scholarly journals RADT-08. ADJUVANT SBRT FOR RESECTED BRAIN METASTASES: THE EFFECT OF TIMING ON LONG-TERM INTENDED-FIELD CONTROL

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii183-ii183
Author(s):  
Evan Bander ◽  
Melissa Yuan ◽  
Anne Reiner ◽  
Katherine Panageas ◽  
Cameron Brennan ◽  
...  

Abstract INTRODUCTION Adjuvant stereotactic body radiation therapy (SBRT) improves the local control of resected brain metastases (BrM). However, the dependency of long-term outcomes on SBRT timing relative to surgery remains unclear. METHODS Retrospective analysis of metastasectomy-plus-adjuvant-SBRT patients at Memorial Sloan Kettering (MSK) between 2013-2016 was conducted. Kaplan-Meier methodology was used to describe overall survival (OS) and cumulative incidence in a competing-risks setting recurrence at the surgical site, other SBRT-treated sites, and elsewhere in the brain as defined by RANO-BM criteria. Recursive partitioning analysis (RPA) and competing-risks regression modeling assessed prognostic variables and associated events of interest. RESULTS Two hundred eighty-two patients with BrM including non-small cell lung (34%), breast (16%), melanoma (13%), and other cancers were included. Median time-to-adjuvant-SBRT (TT-SBRT) was 34 days (IQR: 27-39). Median overall survival (OS) from SBRT was 1.5 years (95% CI: 1.2-2.1) with median follow-up of 49.8 months for survivors. Local surgical recurrence, other irradiated-site, and distant progression rates were 14.3% (95%CI: 10.1-18.5), 4.9% (95%CI: 2.3-7.5), and 47.5% (95%CI: 41.4-53.6) at 5 years, respectively. TT-SBRT as a continuous variable significantly associated with surgical-site recurrence (HR 1.05 [1.02-1.07], p=0.0003), but not with distant or other irradiated-site recurrence nor OS. RPA analysis demonstrated the greatest control rate advantage with TT-SBRT < 39 days (HR for 39+ days: 2.81 [1.50-5.27], p=0.001). No association of TT-SBRT with radiation necrosis, wound complication, or development of leptomeningeal dissemination was identified. CONCLUSIONS Delays in initiation of post-operative SBRT can decrease its efficacy. Efforts must be made to minimize logistical, procedural, and socioeconomic factors responsible for these delays.

2021 ◽  
Author(s):  
Evan D Bander ◽  
Melissa Yuan ◽  
Anne S Reiner ◽  
Katherine S Panageas ◽  
Åse M Ballangrud ◽  
...  

Abstract Background Adjuvant stereotactic radiosurgery (SRS) improves the local control of resected brain metastases (BrM). However, the dependency of long-term outcomes on SRS timing relative to surgery remains unclear. Methods Retrospective analysis of patients treated with metastasectomy-plus-adjuvant-SRS at Memorial Sloan Kettering (MSK) between 2013-2016 was conducted. Kaplan-Meier methodology was used to describe overall survival (OS) and cumulative incidence rates were estimated by type of recurrence, accounting for death as a competing event. Recursive partitioning analysis (RPA) and competing-risks regression modeling assessed prognostic variables and associated events of interest. Results Two hundred eighty-two patients with BrM had a median OS of 1.5 years (95% CI: 1.2-2.1) from adjuvant SRS with median follow-up of 49.8 months for survivors. Local surgical recurrence, other simultaneously SRS-irradiated-site recurrence, and distant central nervous system (CNS) progression rates were 14.3% (95%CI: 10.1-18.5), 4.9% (95%CI: 2.3-7.5), and 47.5% (95%CI: 41.4-53.6) at 5 years, respectively. Median time-to-adjuvant-SRS (TT-SRS) was 34 days (IQR: 27-39). TT-SRS significantly associated with surgical site recurrence rate (p=0.0008). SRS delivered within 1 month resulted in surgical site recurrence rate of 6.1% (95%CI: 1.3-10.9) at 1-year, compared to 9.2% (95%CI: 4.9-13.6) if delivered between 1-2 months, or 27.3% (95%CI: 0.0-55.5) if delivered >2 months after surgery. OS was significantly lower for patients with TT-SRS >~2 months. Post-operative length of stay, discharge to a rehabilitation facility, urgent care visits and/or disease recurrence between surgery and adjuvant SRS associated with increased TT-SRS. Conclusions Adjuvant SRS provides durable local control. However, delays in initiation of post-operative SRS can decrease its efficacy.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2875-2875
Author(s):  
Rudolf A. Benz ◽  
Kornelius Arn ◽  
Martin Andres ◽  
Thomas Pabst ◽  
Urban Novak ◽  
...  

Abstract Introduction : Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with a very indolent clinical course and patients may survive for many decades. First-line treatment with purine analogues such as cladribine (Cld) is considered standard of care since it is very efficient and induces profound remissions. However, patients with HCL often relapse after purine analogues and repeated treatment may increase morbidity and mortality. Despite good clinical evidence of long term control of the disease by several mainly single center studies of patients treated with purine analogues, there is only one study analyzing mainly subcutaneous (sc) treated patients based on registry data. We therefore performed a pooled long-term follow-up analysis of our prospective multicenter studies treating patients with sc Cld focusing on survival, secondary malignancy and retreatment. Materials and Methods : The SAKK included patients treated for HCL in 4 studies between 1993 and 2005. Three studies focused on first-line regimens with sc Cld, whereas the fourth protocol focused on the effect of Rituximab monotherapy in patients pretreated with Cld. Classical morphologic, immunohistochemistry and flow cytometry criteria were used as inclusion criteria and response was assessed by established criteria. Treatment algorithms in the 4 studies were as follows: 1) 5 days of Cld 0.14mg/kg sc followed by max 2 cycles of 7 days of Cld 0.1mg/kg sc in case of minor response or no response (SAKK 32/93); 2) Single shot of Cld 0.25mg/kg sc followed by a maximum of 2 cycles of 0.14mg/kg sc for 5 day in case of minor response, no response or relapse (SAKK 32/95); 3) 5 consecutive days of Cld 0.14mg/kg sc versus the same dose in 5 weekly applications (SAKK 32/98); 4) Rituximab 375 mg/m2iv weekly for 4 weeks in relapsed patients (SAKK 31/98). SAKK 32/93 included 63, SAKK 32/95 74 and SAKK 32/98 100 patients. Of the 26 patients registered in 31/98 20 were already in SAKK 32/93, 32/95 and 32/98. Therefore, we also included the treatment information and follow-up data of these 20 patients. All patients were subject to life-long follow-up within the clinical trials. Further information including secondary malignancies and retreatments were obtained by sending out questionnaires to the treating physicians of the study patients. Of the 237 patients 4 patients were in two of the studies and 10 patients have been excluded because of non-classical HCL phenotype. Therefore, a total of 223 patients were included in the analysis. Overall survival and follow-up time were assessed by Kaplan-Meier and reverse Kaplan-Meier method, respectively. Results : The median age of patients at the time of diagnosis was 55 (range 21 to 96) years, 50 patients were female (22.4%) and 173 (77.6%) male. At the time of data analysis, the median follow-up time was 12.1 (95%-CI 10.0 to 14.0) years. A total of 129 (57.8%) patients had the last follow-up information more than two years prior to the data cut-off in May 2016, however, the available information of all patients was used for the sub-analyses including secondary malignancies or retreatment. By the cut-off date, 49 patients have died, 14 (28.6%) due to secondary malignancies and 7 (14.3%) due to HCL progression. Median overall survival from diagnosis was 31.6 (95%-CI 31.6 to 37.8) years. Retreatment was necessary in 53 (23.7%) patients after a mean of 6 (0.2 to 20.4) years and first retreatment was mainly Cld (64%), rituximab (19%) or Cld and rituximab (13%). 21 patients (9.4%) required more than one retreatment with a mean number of 1.57 (range 1 to 5) treatments. A total of 42 (18.8%) patients developed secondary malignancies with an average time to occurrence of 7.1 (range: 0.1 to 17.7) years. The majority of the secondary malignancies were of non-hematological origin (85.9%), most frequently skin cancer (31.0%), followed by prostate cancer (19.0%) and colorectal cancer (16.7%). Six patients (14.4%) developed hematological secondary malignancies with a predominance of B-lymphoid neoplasms. Conclusion : Long-term overall survival in HCL patients treated with sc Cld was excellent and comparable to studies using iv Cld. Despite the long follow-up, sc Cld had a curative potential and relapses requiring re-treatment were observed only in a minority of patients. Secondary malignancies were predominantly non-hematological. These data indicate that patients need to be followed carefully with a special focus on secondary malignancies. Disclosures Chalandon: Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs.


2019 ◽  
Vol 7 (4) ◽  
pp. 400-408
Author(s):  
Zaid A Siddiqui ◽  
Bryan S Squires ◽  
Matt D Johnson ◽  
Andrew M Baschnagel ◽  
Peter Y Chen ◽  
...  

Abstract Background The long-term risk of necrosis after radiosurgery for brain metastases is uncertain. We aimed to investigate incidence and predictors of radiation necrosis for individuals with more than 1 year of survival after radiosurgery for brain metastases. Methods Patients who had a diagnosis of brain metastases treated between December 2006 and December 2014, who had at least 1 year of survival after first radiosurgery were retrospectively reviewed. Survival was analyzed using the Kaplan-Meier estimator, and the incidence of radiation necrosis was estimated with death or surgical resection as competing risks. Patient and treatment factors associated with radiation necrosis were also analyzed. Results A total of 198 patients with 732 lesions were analyzed. Thirty-four lesions required salvage radiosurgery and 10 required salvage surgical resection. Median follow-up was 24 months. The estimated median survival for this population was 25.4 months. The estimated per-lesion incidence of radiation necrosis at 4 years was 6.8%. Medical or surgical therapy was required for 60% of necrosis events. Tumor volume and male sex were significant factors associated with radiation necrosis. The per-lesions incidence of necrosis for patients undergoing repeat radiosurgery was 33.3% at 4 years. Conclusions In this large series of patients undergoing radiosurgery for brain metastases, patients continued to be at risk for radiation necrosis throughout their first 4 years of survival. Repeat radiosurgery of recurrent lesions greatly exacerbates the risk of radiation necrosis, whereas treatment of larger target volumes increases the risk modestly.


Neurosurgery ◽  
2017 ◽  
Vol 83 (2) ◽  
pp. 203-209
Author(s):  
Emile Gogineni ◽  
John A Vargo ◽  
Scott M Glaser ◽  
John C Flickinger ◽  
Steven A Burton ◽  
...  

Abstract BACKGROUND Historically, survival for even highly select cohorts of brain metastasis patients selected for SRS alone is <2 yr; thus, limited literature on risks of recurrence exists beyond 2 yr. OBJECTIVE To investigate the possibility that for subsets of patients the risk of intracranial failure beyond 2 yr is less than the commonly quoted 50% to 60%, wherein less frequent screening may be appropriate. METHODS As a part of our institutional radiosurgery database, we identified 132 patients treated initially with stereotactic radiosurgery (SRS) alone (± pre-SRS surgical resection) with at least 2 yr of survival and follow-up from SRS. Primary study endpoints were rates of actuarial intracranial progression beyond 2 yr, calculated using the Kaplan–Meier and Cox regression methods. RESULTS The median follow-up from the first course of SRS was 3.5 yr. Significant predictors of intracranial failure beyond 2 yr included intracranial failure before 2 yr (52% vs 25%, P < .01) and total SRS tumor volume ≥5 cc (51% vs 25%, P < .01). On parsimonious multivariate analysis, failure before 2 yr (HR = 2.2, 95% CI: 1.2-4.3, P = .01) and total SRS tumor volume ≥5 cc (HR = 2.3, 95% CI: 1.2-4.3, P = .01) remained significant predictors of intracranial relapse beyond 2 yr. CONCLUSION Relapse rates beyond 2 yr following SRS alone for brain metastases are low in patients who do not suffer intracranial relapse within the first 2 yr and with low-volume brain metastases, supporting a practice of less frequent screening beyond 2 yr. For remaining patients, frequent (every 3-4 mo) screening remains prudent, as the risk of intracranial failure after 2 yr remains high.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Roberto José Barone ◽  
María Inés Cámpora ◽  
Nélida Susana Gimenez ◽  
Liliana Ramirez ◽  
Sergio Alberto Panese ◽  
...  

For renal replacement therapy, overall survival is more important than the choice of currently available individual therapy.Objectives. To compare patients and technique survival on peritoneal dialysis as first treatment (PDF) versus after previous haemodialysis (HDPD) and other indicators of follow-up.Methods. We prospectively studied 110 incident patients, during the period from August 4, 1993, to June 30, 2012, for patients and technique survival (Kaplan-Meier) (log rankP< 0.05).Results. Groups: (A) PDF: 37 patients, 24 females, age: 52.2 ± 14.9 years old, time at risk: 2123 patient-months (p/m), mean: 57 ± 42 months; (B) HDPD: 73 patients, 42 females, age: 52.45 ± 14.7 years old, time in haemodialysis: 3569.2 (p/m), range: 3–216 months, mean: 49 ± 45 months, time at risk in PD: 3700 (p/m), mean: 51 ± 49 months. Patients’ survival: (A) PDF: 100%, 76.6%, 65.6%, and 19.7%; (B) HDPD: 95.4%, 65.6%, 43%, and 43% at 12, 60, 120, and 144 months, respectively,P=0.34. Technique: (A) PDF: 100%, 90%, 59.8%, and 24%; (B) HDPD: 94%, 75%, 32%, and 32% at 12, 60, 120, and 144 months, respectively,P=0.40.Conclusions. Comparable patient and technique survival were observed. Peritoneal dialysis enables a greater extension of renal replacement therapy for patients with serious difficulties continuing with haemodialysis.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4780-4780
Author(s):  
Martha Q. Lacy ◽  
Betsy R. LaPlant ◽  
Kristina M Laumann ◽  
Shaji Kumar ◽  
Morie A Gertz ◽  
...  

Abstract Background: Pomalidomide has demonstrated excellent activity in patients with relapsed, lenalidomide refractory, multiple myeloma (MM). Between November 2007 and March 2012, we enrolled 285 patients with relapsed MM on 5 sequential phase 2 trials; patients received pomalidomide at 2mg or 4 mg daily with weekly dexamethasone (Pom/dex). The approved dose of pomalidomide is 4 mg for 21 of 28 days. We wished to compare efficacy, tolerability and long-term outcomes between cohorts treated with 2 mg or 4mg daily continuously and 4mg daily for 21/28 days. Methods: After excluding two ineligible patients, 283 patients with lenalidomide refractory, relapsed MM from 5 sequential cohorts were analyzed. These patients were divided into 3 groups: Group1 received Pom 2mg for 28/28 day cycle (N= 69), Group 2 received Pom 4 mg for 28/28 day cycle (N= 95) and Group 3 received Pom 4mg for 21/28 day cycle (N= 119). All patients received oral dexamethasone given 40 mg daily on days 1, 8, 15, and 22. Response was assessed by the IMWG Uniform Response criteria. All patients received aspirin 325 mg daily for DVT prophylaxis or full dose anticoagulation. Results: The median age was 63 years (32-85); 35% were female. The median time from diagnosis was 53 months and the median number of prior regimens was 4. 127 (46%) had high-risk molecular markers. Prior therapies (% received) included lenalidomide (100%), thalidomide (46%), bortezomib (78%), autologous stem cell transplant (71%), and allogeneic transplant (4%). The median follow-up is 16.4 months (3.2-64.4). Forty eight percent are alive and 26% remain progression free; 15 patients are continuing to receive treatment. Frequency of AEs by groups are shown in Table 1. The most notable difference is grade 3+ neutropenia seen in 39% of group 1 and 56% and 57% of groups 2 and 3. Confirmed responses of PR or better were seen in 29% (group1), 35% (group2) and 24% (group3). Median duration of response (DOR) was 14.1 months (group1), 14.5 months (group2) and 10.2 months (group3). Median PFS was 5.5 months (group1), 6.9 months (group2) and 4.3 months (group3). Although the dose level cohorts were sequential rather than randomized, we compared OS between the dose levels in an exploratory manner. There was no significant difference in OS between dose levels (p=0.26). Median overall survival (OS) was 16.6 months (group1), 21.9 months (group2) and 16.0 months (group3). Conclusions: Pom/dex is active and well tolerated even in heavily pretreated patients Responses are durable. Response rates and overall toxicity are similar between the 2 mg and 4 mg doses. Neutropenia is more common in those receiving doses of 4mg daily or for 21/28 days compared to those receiving 2 mg daily. Table 1. All Grades Grade 3+ 2mg 28 Day 4mg 28 Day 4mg 21 Day 2mg 28 Day 4mg 28 Day 4mg 21 Day Anemia 68% 58% 74% 14% 15% 27% Lymphopenia 22% 51% 11% 16% 32% 8% Neutropenia 71% 82% 77% 39% 57% 56% Thrombocytopenia 51% 61% 63% 10% 9% 23% Leukopenia 59% 77% 72% 26% 38% 39% Pneumonia 7% 11% 12% 6% 7% 11% Fatigue 51% 65% 60% 9% 5% 8% Neuropathy 28% 32% 28% 0% 3% 0% Elevated Blood Glucose 10% 21% 8% 4% 6% 3% Pneumonitis 3% 2% 3% 3% 1% 1% VTE (Thrombosis) 3% 3% 3% 1% 3% 3% Secondary Malignancy 0% 2% 1% 0% 2% 1% Figure1. Kaplan Meier Overall Survival Curves Figure1. Kaplan Meier Overall Survival Curves Disclosures Lacy: Celgene: Research Funding. Fonseca:Medtronic, Otsuka, Celgene, Genzyme, BMS, Lilly, Onyx, Binding Site, Millennium, AMGEN: Consultancy, patent for the prognostication of MM based on genetic categorization of the disease. He also has sponsored research from Cylene and Onyx Other, Research Funding. Bergsagel:Novartis: Research Funding; Constellation Pharmaceutical: Research Funding; OncoEthix: Research Funding; MundiPharma: Research Funding. Stewart:Novartis: Consultancy; Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Array BioPharma: Consultancy; Sanofi: Consultancy; Takeda Pharmaceuticals International Co.: Research Funding. Reeder:Millennium, Celgene, Novartis: Research Funding. Mikhael:Onyx: Research Funding; Celgene: Research Funding; Sanofi: Research Funding; Novartis: Research Funding.


2021 ◽  
Vol 20 (4) ◽  
pp. 397-405
Author(s):  
Andrew R Pines ◽  
Richard J Butterfield ◽  
Evelyn L Turcotte ◽  
Jose O Garcia ◽  
Noel De Lucia ◽  
...  

Abstract BACKGROUND Trigeminal neuralgia (TN) refractory to medical management is often treated with microvascular decompression (MVD) involving the intracranial placement of Teflon. The placement of Teflon is an effective treatment, but does apply distributed pressure to the nerve and has been associated with pain recurrence. OBJECTIVE To report the rate of postoperative pain recurrence in TN patients who underwent MVD surgery using a transposition technique with fibrin glue without Teflon. METHODS Patients were eligible for our study if they were diagnosed with TN, did not have multiple sclerosis, and had an offending vessel that was identified and transposed with fibrin glue at our institution. All eligible patients were given a follow-up survey. We used a Kaplan-Meier (KM) model to estimate overall pain recurrence. RESULTS A total of 102 patients met inclusion criteria, of which 85 (83%) responded to our survey. Overall, 76 (89.4%) participants responded as having no pain recurrence. Approximately 1-yr pain-free KM estimates were 94.1% (n = 83), 5-yr pain-free KM estimates were 94.1% (n = 53), and 10-yr pain-free KM estimates were 83.0% (n = 23). CONCLUSION Treatment for TN with an MVD transposition technique using fibrin glue may avoid some cases of pain recurrence. The percentage of patients in our cohort who remained pain free at a maximum of 17 yr follow-up is on the high end of pain-free rates reported by MVD studies using Teflon. These results indicate that a transposition technique that emphasizes removing any compression near the trigeminal nerve root provides long-term pain-free rates for patients with TN.


Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001440
Author(s):  
Shameer Khubber ◽  
Rajdeep Chana ◽  
Chandramohan Meenakshisundaram ◽  
Kamal Dhaliwal ◽  
Mohomed Gad ◽  
...  

BackgroundCoronary artery aneurysms (CAAs) are increasingly diagnosed on coronary angiography; however, controversies persist regarding their optimal management. In the present study, we analysed the long-term outcomes of patients with CAAs following three different management strategies.MethodsWe performed a retrospective review of patient records with documented CAA diagnosis between 2000 and 2005. Patients were divided into three groups: medical management versus percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). We analysed the rate of major cardiovascular and cerebrovascular events (MACCEs) over a period of 10 years.ResultsWe identified 458 patients with CAAs (mean age 78±10.5 years, 74.5% men) who received medical therapy (N=230) or underwent PCI (N=52) or CABG (N=176). The incidence of CAAs was 0.7% of the total catheterisation reports. The left anterior descending was the most common coronary artery involved (38%). The median follow-up time was 62 months. The total number of MACCE during follow-up was 155 (33.8%); 91 (39.6%) in the medical management group vs 46 (26.1%) in the CABG group vs 18 (34.6%) in the PCI group (p=0.02). Kaplan-Meier survival analysis showed that CABG was associated with better MACCE-free survival (p log-rank=0.03) than medical management. These results were confirmed on univariate Cox regression, but not multivariate regression (OR 0.773 (0.526 to 1.136); p=0.19). Both Kaplan-Meier survival and regression analyses showed that dual antiplatelet therapy (DAPT) and anticoagulation were not associated with significant improvement in MACCE rates.ConclusionOur analysis showed similar long-term MACCE risks in patients with CAA undergoing medical, percutaneous and surgical management. Further, DAPT and anticoagulation were not associated with significant benefits in terms of MACCE rates. These results should be interpreted with caution considering the small size and potential for selection bias and should be confirmed in large, randomised trials.


2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Achiraya Teyateeti ◽  
Paul D Brown ◽  
Anita Mahajan ◽  
Nadia N Laack ◽  
Bruce E Pollock

Abstract Background To compare the outcomes between patients with leptomeningeal disease (LMD) and distant brain recurrence (DBR) after stereotactic radiosurgery (SRS) brain metastases (BM) resection cavity. Methods Twenty-nine patients having single-fraction SRS after BM resection who developed either LMD (n = 11) or DBR (n = 18) as their initial and only site of intracranial progression were retrospectively reviewed. Results Patients developing LMD more commonly had a metachronous presentation (91% vs 50%, P = .04) and recursive partitioning class 1 status (45% vs 6%, P = .02). There was no difference in the median time from SRS to the development of LMD or DBR (5.0 vs 3.8 months, P = .68). The majority of patients with LMD (10/11, 91%) developed the nodular variant (nLMD). Treatment for LMD was repeat SRS (n = 4), whole-brain radiation therapy (WBRT; n = 5), resection + WBRT (n = 1), and no treatment (n = 1). Treatment for DBR was repeat SRS (n = 9), WBRT (n = 3), resection + resection cavity SRS (n = 1), and no treatment (n = 5). Median overall survival (OS) from time of resection cavity SRS was 15.7 months in the LMD group and 12.7 months in the DBR group (P = .60), respectively. Median OS in salvage SRS and salvage WBRT were 25.4 and 5.0 months in the nLMD group (P = .004) while 18.7 and 16.2 months in the DBR group (P = .30), respectively. Conclusions Following BM resection cavity SRS, nLMD recurrence is much more frequent than classical LMD. Salvage SRS may be considered for selected patients with nLMD, reserving salvage WBRT for patients with extensive intracranial disease without compromising survival. Further study with larger numbers of patients is needed.


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