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Background: Optimal treatment strategies for retroperitoneal leiomyosarcoma (RPLMS), particularly recurrent disease, are unknown., Methods: We searched the tumor registry at The University of Texas MD Anderson Cancer Center (MDACC) to identify patients with RPLMS treated between 1994 and 2013., Results: We identified 172 patients with a diagnosis of a RPLMS. Among the 85 patients who underwent complete resection included in the survival analysis, the median overall survival (OS) was 8.3 years (95% confidence interval [CI], 5.7-12.3), 5-year local recurrence rate was 21%, and 5-year distant metastasis rate was 47%. Among 114 patients who experienced recurrence, patients who underwent salvage surgery for recurrent disease had longer OS after recurrence than patients who did not undergo salvage surgery (median survival after recurrence 5.6 vs 3.3 years, 3-year OS rates after recurrence 72.6% vs 58.1%, HR 0.402 [95%CI, 0.243-0.666]; P = 0.0004). Whether salvage surgery was performed for local or distant recurrence was not associated with OS. Patients who had a longer disease-free interval (≥12 months) had better progression-free survival after salvage surgery than those who had a shorter interval (HR, 0.437 [95%CI, 0.244-0.783]; P = 0.0055)., Conclusions: We recommend that salvage surgery be considered for selected patients with local or distant recurrence of RP LMS., (© 2017 Wiley Periodicals, Inc.)

Colorectal cancers are common tumors in the United States and appropriate imaging is essential to direct appropriate care. Staging and treatment differs between tumors arising in the colon versus the rectum. Local staging for colon cancer is less integral to directing therapy given radical resection is often standard. Surgical options for rectal carcinoma are more varied and rely on accurate assessment of the sphincter, circumferential resection margins, and peritoneal reflection. These important anatomic landmarks are best appreciated on high-resolution imaging with transrectal ultrasound or MRI. When metastatic disease is suspected, imaging modalities that provide a global view of the body, such as CT with contrast or PET/CT may be indicated. Rectal cancer often metastasizes to the liver and so MRI of the liver with and without contrast provides accurate staging for liver metastases. This article focuses on local and distant staging and reviews the appropriateness of different imaging for both variants. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Although the safety of combination chemotherapy without primary tumor resection (PTR) in patients with stage IV colon cancer has been established, questions remain regarding a potential survival benefit with PTR. The objective of this study was to compare mortality rates in patients who had colon cancer with unresectable metastases who did and did not undergo PTR., Methods: An observational cohort study was conducted among patients with unresectable metastatic colon cancer identified from the National Cancer Data Base (2003-2005). Multivariate Cox regression analyses with and without propensity score weighting (PSW) were performed to compare survival outcomes. Instrumental variable analysis, using the annual hospital-level PTR rate as the instrument, was used to account for treatment selection bias. To account for survivor treatment bias, in situations in which patients might die soon after diagnosis from different reasons, a landmark method was used., Results: In the total cohort, 8641 of 15,154 patients (57%) underwent PTR, and 73.8% of those procedures (4972 of 6735) were at landmark. PTR was associated with a significant reduction in mortality using Cox regression (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.44-0.47) or PSW (HR, 0.46; 95% CI, 0. 44-0.49). However, instrumental variable analysis revealed a much smaller effect (relative mortality rate, 0.91; 95% CI, 0.87-0.96). Although a smaller benefit was observed with the landmark method using Cox regression (HR, 0.6; 95% CI, 0.55-0.64) and PSW (HR, 0.59; 95% CI, 0.54-0.64), instrumental variable analysis revealed no survival benefit (relative mortality rate, 0.97; 95% CI, 0.87-1.06)., Conclusions: Among patients with unresectable metastatic colon cancer, after adjustment for confounder effects, PTR was not associated with improved survival compared with systemic chemotherapy; therefore, routine noncurative PTR is not recommended. Cancer 2017;123:1124-1133. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

OBJECTIVE Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive group of soft tissue sarcomas that can arise sporadically, in the context of neurofibromatosis Type 1 (NF1) or at a site of prior irradiation. Large series profiling the features and outcomes of sporadic, NF1-associated, and radiation-associated MPNSTs are limited. The goal of this study was to elucidate differences between MPNST etiologies in a large single-institution retrospective study. METHODS Patients (n = 317) were identified through the tumor registry of The University of Texas MD Anderson Cancer Center. Clinicopathological features were retrospectively collected. Features were compared among MPNST subtypes for patients who had sufficient clinical history (n = 289), and clinicopathological features were used to identify adverse predictors of recurrence and survival outcomes. RESULTS Five-year local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and disease-specific survival (DSS) estimates were 56.6%, 49.6%, and 53.6%, respectively, for the high-grade MPNST cohort. Five-year DSS was lower in NF1-associated and radiation-associated MPNST than in sporadic MPNST (52%, 47%, and 67%, respectively, p = 0.140). Patients with radiation-associated MPNST had worse 5-year LRFS than those with the sporadic and NF1-associated subtypes (RT-associated vs sporadic, p = 0.010; RT-associated vs NF1-associated, p = 0.232). Truncally located tumors, positive surgical margins, local recurrence, and metastasis were predictors of adverse DSS in multivariate analysis. CONCLUSIONS Radiation-associated MPNSTs are associated with poorer local recurrence-free and disease-specific survival than sporadic and NF1-associated tumors. NF1-associated MPNSTs may have worse survival outcomes owing to large tumor size, compromising truncal location, and lower rate of negative resection margins compared with sporadic tumors.

Purpose: DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer., Methods: Between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. Oncologic treatment and outcomes as well as clinical genetics work-up were examined. Overall and rectal cancer-specific survival were calculated by the Kaplan-Meier method., Results: The median age at diagnosis was 41 years. MMR deficiency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%). After a median follow-up of 6.8 years, the 5-year rectal cancer-specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease. Fluoropyrimidine-based neoadjuvant chemoradiation was associated with a complete pathologic response rate of 27.6%. The extent of surgical resection was influenced by synchronous colonic disease at presentation, tumor height, clinical stage, and pelvic radiation. An informed decision for a limited resection focusing on proctectomy did not compromise overall survival. Five of the 11 (45.5%) deaths during follow-up were due to extracolorectal malignancies., Conclusion: dMMR rectal cancer had excellent prognosis and pathologic response with current multimodality therapy including an individualized surgical treatment plan. Identification of a dMMR rectal cancer should trigger germline testing, followed by lifelong surveillance for both colorectal and extracolorectal malignancies. We herein provide genotype-specific outcome benchmarks for comparison with novel interventions., Competing Interests: Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2016 by American Society of Clinical Oncology.)

Background: The practice of salvaging recurrent rectal cancer has evolved. The aim of this study was to define the evolving salvage potential over time among patients with locally recurrent disease, and to identify durable determinants of long-term success., Methods: The study included consecutive patients with recurrent rectal cancer undergoing multimodal salvage with curative intent between 1988 and 2012. Predictors of long-term survival were defined by Cox regression analysis and compared over time. Re-recurrence and subsequent treatments were evaluated., Results: After multidisciplinary evaluation of 229 patients, salvage therapy with curative intent included preoperative chemotherapy and/or radiotherapy (73·4 per cent; with 41·3 per cent undergoing repeat pelvic irradiation), surgical salvage resection with or without intraoperative irradiation (36·2 per cent), followed by postoperative adjuvant chemotherapy (38·0 per cent). Multivisceral resection was undertaken in 47·2 per cent and bone resection in 29·7 per cent. The R0 resection rate was 80·3 per cent. After a median follow-up of 56·5 months, the 5-year overall survival rate was 50 per cent in 2005-2012, markedly increased from 32 per cent in 1988-1996 (P = 0·044). Long-term success was associated with R0 resection (P = 0·017) and lack of secondary failure (P = 0·003). Some 125 patients (54·6 per cent) developed further recurrence at a median of 19·4 months after salvage surgery. Repeat operative rescue was feasible in 21 of 48 patients with local re-recurrence alone and in 17 of 77 with distant re-recurrence, with a median survival of 19·8 months after further recurrence., Conclusion: The long-term salvage potential for recurrent rectal cancer improved significantly over time, with the introduction of an individualized treatment algorithm of multimodal treatments and surgical salvage. Durable predictors of long-term success were R0 resection at salvage operation, avoidance of secondary failure, and feasibility of repeat rescue after re-recurrence., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Importance: Vascular leiomyosarcomas are a rare subtype of leiomyosarcomas that most commonly affect the inferior vena cava and account for 5% of all leiomyosarcomas. These tumors are aggressive malignant tumors for which adjuvant modalities have not shown increased efficacy compared with surgery., Objectives: To evaluate the outcomes of patients with vascular leiomyosarcoma and the association between vascular leiomyosarcomas and immunohistochemical molecular markers, to determine their potential prognostic and therapeutic utility., Design, Setting, and Participants: Retrospective medical record review of a cohort of 77 patients who presented to the University of Texas MD Anderson Cancer Center in Houston during the period from January 1993 to April 2012. Data were analyzed during the period from November 2012 to May 2015. All of the patients received a confirmed diagnosis of vascular leiomyosarcoma. Immunohistochemical studies for biomarkers were performed on a tissue microarray that included 26 primary specimens of vascular leiomyosarcoma., Main Outcomes and Measures: Demographic and clinical factors were evaluated to assess clinical course, patterns of recurrence, and survival outcomes for patients with primary vascular leiomyosarcoma. A univariate Cox proportional hazards model was used to correlate disease-specific survival and time to recurrence with potential prognostic indicators., Results: Sixty-three patients with localized disease who underwent surgical resection formed the study population, and their data were used for subsequent outcomes analysis. The median age at diagnosis was 58 years (range, 22-78 years). The majority of patients were female (41 patients [65%]) and white (51 patients [81%]). The 5-year disease-specific survival rate after tumor resection was 65%. The median time to local recurrence was 43 months, the median time to distant recurrence was 25 months, and the median time to concurrent local and distant recurrences was 15 months (P = .04). Strong expressions of cytoplasmic β-catenin (hazard ratio, 5.33 [95% CI, 0.97-29.30]; P = .06) and insulinlike growth factor 1 receptor (hazard ratio, 2.74 [95% CI, 1.14-6.56]; P = .02) were associated with inferior disease-specific survival., Conclusions and Relevance: Vascular leiomyosarcomas are aggressive malignant tumors, with high recurrence rates. Expressions of β-catenin and insulinlike growth factor 1 receptor were associated with poor disease-specific survival. Prospective studies should evaluate the clinical and therapeutic utility of these molecular markers.

Background: This study was performed to determine the maximum tolerated dose (MTD) of gemcitabine given concurrently with preoperative, fixed-dose external-beam radiation therapy (EBRT) for patients with resectable, high-risk extremity and trunk soft tissue sarcoma (STS)., Methods: Gemcitabine was administered on days 1, 8, 22, 29, 43, and 50 with EBRT (50 Gy in 25 fractions over 5 weeks). The gemcitabine MTD was determined with a toxicity severity weight method (TSWM) incorporating 6 toxicity types. The TSWM is a Bayesian procedure that choses each cohort's dose to have a posterior mean total toxicity burden closest to a predetermined clinician-defined target. Clinicopathologic and outcome data were also collected., Results: Thirty-six patients completed the study. According to the TSWM, the gemcitabine MTD was 700 mg/m(2). At this dose level, 4 patients (24%) experienced grade 4 toxicity; no toxicity-related deaths occurred. All tumors were resected with microscopically negative margins. Pathologic responses of >90% tumor necrosis were achieved in 17 patients (47%); 14 (39%) had complete responses. With a median follow-up of 6.2 years, the 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 85%, 80%, and 86%, respectively., Conclusions: The TSWM combines data from qualitatively different toxicities and can be used to determine the MTD for a drug given as part of a multimodality treatment. Neoadjuvant gemcitabine plus radiation therapy is feasible and safe in patients with high-risk extremity and trunk STS. Major pathologic responses can be achieved, and after complete resection, long-term clinical outcomes are encouraging., (© 2015 American Cancer Society.)

Crohn disease is a chronic inflammatory disorder involving the gastrointestinal tract, characterized by episodic flares and times of remission. Underlying structural damage occurs progressively, with recurrent bouts of inflammation. The diagnosis and management of this disease process is dependent on several clinical, laboratory, imaging, endoscopic, and histologic factors. In recent years, with the maturation of CT enterography, and MR enterography, imaging has played an increasingly important role in relation to Crohn Disease. In addition to these specialized examination modalities, ultrasound and routine CT have potential uses. Fluoroscopy, radiography, and nuclear medicine may be less beneficial depending on the clinical scenario. The imaging modality best suited to evaluating this disease may change, depending on the target population, severity of presentation, and specific clinical situation. This document presents seven clinical scenarios (variants) in both the adult and pediatric populations and rates the appropriateness of the available imaging options. They are summarized in a consolidated table, and the underlying rationale and supporting literature are presented in the accompanying narrative. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment., (Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with aggressive surgery and radiation therapy (RT) for retroperitoneal sarcomas (RPS)., Methods and Materials: We reviewed the medical records of 121 consecutive patients treated for RPS with surgery and RT between 1965 and 2012. The most common histology was liposarcoma (n = 42; 35%). The median follow-up was 100 months (range: 20-467 months). Eighty-six patients (71%) were treated for initial presentation of RPS, and 35 patients (29%) presented with and were treated for RPS recurrence. RT was preoperative in 88 patients (73%; median dose: 50.4 Gy) and postoperative in 33 patients (27%; median dose: 55 Gy)., Results: Five-year local control and overall survival rates were 56% and 57%, respectively. Two factors were associated with higher risk of any intra-abdominal recurrence at 5 years: positive or uncertain margins (58% vs 30% for negative margins, P < .001; hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.6-4.8) and disease recurrence after previous resection (76% vs 31% for de novo RPS, P < .001; HR: 4.4; 95% CI: 2.5-7.5). The 10-year complication rate was 5%, and RT-related complications were associated with postoperative RT (P < .001) and RT dose of ≥ 60 Gy (P < .001)., Conclusions: Intra-abdominal RPS recurrence continues to be a significant challenge despite the use of aggressive surgery and radiation therapy. Given the complications associated with postoperative radiation therapy, we recommend that preoperative radiation therapy is the preferred strategy when combined modality therapy is recommended., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To ascertain whether the National Quality Forum-endorsed time interval for adjuvant chemotherapy (AC) initiation optimizes patient outcome., Background: Delayed AC initiation for stage III colon cancer is associated with worse survival and the focus of a National Quality Forum quality metric (<4 months among patients aged <80 years)., Methods: Observational cohort study of patients with stage III colon cancer younger than 80 years within the National Cancer Data Base (2003-2010). The primary outcome was 5-year overall survival evaluated using multivariate Cox proportional hazards regression. Aggregate survival estimates for historical surgery-only controls from pooled National Surgical Adjuvant Breast and Bowel Project trial data were also used., Results: Among 51,331 patients (60.8 ± 11.6 years, 50.2% males, and 77.3% white), 76.3% received standard AC (≤ 2 months) and 21.6% delayed (>2 and <4 months) AC. Earlier AC was associated with better 5-year overall survival [standard AC, 69.8%; delayed AC, 62.0%; late AC (4-6 months), 51.4%; log-rank, P < 0.001]. The survival rate after late AC was similar to surgery alone (51.1%; Wilcoxon rank sum, P = 0.10). Compared with late AC, standard AC (hazard ratio, 0.62; 95% confidence interval, 0.54-0.72) and delayed AC (hazard ratio, 0.77; 95% confidence interval, 0.66-0.89) significantly decreased risk of death. Risk of death was also lower for standard AC compared to delayed AC (hazard ratio, 0.81; 95% confidence interval, 0.77-0.86)., Conclusions: One in 5 patients with stage III colon cancer initiates AC within the National Quality Forum-endorsed interval, but does not derive the full benefit. These data support strengthening current quality improvement initiatives and colon cancer treatment guidelines to encourage AC initiation within 2 months of resection when possible, but not beyond 4 months.

Background: We investigated outcomes by primary tumor type in patients who underwent resection of liver metastases from gastrointestinal stromal tumors (GIST), leiomyosarcomas, and other sarcomas., Method: Our institutional liver database was used to identify patients who underwent resection from 1998 through 2013. Histopathological, clinical, and survival data were analyzed., Results: One hundred forty-six patients underwent resection of liver metastases from GIST (n = 49), leiomyosarcomas (n = 47), or other sarcomas (n = 50). The 5-year overall survival (OS) rates in patients with GIST, leiomyosarcomas, and other sarcomas were 55.3, 48.4, and 44.9%, respectively, and the 10-year OS rates were 52.5, 9.2, and 23.0%, respectively. The 5-year recurrence-free survival (RFS) rate was better for GIST (35.7%; p = 0.003) than for leiomyosarcomas (3.4%) and other sarcomas (21.4%). Lung recurrence was more common for leiomyosarcomas (36% of patients; p < 0.0001) than for other sarcomas (12%) and GIST (2%). For GIST, the findings support a benefit of imatinib regarding the 5-year RFS rate compared to resection alone (47.1 vs. 9.5%; p = 0.013). For leiomyosarcoma, primary tumor location did not affect the 5-year RFS rate (intraabdominal 14.5%; other location 0%; p = 0.182)., Conclusion: Liver metastases from GIST, leiomyosarcomas, and other sarcomas should be assessed separately as their survival and recurrence patterns are different. This is especially important for GIST, for which imatinib is now available.

Importance: Colon cancer is increasing among adults younger than 50 years. However, the prognosis of young-onset colon cancer remains poorly defined given significant age-related demographic, disease, and treatment differences., Objective: To define stage-specific treatments and prognosis of colon cancer diagnosed in young adults (ages 18-49 years) vs older adults (ages 65-75 years) outside of the clinical trial setting while accounting for real-world age-related variations in patient, tumor, and treatment factors., Design, Setting, and Participants: A nationwide cohort study was conducted among US hospitals accredited by the American College of Surgeons Commission on Cancer. Participants were 13 102 patients diagnosed as having young-onset colon adenocarcinoma aged 18 to 49 years and 37 007 patients diagnosed as having later-onset colon adenocarcinoma aged 65 to 75 years treated between January 1, 2003, and December 31, 2005, and reported to the National Cancer Data Base., Exposures: Patients who underwent surgical resection and postoperative systemic chemotherapy of curative intent., Main Outcomes and Measures: The primary end point was stage-specific relative survival, an objective measure of survival among patients with cancer, adjusting for baseline mortality rates and independent of the data on cause of death. The secondary end point was stage-specific likelihood of receiving postoperative systemic chemotherapy., Results: Most young-onset colon cancer was initially seen at advanced stages (61.8% had stage III or IV). After adjusting for patient-related and tumor-related factors, young patients were more likely to receive systemic chemotherapy, particularly multiagent regimens, at all stages relative to those with later-onset disease. These odds ratios were 2.88 (95% CI, 2.21-3.77) for stage I, 3.93 (95% CI, 3.58-4.31) for stage II, 2.42 (95% CI, 2.18-2.68) for stage III, and 2.74 (95% CI, 2.44-3.07) for stage IV. The significantly more intense treatments received by younger patients were unmatched by any survival gain, which was nil for stage II (relative risk, 0.90; 95% CI, 0.69-1.17) and marginal for stage III (relative risk, 0.89; 95% CI, 0.81-0.97) and stage IV (relative risk, 0.84; 95% CI, 0.79-0.90)., Conclusions and Relevance: Young adults with colon cancer received significantly more postoperative systemic chemotherapy at all stages, but they experienced only minimal gain in adjusted survival compared with their older counterparts who received less treatment. This mismatch suggests that attention should be given to long-term cancer survivorship in young adults with colon cancer because they likely face survivorship needs that are distinct from those of their older counterparts.

Importance: With the advent of effective modern chemotherapeutic and biologic agents, primary tumor resection for patients with stage IV colorectal cancer (CRC) may not be routinely necessary., Objective: To evaluate the secular patterns of primary tumor resection use in stage IV CRC in the United States., Design, Setting, and Participants: A retrospective cohort study using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results CRC registry. Demographic and clinical factors were compared for 64,157 patients diagnosed with stage IV colon or rectal cancer from January 1, 1988, through December 31, 2010, who had undergone primary tumor resection and those who had not. Rates of primary tumor resection and median relative survival were calculated for each year. Joinpoint regression analysis was used to determine when a significant change in trend in the primary tumor resection rate had occurred. Logistic regression analysis was used to assess factors associated with primary tumor resection., Main Outcomes and Measures: Difference in primary tumor resection rates over time., Results: Of the 64,157 patients with stage IV CRC, 43,273 (67.4%) had undergone primary tumor resection. The annual rate of primary tumor resection decreased from 74.5% in 1988 to 57.4% in 2010 (P<.001), and a significant annual percentage change occurred between 1998-2001 and 2001-2010 (-0.41% vs -2.39%; P<.001). Factors associated with primary tumor resection were age younger than 50 years, female sex, being married, higher tumor grade, and presence of colon tumors. Median relative survival rate improved from 8.6% in 1988 to 17.8% in 2009 (P<.001); the annual percentage change was 2.18% in 1988-2001 and 5.43% in 1996-2009 (P<.001)., Conclusions and Relevance: The majority of patients with stage IV CRC had undergone primary tumor resection but, beginning in 2001, a trend toward fewer primary tumor resections was seen. Despite the decreasing primary tumor resection rate, patient survival rates improved. However, primary tumor resection may still be overused, and current treatment practices lag behind evidence-based treatment guidelines.

Background: With advances in multimodality therapy, colorectal cancer survivors are living longer. However, little is known about the quality of their long-term survival. We investigated the functional outcomes and symptoms among long-term survivors., Methods: A cross-sectional study of 1,215 long-term (>5 years) colorectal cancer survivors was conducted using a validated disease-specific questionnaire. Younger onset survivors (18-50 years) were matched 1:2 to later onset survivors (>50 years). Standardized mean scores were compared using one-way ANOVA. Key patient and treatment factors that impact function and symptoms were assessed by multivariate linear regression., Results: Eight hundred thirty survivors responded at an interval of 10.8 ± 3 years from diagnosis (68% response rate). Younger onset survivors underwent more surgery (97.9 vs. 93.6%, P < 0.001) and received more chemotherapy (86.1 vs. 77.7%, P = 0.004). Anxiety, body image, sexual dysfunction, embarrassment by bowel movements, micturition problems, and impotence were significant concerns. Younger onset survivors reported worse anxiety, body image, and embarrassment with bowel movements, whereas later onset survivors highlighted sexual dysfunction, micturition problems, and impotence. Age at diagnosis was a key independent determinant of long-term function and symptoms., Conclusion: Long-term survivors of CRC face ongoing functional deficits and symptoms, and their survivorship experience differs by age. Age at diagnosis should serve as a basis for tailored, personalized survivorship care plans.

Purpose: Margin positivity after rectal cancer resection is associated with poorer outcomes. We previously developed an instrument for calculating hospital risk-adjusted margin positivity rate (RAMP) that allows identification of performance-based outliers and may represent a rectal cancer surgery quality metric., Methods: This was an observational cohort study of patients with rectal cancer within the National Cancer Data Base (2003 to 2005). Hospital performance was categorized as low outlier (better than expected), high outlier (worse than expected), or non-RAMP outlier using standard observed-to-expected methodology. The association between outlier status and overall risk of death at 5 years was evaluated using Cox shared frailty modeling., Results: Among 32,354 patients with cancer (mean age, 63.8 +/-13.2 years; 56.7% male; 87.3% white) treated at 1,349 hospitals (4.9% high outlier, 0.7% low outlier), 5.6% of patients were treated at high outliers and 3.0% were treated at low outliers. Various structural (academic status and volume), process (pathologic nodal evaluation and neoadjuvant radiation therapy use), and outcome (sphincter preservation, readmission, and 30-day postoperative mortality) measures were significantly associated with outlier status. Five-year overall survival was better at low outliers (79.9%) compared with high outliers (64.9%) and nonoutliers (68.9%; log-rank test, P < .001). Risk of death was lower at low outliers compared with high outliers (hazard ratio [HR], 0.61; 95% CI, 0.50 to 0.75) and nonoutliers (HR, 0.69; 95% CI, 0.57 to 0.83). Risk of death was higher at high outliers compared with nonoutliers (HR, 1.12; 95% CI, 1.03 to 1.23)., Conclusion: Hospital RAMP outlier status is a rectal cancer surgery composite metric that reliably captures hospital quality across all levels of care and could be integrated into existing quality improvement initiatives for hospital performance.

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.

Colorectal cancer is the third leading cause of cancer deaths in the United States. Most colorectal cancers can be prevented by detecting and removing the precursor adenomatous polyp. Individual risk factors for the development of colorectal cancer will influence the particular choice of screening tool. CT colonography (CTC) is the primary imaging test for colorectal cancer screening in average-risk individuals, whereas the double-contrast barium enema (DCBE) is now considered to be a test that may be appropriate, particularly in settings where CTC is unavailable. Single-contrast barium enema has a lower performance profile and is indicated for screening only when CTC and DCBE are not available. CTC is also the preferred test for colon evaluation following an incomplete colonoscopy. Imaging tests including CTC and DCBE are not indicated for colorectal cancer screening in high-risk patients with polyposis syndromes or inflammatory bowel disease. This paper presents the updated colorectal cancer imaging test ratings and is the result of evidence-based consensus by the ACR Appropriateness Criteria Expert Panel on Gastrointestinal Imaging. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment., (Copyright © 2014 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: We evaluated the role of intraoperative radiation therapy (IORT) during radical resection of locally advanced colorectal cancer (CRC)., Methods: We retrospectively evaluated all patients with CRC treated with IORT at our institution from 2001 to 2010. IORT was delivered using high-dose-rate brachytherapy (median 12.5-Gy). We analyzed factors associated with postoperative morbidity, local control (LC), and overall survival (OS)., Results: One hundred patients were evaluated with 70% received IORT for recurrent tumors. R0 resection rate was 58%. Postoperative Grade ≥3 complications (33%) were independently associated with transfusions ≥3 units packed red blood cells (P = 0.016) and body mass index (BMI) ≥35 (P = 0.0499). Eighty-two patients underwent external beam radiation therapy (EBRT) before IORT. Five-year LC was 94%, for primary and 56%, for recurrent tumors, respectively (P = 0.007). Microscopic positive (R1) margins were not associated with LC (P = 0.316). BMI ≥30 (P = 0.048) and post-discharge complications (P = 0.041) were independent risk factors for worse LC. Median post-IORT OS was 67.7 (95% CI 51.1-84.3) months for all patients., Conclusion: For patients with primary or recurrent locally advanced CRC, treatment with radical surgery and IORT achieved excellent LC outcomes irrespective of microscopic margin status. IORT may be indicated for tumors suspected to have close or positive microscopic margins., (© 2014 Wiley Periodicals, Inc.)

Purpose: Health care access and advanced cancer stage are associated with oncologic outcomes for numerous common cancers. However, the impact of patient travel distance to health care on stage at diagnosis has not been well characterized., Methods: This study used a historical cohort of patients with colon cancer in the National Cancer Data Base from 2003 through 2010. The primary outcome, stage at diagnosis, was evaluated using hierarchical regression modeling. A secondary outcome was time to receipt of initial therapy that was evaluated using Cox shared frailty modeling., Results: Among 296,474 patients with colon cancer (mean age, 68 ± 13.6 years; 47.6% male; 78.5% white), 3.9% traveled ≥ 50 miles to the diagnosing facility. Fewer black patients, patients with higher income, and patients with lower education traveled longer distances (trend test P < .001 for all). Patients traveling ≥ 50 miles were more likely to present with metastatic disease compared with those traveling less than 12.5 miles (odds ratio [OR], 1.18; 95% CI, 1.12 to 1.24) or 12.5 to 49.9 miles (OR, 1.18; 95% CI, 1.12 to 1.24). In sensitivity analyses, the association was robust to alternate methods of modeling travel distance (quintile stratification or continuous). Travel distance ≥ 50 miles was also associated with a higher likelihood of earlier initiation of therapy compared with travel distance of less than 12.5 miles (hazard ratio [HR], 1.10; 95% CI, 1.08 to 1.13) or 12.5 to 49.9 miles (HR, 1.11; 95% CI, 1.08 to 1.13)., Conclusion: Advanced colon cancer stage at diagnosis is associated with patient travel distance to health care, which may be a barrier to early cancer screening. Health care reform efforts designed to address only insurance coverage may not mitigate disparities based on difficulties accessing cancer care.

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.

Importance: The circumferential resection margin is the primary determinant of local recurrence and a major factor in survival in rectal cancer. Neither chemotherapy nor chemoradiation compensates for a margin positive for cancer., Objective: To identify treatment-related factors associated with hospital margin-positive resection and to develop a tool that could be used by individual hospitals to assess their outcomes based on their unique mix of patient and tumor characteristics., Design: Retrospective review of the National Cancer Data Base, 1998-2007., Settings: Community and academic/research hospitals., Participants: Individuals with histologically confirmed localized rectal/rectosigmoid adenocarcinoma., Exposure: All individuals underwent radical resection for rectal cancer with or without neoadjuvant therapy., Main Outcomes and Measures: Rate of margin positivity determined and adjusted for patient- and tumor-related factors to calculate expected margin positivity per hospital. An observed to expected ratio was calculated based on patient- and tumor-related factors to identify treatment-associated variation., Results: The overall margin-positive resection rate was 5.2%. Patients with margins positive for cancer were more likely to be older, male, and African American; not have private insurance; and have their cancer diagnosed later in the study period. Associated tumor-related factors include rectal location, higher American Joint Committee on Cancer stage, signet/mucinous histology, and poor/undifferentiated grade. Among hospitals that were significantly low outliers, 47% were comprehensive community hospitals, and 43.9% were academic/research hospitals; of those that were significantly high outliers, 52.3% were comprehensive community hospitals, and 17.8% were academic/research hospitals. High-volume centers made up 80% of significantly low outlier hospitals and 17% of significantly high outlier hospitals. The rates of chemotherapy and radiation were similar, but low outlier hospitals gave more neoadjuvant radiation (26.3% vs 17%)., Conclusions and Relevance: After adjustment for patient- and tumor-related factors, we identified both low and high outlier hospitals for margin positivity at resection, as well as potentially modifiable risk factors. The nomogram created in this model allows for the evaluation of observed and expected event rates for individual hospitals, providing a hospital self-assessment tool for identifying targets for improvement.

Purpose: To evaluate outcomes of conservative surgery and radiation therapy (RT) treatment in patients with dermatofibrosarcoma protuberans., Methods and Materials: We retrospectively reviewed the medical records of 53 consecutive dermatofibrosarcoma protuberans patients treated with surgery and preoperative or postoperative radiation therapy between 1972 and 2010. Median tumor size was 4 cm (range, 1-25 cm). Seven patients (13%) were treated with preoperative RT (50-50.4 Gy) and 46 patients (87%) with postoperative RT (60-66 Gy). Of the 46 patients receiving postoperative radiation, 3 (7%) had gross disease, 14 (30%) positive margins, 26 (57%) negative margins, and 3 (7%) uncertain margin status. Radiation dose ranged from 50 to 66 Gy (median dose, 60 Gy)., Results: At a median follow-up time of 6.5 years (range, 0.5 months-23.5 years), 2 patients (4%) had disease recurrence, and 3 patients (6%) had died. Actuarial overall survival was 98% at both 5 and 10 years. Local control was 98% and 93% at 5 and 10 years, respectively. Disease-free survival was 98% and 93% at 5 and 10 years, respectively. The presence of fibrosarcomatous change was not associated with increased risk of local or distant relapse (P=.43). One of the patients with a local recurrence had gross residual disease at the time of RT and despite RT to 65 Gy developed both an in-field recurrence and a nodal and distant recurrence 3 months after RT. The other patient with local recurrence was found to have in-field recurrence 10 years after initial treatment. Thirteen percent of patients had an RT complication at 5 and 10 years, and 9% had a moderate or severe complication at 5 and 10 years., Conclusions: Dermatofibrosarcoma protuberans is a radioresponsive disease with excellent local control after conservative surgery and radiation therapy. Adjuvant RT should be considered for patients with large or recurrent tumors or when attempts at wide surgical margins would result in significant morbidity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The objective of the current study was to examine the impact of adherence to guidelines on stage-specific survival outcomes in patients with stage III and high-risk stage II colon cancer. The National Comprehensive Cancer Network (NCCN) has established working, expert consensus, and evidence-based guidelines for organ-specific cancer care, including care of patients with colon cancer., Methods: Patients who were diagnosed with colon adenocarcinoma between 1998 and 2002 were selected from within the National Cancer Data Base. The cohort was limited to patients who received their first course of treatment at the reporting facility. Pathologic variables, including tumor depth, lymph node status, and evidence of metastatic disease, were used to restage patients, and the patients were divided into low-risk and high-risk categories on the basis of criteria defined by the NCCN. Relative survival rates were calculated for the entire cohort, stratified according to adherence versus nonadherence to NCCN treatment guidelines., Results: In univariate analysis of treatment adherence patterns for both patient subgroups (high-risk stage II and stage III), several factors were associated with a higher rate of nonadherence in both groups, including older age (P < .001); Medicaid, Medicare, or uninsured status versus private insurance (P < .001); and subsequent treatment at a facility other than the facility at which the cancer was first diagnosed (P < .001). In multivariate analysis, multiple factors were associated with differences in relative survival, although analyses that included the year of diagnosis did not demonstrate significant differences over time., Conclusions: The current study documented practice patterns in a heterogeneous population of patients with colon cancer and demonstrated a survival benefit for patients with stage III and high-risk stage II colon cancer who received treatment that adhered to NCCN guidelines. These data validate the current NCCN practice guidelines for colon cancer and support the concept of guideline-based metrics that can be compared across institutions to assess the quality of cancer care and to compare the quality of cancer care among institutions., (Copyright © 2012 American Cancer Society.)

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: Neuroendocrine tumors (NETs) of the appendix include malignant carcinoid tumor (MCT), goblet cell carcinoid (GCT), and composite goblet cell carcinoid-adenocarcinoma (CGCC-A)., Methods: We compared characteristics and outcomes of these histologic subtypes. Patients with appendiceal NETs were identified from the National Cancer Database (1998-2007). Descriptive statistics were used to compare cohorts and associations between clinicopathologic factors and overall survival (OS) were examined using Cox proportional hazards models., Results: A total of 2,812 patients with appendiceal NETs were identified. The most common histologic subtype was GCT (59.6%), followed by MCT (32.1%), CGCC-A (6.9%), and others (1.4%). CGCC-A had a significantly higher incidence of lymph node metastases (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.1-4.8) and distant metastases (OR, 6.0; 95% CI = 3.8-9.3) than GCT. The 5-year OS was 86.3% (95% CI, 81.4-89.9) for MCT, 77.6% (95% CI, 74.0-80.8) for GCT, and 56.3% (95% CI, 42.1-68.4) for CGCC-A (P < 0.0001)., Conclusion: Appendiceal NETs represent a spectrum of disease with varying malignant potential: MCT (low), GCT (intermediate), and CGCC-A (high). GCTs represent the most common subtype, whereas CGCC-As place the patient at highest risk for regional and distant metastases and have the worst prognosis., (Copyright © 2012 Wiley Periodicals, Inc.)

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.

Background: Local excision, alone or in combination with chemoradiation, is increasingly considered for rectal cancer. Higher risks of disease recurrence have been demonstrated after local excision., Objective: The aim of this study was to examine the outcomes of current-era multimodality salvage for recurrent rectal cancer after local excision., Design: This was a single-institutional retrospective study., Settings: This study was conducted at a tertiary-referral cancer center between 1993 and 2011., Patients: Forty-six patients with recurrent rectal cancer after initial local excision were included., Intervention: Multimodality salvage treatment was performed as appropriate., Main Outcome Measures: The primary outcomes measured were the pattern of disease recurrence, salvage treatments, and resultant overall and re-recurrence-free survival., Results: After the initial local excision, recurrent disease was diagnosed after a median interval of 1.9 years: local/regionally in 67%, distantly in 18%, and both in 15%. Four patients (9%) had recurrence that was unsalvageable, 2 (4%) declined treatment, and 40 (87%) underwent surgical salvage. Preoperative chemoradiation was given in 30 (75%) patients. The R0 resection rate was 80%, requiring multivisceral resection (33%), total pelvic exenteration (5%), and metastasectomy (25%). The rate of sphincter preservation was 33%, and perioperative morbidity was 50%. The first site of failure after salvage was distant in 38% and was local only in 10%. The 5-year overall and 3-year re-recurrence-free survival were 63% and 43%. Pathologic stage at initial local excision, receipt of neoadjuvant chemoradiation before local excision, recurrence pattern after local excision, pathologic stage at salvage, and R0 resection at salvage influenced re-recurrence-free survival., Limitations: This study was limited by the referral and selection biases inherent in a small study cohort., Conclusions: Failure after local excision for rectal cancer may not be salvageable. When feasible, multimodality treatment, including multivisceral resection, pelvic irradiation, and chemotherapy, was associated with potentially lasting treatment-related morbidities and only modest success in long-term disease control. These findings should be compared with the expected stage-specific outcomes of standard proctectomy for early-stage rectal cancer, when local excision is being considered.

Purpose: The aim of this study was to assess preoperative biopsy utilization for patients with soft tissue sarcoma (STS) of ≥5 cm in size and whether or not preoperative biopsy was associated with fewer surgical procedures to adequately treat these tumors., Methods: We identified 899 patients from the Surveillance, Epidemiology, and End Results-Medicare database with a diagnosis of STS and who underwent surgical resection of their tumors between 1992 and 2006. We used diagnosis and procedure codes from claims data to identify which patients had a biopsy performed and the corresponding number of surgical procedures for each patient. Multivariate logistic regression analyses were carried out to assess the influence of patient, tumor, and sociodemographic characteristics on performance of biopsy and the likelihood of multiple STS operations., Results: Only 40.6% of patients with tumors of ≥5 cm in size underwent biopsy as part of initial management of their STS. In multivariate analysis, biopsy utilization varied significantly by sex, tumor size, grade, and geographic region. After adjusting for patient, tumor, and sociodemographic characteristics, receipt of a biopsy was the only factor significantly associated with reduced likelihood of multiple STS operations (odds ratio=0.34, 95% confidence interval, 0.24-0.49)., Conclusion: Preoperative biopsy utilization among Medicare beneficiaries undergoing surgery for STS of ≥5 cm in size is low. Performance of a biopsy for patients with soft tissue tumors of ≥5 cm in size is associated with a decreased likelihood of a patient undergoing multiple surgeries for treatment of STS.

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.

Purpose: Neoadjuvant chemoradiotherapy for rectal cancer is associated with improved local control and may result in complete tumor response. Associations between tumor response and disease control following radical resection should be established before tumor response is used to evaluate treatment strategies. The purpose of this study was to assess and compare oncologic outcomes associated with the degree of pathologic response after chemoradiotherapy., Patients and Methods: All patients with locally advanced (cT3-4 or cN+ by endorectal ultrasonography, computed tomography, or magnetic resonance imaging) rectal carcinoma diagnosed from 1993 to 2008 at our institution and treated with preoperative chemoradiotherapy and radical resection were identified, and their records were retrospectively reviewed. The median radiation dose was 50.4 Gy with concurrent chemotherapy. Recurrence-free survival (RFS), distant metastasis (DM), and local recurrence (LR) rates were compared among patients with complete (ypT0N0), intermediate (ypT1-2N0), or poor (ypT3-4 or N+) response by using Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression., Results: In all, 725 patients were classified by tumor response: complete (131; 18.1%), intermediate (210; 29.0%), and poor (384; 53.0%). Age, sex, cN stage, and tumor location were not related to tumor response. Tumor response (complete v intermediate v poor) was associated with 5-year RFS (90.5% v 78.7% v 58.5%; P < .001), 5-year DM rates (7.0% v 10.1% v 26.5%; P < .001), and 5-year LR only rates (0% v 1.4% v 4.4%; P = .002)., Conclusion: Treatment response to neoadjuvant chemoradiotherapy among patients with locally advanced rectal cancer undergoing radical resection is an early surrogate marker and correlate to oncologic outcomes. These data provide guidance with response-stratified oncologic benchmarks for comparisons of novel treatment strategies.

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.

Purpose: Adherence to evidence-based treatment guidelines has been proposed as a measure of cancer care quality. We sought to determine rates of and factors associated with adherence to the National Comprehensive Cancer Network (NCCN) treatment guidelines for colon cancer., Patients and Methods: Patients within the National Cancer Data Base treated for colon adenocarcinoma (2003 to 2007) were identified. Adherence to stage-specific NCCN guidelines was determined based on disease stage. Hierarchical regression analyses were performed to identify factors predictive of adherence, overtreatment, and undertreatment., Results: A total of 173,243 patients were included in the final cohort, 123,953 (71%) of whom were treated according to NCCN guidelines. Patients with stage I disease were more likely to receive guideline-based treatment (96%) than patients with stage II (low risk, 66%; high risk, 36%), III (71%), or IV (73%) disease (P < .001). Adherence to consensus-based guidelines increased over time. Factors associated with adherence across all stages included age, Charlson-Deyo comorbidity index score, later year of diagnosis, and insurance status. Among patients with high-risk stage II or stage III disease, older patients with pre-existing comorbidities and patients with lower socioeconomic status were less likely to be offered adjuvant chemotherapy. Among patients with stage I and II disease, young, healthy patients were more likely to be recommended chemotherapy, in discordance with NCCN guidelines., Conclusion: Significant variation exists in the treatment of colon cancer, particularly in treatment of high-risk stage II and stage III disease. The impact of nonadherence to guidelines on patient outcomes needs to be further elucidated.

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.

Metaplastic sarcomatoid carcinoma (MSC) of the breast is usually triple receptor (ER, PR, and HER2) negative and is not currently recognized as being more aggressive than other triple receptor-negative breast cancers. We reviewed archival tissue sections from surgical resection specimens of 47 patients with MSC of the breast and evaluated the association between various clinicopathologic features and patient survival. We also evaluated the clinical outcome of MSC patients compared to a control group of patients with triple receptor-negative invasive breast carcinoma matched for patient age, clinical stage, tumor grade, treatment with chemotherapy, and treatment with radiation therapy. Factors independently associated with decreased disease-free survival among patients with stage I-III MSC of the breast were patient age > 50 years (P = 0.029) and the presence of nodal macrometastases (P = 0.003). In early-stage (stage I-II) MSC, decreased disease-free survival was observed for patients with a sarcomatoid component comprising ≥ 95% of the tumor (P = 0.032), but tumor size was the only independent adverse prognostic factor in early-stage patients (P = 0.043). Compared to a control group of triple receptor-negative patients, patients with stage I-III MSC had decreased disease-free survival (two-sided log rank, P = 0.018). Five-year disease-free survival was 44 ± 8% versus 74 ± 7% for patients with MSC versus triple receptor-negative breast cancer, respectively. We conclude that MSC of the breast appears more aggressive than other triple receptor-negative breast cancers.

Objective: To identify cancer-specific predictors of postoperative surgical site infection (SSI), and to develop a risk-stratification prognostic tool and compare its performance with traditional measures., Background: The incidence and risk factors for SSI in cancer patients are unknown; current risk-stratification tools are not cancer-specific., Methods: A prospective cohort study of patients undergoing elective operations (n = 503) at a tertiary cancer center was conducted. SSI was assessed using postdischarge active surveillance. Multivariate logistic regression analyses were performed to identify predictors of SSI, and β-coefficients were used to create a scoring system. The sum of these was used to create a Risk of Surgical Site Infection in Cancer (RSSIC) score. The RSSIC was validated using bootstrapping techniques, and its discrimination was compared with the National Nosocomial Infection Surveillance (NNIS) risk index., Results: The 30-day SSI incidence was 24%. Significant predictors of SSI included preoperative chemotherapy (OR = 1.94 [95% CI, 1.16-3.25]), clean-contaminated wounds (OR = 2.1 [95% CI, 1.24-3.55]), operative time ≥2 hours (OR = 1.75 [95% CI, 1.01-3.04]) and ≥4 hours (OR = 2.24 [95% CI, 1.22-4.1]), and surgical site: groin (OR = 4.65 [95% CI, 1.69-12.83]), and head/neck (OR = 0.12 [95% CI, 0.02-0.89]). The RSSIC score stratified patients into 4 risk strata for SSI. The performance of this score exceeded that of the NNIS score (AUC = 0.70 vs. 0.63, respectively; P = 0.01)., Conclusion: SSIs are common following cancer surgery. Preoperative chemotherapy, in addition to other common risk factors, was identified as a significant predictor for SSI in cancer patients. The RSSIC improves risk-stratification of cancer patients and identifies those that may benefit from more aggressive or novel preventive strategies.

Background: Preoperative chemoradiation for rectal cancer can decrease the number of evaluable lymph nodes. Hence, the prognostic role of lymph node evaluation in patients with rectal cancer who receive preoperative chemoradiation is unclear. The authors of this report evaluated the prognostic impact of the number of lymph nodes examined in patients with rectal cancer who had negative lymph nodes based on the pathologic extent of disease (ypN0) after they received preoperative chemoradiation., Methods: Between 1990 and 2004, 372 patients with nonmetastatic rectal adenocarcinoma received preoperative chemoradiation followed by mesorectal excision and had ypN0 disease. The median radiation dose was 45 gray, and 68% of patients received adjuvant chemotherapy., Results: Patients had a median of 7 lymph nodes examined after preoperative chemoradiation. Compared with patients who had ≤7 lymph nodes examined, patients who had >7 lymph nodes had higher 5-year rates of freedom from relapse (86% vs 72%; log-rank P = .005) and cancer-specific survival (95% vs 86%; log-rank P = .0004), but no significant difference was observed in the overall survival rate (87% vs 81%; log-rank P = .07). Multivariate Cox proportional models demonstrated that patients who had >7 lymph nodes examined had a significantly lower risk of relapse (hazard ratio [HR], 0.39; P = .003) and death from rectal cancer (HR, 0.45; P = .04) but a similar risk of all-cause mortality (HR, 0.75; 95% CI, 0.46-1.20; P = .23) compared with patients who had ≤7 lymph nodes examined., Conclusions: The number of lymph nodes examined was associated independently with disease relapse and cancer-specific survival in patients with rectal cancer who had ypN0 disease after receiving preoperative chemoradiation. Hence, the authors concluded that the number of negative lymph nodes examined may be a prognostic factor in patients with rectal cancer who receive preoperative chemoradiation., (Copyright © 2011 American Cancer Society.)

Background: Although the use of SSM is becoming more common, there are few data on long-term, local-regional, and distant recurrence rates after treatment. The purpose of this study was to examine the rates of local, regional, and systemic recurrence, and survival in breast cancer patients who underwent skin-sparing mastectomy (SSM) or conventional mastectomy (CM) at our institution., Methods: Patients with stage 0 to III unilateral breast cancer who underwent total mastectomy at our center from 2000 to 2005 were included in this study. Kaplan-Meier curves were calculated, and the log-rank test was used to evaluate the differences between overall and disease-free survival rates in the 2 groups., Results: Of 1810 patients, 799 (44.1%) underwent SSM and 1011 (55.9%) underwent CM. Patients who underwent CM were older (58.3 vs 49.3 years, P<.0001) and were more likely to have stage IIB or III disease (53.0% vs 31.8%, P<.0001). Significantly more patients in the CM group received neoadjuvant chemotherapy and adjuvant radiation therapy (P<.0001). At a median follow-up of 53 months, 119 patients (6.6%) had local, regional, or systemic recurrences. The local, regional, and systemic recurrence rates did not differ significantly between the SSM and CM groups. After adjusting for clinical TNM stage and age, disease-free survival rates between the SSM and CM groups did not differ significantly., Conclusions: SSM is an acceptable treatment option for patients who are candidates for immediate breast reconstruction. Local-regional recurrence rates are similar to those of patients undergoing CM. Cancer 2011. © 2010 American Cancer Society., (Copyright © 2010 American Cancer Society.)

Objective: To classify ipsilateral breast tumor recurrences (IBTR) as either new primary tumors (NP) or true local recurrence (TR). We utilized 2 different methods and compared sensitivities and specificities between them. Our goal was to determine whether distinguishing NP from TR had prognostic value., Background: After breast-conservation therapy, IBTR may be classified into 2 distinct types (NP and TR). Studies have attempted to classify IBTR by using tumor location, histologic subtype, DNA flow cytometry data, or gene-expression profiling data., Methods: A total of 447 (7.9%) of 5660 patients undergoing breast-conservation therapy from 1970 to 2005 experienced IBTR. Clinical data from 397 patients were available for review. We classified IBTRs as NP or TR on the basis of either tumor location and histologic subtype (method 1) or tumor location, histologic subtype, estrogen receptor status and human epidermal growth factor receptor 2 status (method 2). Kaplan-Meier curves and log-rank tests were used to evaluate overall and disease-specific survival differences between the 2 groups. Classification methods were validated by calculating sensitivity and specificity values using a Bayesian method., Results: Of 397 patients, 196 (49.4%) were classified as NP by method 1 and 212 (53.4%) were classified as NP by method 2. The sensitivity and specificity values were 0.812 and 0.867 for method 1 and 0.870 and 0.800 for method 2, respectively. Regardless of method used, patients classified as NP developed contralateral breast carcinoma more often but had better 10-year overall and disease-specific survival rates than those classified as TR. Patients with TR were more likely to develop metastatic disease after IBTR., Conclusion: Ipsilateral breast tumor recurrences classified as TR and NP had clinically different features, suggesting that classifying IBTR may provide clinically significant data for the management of IBTR.

Background: Primary soft-tissue sarcomas account for less than 1 percent of all breast malignancies. Many of these are associated with prior radiation therapy. Few studies have evaluated this patient population. The purpose of this study was to examine reconstruction techniques and outcomes in a cohort of patients with breast sarcoma to elucidate the optimal type and timing of reconstruction., Methods: The authors conducted a retrospective review of all patients diagnosed and treated for soft-tissue breast sarcomas between July 1, 1988, and December 9, 2009, at a tertiary cancer center. Data collected included demographics, histology, oncologic and reconstructive treatment, and clinical outcomes., Results: Twenty-three breast sarcoma patients underwent 24 reconstructions. The mean age at diagnosis was 42 years (range, 17 to 78 years). The most common histologic finding was angiosarcoma; six of the 11 angiosarcomas developed following irradiation for either breast carcinoma or lymphoma. The median follow-up was 44 months. Twenty patients were alive through the follow-up period. Reconstruction was immediate in 20 cases and delayed in four. The reconstruction used autologous tissue in 16 cases, implants in five, and both in three. All patients who underwent irradiation during treatment underwent autologous tissue reconstruction. Surgical complications included implant displacement, tissue expander displacement, total flap loss, seroma, implant exposure, and partial skin graft loss., Conclusions: Soft-tissue breast sarcomas are uncommon and demand aggressive, multimodal treatment and well-planned reconstruction. Most sarcoma patients receive radiotherapy; to minimize complications, we recommend delayed autologous reconstruction after completion of radiotherapy.

Background: A wide range of false-negative rates has been reported for sentinel lymph node (SLN) biopsy after preoperative chemotherapy. The purpose of this study was to determine whether histologic findings in negative SLNs after preoperative chemotherapy are helpful in assessing the accuracy of SLN biopsy in patients with confirmed lymph node-positive disease before treatment., Methods: Eighty-six patients with confirmed lymph node-positive disease at presentation underwent successful SLN biopsy and axillary dissection after preoperative chemotherapy at a single institution between 1994 and 2007. Available hematoxylin and eosin-stained sections from patients with negative SLNs were reviewed, and associations between histologic findings in the negative SLNs and SLN status (true negative vs false negative) were evaluated., Results: Forty-seven (55%) patients had at least 1 positive SLN, and 39 (45%) patients had negative SLNs. The false-negative rate was 22%, and the negative predictive value was 67%. The negative SLNs from 17 of 34 patients with available slides had focal areas of fibrosis, some with associated foamy parenchymal histiocytes, fat necrosis, or calcification. These histologic findings occurred in 15 (65%) of 23 patients with true-negative SLNs and in only 2 (18%) of 11 patients with false-negative SLNs (P = .03, Fisher exact test, 2-tailed). The lack of these histologic changes had a sensitivity and specificity for identifying a false-negative SLN of 82% and 65%, respectively., Conclusions: Absence of treatment effect in SLNs after chemotherapy in patients with lymph node-positive disease at initial presentation has good sensitivity but low specificity for identifying a false-negative SLN.

Purpose: To retrospectively determine rates of toxicity, freedom from local progression, and survival in rectal cancer patients treated with reirradiation., Methods and Materials: Between February 2001 and February 2005, 50 patients with a history of pelvic radiotherapy were treated with hyperfractionated accelerated radiotherapy for primary (n = 2 patients) or recurrent (n = 48 patients) rectal adenocarcinoma. Patients were treated with 150-cGy fractions twice daily, with a total dose of 39 Gy (n = 47 patients) if the retreatment interval was >or=1 year or 30 Gy (n = 3) if the retreatment interval was <1 year. Concurrent chemotherapy was administered to 48 (96%) patients. Eighteen (36%) patients underwent surgical resection following radiotherapy., Results: Two patients had grade 3 acute toxicity and 13 patients had grade 3 to 4 late toxicity. The 3-year rate of grade 3 to 4 late toxicity was 35%. The 3-year rate of freedom from local progression was 33%. The 3-year freedom from local progression rate was 47% in patients undergoing surgery and 21% in those not undergoing surgery (p = 0.057). The 3-year overall survival rate was 39%. The 3-year overall survival rate was 66% in patients undergoing surgery and 27% in those not undergoing surgery (p = 0.003). The 3-year overall survival rate was 53% in patients with a retreatment interval of >2 years and 21% in those with a retreatment interval of

Background: This pilot study compared the risk predictive value of preoperative physiological capacity (PC: defined by gas exchange measured during cardiopulmonary exercise testing) with the ASA physical status classification in the same patients (n=32) undergoing major abdominal cancer surgery., Methods: Uni- and multivariate logistic regression models were fitted to measurements of PC and ASA rank data determining their predictive value for postoperative morbidity. Receiver operating characteristic (ROC) curves were used to discriminate between the predictive abilities, exploring trade-offs between sensitivity and specificity., Results: Individual statistically significant predictors of postoperative morbidity included the ASA rank [P=0.038, area under the curve (AUC)=0.688, sensitivity=0.630, specificity=0.750] and three newly identified measures of PC: PAT (% predicted anaerobic threshold achieved, <75% vs > or =75%), DeltaHR1 (heart rate response from rest to the anaerobic threshold), and HR3 (heart rate at the anaerobic threshold). A two-variable model of PC measurements (DeltaHR1+PAT) was also shown to be statistically significant in the prediction of postoperative morbidity (P=0.023, AUC=0.826, sensitivity=0.813, specificity=0.688)., Conclusions: Three newly identified PC measures and the ASA rank were significantly associated with postoperative morbidity; none showed a statistically greater association compared with the others. PC appeared to improve predictive sensitivity. The potential for new unidentified measures of PC to predict postoperative outcomes remains unexplored.

Purpose: We designed this Phase II trial to assess the efficacy and safety of the addition of bevacizumab to concurrent neoadjuvant capecitabine-based chemoradiation in locally advanced rectal cancer., Methods: Between April 2004 and December 2007, 25 patients with clinically staged T3N1 (n = 20) or T3N0 (n = 5) rectal cancer received neoadjuvant therapy with radiotherapy (50.4 Gy in 28 fractions over 5.5 weeks), bevacizumab every 2 weeks (3 doses of 5 mg/kg), and capecitabine (900 mg/m(2) orally twice daily only on days of radiation), followed by surgical resection a median of 7.3 weeks later., Results: Procedures included abdominoperineal resection (APR; 6 patients), proctectomy with coloanal anastamosis (8 patients), low anterior resection (10 patients), and local excision (1 patient). Eight (32%) of 25 patients had a pathologic complete response, and 6 (24%) of 25 had <10% viable tumor cells in the specimen. No patient had Grade 3 hand-foot syndrome, gastrointestinal toxicity, or significant hematologic toxicity. Three wound complications required surgical intervention (one coloanal anastamostic dehiscence requiring completion APR and two perineal wound dehiscences after initial APR). Five minor complications occurred that resolved without operative intervention. With a median follow-up of 22.7 months (range, 4.5-32.4 months), all patients were alive; one patient has had a recurrence in the pelvis (2-year actuarial rate, 6.2%) and 3 had distant recurrences., Conclusions: The addition of bevacizumab to neoadjuvant chemoradiation resulted in encouraging pathologic complete response without an increase in acute toxicity. The impact of bevacizumab on perineal wound and anastamotic healing due to concurrent bevacizumab requires further study., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to determine the prevalence and prognostic significance of acellular mucin within resected specimens of rectal cancer patients with a pCR following preoperative chemoradiation., Summary Background Data: The presence of acellular mucin pools in the resected specimens of patients with a complete response to preoperative chemoradiation is frequently reported as a marker of treatment effect. The clinical significance of the presence of acellular mucin with respect to local recurrence and survival outcomes is unknown., Methods: Data from a rectal cancer database was used to analyze 562 patients with nonmetastatic rectal adenocarcinoma treated between 1989 and 2004. The presence or absence of acellular mucin within the specimen was identified by the surgical pathology reports and confirmed by re-examination of H&E sections of surgical specimens., Results: Among the 562 patients, 100 patients (18%) had pCR. Acellular mucin was present in 27 (27%) of the 100 patients with pCR. The median follow-up interval was 87 months (range, 1-198 months). Local and distant failures occurred in 0 and 2 patients with acellular mucin, and in 1 and 6 patients without acellular mucin, respectively. The actuarial 7-year overall survival rates were 85% for patients with acellular mucin and 92% for patients without acellular mucin (P = 0.954). The actuarial 7-year disease-free survival rates were 81% and 87% (P = 0.764) and the 7-year freedom from relapse rates were 93% and 91% (P = 0.881) in patients with and without acellular mucin, respectively., Conclusions: Acellular mucin is present within 27% of resected specimens in rectal cancer patients with a pCR after preoperative chemoradiation. However, the presence of acellular mucin has no prognostic significance.