Stereotactic radiosurgery as the first-line treatment for intracanalicular vestibular schwannomas

2021 ◽  
pp. 1-7
Author(s):  
Akiyoshi Ogino ◽  
L. Dade Lunsford ◽  
Hao Long ◽  
Stephen Johnson ◽  
Andrew Faramand ◽  
...  

OBJECTIVEThis report evaluates the outcomes of stereotactic radiosurgery (SRS) as the first-line treatment of intracanalicular vestibular schwannomas (VSs).METHODSBetween 1987 and 2017, the authors identified 209 patients who underwent SRS as the primary intervention for a unilateral intracanalicular VS. The median patient age was 54 years (range 22–85 years); 94 patients were male and 115 were female. Three patients had facial neuropathy at the time of SRS. One hundred fifty-five patients (74%) had serviceable hearing (Gardner-Robertson [GR] grades I and II) at the time of SRS. The median tumor volume was 0.17 cm3 (range 0.015–0.63 cm3). The median margin dose was 12.5 Gy (range 11.0–25.0 Gy). The median maximum dose was 24.0 Gy (range 15.7–50.0 Gy).RESULTSThe progression-free survival rates of all patients with intracanalicular VS were 97.5% at 3 years, 95.6% at 5 years, and 92.1% at 10 years. The rates of freedom from the need for any additional intervention were 99.4% at 3 years, 98.3% at 5 years, and 98.3% at 10 years. The serviceable hearing preservation rates in GR grade I and II patients at the time of SRS were 76.6% at 3 years, 63.5% at 5 years, and 27.3% at 10 years. In univariate analysis, younger age (< 55 years, p = 0.011), better initial hearing (GR grade I, p < 0.001), and smaller tumor volumes (< 0.14 cm3, p = 0.016) were significantly associated with improved hearing preservation. In multivariate analysis, better hearing (GR grade I, p = 0.001, HR 2.869, 95% CI 1.569–5.248) and smaller tumor volumes (< 0.14 cm3, p = 0.033, HR 2.071, 95% CI 1.059–4.047) at the time of SRS were significantly associated with improved hearing preservation. The hearing preservation rates of patients with GR grade I VS were 88.1% at 3 years, 77.9% at 5 years, and 38.1% at 10 years. The hearing preservation rates of patients with VSs smaller than 0.14 cm3 were 85.5% at 3 years, 77.7% at 5 years, and 42.6% at 10 years. Facial neuropathy developed in 1.4% from 6 to 156 months after SRS.CONCLUSIONSSRS provided sustained tumor control in more than 90% of patients with intracanalicular VS at 10 years and freedom from the need for additional intervention in more than 98% at 10 years. Patients with initially better hearing and smaller VSs had enhanced serviceable hearing preservation during an observation interval up to 10 years after SRS.

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3745
Author(s):  
Hélène Vellemans ◽  
Marc P. E. André

Hodgkin lymphoma (HL) is a lymphoid-type hematologic disease that is derived from B cells. The incidence of this lymphoid malignancy is around 2–3/100,000/year in the western world. Long-term remission rates are linked to a risk-adapted approach, which allows remission rates higher than 80%. The first-line treatment for advanced stage classical HL (cHL) widely used today is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) chemotherapy. Randomized studies comparing these two regimens and a recently performed meta-analysis have demonstrated consistently better disease control with BEACOPPesc. However, this treatment is not the standard of care, as there is an excess of acute hematological toxicities and therapy-related myeloid neoplasms. Moreover, there is a recurrent controversy concerning the impact on overall survival with this regimen. More recently, new drugs such as brentuximab vedotin and checkpoint inhibitors have become available and have been evaluated in combination with doxorubicin, vinblastine, and dacarbazine (AVD) for the first-line treatment of patients with advanced cHL with the objective of tumor control improvement. There are still major debates with respect to first-line treatment of advanced cHL. The use of positron emission tomography-adapted strategies has allowed a reduction in the toxicity of chemotherapy regimens. Incorporation of new drugs into the treatment algorithms requires confirmation.


2016 ◽  
Vol 125 (Supplement_1) ◽  
pp. 64-72 ◽  
Author(s):  
Shinya Watanabe ◽  
Masaaki Yamamoto ◽  
Takuya Kawabe ◽  
Takao Koiso ◽  
Tetsuya Yamamoto ◽  
...  

OBJECTIVEThe aim of this study was to reappraise long-term treatment outcomes of stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs). The authors used a database that included patients who underwent SRS with a unique dose-planning technique, i.e., partial tumor coverage designed to avoid excess irradiation of the facial and cochlear nerves, focusing on tumor control and hearing preservation. Clinical factors associated with post-SRS tumor control and long-term hearing preservation were also analyzed.METHODSThis institutional review board–approved, retrospective cohort study used the authors' prospectively accumulated database. Among 207 patients who underwent Gamma Knife SRS for VSs between 1990 and 2005, 183 (who were followed up for at least 36 post-SRS months) were studied. The median tumor volume was 2.0 cm3 (range 0.05–26.2 cm3). The median prescribed dose at the tumor periphery was 12.0 Gy (range 8.8–15.0 Gy; 12.0 Gy was used in 171 patients [93%]), whereas tumor portions facing the facial and cochlear nerves were irradiated with 10.0 Gy. As a result, 72%–99% of each tumor was irradiated with the prescribed dose. The mean cochlear doses ranged from 2.3 to 5.7 Gy (median 4.1 Gy).RESULTSThe median durations of imaging and audiometric follow-up were 114 months (interquartile range 73–144 months) and 59 months (interquartile range 33–109 months), respectively. Tumor shrinkage was documented in 110 (61%), no change in 48 (27%), and enlargement in the other 22 (12%) patients. A further procedure (FP) was required in 15 (8%) patients. Thus, the tumor growth control rate was 88% and the clinical control rate (i.e., no need for an FP) was 92%. The cumulative FP-free rates were 96%, 93%, and 87% at the 60th, 120th, and 180th post-SRS month, respectively. Six (3%) patients experienced facial pain, and 2 developed transient facial palsy. Serviceable hearing was defined as a pure tone audiogram result better than 50 dB. Among the 66 patients with serviceable hearing before SRS who were followed up, hearing acuity was preserved in 23 (35%). Actuarial serviceable hearing preservation rates were 49%, 24%, and 12% at the 60th, 120th, and 180th post-SRS month, respectively. On univariable analysis, only cystic-type tumor (HR 3.36, 95% CI 1.18–9.36; p = 0.02) was shown to have a significantly unfavorable association with FP. Multivariable analysis followed by univariable analysis revealed that higher age (≥ 65 years: HR 2.66, 95% CI 1.16–5.92; p = 0.02), larger tumor volume (≥ 8 cm3: HR 5.36, 95% CI 1.20–17.4; p = 0.03), and higher cochlear dose (mean cochlear dose > 4.2 Gy: HR 2.22, 95% CI 1.07–4.77; p = 0.03) were unfavorable factors for hearing preservation.CONCLUSIONSStereotactic radiosurgery achieved good long-term results in this series. Tumor control was acceptable, and there were few serious complications in patients with small- to medium-sized VSs. Unfortunately, hearing preservation was not satisfactory. However, the longer the observation period, the more important it becomes to compare post-SRS hearing decreases with the natural decline in untreated cases.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 466-466 ◽  
Author(s):  
Flavio Augusto Ismael Pinto ◽  
Augusto Akikubo Rodrigues Pereira ◽  
Maria Nirvana Formiga ◽  
Marcello Ferretti Fanelli ◽  
Ludmilla T. D. Chinen ◽  
...  

466 Background: Sunitinib, a multitarget tyrosine-kinase inhibitor, has become a standard of care for first-line low and intermediate risk metastatic renal cell carcinoma (mRCC). Sunitinib-induced hypothyroidism and hypertension have been correlated with better outcomes in those patients. Methods: Fifty patients with mRCC, treated in the first-line with sunitinib, were retrospective analyzed at one brazilian institution, for overall survival (OS), progression free survival (PFS), overall response rate (ORR) and toxicity. We evaluated clinical and laboratory parameters, such as hypothyroidism (TSH level > 5,5 mIU/L) and hypertension, to identify prognostic factors. Results: The median age of patients was 58 years (range: 37-73 years), 82% were male, 54% were ECOG 0 or 1, and 76% were classified in low or intermediate risk. Nefrectomy was performed in 96% of cases. Lung and bone were the most common sites of metastases. The incidence of hypothyroidism and hypertension during treatment were 40% and 34%, respectively. ORR for the entire population was 40% and it was statistically superior in patients that developed hypothyroidism during treatment (90% vs. 20%; p<0,0001). Median survival and PFS were 21.7 months (10.65-17.70 months, 95% CI) and 14.2 months (15.77-27.58 months, 95% CI), respectively. In univariate analysis, ECOG (p<0,0001), MSKCC criteria (p<0,0001), hypothyroidism (p<00001) and hypertension (p=0,001) were associated with OS. In multivariate analysis, ECOG (p<0,0001), MSKCC criteria (p<0,0001) and hypothyroidism (p<00001) were independent prognostic factors for OS. The most common severe adverse events (G3-4) were asthenia (14%), diarrhoea (6%), neutropenia (14%), thrombocytopenia (10%), hand-foot syndrome (6%) and hypertension (8%). Conclusions: Efficacy in survival and toxicity profile of sunitinib in first-line treatment of mRCC in patients out of clinical trials were comparable to prior studies. Hypothyroidism, MSKCC criteria and ECOG were independent prognostic factors for survival.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2422-2422 ◽  
Author(s):  
Andrea Bacigalupo ◽  
Rosi Oneto ◽  
Schrezenmeier Hubert ◽  
Dufour Carlo ◽  
Seiji Kojima ◽  
...  

Abstract Background. Recent studies have suggested inferior outcome of patients treated with rabbit ATG (Thymoglobulin) as compared to horse ATG (ATGAM , Pfizer or Lymphoglobulin, Genzyme- the latter no longer available); other studies have shown comparable responses and survival. However these studies are based on a relatively small number of patients and a short follow up. Aim of the study. The aim of this study was to assess real life outcome of a large number of AA patients , treated in Europe and Asia with rabbit ATG (Thymoglobulin, SANOFI) and cyclosporin, as first line treatment . Methods and patients Eligible for this study were patients with AA treated with Thymoglobulin between 2001 and 2008 (n=501) and 2009-2012 (n=473) in Europe (n=519) or Asia (n=457). Median year of treatment was 2008 : median age (20 and 21 years), interval diagnosis treatment (23 and 25 days) and severity of the disease (46% and 48% with vSAA) were comparable in the 2 time periods. Early mortality. Mortality <90 days was 5,5% and 2.1% in the time period 2001-2008 and 2009-2012 (p=0.007). In patients aged 0-60 early mortality was reduced from 3.5% to 1.4% and in patients over 60 , from 22% to 9%. Response. Overall response was recorded in 799 patients. At 6 months , responses were comparable in the 2 time periods: 56% vs 57%, and at 1 year, 75% vs 73%. Response rates at 6 months were age dependent: 60%, 58%, 52%, 40% respectively in patients aged 0-20, 21-40, 41-60, >60. When non responders at 3 months were re-evaluated at 1 year, 59% had responded , 26% were non responders , 5% had died, and 10% had received other treatment. Survival: The actuarial 10 year survival for the entire population was 73%, and 72%, when patients were censored as surviving at transplant. The actuarial survival has significantly improved after year 2008, from 71% to 81% , not because of more transplants, which have remained stable (29% vs 30% before or after 2008). Other predictors of 10 year survival in univariate analysis were the following : 89%, 86%, 59% for complete, partial responders and non responders (p<0.01), 68% vs 80% for males versus females (p=0.07); 69%, 77%, 78% in patients with neutrophils <0.2x10^9/L, 02-05x10^9/L and >0.5x10^9/L (p<0.001); 77%, 75%, 68% for patients with an interval diagnosis-treatment of <30 days, 31-60 days or > 60 days (p=0.002); 82%, 72%, 66%, 27% in patients aged 0-20, 21-40, 41-60, > 60 years (p<0.001). Survival at 5 years for patients aged 1-60 in the recent period (2009-2012) was 83% and 62% for patients over 60 years; for patients treated within 60 days from diagnosis these figures are 86% and 83%. In multivariate Cox analysis the following variables remained independent predictors of survival : patient age, year of treatment , severity of the disease, interval diagnosis treatment, gender. Conclusions. With a current overall early mortality (<day 90) of 1.4% , a response rate at 6 months of 58% and 5 year survival of 81%, the combination of CsA and Thymoglobulin appears to be safe and effective as first line treatment in patients aged 1-60. In patients over 60 years of age, early mortality is higher , response rate and 5 year survival is lower, but results have improved after year 2008 , and current 5 year survival is 69%, for older patients treated within 2 months from diagnosis. Finally, response rates and survival, in this large retrospective analysis are quite favourable , compared to other recent publications, although a comparison with horse ATG was not the aim of the present study. Disclosures Bacigalupo: PIERRE FABRE: Speakers Bureau; SANOFI: Speakers Bureau. Carlo:Pfizer, Novartis: Consultancy. Kojima:SANOFI: Honoraria, Research Funding.


Neurosurgery ◽  
2011 ◽  
Vol 69 (6) ◽  
pp. 1200-1209 ◽  
Author(s):  
Ake Hansasuta ◽  
Clara Y. H. Choi ◽  
Iris C. Gibbs ◽  
Scott G. Soltys ◽  
Victor C. K. Tse ◽  
...  

Abstract BACKGROUND Single-session stereotactic radiosurgery (SRS) treatment of vestibular schwannomas results in excellent tumor control. It is not known whether functional outcomes can be improved by fractionating the treatment over multiple sessions. OBJECTIVE To examine tumor control and complication rates after multisession SRS. METHODS Three hundred eighty-three patients treated with SRS from 1999 to 2007 at Stanford University Medical Center were retrospectively reviewed. Ninety percent were treated with 18 Gy in 3 sessions, targeting a median tumor volume of 1.1 cm3 (range, 0.02-19.8 cm3). RESULTS During a median follow-up duration of 3.6 years (range, 1-10 years), 10 tumors required additional treatment, resulting in 3- and 5-year Kaplan-Meier tumor control rates of 99% and 96%, respectively. Five-year tumor control rate was 98% for tumors &gt; 3.4 cm3. Neurofibromatosis type 2–associated tumors were associated with worse tumor control (P = .02). Of the 200 evaluable patients with pre-SRS serviceable hearing (Gardner-Robertson grade 1 and 2), the crude rate of serviceable hearing preservation was 76%. Smaller tumor volume was associated with hearing preservation (P = .001). There was no case of post-SRS facial weakness. Eight patients (2%) developed trigeminal dysfunction, half of which was transient. CONCLUSION Multisession SRS treatment of vestibular schwannomas results in an excellent rate of tumor control. The hearing, trigeminal nerve, and facial nerve function preservation rates reported here are promising.


Neurosurgery ◽  
2003 ◽  
Vol 53 (3) ◽  
pp. 577-588 ◽  
Author(s):  
Damien C. Weber ◽  
Annie W. Chan ◽  
Marc R. Bussiere ◽  
Griffith R. Harsh ◽  
Marek Ancukiewicz ◽  
...  

Abstract OBJECTIVE We sought to determine the tumor control rate and cranial nerve function outcomes in patients with vestibular schwannomas who were treated with proton beam stereotactic radiosurgery. METHODS Between November 1992 and August 2000, 88 patients with vestibular schwannomas were treated at the Harvard Cyclotron Laboratory with proton beam stereotactic radiosurgery in which two to four convergent fixed beams of 160-MeV protons were applied. The median transverse diameter was 16 mm (range, 2.5–35 mm), and the median tumor volume was 1.4 cm3 (range, 0.1–15.9 cm3). Surgical resection had been performed previously in 15 patients (17%). Facial nerve function (House-Brackmann Grade 1) and trigeminal nerve function were normal in 79 patients (89.8%). Eight patients (9%) had good or excellent hearing (Gardner-Robertson [GR] Grade 1), and 13 patients (15%) had serviceable hearing (GR Grade 2). A median dose of 12 cobalt Gray equivalents (range, 10–18 cobalt Gray equivalents) was prescribed to the 70 to 108% isodose lines (median, 70%). The median follow-up period was 38.7 months (range, 12–102.6 mo). RESULTS The actuarial 2- and 5-year tumor control rates were 95.3% (95% confidence interval [CI], 90.9–99.9%) and 93.6% (95% CI, 88.3–99.3%). Salvage radiosurgery was performed in one patient 32.5 months after treatment, and a craniotomy was required 19.1 months after treatment in another patient with hemorrhage in the vicinity of a stable tumor. Three patients (3.4%) underwent shunting for hydrocephalus, and a subsequent partial resection was performed in one of these patients. The actuarial 5-year cumulative radiological reduction rate was 94.7% (95% CI, 81.2–98.3%). Of the 21 patients (24%) with functional hearing (GR Grade 1 or 2), 7 (33.3%) retained serviceable hearing ability (GR Grade 2). Actuarial 5-year normal facial and trigeminal nerve function preservation rates were 91.1% (95% CI, 85–97.6%) and 89.4% (95% CI, 82–96.7%). Univariate analysis revealed that prescribed dose (P = 0.005), maximum dose (P = 0.006), and the inhomogeneity coefficient (P = 0.03) were associated with a significant risk of long-term facial neuropathy. No other cranial nerve deficits or cancer relapses were observed. CONCLUSION Proton beam stereotactic radiosurgery has been shown to be an effective means of tumor control. A high radiological response rate was observed. Excellent facial and trigeminal nerve function preservation rates were achieved. A reduced prescribed dose is associated with a significant decrease in facial neuropathy.


2021 ◽  
Author(s):  
Xuetong Rong ◽  
Haiyi Liu ◽  
Hongmei Yu ◽  
Jian Zhao ◽  
Jie Wang ◽  
...  

Abstract Objective: To evaluate the efficacy and safety of apatinib combined with FOLFIRI in the first-line treatment of advanced metastatic colorectal cancer (mCRC) and explore potential factors of efficacy. Methods: Twenty mCRC patients treated at Affiliated Cancer Hospital of Shanxi Medical University from March 2017 to March 2019 were included according to the enrolment criteria. They provided informed consent and were treated with apatinib combined with FOLFIRI according to the scheduled regimen until disease progression or unacceptable toxicity occurred. The primary endpoint was OS. The secondary endpoints included PFS, ORR, DCRand safety. OS and PFS were calculated using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were used to evaluate independent prognostic factors of OS and PFS. R was used to determine cut-off values for biochemical indicators. Forest maps were drawn for Cox univariate results and the relationships between NLR and ECOG, which were significant in univariate analysis, and OS were represented by Kaplan-Meier curves. Results: The median OS and PFS were 16.135 months (95% CI: 9.211–22.929) and 6 months (95% CI: 5.425–6.525). Multivariate Cox analysis showed that NLR and CEA were independent prognostic factors. The most common grade 3–4 adverse events were hypertension, diarrhoea, increased alkaline phosphatase, decreased leukocytes and decreased neutrophils. Conclusion: Apatinib combined with FOLFIRI for the first-line treatment of advanced unresectable mCRC showed good efficacy and safety. The baseline NLR was predictive of efficacy, and a low baseline NLR (HR: 0.2895, P=0.0084) was associated with improved OS.


2012 ◽  
Vol 33 (3) ◽  
pp. E8 ◽  
Author(s):  
Douglas Kondziolka ◽  
Seyed H. Mousavi ◽  
Hideyuki Kano ◽  
John C. Flickinger ◽  
L. Dade Lunsford

Object Management recommendations for patients with smaller-volume or newly diagnosed vestibular schwannomas (< 4 cm3) need to be based on an understanding of the anticipated natural history of the tumor and the side effects it produces. The natural history can then be compared with the risks and benefits of therapeutic intervention using a minimally invasive strategy such as stereotactic radiosurgery (SRS). Methods The authors reviewed the emerging literature stemming from recent recommendations to “wait and scan” (observation) and compared this strategy with published outcomes after early intervention using SRS or results from matched cohort studies of resection and SRS. Results Various retrospective studies indicate that vestibular schwannomas grow at a rate of 0–3.9 mm per year and double in volume between 1.65 and 4.4 years. Stereotactic radiosurgery arrests growth in up to 98% of patients when studied at intervals of 10–15 years. Most patients who select “wait and scan” note gradually decreasing hearing function leading to the loss of useful hearing by 5 years. In contrast, current studies indicate that 3–5 years after Gamma Knife surgery, 61%–80% of patients maintain useful hearing (speech discrimination score > 50%, pure tone average < 50). Conclusions Based on published data on both volume and hearing preservation for both strategies, the authors devised a management recommendation for patients with small vestibular schwannomas. When resection is not chosen by the patient, the authors believe that early SRS intervention, in contrast to observation, results in long-term tumor control and improved rates of hearing preservation.


2019 ◽  
Vol 24 (3) ◽  
pp. 208-215 ◽  
Author(s):  
Elke Bouwens ◽  
Sanne Klaphake ◽  
Karin J Weststrate ◽  
Joep AW Teijink ◽  
Hence JM Verhagen ◽  
...  

Guidelines recommend supervised exercise therapy (SET) as first-line treatment for intermittent claudication. However, the use of revascularization is widespread. We addressed the effectiveness of preventing (additional) invasive revascularization after primary SET or revascularization based on lesion and patient characteristics. In this single-center, retrospective, cohort study, 474 patients with intermittent claudication were included. Patients with occlusive disease of the aortoiliac tract and/or common femoral artery (inflow) were primarily considered for revascularization, while patients with more distal disease (outflow) were primarily considered for SET. In total, 232 patients were referred for SET and 242 patients received revascularization. The primary outcome was freedom from (additional) intervention, analyzed by Kaplan–Meier estimates. Secondary outcomes were survival, critical ischemia, freedom from target lesion revascularization (TLR), and an increase in maximum walking distance. In the SET-first strategy, 71% of patients had significant outflow lesions. Freedom from intervention was 0.90 ± 0.02 at 1-year and 0.82 ± 0.03 at 2-year follow-up. In the primary revascularization group, 90% of patients had inflow lesions. Freedom from additional intervention was 0.78 ± 0.03 at 1-year and only 0.65 ± 0.04 at 2-year follow-up, despite freedom from TLR of 0.91 ± 0.02 and 0.85 ± 0.03 at 1- and 2-year follow-up, respectively. In conclusion, SET was effective in preventing invasive treatment for patients with mainly outflow lesions. In contrast, secondary intervention rates following our strategy of primary revascularization for inflow lesions were unexpectedly high. These findings further support the guideline recommendations of SET as first-line treatment for all patients with intermittent claudication irrespective of level of disease.


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