Postoperative Adjuvant Chemoradiotherapy Research Articles

Postoperative Adjuvant Radiochemotherapy for Patients with Stage III or IV Gastric Cancer

Background and Purpose: It is known that radiotherapy or chemotherapy alone don't represent a standard of care as adjuvant treatment for patients with advanced gastric cancer that underwent surgical resection. The purpose in the approach of this cancer is to find an adjuvant treatment that can affect overall survival. Phase 2 studies and randomized trials suggest that a multimodal approach with chemo radiotherapy (CT-RT) can improve overall survival. We analyze the feasibility and toxic effects of chemo radiotherapy (CT-RT) as a post surgical adjuvant treatment in a cohort of patients with high risk gastric cancer. Methods: We enrolled 48 patients with advanced gastric cancer (Stage III and IV, M0). These patients were submitted to surgical resection and all of them, within 6 weeks, underwent adjuvant chemotherapy with FOLFOX-4 (ie, a combination of folinic acid, fluorouracil, and oxaliplatin) for 8 cycles and concomitant radiotherapy (45 Gy in 25 daily fractions over 5 weeks). Radiotherapy started after the first 2 cycles of FOLFOX-4. Chemotherapy schedule was reduced by 25% during the period of the contemporary radiotherapy treatment. Results: All patients except one ended the combined adjuvant treatment. We observed severe hematologic adverse effects only in less than 10% of patients (4 patients); regarding gastrointestinal toxic effects they occurred in 33% of patients and specifically we noted G1-G3 grade toxicity and no G4 toxicity . Disease-free and overall survival at 1, 2, and 3 years was superior to in untreated patients. One to 3-years Median disease-free and overall survival rates were 27 months and 15 months respectively. Conclusions: A combined trial with chemo radiotherapy (CT-RT ) as adjuvant treatment represents an effective approach for patients with resected advanced gastric cancer.

Transanal endoscopic microsurgery: results of the first 50 cases

The aim of the study was to share the experience and first results of implementation of transanal endoscopic microsurgery (TEM) technique for the removal of rectal adenomas, early rectal cancer or rectal stricture in the Center of Oncosurgery, Oncology Institute of Vilnius University. Materials and methods. From October 2009 to October 2011, a total of 50 patients underwent TEM for rectal adenomas, early rectal cancer or rectal stricture. The patients were 25 women and 25 men, 31 to 87 years of age (average 65 years). Rectal lesions were from 0.9 to 7.0 cm in diameter, 3–13 cm from the anal verge. Full thickness excision with 1 cm safety margin was achieved in all cases except two (mucosal excision), followed by closing of the rectal wall defect in one-layer running monocryl 3.0 suture using silver clips. In one case (TEM was performed for T2 rectal cancer), abdominal cavity was penetrated and two-layer closure was preferred. Results. In these series of 50 patients there was 1 (2%) complication (cystitis). No postoperative exitus occurred. The hospitalisation period ranged from 2 to 13 days (average 6 days). Final histology revealed 30 (60%) tubular or villous adenomas, 6 (12%) carcinomas in situ (pTis), 7 (14%) T1, 4 (8%) T2 cancers, and well-differentiated neuroendocrine tumors in 3 (6%) were diagnosed. One patient underwent open partial TME in pT1 group; the tumor was in the upper third of rectum and preoperatively evaluated as pTis disease. In two cases (pT1 group) lymphovascular invasion was present on final pathology, so they were offered a postoperative adjuvant chemoradiotherapy. Other 4 patients in T1 group are under surveillance. All 4 patients with T2 lesions were offered adjuvant chemoradiotherapy, one patient refused further treatment. Conclusions. TEM is an alternative for transanal excision of rectal adenomas and early rectal cancer. Further follow-up is necessary to evaluate the recurrence rate of cancer in invasive cancer patients group.

Incorporation of laparoscopic D2 dissection into the management of gastric adenocarcinoma (GCa) in a community-based setting.

117 Background: A recent meta-analysis suggests that lymph node (LN) retrieval may be inferior when gastrectomy for GCa is performed laparoscopically rather than open. The purpose of this study was to examine the pathologic evaluation, postoperative morbidity and receipt of adjuvant treatment associated with adoption of D2 lymphadenectomy in a community setting. Methods: Routine D2 LN dissection was instituted as part of laparoscopic GCa resection at two community hospitals in Toronto in July 2008. Sequential cases up to Feb 2011 were identified and charts reviewed retrospectively. LN retrieval, margin status, morbidity, mortality and receipt of adjuvant treatment were examined. Results: Twenty-nine patients were identified; 69% were male and the median age was 69 (28-84). All patients underwent D2 lymphadenectomy, 10 with total gastrectomy (TG) and 19 with subtotal (STG). Pathologic evaluation showed that all patients underwent an R0 resection. Median number of LNs retrieved was 32 (15-62) and 93% of patients had adequate LN assessment according to AJCC 7 staging criteria. Sixty-five percent of patients had nodal metastases. There were 8 major complications in 7 patients including 3 post-operative deaths (10% mortality): one patient died in hospital from anastomotic leak and two after discharge from PE (1) and evisceration through the specimen extraction site (1). Four patients commenced neoadjuvant chemotherapy, but only 2 completed the planned pre-operative regimen. Ten additional patients started post-operative adjuvant chemo-radiotherapy, but only 5 completed it. Fifteen patients received no adjuvant treatment. Reasons for lack of adjuvant treatment were: early stage (n=4), medically unfit (2), post-operative death (2), patient declined (5) and early post-operative distant metastatic disease (2). Conclusions: Laparoscopic gastrectomy with D2 lymphadenectomy can be performed in a community setting with excellent margin status and LN retrieval results and complication rates comparable to those previously reported in prospective trials of open resection. Barriers to receipt/completion of adjuvant therapy in this setting should be explored.

Transanal endoscopic microsurgery: A single centre experience

Introduction: The aim of this study was to evaluate the implementation of transanal endoscopic microsurgery (TEM) technique for the removal of rectal adenomas or early rectal cancer in the Centre of Oncosurgery, Oncology Institute of Vilnius University. Methods: From October 2009 to June 2011 a total of 41 patients underwent TEM for rectal adenomas or early rectal cancer. 19 were women and 22 men, median age was 64 years, range 31 to 87 years. Rectal lesions were from 0 9 to 7 0 cm in diameter, and 3 to 13 cm from the anal verge. Full thickness excision with one cm safety margins was attempted in all cases, followed by closing of the rectal wall defect in one-layer using a running monocryl 3.0 suture using silver clips. In one case (TEM for T2 rectal cancer), the abdominal cavity was penetrated and two-layer closure was performed. Results: In these series of 41 patients there were no complications or deaths. Hospital stay ranged from 2 to 13 days, average 6 days. Final histology revealed 24 (59%) lesions to be tubular or villous adenomas, in 6 (15%) foci of carcinoma in situ (pTis) were present. Five (12%) were TNM stagepT1 and 4 (10%) werepT2 cancers. Well-differentiated neuroendocrine tumors were found in 2 (4%). A 60 year old woman underwent open partial TME in the pT1 group; her tumor was in upper third of the rectum and preoperatively judged as pTis. In another case (pT1 group) in an 81 year old man, lymphovascular invasion was present on final pathology. He received postoperative adjuvant chemoradiotherapy. All patients are under surveillance. Conclusion: TEM is safe and is an alternative to transanal excision for rectal adenomas and early rectal cancer. Further follow-up is necessary to evaluate recurrence rates and oncological results in a subgroup of patients with invasive rectal cancer. Key words: Rectal polyp; Rectal cancer; Transanal endoscopic microsurgery (TEM) DOI: http://dx.doi.org/10.4038/sljs.v29i1.3577 Sri Lanka Journal of Surgery 2011: 29(1) 19-22

The current landscape of locally advanced rectal cancer

Postoperative adjuvant chemoradiotherapy was recommended as the standard treatment for patients with rectal cancer because it reduces local recurrence. This paradigm shifted with the use of neoadjuvant chemoradiotherapy, which not only reduces local recurrence but also improves sphincter preservation and surgical outcomes. However, the treatment of rectal carcinoma remains complicated. The accuracy of tumor staging can be compromised depending on the imaging modality used. The addition of modern chemotherapeutics and biologics to 5-fluorouracil as radiation sensitizers is questionable. Oxaliplatin as a radiation sensitizer has minimal effects on the pathologic complete response, but improves the radiographical response at the expense of an increased risk of toxicities. The role of biologics in addition to radiation therapy continues to be explored. Attention has focused on improving diagnostic imaging, radiation oncology, and surgical techniques, treatment regimens, and on exploring a role of molecular markers for patients with rectal cancers. We review the pivotal trials that have led to the current treatment paradigm for locally advanced rectal cancer and discuss novel methodologies that are being developed for the treatment of this prevalent malignancy.

Pattern of recurrence after curative surgery in thoracic esophageal squamous cell carcinoma: A 6-year experience with 1,020 patients.

e14557 Background: The knowledge of patterns of recurrence for patients with esophageal carcinoma will be of great value in a clinic when designing therapeutic strategies. The current study reports mode, timing and predictive factors of recurrence after curative surgery for thoracic esophageal squamous cell carcinoma (TESCC). Methods: A retrospective study in a series of 1,020 curatively (R0) resected patients from 2003 to 2008 at Zhejiang Cancer Hospital. Results: The 2 and 5 years recurrence rate were 39.0% and 59.2% respectively. Variables associated with a higher rate of recurrence on univariate analysis were male, length of tumor ≥5cm, deeper depth of invasion, more lymph node metastasis, higher histologic grade, vessel involvement positive, postoperative radiotherapy and postoperative chemotherapy. By multivariate analyses, gender (HR 1.7; 95%CI 1.2–2.5; p=0.002), depth of invasion (HR 1.4; 95%CI 1.2–1.6; p<0.001), lymph node involvement (HR 1.4; 95%CI 1.3–1.5; p<0.001) and postoperative adjuvant radiotherapy (HR 1.3; 95%CI 1.0–1.6; p=0.026) or chemotherapy (HR 1.5; 95%CI 1.2–1.8; p=0.001) were independent predictive factors of recurrence. Less than 10% patients with more than 10 metastatic nodes were free from relapse 3 years after surgery. More than 85% recurrence occurred within 36 months. Postoperative radiotherapy or chemotherapy didn't prolong failure free survival (FFS) significantely, especially in patients with early-stage disease. Conclusions: Gender, depth of invasion, lymph node involvement and postoperative adjuvant therapy were independent predictors of recurrence. Postoperative radiotherapy or chemotherapy didn't prolong FFS significantely. For patients with R0 resection of TESCC, postoperative adjuvant radiochemotherapy need to select appropriate patients.

Sites of gastric cancer recurrence after adjuvant chemoradiotherapy.

68 Background: Since the Intergroup 0116 study in 2000, adjuvant post-operative chemoradiotherapy (CRT) has been offered routinely to similar patients with resected gastric cancer at Princess Margaret Hospital (PMH) using CT-planned and 3D conformal/intensity modulated radiotherapy (RT). The objective of this study was to analyze patterns of recurrence with respect to RT treatment volumes. Methods: Date and site (local, locoregional or distant) of first recurrence data was obtained from chart review for all patients treated at PMH with adjuvant CRT for resected gastric adenocarcinoma (Jan. 1, 2000-Nov. 30, 2009). Patients whose recurrences were limited to local (gastric remnant, duodenal margin, gastric bed recurrence) and/or regional sites (regional lymph node recurrence) were selected for analysis. When available, diagnostic imaging of recurrence site was registered to the original planning RT dataset. The center of mass for each recurrence was identified as a point and its location categorized according to the isodose encompassing it; in-field (≥ 90%), marginal (50%-89%), and out-of-field (&lt; 50%). Results: Three-year OS, and RFS were 66% (95% CI: 58-73) and 58% (50-60), respectively. Of 203 patients treated, 75 recurrences were identified (Table). Of the 13 local/locoregional recurrences, 4 were in-field, 1 marginal, 1 could not be registered due to change in body habitus, and 7 did not have an available original dataset. Conclusions: Rates of isolated local and/or regional recurrence in this study were low. This represents a change in the pattern seen with surgery alone suggesting the addition of CRT results in decreased isolated local and/or regional recurrence. Of the small number of local and/or regional recurrences available for analysis, all were in-field or marginal. Further studies involving a larger cohort of patients might allow for more meaningful analysis of trends in recurrence site with evolving RT techniques. [Table: see text] No significant financial relationships to disclose.

Neoadjuvant chemoradiotherapy has a potential role in pancreatic carcinoma

Pancreatic cancer has an extremely poor prognosis, only a small minority of patients undergo a resection with curative intent. Chemotherapy and/or radiochemotherapy may improve this by prolonging survival or disease-free interval and improving resectability and the proportion of microscopically complete (R0) resections. With regard to prolonging survival, both in the postoperative adjuvant setting and in locally advanced disease, chemotherapy has a positive but limited effect on survival and may be considered standard. The role of postoperative adjuvant radiochemotherapy remains debatable. For improving resectability/proportion of R0 resections, many studies suggest that the proportion of patients undergoing a resection during exploration and the proportion of R0 resections increase after neoadjuvant radiochemotherapy. This may improve the prognosis of patients with a resectable or borderline resectable pancreatic carcinoma. The effect of neoadjuvant radiochemotherapy, if any, is modest. The search for better combinations, including targeted therapy, must continue. The interpretation of single-arm studies is hampered by (selection) biases. The reporting of pathology and study endpoints should be internationally standardized. To avoid biases in studies of patients with (borderline) resectable tumours, prospective parallel registration of all patients referred for surgery would help. Ultimately, randomized controlled phase III trials should establish the role of neoadjuvant radiochemotherapy. Thus, neoadjuvant radiochemotherapy has a potential benefit in resectable and borderline resectable pancreatic cancer, but better combinations are warranted.

Postoperative adjuvant chemoradiotherapy versus radiotherapy alone for head and neck squamous cell carcinoma: A meta-analysis evaluating the role of chemotherapy schedules.

5583 Background: To compare concurrent post-operative chemoradiotherapy (POCRT) with post operative radiotherapy alone (PORT) for head and neck squamous cell carcinoma (HNSCC), evaluating different chemotherapy regimens used. Methods: A meta-analysis of RCT was performed comparing POCRT to PORT for HNSCC. The MEDLINE, EMBASE, and Cochrane Library databases, as well as abstracts published in the annual proceedings were systematically searched. We assessed methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment. Results: Pooled results from 8 randomized trials (1,808 patients) evaluating POCRT (3 trials using cisplatin alone, 2 mitomycin –c, 2 carboplatin and 1 cisplatin + 5-FU) in HNSCC showed significant decreased of mortality (OR=0.68, CI95%-0.52, 0.86, p<0.0001) as compared to PORT. In the subgroup analysis cisplatin alone was the only chemotherapy schedule that showed a reduction in overall mortality rate when compared to PORT (OR=0.62, CI95%-0.47, 0.82, p=0.0008). There was significant difference for local recurrence among those patients receiving PORCT and PORT (OR=0.46, CI 95% 0.37-0.58, p<0.0001). In the subgroup analysis the carboplatin schedule was the only subgroup that there was not any difference for local recurrence rates when compared to PORT (OR=0.72, CI 95% 0.46-1.13, p=0.25). Conclusions: Our data demonstrate that adjuvant cisplatin-enhanced radiation therapy is more effective than PORT for high-risk tumors in terms of locoregional control and survival, when compared to other regimens. Results of the present study failed to demonstrate that the addition of carboplatin to PORT provides a statistically significant benefit in terms of local control and survival rate. No significant financial relationships to disclose.

Is Adjuvant Chemoradiotherapy Overtreatment in Cervical Cancer Patients With Intermediate Risk Factors?

To determine whether adjuvant chemoradiotherapy (CRT) improves the outcome of cervical cancer patients with intermediate risk factors. Between January 2000 and June 2006, the medical records of 735 patients who had undergone radical surgery for Stage IB-IIA cervical cancer were reviewed retrospectively. Of the 735 patients, 172 with two or more intermediate risk factors (i.e., lymphovascular space involvement, deep stromal invasion, and tumor size≥2 cm) were grouped as follows according to the adjuvant treatment received: 34 patients, no further treatment; 49 patients, RT; and 89 patients, CRT. The significance of the clinical parameters and recurrence-free survival of each group were analyzed. Of the 172 patients with any of the intermediate risk factors, 137 (79.6%) had two or more intermediate risk factors. Of the 172 patients, 12 developed recurrences (6.4%)->(7.0%), with 6 in the pelvis and 6 in distant sites. All 12 recurrences occurred in those who had two or more intermediate risk factors (sensitivity, 100%); however, only six recurrences were detected in patients who met the Gynecologic Oncology Group criteria for the intermediate-risk group (sensitivity, 50%; Z test, p<.05). A statistically significant difference was found in the 3-year recurrence-free survival rate among the no further treatment, RT, and CRT groups (67.5%, 90.5%, and 97.5%, respectively; p<.05). The incidence of Grade 3-4 hematologic and gastrointestinal toxicities was not significantly different statistically between the RT and CRT groups (6.1% and 13.4%, respectively; p > .05). Postoperative adjuvant CRT can improve the outcome of cervical cancer patients with intermediate risk factors, with low increase in toxicity.

Oncological Outcome of Transoral Laser Surgery in Laryngeal Carcinomas

AbstractThe principles of treatment of laryngeal carcinoma have undergone changes over the last few years and can be very complex with early (I-II) and advanced (III-IV) stage diseases to be differentiated. Recent emphasis is on organ preservation and laryngeal function. Transoral CO2laser surgery has become a standard surgical procedure not only in early stage I and II laryngeal carcinomas but also in advanced stage III cases in combination with postoperative adjuvante radiochemotherapy. This retrospective study reflects the role of transoral laser surgery as a single or multimodality treatment regime with neck dissection and postoperative radiochemotherapy in laryngeal carcinomas.From January 1997 to February 2007, 239 patients (215 men and 24 women; mean age 61 years) were examined with laryngeal squamous cell carcinoma (stage I-IV). 220 out of these 239 patients underwent transoral laser surgery, depending on their tumor stage either as a single or as a multimodality treatment regimen in combination with bilateral neck dissection and postoperative radio-chemotherapy. Thirteen patients underwent a transcervical tumor resection, 5 patients underwent radiochemotherapy alone and one patient refused a treatment of his tumor disease. Median follow-up time was 60 months.The 5-year overall survival rate of the 220 patients who were treated with laser surgery was 86%. The 5-year recurrence-free survival rate was 69.5%. After laser surgical interventions, postoperative complications occurred in 16%.The oncological outcome of transoral laser surgery as a single mode in early laryngeal carcinomas or in combination with bilateral neck dissection and postoperative adjuvant radiochemotherapy in advanced tumor stages is satisfying if clean surgical tumor margins (R0) can be reached. If tumor-free margins cannot be achieved (R1and R2resection) and transoral revision is not possible, transcervical procedures (total or partial laryngectomy) must be considered.

Adjuvant chemotherapy with 5-FU or regimens including oral fluoropyrimidine for curable gastric cancer

Since 2000, several studies have reported positive results in reasonable-size randomized controlled trials of adjuvant treatment for potentially curable gastric cancer. At present, postoperative adjuvant chemoradiotherapy and perioperative chemotherapy are the standard of care in the United States and Europe (including Great Britain), respectively, while postoperative S-1 monotherapy is the standard of care in Japan. The effect of adjuvant treatment varies according to the type of surgery, and the best results so far have been observed in the adjuvant chemotherapy of TS-1 for gastric cancer (ACTS-GC) trial, in which D2 surgery followed by S-1 monotherapy was tested. The role of radiotherapy after D2 dissection remains unclear.

Prognosis of Ampullary Carcinoma after Radical Resection and Its Carcinogenesis

The carcinoma of the ampulla of Vater is the second most common periampullary cancer and also the most common neoplasm of the small intestine. In previous studies, the 5-year survival rate of patients with carcinoma of the ampulla of Vater ranged from 38.0 to 67.7% after pancreaticoduodenectomy. Lymph node involvement, poor differentiation, pancreatic invasion and tumor stage were predictors of a poor prognosis. Results vary among institutions and postoperative adjuvant chemoradiotherapy does not improve long-term survival after radical surgery. Also, in reports from the Surveillance, Epidemiology, and End Results (SEER) program in the United States, the resection rate of ampullary cancer was only 40% and 5-year survival was 36.8% in this large cohort study. From this unbiased registry data, the prognosis of ampullary carcinoma after radical resection is fair and additional treatment modalities are needed to improve survival. The adenoma to carcinoma sequence raises suspicion of carcinoma of the ampulla of Vater. In the carcinogenesis of ampullary carcinoma, possible mechanisms involve include tumor suppressors, oncogenes, DNA replication, cell cycle regulation, growth factors, the cytoskeleton and cell adhesion, among others. Nevertheless, the mechanism, which appears to be complex, remains obscure. Further efforts are needed to elucidate the mechanism and to improve the survival of patients with ampullary carcinoma.

Surgery and adjuvant chemotherapy

It was clearly demonstrated that good local control by either radiotherapy or D2 surgery is essential to cure gastric cancer. D2 surgery can be carried out safely with a large volume of patients and can provide better survival than limited surgery. More extended surgery than D2 cannot provide better survival and causes greater morbidity; therefore, it should not be carried out as prophylactic lymphadenectomy. The effect of adjuvant treatment depends on the type of surgery. Neoadjuvant plus post-operative triplet chemotherapy, postoperative adjuvant chemoradiotherapy, and postoperative S-1 monotherapy now are the standards of care in Europe, the United States, and Japan, respectively.

Perioperative therapy in gastric cancer

Gastric cancer is still one of the predominant causes of death on account of gastrointestinal neoplasias. In recent years, chemotherapy and radiotherapy have substantially improved the outcome in operable gastric cancer patients. A benefit in median overall survival is reported for perioperative chemotherapy as well as for postoperative adjuvant radio-chemotherapy. But there is still a controversy about the best treatment sequence. The aim of this paper is to critically review current literature, to discuss the pros and cons of neoadjuvant (preoperative) or postoperative adjuvant therapy and to give treatment recommendations based on large phase III trials.

Number and percentage of pathologically involved lymph nodes (pLN) in patients (pts) with pancreatic adenocarcinoma (PA) predicts for overall survival (OS) in pts treated with postoperative adjuvant chemoradiotherapy (CRT)

15509 Background: pLN status may predict OS in pts following resection for PA. However, among pts treated with postoperative CRT at our institution, pN0 vs pN1 status as defined by AJCC criteria wa...

Postirradiated Neuroendocrine Carcinoma of the Sinonasal Tract

Neuroendocrine carcinoma (NEC) of the sinonasal tract is rare. In this present study, we report our treatment experience with sinonasal NEC. Retrospective case series. A retrospective review of the clinical outcomes and pathology of 18 patients with NEC arising from the sinonasal region. Ten tumors were primary NEC without previous radiation, and eight tumors were postirradiated NEC occurring within the radiation field for previous nasopharyngeal carcinoma in six patients and tonsillar lymphoma in one and neck metastasis of unknown primary origin in one, with an interval between previous radiotherapy and diagnosis of NEC from 82 to 385 months, with a mean of 197 months. Fifteen tumors were small cell carcinoma, two were atypical carcinoid, and one was typical carcinoid tumor. Fifteen patients underwent surgery with/without postoperative adjuvant chemoradiotherapy. Three patients received induction chemotherapy or primary radiotherapy with further definitive treatment. The 5-year disease-free and overall survival rates of all 18 patients were 56.1% and 62.2%, respectively. In comparing primary NEC with postirradiated NEC, they were similar in age, sex distribution, stage, pathology, and treatment, and the 5-year overall survival rates were 70% and 62.5%, respectively. In this series, postirradiated NEC is common, which may be the result of there being a large number of long-term nasopharyngeal carcinoma survivors. The prognoses of postirradiated NEC and primary NEC appear to be similar despite the relatively short follow-up period in the postirradiated NEC group.

Current status of chemoradiotherapy for gastric cancer in Japan

Chemoradiotherapy (CRT) is the latest modality to be explored as a treatment for gastric cancer. Advances have been made in the United States with CRT as preoperative or postoperative adjuvant treatment. The rationale for preoperative or postoperative adjuvant CRT is to increase the curability of surgery or to prevent local recurrence, because standard surgery (D0 or D1) is not sufficient to control local relapse and improve survival where disease has become advanced. D2 is standard in Japan and D2 gastrectomy plus postoperative adjuvant chemotherapy with S-1 is currently standard for stage II and III cancer. Predominant recurrence patterns associated with these advanced disease stages are peritoneal dissemination and hematogenous metastasis. Local relapse or regional nodal recurrence is infrequent. CRT has been provided at only a limited number of institutions in Japan. The response to and safety of CRT for gastric cancer, in combination with various chemotherapeutic agents, are currently being studied in patients with unresectable or recurrent disease. Considering the high response rate, CRT seems to be an attractive option. In the near future, an examination will be made to ascertain whether neoadjuvant CRT in combination with extensive surgery has survival benefits in the treatment of locally advanced disease. Prior to this, a phase I/II study should be conducted in patients with unresectable or recurrent disease.

Gelatinase B Expression as a Prognostic Factor in Patients With Stage II/III Rectal Carcinoma Treated by Postoperative Adjuvant Therapy

The matrix-metalloproteinases (MMPs) are thought to be critically involved in tumor invasion and metastasis. This retrospective study was aimed both to examine the gelatinase expression status in patients with rectal cancer and to investigate their prognostic value on survival. Sixty patients who underwent postoperative adjuvant chemoradiotherapy for Stage II and III rectal carcinoma were included. Expressions of MMP-2, MMP-9, and tissue inhibitors of MMP (TIMP-1 and TIMP-2) were analyzed by immunohistochemistry in paraffin-embedded primary rectal cancers and graded for the intensity and the percentage of cells stained. The relation between the expression of the markers studied and clinicopathologic features were evaluated for the primary study endpoint. The data were also analyzed using a multivariate Cox proportional hazards model for prognosis as a secondary endpoint. Positive MMP-9 expression was observed in 70% of the tumors. The ratio of tumors with positive MMP-9 expression was increased according to N stage (P = 0.005), AJCC stage (P = 0.005), and tumor differentiation (P = 0.017). Overall survival was reduced in poorly differentiated tumors and tumors with positive MMP-9 expression (P = 0.002). Disease-free survival was lower in patients with positive MMP-9 expression (P = 0.007). Multivariate analysis indicated that positive MMP-9 expression was an independent predictor of reduced overall survival (P = 0.0103) and reduced disease-free survival (P = 0.0360). The other markers studied were associated with neither any clinicopathologic feature nor any survival parameter. MMP-9 expression was observed in the tumors of patients with Stage II and III rectal carcinoma in comparable values and was characterized by poor overall survival and disease-free survival.

Comparative Outcome Between Chemoradiotherapy and Lateral Pelvic Lymph Node Dissection Following Total Mesorectal Excision in Rectal Cancer

To evaluate comparative outcome between adjuvant postoperative chemoradiotherapy (postoperative CRT) and lateral pelvic lymph node dissection (LPLD) following total mesorectal excision (TME) in rectal cancer patients. Although TME results in lower rate of locoregional recurrence compared with conventional surgery, these 2 treatment modalities following TME have not adequately been appraised until the present trend of preoperative chemoradiotherapy. Between 1995 and 2000, patients with stage II and III rectal cancer underwent TME plus postoperative CRT (n = 309) or LPLD (n = 176). Patients in the postoperative CRT group received 8 cycles of 5-fluorouracil plus leucovorin and 45 Gy pelvic radiotherapy. Patients in the LPLD group underwent lateral lymph node dissection outside the pelvic plexus. The 5-year overall and disease-free survival rates were 78.3% and 67.3% in the postoperative CRT group, respectively, and 73.9% and 68.6% in the LPLD group, respectively, without significant differences between these groups. Patients in the LPLD group with stage III lower rectal cancer had a locoregional recurrence rate 2.2-fold greater than those in the postoperative CRT group (16.7% vs. 7.5%, P = 0.044). Multivariate analysis showed that APR and advanced T-category (T4) were significantly associated with locoregional recurrence, whereas lymph node metastases, high preoperative serum carcinoembryonic antigen, and APR were significantly associated with shortening of disease-free survival. Postoperative-CRT and LPLD following TME resulted in comparable survival rates, but the locoregional recurrence rate was higher in the LPLD group. These findings suggest that initial surgery is appropriate for rectal cancer patients who are candidates for low anterior resection without extensive local disease (T1-T3), regardless of lymph node status.