What Factors Predict the Response of Larger Brain Metastases to Radiosurgery?

Neurosurgery ◽  
2011 ◽  
Vol 68 (3) ◽  
pp. 682-690 ◽  
Author(s):  
Huai-che Yang ◽  
Hideyuki Kano ◽  
L Dade Lunsford ◽  
Ajay Niranjan ◽  
John C Flickinger ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Tumor Volume ◽  
Volume Reduction ◽  
Maximum Diameter ◽  
Recent Experience ◽  
Peritumoral Edema ◽  
Persistent Symptoms ◽  
Whole Brain Radiation ◽  
Edema Volume

Abstract BACKGROUND: Approximately 20 to 40% of patients with systemic malignancies develop brain metastases. OBJECTIVE: To assess the potential role of stereotactic radiosurgery (SRS) for larger metastatic brain tumors, we reviewed our recent experience. METHODS: Between 2004 and 2008, 70 patients with a metastatic brain tumor larger than 3 cm in maximum diameter underwent Gamma knife SRS. Thirty-three patients had received previous whole brain radiation therapy (WBRT) and 37 received only SRS. RESULTS: The overall median follow-up was 8.1 months. At the first planned imaging follow-up at 2 months, 29 (41%) tumors had >50% volume reduction, 22 (31%) had 10 to 50% volume reduction, and 19 (28%) were stable or larger. We also evaluated brain edema using MRI T2 images. In 11 patients (16%) the peritumoral edema volume was reduced by more than 50%, in 25 (36%) it was reduced by 10 to 50%, in 21 (30%) it was stable, and in 13 (19%) it was increased. Twenty (36%) discontinued corticosteroids by the time of first imaging follow-up. Because of persistent symptoms, 7 patients (10%) required a craniotomy to remove the tumor. Tumor volume reduction (>50%) was associated with a single metastasis (P = .012), no previous WBRT (P = .002), and a tumor volume <16 cm3 (P = .002). The better peritumoral edema volume reduction (>50%) was associated with a single metastasis (P = .024), no previous WBRT (P = .05), and breast cancer histology (P = .044). CONCLUSION: Surgical resection remains the primary approach for larger brain metastases if feasible. Tumor volume is a better indicator than maximum diameter. Tumor volume and edema responded better in patients who underwent SRS alone.

Gamma Knife radiosurgery for larger-volume vestibular schwannomas

2011 ◽  
Vol 114 (3) ◽  
pp. 801-807 ◽  
Author(s):  
Huai-che Yang ◽  
Hideyuki Kano ◽  
Nasir Raza Awan ◽  
L. Dade Lunsford ◽  
Ajay Niranjan ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Tumor Volume ◽  
Univariate Analysis ◽  
Gamma Knife Radiosurgery ◽  
Volume Reduction ◽  
Vestibular Schwannomas ◽  
Maximum Diameter ◽  
Tumor Control ◽  
Recent Experience

Object Stereotactic radiosurgery (SRS) is an important management option for patients with small- and medium-sized vestibular schwannomas. To assess the potential role of SRS in larger tumors, the authors reviewed their recent experience. Methods Between 1994 and 2008, 65 patients with vestibular schwannomas between 3 and 4 cm in one extracanalicular maximum diameter (median tumor volume 9 ml) underwent Gamma Knife surgery. Seventeen patients (26%) had previously undergone resection. Results The median follow-up duration was 36 months (range 1–146 months). At the first planned imaging follow-up at 6 months, 5 tumors (8%) were slightly expanded, 53 (82%) were stable in size, and 7 (11%) were smaller. Two patients (3%) underwent resection within 6 months due to progressive symptoms. Two years later, with 63 tumors overall after the 2 post-SRS resections, 16 tumors (25%) had a volume reduction of more than 50%, 22 (35%) tumors had a volume reduction of 10–50%, 18 (29%) were stable in volume (volume change < 10%), and 7 (11%) had larger volumes (5 of the 7 patients underwent resection and 1 of the 7 underwent repeat SRS). Eighteen (82%) of 22 patients with serviceable hearing before SRS still had serviceable hearing after SRS more than 2 years later. Three patients (5%) developed symptomatic hydrocephalus and underwent placement of a ventriculoperitoneal shunt. In 4 patients (6%) trigeminal sensory dysfunction developed, and in 1 patient (2%) mild facial weakness (House-Brackmann Grade II) developed after SRS. In univariate analysis, patients who had a previous resection (p = 0.010), those with a tumor volume exceeding 10 ml (p = 0.05), and those with Koos Grade 4 tumors (p = 0.02) had less likelihood of tumor control after SRS. Conclusions Although microsurgical resection remains the primary management choice in patients with low comorbidities, most vestibular schwannomas with a maximum diameter less than 4 cm and without significant mass effect can be managed satisfactorily with Gamma Knife radiosurgery.

The Volumetric Response of Brain Metastases After Stereotactic Radiosurgery and Its Post-treatment Implications

Neurosurgery ◽  
2013 ◽  
Vol 74 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Suzanne R. Sharpton ◽  
Eric K. Oermann ◽  
Dominic T. Moore ◽  
Eric Schreiber ◽  
Riane Hoffman ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Tumor Volume ◽  
Neurological Symptoms ◽  
Volume Reduction ◽  
Whole Brain Radiation ◽  
Local Progression ◽  
Tumor Volume Reduction

Abstract BACKGROUND: Changes in tumor volume are seen on magnetic resonance imaging within weeks after stereotactic radiosurgery (SRS), but it remains unclear what clinical outcomes early radiological changes portend. OBJECTIVE: We hypothesized that rapid, early reduction in tumor volume post-SRS is associated with prolonged local control and favorable clinical outcome. METHODS: A retrospective review of patients treated with CyberKnife SRS for brain metastases at the University of North Carolina from 2007 to 2009 was performed. Patients with at least 1 radiological follow-up, minimal initial tumor volume of 0.1 cm3, no previous focal radiation, and no recent whole-brain radiation therapy were eligible for inclusion. RESULTS: Fifty-two patients with 100 metastatic brain lesions were analyzed and had a median follow-up of 15.6 months (range, 2-33 months) and a median of 2 (range, 1–8) metastatic lesions. In treated metastases in which there was a significant tumor volume reduction by 6 or 12 weeks post-SRS, there was no local progression for the duration of the study. Furthermore, patients with metastases that did not reduce in volume by 6 or 12 weeks post-SRS were more likely to require corticosteroids (P = .01) and to experience progression of neurological symptoms (P = .003). CONCLUSION: Significant volume reductions of brain metastases measured at either 6 or 12 weeks post-SRS were strongly associated with prolonged local control. Furthermore, early volume reduction was associated with less corticosteroid use and stable neurological symptoms.

scholarly journals RADI-27. ROLE OF STEREOTACTIC RADIOSURGERY IN THE CARE OF PATIENTS WITH >/= 25 CUMULATIVE BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i27-i27
Author(s):  
Carolina Benjamin ◽  
Monica Mureb ◽  
Bernadine Donahue ◽  
Erik Sulman ◽  
Joshua Silverman ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Tumor Volume ◽  
Median Number ◽  
Median Dose ◽  
Total Tumor Volume ◽  
Whole Brain Radiation ◽  
Brain Radiation

Abstract INTRODUCTION: Stereotactic radiosurgery (SRS) is an accepted treatment for multiple brain metastases. However, the upper limit of the number of brain metastases over the course of care suitable for this approach is controversial. METHODS: From a review of our prospective registry, 48 patients treated with SRS for ≥ 25 brain metastases in either single or multiple sessions between 2013 and 2019 were identified. Patient, tumor, and treatments characteristics were evaluated. Clinical outcomes and overall survival (OS) were analyzed. RESULTS: Thirty-one females (64.6%) and 17 males (35.4%) with a median age of 56 years (25–91) were included. Primary diagnoses included lung (n=23, 47.9%), breast (n=13, 27.1%), melanoma (n=8, 16.7%), and other (n=4, 8.33%). Initial median GPA index was 2 (0.5–3). Nine patients (18.8%) had received whole brain radiation therapy (WBRT) prior to first SRS treatment, with a median dose of 35Gy (30–40.5Gy). Ten patients (20.8%) received WBRT after initial SRS, with a median dose of 30Gy (20-30Gy). Thus, only 19 patients (40%) ever received WBRT. Median number of radiosurgeries per patient was 3 (1–12). Median number of cumulative tumors irradiated was 31 (25–110). Median number of tumors irradiated at first SRS was 10 (1–35). Median marginal dose for the largest tumor per session was 16Gy (10-21Gy). Median SRS total tumor volume was 6.8cc (0.8–23.4). Median follow-up since initial SRS was 16 months (1–71). At present, 21 (43.7%) are alive. Median OS from the diagnosis of brain metastases was 31 months (2–97), and OS from the time of first SRS, 22 months (1–70). Median KPS at first SRS and last follow-up was the same (90). Sixty-three percent did not require a corticosteroid course. CONCLUSION: In selected patients with a large number of cumulative brain metastases (≥ 25), SRS is effective and safe. Therefore, WBRT may not be required in this population.

scholarly journals Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm

2018 ◽  
Vol 129 (2) ◽  
pp. 366-382 ◽  
Author(s):  
Lilyana Angelov ◽  
Alireza M. Mohammadi ◽  
Elizabeth E. Bennett ◽  
Mahmoud Abbassy ◽  
Paul Elson ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Binary Data ◽  
Tumor Volume ◽  
Demographic Data ◽  
Maximum Diameter ◽  
Local Progression ◽  
Imaging Results ◽  
Increased Risk

OBJECTIVEStereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%–62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy.METHODSFifty-four patients (with 63 brain metastases ≥ 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board–approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study evaluated 3 primary outcomes: 1) response at first follow-up MRI, 2) time to local progression (TTP), and 3) overall survival (OS) with 2-SSRS. Response was analyzed using methods for binary data, TTP was analyzed using competing-risks methods to account for patients who died without disease progression, and OS was analyzed using conventional time-to-event methods. When needed, analyses accounted for multiple lesions in the same patient.RESULTSAmong 54 patients, 46 (85%) had 1 brain metastasis treated with 2-SSRS, 7 patients (13%) had 2 brain metastases concurrently treated with 2-SSRS, and 1 patient underwent 2-SSRS for 3 concurrent brain metastases ≥ 2 cm. The median age was 63 years (range 23–83 years), 23 patients (43%) had non–small cell lung cancer, and 14 patients (26%) had radioresistant tumors (renal or melanoma). The median doses at first and second SSRS were 15 Gy (range 12–18 Gy) and 15 Gy (range 12–15 Gy), respectively. The median duration between stages was 34 days, and median tumor volumes at the first and second SSRS were 10.5 cm3 (range 2.4–31.3 cm3) and 7.0 cm3 (range 1.0–29.7 cm3). Three-month follow-up imaging results were available for 43 lesions; the median volume was 4.0 cm3 (range 0.1–23.1 cm3). The median change in volume compared with baseline was a decrease of 54.9% (range −98.2% to 66.1%; p < 0.001). Overall, 9 lesions (14.3%) demonstrated local progression, with a median of 5.2 months (range 1.3–7.4 months), and 7 (11.1%) demonstrated AEs (6.4% Grade 1 and 2 toxicity; 4.8% Grade 3). The estimated cumulative incidence of local progression at 6 months was 12% ± 4%, corresponding to an LC rate of 88%. Shorter TTP was associated with greater tumor volume at baseline (p = 0.01) and smaller absolute (p = 0.006) and relative (p = 0.05) decreases in tumor volume from baseline to second SSRS. Estimated OS rates at 6 and 12 months were 65% ± 7% and 49% ± 8%, respectively.CONCLUSIONS2-SSRS is an effective treatment modality that resulted in significant reduction of brain metastases ≥ 2 cm, with excellent 3-month (95%) and 6-month (88%) LC rates and an overall AE rate of 11%. Prospective studies with larger cohorts and longer follow-up are necessary to assess the durability and toxicities of 2-SSRS.

scholarly journals Gamma Knife radiosurgery for large vestibular schwannomas greater than 3 cm in diameter

2018 ◽  
Vol 128 (5) ◽  
pp. 1380-1387 ◽  
Author(s):  
Cheng-Wei Huang ◽  
Hsien-Tang Tu ◽  
Chun-Yi Chuang ◽  
Cheng-Siu Chang ◽  
Hsi-Hsien Chou ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Tumor Volume ◽  
Gamma Knife Radiosurgery ◽  
Pure Tone Audiometry ◽  
Volume Reduction ◽  
Vestibular Schwannomas ◽  
Tumor Control ◽  
Recent Experience ◽  
Single Dimension

OBJECTIVEStereotactic radiosurgery (SRS) is an important alternative management option for patients with small- and medium-sized vestibular schwannomas (VSs). Its use in the treatment of large tumors, however, is still being debated. The authors reviewed their recent experience to assess the potential role of SRS in larger-sized VSs.METHODSBetween 2000 and 2014, 35 patients with large VSs, defined as having both a single dimension > 3 cm and a volume > 10 cm3, underwent Gamma Knife radiosurgery (GKRS). Nine patients (25.7%) had previously undergone resection. The median total volume covered in this group of patients was 14.8 cm3 (range 10.3–24.5 cm3). The median tumor margin dose was 11 Gy (range 10–12 Gy).RESULTSThe median follow-up duration was 48 months (range 6–156 months). All 35 patients had regular MRI follow-up examinations. Twenty tumors (57.1%) had a volume reduction of greater than 50%, 5 (14.3%) had a volume reduction of 15%–50%, 5 (14.3%) were stable in size (volume change < 15%), and 5 (14.3%) had larger volumes (all of these lesions were eventually resected). Four patients (11.4%) underwent resection within 9 months to 6 years because of progressive symptoms. One patient (2.9%) had open surgery for new-onset intractable trigeminal neuralgia at 48 months after GKRS. Two patients (5.7%) who developed a symptomatic cyst underwent placement of a cystoperitoneal shunt. Eight (66%) of 12 patients with pre-GKRS trigeminal sensory dysfunction had hypoesthesia relief. One hemifacial spasm completely resolved 3 years after treatment. Seven patients with facial weakness experienced no deterioration after GKRS. Two of 3 patients with serviceable hearing before GKRS deteriorated while 1 patient retained the same level of hearing. Two patients improved from severe hearing loss to pure tone audiometry less than 50 dB.The authors found borderline statistical significance for post-GKRS tumor enlargement for later resection (p = 0.05, HR 9.97, CI 0.99–100.00). A tumor volume ≥ 15 cm3 was a significant factor predictive of GKRS failure (p = 0.005). No difference in outcome was observed based on indication for GKRS (p = 0.0761).CONCLUSIONSAlthough microsurgical resection remains the primary management choice in patients with VSs, most VSs that are defined as having both a single dimension > 3 cm and a volume > 10 cm3 and tolerable mass effect can be managed satisfactorily with GKRS. Tumor volume ≥ 15 cm3 is a significant factor predicting poor tumor control following GKRS.

Incidence, timing, and treatment of new brain metastases after Gamma Knife surgery for limited brain disease: the case for reducing the use of whole-brain radiation therapy

2011 ◽  
Vol 115 (1) ◽  
pp. 37-48 ◽  
Author(s):  
Stephen Rush ◽  
Robert E. Elliott ◽  
Amr Morsi ◽  
Nisha Mehta ◽  
Jeri Spriet ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Metastases ◽  
Gamma Knife ◽  
Gamma Knife Surgery ◽  
Whole Brain Radiation Therapy ◽  
Leptomeningeal Disease ◽  
Whole Brain ◽  
Whole Brain Radiation ◽  
Brain Radiation

Object In this paper, the authors' goal was to analyze the incidence, timing, and treatment of new metastases following initial treatment with 20-Gy Gamma Knife surgery (GKS) alone in patients with limited brain metastases without whole-brain radiation therapy (WBRT). Methods A retrospective analysis of 114 consecutive adults (75 women and 34 men; median age 61 years) with KPS scores of 60 or higher who received GKS for 1–3 brain metastases ≤ 2 cm was performed (median lesion volume 0.35 cm3). Five patients lacking follow-up data were excluded from analysis. After treatment, patients underwent MR imaging at 6 weeks and every 3 months thereafter. New metastases were preferentially treated with additional GKS. Indications for WBRT included development of numerous metastases, leptomeningeal disease, or diffuse surgical-site recurrence. Results The median overall survival from GKS was 13.8 months. Excluding the 3 patients who died before follow-up imaging, 12 patients (11.3%) experienced local failure at a median of 7.4 months. Fifty-three patients (50%) developed new metastases at a median of 5 months. Six (7%) of 86 instances of new lesions were symptomatic. Most patients (67%) with distant failures were successfully treated using salvage GKS alone. Whole-brain radiotherapy was indicated in 20 patients (18.3%). Thirteen patients (11.9%) died of neurological disease. Conclusions For patients with limited brain metastases and functional independence, 20-Gy GKS provides excellent disease control and high-functioning survival with minimal morbidity. New metastases developed in almost 50% of patients, but additional GKS was extremely effective in controlling disease. Using our algorithm, fewer than 20% of patients required WBRT, and only 12% died of progressive intracranial disease.

scholarly journals TRLS-07. BRAINSTORM: OUTCOMES FROM A MULTI-INSTITUTIONAL PHASE I/II STUDY OF RRx-001 IN COMBINATION WITH WHOLE BRAIN RADIATION THERAPY FOR PATIENTS WITH BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i9-i10
Author(s):  
Michelle Kim ◽  
Hemant Parmar ◽  
Matthew Schipper ◽  
Theresa Devasia ◽  
Madhava Aryal ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Metastases ◽  
Phase I ◽  
Tumor Volume ◽  
Whole Brain Radiation Therapy ◽  
Whole Brain ◽  
Dce Mri ◽  
Whole Brain Radiation ◽  
Dose Levels ◽  
Brain Radiation

Abstract INTRODUCTION: To determine the recommended Phase II dose of RRx-001, a radiosensitizer with vascular normalizing properties, when used with whole-brain radiation therapy (WBRT) for brain metastases, and to assess whether quantitative changes in perfusion MRI after RRx-001 correlate with response. METHODS AND MATERIALS: Five centers participated in this phase I/II trial of RRx-001 given once pre-WBRT then twice weekly during WBRT (30 Gy/10 fractions). Four dose levels were planned (5 mg/m2, 8.4 mg/m2, 16.5 mg/m2, 27.5 mg/m2). Dose-escalation was managed by the Time-to-Event Continual Reassessment Model (TITE-CRM). Correlative DCE-MRI was performed in a subset of patients and linear mixed models used to correlate change in 24-hour T1, Ktrans (capillary permeability) and Vp (plasma volume) with change in tumor volume. RESULTS: Between 2015–2017, 31 patients were enrolled. Two patients dropped out prior to any therapy and 7 were treated with concurrent temozolomide following a study amendment. Median age was 60 years (range, 30–76) and 17 were male. The most common tumor types were melanoma (58%) and non-small cell lung cancer (20%). No dose-limiting toxicities were observed. The most common severe adverse event was grade 3 asthenia in 6.9% (2/29). The median intracranial response rate was 46% (95%CI 24–68) and median overall survival was 5.2 months (95%CI 4.5–9.4). No neurologic deaths occurred. Among 10 evaluable patients undergoing DCE-MRI, a reduction in Vp 24 hours after RRx-001 was associated with reduced tumor volume at 1 month and 4 months (p≤0.01). CONCLUSION: The addition of RRx-001 to WBRT is safe and well-tolerated with favorable intracranial response rates. Because activity was observed across all dose levels, and in the absence of a dose response, the recommended Phase 2 dose is 10 mg administered twice weekly. A reduction in Vp by DCE-MRI 24 hours after RRx-001 suggests anti-angiogenic activity that is associated with longer-term tumor response.

Radiosurgery alone for solitary and multiple brain metastasis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1541-1541
Author(s):  
J. L. Fox ◽  
L. Kleinberg ◽  
S. Kharkar ◽  
R. E. Clatterbuck ◽  
P. Wang ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Median Number ◽  
Rank Test ◽  
Small Cell Lung ◽  
Treatment Groups ◽  
Time Commitment ◽  
Whole Brain Radiation ◽  
Log Rank Test ◽  
Brain Radiation

1541 Background: Whole-brain radiation (WBRT) in the management of brain metastases treated with radiosurgery (RS) is controversial. Methods: Ninety-eight patients were treated for brain metastases with RS at Johns Hopkins between 4/03 and 7/05. Twenty-eight patients received RS alone after failing WBRT, 33 received RS alone for initial metastases and 37 received RS along with WBRT. Forty-five patients were women and 53 were men, with a median age of 56 (range, 18–92). Histology was: non-small cell lung cancer - 35, breast -14, melanoma -10, renal cell carcinoma - 9, and other - 30. Ninety-two (94%) pts had a KPS of ≥ 70 (median 80). The median number of metastases was 2 (range, 1–14). Results: Follow-up data from date of RS was available for 96 patients. Among those who received RS along with planned WBRT, median survival (MS) was 6.6 months with 1-yr overall survival (OS) 38%. Among patients treated initially with RS alone, MS was 9.7 months with 1-yr OS 42%. Among patients treated with RS for recurrent metastases after prior WBRT, MS was 6.8 months with 1-yr OS 24%. There were no significant differences in survival amongst these 3 treatment groups (p=0.73, log-rank test). For patients with 1–3 metastases (n=66), 1-yr OS was 38% versus 32% for those with ≥ 4 (n=32). Median survivals were 8.4 and 6.7 months, respectively (p=NS). Of patients treated with RS for recurrence, 7 of 25 (28%) with available follow-up data developed recurrent or new metastases whereas 11/27 (41%) treated with RS and planned WBRT and 15/27 (56%) who had RS alone as initial treatment had documented recurrent or new metastases. Conclusions: RS alone may be an effective treatment that preserves survival for those with single or multiple brain metastases at initial presentation or recurrence, but the tradeoff between the marginal increase in risk of brain recurrence versus toxicity and time commitment for WBRT needs further evaluation. The ongoing US Intergroup randomized trial, N0572/Z300, will address some of these questions. No significant financial relationships to disclose.

A phase II trial of temozolomide and vinorelbine for patients with recurrent brain metastases

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2050-2050
Author(s):  
F. M. Iwamoto ◽  
A. M. Omuro ◽  
J. J. Raizer ◽  
C. P. Nolan ◽  
A. Hormigo ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Minor Response ◽  
Radiographic Response ◽  
Whole Brain Radiation ◽  
Heavily Pretreated ◽  
Grade 3

2050 Background: Temozolomide has shown modest efficacy in the treatment of recurrent brain metastases. We designed a regimen combining temozolomide with vinorelbine, a lipophilic agent that crosses the blood-brain barrier, trying to improve efficacy. Methods: This is a phase II trial with 28-day cycles using temozolomide (150 mg/m2, days 1–7 and 15–21) and vinorelbine on days 1 and 8. We previously reported a phase I trial that established an MTD of 30 mg/m2 of vinorelbine in this combination, but the dose was decreased to 25 mg/m2 in this phase II trial. The phase II component was planned as a two-stage clinical trial. Since two or more responses were observed after the 20 initial patients, 15 more assessable patients were required. This design had a 91% probability to detect a true response rate of 20% or more. The primary endpoint was objective radiographic response. Secondary endpoints include OS, PFS and toxicity. Patients = 18 years old with KPS = 60, adequate organ function and progressive or recurrent brain metastases were eligible. Results: Thirty-six patients (13 men, 23 women) with a median age of 56 years (range, 38–76) and median KPS of 80 were enrolled. The primary tumor sites were lung (n=19), breast (n=11), colon (n=2), bladder (n=1), endometrium (n=1), head/neck (n=1) and kidney (n=1). Prior therapies included whole-brain radiation therapy (81%), chemotherapy (97%), radiosurgery (42%) and brain metastasis resection (47%). Objective radiographic response was 7% (1 CR and 1 minor response); 4 patients had SD and 23 PD. Three patients withdrew consent and did not undergo follow-up scans, 2 patients did not receive the planned treatment and 2 patients recently began treatment and have not been assessed. The median follow-up was 12.3 weeks and 72% of patients have died. Median PFS and OS were 8.3 weeks and 5 months, respectively. Grade 3/4 toxicities were mainly hematological and 3 patients were removed from the study due to myelosuppression. Conclusions: In this heavily pretreated population of patients with brain metastases, adding vinorelbine to temozolomide does not seem to improve response rates as compared to temozolomide alone. Single-agent temozolomide also has a more favorable toxicity profile. [Table: see text]

Single-institution experience with neoadjuvant chemotherapy for metaplastic breast cancer (MBC).

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 140-140
Author(s):  
Anna Kaminsky
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Tumor Volume ◽  
Triple Negative ◽  
Volume Reduction ◽  
Tumor Volume Reduction ◽  
Metaplastic Breast Carcinoma

140 Background: Metaplastic breast carcinoma (MBC) is a rare subtype that accounts for <1% of all breast carcinomas. MBC is frequently triple-negative and neoadjuvant chemotherapy (NAC) is often used in triple-negative breast cancer (TNBC). The objective of this analysis is to ascertain response rates of MBC to NAC as compared to non-metaplastic TNBC. Methods: We searched the Magee Women’s Cancer Center of UPMC IRB-approved neo-adjuvant treatment database which contains outcome data on 594 patients treated from 2004-2010. 116 patients with triple negative breast cancer (ER /PR negative or ER /PR weakly positive [H score of 10 or less] and HER2 negative or indeterminate [HER2 1+ or 2+ without amplification by FISH]), were identified. Nine of these TNBCs had metaplastic subtype and two groups were analyzed: metaplastic breast carcinoma (MBC) (N= 9) and non-metaplastic breast carcinoma (NMBC) (N = 107). Tumor volume reduction (TVR), pathologic complete response (pCR), recurrence and mortality were compared in both groups. Results: Average follow-up in MBC group was 43 months and no patients were lost to follow-up. Average tumor size on presentation in MBC group was 4.47 cm while in NMBC group it was 3.33 cm. pCR was noted in 0/9 MBC and 43/107 NMBC cases (p = 0.0253). 6/9 patients had mastectomy, 2/9 had breast conserving surgery (BCS) and 1/9 patients did not have a surgery yet. Average TVR was 28% in MBC cases compared to 74% in NMBCs when cases with pCR were included (p = 0.0001) and 56% when cases with pCR were excluded (p = 0.0202). Follow up on 9 MBC cases revealed 1 recurrence and subsequent death (11%). Follow-up on 64 NMBC patients who failed to achieve pCR revealed 22 recurrences (34%) and 18 of them subsequently died (28%). Follow-up on 43 NMBC cases that achieved pCR revealed 3 recurrences (7%) and 1 death (2%). Conclusions: MBC was characterized by larger size at baseline as compared to NMBC. There were no pCR’s seen in MBC, but some MBC did achieve response that allowed for breast conservation. Although the average tumor volume reduction was significantly less in MBC compared to NMBC, the NMBC that failed to achieve pCR fared much worse than MBC who did not achieve pCR. Therefore, the triple-negative paradox is likely not applicable to MBC.

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