abstract PURPOSE We report the treatment results of AVAgamma therapy combining gamma knife (GK) and bevacizumab for recurrent glioblastoma. SUBJECTS From August 2013 to April 2018, 42 patients (183 lesions) with recurrent glioblastoma treated with AVAgamma therapy as salvage therapy at the time of relapse after initial treatment. The average age is 61.1 years, with 25 men and 17 women. The tumor volume is 100 ml or less, and KPS is 40% or more as the indication of AVAgamma therapy. When the irradiation volume of GK is 15 ml or less, a single irradiation with a boundary dose of 20 Gy was performed, and when the irradiation volume was 15 ml or more, a single irradiation boundary dose was divided into two divided irradiations of 12 to 15 Gy. The mean therapeutic borderline dose was 24 Gy. Bevacizumab was administered 10 mg / kg or 15 mg / kg 1 to 10 times after GK. METHODS Median progression-free survival (mPFS), 6-month progression-free survival (PFS-6m), 6-month survival (OS-6m), median survival (mOS) from treatment with AVAgamma Considered mOS from initial treatment. [Results]: The mPFS from AVAgamma therapy was 5 months, PFS-6m was 37%, OS-6m was 84%, and mOS was 9 months. The mOS from initial treatment were 25 months. In relapsing glioma RPA classification, NABTT CNC class 5 mOS is 5.6 months, class 6 mOS is 6.4 months, but mOS from AVAgamma therapy is 9 months in class 5, 9 months in class 6. The survival time has been extended. DISCUSSION By AVAgamma therapy, it was thought that recurrent lesions were locally controlled and life prognosis was prolonged. CONCLUSION AVAgamma therapy is thought to prolong the survival of recurrent glioblastoma and play an important role as salvage treatment.

scholarly journals RT-1 Treatment results of salvage gamma knife stereotactic radiosurgery and bevacizumab (AVAgamma therapy) for recurrent malignant glioma

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi14-vi15
Author(s):  
Kenichi Sato ◽  
Taku Asanome ◽  
Yuuki Ishida ◽  
Hironori Sugio ◽  
Hirohiko Nakamura
Keyword(s):  
Malignant Glioma ◽  
Gamma Knife ◽  
Initial Treatment ◽  
Progression Free Survival ◽  
Recurrent Malignant Glioma ◽  
Treatment Results ◽  
Life Prognosis ◽  
Irradiation Volume ◽  
Gamma Knife Stereotactic Radiosurgery

Abstract Purpose: We report the treatment results of AVAgamma therapy combining gamma knife (GK) and bevacizumab for recurrent malignant glioma. Subjects: From August 2013 to January 2021, 71 patients (Grade 2:8 patients, Grade3:16 patients, Grade 4:47 patients) with recurrent malignant glioma treated with AVAgamma therapy as salvage therapy at the time of relapse after initial treatment. The average age is 55.7 years, with 44 men and 27 women. The tumor volume is 150 ml or less, and KPS is 40% or more as the indication of AVAgamma therapy. When the irradiation volume of the gamma knife was 15 ml or less, the marginal dose was 20 to 26 Gy, and when the irradiation volume was 15 ml or more, the marginal dose was 12 to 15 Gy in two divided doses.The mean therapeutic borderline dose was 24 Gy. Bevacizumab was administered 10 mg / kg or 15 mg / kg 1 to 10 times after GK. Methods: Median progression-free survival (mPFS) from AVAgamma treatment, median survival (mOS), and mOS from initial treatment were examined and compared with mOS in the RPA classification of recurrent glioma. Results: In relapsing glioma RPA classification, NABTT CNC class 2 mOS is 17.2 months, class 3 mOS is 3.8 months, class 5 mOS is 5.6 months, class 6 mOS is 6.4 months, but mOS from AVAgamma therapy is 18 months in class 3, 11 months in class 5, 9 months in class 6. The survival time has been extended in class3, class5, class6. Discussion: By AVAgamma therapy, it was thought that recurrent lesions were locally controlled and life prognosis was prolonged. Conclusion: AVAgamma therapy is thought to prolong the survival of recurrent malignant glioma and play an important role as salvage treatment.

Gamma Knife surgery for parasellar meningiomas: long-term results including complications, predictive factors, and progression-free survival

2011 ◽  
Vol 114 (6) ◽  
pp. 1571-1577 ◽  
Author(s):  
Brian J. Williams ◽  
Chun Po Yen ◽  
Robert M. Starke ◽  
Bhuvaneswara Basina ◽  
James Nguyen ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Cranial Nerve ◽  
Tumor Volume ◽  
Progression Free Survival ◽  
Gamma Knife Surgery ◽  
Tumor Control ◽  
Free Survival ◽  
Factors Associated ◽  
The Mean

Object Stereotactic radiosurgery serves as an important primary and adjuvant treatment option for patients with many types of intracranial meningiomas. This is particularly true for patients with parasellar meningiomas. In this study, the authors evaluated the outcomes of Gamma Knife surgery (GKS) used to treat parasellar meningiomas. Methods The study is a retrospective review of the outcomes in 138 patients with meningiomas treated at the University of Virginia from 1989 to 2006; all patients had a minimum follow-up of 24 months. There were 31 men and 107 women whose mean age was 54 years (range 19–85 years). Eighty-four patients had previously undergone resection. The mean pre-GKS tumor volume was 7.5 ml (range 0.2–54.8 ml). Clinical and radiographic evaluations were performed, and factors related to favorable outcomes in each case were assessed. Results The mean follow-up duration was 84 months (median 75.5 months, range 24–216 months). In 118 patients (86%), the tumor volume was unchanged or had decreased at last follow-up. Kaplan-Meier analysis demonstrated radiographic progression-free survival at 5 and 10 years to be 95.4% and 69%, respectively. Fourteen patients (10%) developed new cranial nerve palsies following GKS. Factors associated with tumor control included younger age, a higher isodose, and smaller tumor volume. A longer follow-up duration was associated with either a decrease or increase in tumor volume. Fourteen patients (10%) experienced new or worsening cranial nerve deficits after treatment. Factors associated with this occurrence were larger pretreatment tumor volume, lower peripheral radiation dose, lower maximum dose, tumor progression, and longer follow-up. Conclusions Gamma Knife surgery offers an acceptable rate of tumor control for parasellar meningiomas and accomplishes this with a low incidence of neurological deficits. Radiological control after radiosurgery is more likely in those patients with a smaller tumor volume and a higher prescription dose.

NIMG-54. RADIOMIC FEATURES FROM LESION HABITAT PREDICT RESPONSE TO COMBINATION OF NIVOLUMAB AND BEVACIZUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA: A FEASIBILITY STUDY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi141-vi141
Author(s):  
Ruchika Verma ◽  
Yasmeen Rauf ◽  
Ipsa Yadav ◽  
Volodymyr Statsevych ◽  
Jonathan Chen ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Poor Response ◽  
Response Assessment ◽  
Complete Response ◽  
Recurrent Glioblastoma ◽  
Proportional Hazard ◽  
Free Survival ◽  
Cox Proportional Hazard ◽  
Expert Radiologist ◽  
Mri Scans

Abstract PURPOSE The use of immunotherapy in glioblastoma management is under active investigation. Glioblastomas are “cold” tumors, meaning that they have inactivated or fewer tumor infiltrative lymphocytes in addition to substantial tumor necrosis, attributing to their poor response to immunotherapy. A significant challenge is the apriori identification of Glioblastoma patients who will respond favorably to immunotherapy. In this work, we evaluated the ability of computerized MRI-based quantitative features (radiomics) extracted from the lesion habitat (including enhancing lesion, necrosis, and peritumoral hyperintensities) to predict response and progression-free survival (PFS) in recurrent GBM patients treated with combination of Nivolumab and Bevacizumab. METHODS Immunotherapy response assessment in neuro-oncology (iRANO) criteria along with PFS were used to analyze n=50 patients enrolled in a randomized clinical trial where patients received Nivolumab with either standard or low dose Bevacizumab. These patients were assessed to see if they had complete response, partial response, stable disease (i.e. responders, n=31), or disease progression (i.e. non-responders, n=19). Lesion habitat constituting necrotic core, enhancing tumor, and edema were delineated by expert radiologist on Gd-T1w, T2w and FLAIR MRI scans. COLIAGE radiomic features from each of the delineated regions were selected using minimum redundancy maximum relevance (mRMR) via cross-validation, to segregate non-responder patients from responders. A multivariable cox proportional hazard model was used to predict survival (PFS). RESULTS CoLlAGe correlation, sum average, and sum variance features (capture local heterogeneity) from the lesion habitat, were found to segregate non-responder patients from responders with an accuracy of 86%, followed by 80% using features from peritumoral hyperintensities and 78% from enhancing tumor. In our survival analysis, C-index of 0.688 was obtained using features from the entire lesion habitat, followed by peritumoral hyperintensities (0.675) and enhancing tumor (0.656). CONCLUSION Radiomic features from the lesion habitat may predict response to combination of Nivolumab and Bevacizumab in recurrent Glioblastomas.

scholarly journals Treatment of Residual, Recurrent, or Metastatic Intracranial Hemangiopericytomas With Stereotactic Radiotherapy Using CyberKnife

2021 ◽  
Vol 11 ◽  
Author(s):  
Lichao Huang ◽  
Jingmin Bai ◽  
Yanyang Zhang ◽  
Zhiqiang Cui ◽  
Zhizhong Zhang ◽  
...  
Keyword(s):  
Stereotactic Radiotherapy ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Tumor Control ◽  
Intracranial Metastasis ◽  
Free Survival ◽  
The Mean ◽  
Aggressive Tumors

PurposeHemangiopericytomas are aggressive tumors known for their recurrence. The purpose of this study was to evaluate the management of residual, recurrent, and metastatic intracranial hemangiopericytomas using CyberKnife (CK) stereotactic radiotherapy (SRT).Materials and MethodsData were collected from 15 patients (28 tumors; eight men and seven women; 32–58 years) with residual, recurrent, or metastatic intracranial hemangiopericytomas, who were treated with stereotactic radiotherapy using CyberKnife between January 2014 and August 2019. All patients had previously been treated with surgical resection. Initial tumor volumes ranged from 0.84 to 67.2 cm3, with a mean volume of 13.06 cm3. The mean marginal and maximum radiosurgical doses to the tumors were 21.1 and 28.76 Gy, respectively. The mean follow-up time for tumors was 34.5 months, ranging from 13 to 77 months.Results15 patients were alive after treatment; the mean post-diagnosis survival at censoring was 45.6 months (range 13–77 months). The volumes of the 28 tumors in the 15 followed patients were calculated after treatment. Postoperative magnetic resonance imaging revealed a mean tumor volume of 6.72 cm3 and a range of 0–67.2 cm3, with the volumes being significantly lower than pretreatment values. Follow-up imaging studies demonstrated tumor disappearance in seven (25%) of 28 tumors, reduction in 14 (50%), stability in one (3.57%), and recurrence in six (21.4%). Total tumor control was achieved in 22 (78.5%) of 28 tumors. The tumor grade and fraction time were not significantly associated with progression-free survival. Intracranial metastasis occurred in three patients, and extraneural metastasis in one patient.ConclusionsOn the basis of the current results, stereotactic radiotherapy using CyberKnife is an effective and safe option for residual, recurrent, and metastatic intracranial hemangiopericytomas. Long-term close clinical and imaging follow-up is also necessary.

The influence of overall treatment time to the efficiency of chemo-radiotherapy for locally advanced cervical cancer

2017 ◽  
Vol 17 (1) ◽  
pp. 124-130
Author(s):  
Ekkasit Tharavichitkul ◽  
Panupat Rugpong ◽  
Nisa Chawapun ◽  
Razvan M. Galalae
Keyword(s):  
Cervical Cancer ◽  
Treatment Time ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Intracavitary Brachytherapy ◽  
Treatment Results ◽  
Overall Treatment Time ◽  
Free Survival ◽  
Significant Difference ◽  
The Mean

AbstractPurposeThis study aims to clarify the influence of overall treatment time (OTT) on the efficiency of combined chemo-radiotherapy in cervical cancer.Material and methodsThis retrospective study enrolled 122 cervical cancer patients who had squamous cell carcinoma and had undergone definitive chemo-radiotherapy from 2009 to 2013. All patients received whole pelvic radiotherapy (WPRT) with the dose of 50 Gy in 25 fractions (with central shielding after 44 Gy) plus intracavitary brachytherapy with the dose of 28 Gy in four fractions. During WPRT, all patients received concurrent chemotherapy with weekly platinum-based regimen. The data of patient characteristics, OTT, treatment results and toxicities were collected and evaluated.ResultsThe mean follow-up time was 36 months. The mean age of patients was 52 years old; 68% of patients were stage IIB related to International Federation of Gynaecology and Obstetrics staging. Pelvic control (PC), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) rates did not differ significantly in the data-derived cut points of 55·8 and 53 days. No statistically significant difference in treatment results between the two groups of OTT<49 and OTT≥62 days was observed.ConclusionsIn our data-derived cut point, OTT did not influence to PC, DMFS, DFS and OS. The influence of OTT on treatment results may be found in longer periods.

Phase 1, 2 trial of concurrent anti-PD1 and stereotactic radiosurgery for melanoma and non-small cell lung cancer brain metastases (NCT02858869).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2022-2022
Author(s):  
Mohammad Khurram Khan ◽  
Tahseen Nasti ◽  
Troy Kleber ◽  
David H. Lawson ◽  
Melinda Lynne Yushak ◽  
...  
Keyword(s):  
T Cells ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Clinical Benefit ◽  
Progression Free Survival ◽  
Free Survival ◽  
Early Activation ◽  
Previously Treated ◽  
The Mean ◽  
Grade 3

2022 Background: The safety and efficacy of concurrent pembrolizumab (anti-PD1) and stereotactic radiosurgery (SRS) for brain metastases (BM) is unknown. Methods: Patients with melanoma or NSCLC, 1-10 brain metastases, ≥ 1 extra-cranial lesion, age ≥ 18, and ECOG 0-1 were treated with anti-PD1 every 3 weeks. SRS was administered 1-2 days after starting anti-PD1. SRS used three different radiation arms: Arm A used 6 Gray (Gy) in 5 fractions (fx), Arm B used 9 Gy in 3 fx, and Arm C used 18-21 Gy in single fx. Primary endpoint was grade 3 CNS toxicity at 3 months (CTCAE v 4.0). Secondary endpoints were overall survival (OS), local control (LC) within the SRS field, intra-cranial progression free survival (IC-PFS), extra-cranial progression free survival (EC-PFS), rate of extra-cranial clinical benefit, and immunological changes. OS, LC, IC-PFS, and EC-PFS were estimated using the Kaplan-Meier method, and covariates were compared using log-rank tests. 95% confidence intervals for 6-month and 12-month were estimated using Greenwood’s formula. Results: 25 patients were treated from 2016 until 2020. The mean age was 61. The mean number of CNS lesions was 2.7. The mean number of extra-cranial lesions was 2.5. Six were enrolled on Arm A, 12 on Arm B, and 7 on Arm C. 21 had melanoma. 4 had NSCLC. Of the melanoma, 8 were BRAF-, 10 were BRAF+, and 3 had unknown mutation status. 12 patients (48%) had progressed on prior immunotherapy and/or other oncological therapies. The trial met its primary endpoint, with no grade 3 CNS toxicity at 3 months. Two patients (8%) experienced ≥ Grade 3 anti-PD1 related toxicity, and no grade 5 toxicity was noted. The median OS was 32.8 months. The 6 and 12 month OS were 79.1% (56.5-90.8%) and 67.8% (43.3-83.5%), respectively. The 1 year OS was similar between previously treated and treatment naïve patients (71.8% vs. 65.6%), suggesting some role for SRS in overcoming therapy resistance. However, with longer follow-up, the OS trended worse (p=0.07) for previously treated patients. LC was 95.7% (72.9-99.4%) at 6 and 12 months. IC-PFS at 6 months was 69.1% (45.8-83.9%), and at 12 months was 57.5% (33.7-75.5%). The EC-PFS at 6 and 12 month was 54.5% (32.1-72.4%) and 43.6% (22.3-63.2%), respectively. Clinical benefit, which was defined as a best overall response of stable disease or better according to RECIST 1.1, occurred in 12 patients (48%). No outcome differences were noted amongst the three different SRS arms. 70% of the patients demonstrating early activation (within 3 weeks of starting SRS/anti-PD1) of CD8+PD1+Ki67+ T cells demonstrated a clinical benefit. 100% of patients that failed to show early activation of CD8+PD1+Ki67+ T cells progressed. Conclusions: Concurrent pembrolizumab (Anti-PD-1) and SRS is safe and effective. Early activation of CD8+PD1+Ki67+ T cells correlates with improved outcome. Further trials testing pembrolizumab and SRS are justified. Clinical trial information: NCT02858869.

Comparative Analysis of Durable Responses on Immune Checkpoint Inhibitors Versus Other Systemic Therapies: A Pooled Analysis of Phase III Trials

2019 ◽  
pp. 1-10 ◽  
Author(s):  
Elvire Pons-Tostivint ◽  
Aurélien Latouche ◽  
Pauline Vaflard ◽  
Francesco Ricci ◽  
Delphine Loirat ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Durable Response ◽  
Free Survival ◽  
Drug Classes ◽  
Metastatic Setting ◽  
The Mean

PURPOSE Immune checkpoint inhibitors (ICIs) have been demonstrated to improve overall survival (OS) in several tumor types. Durable responses have been reported with these agents in patients with melanoma and lung cancer. We aimed to quantify the proportion of patients who experience durable responses on ICIs and to compare it with other drug classes. PATIENTS AND METHODS We retrieved published phase III randomized trials that included at least one ICI arm in the recurrent and/or metastatic setting. A durable response to treatment was defined as a progression-free survival that exceeded three times the median progression-free survival of the whole population. The proportion of patients who experienced an OS that exceeded two times the median OS of the whole patient population also was estimated. RESULTS Nineteen studies involving 11,640 patients treated in 42 treatment arms (26 ICI and 16 non-ICI arms) were included. The mean proportion of patients who experienced a durable response was 2.3 times higher in those treated with an ICI compared with those treated in the control arms (25% v 11%). Durable responses were more frequent in patients treated with anti–PD-1/PD-L1 agents than in patients treated with anti–CTLA-4 agents (28% v 18%). The mean proportion of patients who had an OS that exceeded two times the median OS was also higher in those treated with ICIs than in those treated in the control arms (30% v 23%). In multivariable analysis, the effects of treatment with anti–PD-1/PD-L1 agents and of first-line treatment were statistically associated with a higher mean proportion of durable responses. CONCLUSION Durable responses were more frequent in patients treated with ICIs, although they also occurred in patients treated with other drug classes.

scholarly journals P14.15 Benefit of Bevacizumab for recurrent glioblastoma. Results of 81 patients from a single institution

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii69-iii69
Author(s):  
O Absalyamova ◽  
G Kobiakov ◽  
G Agabekyan ◽  
A Poddubsky ◽  
A Belyashova ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Rapid Progression ◽  
Concomitant Disease ◽  
Free Survival ◽  
Phase Iii Trials ◽  
Continuous Application

Abstract BACKGROUND No standard of care has been established for patients with progressive glioblastoma (rGBM). Previous studies suggested that bevacizumab (BEV) is safe and produces responses that result in a decreased use of glucocorticoids and increased progression-free survival (PFS) with an unclear effect on overall survival (OS). Crossover to BEV in the control arm is the possible reason why the advantage of BEV has not been proven in Phase III trials. We retrospectively analyzed own results of BEV treatment in rGBM. MATERIAL AND METHODS 81 patients progressed after radiotherapy plus concomitant and maintenance temozolomide (TMZ) and undergo BEV as monotherapy (BevMo, 11 patients) or in combinations (Irinotecan (BevI) - 53, lomustine (BevL)- 11, TMZ (BevT) - 6. Median age 54 years. Among them 33 patients were re-irradiated: 11 - radiosurgery (RS), 20 fractionated irradiation (RT), 2 - RS+RT. 33 patients continued BEV after progression with changing or adding cytostatic. PFS was calculated from the date of verification, PFS1 - from the date of 1-st progression, PFS2 - from the date of 2-nd progression. RESULTS Median PFS was 9.0 ([CI] 7.0–10.9) months. Median PFS1 was 10.5 ([CI] 8.1–12.9) months. In the BevMo, BevI, BevL, BevT group PFS1 was 15.7, 10.1, 10.5, 13.2 months, respectively, p=0.7. Objective response (OR) was reached in 34%, stable disease (SD) in 28%, progression (PD) in 37% patients. 16 patients stopped BEV without progression (4-patient`s decision, 7- doctor`s decision, 2 - adverse event, 3 - concomitant disease). Median time of BEV treatment was 11.6 months. Median BEV-free interval till progression was 3.7 months. 33 patients continued or restarted BEV after progression. Median PFS2 was 8.0 ([CI] 4.9–11.1) months. The median OS from the date of 1-st progression was 23.5 months ([CI] 18.7–27.4). In groups with RT, RS, RS+RT and no re-irradiarion OS was 24.6 ([CI] 17.6–31.5), 35.4 ([CI] 35.0–35.8), 17.8, 20.6 ([CI] 15.2–26.0), respectively, p=0.2. CONCLUSION OS in our group is outrageously high. Maintaining BEV after progression was effective. In our group BEV discontinuation led to rapid progression. The resumption of Bev with progression was effective, which indicates the advisability of its continuous application.

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