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Murray F Brennan

Publications and source records attributed to Murray F Brennan.

At least 19 recordsLinked to original sources
PubMed2007

Outcome of patients with known metastatic gastric cancer undergoing resection with therapeutic intent.

BACKGROUND: Metastatic gastric cancer has a dismal prognosis. We identified a subset of patients where surgical resection with therapeutic intent was undertaken in the setting of known metastatic disease. METHODS: Review of a prospectively maintained database of gastric cancer patients at a single institution over a 19-year period was performed. RESULTS: Thirty-seven patients with metastatic disease known prior to resection with therapeutic intent were identified out of 3384 patients with gastric cancer (1%). Twelve patients had positive peritoneal cytology as the only evidence of metastasis, 21 had gross metastasis limited to peritoneal surfaces, one had peritoneal and ovarian metastasis, one had liver metastasis, one had retropancreatic lymph node metastasis, and one had a malignant pleural effusion. Thirty-six patients (97%) received chemotherapy prior to resection, and 30 (81%) received postoperative chemotherapy. The median time from diagnosis to resection was 4.5 months (range 1-22) in patients receiving preoperative chemotherapy. Median survival was 12 months after resection with no three-year survivors. Predictors of worse prognosis were cytologic or pathologic evidence of persistent metastatic disease at the time of resection or at laparoscopy within six weeks of resection (P < .01), N3 disease (P = .03), and total gastrectomy or additional organ resection (P = .04). Metastatic disease as evidenced by cytology only was not associated with improved prognosis. CONCLUSIONS: Highly selected patients with metastatic gastric cancer undergoing surgical resection with therapeutic intent have a relatively poor prognosis. Persistent detectable metastatic disease after preoperative chemotherapy portends a particularly poor prognosis.

Adult↗
PubMed2006

Lymphadenectomy for adenocarcinoma of the gastroesophageal junction (GEJ): impact of adequate staging on outcome.

INTRODUCTION: Adequate staging of gastric cancer requires examination of at least 15 lymph nodes. Most resected patients are inadequately staged potentially confounding the interpretation of clinical data. The aim of this study was to determine whether adequate staging revealed different prognostic factors or improved survival compared with patients with <15 nodes examined after R0 resection for GEJ cancer. METHODS: A prospectively maintained database identified 366 patients with Siewert types II and III adenocarcinoma of the GEJ who underwent R0 resection without neoadjuvant therapy at a single institution. Patients were grouped into adequately (>or=15 nodes examined) or inadequately staged (<15 nodes examined). Median follow up was 51 months. RESULTS: From 1985 through 2003, 250/366 (68%) patients were adequately staged and 116/366 (32%) were inadequately staged. There was no difference in operative mortality between adequately staged (5.2%) and inadequately staged patients (4.3%, P = NS). Adequately staged patients had more positive lymph nodes (median 2) compared with inadequately staged patients (median 1, P < 0.01). Multivariable analysis of adequately staged patients found the number of positive lymph nodes, T stage, and lymphovascular invasion to be independent prognostic factors for overall survival (OS). For inadequately staged patients only the number of positive lymph nodes and T stage were independent prognostic factors. Adequate staging was an independent prognostic factor for patients with advanced (T >or= 2 Nany) tumors. For T1 tumors adequate staging was not associated with improved survival. CONCLUSIONS: Patients with GEJ cancer should undergo adequate lymphadenectomy to permit examination of >or=15 lymph nodes allowing the accurate identification of prognostic variables. Removal of >or=15 lymph nodes is associated with more accurate survival estimates for patients with advanced disease.

Adenocarcinoma↗
PubMed2006

Outcome of metastatic GIST in the era before tyrosine kinase inhibitors.

BACKGROUND: Treatment of metastatic GIST with imatinib mesylate results in a 2-year survival of approximately 72%. The outcome of patients with metastatic GIST not treated with tyrosine kinase inhibitors is not well defined. METHODS: One hundred nineteen patients with metastatic GIST diagnosed prior to July 1, 1998 (approximately 2 years prior to the use of imatinib for GIST) were identified from an institutional database of patients with pathologically confirmed GIST. Mutational analysis was performed in cases with available tissue. The log rank test and Cox regression models were used to assess prognostic factors. RESULTS: Median survival was 19 months with a 41% 2-year survival and a 25% 5-year survival. Resection of metastatic GIST was performed in 81 patients (68%), while 50 (42%) received conventional chemotherapy. Twelve patients (10%) were eventually started on imatinib. Primary tumor size <10 cm, <5 mitoses/50 HPF in the primary tumor, epithelioid morphology, longer disease-free interval, and surgical resection were independent predictors of improved survival on multivariate analysis. Mutational status did not predict outcome. In patients who underwent resection, the 2 year survival was 53%, and negative microscopic margins also independently predicted improved survival. CONCLUSIONS: Treatment with imatinib appears to improve 2-year survival of metastatic GIST by approximately 20% when compared to surgery alone. The combination of imatinib and surgery for the treatment of metastatic GIST therefore warrants investigation.

Adult↗
PubMed2006

Evaluation of preoperative therapy for pancreatic cancer using a prognostic nomogram.

BACKGROUND: Theoretical benefits of preoperative chemoradiation therapy (preop CRT) for pancreatic cancer include improved efficacy, resectability, and patient selection. The goal of this study was to evaluate the applicability of a nomogram, which was developed for patients undergoing resection without preop CRT and which incorporates several post-resection pathological factors, to a population of patients who received preop CRT prior to resection. METHODS: From 1994 to 2004, 82 patients with biopsy-proven, radiographically localized adenocarcinoma of the pancreatic head underwent preop CRT followed by pancreaticoduodenectomy (PD); 50 concurrent patients underwent PD without preop CRT. Mean nomogram-predicted disease-specific survival (DSS) rates were compared with observed DSS rates from the time of resection. RESULTS: Despite having more locally advanced tumors on initial staging (21 vs. 8%; P < .05), patients who received preop CRT had smaller resected tumors (mean 2.3 vs. 3.1 cm; P < .01), were less likely to have T3 tumors (54 vs. 80%, P < .01), were less likely to have positive lymph nodes (29 vs. 58%, P < .01), and had fewer positive lymph nodes (mean .4 vs. 1.9, P < .01), all factors that imply treatment effect and favorably impact on nomogram-predicted DSS. Observed DSS was similar to predicted DSS in both groups. CONCLUSIONS: The similarity in observed and predicted DSS following resection in patients who received preop CRT suggests that the effects of preop CRT-whether treatment, selection, or no effect-are reflected by the nomogram. The ability of the nomogram to evaluate the effects of preop CRT on survival is limited by the potential effects of preop CRT on factors within the nomogram.

Adenocarcinoma↗
PubMed2006

Selection of patients with gastric adenocarcinoma for laparoscopic staging.

BACKGROUND: To refine selection criteria for laparoscopic staging of gastric adenocarcinoma, preoperatively available clinical and radiologic factors that may predict the risk of M1 disease were investigated. METHODS: During 1993-2002, laparoscopy was performed if patients had minimal symptoms and there was no definite M1 disease at computed tomography (CT) scanning. High-quality, spiral, CT scans were reviewed in detail for 65 recent patients. RESULTS: Laparoscopy was conducted for 657 patients and M1 was detected in 31%. M1 was significantly more prevalent with tumor location at the gastroesophageal junction (GEJ; M1 in 42%) or whole stomach (66%), poor differentiation (36%) or age < or = 70 years (34%). On spiral CT scan, lymphadenopathy > or = 1 cm (49%) or T3/T4 tumors (63%) were associated with significantly higher prevalence of M1. On multivariate analyses, only tumor location (GEJ or whole stomach) and lymphadenopathy were independently significant and M1 was not detected in any patient with neither risk factor. CONCLUSIONS: With spiral CT staging, laparoscopy may be avoided if the primary tumor is not at the GEJ or whole stomach and there is no lymphadenopathy.

Adenocarcinoma↗
PubMed2006

Central pancreatectomy revisited.

Central pancreatectomy is a surgical procedure that removes the middle segment of the pancreas and preserves the distal pancreas and spleen. This limited resection has the advantage of conserving normal, uninvolved pancreatic parenchyma, thus reducing the possibility of postoperative exocrine and endocrine dysfunction. While the incidence of postoperative endocrine insufficiency may be as low as 4%, procedural morbidity, specifically pancreatic fistula, appears to exceed the published rates for standard resections (i.e., distal/subtotal pancreatectomy or pancreaticoduodenectomy). We have reviewed our prospective pancreatic cancer database to determine the utilization of central pancreatectomy in a major cancer center with expertise in pancreatic surgery. We identified only 10 cases of central pancreatectomy over the past 13 years. Six (60%) had postoperative complications including three cases (30%) of pancreatic fistula. No patients died as a result of the procedure. At a median follow-up of 13.6 months (mean, 25.2 months), only one patient had mild endocrine insufficiency and no patients had clinically significant exocrine dysfunction. The associated morbidity of central pancreatectomy may outweigh any potential benefit in long-term pancreatic secretory function. We suggest that such a procedure be used selectively, where preservation of the pancreas appears essential.

Adenoma, Islet Cell↗
PubMed2006

Angiogenic profile of soft tissue sarcomas based on analysis of circulating factors and microarray gene expression.

BACKGROUND: Broader understanding of diverse angiogenic pathways in a particular cancer can lead to better utilization of anti-angiogenic therapies. The aim of this study was to develop profiles of angiogenesis-related gene and protein expression for various histologic subtypes of soft tissue sarcomas (STS) growing in different sites. MATERIALS AND METHODS: Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiopoietin 2 (Ang2), and leptin were determined in 108 patients with primary STS. Gene expression patterns were analyzed in 38 STS samples and 13 normal tissues using oligonucleotide microarrays. RESULTS: VEGF and bFGF plasma levels were elevated 10-13 fold in STS patients compared to controls. VEGF levels were broadly elevated while bFGF levels were higher in patients with fibrosarcomas and leiomyosarcomas. Ang2 levels correlated with tumor size and were most elevated for tumors located in the trunk, while leptin levels were highest in patients with liposarcomas. Hierarchical clustering of microarray data based on angiogenesis-related gene expression demonstrated that histologic subtypes of STS often shared similar expression patterns, and these patterns were distinctly different from those of normal tissues. Matrix metalloproteinase 2, platelet-derived growth factor receptor, alpha and Notch 4 were among several genes that were up-regulated at least 7-fold in STS. CONCLUSIONS: STS demonstrate significant heterogeneity in their angiogenic profiles based on size, histologic subtype, and location of tumor growth, which may have implications for anti-angiogenic strategies. Comparison of STS to normal tissues reveals a panel of upregulated genes that may be targets for future therapies.

Angiopoietin-2↗
PubMed2006

Adult genitourinary sarcoma: the 25-year Memorial Sloan-Kettering experience.

PURPOSE: Urological sarcomas are rare. We describe a continued single institutional experience during 25 years. MATERIALS AND METHODS: The records from July 1977 to July 2003 were reviewed of all patients at our institution with sarcoma arising in the urinary tract or male genital system who were 16 years or older at diagnosis. RESULTS: The primary tumor site in 131 patients was the bladder in 20, the kidney in 26, paratesticular in 57, the prostate in 21 and other in 7. Median followup was 4.0 years. The most common histological subtypes were leiomyosarcoma in 29% of cases and liposarcoma in 26%. Median tumor size was 7 cm and 78% of lesions were high grade. Of the patients 28 (21%) presented with metastatic disease and their median survival was 1.4 years compared to 10.7 years in patients without metastatic disease (p < 0.0001). Disease specific survival was 56% and 42% at 5 and 10 years, respectively and median survival was 7.6 years. On univariate analysis unfavorable prognostic variables for disease specific survival were metastasis at presentation, high tumor grade, a lack of leiomyosarcoma and liposarcoma histological subtypes, prostate sarcoma and large tumor size, incomplete surgical resection and positive surgical margin. Patient sex, age and surgical margin status were not significant predictors. On multivariate analysis 2 variables remained significant predictors of disease specific survival, including tumor size (HR 1.1, 95% CI 1.02 to 1.17) and absent metastasis at diagnosis (HR 4.9, 95% CI 1.4 to 17.2). CONCLUSIONS: Predictors of disease specific survival include local disease at presentation, complete tumor resection and tumor grade, size, location and histological subtype. With adequate surgical treatment most patients who presented with primary disease and underwent complete surgical resection achieved prolonged disease specific survival.

Adolescent↗
PubMed2006

Predicting individual survival after gastric cancer resection: validation of a U.S.-derived nomogram at a single high-volume center in Europe.

OBJECTIVE: Validation of a U.S.-derived nomogram for individual prediction of disease-specific gastric cancer survival at a European institution. SUMMARY BACKGROUND DATA: One major issue of modern cancer treatment is the individualization of therapy. For gastric cancer, Kattan et al, at Memorial Sloan-Kettering Cancer Center, New York, NY, developed a nomogram, allowing to predict individual patient risk of tumor-related death after R0 resection from basic patient-related variables. The validity of the nomogram has not yet been shown in patients from other institutions. The accuracy of the nomogram when applied to patients after having undergone R0 gastric cancer resection at a European high-volume center was investigated. METHODS: Clinical data from patients who underwent R0 gastric cancer resection at Klinikum rechts der Isar, Technical University of Munich, Germany and fitted the respective derivation criteria were used for external validation (n = 862). Nomogram predictions for 60- and 108-month disease-specific survival were calculated for each patient and compared with actual survival. The concordance index was used as an accuracy measure. RESULTS: The bootstrap-corrected concordance index was 0.77 and was superior when compared with the predictive ability of International Union Against Cancer tumor stage (P < 0.008). Nomogram calibration was excellent for 60-month disease-specific survival. Nomogram predictions showed the trend to underestimate survival in stage II/III disease of the MRI patients. CONCLUSIONS: The use of the nomogram created by Kattan et al is not only confined to the institution where it was created, but it can be adopted by other institutions with similar surgical strategies.

Adenocarcinoma↗
PubMed2006

Clinical outcomes with laparoscopic stage M1, unresected gastric adenocarcinoma.

OBJECTIVE: For patients with laparoscopic stage M1 gastric adenocarcinoma, no resection of the primary tumor, and systemic chemotherapy, this study investigated the incidence of subsequent palliative intervention and survival. SUMMARY BACKGROUND DATA: Laparoscopy was performed for patients with computed tomography scan stage M0 disease and no significant obstruction or bleeding. METHODS: A prospectively maintained database for 1993 to 2002 was used to identify 165 patients (median age, 63 years) with laparoscopic M1 disease in the peritoneum (P1, adjacent to stomach, 9%; P2, few distant sites, 35%; or P3, disseminated, 30%) or liver (10%) or both (16%). Functional performance status (FPS, Eastern Cooperative Oncology Group) was 0 to 1 (84%) or 2 (16%). RESULTS: Subsequent intervention was performed on 50% of patients, at median interval of 4 months (range, 1-35 months) after laparoscopy. Intervention was performed on the stomach for obstruction (33%), bleeding (8%), or perforation (1%) or on a distant site for a metastasis-related complication (20%). More than one intervention (maximum, 4) was performed in 21%. Laparotomy was necessary in 12%; the remainder had endoscopic or radiologic procedures or radiation therapy only. There was one intervention-related death. Median survival was 10 months, with 1-year survival of 39%. On multivariate analysis, better FPS (0-1; odds ratio, 4; P=0.001) and limited peritoneal metastasis (P1 or P2; 2; P=0.01) were independently associated with improved survival. CONCLUSIONS: The incidence of subsequent intervention was 50%, but few patients had laparotomy. Intervention-related mortality was minimal. The burden of metastatic disease and functional performance status were important prognostic factors.

Adenocarcinoma↗
PubMed2006

Subtype specific prognostic nomogram for patients with primary liposarcoma of the retroperitoneum, extremity, or trunk.

OBJECTIVE: To determine the prognostic significance of histologic subtype in a large series of patients with primary liposarcoma (LS) and to construct a LS-specific postoperative nomogram for disease-specific survival (DSS). SUMMARY BACKGROUND DATA: Nomograms, used to define and predict outcome following operative intervention, may contain variables not conventionally used in standard staging systems. A 12-year DSS postoperative nomogram for all sarcomas has already been established. METHODS: From a single-institution prospective sarcoma database, patients with primary extremity, truncal, or retroperitoneal LS treated between 1982 and 2005 were identified. Histology was reviewed by a sarcoma pathologist and divided into 5 subtypes. A nomogram predictive of 5- and 12-year DSS was developed. RESULTS: Of 801 patients with primary LS resected with curative intent, 369 (46%) presented with well-differentiated, 143 (18%) dedifferentiated, 144 (18%) myxoid, 81 (10%) round cell, and 64 (8%) pleomorphic histology. The median tumor burden was 15 cm (range, 1-139 cm). At last follow-up, 560 patients were alive with a median follow-up time of 45 months (range, 1-264 months) and 51 months for surviving patients. The 5- and 12-year DSS rates were 83% (95% confidence interval [CI], 80%-86%) and 72% (95% CI, 67%-77%), respectively. The nomogram was drawn on the basis of a Cox regression model. The independent predictors of DSS were age, presentation status, histologic variant, primary site, tumor burden, and gross margin status. The nomogram was internally validated using bootstrapping and shown to have excellent calibration. The concordance index was 0.827 compared with 0.776 for the general sarcoma postoperative nomogram for 12-year DSS. CONCLUSION: The LS-specific nomogram based on histologic subtype provides more accurate survival predictions for patients with primary LS than the previously established generic sarcoma nomogram. DSS nomograms aid in more accurate counseling of patients, identification of patients appropriate for adjuvant therapy, and stratification of patients for clinical trials and molecular analysis.

Adolescent↗
PubMed2006

A selective approach to the resection of cystic lesions of the pancreas: results from 539 consecutive patients.

OBJECTIVE: To define a group of patients with pancreatic cysts who do not require resection. SUMMARY BACKGROUND DATA: The increased use of cross-sectional imaging has resulted in an increased identification of small, asymptomatic pancreatic cysts. Data have not been available to determine which lesions should be resected. METHODS: All patients evaluated at our institution between January 1995 and January 2005 for the ICD-9 diagnosis of pancreatic cyst were reviewed. Analysis was performed to identify associations between patient and cyst characteristics, and selection of operative or nonoperative management. RESULTS: Pancreatic cysts were evaluated in 539 patients. Initial management was operative in 170 patients (32%), and nonoperative (radiographic follow-up) in 369 patients (68%). Factors associated with initial operative management included presence of a solid component (45% vs. 6%, P < 0.001), larger size of the lesion (mean 4.8 cm vs. 2.4 cm, P = 0.001), and presence of symptoms (44% vs. 16%, P = 0.001). Malignancy was present in 18% (32 of 170) of patients initially resected. Mucinous tumors (n = 18) were the most common malignant histologic subtype. None of the invasive cancers arising from mucinous cysts was <3 cm. Median radiographic follow-up in patients initially managed nonoperatively was 24 months (range, 1-172 months). In 29 patients (8%), changes developed within the cyst that resulted in resection; malignancy was present in 11 of 39 (38%), representing 3% (11 of 369) of all patients being followed radiographically. CONCLUSIONS: Selected patients with cystic lesions <3 cm in diameter and without a solid component may be followed radiographically with a malignancy risk (3% this study) that approximates the risk of mortality from resection. Malignancy within mucinous tumors is associated with size, and small mucinous tumors are very unlikely to be malignant.

Adult↗
PubMed2006

Lessons learned...

Explore the source record for details and available documents.

Biomedical Research↗
PubMed2005

Limitations of ampullectomy in the treatment of nonfamilial ampullary neoplasms.

BACKGROUND: Pancreaticoduodenectomy (PD) is the standard surgical management of invasive ampullary neoplasms. A rational plan to use ampullectomy (AMP) for lesions at this location requires careful analysis of preoperative clinical information (comorbidity, lesion size, and histopathology) and intraoperative data (frozen section pathology and clinical impression) to properly select patients for this treatment. METHODS: We identified 140 consecutive cases of nonfamilial ampullary neoplasms from our prospective institutional database over a 7-year period (1996-2003). Preoperative and intraoperative factors were analyzed and related to outcomes. RESULTS: AMP was planned for 37 patients with small lesions (median, 1.86 cm [range, 0-3 cm] vs. 2.6 cm [range, 0-8 cm] in PD). AMP was converted to PD because of the extent of disease in three and an intraoperative diagnosis of invasive cancer in five patients. Preoperative biopsy had a diagnostic accuracy of 79% (97 of 123) but missed 23 cancers. Intraoperative frozen section had a diagnostic accuracy of 84%; two cases of high-grade dysplasia and invasive cancer were missed. Patients with invasive cancer treated by AMP had a decreased recurrence-free and disease-specific survival compared with those treated by PD. Lymphatic spread of disease was associated with diminished long-term survival. Although both vascular invasion and tumor stage independently predicted lymphatic metastases, both were limited by their sensitivity. CONCLUSIONS: The reduced morbidity and mortality of AMP makes this the preferred treatment for benign lesions of the ampulla. Conversion to PD should be considered when intraoperative or final pathology identifies invasive adenocarcinoma. Refinement of clinicopathologic factors may reduce the occasional PD for benign disease and AMP for malignancy.

Adenocarcinoma↗
PubMed2005

Effectiveness of palliative procedures for intra-abdominal sarcomas.

BACKGROUND: Nearly half of patients with intra-abdominal (retroperitoneal, visceral, or pelvic) sarcoma undergo more than one operation. When the objective shifts from cure to palliation, the clinical quandary of doing no harm and maximizing benefit is magnified. Knowledge of the effectiveness of a procedure at achieving its palliative intent, as well as its attendant morbidity and mortality, is therefore paramount during this deliberation. METHODS: A retrospective review was performed of all patients with a diagnosis of intra-abdominal sarcoma who underwent a palliative procedure between 1982 and 2003. A procedure was defined as palliative if it was explicitly performed to relieve symptoms. RESULTS: Ten percent (112 of 1084) of patients with a diagnosis of intra-abdominal sarcoma underwent a total of 156 palliative procedures. The most frequent system for which a palliative procedure was performed was gastrointestinal (68 of 156; 44%). Overall, 71% of patients had improvement of symptoms 30 days after the operation, whereas only 54% of patients remained symptom free after 100 days. Although 54% of gastrointestinal tract obstructive symptoms were successfully relieved at 30 days, only 23% of patients remained symptom free at 100 days. The overall operative morbidity was 29%, and postoperative mortality was 12%. Patients undergoing procedures intended to palliate gastrointestinal obstruction encountered the greatest morbidity (19 of 40; 48%). CONCLUSIONS: Successful palliation of many symptoms associated with advanced intra-abdominal sarcoma may be achieved. However, even in highly selected patients, the progressive and pervasive nature of the disease limits the opportunity to attain sustained relief for gastrointestinal obstructive symptoms.

Abdominal Neoplasms↗
PubMed2005

Validation of a postresection pancreatic adenocarcinoma nomogram for disease-specific survival.

PURPOSE: Nomograms are statistically based tools that provide the overall probability of a specific outcome. They have shown better individual discrimination than the current TNM staging system in numerous patient tumor models. The pancreatic nomogram combines individual clinicopathologic and operative data to predict disease-specific survival at 1, 2, and 3 years from initial resection. A single US institution database was used to test the validity of the pancreatic adenocarcinoma nomogram established at Memorial Sloan-Kettering Cancer Center. PATIENTS AND METHODS: The nomogram was created from a prospective pancreatic adenocarcinoma database that included 555 consecutive patients between October 1983 and April 2000. The nomogram was validated by an external patient cohort from a retrospective pancreatic adenocarcinoma database at Massachusetts General Hospital that included 424 consecutive patients between January 1985 and December 2003. RESULTS: Of the 424 patients, 375 had all variables documented. At last follow-up, 99 patients were alive, with a median follow-up time of 27 months (range, 2 to 151 months). The 1-, 2-, and 3-year disease-specific survival rates were 68% (95% CI, 63% to 72%), 39% (95% CI, 34% to 44%), and 27% (95% CI, 23% to 32%), respectively. The nomogram concordance index was 0.62 compared with 0.59 with the American Joint Committee on Cancer (AJCC) stage (P = .004). This suggests that the nomogram discriminates disease-specific survival better than the AJCC staging system. CONCLUSION: The pancreatic cancer nomogram provides more accurate survival predictions than the AJCC staging system when applied to an external patient cohort. The nomogram may aid in more accurately counseling patients and in better stratifying patients for clinical trials and molecular tumor analysis.

Adenocarcinoma↗
PubMed2005

Influence of site on the therapeutic ratio of adjuvant radiotherapy in soft-tissue sarcoma of the extremity.

PURPOSE: The ultimate goal of adjuvant radiotherapy (RT) in soft-tissue sarcoma of the extremity is to improve the therapeutic ratio by increasing local control while minimizing morbidity. Most efforts in trying to improve this ratio have focused on the sequencing of RT and surgery, with little attention to the potential influence of the tumor site. The purpose of this study was to determine the influence of tumor site on local control and complications in a group of patients with primary high-grade soft-tissue sarcoma of the extremity treated at a single institution with postoperative RT. METHODS AND MATERIALS: Between July 1982 and December 2000, 369 adult patients with primary high-grade soft-tissue sarcoma of the extremity were treated with limb-sparing surgery and postoperative RT. Patients who underwent surgery or RT outside our institution were excluded. The tumor site was the upper extremity (UE) in 103 (28%) and the lower extremity (LE) in 266 (72%). The tumor was < or = 5 cm in 98 patients (27%), and the microscopic margins were positive in 44 (12%). Of the 369 patients, 104 (28%) underwent postoperative external beam RT (EBRT), 233 (63%) postoperative brachytherapy (BRT), and 32 underwent a combination (9%); 325 (88%) received a "conventional" radiation dose, defined as 60-70 Gy for EBRT, 45 Gy for BRT, and 45-50 Gy plus 15-20 Gy for EBRT plus BRT. Complications were assessed in terms of wound complications requiring repeat surgery, fracture, joint stiffness, edema, and Grade 3 or worse peripheral nerve damage. RESULTS: The UE and LE groups were balanced with regard to age, depth, margin status, and type of RT (EBRT vs. BRT +/- EBRT). However, more patients in the UE group had tumors < or = 5 cm and more received a conventional radiation dose (p = 0.01 and P = 0.03, respectively). With a median follow-up of 50 months, the 5-year actuarial rate of local control, distant relapse-free survival, and overall survival for the whole population was 82% (95% confidence interval [CI], 77-86%), 61% (95% CI, 56-66%), and 71% (95% CI, 66-76%), respectively. The 5-year local control rate in patients with UE STS was 70% (95% CI, 60-80%) compared with 86% (95% CI, 81-91%) for LE STS (p = 0.0004). On multivariate analysis, an UE site (p = 0.001; relative risk [RR], 3; 95% CI, 2-5) and positive resection margins (p = 0.02; RR, 2; 95% CI, 1-4) were significant predictors of poor local control. The RT type or radiation dose, age, tumor depth, and size were not significant predictors of local control. The 5-year wound reoperation rate was 1% (95% CI, 0-3) in the UE compared with 11% (95% CI, 7-15) in the LE (p = 0.002). On multivariate analysis, the UE site retained its significance as a predictor of low wound complications (p = 0.001; RR, 0.08; 95% CI, 0.01-0.7). The site did not significantly influence the incidence of fracture (p = 0.7), joint stiffness (p = 0.2), edema (p = 0.5), or Grade 3 or worse peripheral nerve damage (p = 0.3). CONCLUSION: The UE site is associated with a greater rate of local recurrence compared with the LE. This difference was independent of other variables and could not be accounted for by an imbalance between the two groups. With a lower wound complication rate associated with an UE site, it would be of interest to determine whether preoperative RT and/or intensity-modulated RT can increase the local control in UE sarcomas, thus improving the therapeutic ratio.

Adolescent↗