The Impact of Competing Risks on Actuarial Estimates of Local Control in Patients with Brain Metastases

1997 ◽  
pp. 86-93
Author(s):  
L.B. Marks ◽  
B.L. Peterson ◽  
E.C. Halperin
2017 ◽  
Vol 2 (3) ◽  
pp. 391-397 ◽  
Author(s):  
Rachel B. Jimenez ◽  
Brian M. Alexander ◽  
Anand Mahadevan ◽  
Andrzej Niemierko ◽  
Selvan Rajakesari ◽  
...  

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii13-iii14
Author(s):  
Jessica Wilcox ◽  
Samantha Brown ◽  
Anne Reiner ◽  
Robert Young ◽  
Justin Chen ◽  
...  

Abstract Background The efficacy of salvage resection (SR) of recurrent brain metastases (BrM) post-stereotactic radiosurgery (SRS) is not well described. We sought to characterize the impact of adjuvant post-salvage radiation therapy (PSRT) in this setting and identify tumor-specific variables that influence local control. Methods Retrospective analysis of post-SRS recurrent BrM that underwent SR between 2003–2020 at Memorial Sloan Kettering Cancer Center was performed. Cases with histologically-viable malignancy were included and stratified by receipt of adjuvant PSRT within 60 days of SR (PSRT cohort) vs. observation (observation cohort). Resection-site outcomes were described using cumulative incidences and univariate and multivariate competing risks regression accounting for clustering. Results One-hundred fifty-five recurrent BrM in 135 patients were included. Thirty-nine (25.2%) of the post-operative cavities were treated with adjuvant PSRT, and the remaining 116 (74.8%) cavities were initially observed. Gross- or near-total resection was associated with significantly improved local control compared to subtotal resection (p=0.007). Adjuvant PSRT was associated with a reduced rate of LR at 6 months [18.0% (95%CI: 9.8–33.1%) vs. 35.9% (95%CI: 27.9–46.2%) with initial observation] and 12 months [28.8% (95%CI: 17.0–48.8%) vs. 43.9% (95%CI: 36.2–53.4%)]. On multivariate analysis, adjuvant PSRT (p=0.095), low tumor-viability within the resected BrM (p=0.17), and first-time resection (p=0.035) all independently trended towards improved local control. BrM size at SR (≥3cm vs. <3cm, p=0.48), primary malignancy (p=0.35), and specific PSRT modality (whole or partial brain radiation vs. SRS, p=0.43) were not associated with differences in LR rate. Radiation necrosis (RN) was significantly increased in the PSRT cohort (HR 4.55, 95%CI: 1.26–16.39, p=0.02), though the total percentage with symptomatic RN remained low (PSRT cohort 5.1% vs observation cohort 0.9%). Conclusions Local control after SR of a recurrent BrM may be optimized with gross- or near-total resection and adjuvant post-operative re-irradiation, with low symptomatic RN.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2091-2091
Author(s):  
Eric Karl Oermann ◽  
Jing Wu ◽  
Brian Timothy Collins ◽  
David E. Morris ◽  
Matthew G. Ewend

2091 Background: Melanoma and renal cell carcinoma are commonly called radiation resistant tumors due to the decreased response rate to traditional radiation (1.8-2 Gy /Fraction). Large brain metastases from radioresistant primaries are clinical challenges. This study examines the impact of fractionation on the treatment of intracranial metastases from radiation resistant tumors. Methods: Patients with a primary diagnosis of melanoma or renal cell carcinoma and intracranial metastases who completed treatment at The University of North Carolina with frameless robotic radiosurgery between 2007-2011 were retrospectively analyzed. Patients were treated with either single or 3-5 fractions depending on volume. The study’s primary endpoints were overall survival (OS) and local control (LC), and its secondary endpoint was patient steroid requirements. Outcomes data and pre-treatment variables were analyzed for significance using appropriate non-parametric tests. Results: 25 patients were included in the single fraction arm and 13 patients in the multi-fraction arm, and both had equivalent pre-treatment characteristics with the exception of tumor volume which was larger in the multi-fraction arm (p=0.01). At a median follow-up of 4.7 months (range, 1.8-11.6), the median OS for all patients was 6.2 months. One year survival was 35.1% and 5 patients (13%) had local failures at a median time to local failure of 5.5 months. Patients in the multi-fraction arm failed at a higher rate (10.5%) than patients in the single fraction arm (2.6%) (p=0.04), but there was no difference in OS (p=0.34). There was no difference between pre-treatment and post-treatment steroid requirements between the two arms (p=0.351). Conclusions: Fractionation is intended to facilitate radiosurgery in large tumors by limiting high doses of radiation to a large portion of normal brain. In our study of radioresistant intracranial metastases, large tumors receiving multi-fraction radiosurgery had decreased local control with no difference in toxicity or OS. These results suggest a need for either dose escalation, or combination therapy designed to reduce tumor size (resection or aspiration) in order to facilitate single fraction treatment.


2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Emily S. Kowalski ◽  
Jill S. Remick ◽  
Kai Sun ◽  
Gregory S. Alexander ◽  
Rahul Khairnar ◽  
...  

Abstract Purpose Stereotactic radiation therapy (SRT) and immune checkpoint inhibitors (ICI) may act synergistically to improve treatment outcomes but may also increase the risk of symptomatic radiation necrosis (RN). The objective of this study was to compare outcomes for patients undergoing SRT with and without concurrent ICI. Methods and materials Patients treated for BMs with single or multi-fraction SRT were retrospectively reviewed. Concurrent ICI with SRT (SRT-ICI) was defined as administration within 3 months of SRT. Local control (LC), radiation necrosis (RN) risk and distant brain failure (DBF) were estimated by the Kaplan-Meier method and compared between groups using the log-rank test. Wilcoxon rank sum and Chi-square tests were used to compare covariates. Multivariate cox regression analysis (MVA) was performed. Results One hundred seventy-nine patients treated with SRT for 385 brain lesions were included; 36 patients with 99 lesions received SRT-ICI. Median follow up was 10.3 months (SRT alone) and 7.7 months (SRT- ICI) (p = 0.08). Lesions treated with SRT-ICI were more commonly squamous histology (17% vs 8%) melanoma (20% vs 2%) or renal cell carcinoma (8% vs 6%), (p < 0.001). Non-small cell lung cancer (NSCLC) compromised 60% of patients receiving ICI (n = 59). Lesions treated with SRT-ICI had significantly improved 1-year local control compared to SRT alone (98 and 89.5%, respectively (p = 0.0078). On subset analysis of NSCLC patients alone, ICI was also associated with improved 1 year local control (100% vs. 90.1%) (p = 0.018). On MVA, only tumor size ≤2 cm was significantly associated with LC (HR 0.38, p = 0.02), whereas the HR for concurrent ICI with SRS was 0.26 (p = 0.08). One year DBF (41% vs. 53%; p = 0.21), OS (58% vs. 56%; p = 0.79) and RN incidence (7% vs. 4%; p = 0.25) were similar for SRT alone versus SRT-ICI, for the population as a whole and those patients with NSCLC. Conclusion These results suggest SRT-ICI may improve local control of brain metastases and is not associated with an increased risk of symptomatic radiation necrosis in a cohort of predominantly NSCLC patients. Larger, prospective studies are necessary to validate these findings and better elucidate the impact of SRT-ICI on other disease outcomes.


Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1857
Author(s):  
Valentina Borzillo ◽  
Rossella Di Franco ◽  
Diana Giannarelli ◽  
Fabrizio Cammarota ◽  
Esmeralda Scipilliti ◽  
...  

The median overall survival (OS) and local control (LC) of patients with melanoma brain metastases (MBMs) are poor even with immune checkpoint inhibitors and/or radiotherapy (RT). The aims of the study were to evaluate the association and timing of stereotactic radiotherapy (SRT)/radiosurgery (SRS) performed with the CyberKnife® System and ipilimumab (IPI). A total of 63 MBMs patients were analyzed: 53 received RT+IPI and 10 RT alone. Therefore, the patients were divided into four groups: RT PRE-PI (>4 weeks before IPI) (18), RT CONC-IPI (4 weeks before/between first and last cycle/within 3 months of last cycle of IPI) (20), RT POST-IPI (>3 months after IPI) (15), and NO-IPI (10). A total of 127 lesions were treated: 75 with SRS (one fraction) and 24 with SRT (three to five fractions). The median follow-up was 10.6 months. The median OS was 10.6 months for all patients, 10.7 months for RT+IPI, and 3.3 months for NO-IPI (p = 0.96). One-year LC was 50% for all patients, 56% for RT+IPI, and 18% for NO-IPI (p = 0.08). The 1-year intracranial control was 45% for all patients, 44% for RT+IPI, and 51% for NO-IPI (p = 0.73). IPI with SRS/SRT in MBMs treatment could improve LC. However, the impact and timing of the two modalities on patients’ outcomes are still unclear.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jie Wu ◽  
Yu-Chen Wang ◽  
Wen-Jie Luo ◽  
Bo-Dai ◽  
Ding-Wei Ye ◽  
...  

Abstract Background Primary urethral carcinoma (PUC) is a rare genitourinary malignancy with a relatively poor prognosis. The aim of this study was to examine the impact of surgery on survival of patients diagnosed with PUC. Methods A total of 1544 PUC patients diagnosed between 2004 and 2016 were identified based on the SEER database. The Kaplan-Meier estimate and the Fine and Gray competing risks analysis were performed to assess overall survival (OS) and cancer-specific mortality (CSM). The multivariate Cox regression model and competing risks regression model were used to identify independent risk factors of OS and cancer-specific survival (CSS). Results The 5-yr OS was significantly better in patients who received either local therapy (39.8%) or radical surgery (44.7%) compared to patients receiving no surgery of the primary site (21.5%) (p < 0.001). Both local therapy and radical surgery were each independently associated with decreased CSM, with predicted 5-yr cumulative incidence of 45.4 and 43.3%, respectively, compared to 64.7% for patients receiving no surgery of the primary site (p < 0.001). Multivariate analyses demonstrated that primary site surgery was independently associated with better OS (local therapy, p = 0.037; radical surgery, p < 0.001) and decreased CSM (p = 0.003). Similar results were noted regardless of age, sex, T stage, N stage, and AJCC prognostic groups based on subgroup analysis. However, patients with M1 disease who underwent primary site surgery did not exhibit any survival benefit. Conclusion Surgery for the primary tumor conferred a survival advantage in non-metastatic PUC patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Jin Lim ◽  
Jaemoon Koh

AbstractAlthough radiation-induced cardiotoxicity has been addressed, its prognostic relevance to modern radiotherapy (RT) techniques is unclear. This study assessed the impact of adjuvant RT on heart-related deaths in patients with ductal carcinoma in situ. Patients who underwent adjuvant RT after breast-conserving surgery between 1988 and 2008 were identified from the Surveillance, Epidemiology, and End Results database. Kaplan‒Meier and competing risks analyses were conducted after propensity score-matching according to tumor laterality. A total of 41,526 propensity-matched patients were identified (n = 20,763 for either left- or right-sided tumor). In the analysis of the cumulative incidence of heart-related mortality events, there was a greater risk increment in the left-sided group over the first to second decades after RT in patients aged ≤ 50 years (P = 0.048). Competing risks analysis of the young patients showed that left-sided RT was associated with higher heart-related mortality rates (Grey’s test, P = 0.049). The statistical significance remained after adjusting for other covariates (subdistribution hazard ratio 2.35; 95% confidence interval 1.09‒5.10). Regarding the intrinsic effect of modern RT techniques, further strategies to reduce heart-related risks are needed for young patients. Close surveillance within an earlier follow-up period should be considered for these patients in clinics.


1990 ◽  
Vol 8 (6) ◽  
pp. 1042-1049 ◽  
Author(s):  
M P Dearing ◽  
S M Steinberg ◽  
R Phelps ◽  
M J Anderson ◽  
J L Mulshine ◽  
...  

In a study of 411 patients with small-cell lung cancer (SCLC) entered on therapeutic clinical trials between 1973 and 1987, we analyzed whether changes in the prognostic importance of pretreatment factors had occurred during the 14-year time period. After adjusting for other prognostic factors, brain involvement was associated with shorter survival in patients treated before December 1979 (P = .024) but not in patients treated thereafter (P = .54). The patients diagnosed before 1979 had brain metastases documented by radionuclide scan while computed cranial tomography (CCT) was more commonly used after 1979. Patients who had brain metastases diagnosed by radionuclide scan lived a shorter period of time than patients who had the diagnosis made by the more sensitive CCT scan (P = .031). In contrast, Cox proportional hazards modeling showed that liver metastases in patients were associated with shorter survival in patients treated after 1979 (P = .0007) but not in patients treated before then (P = .30). A larger proportion of patients had a routine liver biopsy before 1979 than after 1979 when more patients had the liver staged with less sensitive imaging studies and biochemical parameters. Patients with SCLC whose cancer was confined to the thorax but had medical or anatomic contraindications to intensive chest radiotherapy had similar survival compared with patients with limited-stage SCLC who were treated with combination chemotherapy alone (P = .68). From these data we conclude: (1) the sensitivity of the staging procedures used can affect the impact on survival of cancer involvement of a given site; and (2) patients with cancer confined to their chest with medical or anatomic contraindications to chest radiotherapy do not have a shorter survival than patients with limited-stage disease treated with chemotherapy alone.


Author(s):  
Diana A. Roth O‘Brien ◽  
Phillip Poppas ◽  
Sydney M. Kaye ◽  
Sean S. Mahase ◽  
Anjile An ◽  
...  

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