Use Of Preoperative Radiation Therapy Research Articles

Recent advances in the understanding and management of liposarcoma.

Liposarcomas are a common subfamily of soft tissue sarcoma with several subtypes recognized by the World Health Organization: atypical lipomatous tumors (ALT)/well-differentiated liposarcoma (WDLPS), dedifferentiated liposarcoma (DDLPS), myxoid liposarcoma (MLPS), pleomorphic liposarcoma (PLPS), and myxoid pleomorphic liposarcoma (MPLPS). Despite shared adipocytic features among liposarcomas, the clinical approach to each subtype differs based on histology, location, clinical behavior, and specific oncogenic drivers. In this review, we highlight subtype-specific molecular features with the potential to generate novel therapies. We discuss recent clinical trials investigating the use of preoperative radiation therapy for retroperitoneal liposarcoma, chemotherapy, small molecule inhibitors, and innovative immunotherapy approaches and describe how we incorporate these advancements into the management of liposarcoma.

Use of Preoperative Radiation Therapy in Early-stage and Locally Advanced Breast Cancer.

PurposeThere is growing interest in delivering radiation preoperatively (preopRT) rather than postoperatively (postopRT) for breast cancer. Using the National Cancer Database, we evaluated the use and outcomes of preopRT in breast cancer.MethodsWe identified adult females diagnosed with non-metastatic breast cancer treated with definitive surgery and radiation between 2004 and 2014. Logistic regression models evaluated factors associated with use of preopRT in early-stage (clinical T1-3/N0-1) and locally advanced (clinical T4/N2-3) disease. Rates of breast-conserving surgery, breast reconstruction, positive surgical margins, and 30-day surgical readmissions were compared between patients receiving preopRT and postopRT.ResultsOf 373,595 patients who met our inclusion criteria, 1,245 (0.3%) patients received preopRT. Patients receiving preopRT were more likely to be of lower socioeconomic status and have tumors with higher T stage. Younger age and N1 (vs N0) disease predicted for use of preopRT in early-stage disease, while older age and N0 disease predicted for use of preopRT in the locally advanced setting. PreopRT patients were less likely to undergo breast-conserving surgery and more likely to have positive surgical margins. Rates of unplanned readmissions within 30 days of surgery were similar among patients treated with preopRT and postopRT.ConclusionsPreopRT is a new treatment strategy for patients with breast cancer with different clinical and sociodemographic drivers of its use in the early-stage and locally advanced settings. We await the results of clinical trials studying the efficacy of this approach.

A Phase 1 Pilot Study of Preoperative Radiation Therapy for Prostate Cancer: Long-Term Toxicity and Oncologic Outcomes

Neoadjuvant radiation therapy (RT) improves disease control in various cancers and has become an established oncologic treatment strategy. During 2001 to 2004, we conducted a phase 1 pilot study assessing the role of short-course preoperative RT (PreORT) for men with unfavorable intermediate- and high-risk localized prostate cancer. Herein, we present long-term follow-up toxicity and oncologic outcomes. Eligible patients had histologically proven prostate cancer, cT1-T2N0M0 disease, prostate-specific antigen >15 to 35ng/mL regardless of Gleason score, or prostate-specific antigen 10 to 15ng/mL with Gleason score ≥7. Patients received 25Gy in 5 consecutive daily fractions (5Gy per fraction) to the prostate only, followed by radical prostatectomy within 14days after RT completion. Primary outcomes were intraoperative morbidity and late genitourinary (GU) and gastrointestinal toxicities. In total, 15 patients were enrolled; 14 patients completed PreORT followed by radical prostatectomy, which also included bilateral lymph node dissections in 13 cases. Median follow-up was 12.2years (range, 6.7-16.3). Late GU toxicity was common, with 2 patients (13.3%) experiencing G2 toxicity and 6 patients (40%) G3 toxicity. There were no patients with G4 to G5 late GU toxicity. Late gastrointestinal toxicity was infrequent, with only 1 patient (6.7%) experiencing transient G2 proctitis. At last follow-up, 8 (53.3%) and 6 (40%) patients experienced biochemical and metastatic disease recurrence, respectively. The use of PreORT in men with high-risk prostate cancer is associated with unexpected high rates of late GU toxicity. Future studies examining the role of RT preradical prostatectomy must cautiously select RT technique and dose schedule. Importantly, long-term follow-up data are essential to fully determine the therapeutic index of PreORT in the management of localized disease.

Use of Preoperative Radiation Therapy in Early and Advanced Stage Breast Cancer

Use of Preoperative Radiation Therapy in Early and Advanced Stage Breast Cancer

Preoperative vs postoperative radiation therapy in localized soft tissue sarcoma: Nationwide patterns of care and trends in utilization

PurposeThe timing of perioperative radiation therapy (RT) in the treatment of soft tissue sarcoma (STS) varies among institutions. This study examines patterns of care, trends in utilization, and survival with preoperative versus postoperative RT for primary STS. Methods and materialsUsing the National Cancer Data Base, we identified patients with stage I-III STS who underwent definitive surgery with either preoperative or postoperative RT between 2004 and 2012. Univariate, bivariate, and multivariate analyses were performed to identify factors predicting receipt of preoperative versus postoperative RT. Overall survival (OS) was analyzed using the log-rank test, Kaplan-Meier method, and Cox proportional-hazards model. ResultsThis study included 9604 patients: 7246 (75.4%) received postoperative and 2358 (24.6%)-preoperative RT. Chemotherapy was administered to 27.0% patients in the preoperative and 13.0% in the postoperative cohort. Use of preoperative RT increased over time, from 16.8% in 2004 to 29.7% in 2012. Multivariate analysis revealed that preoperative RT utilization increased with the following factors: higher educational attainment, treatment at an academic facility, further distance from facility (>60 miles), receipt of chemotherapy, tumor originating in lower extremities, >10 cm tumors, and myxoid liposarcoma. OS analysis revealed no difference between the 2 treatment cohorts. ConclusionsPostoperative RT is used much more commonly than preoperative RT in localized STS; however, preoperative RT use has increased in recent years. Multiple demographic and clinicopathologic factors were predictive of preoperative RT use. Consistent with randomized phase 3 data, there was no difference in OS.

Perioperative chemotherapy using FOLFOX with panitumumab for locally advanced rectal cancer: Phase II trial.

502 Background: Neoadjuvant chemotherapy for locally advanced rectal cancer is required to achieve tumor reduction when skipping routine use of preoperative radiation therapy. It is known that EGFR inhibitor has impact on early tumor shrinkage in metastatic colorectal cancer. We evaluated the effect of preoperative infusional fluorouracil, leucovolin, and oxaliplatin (FOLFOX) with panitumumab. Methods: Forty-three patients with clinical stage III rectal cancer without invasion to other organs were enrolled in this multicenter phase II trial. All patients had KRAS wild tumors confirmed by biopsy. Patients received six cycles of FOLFOX with panitumumab. Reduction rate of primary tumor was measured by T2 weighted sagittal image of magnetic resonance imaging. Excluding patients whose disease progressed after the six cycles, total mesorectal excision was performed two weeks after neoadjuvant chemotherapy. After surgery, adjuvant chemotherapy with six cycles of FOLFOX without panitumumab was planned before diverting stoma closure. The primary outcome was the response rate of the primary lesion. Results: Between January 2012 and December 2014, 42 out of 43 patients completed preoperative chemotherapy; one patient did not complete the regimen due to grade III neutropenia. There was no progressive disease in the 42 patients and response rate was 69.8% in this series. Average reduction rate of the primary lesion was 47.6%. All of the 43 participants had R0 resections without mortality or severe complications. Pathological complete response rate to chemotherapy was 7.0% (3 of 43). Thirty-eight out of 43 patients started adjuvant chemotherapy and 32 patients completed the regimen. Grade 3 or worse peripheral neuropathy was not seen during neoadjuvant chemotherapy and seen in 2.6% (1 of 38) during adjuvant chemotherapy. Conclusions: Periopative chemotherapy using FOLFOX with panitumumab seemed to have two advantages; one is tumor reduction which enables skipping neoadjuvant radiation therapy, the other is safely administering a larger dose of chemotherapy than adjuvant only in locally advanced rectal cancer. Additional impact of EGFR inhibitor should be followed in long term results. Clinical trial information: UMIN000006039.

Trends in the use of pre-operative radiation for adenocarcinoma of the pancreas in the United States

BackgroundThe benefit and timing of radiation therapy (RT) for patients undergoing a resection for pancreatic adenocarcinoma remains unclear. This study identifies trends in the use of radiation over a 10-year period and factors associated with the use of pre-operative radiation, in particular. MethodsThe Surveillance, Epidemiology and End Results registry was used to identify patients aged ≥18 years with pancreatic adenocarcinoma who underwent a surgical resection between 2000 and 2010. Logistic regression was used to identify time trends and factors associated with the use of pre-operative radiation. ResultsThe overall use of radiation decreased with time among the 8474 patients who met the inclusion criteria. However, the use of pre-operative radiation increased from 1.8% to 3.9% (P ≤ 0.05). Factors significantly associated with receipt of pre-operative radiation were younger age, treatment in more recent years and having an advanced T-stage tumour. The 5-year hazard of death was significantly less for those who received pre-operative radiation versus surgery alone [hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.55–0.74] and for those who received post-operative radiation versus surgery alone (HR 0.69, 95% CI 0.65–0.73). DiscussionThe use of pre-operative radiation significantly increased during the study period. However, the overall use of pre-operative radiation therapy remains low in spite of the potential benefits.

Improvements in 5-year Outcomes of Stage II/III Rectal Cancer Relative to Colon Cancer

Stage for stage, rectal cancer has historically been associated with inferior survival compared with colon cancer. Randomized trials of rectal cancer have generally demonstrated improvements in locoregional relapse but not survival. We compared therapy and outcomes of colon versus rectal cancer in 2 time cohorts to determine if relative improvements have occurred. Patients with resected stage II/III colorectal cancer referred to the British Columbia Cancer Agency in 1989/1990 and 2001/2002 were identified. The higher of clinical or pathologic stage was used for patients receiving preoperative chemoradiation. Disease-specific survival (DSS) and overall survival (OS) were compared for rectal and colon cancer between the 2 cohorts. Kaplan-Meier method was used for survival analysis. A total of 1427 patients were included, with 375 from 1989/1990 and 1052 from 2001/2002. Between 1989/1990 and 2001/2002 there were significant increases in the use of perioperative chemotherapy for both rectal and colon cancer (P<0.001) and use of preoperative radiation therapy (P<0.001) and total mesorectal excision (P<0.001) in rectal cancer. DSS significantly improved for rectal (P<0.001) but not colon cancer (P=0.069). Five-year OS was significantly inferior for rectal versus colon cancer in 1989/1990 (46.1% vs. 57.2%, P=0.023) and was similar to that of colon cancer in 2001/2002 (63.7% vs. 66.2%, P=0.454). Advances in locoregional and systemic therapy significantly improved survival among patients with rectal cancer. DSS and OS are now similar between colon and rectal cancer for both stage II and III disease.

Patterns of use and outcomes for radiation therapy in the Quality Initiative in Rectal Cancer (QIRC) trial

The Quality Initiative in Rectal Cancer (QIRC) trial targeted surgeon intraoperative technique and not radiation therapy (RT) use. We performed a post hoc analysis of RT use among patients in the QIRC trial, not by arm of trial but rather for the entire group. We wished to identify associations between local recurrence risk and use of preoperative, postoperative or no RT. We compared demographic, tumour and process of care measures among patients receiving preoperative, postoperative or no RT. A multivariable Cox regression model assessed local recurrence risk. The QIRC trial enrolled 1015 patients at 16 hospitals between 2002 and 2004. Radiation therapy use did not differ between trial arms, and median follow-up was 3.6 years. For the preoperative, postoperative and no RT groups, respectively, the percentage of patients was 12.8%, 19.3% and 67.9%; the percentage of stage II/III tumours was 57.0%, 88.7% and 48.1%; and the local recurrence rate was 5.3%, 10.2% and 5.5% (p = 0.05). After controlling for patient and tumour characteristics, including tumour stage, the hazard ratio (HR) for local recurrence was increased in the postoperative RT versus the no RT group (HR 1.64, 95% confidence interval 1.04-2.58, p = 0.027). Use of preoperative RT was low; most patients with stage II/III disease did not receive RT and, as expected, the postoperative RT group had the highest risk of local recurrence. Our results suggest opportunities to improve rectal cancer RT use in Ontario.

Quality Research in Radiation Oncology Analysis of Clinical Performance Measures in the Management of Gastric Cancer

The specific aim was to determine national patterns of radiation therapy (RT) practice in patients treated for stage IB-IV (nonmetastatic) gastric cancer (GC). A national process survey of randomly selected US RT facilities was conducted which retrospectively assessed demographics, staging, geographic region, practice setting, and treatment by using on-site record review of eligible GC cases treated from 2005 to 2007. Three clinical performance measures (CPMs), (1) use of computed tomography (CT)-based treatment planning; (2) use of dose volume histograms (DVHs) to evaluate RT dose to the kidneys and liver; and (3) completion of RT within the prescribed time frame; and emerging quality indicators, (i) use of intensity modulated RT (IMRT); (ii) use of image-guided tools (IGRT) other than CT for RT target delineation; and (iii) use of preoperative RT, were assessed. CPMs were computed for 250 eligible patients at 45 institutions (median age, 62 years; 66% male; 60% Caucasian). Using 2000 American Joint Committee on Cancer criteria, 13% of patients were stage I, 29% were stage II, 32% were stage IIIA, 10% were stage IIIB, and 12% were stage IV. Most patients (43%) were treated at academic centers, 32% were treated at large nonacademic centers, and 25% were treated at small to medium sized facilities. Almost all patients (99.5%) underwent CT-based planning, and 75% had DVHs to evaluate normal tissue doses to the kidneys and liver. Seventy percent of patients completed RT within the prescribed time frame. IMRT and IGRT were used in 22% and 17% of patients, respectively. IGRT techniques included positron emission tomography (n=20), magnetic resonance imaging (n=1), respiratory gating and 4-dimensional CT (n=22), and on-board imaging (n=10). Nineteen percent of patients received preoperative RT. This analysis of radiation practice patterns for treating nonmetastatic GC indicates widespread adoption of CT-based planning with use of DVH to evaluate normal tissue doses. Most patients completed adjuvant RT in the prescribed time frame. IMRT and IGRT were not routinely incorporated into clinical practice during the 2005-2007 period. These data will be a benchmark for future Quality Research in Radiation Oncology GC surveys.

Effect of systematic education courses on rectal cancer treatments in a population

Purpose In a strategy aimed to improve perioperative and operative management of rectal cancer in British Columbia (BC), a series of educational events were provided for BC surgeons, radiation oncologists, and pathologists including teaching on the use of preoperative radiation, surgical technique with total mesorectal excision (TME), and pathology reporting. Seminars were offered during 2002 and 2003 each over 2 days with documented attendance from 30 hospitals in the province. We wished to determine whether frequency of preoperative radiation and TME surgery changed on a population level after the rectal cancer education courses in 2002 and 2003. Methods All patients were referred to the BC Cancer Agency, the only center for radiation in BC. Treatments and data were abstracted from the Colorectal Cancer Outcomes Unit database. Patients with resected stage I to III rectal cancer were included who were diagnosed before (2000–2001) and after (2004) the education courses. We used changes from 2000 to 2001 to reflect effects of sporadic continued medical education (CME) compared with effects of formal systematic provincial education courses (changes from 2001 to 2004). Results A total of 778 eligible patients were included from 2000 (n = 264), 2001 (n = 202), and 2004 (n = 312). The percentage of stage III patients was similar in the 3 time periods. The use of preoperative radiation therapy increased significantly over time, 43% (114/264), 56% (113/202), and 86% (268/312) ( P < .0001). TME use also increased significantly, 35%, 44%, and 71% ( P < .0001). Conclusions The implementation of guidelines for the use of preoperative radiation and TME by formal systematic provincial education courses for surgeons, radiation oncologists, and pathologists resulted in significant improvements in rectal cancer management on a provincial level. Such programs may be more effective than “sporadic” CME, particularly in multidisciplinary and complex care settings like adjuvant rectal cancer therapy.

Adoption of Preoperative Radiation Therapy for Rectal Cancer From 2000 to 2006: A Surveillance, Epidemiology, and End Results Patterns-of-Care Study

The German rectal study determined that preoperative radiation therapy (RT) as a component of combined-modality therapy decreased local tumor recurrence, increased sphincter preservation, and decreased treatment toxicity compared with postoperative RT for rectal cancer. We evaluated the use of preoperative RT after the presentation of the landmark German rectal study results and examined the impact of tumor and sociodemographic factors on receiving preoperative RT. In total, 20,982 patients who underwent surgical resection for T3-T4 and/or node-positive rectal adenocarcinoma diagnosed from 2000 through 2006 were identified from the Surveillance, Epidemiology, and End Results tumor registries. We analyzed trends in preoperative RT use before and after publication of the findings from the German rectal study. We also performed multivariate logistic regression to identify factors associated with receiving preoperative RT. Among those treated with RT, the proportion of patients treated with preoperative RT increased from 33.3% in 2000 to 63.8% in 2006. After adjustment for age; gender; race/ethnicity; marital status; Surveillance, Epidemiology, and End Results registry; county-level education; T stage; N stage; tumor size; and tumor grade, there was a significant association between later year of diagnosis and an increase in preoperative RT use (adjusted odds ratio, 1.26/y increase; 95% confidence interval, 1.23-1.29). When we compared the years before and after publication of the German rectal study (2000-2003 vs. 2004-2006), patients were more likely to receive preoperative RT than postoperative RT in 2004-2006 (adjusted odds ratio, 2.35; 95% confidence interval, 2.13-2.59). On multivariate analysis, patients who were older, who were female, and who resided in counties with lower educational levels had significantly decreased odds of receiving preoperative RT. After the publication of the landmark German rectal study, there was widespread, rapid adoption of preoperative RT for locally advanced rectal cancer. However, preoperative RT may be underused in certain sociodemographic groups.

Temporal and Regional Variations in the Use of Preoperative Radiation Therapy for Rectal Cancer

Preoperative (preop) chemoradiation therapy improves local control and reduces toxicity for stage II/III rectal cancer better than postoperative (postop) chemoradiation therapy. We examined the temporal and regional variations in the use of preop radiotherapy (RT) across the United States. Patients with stage II/III rectal cancer diagnosed between 1998 and 2005 who had a primary site resection were identified from the SEER database. The rate of preop RT use over time was plotted. Regression models were used to analyze regional variations. From 1998 to 2005, an increase of 1.7 in the ratio of preop RT/postoperative RT was noted, whereas the ratio of RT/no RT increased only by 0.7. The ratio of preop RT/postop RT increased from 0.5 to 1 in 5 years (1998-2003) but from 1 to 1.5 in 2 years (2003-2005). Multivariate regression analysis showed: patients with stage II disease were more likely than those with stage III disease, younger patients were more likely than older patients, and males were more likely than females to receive preop RT. Whites were more likely to receive preop RT than nonwhites for stage III disease only. Patients treated in the San Francisco region, Hawaii, New Mexico, Seattle, and Los Angeles were more likely to receive preop RT than were patients in the Connecticut, Detroit, Iowa, Utah, Atlanta, and San Jose/Monterey regions. The increasing use of preop RT varies across US regions and patient subgroups. Further studies should evaluate potentially modifiable factors contributing to these variations.

Association of Patient Factors with use of Preoperative Radiation Therapy for Stage II and III Rectal Cancer

Association of Patient Factors with use of Preoperative Radiation Therapy for Stage II and III Rectal Cancer

Comparison of rectal and colon cancer outcomes: A population based analysis

4040 Background: Rectal cancer has previously been associated with inferior five year survival in comparison to colon cancer. Total mesorectal excision (TME) and adjuvant therapy have reduced locoregional recurrence and, in some studies, improved rectal cancer survival. Therapy and outcomes of colon and rectal cancer were compared among 3 patient cohorts referred to the British Columbia Cancer Agency (BCCA) between 1990 and 2002. Methods: Patients with resected, pathological stage II or III colorectal cancer referred to BCCA in 1990, 1995/96, and 2001/02 were included. For those patients receiving long-course preoperative radiation, the higher of clinical or pathological stage was used. Kaplan Meier method was used for survival analysis. Results: 1,851 patients were included with a median age range of 64–69 and follow up time of 15.7 [1990], 10.8 [1995/96] and 5.3 [2001/02] years. Between 1990 and 2001/02 the use of adjuvant chemotherapy increased significantly for rectal cancer from 14.7% to 68.5% (p<0.001) and for colon cancer from 32.9% to 54% (p<0.001). The use of preoperative radiation therapy (RT) (p<0.001) and total mesorectal excision (TME) (p<0.001) in rectal cancer also significantly increased. 5 year overall survival (OS) was numerically inferior for rectal compared to colon cancer in 1990 and similar to colon cancer in the later cohorts (Table). The analysis was limited by small sample size and an expanded cohort will be presented. 5 year OS significantly improved for both rectal (p<0.001) and colon cancer (p=0.025) between 1990 and 2001/02. Conclusions: In this population based study, 5 year OS for stage II/III rectal and colon cancer significantly improved between 1990 and 2001/02, with similar outcomes now apparent for both sites. With respect to rectal cancer, improved outcomes are likely related to increased use of TME technique, preoperative RT and adjuvant chemotherapy. Improved outcomes for colon cancer likely reflect increased use of adjuvant chemotherapy. 5 year overall survival for colon and rectal cancer Year N 5 Y Overall Survival (%) Rectal Cancer 5 Y Overall Survival (%) Colon Cancer P-Value 1990 236 43.8 [34.9, 54.9] 53.7 [46.0, 62.7] 0.0969 Stage II 83 55.2 [39.7, 76.6] 63.6 [51.8, 78.2] 0.3954 Stage III 153 38.8 [28.7, 52.4] 47.7 [38.2, 59.5] 0.2088 1995–96 563 59.3 [53.1, 66.3] 61.7 [56.7, 67.2] 0.5607 Stage II 233 68 [58.3, 79.2] 72.3 [65.3, 80] 0.4675 Stage III 330 54.4 [46.6, 63.4] 53.5 [46.8, 61.2] 0.8654 2001–02 1052 63.7 [58.5, 69.4] 66.2 [62.4, 70.1] 0.4543 Stage II 430 70.6 [63.1, 78.9] 77.1 [71.9, 82.7] 0.158 Stage III 622 58.4 [51.4, 66.4] 59.1 [54.2, 64.4] 0.8818 No significant financial relationships to disclose.

Determinants of lymph node yield in colorectal cancer: Analysis of 9,867 patients from prospective Australian databases

4047 Background: For colorectal cancer (CRC) lymph node yield (LNY) is a measure of quality of care, and also a strong prognostic factor. Small series suggest that multiple clinical and pathologic factors may influence LNY, but the true impact of these has yet to be defined. Methods: Analysis of prospective CRC databases from 11 centres in Australia between 1/2000 - 12/2007. Results: 9,867 cases, 5,121M : 4,362F, were identified where detail regarding age, sex, tumour site, differentiation, and use of radiation therapy (RT) was available. Overall median LNY was 12 (range 0 - 174), with the median varying from 10–15 per centre (p<.0001). Tumour stage and differentiation did not influence node yield, but all other factors examined did (as shown in Table). For patients with rectal cancer the LNY was impacted by type of operation performed and use of preoperative RT. Multivariate analysis will be presented. A nomogram has been developed to predict lymph node yield for a specific patient. Conclusion: Multiple clinicopathologic factors affect LNY, with specific subgroups of patients having widely divergent yields. Median Node yield P value Sex <.01 Male 11 Female 12 Age <.01 < 50 y.o 13 50 - 65 y.o. 12 65 - 75 y.o 12 > 75 y.o. 11 Site <.01 Right colon (n=3,554) 13 Left colon (n=3,294) 11 Rectum (n=3,019) 11 No radiotherapy 11 Preoperative RT 10 Rectal cancer operation <.01 Low anterior resection 13 Ultralow AR 11 APR 10 (no RT), 8 (+ RT) No significant financial relationships to disclose.

Preoperative bi-fractionated accelerated radiation therapy for combined treatment of locally advanced rectal cancer in a consectutive series of unselected patients

Backgroundalthough preoperative RT (Radiation Therapy) is becoming the preferred approach for combined treatment of locally advanced rectal adenocarcinoma, no regimen can be now considered as a standard. Since the toxicity of preoperative RT isn't yet completely known, and the advantages of preoperative RT could be counterbalanced by increased postoperative morbidity and mortality, a monocentre series of preoperative bifractionated accelerated RT was retrospectively reviewed to clarify toxicity and outcomes after a prolonged follow up.Methodspatients were screened following these eligibility criteria: histology-proven adenocarcinoma of the rectum; distal tumour extent at 12 cm or less from the anal verge; clinical stage T3–4/anyN, or anyT/N1–2; ECOG Performance Status 0–2. A total dose of 41.6 Gy (26 twice daily fractions of 1.6 Gy) was delivered. Surgery was carried out 17 ± 2 days after RT completion, adopting the total mesorectal excision technique.Results24 men and 23 women were enrolled; median age was 55 years (r.: 39–77). Twenty-eight patients were stage II and 19 stage III. 9 patients suffered from a recurrent tumour. 2 patients experienced a severe grade 4 gastrointestinal toxicity (a colo-vaginal fistula and an intestinal obstruction, both successfully treated). Operative mortality was nil; postoperative early complications occurred in 13 cases; mean length of hospital stay was 15 days. After a mean follow up of 44 months (r.: 18–84) 8 patients had deceased for recurrent disease, 15 were alive with a disease progression (2 pelvic recurrences and 13 pure distant deposits) and 24 were alive, without disease. The 5-year actuarial overall survival was 74.2%, the disease-free survival 62.9% and the regional control rate 84.7%. Long-term complications included 1 case of radiation enteritis requiring surgery, 2 cases of anastomotic stricture and 3 cases of bladder incontinence.Conclusionbifractionated accelerated RT administered in the preoperative setting to patients bearing locally advanced rectal cancer is reliable and safe, as its immediate and late toxicity (mainly infectious) is acceptably low and long-term survivals are achievable. These findings support the increasing use of preoperative RT for treatment of this malignancy in experienced centres. Ongoing multicentric trials are expected to address still unsolved issues, including the benefit of CT adjunct to preoperative RT.

Primary Perineal Wound Closure After Preoperative Radiotherapy and Abdominoperineal Resection has a High Incidence of Wound Failure

Neoadjuvant radiation therapy has been used increasingly to downstage rectal cancer and decrease local recurrence. Despite its efficacy, preoperative radiation therapy may inhibit healing and contribute to wound complications. This study was designed to evaluate perineal wound complications after abdominoperineal resection. The clinical records of a consecutive series of patients who underwent abdominoperineal resection for rectal carcinoma between 1988 and 2002 were reviewed. Demographic data, disease stage, and use of preoperative radiation therapy were recorded. Major wound complications included delayed wound healing (>1 month), wound infection requiring drainage/debridement, or reoperation. A total of 160 patients underwent abdominoperineal resection with primary closure of the perineal wound (mean age, 63 +/- 12 years); 117 (73 percent) patients received preoperative radiation therapy; 114 received radiation therapy for rectal cancer (radiation therapy + chemotherapy = 107, radiation therapy alone = 7); 3 received radiation therapy for other pelvic malignancies. Median radiation dose was 5,040 (range, 900-5,400) cGY. Overall wound complication rate was 41 percent. Major wound complication rate was 35 percent. Delayed healing was the most common complication (24 percent), followed by infection (10 percent). Radiation therapy increased the risk of any wound complication (47 vs. 23 percent; P = 0.005), risk of a major wound complication (41 vs. 19 percent; P = 0.021), and risk of infection (14 vs. 0 percent; P = 0.015). Risk of wound complications did not correlate with age, gender, disease stage, smoking, or diabetes. Wound complications are frequent after abdominoperineal resection and primary closure of the perineum. Preoperative radiation therapy doubles the rate of total and major perineal wound complications. Alternatives to primary perineal closure should be considered, particularly after radiation therapy.

Adjuvant Radiation for Rectal Cancer: Do We Measure Up to the Standard of Care? An Epidemiologic Analysis of Trends Over 25 Years in the United States

In the United States, adjuvant radiation therapy is currently recommended for most patients with rectal cancer. We conducted this population-based study to evaluate the rate of radiation therapy and the factors affecting its delivery. We used the Surveillance Epidemiology and End Results database to assess treatment of patients with nonmetastatic rectal cancer diagnosed over a 25-year period (1976 through 2000). We evaluated the rate of radiation therapy use and its timing (preoperative vs. postoperative) and the influence of factors such as tumor stage and grade; patient gender and race; and geographic location. In this 25-year period, 45,627 patients met our selection criteria. The rate of radiation therapy use increased dramatically over time: from 17 percent of advanced-stage patients in 1976 to 65 percent in 2000 (P < 0.0001). Until 1996, the increase was due almost entirely to postoperative radiation therapy. Since 1996, the rate of preoperative radiation therapy use has increased (P < 0.0001) and the rate of postoperative radiation therapy use has begun to decline. We found, after controlling for the year of diagnosis, that female patients, African Americans, older patients, and patients with low-grade lesions were less likely to undergo radiation therapy (P < 0.0001). Geographic location was also an important predictor of radiation therapy use. The use of radiation therapy for patients with rectal cancer has dramatically increased over the 25-year period studied, with a recent shift to the use of preoperative radiation therapy; however, in 2000, over 30 percent of patients with advanced-stage nonmetastatic rectal cancer did not undergo radiation therapy. Given the variation in radiation therapy use that we found to be due to demographic factors, access to adjuvant radiation therapy can be improved.

Long-term prospective assessment of functional results after proctectomy with coloanal anastomosis

The objective of this study was to prospectively assess the long-term functional results after restorative proctectomy with coloanal anastomosis for rectal cancer. Thirty consecutive patients (18 males; mean age 59.6 ± 9.8 years, range 40 to 75 years) underwent proctectomy with coloanal anastomosis for rectal cancer between January 1990 and March 1997. Cancers were located between 5 and 12 cm from the anal verge. Differences existed in the administration of adjuvant therapy and in the kind of anastomotic reconstruction. An 8 cm colonic J-pouch was fashioned in 11 patients. The coloanal anastomosis was protected by a diverting loop ileostomy in 22 patients. All patients were evaluated using a prospective patient-completed protocol to record daily bowel activity over a 1-week period at 3, 6, and 12 months, and yearly thereafter. Mean follow-up extends to 55.5 ± 27 months (range 7 to 117 months). There were no perioperative deaths. Four patients (13.3%) developed a clinically evident anastomotic dehiscence. Overall, stool frequency decreased from 4.4 ± 2.5 bowel movements per day at 3 months to 3.0 ± 2.8 bowel movements per day at 5 years. Patients with a J-pouch had a lower stool frequency in comparison to patients with an end-to-end coloanal anastomosis during the entire study period (from 3.2 ± 2.2 vs. 3.9 ± 2.7 bowel movements per day at 6 months to 2.8 ± 1.9 vs. 3.4 ± 4.0 bowel movements per day at 5 years; no statistical significance). The percentage of continent patients increased from 50% at 6 months to 75% at 5 years; the percentage of patients with incontinence for solid stool and with frequent incontinence (≥7 episodes per week) decreased from 35.7% at 6 months to 12.5% at 5 years. The influence of the type of anastomosis, dehiscence, protective stoma, J-pouch, radiation therapy, and gender was evaluated with univariate analysis. Although there was no statistically significant correlation between any of these variables and the development of incontinence, when incontinence occurred, a history of anastomotic dehiscence increased the number of episodes of incontinence per week and the percentage of episodes of incontinence for solid stools at 6 months, 2 years, and 5 years ( P <0.05 and P <0.001, respectively); the use of preoperative radiation therapy increased the number of episodes of incontinence per week at 6 months, 1 year, 2 years, and 5 years ( P <0.01) and the percentage of episodes of incontinence for solid stools at 3 and 6 months and 1 and 2 years ( P <0.04); and the presence of a J-pouch increased the number of episodes of incontinence per week at 1 and 2 years ( P <0.03 and 0.005, respectively) and the percentage of episodes of incontinence for solid stools at 2, 3, and 4 years ( P <0.05). These data suggest that the functional results after proctectomy with coloanal anastomosis improve at least over the course of the first 5 postoperative years. Furthermore, when incontinence develops, its severity is made worse by the occurrence of an anastomotic dehiscence, the use of preoperative radiation therapy, and the presence of a J-pouch.