10.1007/s11060-009-0051-x</TIT= LE> <META http-equiv=3DContent-Type content=3D"text/html; = charset=3DISO-8859-1"><LINK=20 href=3D"http://www.springerlink.com/config/css/A++_common.css" = type=3Dtext/css=20 rel=3DstyleSheet><LINK=20 href=3D"http://www.springerlink.com/config/css/content_A++_SpringerLink.c= ss"=20 type=3Dtext/css rel=3DstyleSheet> <META content=3D"MSHTML 6.00.6000.16939" name=3DGENERATOR></HEAD> <BODY class=3Dfor-print> <TABLE cellPadding=3D2 border=3D1> <TBODY> <TR class=3Dheader> <TD>Journal of Neuro-Oncology</TD></TR> <TR> <TD>=A9 Springer Science+Business Media, = LLC. 2009</TD></TR> <TR> <TD>10.1007/s11060-009-0051-x</TD></TR></TBODY></TABLE> <H2 class=3Drubric>Clinical Study - Patient Study</H2> <DIV class=3DHeading1><A name=3Dtitle></A>Adjuvant Gamma Knife = radiosurgery=20 following surgical resection of brain metastases: a 9-year retrospective = cohort=20 study </DIV> <P class=3DAuthorGroup>Steven W. Hwang<SUP>1</SUP>,=20 Mohab M. Abozed<SUP>1</SUP>, Andrew Hale<SUP>1</SUP>,=20 Rebecca L. Eisenberg<SUP>2</SUP>, = Tomas Dvorak<SUP>3</SUP>,=20 Kevin Yao<SUP>1</SUP>, Rolf Pfannl<SUP>4</SUP>,=20 John Mignano<SUP>3</SUP>, Jay-Jiguang Zhu<SUP>2, 5</SUP>,=20 Lori Lyn Price<SUP>6</SUP>, = Gary M. Strauss<SUP>2</SUP> and=20 Julian K. Wu<SUP>1 <A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#ContactOfAuthor12"><IMG=20 alt=3D"Contact Information"=20 src=3D"http://www.springerlink.com/content/m1162h5155750653/contact.gif" = border=3D0></A></SUP></P> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><SPAN class=3DAffiliation><A = name=3DAff1></A>(1) </SPAN></TD> <TD><SPAN class=3DAffiliation>Department of Neurosurgery, Tufts = Medical=20 Center, 800 Washington Street, Boston, MA 02111,=20 USA</SPAN></TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><SPAN class=3DAffiliation><A = name=3DAff2></A>(2) </SPAN></TD> <TD><SPAN class=3DAffiliation>Division of Hematology-Oncology, = Department of=20 Medicine, Tufts Medical Center, Boston, MA, = USA</SPAN></TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><SPAN class=3DAffiliation><A = name=3DAff3></A>(3) </SPAN></TD> <TD><SPAN class=3DAffiliation>Department of Radiation Oncology, = Tufts=20 Medical Center, Boston, MA, USA</SPAN></TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><SPAN class=3DAffiliation><A = name=3DAff4></A>(4) </SPAN></TD> <TD><SPAN class=3DAffiliation>Department of Anatomic Pathology, = Tufts=20 Medical Center, Boston, MA, USA</SPAN></TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><SPAN class=3DAffiliation><A = name=3DAff5></A>(5) </SPAN></TD> <TD><SPAN class=3DAffiliation>Department of Neurology, Tufts Medical = Center,=20 Boston, MA, USA</SPAN></TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><SPAN class=3DAffiliation><A = name=3DAff6></A>(6) </SPAN></TD> <TD><SPAN class=3DAffiliation>Institute for Clinical Research and = Health=20 Policy Studies, Tufts Medical Center, Boston, MA,=20 USA</SPAN></TD></TR></TBODY></TABLE> <P><A name=3DContactOfAuthor12></A></P> <TABLE class=3DContact> <TBODY> <TR> <TD vAlign=3Dtop><IMG alt=3D"Contact Information"=20 = src=3D"http://www.springerlink.com/content/m1162h5155750653/contact.gif" = border=3D0></TD> = <TD><STRONG>Julian </STRONG><STRONG>K. </STRONG><STRONG>Wu</STR= ONG><STRONG></STRONG><BR><STRONG>Email:=20 </STRONG><A=20 = href=3D"mailto:jwu3@tuftsmedicalcenter.org">jwu3@tuftsmedicalcenter.org</= A></TD></TR></TBODY></TABLE> <P class=3DAffiliation><STRONG>Received:=20 </STRONG>22 March 2009 <STRONG>Accepted:=20 </STRONG>26 October 2009 <STRONG>Published online:=20 </STRONG>12 November 2009 </P> <DIV class=3DAbstract><A name=3DAbs1></A><SPAN=20 class=3DAbstractHeading>Abstract </SPAN>Given the potential = morbidity=20 of whole brain radiation therapy (WBRT), there has been an increasing = trend to=20 defer WBRT and deliver Gamma Knife stereotactic radiosurgery (GKS) to = cerebral=20 metastatic lesions. We analyzed our experience delivering GKS to the = tumor=20 cavity following surgical resection of brain metastases and compared our = results=20 to patients receiving WBRT after surgical resection of a metastatic = lesion. We=20 performed a retrospective review of patients undergoing surgical = resection of at=20 least one brain metastasis between December 1999 and December 2008. Both = univariate and multivariate Cox proportional hazards regression were = utilized to=20 analyze the influence of various prognostic factors on survival. = Twenty-five=20 patients had a metastatic lesion resected followed by adjuvant GKS to = the=20 resection cavity while another 18 had surgical resection followed by = WBRT. Aside=20 from a disparity in gender distribution (72% of GKS patients were female = while=20 women only constituted 28% of the WBRT group), no significant = differences=20 existed between groups. The median survival for patients receiving GKS = was=20 15.00 months as compared to 6.81 months among those receiving = WBRT=20 (<I>P</I> =3D 0.08). Univariate Cox regression analysis = identified the=20 number of metastases (HR 1.65, 95% CI 1.07=962.54, = <I>P</I> =3D 0.02) and=20 regional recurrence (RR 5.23, 95% CI 1.78=9615.38, = <I>P</I> =3D 0.003) as=20 poor prognostic factors. Multivariate regression analysis showed that = regional=20 recurrence (HR 5.17, 95% CI 1.69=9615.78, <I>P</I> =3D 0.004) = was again=20 strongly associated with worse survival. Although limited by the = retrospective=20 nature of our study and lack of some clinical measures, patients = undergoing GKS=20 to the resection cavity had a trend towards longer median survival. = </DIV> <P class=3DKeyword><SPAN = class=3DKeywordHeading>Keywords </SPAN>Gamma=20 Knife - Radiosurgery - Cerebral = metastasis - Brain=20 metastasis - Brain neoplasms - Craniotomy </P> <DIV class=3DFulltext> <DIV class=3D""><A name=3DSec1></A> <HR> <DIV class=3Dheading2>Introduction</DIV> <P class=3D"">Brain metastases represent the most common intracranial = tumor and=20 have been reported to occur in 20=9640% of cancer patients [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR1">1</A></CITE>=96<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR3">3</A></CITE>].=20 The increasing frequency of brain metastases may be secondary to = improved=20 methods of detection such as routine screening with magnetic resonance = imaging=20 (MRI), and prolonged survival with better systemic control of disease = [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR1">1</A></CITE>].=20 However, brain metastases still portend a poor prognosis and = historically,=20 untreated patients have had a median survival of approximately = 4 weeks=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR2">2</A></CITE>].=20 The median survival of patients with cerebral metastases has been = prolonged with=20 adjuvant treatments such as steroid administration, as well as radiation = therapy=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR3">3</A></CITE>=96<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR5">5</A></CITE>].=20 </P> <P class=3D"">Survival of patients with brain metastases has been = improved by the=20 use of whole brain radiation therapy (WBRT), surgery, and stereotactic=20 radiosurgery (SRS) in conjunction with systemic therapies. WBRT has been = the=20 standard treatment for brain metastases and continues to be used = extensively in=20 patients with poor prognosis, multi-focal disease and in combination = with other=20 modalities [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR1">1</A></CITE>].=20 However, more recently there has been an increasing trend to treat = cerebral=20 metastases with local therapies such as surgical resection and SRS = [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR6">6</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR7">7</A></CITE>].=20 </P> <P class=3D"">Our study was performed to retrospectively analyze = outcomes from a=20 cohort of patients, treated at our institution over a 9 year = period, who=20 underwent surgical resection of brain metastases followed either by GKS = to the=20 resection cavity or WBRT. We sought to evaluate the survival outcomes = for=20 different subgroups of patients and to determine if patient survival was = adversely affected by deferring WBRT. </P></DIV> <DIV class=3D""><A name=3DSec2></A> <HR> <DIV class=3Dheading2>Patients and methods</DIV> <P class=3D"">Institutional review board approval was obtained through = the Tufts=20 Medical Center Institutional Review Board (IRB). Medical records were = obtained=20 on all patients including the hospital primary computer-based records as = well as=20 neurosurgery office charts, radiation oncology clinic charts, pathology = reports,=20 and the hematology-oncology clinic charts. Post-operative imaging was = reviewed=20 to determine the extent of surgical resection. The Social Security Death = Index=20 was searched to confirm date of death. Attempts were made to contact all = living=20 patients by letter and phone call to perform a brief phone survey to = gather=20 additional data. Referring physicians were also contacted by telephone = and=20 letter to request additional information on patients who received = treatment=20 outside of our institution. </P> <DIV class=3DPara> <DIV class=3D"">Patients who had undergone surgical resection of at = least one=20 brain metastasis between December 1999 and December 2008 were identified = by=20 billing codes from the Department of Neurosurgery at Tufts Medical = Center.=20 Inclusion criteria included age greater than or equal to 18 years,=20 documented brain metastasis from systemic cancer, and surgical resection = of at=20 least one brain metastasis with adjuvant GKS or WBRT. Patients included = in our=20 study who received GKS were planned for treatment within 30 days of = their=20 surgical resection, although systemic treatment or travel distances may = have=20 delayed some cases. Patients with primary brain tumors, or the diagnoses = of=20 lymphoma or multiple myeloma were excluded as well as patients who had = received=20 both GKS and WBRT. One patient was excluded who died before completion = of his=20 WBRT treatment secondary to cardiopulmonary complications. In all cases, = either=20 a resection cavity or residual enhancement was visible on a GKS planning = MRI.=20 The treatment target included any residual enhancement and the resection = cavity.=20 Dosimetry was based on the RTOG 90-05 recommendations of a mean = peripheral dose=20 (50% isodose) ranging from 15-20 Gy depending on the size of the = cavity=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR8">8</A></CITE>].=20 We therefore targeted 15-20 Gy at the 50% isodose line to the = resection=20 margin (Fig. <A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#Fig1">1</A>).=20 Patients with >3 other lesions were treated with WBRT, otherwise = patients=20 were recommended for GKS but the final decision was determined by the = patient=20 after a detailed discussion.=20 <DIV class=3DFigure><A name=3DFig1></A><IMG=20 alt=3DMediaObjects/11060_2009_51_Fig1_HTML.jpg=20 src=3D"http://www.springerlink.com/content/m1162h5155750653/MediaObjects/= 11060_2009_51_Fig1_HTML.jpg"></DIV> <DIV class=3DCapt><SPAN class=3DCaptNr>Fig. 1 </SPAN>Example = of Gamma=20 Knife radiosurgery planning to the resection cavity </DIV> <HR> </DIV></DIV> <P class=3D"">T-tests, chi-square and Wilcoxon-Rank Sum tests were used = as=20 appropriate to compare baseline characteristics among groups. = Kaplan-Meier and=20 the log-rank test were used to graphically compare survival across = different=20 groups. Cox regression was used to identify factors associated with = worse=20 prognosis. Recurrence status (local, regional, none) was treated as a = class=20 variable with no recurrence as the reference group. Candidate variables = (# of=20 metastases, age, NSCLCA vs. other diagnosis, gender, recurrence status,=20 resection and treatment groups) were first examined in a univariate Cox=20 regression model (<I>P</I>-values <0.05 were considered statistically = significant). Due to our small dataset and only 30 deaths, we were = limited as to=20 the number of variables we could put in the multivariable Cox regression = model=20 to avoid overfitting. Given these limitations, we chose to analyze = treatment=20 group and recurrence status. SAS 9.2 (Cary, NC) was used to perform all=20 analyses. R 2.6 (Free Software Foundation, Boston, MA) was used to = create the=20 Kaplan-Meier figures. </P></DIV> <DIV class=3D""><A name=3DSec3></A> <HR> <DIV class=3Dheading2>Results</DIV> <DIV class=3DPara> <DIV class=3D"">A total of 43 patients underwent surgical excision of an = intracranial metastasis from our cohort with a mean age of = 56.68 years.=20 Twenty-five patients received post-operative Gamma Knife radiation to = the=20 surgical resection cavity and 18 received post-operative WBRT. The = median time=20 interval from surgery to GKS was 0.92 months as compared to=20 0.58 months for those who received WBRT = (<I>P</I> =3D 0.13). A=20 greater portion of the cohort receiving GKS was female (72%) as compared = to the=20 WBRT sample (28%). Otherwise, the two groups did not differ = significantly=20 (Table <A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#Tab1">1</A>).<A=20 name=3DTab1></A> <DIV class=3DCapt><SPAN class=3DCaptNr>Table 1 </SPAN>Baseline = characteristics </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dchar char=3D"."></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> </TH> <TH align=3Dleft> <P class=3D"">Gamma Knife (<I>n</I> =3D 25) </P></TH> <TH align=3Dleft> <P class=3D"">WBRT (<I>n</I> =3D 18) </P></TH> <TH align=3Dleft char=3D"."> <P class=3D""><I>P</I>-value </P></TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Mean age (years) =B1 standard = deviation</P></TD> <TD align=3Dleft> <P class=3D"">59.47 =B1 11.50</P></TD> <TD align=3Dleft> <P class=3D"">52.80 =B1 11.52</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.07</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""># Female patients (%)</P></TD> <TD align=3Dleft> <P class=3D"">18 (72.00)</P></TD> <TD align=3Dleft> <P class=3D"">5 (27.78)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.004</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Mean # of metastases =B1 standard = deviation</P></TD> <TD align=3Dleft> <P class=3D"">1.54 =B1 0.72</P></TD> <TD align=3Dleft> <P class=3D"">1.67 =B1 0.91</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.62</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Patholological subtype (%)</P></TD> <TD align=3Dleft> </TD> <TD align=3Dleft> </TD> <TD align=3Dchar rowSpan=3D7 char=3D"."> <P class=3D"">0.66<SUP>a</SUP> </P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> NSCLC</P></TD> <TD align=3Dleft> <P class=3D"">15 (60.00)</P></TD> <TD align=3Dleft> <P class=3D"">12 (66.67)</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> SCLC</P></TD> <TD align=3Dleft> <P class=3D"">1 (4.00)</P></TD> <TD align=3Dleft> <P class=3D"">1 (5.56)</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> Breast</P></TD> <TD align=3Dleft> <P class=3D"">4 (16.00)</P></TD> <TD align=3Dleft> <P class=3D"">1 (5.56)</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> GU</P></TD> <TD align=3Dleft> <P class=3D"">0 (0.00)</P></TD> <TD align=3Dleft> <P class=3D"">2 (11.11)</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> GI</P></TD> <TD align=3Dleft> <P class=3D"">0 (8.00)</P></TD> <TD align=3Dleft> <P class=3D"">1 (5.56)</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> Other</P></TD> <TD align=3Dleft> <P class=3D"">3 (12.00)</P></TD> <TD align=3Dleft> <P class=3D"">1 (5.56)</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Resection (%)</P></TD> <TD align=3Dleft> </TD> <TD align=3Dleft> </TD> <TD align=3Dchar rowSpan=3D3 char=3D"."> <P class=3D"">0.35</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> Total</P></TD> <TD align=3Dleft> <P class=3D"">19 (95.00)</P></TD> <TD align=3Dleft> <P class=3D"">12 (85.71)</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> Incomplete</P></TD> <TD align=3Dleft> <P class=3D"">1 (5.00)</P></TD> <TD align=3Dleft> <P class=3D"">2 (14.29)</P></TD></TR></TBODY></TABLE> <DIV class=3DCapt> <DIV class=3DCaptCont> <DIV class=3D""><SUP>a</SUP>Comparing NSCLC to all other pathological = subtypes=20 combined </DIV></DIV></DIV></DIV></DIV> <DIV class=3DPara> <DIV class=3D"">Median survival for those treated with GKS was = 15.00 months=20 (6.05=9635.82) compared to 6.81 months (2.20=9619.05) among those = receiving=20 WBRT (Fig. <A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#Fig2">2</A>,=20 <I>P</I> =3D 0.08). Seventeen of twenty-five patients (68%) = were=20 deceased at last follow-up in the GKS group and 15 of 18 (83%) in the = WBRT=20 group. None of the patients treated with GKS had known local failure, 7 = had=20 regional recurrences, 14 patients had no failure and 4 had unknown = radiographic=20 status at follow-up. The 3 local failures all occurred in the patients = treated=20 with WBRT. The WBRT group also had 3 regional recurrences, 6 without = failure and=20 6 with unknown radiographic status.=20 <DIV class=3DFigure><A name=3DFig2></A><IMG=20 alt=3DMediaObjects/11060_2009_51_Fig2_HTML.gif=20 src=3D"http://www.springerlink.com/content/m1162h5155750653/MediaObjects/= 11060_2009_51_Fig2_HTML.gif"></DIV> <DIV class=3DCapt><SPAN class=3DCaptNr>Fig. 2 </SPAN>KM = survival curve=20 comparing patients treated with GKS to WBRT </DIV> <HR> </DIV></DIV> <DIV class=3DPara> <DIV class=3D"">By univariate analysis, local failure had a trend = towards=20 significance (HR 3.52, 95% CI 0.91=9613.66, <I>P</I> =3D 0.07) = but only=20 the number of metastases (HR 1.65, 95% CI 1.07=962.54, = <I>P</I> =3D 0.02)=20 and presence of regional failure (RR 5.23, 95% CI 1.78=9615.38,=20 <I>P</I> =3D 0.003) were statistically significant predictors = of poorer=20 survival (Table <A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#Tab2">2</A>).=20 The number of metastases did not differ significantly between the GKS = and WBRT=20 groups (Table <A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#Tab1">1</A>).<A=20 name=3DTab2></A> <DIV class=3DCapt><SPAN = class=3DCaptNr>Table 2 </SPAN>Univariate Cox=20 proportional hazards models </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dchar char=3D"("> <COL align=3Dchar char=3D"."></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> <P class=3D"">Parameters</P></TH> <TH align=3Dleft char=3D"("> <P class=3D"">HR (95% CI)</P></TH> <TH align=3Dleft char=3D"."> <P class=3D""><I>P</I>-value </P></TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""># metastases</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">1.65 (1.07, 2.54)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.02</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Age</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">1.01 (0.98,1.05)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.59</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Age ≥50</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">0.71 (0.33, 1.50)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.36</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">NSCLC (pathological subtype)</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">0.82 (0.35, 1.92)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.65</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Male gender</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">1.55 (0.77, 3.13)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.22</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft colSpan=3D3> <P class=3D"">Recurrence</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> Local</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">3.52 (0.91, 13.66)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.07</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> Regional</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">5.23 (1.78, 15.38)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.003</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Gross total resection</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">3.15 (0.87, 11.35)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.08</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">GKS vs. WBRT</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">0.53 (0.26, 1.09)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.08</P></TD></TR></TBODY></TABLE></DIV></DIV> <P class=3D"">Multivariate regression analysis was performed with = treatment (GKS=20 versus WBRT), local recurrence and regional recurrence as variables. = Other=20 variables that were examined in our univariate analysis were not = included in the=20 multivariate analysis as the small dataset precluded further meaningful=20 multivariate analysis. Regional recurrence (HR 5.17, 95% CI = 1.69=9615.78,=20 <I>P</I> =3D 0.004) was again strongly associated with worse = survival.=20 Local recurrence was associated with worse prognosis, although it did = not reach=20 statistical significance (HR 3.40, 95% CI 0.70=9616.61,=20 <I>P</I> =3D 0.13). Survival for GKS versus WBRT was not = statistically=20 significant (HR 1.02, 85% CI 0.60=961.73, <I>P</I> =3D 0.93) = once=20 recurrence was added to the model. </P></DIV> <DIV class=3D""><A name=3DSec4></A> <HR> <DIV class=3Dheading2>Discussion</DIV> <P class=3D"">At least 50% of patients with brain metastases present = with=20 multi-focal disease and traditionally have not been candidates solely = for local=20 treatments [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR9">9</A></CITE>].=20 Whole brain radiation (WBRT) is often the treatment of choice for such = patients=20 with improvement in median survival to 3=966 months [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR10">10</A></CITE>].=20 However, whole brain radiation is associated with hair loss, somnolence, = hearing=20 loss, skin reactions as well as neurological deficits such as cognitive = and=20 memory loss and requires 2 or more weeks of daily hospital visits for = treatments=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR1">1</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR11">11</A></CITE>].=20 Though long-term complications are uncommon in a population with such = limited=20 survival, at least one retrospective study has suggested an 11% rate of = dementia=20 in patients treated with WBRT who survived for greater than 1 year=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR12">12</A></CITE>].=20 Another recent study showed that tumor regression after WBRT is = associated with=20 improvement in neurocognitive function in long-term survivors [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR13">13</A></CITE>].=20 Nonetheless, WBRT is associated with diffuse bilateral white matter = changes on=20 T2-weighted MRI scans and as patients are living longer with their = systemic=20 disease it is becoming more important to delay neurocognitive decline = [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR14">14</A></CITE>].=20 </P> <P class=3D"">The introduction of stereotactic radiosurgery (SRS) has = broadened=20 the therapeutic options for patients with brain metastases. Though = results with=20 SRS are promising, its precise role is not fully defined in the current=20 literature. SRS has been broadly applied in initial treatment, = recurrence and=20 adjuvant regiments combined with surgery or WBRT [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR15">15</A></CITE>=96<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR17">17</A></CITE>].=20 The non-invasiveness, single out-patient visit, high local control rate, = and low=20 morbidity have all been cited for the increased utility of this = therapeutic=20 option [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR1">1</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR7">7</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR15">15</A></CITE>=96<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR17">17</A></CITE>].=20 Although no prospective trial has compared SRS to surgical resection = alone,=20 multiple uncontrolled studies suggest that SRS may have at least equal = efficacy=20 to surgical resection of brain metastases and achieve local control = rates of=20 64=9697% with a low risk of complications [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR8">8</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR18">18</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR19">19</A></CITE>].=20 Our local control rate was 100% with GKS as compared to 75% with the = WBRT group.=20 These results are likely falsely elevated from our small sample size and = exaggerated from the lack of data on 10 patients, therefore cautioning = against=20 drawing any definitive conclusions. However, even assuming that all 4 = patients=20 from the GKS group with unknown recurrence status had local failure, our = local=20 control rate would then only decrease to 84%. </P> <P class=3D"">With more treatment modalities available, selecting and = combining=20 the best options for patients is an increasing challenge. The benefit of = adding=20 SRS to WBRT has been evaluated in 3 prospective randomized trials, the = larger of=20 which was the Radiation Therapy Oncology Group Trial (RTOG) 9508 with = 333=20 patients [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR17">17</A></CITE>].=20 Though this trial failed to show a difference in overall survival based = on=20 treatment, the subsets of patients with a single metastasis (6.5 versus=20 4.9 months median survival) and with a favorable systemic prognosis = (11.6=20 versus 9.6 months) had improved survivals. </P> <P class=3D"">Similarly the benefit of adding WBRT after either surgical = resection=20 or SRS has been evaluated in prospective randomized trials with the = rationale=20 that additional WBRT would eliminate residual distant brain or regional = disease.=20 In a more recent study, examining the adjunctive role of WBRT after SRS, = 132=20 patients were randomized to SRS alone or SRS followed by WBRT [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR15">15</A></CITE>].=20 They concluded that the omission of WBRT was associated with an increase = in=20 brain tumor recurrence, but no difference in overall survival, death = from=20 neurological cause or preservation of neurological function. The finding = that=20 delay of WBRT does not adversely influence survival has been = corroborated by=20 several different studies [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR15">15</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR18">18</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR20">20</A></CITE>].=20 </P> <P class=3D"">Since 1999 we have treated surgical resection cavities = with GKS and=20 delayed using WBRT for salvage treatment. We retrospectively reviewed = our series=20 of patients treated with surgery for their brain metastases over the = past=20 9 years to evaluate whether this regimen negatively impacted = patient=20 survival. As we were preparing our report, two retrospective series of = SRS to=20 resection cavities of brain metastases have been reported [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR6">6</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR7">7</A></CITE>].=20 They reported good local control (73 and 79% at 1 year), median = survivals=20 (13 months and 15.1 months) and minimal morbidity. Neither of = these=20 studies compared their SRS results to patients treated with WBRT after = resection=20 of brain metastases. Our median survival for patients treated with GKS = after=20 resection is comparable to those published by Soltys et al and Mathieu = et al.=20 Furthermore, our group of patients that received GKS after surgery had a = median=20 survival of 15.0 months compared to the group with WBRT of = 6.8 months.=20 However, the survival difference was not statistically significant=20 (<I>P</I> =3D 0.08). In our multivariate regression model, = regional=20 recurrences of brain metastases were much more significant in predicting = poorer=20 survival than treatment with GKS or WBRT. </P> <P class=3D"">In this study we sought to compare the survival of = patients treated=20 after surgical resection of cerebral metastases with post-operative GKS = versus=20 those with WBRT. As with all retrospective studies, there are = limitations to our=20 data and analysis. Many patients received their primary oncologic care = at other=20 facilities and were referred to our institution for neurosurgery and/or = GKS and=20 therefore their systemic therapies varied significantly. Data was = obtained on=20 all patients regarding GKS and WBRT, but additional data was not = available on a=20 sufficient number patients to permit comparisons of performance status, = measures=20 of neurological function, date of neurologic progression, cause of death = and=20 control of systemic disease. Clearly clinical performance and control of = systemic disease influence overall survival and are unaccounted for in = our=20 study. Aside from gender, demographic data between groups were = comparable, but a=20 selection bias may have existed and may have favored WBRT for more = systemically=20 ill patients. The asymmetric gender distribution also reflects the = distribution=20 of pathological subtypes with more breast cancers treated using GKS. = These=20 differences may also skew our results and limit interpretation of our = data. </P> <P class=3D"">Although the use of SRS after surgical resection of brain = metastases=20 has entered clinical practice, the benefit of this has just begun to be=20 evaluated [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR6">6</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR7">7</A></CITE>].=20 Ours is a relatively small, single-institution, retrospective study with = all the=20 limitations innate to this type of study. Despite these flaws in the = data, a=20 trend towards improvement in overall survival was seen with the use of = GKS as=20 compared to WBRT after resection of brain metastases. Future prospective = trials=20 need to be carried out to more definitively delineate the efficacy of = SRS to the=20 surgical cavity of resected brain metastases </P></DIV> <P></P> <HR> <H2><A name=3DBib1></A>References </H2> <TABLE> <TBODY class=3DCitation> <TR vAlign=3Dtop> <TD>1.</TD> <TD><A name=3DCR1></A>Patchell RA (2003) The management of brain = metastases.=20 Cancer Treat Rev 29:533=96540<BR><A=20 href=3D"http://dx.doi.org/10.1016/S0305-7372(03)00105-1" = target=3D_blank><IMG=20 height=3D20 alt=3DCrossRef=20 = src=3D"http://www.springerlink.com/content/m1162h5155750653/crossref_link= .gif"=20 width=3D65 border=3D0></A> <A=20 = href=3D"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=3DRetrieve&= db=3DPubMed&dopt=3DAbstract&list_uids=3D14585263"=20 target=3D_blank><IMG height=3D20 alt=3DPubMed=20 = src=3D"http://www.springerlink.com/content/m1162h5155750653/pubmed_link.g= if"=20 width=3D65 border=3D0></A> </TD></TR> <TR> <TD> </TD></TR> <TR vAlign=3Dtop> <TD>2.</TD> <TD><A name=3DCR2></A>Bradley KA, Mehta MP (2004) Management of = brain=20 metastases. 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Int J Radiat Oncol Biol Phys=20 47:993=96999<BR><A=20 = href=3D"http://chemport.cas.org/cgi-bin/sdcgi?APP=3Dftslink&action=3D= reflink&origin=3Dspringer&version=3D1.0&coi=3D1%3ASTN%3A280%3= ADC%252BD3czitlaguw%253D%253D&md5=3D0a2ac562335c14a7715c8ced8fbfc414"= =20 target=3D_blank><IMG height=3D20 alt=3DChemPort=20 = src=3D"http://www.springerlink.com/content/m1162h5155750653/chemport_link= .gif"=20 width=3D65 border=3D0></A> <A=20 = href=3D"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=3DRetrieve&= db=3DPubMed&dopt=3DAbstract&list_uids=3D10863070"=20 target=3D_blank><IMG height=3D20 alt=3DPubMed=20 = src=3D"http://www.springerlink.com/content/m1162h5155750653/pubmed_link.g= if"=20 width=3D65 border=3D0></A> </TD></TR> <TR> <TD> </TD></TR></TBODY></TABLE></DIV></BODY></HTML> ------=_NextPart_000_0000_01CA7279.774C0340 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://www.springerlink.com/content/m1162h5155750653/contact.gif 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From: Subject: 10.1007/s11060-009-0051-x Date: Tue, 1 Dec 2009 11:28:55 +0100 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01CA7279.774C0340" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01CA7279.774C0340 Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.springerlink.com/content/m1162h5155750653/fulltext.html 10.1007/s11060-009-0051-x</TIT= LE> <META http-equiv=3DContent-Type content=3D"text/html; = charset=3DISO-8859-1"><LINK=20 href=3D"http://www.springerlink.com/config/css/A++_common.css" = type=3Dtext/css=20 rel=3DstyleSheet><LINK=20 href=3D"http://www.springerlink.com/config/css/content_A++_SpringerLink.c= ss"=20 type=3Dtext/css rel=3DstyleSheet> <META content=3D"MSHTML 6.00.6000.16939" name=3DGENERATOR></HEAD> <BODY class=3Dfor-print> <TABLE cellPadding=3D2 border=3D1> <TBODY> <TR class=3Dheader> <TD>Journal of Neuro-Oncology</TD></TR> <TR> <TD>=A9 Springer Science+Business Media, = LLC. 2009</TD></TR> <TR> <TD>10.1007/s11060-009-0051-x</TD></TR></TBODY></TABLE> <H2 class=3Drubric>Clinical Study - Patient Study</H2> <DIV class=3DHeading1><A name=3Dtitle></A>Adjuvant Gamma Knife = radiosurgery=20 following surgical resection of brain metastases: a 9-year retrospective = cohort=20 study </DIV> <P class=3DAuthorGroup>Steven W. Hwang<SUP>1</SUP>,=20 Mohab M. Abozed<SUP>1</SUP>, Andrew Hale<SUP>1</SUP>,=20 Rebecca L. Eisenberg<SUP>2</SUP>, = Tomas Dvorak<SUP>3</SUP>,=20 Kevin Yao<SUP>1</SUP>, Rolf Pfannl<SUP>4</SUP>,=20 John Mignano<SUP>3</SUP>, Jay-Jiguang Zhu<SUP>2, 5</SUP>,=20 Lori Lyn Price<SUP>6</SUP>, = Gary M. Strauss<SUP>2</SUP> and=20 Julian K. Wu<SUP>1 <A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#ContactOfAuthor12"><IMG=20 alt=3D"Contact Information"=20 src=3D"http://www.springerlink.com/content/m1162h5155750653/contact.gif" = border=3D0></A></SUP></P> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><SPAN class=3DAffiliation><A = name=3DAff1></A>(1) </SPAN></TD> <TD><SPAN class=3DAffiliation>Department of Neurosurgery, Tufts = Medical=20 Center, 800 Washington Street, Boston, MA 02111,=20 USA</SPAN></TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><SPAN class=3DAffiliation><A = name=3DAff2></A>(2) </SPAN></TD> <TD><SPAN class=3DAffiliation>Division of Hematology-Oncology, = Department of=20 Medicine, Tufts Medical Center, Boston, MA, = USA</SPAN></TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><SPAN class=3DAffiliation><A = name=3DAff3></A>(3) </SPAN></TD> <TD><SPAN class=3DAffiliation>Department of Radiation Oncology, = Tufts=20 Medical Center, Boston, MA, USA</SPAN></TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><SPAN class=3DAffiliation><A = name=3DAff4></A>(4) </SPAN></TD> <TD><SPAN class=3DAffiliation>Department of Anatomic Pathology, = Tufts=20 Medical Center, Boston, MA, USA</SPAN></TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><SPAN class=3DAffiliation><A = name=3DAff5></A>(5) </SPAN></TD> <TD><SPAN class=3DAffiliation>Department of Neurology, Tufts Medical = Center,=20 Boston, MA, USA</SPAN></TD></TR></TBODY></TABLE> <TABLE> <TBODY> <TR vAlign=3Dtop> <TD><SPAN class=3DAffiliation><A = name=3DAff6></A>(6) </SPAN></TD> <TD><SPAN class=3DAffiliation>Institute for Clinical Research and = Health=20 Policy Studies, Tufts Medical Center, Boston, MA,=20 USA</SPAN></TD></TR></TBODY></TABLE> <P><A name=3DContactOfAuthor12></A></P> <TABLE class=3DContact> <TBODY> <TR> <TD vAlign=3Dtop><IMG alt=3D"Contact Information"=20 = src=3D"http://www.springerlink.com/content/m1162h5155750653/contact.gif" = border=3D0></TD> = <TD><STRONG>Julian </STRONG><STRONG>K. </STRONG><STRONG>Wu</STR= ONG><STRONG></STRONG><BR><STRONG>Email:=20 </STRONG><A=20 = href=3D"mailto:jwu3@tuftsmedicalcenter.org">jwu3@tuftsmedicalcenter.org</= A></TD></TR></TBODY></TABLE> <P class=3DAffiliation><STRONG>Received:=20 </STRONG>22 March 2009 <STRONG>Accepted:=20 </STRONG>26 October 2009 <STRONG>Published online:=20 </STRONG>12 November 2009 </P> <DIV class=3DAbstract><A name=3DAbs1></A><SPAN=20 class=3DAbstractHeading>Abstract </SPAN>Given the potential = morbidity=20 of whole brain radiation therapy (WBRT), there has been an increasing = trend to=20 defer WBRT and deliver Gamma Knife stereotactic radiosurgery (GKS) to = cerebral=20 metastatic lesions. We analyzed our experience delivering GKS to the = tumor=20 cavity following surgical resection of brain metastases and compared our = results=20 to patients receiving WBRT after surgical resection of a metastatic = lesion. We=20 performed a retrospective review of patients undergoing surgical = resection of at=20 least one brain metastasis between December 1999 and December 2008. Both = univariate and multivariate Cox proportional hazards regression were = utilized to=20 analyze the influence of various prognostic factors on survival. = Twenty-five=20 patients had a metastatic lesion resected followed by adjuvant GKS to = the=20 resection cavity while another 18 had surgical resection followed by = WBRT. Aside=20 from a disparity in gender distribution (72% of GKS patients were female = while=20 women only constituted 28% of the WBRT group), no significant = differences=20 existed between groups. The median survival for patients receiving GKS = was=20 15.00 months as compared to 6.81 months among those receiving = WBRT=20 (<I>P</I> =3D 0.08). Univariate Cox regression analysis = identified the=20 number of metastases (HR 1.65, 95% CI 1.07=962.54, = <I>P</I> =3D 0.02) and=20 regional recurrence (RR 5.23, 95% CI 1.78=9615.38, = <I>P</I> =3D 0.003) as=20 poor prognostic factors. Multivariate regression analysis showed that = regional=20 recurrence (HR 5.17, 95% CI 1.69=9615.78, <I>P</I> =3D 0.004) = was again=20 strongly associated with worse survival. Although limited by the = retrospective=20 nature of our study and lack of some clinical measures, patients = undergoing GKS=20 to the resection cavity had a trend towards longer median survival. = </DIV> <P class=3DKeyword><SPAN = class=3DKeywordHeading>Keywords </SPAN>Gamma=20 Knife - Radiosurgery - Cerebral = metastasis - Brain=20 metastasis - Brain neoplasms - Craniotomy </P> <DIV class=3DFulltext> <DIV class=3D""><A name=3DSec1></A> <HR> <DIV class=3Dheading2>Introduction</DIV> <P class=3D"">Brain metastases represent the most common intracranial = tumor and=20 have been reported to occur in 20=9640% of cancer patients [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR1">1</A></CITE>=96<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR3">3</A></CITE>].=20 The increasing frequency of brain metastases may be secondary to = improved=20 methods of detection such as routine screening with magnetic resonance = imaging=20 (MRI), and prolonged survival with better systemic control of disease = [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR1">1</A></CITE>].=20 However, brain metastases still portend a poor prognosis and = historically,=20 untreated patients have had a median survival of approximately = 4 weeks=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR2">2</A></CITE>].=20 The median survival of patients with cerebral metastases has been = prolonged with=20 adjuvant treatments such as steroid administration, as well as radiation = therapy=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR3">3</A></CITE>=96<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR5">5</A></CITE>].=20 </P> <P class=3D"">Survival of patients with brain metastases has been = improved by the=20 use of whole brain radiation therapy (WBRT), surgery, and stereotactic=20 radiosurgery (SRS) in conjunction with systemic therapies. WBRT has been = the=20 standard treatment for brain metastases and continues to be used = extensively in=20 patients with poor prognosis, multi-focal disease and in combination = with other=20 modalities [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR1">1</A></CITE>].=20 However, more recently there has been an increasing trend to treat = cerebral=20 metastases with local therapies such as surgical resection and SRS = [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR6">6</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR7">7</A></CITE>].=20 </P> <P class=3D"">Our study was performed to retrospectively analyze = outcomes from a=20 cohort of patients, treated at our institution over a 9 year = period, who=20 underwent surgical resection of brain metastases followed either by GKS = to the=20 resection cavity or WBRT. We sought to evaluate the survival outcomes = for=20 different subgroups of patients and to determine if patient survival was = adversely affected by deferring WBRT. </P></DIV> <DIV class=3D""><A name=3DSec2></A> <HR> <DIV class=3Dheading2>Patients and methods</DIV> <P class=3D"">Institutional review board approval was obtained through = the Tufts=20 Medical Center Institutional Review Board (IRB). Medical records were = obtained=20 on all patients including the hospital primary computer-based records as = well as=20 neurosurgery office charts, radiation oncology clinic charts, pathology = reports,=20 and the hematology-oncology clinic charts. Post-operative imaging was = reviewed=20 to determine the extent of surgical resection. The Social Security Death = Index=20 was searched to confirm date of death. Attempts were made to contact all = living=20 patients by letter and phone call to perform a brief phone survey to = gather=20 additional data. Referring physicians were also contacted by telephone = and=20 letter to request additional information on patients who received = treatment=20 outside of our institution. </P> <DIV class=3DPara> <DIV class=3D"">Patients who had undergone surgical resection of at = least one=20 brain metastasis between December 1999 and December 2008 were identified = by=20 billing codes from the Department of Neurosurgery at Tufts Medical = Center.=20 Inclusion criteria included age greater than or equal to 18 years,=20 documented brain metastasis from systemic cancer, and surgical resection = of at=20 least one brain metastasis with adjuvant GKS or WBRT. Patients included = in our=20 study who received GKS were planned for treatment within 30 days of = their=20 surgical resection, although systemic treatment or travel distances may = have=20 delayed some cases. Patients with primary brain tumors, or the diagnoses = of=20 lymphoma or multiple myeloma were excluded as well as patients who had = received=20 both GKS and WBRT. One patient was excluded who died before completion = of his=20 WBRT treatment secondary to cardiopulmonary complications. In all cases, = either=20 a resection cavity or residual enhancement was visible on a GKS planning = MRI.=20 The treatment target included any residual enhancement and the resection = cavity.=20 Dosimetry was based on the RTOG 90-05 recommendations of a mean = peripheral dose=20 (50% isodose) ranging from 15-20 Gy depending on the size of the = cavity=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR8">8</A></CITE>].=20 We therefore targeted 15-20 Gy at the 50% isodose line to the = resection=20 margin (Fig. <A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#Fig1">1</A>).=20 Patients with >3 other lesions were treated with WBRT, otherwise = patients=20 were recommended for GKS but the final decision was determined by the = patient=20 after a detailed discussion.=20 <DIV class=3DFigure><A name=3DFig1></A><IMG=20 alt=3DMediaObjects/11060_2009_51_Fig1_HTML.jpg=20 src=3D"http://www.springerlink.com/content/m1162h5155750653/MediaObjects/= 11060_2009_51_Fig1_HTML.jpg"></DIV> <DIV class=3DCapt><SPAN class=3DCaptNr>Fig. 1 </SPAN>Example = of Gamma=20 Knife radiosurgery planning to the resection cavity </DIV> <HR> </DIV></DIV> <P class=3D"">T-tests, chi-square and Wilcoxon-Rank Sum tests were used = as=20 appropriate to compare baseline characteristics among groups. = Kaplan-Meier and=20 the log-rank test were used to graphically compare survival across = different=20 groups. Cox regression was used to identify factors associated with = worse=20 prognosis. Recurrence status (local, regional, none) was treated as a = class=20 variable with no recurrence as the reference group. Candidate variables = (# of=20 metastases, age, NSCLCA vs. other diagnosis, gender, recurrence status,=20 resection and treatment groups) were first examined in a univariate Cox=20 regression model (<I>P</I>-values <0.05 were considered statistically = significant). Due to our small dataset and only 30 deaths, we were = limited as to=20 the number of variables we could put in the multivariable Cox regression = model=20 to avoid overfitting. Given these limitations, we chose to analyze = treatment=20 group and recurrence status. SAS 9.2 (Cary, NC) was used to perform all=20 analyses. R 2.6 (Free Software Foundation, Boston, MA) was used to = create the=20 Kaplan-Meier figures. </P></DIV> <DIV class=3D""><A name=3DSec3></A> <HR> <DIV class=3Dheading2>Results</DIV> <DIV class=3DPara> <DIV class=3D"">A total of 43 patients underwent surgical excision of an = intracranial metastasis from our cohort with a mean age of = 56.68 years.=20 Twenty-five patients received post-operative Gamma Knife radiation to = the=20 surgical resection cavity and 18 received post-operative WBRT. The = median time=20 interval from surgery to GKS was 0.92 months as compared to=20 0.58 months for those who received WBRT = (<I>P</I> =3D 0.13). A=20 greater portion of the cohort receiving GKS was female (72%) as compared = to the=20 WBRT sample (28%). Otherwise, the two groups did not differ = significantly=20 (Table <A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#Tab1">1</A>).<A=20 name=3DTab1></A> <DIV class=3DCapt><SPAN class=3DCaptNr>Table 1 </SPAN>Baseline = characteristics </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dleft> <COL align=3Dchar char=3D"."></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> </TH> <TH align=3Dleft> <P class=3D"">Gamma Knife (<I>n</I> =3D 25) </P></TH> <TH align=3Dleft> <P class=3D"">WBRT (<I>n</I> =3D 18) </P></TH> <TH align=3Dleft char=3D"."> <P class=3D""><I>P</I>-value </P></TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Mean age (years) =B1 standard = deviation</P></TD> <TD align=3Dleft> <P class=3D"">59.47 =B1 11.50</P></TD> <TD align=3Dleft> <P class=3D"">52.80 =B1 11.52</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.07</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""># Female patients (%)</P></TD> <TD align=3Dleft> <P class=3D"">18 (72.00)</P></TD> <TD align=3Dleft> <P class=3D"">5 (27.78)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.004</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Mean # of metastases =B1 standard = deviation</P></TD> <TD align=3Dleft> <P class=3D"">1.54 =B1 0.72</P></TD> <TD align=3Dleft> <P class=3D"">1.67 =B1 0.91</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.62</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Patholological subtype (%)</P></TD> <TD align=3Dleft> </TD> <TD align=3Dleft> </TD> <TD align=3Dchar rowSpan=3D7 char=3D"."> <P class=3D"">0.66<SUP>a</SUP> </P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> NSCLC</P></TD> <TD align=3Dleft> <P class=3D"">15 (60.00)</P></TD> <TD align=3Dleft> <P class=3D"">12 (66.67)</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> SCLC</P></TD> <TD align=3Dleft> <P class=3D"">1 (4.00)</P></TD> <TD align=3Dleft> <P class=3D"">1 (5.56)</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> Breast</P></TD> <TD align=3Dleft> <P class=3D"">4 (16.00)</P></TD> <TD align=3Dleft> <P class=3D"">1 (5.56)</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> GU</P></TD> <TD align=3Dleft> <P class=3D"">0 (0.00)</P></TD> <TD align=3Dleft> <P class=3D"">2 (11.11)</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> GI</P></TD> <TD align=3Dleft> <P class=3D"">0 (8.00)</P></TD> <TD align=3Dleft> <P class=3D"">1 (5.56)</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> Other</P></TD> <TD align=3Dleft> <P class=3D"">3 (12.00)</P></TD> <TD align=3Dleft> <P class=3D"">1 (5.56)</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Resection (%)</P></TD> <TD align=3Dleft> </TD> <TD align=3Dleft> </TD> <TD align=3Dchar rowSpan=3D3 char=3D"."> <P class=3D"">0.35</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> Total</P></TD> <TD align=3Dleft> <P class=3D"">19 (95.00)</P></TD> <TD align=3Dleft> <P class=3D"">12 (85.71)</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> Incomplete</P></TD> <TD align=3Dleft> <P class=3D"">1 (5.00)</P></TD> <TD align=3Dleft> <P class=3D"">2 (14.29)</P></TD></TR></TBODY></TABLE> <DIV class=3DCapt> <DIV class=3DCaptCont> <DIV class=3D""><SUP>a</SUP>Comparing NSCLC to all other pathological = subtypes=20 combined </DIV></DIV></DIV></DIV></DIV> <DIV class=3DPara> <DIV class=3D"">Median survival for those treated with GKS was = 15.00 months=20 (6.05=9635.82) compared to 6.81 months (2.20=9619.05) among those = receiving=20 WBRT (Fig. <A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#Fig2">2</A>,=20 <I>P</I> =3D 0.08). Seventeen of twenty-five patients (68%) = were=20 deceased at last follow-up in the GKS group and 15 of 18 (83%) in the = WBRT=20 group. None of the patients treated with GKS had known local failure, 7 = had=20 regional recurrences, 14 patients had no failure and 4 had unknown = radiographic=20 status at follow-up. The 3 local failures all occurred in the patients = treated=20 with WBRT. The WBRT group also had 3 regional recurrences, 6 without = failure and=20 6 with unknown radiographic status.=20 <DIV class=3DFigure><A name=3DFig2></A><IMG=20 alt=3DMediaObjects/11060_2009_51_Fig2_HTML.gif=20 src=3D"http://www.springerlink.com/content/m1162h5155750653/MediaObjects/= 11060_2009_51_Fig2_HTML.gif"></DIV> <DIV class=3DCapt><SPAN class=3DCaptNr>Fig. 2 </SPAN>KM = survival curve=20 comparing patients treated with GKS to WBRT </DIV> <HR> </DIV></DIV> <DIV class=3DPara> <DIV class=3D"">By univariate analysis, local failure had a trend = towards=20 significance (HR 3.52, 95% CI 0.91=9613.66, <I>P</I> =3D 0.07) = but only=20 the number of metastases (HR 1.65, 95% CI 1.07=962.54, = <I>P</I> =3D 0.02)=20 and presence of regional failure (RR 5.23, 95% CI 1.78=9615.38,=20 <I>P</I> =3D 0.003) were statistically significant predictors = of poorer=20 survival (Table <A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#Tab2">2</A>).=20 The number of metastases did not differ significantly between the GKS = and WBRT=20 groups (Table <A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#Tab1">1</A>).<A=20 name=3DTab2></A> <DIV class=3DCapt><SPAN = class=3DCaptNr>Table 2 </SPAN>Univariate Cox=20 proportional hazards models </DIV> <TABLE border=3D1> <COLGROUP> <COL align=3Dleft> <COL align=3Dchar char=3D"("> <COL align=3Dchar char=3D"."></COLGROUP> <THEAD> <TR class=3Dheader> <TH align=3Dleft> <P class=3D"">Parameters</P></TH> <TH align=3Dleft char=3D"("> <P class=3D"">HR (95% CI)</P></TH> <TH align=3Dleft char=3D"."> <P class=3D""><I>P</I>-value </P></TH></TR></THEAD> <TBODY> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""># metastases</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">1.65 (1.07, 2.54)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.02</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Age</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">1.01 (0.98,1.05)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.59</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Age ≥50</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">0.71 (0.33, 1.50)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.36</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">NSCLC (pathological subtype)</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">0.82 (0.35, 1.92)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.65</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Male gender</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">1.55 (0.77, 3.13)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.22</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft colSpan=3D3> <P class=3D"">Recurrence</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> Local</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">3.52 (0.91, 13.66)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.07</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D""> Regional</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">5.23 (1.78, 15.38)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.003</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">Gross total resection</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">3.15 (0.87, 11.35)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.08</P></TD></TR> <TR class=3Dnoclass> <TD align=3Dleft> <P class=3D"">GKS vs. WBRT</P></TD> <TD align=3Dchar char=3D"("> <P class=3D"">0.53 (0.26, 1.09)</P></TD> <TD align=3Dchar char=3D"."> <P class=3D"">0.08</P></TD></TR></TBODY></TABLE></DIV></DIV> <P class=3D"">Multivariate regression analysis was performed with = treatment (GKS=20 versus WBRT), local recurrence and regional recurrence as variables. = Other=20 variables that were examined in our univariate analysis were not = included in the=20 multivariate analysis as the small dataset precluded further meaningful=20 multivariate analysis. Regional recurrence (HR 5.17, 95% CI = 1.69=9615.78,=20 <I>P</I> =3D 0.004) was again strongly associated with worse = survival.=20 Local recurrence was associated with worse prognosis, although it did = not reach=20 statistical significance (HR 3.40, 95% CI 0.70=9616.61,=20 <I>P</I> =3D 0.13). Survival for GKS versus WBRT was not = statistically=20 significant (HR 1.02, 85% CI 0.60=961.73, <I>P</I> =3D 0.93) = once=20 recurrence was added to the model. </P></DIV> <DIV class=3D""><A name=3DSec4></A> <HR> <DIV class=3Dheading2>Discussion</DIV> <P class=3D"">At least 50% of patients with brain metastases present = with=20 multi-focal disease and traditionally have not been candidates solely = for local=20 treatments [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR9">9</A></CITE>].=20 Whole brain radiation (WBRT) is often the treatment of choice for such = patients=20 with improvement in median survival to 3=966 months [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR10">10</A></CITE>].=20 However, whole brain radiation is associated with hair loss, somnolence, = hearing=20 loss, skin reactions as well as neurological deficits such as cognitive = and=20 memory loss and requires 2 or more weeks of daily hospital visits for = treatments=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR1">1</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR11">11</A></CITE>].=20 Though long-term complications are uncommon in a population with such = limited=20 survival, at least one retrospective study has suggested an 11% rate of = dementia=20 in patients treated with WBRT who survived for greater than 1 year=20 [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR12">12</A></CITE>].=20 Another recent study showed that tumor regression after WBRT is = associated with=20 improvement in neurocognitive function in long-term survivors [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR13">13</A></CITE>].=20 Nonetheless, WBRT is associated with diffuse bilateral white matter = changes on=20 T2-weighted MRI scans and as patients are living longer with their = systemic=20 disease it is becoming more important to delay neurocognitive decline = [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR14">14</A></CITE>].=20 </P> <P class=3D"">The introduction of stereotactic radiosurgery (SRS) has = broadened=20 the therapeutic options for patients with brain metastases. Though = results with=20 SRS are promising, its precise role is not fully defined in the current=20 literature. SRS has been broadly applied in initial treatment, = recurrence and=20 adjuvant regiments combined with surgery or WBRT [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR15">15</A></CITE>=96<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR17">17</A></CITE>].=20 The non-invasiveness, single out-patient visit, high local control rate, = and low=20 morbidity have all been cited for the increased utility of this = therapeutic=20 option [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR1">1</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR7">7</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR15">15</A></CITE>=96<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR17">17</A></CITE>].=20 Although no prospective trial has compared SRS to surgical resection = alone,=20 multiple uncontrolled studies suggest that SRS may have at least equal = efficacy=20 to surgical resection of brain metastases and achieve local control = rates of=20 64=9697% with a low risk of complications [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR8">8</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR18">18</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR19">19</A></CITE>].=20 Our local control rate was 100% with GKS as compared to 75% with the = WBRT group.=20 These results are likely falsely elevated from our small sample size and = exaggerated from the lack of data on 10 patients, therefore cautioning = against=20 drawing any definitive conclusions. However, even assuming that all 4 = patients=20 from the GKS group with unknown recurrence status had local failure, our = local=20 control rate would then only decrease to 84%. </P> <P class=3D"">With more treatment modalities available, selecting and = combining=20 the best options for patients is an increasing challenge. The benefit of = adding=20 SRS to WBRT has been evaluated in 3 prospective randomized trials, the = larger of=20 which was the Radiation Therapy Oncology Group Trial (RTOG) 9508 with = 333=20 patients [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR17">17</A></CITE>].=20 Though this trial failed to show a difference in overall survival based = on=20 treatment, the subsets of patients with a single metastasis (6.5 versus=20 4.9 months median survival) and with a favorable systemic prognosis = (11.6=20 versus 9.6 months) had improved survivals. </P> <P class=3D"">Similarly the benefit of adding WBRT after either surgical = resection=20 or SRS has been evaluated in prospective randomized trials with the = rationale=20 that additional WBRT would eliminate residual distant brain or regional = disease.=20 In a more recent study, examining the adjunctive role of WBRT after SRS, = 132=20 patients were randomized to SRS alone or SRS followed by WBRT [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR15">15</A></CITE>].=20 They concluded that the omission of WBRT was associated with an increase = in=20 brain tumor recurrence, but no difference in overall survival, death = from=20 neurological cause or preservation of neurological function. The finding = that=20 delay of WBRT does not adversely influence survival has been = corroborated by=20 several different studies [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR15">15</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR18">18</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR20">20</A></CITE>].=20 </P> <P class=3D"">Since 1999 we have treated surgical resection cavities = with GKS and=20 delayed using WBRT for salvage treatment. We retrospectively reviewed = our series=20 of patients treated with surgery for their brain metastases over the = past=20 9 years to evaluate whether this regimen negatively impacted = patient=20 survival. As we were preparing our report, two retrospective series of = SRS to=20 resection cavities of brain metastases have been reported [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR6">6</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR7">7</A></CITE>].=20 They reported good local control (73 and 79% at 1 year), median = survivals=20 (13 months and 15.1 months) and minimal morbidity. Neither of = these=20 studies compared their SRS results to patients treated with WBRT after = resection=20 of brain metastases. Our median survival for patients treated with GKS = after=20 resection is comparable to those published by Soltys et al and Mathieu = et al.=20 Furthermore, our group of patients that received GKS after surgery had a = median=20 survival of 15.0 months compared to the group with WBRT of = 6.8 months.=20 However, the survival difference was not statistically significant=20 (<I>P</I> =3D 0.08). In our multivariate regression model, = regional=20 recurrences of brain metastases were much more significant in predicting = poorer=20 survival than treatment with GKS or WBRT. </P> <P class=3D"">In this study we sought to compare the survival of = patients treated=20 after surgical resection of cerebral metastases with post-operative GKS = versus=20 those with WBRT. As with all retrospective studies, there are = limitations to our=20 data and analysis. Many patients received their primary oncologic care = at other=20 facilities and were referred to our institution for neurosurgery and/or = GKS and=20 therefore their systemic therapies varied significantly. Data was = obtained on=20 all patients regarding GKS and WBRT, but additional data was not = available on a=20 sufficient number patients to permit comparisons of performance status, = measures=20 of neurological function, date of neurologic progression, cause of death = and=20 control of systemic disease. Clearly clinical performance and control of = systemic disease influence overall survival and are unaccounted for in = our=20 study. Aside from gender, demographic data between groups were = comparable, but a=20 selection bias may have existed and may have favored WBRT for more = systemically=20 ill patients. The asymmetric gender distribution also reflects the = distribution=20 of pathological subtypes with more breast cancers treated using GKS. = These=20 differences may also skew our results and limit interpretation of our = data. </P> <P class=3D"">Although the use of SRS after surgical resection of brain = metastases=20 has entered clinical practice, the benefit of this has just begun to be=20 evaluated [<CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR6">6</A></CITE>,=20 <CITE><A=20 href=3D"http://www.springerlink.com/content/m1162h5155750653/fulltext.htm= l#CR7">7</A></CITE>].=20 Ours is a relatively small, single-institution, retrospective study with = all the=20 limitations innate to this type of study. Despite these flaws in the = data, a=20 trend towards improvement in overall survival was seen with the use of = GKS as=20 compared to WBRT after resection of brain metastases. Future prospective = trials=20 need to be carried out to more definitively delineate the efficacy of = SRS to the=20 surgical cavity of resected brain metastases </P></DIV> <P></P> <HR> <H2><A name=3DBib1></A>References </H2> <TABLE> <TBODY class=3DCitation> <TR vAlign=3Dtop> <TD>1.</TD> <TD><A name=3DCR1></A>Patchell RA (2003) The management of brain = metastases.=20 Cancer Treat Rev 29:533=96540<BR><A=20 href=3D"http://dx.doi.org/10.1016/S0305-7372(03)00105-1" = target=3D_blank><IMG=20 height=3D20 alt=3DCrossRef=20 = src=3D"http://www.springerlink.com/content/m1162h5155750653/crossref_link= .gif"=20 width=3D65 border=3D0></A> <A=20 = href=3D"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=3DRetrieve&= db=3DPubMed&dopt=3DAbstract&list_uids=3D14585263"=20 target=3D_blank><IMG height=3D20 alt=3DPubMed=20 = src=3D"http://www.springerlink.com/content/m1162h5155750653/pubmed_link.g= if"=20 width=3D65 border=3D0></A> </TD></TR> <TR> <TD> </TD></TR> <TR vAlign=3Dtop> <TD>2.</TD> <TD><A name=3DCR2></A>Bradley KA, Mehta MP (2004) Management of = brain=20 metastases. 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Int J Radiat Oncol Biol Phys=20 47:993=96999<BR><A=20 = href=3D"http://chemport.cas.org/cgi-bin/sdcgi?APP=3Dftslink&action=3D= reflink&origin=3Dspringer&version=3D1.0&coi=3D1%3ASTN%3A280%3= ADC%252BD3czitlaguw%253D%253D&md5=3D0a2ac562335c14a7715c8ced8fbfc414"= =20 target=3D_blank><IMG height=3D20 alt=3DChemPort=20 = src=3D"http://www.springerlink.com/content/m1162h5155750653/chemport_link= .gif"=20 width=3D65 border=3D0></A> <A=20 = href=3D"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=3DRetrieve&= db=3DPubMed&dopt=3DAbstract&list_uids=3D10863070"=20 target=3D_blank><IMG height=3D20 alt=3DPubMed=20 = src=3D"http://www.springerlink.com/content/m1162h5155750653/pubmed_link.g= if"=20 width=3D65 border=3D0></A> </TD></TR> <TR> <TD> </TD></TR></TBODY></TABLE></DIV></BODY></HTML> ------=_NextPart_000_0000_01CA7279.774C0340 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://www.springerlink.com/content/m1162h5155750653/contact.gif 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