Surgical management of metastatic sarcoma to the brain

2009 ◽  
Vol 110 (1) ◽  
pp. 181-186 ◽  
Author(s):  
Benjamin D. Fox ◽  
Akash Patel ◽  
Dima Suki ◽  
Ganesh Rao

Object Metastatic sarcoma to the brain is rare and represents a therapeutic challenge due to its relative resistance to radio- and chemotherapy. Resection has traditionally been the mainstay of treatment. The authors reviewed a series of patients with metastatic sarcoma to the brain treated surgically to determine outcomes and identify predictors of survival in these patients. Methods A retrospective review of prospectively collected data was undertaken on patients undergoing surgery between 1993 and 2005 for metastatic sarcoma to the brain at The University of Texas, M.D. Anderson Cancer Center. Results During the study period, 62 patients underwent 84 operations for metastatic sarcoma to the brain. The median postoperative overall and progression-free survival rates were 7.5 and 4.7 months, respectively. Fifty-nine (95%) of 62 patients had a gross-total resection. The 30-day mortality rate was 4.2%. The Karnofsky Performance Scale scores at discharge from the hospital and 3 months postoperatively were the same or improved in 50 (85%) of 59 and 26 (51%) of 51, respectively. Overall postcraniotomy survival was 62% at 6 months, 39% at 1 year, 21% at 2 years, and 8% at 5 years. In multivariate and univariate analysis, control of systemic disease, and sarcomas originating from bone, cartilage, or soft tissue were predictors of survival. Patients with control of systemic disease had survival advantage when compared with those who did not. In patients with alveolar soft-part sarcoma, there was a significantly increased survival advantage compared with all other histological subgroups. Conclusions The authors' results suggest that in selected patients, resection of metastatic sarcoma to the brain is associated with a relatively low risk of operative death and results in improvement in neurological function. Patients with systemic control of their primary disease and certain histological subtypes (specifically alveolar soft-part sarcoma) have improved overall and progression-free survival.

2014 ◽  
Vol 32 (34) ◽  
pp. e114-e116 ◽  
Author(s):  
John M. Goldberg ◽  
Tara Gavcovich ◽  
Gaurav Saigal ◽  
Jonathan W. Goldman ◽  
Lee S. Rosen

2021 ◽  
Vol 42 (01) ◽  
pp. 051-060
Author(s):  
Vineet Agrawal ◽  
Smita Kayal ◽  
Prasanth Ganesan ◽  
Biswajit Dubashi

Abstract Background Treatment protocols for acute lymphoblastic leukemia (ALL) have evolved over time to give excellent cure rates in children and moderate outcomes in adults; however, little is known how delays in chemotherapy affect long-term survival. Objectives To find the association of delays during different treatment phases on the survival outcomes. Materials and Methods Data from 149 ALL cases treated between 2009 and 2015 were retrospectively analyzed. Treatment course in commonly used protocols was divided into three phases—induction, consolidation (postremission), maintenance, and also a combined intensive phase (induction plus consolidation) for the purpose of analysis, and delay in each phase was defined based on clinically acceptable breaks. Analysis was done to find the impact of treatment delay in each phase on the survival outcomes. Results The median age was 12 years (range, 1–57). Multi-center Protocol-841 (MCP-841) was used for 72%, German Multicenter Study Group for Adult ALL (GMALL) for 19%, and Berlin, Frankfurt, Muenster, 95 protocol (BFM-95) for 9% of patients. Delay in induction was seen in 52%, consolidation in 66%, and during maintenance in 42% of patients. The median follow-up was 41 months, and 3-year survival outcomes for the entire cohort were event-free survival (EFS)—60%, relapse-free survival (RFS)—72%, and overall survival (OS)—68%. On univariate analysis, delay in induction adversely affected EFS (hazard ratio [HR] = 1.78, p = 0.04), while delay in intensive phase had significantly worse EFS and RFS (HR = 2.41 [p = 0.03] and HR = 2.57 [p = 0.03], respectively). On separate analysis of MCP-841 cohort, delay in intensive phase affected both EFS (HR = 3.85, p = 0.02) and RFS (HR = 3.42, p = 0.04), whereas delay in consolidation significantly affected OS with (HR = 4.74, p = 0.04) independently. Conclusion Treatment delays mostly in intensive phase are associated with worse survival in ALL; attempts should be made to maintain protocol-defined treatment intensity while adequately managing toxicities.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii102-ii103
Author(s):  
Syed Faaiz Enam ◽  
Jianxi Huang ◽  
Cem Kilic ◽  
Connor Tribble ◽  
Martha Betancur ◽  
...  

Abstract As a cancer therapy, hypothermia has been used at sub-zero temperatures to cryosurgically ablate tumors. However, these temperatures can indiscriminately damage both tumorous and healthy cells. Additionally, strategies designed to kill tumor typically accelerate their evolution and recurrence can be inevitable in cancers such as glioblastoma (GBM). To bypass these limitations, here we studied the use of hypothermia as a cytostatic tool against cancer and deployed it against an aggressive rodent model of GBM. To identify the minimal dosage of ‘cytostatic hypothermia’, we cultured at least 4 GBM lines at 4 continuous or intermittent degrees of hypothermia and evaluated their growth rates through a custom imaging-based assay. This revealed cell-specific sensitivities to hypothermia. Subsequently, we examined the effects of cytostatic hypothermia on these cells by a cursory study of their cell-cycle, energy metabolism, and protein synthesis. Next, we investigated the use of cytostatic hypothermia as an adjuvant to chemotherapy and CAR T immunotherapy. Our studies demonstrated that cytostatic hypothermia did not interfere with Temozolomide in vitro and may have been synergistic against at least 1 GBM line. Interestingly, we also demonstrated that CAR T immunotherapy can function under cytostatic hypothermia. To assess the efficacy of hypothermia in vivo, we report the design of an implantable device to focally administer cytostatic hypothermia in an aggressive rodent model of F98 GBM. Cytostatic hypothermia significantly doubled the median survival of tumor-bearing rats with no obvious signs of distress. The absence of gross behavioral alterations is in concurrence with literature suggesting the brain is naturally resilient to focal hypothermia. Based on these findings, we anticipate that focally administered cytostatic hypothermia alone has the potential to delay tumor recurrence or increase progression-free survival in patients. Additionally, it could also provide more time to evaluate concomitant, curative cytotoxic treatments.


2021 ◽  
pp. 78-81
Author(s):  
Devashish Kaushal ◽  
Rajeev Sood

Introduction: Studies on the effects of chemotherapy in Indian Castration-Resistant Prostate Cancer (CRPC) patients are very limited and world data is inconsistent. The purpose of the present study is to assess the effects of Docetaxel therapy in CRPC in Indian patients in terms of survival benet, both progression-free survival, and overall survival. This study also analyzes the effects of various factors on the survival of CRPC patients. Methodology: This is a single institutional prospective observational study. CRPC patients were treated with Docetaxel and followed till death as the primary endpoint or till the end of the study. Survivals were calculated with the Kaplan Meier method. Factors affecting survival were analyzed with univariate and multivariate analysis by log-rank t-test and Cox proportion hazard regression analysis. Result: Out of enrolled 101 patients, 78 were treated with Docetaxel. A decline in PSA (>50% reduction) was observed in 61.54%. Radiological response of regression noted in 40 % Nuclear Bone Scan and 19.23% CT/MRI by RECIST criteria. Progression-free survival and overall survival with Docetaxel (n=78) were 11.8 and 21 months respectively. Hemoglobin less than 11 gm%, Alkaline phosphatase more than 115 IU/dl, PSAmore than 14 ng/ml, Gleason score more than 7 and duration from diagnosis of carcinoma prostate to CRPC less than 24 months, the number of chemotherapy cycles less than 6 were all found to be signicantly associated with poor overall survival in univariate analysis while only Hemoglobin (P=0.0159) showed an independent association with overall survival in multivariate analysis. Conclusion: Overall and progression-free survival of CRPC patients with Docetaxel is 21 & 11.8 months respectively. Hemoglobin, Alkaline phosphatase, PSA, Gleason score, Docetaxel cycle, and duration from diagnosis of carcinoma prostate to CRPC were found to be signicantly associated with poor overall survival.


2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 41-42
Author(s):  
Luis Alberto de Padua Covas Lage ◽  
Gisele Rodrigues Gouveia ◽  
Suzete Cleusa Ferreira ◽  
Sheila Aparecida Coelho de Siqueira ◽  
Abrahão Elias Hallack Neto ◽  
...  

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoid malignancy, representing 30-40% of all non-Hodgkin's lymphomas (NHLs). They comprise a group of aggressive and heterogeneous neoplasms in terms of clinical presentation, response to therapy and prognosis. The OCT-1 gene is a member of the homodomain-POU family of transcriptional regulators of B-lymphoid differentiation. OCT-1 acts by controlling the expression of specific B-cell genes, such as BCL-2, a potent inhibitor of apoptosis that is essential for the differentiation of B-cells in the germinal center. These genes can be expressed in DLBCL, but the role of BCL-2 in its prognosis has been contradictory and the prognostic impact of the OCT-1 gene has not yet been tested in this lymphoma. Methods: In this observational, retrospective, single-center study, we investigated the prognostic impact of BCL-2 and OCT-1 gene expression in Brazilian patients with DLCBL treated with immunopolychemotherapy R-CHOP in a real-world context. The BCL-2 and OCT-1 genes were assessed in 78.5% (77/98) DLBCL patients, and the RNA for quantitative real-time PCR (qRT-PCR) was isolated from formalin-fixed and paraffin-embedded (FFPE) samples. The values obtained for gene expression were transformed into categorical variables according to their medians (6.27 for BCL-2 and 24.5 for OCT-1). The association between clinical and laboratory variables and results of gene expression was verified by the Fischer test. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariate analysis was performed using Cox's bivariate regression method and multivariate analysis using Cox multiple regression methodology. Results: The median age of the cohort was 54.5 years (15-84), 50% (49/98) were male, 49.4% (38/77) and 51.4% (40/77) showed expression of OCT-1 and BCL- 2 ≥ median, respectively. The clinical characteristics of the 98 Brazilian patients with DLBCL that comprised our cohort are summarized in Table 1. The overall response rate (ORR) in all patients was 68.4% (67/98), 65.3% (64/98) showed a complete response (CR), and 3.1% (3/98) showed partial response (PR), while 6.1% (6/98) were primary refractory. With a median follow-up of 3.77 years (95% CI: 3.2-4.1), the median overall survival (OS) was 5.43 years (95% CI: 2.2-NR) and the median progression-free survival (PFS) was 5.15 years (95% CI: 2.9-NR). The 5-year OS and PFS was 54.2% (42.2% -64.8%) and 52.0% (40.1-62.6%), respectively. In the univariate analysis OCT-1 ≥ median was associated with shortened OS (HR: 2.45, 95% CI: 1.21-4.96, p = 0.013) and PFS (HR: 2.27, 95% CI: 1.14-4.51, p = 0.019). Overexpression of BCL-2 was associated with worse PFS (HR: 2.00, 95% CI: 1.02-3.95, p = 0.043). Subgroup analysis showed that OCT-1 overexpression predominated in elderly individuals (≥ 60 years) in a statistically significant mode (29/38 cases - 76.3%, p = 0.029). It was also observed that overexpression of OCT-1 was associated with worse OS in the high-risk adjusted International Prognostic Index (aIPI) subgroup (p = 0.048) - Figure 1, and worse PFS in patients ≥ 60 years old (p = 0.025) - Figure 2. In the multivariate analysis, overexpression of OCT-1 was associated with poor PFS (HR: 2.22, 95% CI: 1.06-4.76, p = 0.035). Conclusion: In this study, we demonstrated that overexpression of the OCT-1 gene was an independent prognostic factor associated with adverse outcomes in Brazilian patients with DLCBL. We also show that in patients with unfavorable risk, such as the elderly and those with intermediate-high and high-risk IPI, overexpression of OCT-1 contributed to the identification of a very high-risk clinical-molecular subgroup, where the results with standard R-CHOP therapy are unsatisfactory, and they may benefit from intensified therapeutic strategies. Our results are preliminary and need to be validated in subsequent studies of prospective nature and with an expanded sample. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 11 ◽  
Author(s):  
Juan Briones ◽  
Maira Khan ◽  
Amanjot K. Sidhu ◽  
Liying Zhang ◽  
Martin Smoragiewicz ◽  
...  

BackgroundBoth Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is limited data on the comparative real-world effectiveness of adding DOC or ABI to androgen deprivation therapy (ADT).MethodsWe conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC n = 79, ABI n = 42). The primary endpoint studied was progression free survival (PFS), defined as the interval from start of ADT to either (i) biochemical, radiological, or symptomatic progression, (ii) start of first-line systemic therapy for castration-resistant prostate cancer (CRPC), or (iii) death, whichever occurred first. To identify independent predictive factors for PFS in the entire cohort, a Cox proportional hazard model (stepwise selection) was applied. Overall survival (OS) was among secondary endpoints.ResultsAfter a median follow-up of 39.6 and 25.1 months in the DOC and ABI cohorts, respectively, 79.7% of men in the DOC and 40.5% in the ABI group experienced a progression event. PFS favored the ABI cohort (p = 0.0038, log-rank test), with 78.0% (95%CI 66.4–91.8%) of ABI versus 67.1% (57.5–78.3%) of DOC patients being free of progression at 12 months. In univariate analysis superior PFS was significantly related to older age at diagnosis of mCSPC, metachronous metastatic presentation, low-volume (CHAARTED), and low-risk (LATITUDE) disease, ≥90% PSA decrease at 3 months (PSA90), and PSA nadir ≤0.2 at 6 months. Age (HR = 0.955), PSA90 (HR = 0.462), and LATITUDE risk stratification (HR = 1.965) remained significantly associated with PFS in multivariable analysis. OS at 12 months was 98.7% (96.3–100%) and 92.7% (85.0–100%) in the DOC and ABI groups (p = 0.97), respectively.ConclusionsIn this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in OS, but PFS was favoring ABI. Age at diagnosis of mCSPC, PSA90 at 3 months and LATITUDE risk classification are predictive factors of PFS in men with mCSPC.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23528-e23528
Author(s):  
Anastasia Alekseevna Tararykova ◽  
Beniamin Bokhyan ◽  
Andrey A. Konev ◽  
Polina A. Falkina ◽  
Zaur Yu. Kumekhov ◽  
...  

e23528 Background: Sarcoma is a heterogeneous group of tumors that arise from connective tissue. The most frequent localizations of primary tumors are soft tissues and bones of the extremities, and the lungs is the most common localization of metastases. Pazopanib is an antineoplastic agent, multi-kinase inhibitor that retards angiogenesis in tumor tissues and has been shown to be effective in the treatment of patients with advanced sarcoma. Median progression-free survival was 4,6 months (95% CI 3,7–4,8) for pazopanib compared with 1,6 months (0,9–1,8) for placebo in the PALETTE clinical trial. This study designed to detect epidemiology data as well as the pazopanib efficiency for rare sarcoma subtypes. Methods: We collected data from 109 cases with 20 different sarcoma histotypes and 15 localizations, at N.N. Blokhin National Medical Research Center of Oncology from 2018 till 2020. Disease was histologically confirmed by a sarcoma pathologist. The average age of patients was 47.8 years and the women and men ratio was about 2:1. Patients received pazopanib 800 mg once daily and passed control examinations every 2 or 3 months (CT/MRI). Treatment response was assessed by RECIST criteria. Results: The most frequent localizations of primary tumors were the soft tissues of the extremities (39.6%), the uterus (16.9%) and the retroperitoneum (13.2%). The main histological subtypes were leiomyosarcoma (33.6%) and synovial sarcoma (14.9%). There were also included such types like a embryonal rhabdomyosarcoma, chondrosarcoma, Ewing tumors, EHE, alveolar soft part sarcoma, PEComa, clear cell sarcoma, adamantinoma, solitary fibrous tumor, epithelioid sarcoma and myxoid liposarcoma. The majority of patients (61%) received more than 2 of therapy. The average duration of therapy was 7.5 months. Best tumor response by RECIST was as follows: complete response 0 (0%), partial response 2 (2%), stable disease 81 (88,3%), progression disease 25 (27,3%) cases. Median progression-free survival was 8 months (95% CI 6,7-9,2) for pazopanib. Median overall survival was not reached. Overall pazopanib was well tolerated, except one case with SAE. Conclusions: In this study we observed pazopanib efficiency in a rare for pazopanib sarcoma subtypes such as myxoid liposarcoma (1 PR), PEComa, adamantinoma, embryonal rhabdomyosarcoma, malignant peripheral nerve sheath tumor and Ewing tumors. Also our study confirms pazopanib long-term disease control in alveolar soft part sarcoma, clear cell sarcoma, leiomyosarcoma, synovial sarcoma and undifferentiated pleomorphic sarcoma which explains median PFS 8 months.


2012 ◽  
Vol 27 (3) ◽  
pp. 212-218 ◽  
Author(s):  
Hong-Qiang Guo ◽  
Guo-Liang Huang ◽  
Ou-Fei Liu ◽  
Yan-Yan Liu ◽  
Zhi-Hua Yao ◽  
...  

p63 is highly expressed in some malignant tumors and is associated with tumorigenesis, invasion and metastasis. The aim of our study was to evaluate the clinical significance of p63 in colorectal cancer (CRC). p63 expression was detected by immunohistochemistry in 66 CRC patients. Correlations between p63 expression and clinicopathological factors, progression-free survival (PFS) and overall survival (OS) were analyzed. Among the 66 CRC cases, 31 cases (47%) exhibited a high score of p63 expression, while 35 cases (53%) were marked with a low score. The p63 level correlated with peritumoral deposits (p=0.021). The 5-year OS rates in the low p63 score and high p63 score groups were, respectively, 49% and 74% (p<0.001). The 5-year PFS rates in the low p63 score and high p63 score groups were, respectively, 44% and 71% (p<0.001). Univariate analysis revealed that p63 expression was correlated with OS and PFS. Multivariate analysis suggested that p63 expression was an independent prognostic factor for OS (p=0.035). In conclusion, p63 was negatively correlated with peritumoral deposits and positively associated with OS and PFS in CRC. The data suggest that p63 is a potential prognostic factor for CRC.


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