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The article discusses a study on lymph nodes (LN) status after neoadjuvant radiotherapy (NR) for rectal cancer as a biologic predictor. It states that preoperative radiotherapy affects LN after rectal cancer surgery. The subjects of the study were patients who underwent resection for rectal adenocarcinoma. The study found that preoperative patients were younger and free of detectable nodal metastasis. Researchers revealed that LN status after NR for rectal cancer is a biologic marker.

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 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 χ2 tests. Odds ratios of surgical and adjuvant therapy and 95% confidence intervals were calculated by logistic regression. A total of 51% of patients were age ≥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 ≥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. 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. [ABSTRACT FROM AUTHOR]

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. 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 m99Tc 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. 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). 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. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the predictive factors for pathologic complete response and tumor downstaging after preoperative chemoradiation for rectal cancer. The study employed 562 patients with nonmetastatic rectal adenocarcinoma who received preoperative chemoradiation and underwent mesorectal excision between 1989 and 2004. The study found that 19% of patients achieved a pathologic complete response, whereas 20% had only microscopic residual disease at surgery, and 61% had macroscopic residual disease at surgery.

Background Adequate lymph node evaluation for cancer involvement is important for prognosis and treatment of patients with colon cancer. The number of lymph nodes evaluated may be a measure of quality in colon cancer care and appears to be inadequate in most patients treated for colon cancer. We performed a systematic review of the evidence for the association between lymph node evaluation and oncologic outcomes in patients with colon cancer. Methods Medline, Scopus, Cochrane, and the National Guidelines Clearinghouse databases were searched from January 1, 1990, through June 30, 2006, for studies in which survival data as a function of number of lymph nodes evaluated were available. These studies were evaluated for methodologic quality, design, and data source. A total of 61 371 patients were included. Results Seventeen studies from nine countries were eligible for systematic review, including two secondary analyses of multicenter randomized trials of adjuvant chemotherapy for colon cancer, five population-based observational studies, and 10 single-institution retrospective cohort studies. Despite heterogeneity in methodology and differences in threshold numbers of lymph nodes evaluated (range = 6-40 lymph nodes), 16 of 17 studies reported that increased survival of patients with stage II colon cancer was associated with increased numbers of lymph nodes evaluated. Four of six studies with data from stage Ill patients also reported a positive association with survival among patients with stage Ill colon cancer. Conclusions The number of lymph nodes evaluated after surgical resection was positively associated with survival of patients with stage II and stage Ill colon cancer. These results support consideration of the number of lymph nodes evaluated as a measure of the quality of colon cancer care. [ABSTRACT FROM AUTHOR]

PURPOSE: Few biologic markers have been studied as prognostic factors in recurrent rectal carcinoma patients. We sought to determine the influence of clinical, pathologic, and biologic (p53, bcl-2, and ki-67) variables on survival after curative resection of locally recurrent rectal cancer. METHODS: Retrospective review of patients with locally recurrent rectal cancer who received surgery with curative intent. RESULTS: From 1988 to 1998, 134 patients with locally recurrent rectal cancer underwent operative exploration. Curative resection was performed in 85 patients. Median follow-up was 43 (range, 1.3–149) months. On multivariate analysis, negative predictors of overall survival included an elevated carcinoembryonic antigen level (P = 0.02; hazard ratio 2.41; 95 percent confidence interval, 1.19–4.89) and an R1 resection margin (P = 0.01; hazard ratio, 2.81; 95 percent confidence interval, 1.27–6.21). In 26 patients for whom biologic variables were available, p53, bcl-2, and ki-67 did not significantly impact disease-specific survival or overall survival. Five-year disease-specific survival, overall survival, and pelvic control rates were 46, 36, and 51 percent respectively. Of the 50 patients who relapsed, time to second local recurrence was longer than time to development of metastasis (median, 16.5 vs. 9 months). Median survival for patients with metastatic recurrence was 26.1 vs. 41.5 months for those with a subsequent local recurrence alone. CONCLUSIONS: Approximately two-thirds of patients with locally recurrent rectal cancer can be resected for cure. Preoperative carcinoembryonic antigen and an R0 resection margin were the only significant predictors of overall survival. p53, bcl-2, and ki-67 did not impact survival outcomes. [ABSTRACT FROM AUTHOR]

Preoperative chemoradiation therapy (CRT) in patients with locally advanced rectal cancer allows for radical surgery with sphincter preservation in many patients. To determine whether patients downsized with preoperative CRT may be potential candidates for local excision, we investigated residual disease patterns after neoadjuvant treatment. A retrospective analysis was carried out of patients with T3 or T4 rectal adenocarcinoma who were treated with neoadjuvant CRT. Clinical and pathologic data were analyzed to (1) determine the response rates to preoperative CRT in the tumor bed and regional nodal basin and (2) identify the incidence of residual disease in the mesorectum in patients downsized to &les;T2. A total of 219 patients met the inclusion criteria. Preoperatively 193 patients (88%) were staged as T3, and 99 patients (47%) had clinical N1 disease. The pathologic complete response rate was 20% (43 of 219 patients). T stage was downsized in 64% of the patients (140 of 219), and 69% (67 of 97) of the patients with clinical N1 disease were rendered node negative. Seventeen percent (21 of 122) of patients downsized to &les;T2 had residual disease in the mesentery. With a median follow-up of 40 months, 182 patients (83%) remain alive and free of disease. Nine patients (4.1%) have had a local recurrence. Although tumor response rates to preoperative CRT within the bowel wall and lymph node basin are similar, one in six patients with pT0–2 tumors will have residual disease in the rectal mesentery and nodes. Despite a substantial reduction in tumor volume with neoadjuvant CRT, local excision should be recommended with caution in patients with locally advanced rectal cancer. [Copyright &y& Elsevier]

Simple Summary: Total neoadjuvant therapy (TNT) for rectal cancer is expected to improve oncologic outcomes and organ preservation. Clinicians need to understand the advantages and limitations of the available regimens for multidisciplinary decision making. This article reviews the updated evidence on TNT and addresses tailor-made use of TNT regimens based on tumor location and local and systemic risk. Total neoadjuvant therapy (TNT) is a novel strategy for rectal cancer that administers both (chemo)radiotherapy and systemic chemotherapy before surgery. TNT is expected to improve treatment compliance, tumor regression, organ preservation, and oncologic outcomes. Multiple TNT regimens are currently available with various combinations of the treatments including induction or consolidation chemotherapy, triplet or doublet chemotherapy, and long-course chemoradiotherapy or short-course radiotherapy. Evidence on TNT is rapidly evolving with new data on clinical trials, and no definitive consensus has been established on which regimens to use for improving outcomes. Clinicians need to understand the advantages and limitations of the available regimens for multidisciplinary decision making. This article reviews currently available evidence on TNT for rectal cancer. A decision making flow chart is provided for tailor-made use of TNT regimens based on tumor location and local and systemic risk. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic colectomy has been shown to have equivalent oncologic outcomes to open colectomy for the management of colon cancer, but its adoption nationally has been slow. This study investigates the prevalence and factors associated with laparoscopic colorectal resection at National Comprehensive Cancer Network (NCCN) centers.Methods: Data on patients undergoing surgery for colon and rectal cancer at NCCN centers from 2005 to 2010 were obtained from chart review of medical records for the NCCN Outcomes Project and included information on socioeconomic status, insurance coverage, comorbidity, and physician-reported Eastern Cooperative Oncology Group (ECOG) performance status. Associations between receipt of minimally invasive surgery and patient and clinical variables were analyzed with univariate and multivariable logistic regression. All statistical tests were two-sided.Results: A total of 4032 patients, diagnosed between September 2005 and December 2010, underwent elective colon or rectal resection for cancer at NCCN centers. Median age of colon cancer patients was 62.6 years, and 49% were men. The percent of colon cancer patients treated with minimally invasive surgery (MIS) increased from 35% in 2006 to 51% in 2010 across all centers but varied statistically significantly between centers. On multivariable analysis, factors associated with minimally invasive surgery for colon cancer patients who had surgery at an NCCN institution were older age (P = .02), male sex (P = .006), fewer comorbidities (P ≤ .001), lower final T-stage (P < .001), median household income greater than or equal to $80000 (P < .001), ECOG performance status = 0 (P = .02), and NCCN institution (P ≤ .001).Conclusions: The use of MIS increased at NCCN centers. However, there was statistically significant variation in adoption of MIS technique among centers. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic colectomy has been shown to have equivalent oncologic outcomes to open colectomy for the management of colon cancer, but its adoption nationally has been slow. This study investigates the prevalence and factors associated with laparoscopic colorectal resection at National Comprehensive Cancer Network (NCCN) centers. Methods: Data on patients undergoing surgery for colon and rectal cancer at NCCN centers from 2005 to 2010 were obtained from chart review of medical records for the NCCN Outcomes Project and included information on socioeconomic status, insurance coverage, comorbidity, and physician-reported Eastern Cooperative Oncology Group (ECOG) performance status. Associations between receipt of minimally invasive surgery and patient and clinical variables were analyzed with univariate and multivariable logistic regression. All statistical tests were two-sided. Results: A total of 4032 patients, diagnosed between September 2005 and December 2010, underwent elective colon or rectal resection for cancer at NCCN centers. Median age of colon cancer patients was 62.6 years, and 49% were men. The percent of colon cancer patients treated with minimally invasive surgery (MIS) increased from 35% in 2006 to 51% in 2010 across all centers but varied statistically significantly between centers. On multivariable analysis, factors associated with minimally invasive surgery for colon cancer patients who had surgery at an NCCN institution were older age (P = .02), male sex (P = .006), fewer comorbidities (P ≤ .001), lower final T-stage (P < .001), median household income greater than or equal to $80000 (P < .001), ECOG performance status = 0 (P = .02), and NCCN institution (P ≤ .001). Conclusions: The use of MIS increased at NCCN centers. However, there was statistically significant variation in adoption of MIS technique among centers. [ABSTRACT FROM PUBLISHER]

Simple Summary: While anti-PD1 antibodies have demonstrated efficacy in some patients with metastatic anal cancer, these agents have no proven benefit for those with localized disease treated with chemoradiation. Difficulty procuring fresh tumor tissue required for RNA and protein expression analysis has limited extensive molecular profiling for this rare cancer. Our team utilized a novel digital spatial profiling technology on pretreatment anal cancer specimens to identify biomarkers associated with recurrence after chemoradiation. We observed that recurrent tumors had higher baseline expression of immune checkpoint biomarkers, higher MAPK signaling activation and higher PI3K/Akt signaling activation. These findings provide a rationale that supports future clinical trials with immunotherapy that seek to improve survival beyond chemoradiation for patients with localized squamous cell cancer of the anus. The identification of transcriptomic and protein biomarkers prognosticating recurrence risk after chemoradiation of localized squamous cell carcinoma of the anus (SCCA) has been limited by a lack of available fresh tissue at initial presentation. We analyzed archival FFPE SCCA specimens from pretreatment biopsies prior to chemoradiation for protein and RNA biomarkers from patients with localized SCCA who recurred (N = 23) and who did not recur (N = 25). Tumor cells and the tumor microenvironment (TME) were analyzed separately to identify biomarkers with significantly different expression between the recurrent and non-recurrent groups. Recurrent patients had higher mean protein expression of FoxP3, MAPK-activation markers (BRAF, p38-MAPK) and PI3K/Akt activation (phospho-Akt) within the tumor regions. The TME was characterized by the higher protein expression of immune checkpoint biomarkers such as PD-1, OX40L and LAG3. For patients with recurrent SCCA, the higher mean protein expression of fibronectin was observed in the tumor and TME compartments. No significant differences in RNA expression were observed. The higher baseline expression of immune checkpoint biomarkers, together with markers of MAPK and PI3K/Akt signaling, are associated with recurrence following chemoradiation for patients with localized SCCA. These data provide a rationale towards the application of immune-based therapeutic strategies to improve curative-intent outcomes beyond conventional therapies for patients with SCCA. [ABSTRACT FROM AUTHOR]

Simultaneous resection of colorectal liver metastases (CLM) and primary colorectal cancers (CRC) is nuanced without firm rules for selection. This study aimed to identify factors associated with morbidity after simultaneous resection. Using a prospective database, patients undergoing simultaneous CLM-CRC resection from 1/1/2017-7/1/2020 were analyzed. Regression modeling estimated impact of colorectal resection type, Kawaguchi–Gayet (KG) hepatectomy complexity, and perioperative factors on 90-day complications. Overall, 120 patients underwent simultaneous CLM-CRC resection. Grade≥2 complications occurred in 38.3% (n = 46); these patients experienced longer length of stay (median LOS 7.5 vs. 4, p < 0.001) and increased readmission (39% vs. 1.4%, p < 0.001) compared to patients with zero or Grade 1 complications. Median OR time was 298 min. Patients within highest operative time quartile (>506 min) had higher grade≥2 complications (57%vs. 23%, p = 0.04) and greater than 4-fold increased odds of grade≥2 morbidity (OR 4.3, 95% CI (Confidence Interval) 1.41–13.1, p = 0.01). After adjusting for Pringle time, KG complexity and colorectal resection type, increasing operative time was associated with grade≥2 complications, especially for resections in highest quartile of operative time (OR 7.28, 95% CI 1.73–30.6, p = 0.007). In patients undergoing simultaneous CLM-CRC resection, prolonged operative time is independently associated with grade≥2 complications. Awareness of cumulative operative time may inform intraoperative decision-making by surgical teams. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer in young adults is on the rise. This rise combined with delayed childbearing increases the likelihood of colorectal cancer diagnosed during pregnancy or in the postpartum period. Methods: Electronic health records were used to identify individuals with colorectal cancer in pregnancy or the postpartum period from 1 August 2007 to 1 August 2019. Results: Forty-two cases were identified. Median age at diagnosis was 33 years. Most (93%) were diagnosed in an advanced stage (III or IV) and had left-sided colorectal cancer tumors (81%). Molecular analysis was completed in 18 (43%) women with microsatellite status available in 40 (95%). The findings were similar to historical controls. Sixty percent were diagnosed in the postpartum period. Common presenting symptoms were rectal bleeding and abdominal pain. Conclusion: Currently there is no consensus recommendation regarding how to manage colorectal cancer during pregnancy. Given the overlapping symptoms with pregnancy, patients often present with advanced disease. We encourage all health care professionals caring for pregnant women to fully evaluate women with persistent gastrointestinal symptoms to rule out colorectal cancer. [ABSTRACT FROM AUTHOR]

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 ≥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 ≤2 years (p = 0.001). Conclusions: Hyperfractionated, accelerated reirradiation was well tolerated, with low rates of acute toxicity and moderate rates of late toxicity. Reirradiation may help improve pelvic control in rectal cancer patients with a history of pelvic radiotherapy. [Copyright &y& Elsevier]

Purpose: Colorectal cancer (CRC) is a malignancy that usually occurs in older age individuals. However, CRC cases in young adults are on the rise, and this increase is expected to continue. Young adult CRC requires the healthcare team to familiarize themselves with the unique needs of this population, including concerns about treatment-related infertility. We performed a retrospective review to determine how often our patients, 18–39 years old (yo), had discussions regarding fertility preservation prior to starting stage III CRC treatment. Methods: Our electronic health record was utilized to identify adult patients < 40 yo with a stage III CRC diagnosis during 1/1/2015–9/1/2019. Fertility preservation discussions were determined by searching the patient's EHR chart. Progress notes from the medical oncology, surgery, and/or radiation oncology teams were reviewed. Additionally, notes from our fertility specialist's team were reviewed when consulted. Results: One hundred and three patients met criteria. Patients were 21–39 yo at diagnosis (median age of 34 yo). Fifty-two percent were male while the remaining 48% were female. Forty-six percent had stage III colon cancer while 54% had stage III rectal cancer. Search terms and progress notes were utilized to determine if discussions were documented. Fertility discussions were documented in 73% of cases while 27% of patients lacked documentation regarding fertility. Conclusion: Our results show that most of our young adult stage III CRC population participate in fertility preservation discussions. However, in order to capture all patients, we recognize that a more formal approach is warranted. We additionally recommend these discussions occur with all patients of child-bearing age. [ABSTRACT FROM AUTHOR]

Introduction: In the majority of US institutions, gastrectomy specimens are sent for pathologic examination without surgeon assessment or standardized technique of lymph node (LN) assessment for gastric cancer. We conducted a quality improvement project at a US cancer center utilizing surgeon assessment of gastric LNs, and created a video to illustrate a technique of standardized lymph node assessment.Methods: Convenience sampling was employed among patients with gastric adenocarcinomas who underwent curative-intent D2 gastrectomy between July 2016 and June 2017. For each patient, a surgeon assessed gastric LNs by harvesting individual LNs, followed by conventional evaluation by a pathologist.Results: We enrolled 17 patients for this quality improvement project. Eight patients underwent total gastrectomy, and nine patients underwent subtotal gastrectomy. Twelve patients underwent preoperative chemoradiation therapy, three underwent preoperative chemotherapy alone, and two underwent upfront surgery. The median number of examined LNs was 43. All patients had ≥ 16 LNs examined, and 88% of patients had ≥ 30 LNs examined.Conclusion: Surgeon assessment of gastric LN specimens was feasible and effective to provide high-quality pathologic LN assessment after gastrectomy in gastric adenocarcinoma patients. Standardization of the technical methods for gastric LN evaluation is needed to improve the accuracy and quality of gastric cancer staging in the US. The provided video can help inform standardization of gastric LN assessment. [ABSTRACT FROM AUTHOR]

Background and purpose To evaluate outcomes and toxicity in patients treated with hyperfractionated pelvic reirradiation for recurrent rectal cancer. Materials and methods 102 patients with recurrent rectal adenocarcinoma were treated with pelvic reirradiation with a hyperfractionated accelerated approach, consisting of 1.5 Gy twice daily fractions to a total dose of 30–45 Gy (median 39 Gy), with the most common total dose 39 Gy ( n = 90, 88%). The median dose of prior pelvic radiation therapy (RT) was 50.4 Gy (range: 25–63 Gy). Results The median follow-up was 40 months for living patients (range, 3–150 months). The 3-year freedom from local progression (FFLP) rate was 40% and the 3-year overall survival (OS) rate was 39%. Treatment with surgery was significantly associated with improved FFLP and OS, with 3-year FFLP rate of 49% vs. 30% ( P = 0.013), and 3-year OS rate of 62% vs. 20% ( P < 0.0001), compared to those without surgery. The actuarial 3-year rate of grade 3–4 late toxicity was 34%; patients who underwent surgery had a significantly higher rate of grade 3–4 late toxicity compared to those without surgery (54% vs. 16%, P = 0.001). Conclusions This large, retrospective, single-institution study shows that hyperfractionated accelerated reirradiation was well tolerated. The rate of FFLP was promising, given that the study comprised heavily pre-treated patients with recurrences. Rates of FFLP and OS were particularly impressive in patients who underwent both reirradiation and surgery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this phase 1 trial was to determine the maximum tolerated dose (MTD) of concurrent capecitabine, bevacizumab, and erlotinib with preoperative radiation therapy for rectal cancer. Methods and Materials: Patients with clinical stage II to III rectal adenocarcinoma, within 12 cm from the anal verge, were treated in 4 escalating dose levels, using the continual reassessment method. Patients received preoperative radiation therapy with concurrent bevacizumab (5 mg/kg intravenously every 2 weeks), erlotinib, and capecitabine. Capecitabine dose was increased from 650 mg/m2 to 825 mg/m2 orally twice daily on the days of radiation therapy; erlotinib dose was increased from 50 mg orally daily in weeks 1 to 3, to 50 mg daily in weeks 1 to 6, to 100 mg daily in weeks 1 to 6. Patients underwent surgery at least 9 weeks after the last dose of bevacizumab. Results: A total of 19 patients were enrolled, and 18 patients were considered evaluable. No patient had grade 4 acute toxicity, and 1 patient had grade 3 acute toxicity (hypertension). The MTD was not reached. All 18 evaluable patients underwent surgery, with low anterior resection in 7 (39%), proctectomy with coloanal anastomosis in 4 patients (22%), posterior pelvic exenteration in 1 (6%), and abdominoperineal resection in 6 (33%). Of the 18 patients, 8 (44%) had pathologic complete response, and 1 had complete response of the primary tumor with positive nodes. Three patients (17%) had grade 3 postoperative complications (ileus, small bowel obstruction, and infection). With a median follow-up of 34 months, 1 patient developed distant metastasis, and no patient had local recurrence or died. The 3-year disease-free survival was 94%. Conclusions: The combination of preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib was well tolerated. The pathologic complete response rate appears promising and may warrant further investigation. [ABSTRACT FROM AUTHOR]

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/m2 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 &y& Elsevier]

Purpose: Sacral insufficiency (SI) fractures can occur as a late side effect of pelvic radiation therapy. Our goal was to determine the incidence, risk factors, and clinical course of SI fractures in patients treated with preoperative chemoradiation for rectal cancer. Materials and Methods: Between 1989 and 2004, 562 patients with non-metastatic rectal adenocarcinoma were treated with preoperative chemoradiation followed by mesorectal excision. The median radiotherapy dose was 45 Gy. The hospital records and radiology reports of these patients were reviewed to identify those with pelvic fractures. Radiology images of patients with pelvic fractures were then reviewed to identify those with SI fractures. Results: Among the 562 patients, 15 had SI fractures. The 3-year actuarial rate of SI fractures was 3.1%. The median time to SI fractures was 17 months (range, 2–34 months). The risk of SI fractures was significantly higher in women compared to men (5.8% vs. 1.6%, p = 0.014), and in whites compared with non-whites (4% vs. 0%, p = 0.037). On multivariate analysis, gender independently predicted for the risk of SI fractures (hazard ratio, 3.25; p = 0.031). Documentation about the presence or absence of pain was available for 13 patients; of these 7 (54%) had symptoms requiring pain medications. The median duration of pain was 22 months. No patient required hospitalization or invasive intervention for pain control. Conclusions: SI fractures were uncommon in patients treated with preoperative chemoradiation for rectal cancer. The risk of SI fractures was significantly higher in women. Most cases of SI fractures can be managed conservatively with pain medications. [Copyright &y& Elsevier]

purpose: To assess the pelvic failure among patients with T3 rectal cancer treated with local excision after preoperative chemoradiation.Methods and materials: Between January 1990 and June 2002, 431 patients with clinically staged T3 rectal cancer were treated with preoperative chemoradiation followed by surgical resection. Full-thickness local excision [Kraske (n = 3) or a transanal excision (n = 23)] was performed in 26 patients because of patient refusal of abdominoperineal resection (APR) (n = 13), medical comorbidity (n = 4), physician preference after a complete clinical response (n = 6), and other reasons (n = 3). All patients were treated with continuous-infusion 5-fluorouracil (5-FU) (300 mg/m2 Monday to Friday) and concomitant pelvic radiation (45 Gy in 25 fractions with a 3-field belly board technique). Ten local-excision patients received a concomitant boost during the last week of therapy (1.5-Gy second daily fractions) for a total dose of 52.5 Gy. Similar preoperative treatment was followed by total mesorectal excision in 405 patients. Among the local-excision patients, the median tumor size was 3.5 cm (range, 0.5–7 cm). Well-differentiated or moderately-differentiated histology was present in all but 3 cases, and endoscopic ultrasound staging examination was performed in 25 of 26 patients. Based on CT findings, 1 patient was node positive. The median circumference involved by tumor was 33%, (20%–75%). The median distance from the anal verge was 3 cm (range, 1–8 cm).Results: The mean follow-up was 46 months (range, 5–109 months) in the local-excision group. In the local-excision group, 19 of 26 patients had only residual scarring noted on digital rectal examination and rigid proctoscopy before surgery. Fourteen patients (54%) had a complete histologic response to chemoradiation, 9 patients (35%) had microscopic residual disease, and 3 patients (12%) had gross residual disease. Two intrapelvic recurrences occurred at 76 and 20 months among the 26 patients treated with local excision (6% 5-year actuarial pelvic recurrence rate). This rate compared with an 8% 5-year actuarial pelvic recurrence rate among T3 patients treated with mesorectal excision and a 6% pelvic recurrence rate in the subgroup of mesorectal-excision patients with a complete clinical response to preoperative chemoradiation. One additional local-excision patient recurred in an inguinal lymph node after local excision and subsequently died of metastatic disease. A total of 2 local-excision patients died of metastatic rectal cancer. Actuarial overall survival at 5 years was 86% in the local-excision group compared with 81% among mesorectal-excision patients (p = NS), and 85% in patients with a complete clinical response to chemoradiation followed by mesorectal excision by APR or LAR (p = NS).Conclusions: In an experience stimulated by patient refusal of APR, highly selected patients who responded well to conventional external-beam radiotherapy (CXRT) were selected to undergo local excision. Most of these patients had pathologic complete response. Local control and survival rates are comparable to those achieved with chemoradiation followed by mesorectal excision. This strategy should be prospectively studied in a group of patients with low rectal cancer who have no clinical evidence of tumor after chemoradiation. [Copyright &y& Elsevier]