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Background: Regional lymph node metastasis in extremity and trunk soft tissue sarcoma (ETSTS) is rare with no standardized management. We sought to determine management patterns for regional lymph node metastasis in ETSTS., Methods: A survey regarding the management of ETSTS lymph node metastasis was distributed to the membership of the Musculoskeletal Tumor Society (MSTS) and the Society of Surgical Oncology (SSO) in January 2022. The survey queried the type of training (surgical oncology, orthopedic oncology), details of their practice setting, and management decisions of hypothetical ETSTS scenarios that involved potential or confirmed lymph node metastasis., Results: The survey was distributed to 349 MSTS members (open rate of 63%, completion rate 21%) and 3026 SSO members (open rate of 55%, completion rate 4.7%) and was completed by 214 respondents, of whom 73 (34.1%) and 141 (65.9%) were orthopedic oncology and surgical oncology fellowship-trained, respectively. The majority of respondents practiced in an academic setting (n = 171, 79.9%) and treat >10 extremity sarcoma cases annually (n = 138, 62.2%). In scenarios with confirmed nodal disease for clear cell and epithelioid sarcoma, surgical oncologists were inclined to perform lymphadenectomy, while orthopedic oncologists were inclined to offer targeted lymph node excision with adjuvant radiation (p < 0.001). There was heterogeneity of responses regarding the management of nodal disease regardless of training background., Conclusion: Self-reported management of nodal disease in ETSTS was variable among respondent groups with differences and similarities based on training background. These data highlight the variability of practice for nodal disease management and the need for consensus-based guidelines., (© 2023. Society of Surgical Oncology.)

Introduction: EORTC-62092 (STRASS) was a phase 3, randomized study that compared surgery alone versus surgery plus neoadjuvant radiotherapy (RT) for retroperitoneal sarcomas. RT was not associated with improved abdominal recurrence-free survival, the primary outcome measure, although on subanalysis, there may have been benefit for well-differentiated (WD) liposarcoma. This study investigated the real-world use and outcomes of RT (neoadjuvant and adjuvant) for the management of retroperitoneal liposarcoma., Methods: We queried the National Cancer Database (NCDB) (2004-2017) for patients with nonmetastatic, primary retroperitoneal liposarcoma treated with resection with or without RT (n = 3911). Patients were stratified by treatment type and histology [WD (n = 2252), dedifferentiated (DD) (n = 1659)]. Propensity score (PS) matching was used before comparison of treatment groups. Overall survival (OS) was the primary outcome measure., Results: Median follow-up time was 4.1 years, and median OS was 10.7 years. There was no association between RT and OS for either WDLPS or DDLPS cohorts. We performed a subgroup analysis of neoadjuvant RT only, similar to STRASS. For WDLPS after PS matching (n = 208), neoadjuvant RT was not associated with OS (hazard ratio [HR] 1.01, p = 0.0523) but was associated with longer postoperative hospital stay (p = 0.012). For DDLPS after PS matching (n = 290), neoadjuvant RT was not associated with OS (HR 1.02, p = 0.889). For both WD-LPS and DD-LPS, utilization of neoadjuvant RT was associated with treatment at high-volume (≥ 10 cases/year) and academic/network facilities., Conclusions: For primary retroperitoneal liposarcoma treated with surgical resection, radiotherapy was not associated with an overall survival benefit in this propensity-matched, adjusted analysis of the NCDB., (© 2022. Society of Surgical Oncology.)

Background: Patients with unplanned excision (UPE) of trunk and extremity soft tissue sarcoma (STS) present a significant management challenge for sarcoma specialists. Oncologic re-resection has been considered standard practice after UPE with positive or uncertain margins. A strategy of active surveillance or "watch and wait" has been suggested as a safe alternative to routine re-excision. In this context, the current study sought to evaluate short-term outcomes and morbidity after re-resection to better understand the risks and benefits of this treatment strategy., Methods: A retrospective, single-institution study reviewed patients undergoing oncologic re-resection after UPE of an STS during a 5-year period (2015-2020), excluding those with evidence of gross residual disease. Short-term clinical outcomes were evaluated together with final pathologic findings., Results: The review identified 67 patients undergoing re-resection after UPE of an STS. Of these 67 patients, 45 (67%) were treated with a combination of external beam radiation therapy (EBRT) and surgery. Plastic surgery was involved for reconstruction in 49 cases (73%). The rate of wound complications after re-resection was 45 % (n = 30), with 15 % (n = 10) of the patients experiencing a major wound complication. Radiation therapy and plastic surgery involvement were independently associated with wound complications. Notably, 45 patients (67%) had no evidence of residual disease in the re-resection specimen, whereas 13 patients (19 %) had microscopic disease, and 9 patients (13%) had indeterminate pathology., Conclusion: Given the morbidity of re-resection and limited identification of residual disease, treatment plans and discussions with patients should outline the expected pathologic findings and morbidity of surgery., (© 2022. Society of Surgical Oncology.)

Background: Lymph node metastases (LNMs) are rare in patients with soft tissue sarcoma (STS), and there is limited evidence to guide clinical management. We describe our experience with sentinel lymph node biopsy (SLNB) and lymphadenectomy in STS patients., Methods: A single-center, retrospective review was performed for patients with STS treated with SLNB and/or lymphadenectomy from 1994 to 2018. Clinicopathologic characteristics, multimodality treatment, regional/distant recurrence-free survival (RFS), and overall survival (OS) were examined., Results: Eighty-six patients underwent SLNB (n = 34) and/or lymphadenectomy (n = 60) for STS. The most frequent histologic subtypes were epithelioid, clear cell, and undifferentiated pleomorphic sarcoma. Eight of 34 (23.5%) patients had a positive SLNB with 5-year OS of 71.4% compared with 71.9% for those with a negative SLNB. Eight of the 26 SLN-negative patients (30.8%) eventually developed nodal recurrence (n = 2) and/or (n = 6) distant metastasis with an estimated 5-year OS of 50%. Of patients undergoing lymphadenectomy, estimated 5-year OS was 44.6% and median RFS was 12 months. Eight (13.3%) had distant disease at time of lymphadenectomy, 20 (33.3%) developed distant recurrence after lymphadenectomy, and 6 (10%) developed regional-only recurrence. Patients with regional-only recurrence after lymphadenectomy had an estimated 5-year OS of 66.7% compared with 29.1% for those who recurred distantly., Conclusions: Patients with positive SLNB had similar survival to those with negative SLNB. Lymphadenectomy for isolated nodal disease is associated with poor RFS but reasonable 5-year OS when recurrence is regional-only. In STS, regional disease appears clinically distinct from distant metastatic disease and has better outcomes., (© 2022. Society of Surgical Oncology.)

Background: Sarculator is an online validated nomogram that predicts overall survival of patients with resected, primary extremity sarcomas. However, its ability to accurately predict outcomes in US patients with sarcoma is unknown., Patients and Methods: Patients from the National Cancer Data Base (NCDB) (2006-2016) with resected stage I-III primary extremity or trunk sarcoma were included. Predicted overall survival (pOS) was calculated using the Sarculator algorithm, which includes patient age, tumor size (cm), grade (1-3), and histology, and compared with actual overall survival (aOS). Harrell's C-index was calculated to determine the discriminatory ability of Sarculator (0.7 = good, 0.8 = strong, 1.0 = perfect model), and calibration plots were created., Results: In total, 9738 patients were included. Five-year pOS was 73.7% compared with aOS of 68.9%. The C-index for the entire cohort was 0.726. By stage, the C-index was 0.730 for stage I, 0.708 for stage II, and 0.679 for stage III. By histology, C-indices were highest for leiomyosarcoma (0.745), myxofibrosarcoma (0.722), and other histologies (0.721). By sociodemographic variables, Sarculator performed better for patients < 50 years (C-index 0.722), of other/unknown race (C-index 0.781), with private insurance (C-index 0.715), treated at a center other than a community cancer programs (C-index > 0.7), and with no comorbidities (C-index 0.716). Outcomes by zip code educational attainment and income were not markedly different (all C-indices > 0.7)., Conclusions: Sarculator is overall a good predictor of aOS and useful tool for clinicians to aid in survival prognostication. However, clinicians should be aware of populations for whom Sarculator's predictions may be less accurate. Future work could focus on enhancing the Sarculator algorithm specifically for US patients by including demographic variables., (© 2022. Society of Surgical Oncology.)

Background: Imatinib decreases recurrence risk and improves overall survival (OS) in localized gastrointestinal stromal tumors (GISTs); however, the extent to which patients receive appropriate treatment in the US has not been well characterized., Methods: Patients with non-metastatic, resectable GIST were included in this study (National Cancer Database, 2010-2015). Those with a low-risk of recurrence were classified as receiving overtreatment or guideline-concordant treatment, while those with a high-risk of recurrence were classified as receiving undertreatment or guideline-concordant treatment. Multivariable logistic regression was used to determine factors associated with non-concordant treatment. The association between non-concordant treatment and OS was evaluated using multivariable Cox regression and propensity score matching., Results: Among 3088 patients with high-risk GIST, 41% were undertreated, and among 3908 patients with low-risk GIST, 18.8% were overtreated. For patients with high-risk GIST, age > 60 years, African American race, and treatment at a community or comprehensive cancer program were associated with undertreatment. Among low-risk patients, small bowel primary, tumor size > 2 cm, and tumors with > 1 mitotic figure per 50 high-power fields were more likely to be overtreated. After propensity score matching, guideline-concordant therapy was associated with an 8.8% improvement in 5-year OS (81.9% vs. 73.1%, p = 0.002) for those with high-risk GIST and decreased risk of death (hazard ratio 0.63, 95% confidence interval 0.47-0.84). There was no statistically significant difference in survival for patients with low-risk GIST with the addition of imatinib overtreatment (overtreatment 93.9% vs. 89.6%, p = 0.053)., Conclusions: Nearly 30% of GIST patients do not receive guideline-concordant treatment and future work is needed to understand the factors driving non-concordant treatment., (© 2021. Society of Surgical Oncology.)

Background: Resection of recurrent retroperitoneal well-differentiated liposarcoma (RP-WDLPS) is unlikely to result in cure. Thus, most clinicians delay surgery after recurrence until symptom intolerance or increasing rate of disease progression. The aim of this study was to determine whether longer surveillance intervals in this population would impact outcomes or delay treatment in those who recur., Methods: A retrospective review of patients with primary RP-WDLPS who underwent resection between April 1996 and April 2017 and surveillance at MDACC (n = 91) was performed., Results: Median age at diagnosis of primary RP-WDLPS was 61 years; median tumor size was 30 cm. Complete resection was achieved in 85 (93.4%) patients. Among patients who underwent complete resection, recurrence occurred in 53 (60.2%) with median time to recurrence of 27.0 months. Thirty-six (69.6%) of these patients underwent resection of recurrent disease at a median 40.2 months from primary tumor resection. Surveillance imaging at 4-month (vs 3-month) intervals would not have impacted recurrence management in 84 (95.5%) patients; imaging at 6-month (vs 3-month) intervals would not have impacted management of recurrence in 80 (90.9%)., Conclusions: Recurrence was common, often occurring beyond the early postoperative period following primary RP-WDLPS resection. More frequent surveillance imaging (q3-4 vs q6 months) in the first 2 years following primary RP-WDLPS resection may not significantly impact timing of surgery or systemic therapy for recurrence. If longer surveillance intervals were shown to be safe with equivalent outcomes in prospective studies, the resulting change in practice could lead to decreased anxiety and cost for patients and healthcare systems.

Introduction: The management of perirectal tumors often requires rectal wall resection, and sometimes a complete proctectomy is required. Access to posterior perirectal masses via a posterior, transcoccygeal approach (Kraske procedure) avoids dissection of the intraperitoneal rectum., Patient: The patient was a 63-year-old male who presented to his primary care physician with debilitating perirectal pain of several months' duration. He did not respond to therapy with pain medications and topical agents, and underwent a lateral internal sphincterotomy for what was thought to be an anal fissure, without relief prior to referral. Diagnostic workup showed a low signal intensity mass on magnetic resonance imaging (MRI), and biopsy revealed high-grade leiomyosarcoma with myxoid features. Staging workup included a contrast-enhanced computed tomography chest, abdomen and pelvis, flexible sigmoidoscopy and endoscopic ultrasound. A lytic lesion in his left ilium on MRI was found to be avid on fluorodeoxyglucose-positron emission tomography scan and was therefore consistent with oligometastatic disease. He received six cycles of adriamycin, cyclophosphamide and dacarbazine, with good response. The metastatic lesion was treated with 24 Gy of radiotherapy, while the primary tumor was treated with 50 Gy of radiotherapy. The patient underwent the Kraske approach with radical resection of the perirectal mass. The rectal wall was closed with interrupted silk sutures, and layered closure of incision over a drain was performed. An R0 resection was achieved. A laparoscopic diverting loop ileostomy to protect the rectal repair was performed., Conclusion: The Kraske approach allows for adequate resection, while avoiding the morbidity of the transabdominal approach, and allowing the patient to maintain a continent rectum.

Purpose: Current evidence regarding salvage resection for recurrent retroperitoneal (RP) sarcomas generally lacks detailed histology-specific analyses, but the aggressiveness of these tumors varies widely by histology. We investigated associations between timing and extent of salvage surgery and survival outcomes in patients with recurrent RP well-differentiated liposarcoma (WDLPS)., Methods: The University of Texas MD Anderson Cancer Center Surgical Oncology sarcoma database was reviewed to identify patients with RP WDLPS who underwent surgical resection for first recurrent disease (salvage surgery) in 1995-2015. Medical records were retrospectively reviewed to identify factors associated with overall survival and disease-free survival., Results: We identified 52 patients who underwent salvage surgery for RP WDLPS for first local recurrence; 28 (54%) underwent salvage surgery within 6 months after recurrence. Concomitant organ resections were performed in 32 (62%) patients, 4 (13%) of whom had pathologic invasion of resected organs. After R0/R1 resections (n = 45), 38 (84%) experienced a second local recurrence. Multivariable analyses revealed that organ invasion at the primary surgery [hazard ratio (HR) 13.08; p = 0.005] and disease-free interval < 1 year (HR 3.64; p = 0.044) were associated with shorter overall survival. Recurrence-to-salvage interval < 6 months was associated with shorter disease-free survival (HR 2.18; p = 0.025). Concomitant organ resection was associated with a longer hospital stay: ≥ 14 days (odds ratio 21.58; p = 0.007)., Conclusions: Early salvage surgery may not always be the best approach for recurrent RP WDLPS patients. Because organ invasion is rare among recurrent RP WDLPS patients and concomitant organ resection is associated with a longer hospital stay, preservation of uninvolved organs should be considered.

Background: The 8th edition American Joint Committee on Cancer (AJCC) staging for soft tissue sarcomas of the trunk/extremities divides T stage into four categories and upstages nodal disease to stage IV. We used the National Cancer Database (NCDB) to evaluate the prognostic power of the new system., Methods: A total of 26,144 patients were identified from the NCDB from 2004 to 2013. Overall survival (OS) was compared using Kaplan-Meier and Cox proportional hazard models., Results: Including T3 (10 cm > × >15 cm) and T4 (> 15 cm) categories resulted in an increased number of patients classified as stage III (5120 as IIIA [19.6%] and 4280 as IIIB [16.4%], vs. 7882 [30.1%] previously), and there was a small increase in the number of patients classified as stage IV (2776 [10.6%], vs. 2565 [9.8%] previously). In the 7th edition, the hazard ratio (HR) for death increases with stage, with large incremental increases between stages II-III and III-IV. In the 8th edition, the HR for death demonstrates smaller incremental increases between each stage. Five-year OS for 7th edition T1 and T2 patients was 78.8 and 58.8% (p < 0.01), respectively, versus 62.6, 53.5, and 56.1% for T2, T3, and T4 patients, respectively, in the 8th edition (p < 0.01). Patients with isolated nodal disease (n = 211) had a better 5-year OS than those with distant metastases (33.1% vs. 12.4%, p < 0.001)., Conclusions: The AJCC 8th edition uses T stage to more accurately stratify OS in patients with large, high-grade tumors (T3/4) compared with those patients with T2 tumors, which facilitates risk assessment. The distinction between T3 and T4 may not be clinically significant. Patients with metastatic nodal disease have a survival outcome intermediate to those with stages III and IV disease.

Background: Non-gastrointestinal stromal tumor sarcomas (NGSs) have heterogeneous histology, and this heterogeneity may lead to uncertainty regarding the prognosis of patients with liver metastases from NGS (NGSLM) and decision regarding their surgical management. Furthermore, the role of preoperative chemotherapy in treatment of NGSLM remains poorly defined. We investigated long-term survival and its correlation to response to preoperative chemotherapy in patients with NGSLM., Patients and Method: Patients who underwent liver resection for NGSLM during 1998-2015 were identified. Clinical, histopathologic, and survival data were analyzed. Multivariate analysis was performed using a Cox proportional hazards model., Results: 126 patients [62 (49%) with leiomyosarcoma] were included. Five-year overall survival (OS) and recurrence-free survival (RFS) rates were 49.3 and 14.9%, respectively. Survival did not differ by histologic subtype, primary tumor location, or use of preoperative or postoperative chemotherapy. NGSLM ≥ 10 cm and extrahepatic metastases at NGSLM diagnosis were the only independent risk factors for OS. In the 83 (66%) patients with metachronous NSGLM, disease-free interval > 6 months was associated with improved OS and RFS. Among the 65 patients (52%) who received preoperative chemotherapy, radiologic response according to Choi criteria specifically was associated with improved OS (p = 0.04), but radiologic response according to RECIST 1.1 criteria was not., Conclusions: Resection of NGSLM led to a 5-year OS rate of 49%, independent of histologic subtype and primary tumor location. Choi criteria (which take into account tumor density) are superior to RECIST 1.1 in assessing radiologic response and should be used to assess response to preoperative chemotherapy.

Background: The National Comprehensive Cancer Network (NCCN) has instituted treatment guidelines for stage 2A and stages 2B and 3 extremity and superficial trunk soft tissue sarcomas (ETSTS). This study examined adherence to the NCCN guidelines and factors associated with nonadherent treatment and survival outcomes., Methods: Patients with stage 2A and stages 2B and 3 ETSTS (n = 15,957) were categorized as undergoing adherent or nonadherent treatment based on the 2014 NCCN guidelines. Multivariate logistic regression models were used to determine factors associated with nonadherent treatment. Overall survival (OS) and disease-specific survival (DSS) were calculated, and Cox models were used to generate adjusted survival curves and hazard ratios (HRs)., Results: The findings showed that 87.2% of the patients with stage 2A disease and 58.3% of the patients with stage 2B or 3 disease received adherent treatment. Community treatment facilities and uninsured or unknown insurance status were associated with nonadherent treatment for both stage groups. Adherent treatment was associated with higher 5-year adjusted OS and DSS for stage 2A and stage 2B or 3 patients. In Cox models, nonadherent treatment was associated with worse survival for both stage 2A disease (HR, 2.31; 95% confidence interval [CI], 2.02-2.63) and stages 2B and 3 disease (HR, 1.63; 95% CI, 1.53-1.73). Increasing age and non-private insurance were associated with poorer outcomes. For stages 2B and 3 disease, treatment at a community center and African American race were associated with worse survival., Conclusions: Adherence to NCCN guidelines is excellent for stage 2A and poor for stages 2B and 3 ETSTS. Adherent treatment was associated with improved survival outcomes, highlighting the importance of adherence to NCCN guidelines.

Background: Management of gastrointestinal stromal tumors (GISTs) has been transformed with tyrosine kinase inhibitors (TKIs). While data on optimal duration of adjuvant imatinib remains elusive, guidelines for administration of neoadjuvant TKIs remain unknown., Methods: Under an institutional review board-approved protocol, patients at our institution with a diagnosis of GIST treated with neoadjuvant TKIs and surgical resection were identified. Clinical and pathologic characteristics were obtained from medical records., Results: Ninety-three patients underwent surgical resection after neoadjuvant TKI therapy; 41 had primary and 52 had recurrent/metastatic GIST. Median follow-up was 2.4 years. Median duration of neoadjuvant therapy was 315 (range 3-1,611) days for primary and 537 (range 4-3,257) days for recurrent/metastatic GIST (p = 0.001). Two-year, recurrence-free survival (RFS) was 85 and 44 % for primary and recurrent/metastatic disease, respectively, whereas 2-year overall survival (OS) was 97 % for primary and 73 % for recurrent/metastatic GIST. For primary GIST, duration of neoadjuvant therapy >365 days (p = 0.02) was associated with higher risk of recurrence on univariate analysis, whereas none of the clinicopathologic factors impacted OS. For recurrent/metastatic disease, disease progression was associated with a shorter OS (p = 0.001), but no factors were found to impact RFS. Lastly, when examining all patients, KIT mutations (p = 0.03) and multivisceral resection (p = 0.011) predicted shorter RFS., Conclusions: Neoadjuvant TKIs can be effectively used for the treatment of primary and recurrent/metastatic GIST. While duration of neoadjuvant therapy, KIT mutation status, and the need for multivisceral resection can help to predict higher risk for recurrence, progression on neoadjuvant TKIs can aid in selection of patients with recurrent/metastatic disease for surgical resection.

Background: To evaluate the role of ertapenem versus other standard antibiotic prophylaxis in patients with cancer undergoing intra-abdominal surgery., Methods: Our study was a retrospective cohort study consisting 615 patients who underwent intra-abdominal surgery at our institution between January 2007 and December 2010. The groups were divided among patients who received ertapenem as perioperative prophylaxis (ertapenem group) and patients who received other antibiotics (nonertapenem group). Groups were similar with respect to age, gender, and type of surgery., Results: A total of 315 patients underwent colorectal and 300 noncolorectal surgeries. In a multivariate logistic regression model, the main factors associated with risk of surgical site infections (SSI) were as follows: antibiotics within 3 months of surgery (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.04-1.54; p = 0.05), prior hospitalization within 1 year (OR 1.21, 95% CI 1.02-1.43; p = 0.05), diabetes mellitus (OR 2.1, 95% CI 1.7-3.4; p = 0.04), and perioperative prophylaxis other than ertapenem (OR 1.7, 95% CI 1.2-2.3; p = 0.04). Notably, patients who underwent colorectal surgery and received ertapenem had a lower rate of SSI (4% ertapenem vs. 13% nonertapenem, p = 0.01), whereas the frequency of infections was not different in patients who underwent other intra-abdominal surgery whether they received ertapenem or not., Conclusions: The use of ertapenem for perioperative prophylaxis in patients with colorectal surgery was associated with lower rates of SSI, while there was no difference in rates of infection in other intra-abdominal surgery.

Background: Radical resection is the primary treatment for rectal cancer. When anastomosis is possible, a temporary ileostomy is used to decrease morbidity from a poorly healed anastomosis. However, ileostomies are associated with complications, dehydration, and need for a second operation. We sought to evaluate the impact of ileostomy-related complications on the treatment of rectal cancer., Methods: We conducted a retrospective study of patients who underwent sphincter-preserving surgery between January 2005 and December 2010 at a tertiary cancer center. The primary outcome was the overall rate of ileostomy-related complications. Secondary outcomes included complications related to ileostomy status, ileostomy closure, anastomotic complications at primary resection, rate of stoma closure, and completion of adjuvant chemotherapy assessed by multivariate logistic regression., Results: Of 294 patients analyzed, 32% (n = 95) were women. Two hundred seventy-one (92%) received neoadjuvant chemoradiation. The median tumor distance from the anal verge was 7 cm (interquartile range 5-10 cm). Two hundred eighty-one (96%) underwent stoma closure at a median of 7 months (interquartile range 5.4-8.3 months). The most common complication related to readmission was dehydration (n = 32-11%). Readmission within 60 days of primary resection was associated with delay in initiating adjuvant chemotherapy (odds ratio 3.01, 95% confidence interval 1.42-6.38, p = 0.004)., Conclusions: Diverting ileostomies created during surgical treatment of rectal cancers are associated with morbidity; however, this is balanced against the risk of anastomosis-related morbidity at rectal resection. Given the potential benefit of fecal diversion, patient-oriented interventions to improve ostomy management, particularly during adjuvant chemotherapy, can be expected to yield marked benefits.

Background: With increasing interest in neuroendocrine tumors (NETs), three staging systems for NETs of the colon and rectum have been published. Their prognostic relevance has not been examined and compared in an independent clinical database., Methods: From the National Cancer Database (NCDB), 5457 patients diagnosed with colorectal neuroendocrine tumor (CRNETs) between 1998 and 2002 were staged according to the staging systems from (1) European Neuroendocrine Tumor Society (ENETS, 2006; n = 1537); (2) American Joint Committee on Cancer (AJCC, 2009; n = 1140); and (3) location-specific staging systems from the Surveillance Epidemiology and End Results (SEER, 2008; n = 942). Stage-stratified overall survival (OS) and Cox-specific concordance indices were calculated for each system. Independent prognostic factors were identified by multivariate analysis., Results: Five-year OS for stage I, II, III, and IV CRNETs as defined by the ENETS staging system were 90.8, 77.3, 53.1, and 14.8 %, respectively. For well-differentiated CRNETs, the 5-year OS for stage I, II, III, and IV as defined by the AJCC staging system were superior: 90.6, 83.9, 64.8, and 24.9 %, respectively. Both staging systems had a concordance index of 0.72. After specifying location in the colon versus rectum, all three systems demonstrated acceptable performance. Histologic grade was a significant independent predictor of OS not currently incorporated in the staging systems., Conclusions: The three staging systems showed comparable prognostic stratification of CRNETs, while the AJCC and ENETS systems are the most parsimonious. The current analysis supports the use of the AJCC for well-differentiated disease and ENETS systems for all CRNETs until there is further evidence for modification.

Background: Radiation-associated angiosarcoma (RAAS) is a devastating disease occasionally observed in breast cancer patients treated with radiation. Due to its rarity, our knowledge-of disease risk factors, epidemiology, treatment, and outcome-is extremely limited. Therefore, we sought to identify clinicopathologic factors associated with local and distant recurrence and disease-specific survival (DSS)., Methods: Radiation-associated angiosarcoma was defined as pathologically confirmed breast or chest wall angiosarcoma arising within a previously irradiated field. A comprehensive search of our institutional tumor registry (1/1/93 through 2/28/11) was used to identify patients (n = 95 females). Patient, original tumor, RAAS treatment, and outcome variables were retrospectively retrieved and assembled into a database., Results: The median follow-up for all RAAS patients was 10.3 (range, 2.4-31.8) years. The latency period following radiation exposure ranged from 1.4 to 26 (median, 7) years. One-year and 5-year DSS rates were 93.5 and 62.6 %, respectively. Reduced risk of local recurrence was observed in patients who received chemotherapy (P = 0.0003). In multivariable analysis, size was found to be an independent predictor of adverse outcome (P = 0.015)., Conclusions: Our study demonstrates that RAAS exhibits high recurrence rates. It also highlights the need for well-designed, multicenter, clinical trials to inform the true utility of chemotherapy in this disease.

Background: Proctectomy after hepatectomy, or the reverse approach, is an alternative to traditional sequencing for advanced liver metastases with asymptomatic colorectal primary tumors. We sought to evaluate the surgical morbidity of proctectomy for colorectal cancer after previous liver surgery., Methods: A single-institution colorectal database was queried for patients treated with proctectomy after previous hepatectomy from 2003 to 2011. Reverse-approach patients (n = 31) were matched 1:2 with a cohort of standard proctectomy patients (n = 62) using operation, age, gender, and surgeon. Perioperative factors were analyzed by univariate/multivariate models for associations with complications graded by Dindo-Clavien criteria., Results: Thirty-one patients with adenocarcinoma ≤ 20 cm from the anal verge underwent proctectomy after hepatectomy. Median time from hepatectomy to proctectomy was 5.1 months. Median tumor distance was 8.5 cm. Before proctectomy, patients underwent 28 (90 %) major hepatectomies and 7 (22 %) portal vein embolizations. There were no perioperative deaths. Reverse-approach patients did not differ from control patients in operation, demographics, body mass index (BMI), comorbidities, tumor distance, operative time, estimated blood loss, length of stay, or complication rates (p > 0.05). Grade 2 or higher complications developed in 42 % of reverse-approach and 27 % of standard proctectomies (p = 0.17). Grade 3 or higher complications developed in 10 % and 8 %, respectively (p = 1.00). Independent predictors of complications of grade 2 or higher were BMI ≥30 kg/m(2) (p = 0.007), operative time ≥300 min (p = 0.012), intraoperative transfusion (p = 0.044), concurrent procedures (p = 0.024), and age ≥50 years (p = 0.030)., Conclusions: Risk factors for morbidity of staged proctectomy are similar to those for standard proctectomy. In selected patients, the reverse-approach proctectomy is safe with acceptable morbidity.

Purpose: We evaluated clinical features and survival outcomes among patients with signet ring and mucinous histologies of colorectal adenocarcinoma by using data from the National Cancer Data Base (NCDB)., Methods: Patients aged 18-90 years with colorectal adenocarcinoma diagnosed between 1998 and 2002 were identified from the NCDB. Site-stratified (colon vs. rectum) survival analysis was performed by multivariate relative survival adjusted for multiple clinicopathologic and treatment variables., Results: The study included 244,794 patients: 25,546 (10%) with mucinous, 2,260 (1%) with signet ring, and 216,988 (89%) with nonmucinous, non-signet ring adenocarcinoma. Mucinous and signet ring cancers were more frequently right-sided (60% and 62%, respectively) than were nonmucinous, non-signet ring adenocarcinomas (42%, P < 0.001). Signet ring histology was associated with a higher stage (P < 0.001), and 77.2% of signet ring tumors were high-grade lesions, compared with 20% of mucinous and 17% of non-signet ring, nonmucinous adenocarcinomas (P < 0.001). After adjustment for covariates, signet ring histology was independently associated with higher risk of death [hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51, and HR 1.57, CI 1.38-1.77, for tumors located in the colon and rectum, respectively]. Mucinous tumors of the rectum (HR 1.22, CI 1.16-1.29), but not the colon (HR 1.03, CI 1.00-1.06), were associated with increased risk of death., Conclusions: Signet ring cell adenocarcinomas of the colon and rectum and mucinous adenocarcinomas of the rectum are associated with poorer survival. These aggressive histologic variants of colorectal adenocarcinoma should be targeted for research initiatives to improve outcomes.

Background: Psychological effects of mastectomy for women with breast cancer have driven treatments that optimize cosmesis while strictly adhering to oncologic principles. Although skin-sparing mastectomy is oncologically safe, questions remain regarding the use of nipple-areola complex (NAC)-sparing mastectomy (NSM). We prospectively evaluated NSM for patients undergoing mastectomy for early-stage breast cancer or risk reduction., Methods: We enrolled 33 early-stage breast cancer and high-risk patient; 54 NSMs were performed. NAC viability and surgical complications were evaluated. Intraoperative and postoperative pathologic assessments of the NAC base tissue were performed. NAC sensory, cosmetic and quality of life (QOL) outcomes were also assessed., Results: Twenty-one bilateral and 12 unilateral NSMs were performed in 33 patients, 37 (68.5%) for prophylaxis and 17 (31.5%) for malignancy. Mean age was 45.4 years. Complications occurred in 16 NACs (29.6%) and 6 skin flaps (11.1%). Operative intervention for necrosis resulted in 4 NAC removals (7.4%). Two (11.8%) of the 17 breasts with cancer had ductal carcinoma-in-situ at the NAC margin, necessitating removal at mastectomy. All evaluable patients had nipple erection at 6 and 12 months postoperatively. Cosmetic outcome, evaluated by two plastic surgeons, was acceptable in 73.0% of breasts and 55.8% of NACs, but lateral displacement occurred in most cases. QOL assessment indicated patient satisfaction., Conclusions: NSM is technically feasible in select patients, with a low risk for NAC removal resulting from necrosis or intraoperative detection of cancer, and preserves sensation and QOL. Thorough pathologic assessment of the NAC base is critical to ensure disease eradication.

Background: Hospital attributes have been shown to impact short- and long-term outcomes after cancer surgery. However, the effect of hospital attributes on processes of cancer care in terms of delivery of guideline recommended care has not been evaluated. We examined the impact of hospital attributes (volume and type) on guideline-recommended care in patients treated for gastric cancer., Methods: We identified patients who were surgically treated for gastric cancer at Commission on Cancer (CoC) hospitals from 2001 to 2006. Patient, tumor, and treatment factors were compared separately by hospital volume and type. Multivariable analyses were used to evaluate the impact of hospital attributes on delivery of guideline recommended gastric cancer care: adequate lymphadenectomy (≥15 lymph nodes), and adjuvant multimodality therapy (for AJCC Ib-IVM0), controlling for covariates., Results: More than 1,490 CoC hospitals performed 37,124 gastrectomies. High-volume and teaching CoC hospitals were more likely to treat younger patients, non-whites, patients with lower AJCC stage, and to perform adequate lymphadenectomy than low-volume and community CoC hospitals (p ≤ 0.001). Hospital volume and type, however, were not associated with receipt of adjuvant multimodality therapy. These associations persisted in our multivariable analyses to show that CoC hospital attributes were associated with adequate lymphadenectomy, but marginally predictive of receipt of adjuvant multimodality therapy., Conclusions: The strong association between CoC hospital volume or type and guideline-recommended care diminishes after gastric cancer surgery. Variations in referral, insurance, and documentation patterns are potential explanations for these findings. These results highlight some limitations of using hospital attributes as a sole predictor of optimal cancer care.

Background: Gastrointestinal stromal tumors (GIST) treatment changed considerably with introduction of imatinib in 2001 and reports of early successes. However, little is known about imatinib incorporation into practice. Our objective was to examine the integration of adjuvant systemic therapy into GIST management., Methods: Patients with gastric GIST were identified (n = 4508) from the National Cancer Data Base (2001-2007). Separate regression models were developed to examine factors associated with adjuvant and neoadjuvant therapy use., Results: A total of 3050 patients underwent surgical resection. From 2001-2003 to 2006-2007, use of adjuvant therapy increased from 29 to 47% (P < 0.001). Patients were less likely to receive adjuvant therapy if tumors were <3 cm, low grade, had negative margins, were treated at low-volume centers, or were diagnosed during 2001-2003 (P < 0.01). Adjuvant systemic therapy for lesions <3 cm also increased (17 to 25%, P = 0.001). For high-risk GISTs, adjuvant therapy use increased from 41 to 58% overall, with increases of 46 to 70% at high-volume centers and 40 to 48% at low-volume centers (P < 0.001). Neoadjuvant therapy increased from 0 to 8%; patients were more likely to receive neoadjuvant treatment if their tumor was >6 cm, treated at high-volume centers, or were diagnosed during 2006-2007 (P < 0.001)., Conclusions: Adjuvant systemic therapy use for GISTs was increasing and widespread prior to FDA approval of adjuvant imatinib, suggesting that contemporaneous advances in management of advanced GIST were being simultaneously and rapidly translated into the adjuvant setting. As relatively costly therapies are integrated into practice, more robust tracking systems are needed to monitor the incorporation of new treatments.

Background: We previously reported 26 patients who underwent preoperative chemoradiotherapy (CXRT) for T3 rectal cancer and were subsequently offered full-thickness local excision (LE) as an alternative to total mesorectal excision (TME). At nearly 4 years' follow-up, no difference in outcome was observed. This study compares outcomes in a larger cohort of patients and reevaluates the original 26 patients after longer follow-up., Methods: Retrospective review was performed of patients who underwent preoperative CXRT (radiation doses of 45, 50.4, or 52.5 Gy with concurrent 5-fluorouracil-based chemotherapy) followed by surgery for T3 rectal cancer. Forty-seven patients underwent LE (Kraske [n = 6] or transanal excision [n = 41]). 473 patients underwent TME (abdominoperineal resection [n = 141] or low anterior resection [n = 332]). Local recurrence, disease-free survival (DFS), disease-specific survival, and overall survival (OS) rates were compared., Results: Median follow-up was 63 months for the LE group and 59 months for the TME group. Twenty-three LE patients (49%) had a complete response to CXRT, 17 (36%) had microscopic residual disease, and 7 (15%) had gross residual disease, compared with 108 (23%), 89 (19%), and 276 (58%) TME patients, respectively. There was no significant difference between the 10-year actuarial local recurrence rate for the LE group versus the TME group (10.6% and 7.6%, respectively; P = .52), and no significant difference in DFS, disease-specific survival, or OS rates between groups., Conclusions: In selected patients who demonstrate an excellent response to preoperative CXRT for T3 rectal cancer, full-thickness LE offers comparable local control, DFS, and OS to that achieved with proctectomy and TME.

Background: Isolated tumor cells (ITC) are more likely to be identified when serial sectioning and immunohistochemical staining are used to evaluate sentinel lymph nodes (SLN). Our goal was to identify clinicopathologic features associated with ITC in patients undergoing sentinel lymph node dissection (SLND)., Methods: We reviewed clinicopathologic data for 3557 patients with no clinical evidence of lymph node metastases undergoing SLND between November 1993 and March 2007. Patients were staged according to the 6th edition of the American Joint Committee on Cancer staging system, with metastasis

Background: Recent studies suggest that older patients and minorities are less likely to receive surgical and adjuvant therapy for rectal cancer. We analyzed the independent effect of age and race/ethnicity on treatment for rectal cancer controlling for comorbidity and socioeconomic status using a nationwide sample, Methods: We identified 35,695 patients with rectal adenocarcinoma diagnosed between 2003 and 2005 using the National Cancer Data Base. Comorbidity was calculated from medical records and administrative data. Educational level and income were estimated from census data. Characteristics were compared across groups by chi(2) tests. Odds ratios of surgical and adjuvant therapy and 95% confidence intervals were calculated by logistic regression., Results: A total of 51% of patients were age > or =65, 8.7% were African American, and 4.9% were Hispanic. Younger patients, African Americans, and Hispanics were more likely to present with advanced disease compared with older, white patients (P < .001). Age > or =65 was associated with underuse of surgery and adjuvant therapy (P < .001). Only 85.1% of African Americans were resected, compared with 90.7% of whites (adjusted odds ratio, .62; 95% confidence interval, .54-.71). Among resected patients, race/ethnicity had no effect on rates of sphincter preservation or adjuvant therapy., Conclusions: A high proportion of older patients with rectal cancer do not receive appropriate surgical or adjuvant therapy, even when controlling for comorbidity. African American patients are also less likely to undergo resection, but are equally likely to undergo sphincter preservation and adjuvant therapy compared with whites. Efforts are needed to uncover the root causes underlying these observations and optimize treatment of rectal cancer.

Background: Recent studies demonstrate improved progression-free survival (PFS) and improved overall survival (OS) with extirpation of the primary tumor in breast cancer patients who present with metastatic disease at initial diagnosis. The subset of patients who would most benefit from surgery remains unclear. This study evaluates the pathological attributes and optimum timing for surgery in patients who present with stage IV breast cancer and an intact primary., Methods: Retrospective, single-institution review of all breast cancer patients between 1997 and 2002 presenting with an intact tumor and synchronous metastatic disease. Information collected included: demographics, tumor characteristics, metastatic sites, type/timing of surgery, and radiation/systemic therapy received. Patients initiated treatment within 3 months of their diagnosis. Patients were divided into three groups based on time interval from diagnosis date to surgery date. Disease progression and vital status at last follow-up were evaluated. Analysis of metastatic PFS (defined by progression of systemic disease) benefit in relation to surgical timing was performed., Results: Multivariate analysis revealed patients having only one site of metastasis, negative margins, and Caucasian race had improved PFS. Further analysis revealed non-Caucasian patients more often underwent surgical intervention for palliation versus surgery for curative intent, possibly explaining their worse outcome. Patients who underwent surgery in the 3-8.9 month or later period had improved metastatic PFS., Conclusions: Surgical extirpation of the primary tumor in patients with synchronous stage IV disease is associated with improved metastatic PFS when performed more than 3 months after diagnosis. Resection should be planned with the intent of obtaining negative margins.

Background: Lymph node involvement is an important prognostic factor in colorectal cancer. Sentinel lymph node (SLN) evaluation for assessing lymph node status in colorectal cancer remains controversial. Here we evaluated the sensitivity, predictive value, and accuracy of SLN evaluation for determining lymph node status in resectable colon cancer., Methods: A prospective phase 2 cohort study of SLN evaluation in colon cancer was conducted from September 1998 to April 2006. Patients underwent resection and SLN mapping with 1% isosulfan blue and (m99)Tc sulfur colloid injection. SLNs were evaluated by hematoxylin and eosin (HE) staining and, if findings were negative, by additional thin HE sections and immunohistochemical (IHC) staining for pancytokeratin and MOC31. Overall survival for patients with IHC-positive disease was evaluated by Kaplan-Meier analysis and the log rank test., Results: SLNs were identified in 119 (99%) of the 120 patients eligible for the study. Median number of SLNs identified was 4 (range, 0-13). Forty-nine patients (40%) had nodal metastases on HE. The SLN accurately identified nodal metastases in 29 (59%) of these 49 patients and was negative for metastases in 22 patients (41%). SLNs in eight patients (7%) were negative by HE but positive by IHC staining. Positive IHC status did not affect survival after a median follow-up of 33 months (P = .41)., Conclusions: The low sensitivity and high false-negative rate of SLN evaluation does not support this technique for improving the accuracy of nodal staging for patients with colon cancer. The significance of IHC-positive SLNs remains uncertain.

Background: Cancer patients may be at increased risk for pneumoperitoneum due to local tumor invasion, immunosuppression, chemotherapy, and frequent endoscopy. The purpose of this study was to characterize clinical presentations and management strategy for pneumoperitoneum in cancer patients., Methods: All patients with an ICD-9 diagnosis of visceral perforation or who had undergone a surgical oncology consultation between January 2000 and October 2006 were identified. Those patients with evidence of pneumoperitoneum on radiography underwent chart review. Patients were grouped according to treatment with or without surgery and results were compared using Chi-square and Kaplan Meier analysis., Results: Of 1,750 patients identified, 123 had 124 episodes of pneumoperitoneum. Treatment given was comfort care (n = 19), non-operative management (n = 33), or surgery (n = 72). Disease stage was IV in 89% of the comfort care group, 70% of the non-operative group, and 65% of the surgery group (P = 0.6). Factors predictive of management on univariate analysis were the presence of symptoms at presentation, abdominal tenderness, fever, pneumatosis on imaging, and prior abdominal radiation; but only fever, abdominal tenderness, and abdominal radiation were significant in multivariate analysis. With comfort care, non-operative management, and surgery, 30-day mortality rates were 100%, 12%, and 15%, respectively., Conclusions: Pneumoperitoneum in cancer patients requires a tailored approach that considers both clinical presentation and oncological prognosis. Conventional wisdom for surgical evaluation--symptom severity, pain, and tenderness--still applies, but some patients can be successfully treated without surgery.

Background: Treatment of peritoneal recurrence following surgical resection of intra-abdominal sarcomas presents a significant challenge to clinicians. Historically, treatment with systemic chemotherapy has been ineffective and surgical resection alone has not been durable. We prospectively evaluated the feasibility of cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin (CDDP) alone or in combination with mitoxantrone (MITOX) for the treatment of sarcomatosis., Methods: Two phase I trials of HIPEC were conducted (1998-2003). Eligible patients with evidence of sarcomatosis underwent cytoreductive surgery followed by HIPEC. In the first trial, CDDP dosing was established as 90 mg/m2 with a perfusate time of 90 minutes and temperature of 41 degrees C. In the second trial, MITOX (20 mg/m2) was instilled following perfusion with CDDP. Toxicity, efficacy, and quality of life (QOL) were evaluated., Results: A total of 28 patients were enrolled in the two trials. We noted a higher overall toxicity score and complication rate with combination CDDP/MITOX versus CDDP alone and shorter overall survival duration (5.5 months vs 16.9 months, respectively). In addition, local recurrence rates were similar in both groups (CDDP 79% vs CDDP/MITOX 68%). As expected, QOL scores at 6-8 weeks following HIPEC were 15-25% lower than the baseline scores; however, they returned to baseline at 3-6 months., Conclusions: Although the HIPEC technique is feasible for patients with sarcomatosis, it is associated with significant toxicity and limited clinical benefit. Combination CDDP/MITOX failed to demonstrate any benefit over CDDP alone; moreover, there was an increase in toxicity.

Background: Significant tumor downstaging has been achieved in patients with localized gastric or gastroesophageal adenocarcinoma by induction chemotherapy and preoperative chemoradiotherapy (CTX-CTXRT). However, the influence of CTX-CTXRT on operative morbidity and mortality has not yet been clarified. The aim of the present study was to document the frequency and nature of morbidity and mortality after surgery combined with CTX-CTXRT, and identify factors predictive of postoperative complications in patients with localized gastric or gastroesophageal adenocarcinoma., Methods: A prospectively collected database on 71 consecutive patients who underwent CTX-CTXRT at M.D. Anderson Cancer Center between January 1997 and August 2004 was reviewed. Postoperative morbidity and mortality were investigated, and risk factors for overall complications were identified by multivariate logistic regression analysis., Results: Overall morbidity and mortality rates were 38.0% (27 patients) and 2.8% (2 patients), respectively. Age greater than 60 years [relative risk 11.3 (95% confidence interval 2.50-50.6)] and body mass index (BMI) of 26 kg/m(2) or above [relative risk 4.08 (95% confidence interval 1.08 to 15.4)] were significant risk factors for overall complications., Conclusions: CTX-CTXRT can be performed safely with an acceptable operative morbidity and a low operative mortality rate in patients with gastric or gastroesophageal cancer, with careful consideration of added risk associated with age and obesity.

Background: Treatment of locally advanced rectal carcinoma (LARC) often involves exenterative surgery, which can be associated with high perioperative morbidity and mortality. To assist in patient selection for radical surgery, we sought to determine clinicopathologic factors influencing recurrence and disease-free survival (DFS) of LARC., Methods: Consecutive patients with LARC undergoing exenterative surgery were retrospectively identified in our institutional database. Factors evaluated included age, sex, primary versus recurrent tumors, neoadjuvant or adjuvant chemoradiotherapy, resection margin status, recurrence, time to recurrence, and survival. The primary outcome was DFS. Secondary outcomes were overall survival and perioperative morbidity., Results: A total of 72 patients were identified; median age was 52 years, and median follow-up time was 30 months. The overall complication rate was 43%; rates were similar among the patients with primary (47%) or recurrent (37%) LARC. Primary or recurrent tumor status was the only factor significantly predictive of outcome after exenteration. Local recurrence rates were lower in the primary group (primary 22%, recurrent 52%, P = .05). A significant difference in 5-year DFS was found between primary and recurrent tumor (52% vs. 13%; P < .01). The median time to recurrence was longer in the patients with primary LARC (17 months vs. 8 months; P < .01)., Conclusions: The complication rates for pelvic exenteration remain high, but the morbidity can typically be managed without a clinically important increase in hospitalization. In primary LARC, an aggressive surgical approach provides most patients 5-year DFS. Select patients with recurrent LARC will also benefit from pelvic exenteration.

Background: Positive/close margins are associated with higher in-breast failure rates after breast-conserving surgery (BCS). We investigated whether intraoperative margin assessment aids in obtaining negative margins, and to evaluate the local control thus achieved., Methods: Between 1994 and 1996, 264 patients underwent BCS for stages 0-III breast cancer [invasive, n = 200; ductal carcinoma in situ (DCIS), n = 64]. Intraoperative margin assessment included gross tissue inspection, specimen radiography, with or without frozen section., Results: Ninety-two patients (46%) with invasive cancer and 24 (38%) with DCIS had positive/close margins on the permanent section analysis of their initial surgical specimens. Fifty-eight patients (29%) with invasive cancer and six (9%) with DCIS had initial positive/close margins, and were rendered margin-negative by intraoperative analysis and immediate re-excision. Final margins on permanent pathology were positive/close in 52 patients (20%): 34 patients (17%) with invasive cancer and 18 patients (28%) with DCIS. By multivariate analysis, excisional biopsy for diagnosis, larger tumor size, and multifocality were associated with final positive/close margins. Of these 52 patients, 23 underwent a second operation to achieve widely negative margins (13 completion mastectomies, 10 re-excisions). The 5-year ipsilateral breast recurrence-free survival rates after BCS and radiation were 99% for invasive cancer (n = 167) and 100% for DCIS (n = 27)., Conclusions: Intraoperative assessment of margins assisted in identifying positive/close margins and allowed over a quarter of the patients to be rendered margin-negative with intraoperative re-excision at their original operation. This approach resulted in excellent local control in patients treated with BCS and radiation.

Background: The standard treatment for epidermoid carcinoma of the anal canal consists of combined radiation and chemotherapy. For patients who present with persistent or locally recurrent disease, salvage abdominoperineal resection is the treatment of choice. The purpose of this study is to review our experience with salvage surgery in this group of patients., Methods: From 1990-2002, 31 patients underwent radical salvage surgery with curative intent after failure of initial sphincter-conserving therapy, and the medical records of these patients were retrospectively reviewed. Clinicopathologic variables were determined and comparisons performed with the Cox proportional hazards model. Survival was calculated by the Kaplan-Meier method., Results: Eleven patients underwent radical salvage surgery for persistent disease and 20 patients for recurrent disease. The median follow-up time was 29 months. The actuarial 5-year overall survival was 64%. Twelve patients developed recurrent disease after radical salvage surgery. Patients who received an initial radiation dose of less than 55 Gy had a significantly worse survival than those who received at least 55 Gy as part of their initial treatment (5-year overall survival 37.5% vs. 75%; age-adjusted hazard ratio 8.2 [95% CI: 1.1-59.8], P = .037). The presence of positive lymph nodes at presentation also adversely affected survival (P < .05). Factors that were not found to have an impact on survival included the presence of persistent versus recurrent disease, tumor (T) stage, and margin status of resection., Conclusions: Long-term survival following salvage surgery for persistent or locally recurrent epidermoid carcinoma of the anal canal can be achieved in the majority of patients. However, patients who initially present with node-positive disease and patients who receive a radiation dose of less than 55 Gy as part of their initial chemoradiation therapy regimen have a worse prognosis after radical salvage surgery.

Background: Surgical resection of gastrointestinal stromal tumors (GISTs) has been the most effective therapy for these rare tumors. Imatinib has been introduced as systemic therapy for locally advanced and metastatic GIST. In this study, the surgical resection rates and long-term outcomes of patients treated with preoperative imatinib for locally advanced primary, recurrent, or metastatic GISTs were evaluated., Methods: Patients were retrospectively assessed for completeness of surgical resection and for disease-free and overall survival after resection., Results: Forty-six patients underwent surgery after treatment with imatinib. Eleven were treated for locally advanced primary GISTs for a median of 11.9 months, followed by complete surgical resection. All eleven were alive at a median of 19.5 months, and ten were free of disease. Thirty-five patients were treated for recurrent or metastatic GIST. Of these, eleven underwent complete resection. Six of the eleven patients had recurrent disease at a median of 15.1 months. All eleven patients were alive at a median of 30.7 months. Patients with a partial radiographic tumor response to imatinib had significantly higher complete resection rates than patients with progressive disease (91% vs. 4%; P < .001). Of the 24 patients with incomplete resection, 18 initially responded to imatinib but were unable to undergo complete resection after they progressed before surgery., Conclusions: Preoperative imatinib can decrease tumor volume and is associated with complete surgical resection in locally advanced primary GISTs. Early surgical intervention should be considered for imatinib-responsive recurrent or metastatic GIST, since complete resection is rarely achieved once tumor progression occurs.

Background: Major wound complications (MWCs) are frequent after preoperative radiotherapy (RT) for extremity soft-tissue sarcoma (STS). We examined the rate of MWCs at a single institution with readily available reconstructive surgery., Methods: The medical records of consecutively treated extremity STS patients treated with preoperative external-beam RT and surgical resection from June 1996 through February 2003 were reviewed. Patients underwent RT (median 50 Gy), followed by resection 4-8 weeks later. Patients believed to be at higher risk for MWC underwent wound closure by the reconstructive surgery service (RSS). MWCs included secondary operation, invasive procedure, hospital readmission, or persistent deep packing or dressing changes., Results: A total of 173 patients underwent preoperative RT. Median age was 54 years; 51% were female; 80% had lower extremity STS. Wound closure was performed by the primary surgeon in 91 cases (53%). The RSS performed wound closure in the remaining 82 patients (47%). One or more MWCs occurred in 55 patients (32%). Wound complications were more likely in patients with lower extremity (49/138, 36%) than upper extremity (6/35, 17%) STS (P = 0.03). Among patients with lower-risk wounds closed by the primary surgical team, 29 (32%) experienced MWC, whereas in the higher-risk patients closed by the RSS, MWC occurred in 26 (32%)., Conclusions: MWCs are frequent after preoperative RT and occur more commonly in patients with lower extremity tumors. The MWC rate observed in a single-institution setting was comparable to that observed in the preoperative therapy arm of a multicenter Canadian trial. Patients believed to be at higher risk for MWCs undergoing RSS closure have MWC rates comparable to those with lower-risk wounds closed by the primary team.

Background: Currently, therapy for breast cancer patients with stage IV disease and an intact primary tumor is metastasis directed; the primary tumor is treated only when it causes symptoms. A recent review suggested that surgery may improve long-term survival in such patients. We evaluated the effect of surgery in such patients on long-term survival and disease progression., Methods: We reviewed the records of all breast cancer patients treated at our institution between 1997 and 2002 who presented with stage IV disease and an intact primary tumor. Information collected included demographics, tumor characteristics, site(s) of metastases, type/date of operation, use of radiotherapy, chemotherapy and hormonal therapy, disease progression (time to progression and location of progression) in the first year after diagnosis, and last follow-up. Overall and metastatic progression-free survival were compared between surgery and nonsurgery patients., Results: Of 224 patients identified, 82 (37%) underwent surgical extirpation of the primary tumor (segmental mastectomy in 39 [48%] and mastectomy in 43 [52%]), and 142 (63%) were treated without surgery. The median follow-up time was 32.1 months. After adjustment for other covariates, surgery was associated with a trend toward improvement in overall survival (P=.12; relative risk, .50; 95% confidence interval, .21-1.19) and a significant improvement in metastatic progression-free survival (P=.0007; relative risk, .54; 95% confidence interval, .38-.77)., Conclusions: Removal of the intact primary tumor for breast cancer patients with synchronous stage IV disease is associated with improvement in metastatic progression-free survival. Prospective studies are needed to validate these findings.

Background: The reported data on surgery plus radiotherapy for retroperitoneal soft tissue sarcomas (RPS) have been mostly from retrospective studies. We evaluated the long-term outcome of patients with operable RPS who were treated with protocol-based preoperative radiotherapy followed by complete surgical resection., Methods: Data from two prospective trials that included preoperative radiotherapy and surgery for patients with radiographically resectable RPS were combined to define long-term relapse rates and survival., Results: Seventy-two patients with intermediate- or high-grade RPS were treated with preoperative radiotherapy (median dose, 45 Gy; range, 18.0-50.4 Gy). Fifty-four patients (75%) had primary RPS, whereas 18 (25%) had recurrent disease. The median tumor size was 15.5 cm. Sixty-four patients completed the planned preoperative radiotherapy; 57 (89%) underwent laparotomy with curative intent, and 54 (95%) had a macroscopically complete (R0 or R1) resection. With a median follow-up of 40.3 months, 28 patients (52%) who received preoperative radiotherapy and underwent a macroscopically complete resection had recurrences. For the 54 patients who underwent R0 or R1 resection after preoperative radiotherapy, the 5-year local recurrence-free, disease-free, and overall survival rates were 60%, 46%, and 61%, respectively. The median overall survival has not been reached (>60 months)., Conclusions: Patients with intermediate- or high-grade RPS treated with preoperative radiotherapy plus complete resection had a median survival >60 months. This compares favorably to historical data for similar patients treated with surgery alone.

Background: The optimal surgical management of Paget's disease of the breast remains to be defined. Mastectomy has been the standard of care, but several institutions have recently advocated breast-conserving surgery, particularly for patients with minimal disease. In an effort to develop rational treatment guidelines, we examined our institutional experience with Paget's disease of the breast., Methods: Patients with Paget's disease of the breast who had surgical therapy at our institution between 1949 and 1993 were reviewed. In addition to patient and tumor characteristics, charts were reviewed for treatment modalities, locoregional recurrence patterns, and survival. Subgroups were compared for differences in survival in both univariate and multivariate analyses., Results: A total of 104 patients met the study criteria. The most common presenting symptoms were nipple discharge and eczematous changes of the nipple/areola complex. Ninety-seven patients (93.2%) had an underlying invasive or noninvasive cancer associated with Paget's disease. Ninety-two patients (88.5%) underwent mastectomy, and 12 (11.5%) had a breast-conserving procedure. On univariate analysis, patients with age <60 years at diagnosis, stage II disease, positive lymph nodes, invasive disease, or a palpable mass had significantly lower 10-year disease-specific and recurrence-free survival. There were four locoregional recurrences (three after mastectomy and one after breast conservation). There were no significant differences in overall, disease-specific, or recurrence-free survival according to the type of surgery., Conclusions: Paget's disease of the breast is almost always associated with an underlying breast cancer. Breast-conserving approaches result in local control and survival rates similar to those achieved with mastectomy.

Background: Ultrasonography and fine-needle aspiration (FNA) are used to evaluate the breast and regional nodes in breast cancer patients. We sought to identify factors influencing the sensitivity of ultrasonography for detection of nodal metastasis., Methods: Patients with a clinically negative axilla who underwent axillary ultrasonography and sentinel lymph node biopsy were included., Results: Of 208 patients, axillary ultrasonography was negative in 180 (86%) and suspicious or indeterminate in 28 (14%). FNA was performed in 22 patients whose findings were indeterminate or suspicious, and 3 were positive for malignancy. Final pathological examinations revealed positive nodes in 53 patients: 39 (22%) of 180 with negative ultrasonographic findings and 14 (50%) of 28 with indeterminate or suspicious ultrasonographic findings (P =.001). Excisional biopsy was more common for patients with indeterminate or suspicious findings on preoperative ultrasonography (P =.038). There were no significant differences in tumor size, histological features, size of nodal metastasis, or number of positive nodes between patients whose ultrasonography findings were negative and those whose findings were indeterminate or suspicious., Conclusions: Ultrasonographically suggested nodal metastasis is associated with the finding of nodal disease on final pathological examination. No significant clinicopathologic criteria were found to impact sensitivity of ultrasonography; however, excisional biopsy for diagnosis may be a confounding variable in subsequent axillary ultrasonography.

Background: Chest wall recurrence (CWR) after mastectomy often forecasts a grim prognosis. Predictors of outcome after CWR, however, are not clear., Methods: From 1988 to 1998, 130 patients with isolated CWRs were seen at our center. Clinicopathologic factors were studied by univariate and multivariate analyses for distant metastasis-free survival after CWR. The median post-CWR follow-up was 37 months., Results: Initial nodal status was the strongest predictor of outcome by univariate analysis. Other significant factors included initial T4 disease, primary lymphovascular invasion, treatment of the primary tumor with neoadjuvant therapy or radiation, time to CWR >24 months, and treatment for CWR (surgery, radiation, or multimodality therapy). Multivariate analysis also found initial nodal status to have the greatest effect; time to CWR and use of radiation for CWR were also independent predictors. Three groups of patients were identified. Low risk was defined by initial node-negative disease, time to CWR >24 months, and radiation for CWR; intermediate risk had one or two favorable features; and high risk had none. The median distant metastasis-free survival after CWR was significantly different among these groups (P <.0001)., Conclusions: Patients with CWR are a heterogeneous population. Patients with initial node-negative disease who develop CWR after 24 months have an optimistic prognosis, especially if they are treated with radiation.

Background: Breast-conservation surgery plus radiotherapy has become the standard of care for early-stage breast cancer; we evaluated its long-term complications., Methods: We selected patients treated with surgery and radiotherapy between January 1990 and December 1992 (an era in which standard radiation dosages were used) with follow-up for at least 1 year. Patients were prospectively monitored for treatment-related complications. Median follow-up time was 89 months., Results: A total of 294 patients met the selection criteria. Grade 2 or higher late complications were identified in 29 patients and included arm edema in 13 patients, breast skin fibrosis in 12, decreased range of motion in 4, pneumonitis in 2, neuropathy in 2, fat necrosis in 1, and rib fracture in 1. Arm edema was more common after lumpectomy plus axillary node dissection than after lumpectomy alone. Arm edema occurred in 18% of patients who underwent surgery plus irradiation of the lymph nodes and 10% who underwent surgery without nodal irradiation., Conclusions: Breast-conservation surgery plus radiotherapy was associated with grade 2 or higher complications in only 9.9% of patients. Half of these complications were attributable to axillary dissection, it is hoped that lower complication rates can be achieved with sentinel lymph node biopsy. Breast-conservation surgery and radiotherapy is associated with grade 2 or greater complications in only 9.9% of patients. Nearly half of these complications are attributable to axillary dissection.

Background: Our aim was to identify predictors of locoregional recurrence (LRR) in patients with early-stage breast cancer treated with breast-conserving therapy (BCT) and long-term follow-up., Methods: From 1970 to 1994, 1153 patients with stage I to II breast cancer underwent BCT and radiotherapy at our institution. Patients with prior breast cancer or other primary malignancies were excluded. Clinical and pathologic characteristics evaluated were age, race, tumor size, stage, pathologic tumor margins, axillary nodal involvement, estrogen and progesterone receptor status, Black's nuclear grade, type of surgery, and use of adjuvant therapy., Results: Of 1083 patients, 54% presented with stage I disease and 46% with stage II disease. Median age was 50 years, and median follow-up was 9 years. Axillary nodes were positive in 31% of the patients who underwent axillary dissection. LRR developed in 6%, LRR followed by systemic recurrence in 5%, and systemic recurrence alone in 13%; 76% had no evidence of recurrence at last follow-up. Age, tumor size, positive lymph nodes, and not receiving chemotherapy or hormonal therapy were independent predictors of LRR. Disease-specific survival among patients with LRR was similar to that among patients with no recurrence., Conclusions: Multidisciplinary treatment strategies should be used to accomplish durable locoregional control after BCT.

Background: The goals of this study were to assess the feasibility and toxicity of a regimen of preoperative chemoradiotherapy, surgery, and intraoperative radiotherapy in the treatment of patients with potentially resectable gastric cancer. A secondary objective was to assess pathologic response to chemoradiotherapy in the treated tumors., Methods: Twenty-four patients were entered in the protocol. Treatment regimen consisted of 45 Gy of external beam radiotherapy with concurrent 5-FU given as a continuous infusion at a dose of 300 mg/m2. Patients were restaged 4-6 weeks after chemoradiotherapy and then underwent surgical resection and intraoperative radiotherapy to a dose of 10 Gy., Results: Twenty-three patients (96%) completed chemoradiotherapy in accordance with the study protocol. Nineteen (83%) of 23 patients who completed chemoradiotherapy underwent surgical resection with D2 lymphadenectomy. Four patients (17%) had progressive disease and were not resected. The morbidity and mortality rates were 32% and 5%, respectively. Of the resected patients, two (11%) had complete pathologic responses while 12 (63%) had pathologic evidence of significant treatment effect., Conclusions: Preoperative chemoradiotherapy for gastric cancer can be delivered safely and is well tolerated. The rate of surgical complications is consistent with that of other recently reported prospective trials of gastrectomy alone. Preoperative chemoradiotherapy resulted in significant pathologic responses in the majority of treated tumors, and complete pathologic responses were achieved in some patients.

Background: The role of breast-conserving therapy (BCT) in the management of ductal carcinoma-in-situ (DCIS) is controversial because of reported high recurrence rates. We reviewed our experience to determine whether the rate and pattern of locoregional recurrence after BCT were similar in patients with DCIS and patients with early-stage (T1) invasive breast tumors and whether local recurrence affected survival., Methods: Between 1973 and 1994, 87 patients with DCIS alone, 22 patients with DCIS with microinvasion (DCIS-M), and 646 patients with invasive breast cancer 2 cm or smaller in diameter were treated with BCT (wide local excision with radiotherapy) at The University of Texas M. D. Anderson Cancer Center. Survival was calculated by the Kaplan-Meier method. The median follow-up times were 11 years for patients with DCIS alone, 12 years for patients with DCIS-M, and 8 years for patients with invasive breast cancer., Results: Eleven (13%) of 87 patients with DCIS and 5 (23%) of 22 patients with DCIS-M had developed locoregional recurrences at follow-up. Two patients with DCIS with locoregional recurrence died of breast cancer. Of the 646 patients with invasive breast cancer, 56 (9%) had a locoregional recurrence, and 16 (2%) died of breast cancer. The median time to locoregional recurrence was significantly longer in patients with DCIS or DCIS-M (9-10 years) than patients with invasive tumors (5 years)., Conclusions: DCIS is a favorable disease with an excellent long-term survival. The locoregional recurrence rate in patients with DCIS treated with BCT is similar to that in patients with early-stage invasive breast cancer treated with BCT, but time to locoregional recurrence is significantly longer in patients with DCIS. In patients with DCIS treated with BCT, intense surveillance for locoregional recurrence needs to be maintained for the patient's lifetime.

Background: Although preoperative chemotherapy has become the standard of care for inoperable locally advanced breast cancer, its role for downstaging resectable primary tumors is still evolving. The purpose of this study was to determine whether the prognostic information from an axillary node dissection in patients with clinical T3N0 breast cancer was altered by preoperative chemotherapy compared with surgery de novo., Methods: Between 1976 and 1994, 91 patients with clinically node-negative operable T3 breast cancer received doxorubicin-based combination chemotherapy on protocol at one institution. Fifty-three patients received both preoperative and postoperative chemotherapy (PreopCT), and 38 received postoperative chemotherapy only (PostopCT). All patients underwent axillary lymph node dissection as part of their definitive surgical treatment. There were no differences between the PreopCT and PostopCT groups in median age (51 vs. 49 years), median tumor size at presentation (6 cm vs. 6 cm), tumor grade, or estrogen receptor status (estrogen receptor negative 38% vs. 32%). The median follow-up time was 7 years., Results: Patients in the PreopCT group had fewer histologically positive lymph nodes (median, 0 vs. 3, P < .01), and a lower incidence of extranodal extension (19% vs. 42%, P = .02). By univariate analysis, the number of pathologically positive lymph nodes (P < .01) and extranodal extension (P < .01) were predictors of disease-specific survival in PreopCT patients. Multivariate analysis showed that extranodal extension was the only independent prognostic factor in PreopCT patients (P < .01). Overall, PreopCT and PostopCT patients had similar 5-year disease-free survival rates (66% vs. 57%); however, PreopCT patients had worse disease-free (P = .01) and disease-specific survival (P = .04) when survival was compared after adjustment for the number of positive lymph nodes. Furthermore, PreopCT patients with 4-9 positive lymph nodes had a lower 5-year disease-free survival rate than PostopCT patients with 4-9 positive nodes (17 vs. 48%, P = .04)., Conclusions: Axillary lymph node status remains prognostic after chemotherapy. Pathologically positive lymph nodes after preoperative chemotherapy are associated with a worse prognosis than the same nodal status before chemotherapy.

Background: Routine use of axillary lymph node dissection is being questioned, especially in clinically NO patients. The goal of this study was to determine whether primary tumor response to induction chemotherapy (IC) can predict the histological volume of residual axillary disease in patients who were candidates for breast conservation surgery after IC., Methods: Forty-seven patients with stage II or IIIA breast cancer who received breast conservation surgery were selected from a population of patients randomized to receive four cycles of IC. Largest clinical tumor size before and after IC was determined by physical examination, mammography, and breast ultrasound. Clinical nodal status was determined by physical examination and axillary ultrasound and compared with histological findings., Results: In patients with at least 50% reduction in primary tumor size after IC, 12 of 14 (86%) NO patients and 11 of 17 (65%) N1 patients were histologically negative. In patients with a less than 50% reduction, 0 of 3 NO patients and 2 of 13 (15%) N1 patients were histologically negative., Conclusions: There is significantly less axillary disease in responders than in nonresponders after IC. For NO responders, axillary irradiation may be an acceptable alternative to axillary lymph node dissection, and could easily be incorporated into the postsurgical radiotherapy that is standard protocol for breast conservation therapy. The more aggressive disease in nonresponders is best treated by axillary lymph node dissection, pending further study.