Clinical aspects of multimodality therapy for resectable locoregional esophageal cancer.

Radical resection has been considered the only possible way to save the lives of patients with esophageal cancer. Therefore, tremendous efforts have been made in order to improve the surgical results for resectable locoregional esophageal cancer. Various surgical approaches have been developed. Combination therapies such as neoadjuvant, adjuvant chemotherapy, and neoadjuvant chemoradiation have been extensively investigated in numerous randomized clinical trials. Due to insufficient surgical results and high postoperative mortality rates, definitive chemoradiation has been studied as alternative treatment in selected patients, based on the concept that combined-modality therapy allows simultaneous treatment of locoregional disease and systemic micrometastases. Chemoradiation has shown survival rates equivalent to surgery in some non-randomized comparative studies. Presently, concerns appear to be shifting to the question of whether definitive chemoradiation could be an alternative to surgery in the primary treatment of resectable locoregional esophageal cancer. Recently, 2 randomized trials, comparing definitive chemoradiation with chemoradiation and surgery were published. These trials seem to show at first glance that definitive chemoradiation can achieve results comparable to surgery with neoadjuvant chemoradiation. More sophisticated trials should be conducted as treatment modalities used in these trials are far from routine.     

Predictive value of 18-fluoro-deoxy-glucose-positron emission tomography (18F-FDG-PET) in the identification of responders to chemoradiation therapy for the treatment of locally advanced esophageal cancer

OBJECTIVE: To evaluate the utility of F-FDG-PET in predicting response to concomitant chemoradiation in locally-advanced esophageal cancer. SUMMARY BACKGROUND DATA: Approximately 25% of esophageal cancer patients experience a pathologic complete response (pCR) to preoperative chemoradiation therapy. Computed tomography, endoscopy, and endoscopic ultrasound are unable to identify patients experiencing a pCR. Growing evidence supports the use of F-FDG-PET in the staging of esophageal cancer in its ability to detect occult metastatic and lymph nodal disease. The identification of patients with a pCR to chemoradiation could potentially spare those patients the morbidity associated with a resection. METHODS: Eligibility criteria included T3-T4N0M0 or T1-T4N1M0 esophageal cancer. Patients underwent an initial F-FDG-PET before treatment and then repeated 4 to 6 weeks after chemoradiation, prior to the esophagectomy. Chemoradiation consisted of: cisplatinum, 5-fluorouracil, and radiation to a median dose of 50.4 Gy. Pathologic response was determined from a systematic review of the esophagectomy specimens. RESULTS: Sixty-four patients have completed therapy to date. Response was as follows: pCR 27%, pathologic residual microscopic (pCRmicro) 14.5%, partial response 19%, and stable or progressive disease 39.5%. A pretreatment standardized uptake value (SUVmax1hour) > or = 15 was associated with an observed 77.8% significant response (pCR + pCRmicro) compared with 24.2% for patients with a pretreatment SUVmax1hour < 15 (P = 0.005). Significant response was observed in 71.4% of patients with a decrease in SUVmax1hour > or = 10 compared with 33.3% when the SUVmax1hour decreased <10 (P = 0.004). CONCLUSIONS: Pretreatment and posttreatment F-FDG-PET can be useful for predicting significant response to chemoradiation in esophageal cancer. These data should be considered in evaluation of patients for esophagectomy after chemoradiation.     

Is Final TNM Staging A Predictor for Survival in Locally Advanced Rectal Cancer after Preoperative Chemoradiation Therapy?

Background Neoadjuvant chemoradiation therapy has improved the local control rate and overall survival in locally advanced rectal cancers. The purpose of this retrospective study is to evaluate the correlation between the final pathologic stage and survival in these patients. Methods Patients with biopsy-proven rectal carcinoma, pretreatment staging by magnetic resonance imaging such as T3 or T4 tumors, or node-positive disease were treated with preoperative concomitant 5-fluorouracil-based chemotherapy and radiation, followed by radical surgical resection. Clinical outcome with survival, disease-free survival, recurrence rate, and local recurrence rate were compared with each T and N findings using the American Joint Committee on Cancer Tumor-Node-Metastasis (TNM) staging system. Results A total of 248 patients were enrolled in this study. Overall survival and disease-free survival at 1, 3, and 5 years were 97.1, 92, and 89.9% and 87.5, 71.1, and 69.5%, respectively. Thirty-six patients (14.5%) had a pathologic complete response after neoadjuvant therapy. The recurrence rate was significantly different between the pathologic complete response group and residual group (5.6 vs 31.1%; P = .002). Five-year disease-free survival was significantly better in the complete response group than the residual tumor group (93 vs 66%; P = .0045). There was no statistical difference in survival or locoregional recurrence rate between these two groups. Conclusions Posttreatment pathologic TNM stage is correlated to disease-free survival and tumor recurrence rate in locally advanced rectal cancer after preoperative chemoradiation. Also, pathologic complete response to neoadjuvant treatment has its oncologic benefit in both overall recurrence and disease-free survival.     

Staging of pancreatic cancer before and after neoadjuvant chemoradiation

Neoadjuvant chemoradiation therapy is used at many institutions for treatment of localized adenocarcinoma of the pancreas. Accurate staging before neoadjuvant therapy identifies patients with distant metastatic disease, and restaging after neoadjuvant therapy selects patients for laparotomy and attempted resection. The aims of this study were to (1) determine theutilityof staging laparoscopy in candidates for neoadjuvant therapy and (2) evaluate the accuracy of restaging CT following chemoradiation. Staging laparoscopy was performed in 98 patients with radiographically potentially resectable (no evidence of arterial abutment or venous occlusion) or locally advanced (arterial abutment or venous occlusion) adenocarcinoma of the pancreas. Unsuspected distant metastasis was identified in 8 (18%) of 45 patients with potentially resectable tumors and 13 (24%) of 55 patients with locally advanced tumors by CT Neoadjuvant chemoradiation therapy and restaging CT were completed in a total of 103 patients. Thirty-three patients with potentially resectable tumors by restaging CT underwent surgical exploration and resections were performed in 27 (82%). Eleven (22%) of 49 patients with locally advanced tumors by restaging CT were resected, with negative margins in 55%; the tumors in these 11 patients had been considered locally advanced because of arterial involvement on restaging CT Staging laparoscopy is useful for the exclusion of patients with unsuspected metastatic disease from aggressive neoadjuvant chemoradiation protocols. Following neoadjuvant chemoradiation, restaging CT guides the selection of patients for laparotomy but may overestimate unresectability to a greater extent than does prechemoradiation CT. Presented at the 2001 Americas Congress of the American Hepatopancreatobiliary Association, Miami, Fla., February 25, 200l.     

Staging accuracy of endoscopic ultrasound based on pathologic analysis after minimally invasive esophagectomy

Endoscopic ultrasonography (EUS) is a common staging modality used in patients with esophageal cancer. The objective of this analysis was to evaluate the accuracy and sensitivity of EUS in determining the depth of penetration (T stage) and nodal status (N stage) in patients with esophageal cancer who underwent minimally invasive esophagectomy (MIE). A retrospective analysis of all patients at a university hospital who underwent preoperative EUS followed by MIE for cancer was performed. We compared the results of preoperative EUS to final pathologic analyses of the esophageal specimen, examining the accuracy of EUS staging. Ninety-five patients with esophageal cancer who underwent MIE had preoperative EUS. Twenty-four of the 95 patients were excluded for lack of a repeat EUS after neoadjuvant therapy before resection. Hence, 71 patients were evaluated for the accuracy of EUS staging. The accuracy of EUS for T0 disease was 80 per cent; T1 disease was 75 per cent; T2 disease was 39 per cent; and T3 disease was 88 per cent. The overall EUS accuracy for T stage was 72 per cent with overstaging occurring mostly for pathologic T1 tumors in 18 per cent and understaging occurring mostly for pathologic T3 tumors in 11 per cent. The sensitivity and specificity for detection of nodal involvement were 79 per cent and 74 per cent, respectively. However the accuracy for T and N staging by EUS after neoadjuvant therapy decreased to 63 per cent and 38 per cent, respectively. Endoscopic ultrasound in the absence of neoadjuvant therapy is a relatively accurate and sensitive modality for determining the depth of tumor penetration and the presence of nodal disease in patients with esophageal carcinoma. The accuracy for T and N staging is less reliable after neoadjuvant therapy.     

Presentation of gastroesophageal junction adenocarcinoma with synchronous metastases at the small intestine. Could treatment with curative intent be considered? A case report

IntroductionIntroduction of multimodality treatment as the standard of care for management of esophageal and gastroesophageal junction (GEJ) cancer over the last years has led to significant improvement in survival for patients with localized disease. Nevertheless, treatment with curative intent is not considered in the case of metastatic disease. We report a case of a locally advanced GEJ adenocarcinoma with solitary resectable synchronous metastases at the jejunum and a good response to neoadjuvant therapy followed by esophagectomy with curative intention.Case presentationThis is the case of a patient with poorly differentiated adenocarcinoma of the GEJ with synchronous metastases at the jejunum. The patient underwent extensive work-up including PET-CT. The metastases at the jejunum were completely resected during an initial staging laparoscopy and there was no evidence of further metastatic disease. The patient received chemotherapy and re-staging showed remarkable tumor response. Esophagectomy with curative intent was performed. Histopathology showed complete pathologic response after chemotherapy. Although our patient had a stage IV disease at presentation, he remained metastasis-free for a significant period of time, with no evidence of any distant recurrence during a follow-up of 16 months after esophagectomy.Discussion and conclusionsSynchronous metastasis to the small bowel from an esophageal carcinoma is a rare entity. Routine PET-CT in addition to conventional CT may assist in more precise staging of a patient with resectable disease. Stage IV esophageal cancer with limited and resectable metastatic disease and good tumor response to oncological therapy may be considered for treatment with potentially curative intent.     

The effects of neoadjuvant chemoradiation on pTNM staging and its prognostic significance in esophageal cancer

For esophageal cancer, it is not clear if pathologic TNM staging after chemoradiation and resection will have the same prognostic significance compared with patients who undergo resection only. From 1995 to 2004, prospectively collected data from 279 patients with intrathoracic squamous cell cancers were analyzed. Patients were given chemoradiation either as part of a randomized trial comparing neoadjuvant chemoradiation with surgical resection alone, or because of advanced disease at presentation. One hundred seventy patients had surgical resection only (surgery), and 109 had neoadjuvant chemoradiation (CRT plus surgery). In the surgery group, pT1, 2, 3, and 4 disease was found in 15, 17, 104, and 34 patients, respectively; their respective pN1 rates were 13.3%, 29.4%, 57.7%, and 64.7%, P<0.01. In CRT plus surgery, pT0, T1, 2, 3, and 4 were found in 48, 12, 23, 21, and 5 patients, respectively; their respective pN1 rates were 31.3%, 16.7%, 21.7%, 52.4%, and 20%, P=0.44. Logistic regression analysis of factors predictive of pN1 showed that pT stage correlated with pN1 status (P=0.005) in the surgery group, but not for the CRT plus surgery group. Cox regression analysis demonstrated that in the surgery group, pT, pN, and R category, and overall pTNM stage, were independent prognostic factors, whereas pN, R category, and gender were identified as relevant for CRT plus surgery. After chemoradiation, pT and overall pTNM stage groupings were not as clearly prognostic as in patients without prior therapy. Nodal status remains an important prognostic factor. Presented at the Forty-Seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, Los Angeles, California, May 20–24, 2006 (oral presentation).     

A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer

BACKGROUND: Esophagectomy is a standard treatment for resectable esophageal cancer but relatively few patients are cured. Combining neoadjuvant chemoradiation with surgery may improve survival but treatment morbidity is a concern. We performed a meta-analysis of randomized controlled trials (RCTs) that compared the use of neoadjuvant chemoradiation and surgery with the use of surgery alone for esophageal cancer. METHODS: Medline and manual searches were done to identify all published RCTs that compared neoadjuvant chemoradiation and surgery with surgery alone for esophageal cancer. A random-effects model was used and the odds ratio (OR) was the principal measure of effect. Systematic quantitative review was done for outcomes unique to the neoadjuvant chemoradiation treatment group, such as pathological complete response. RESULTS: Nine RCTs that included 1,116 patients were selected with quality scores ranging from 1 to 3 (5-point Jadad scale). Odds ratio (95% confidence interval [CI]; P value), expressed as chemoradiation and surgery versus surgery alone (treatment versus control; values <1 favor chemoradiation-surgery arm), was 0.79 (0.59, 1.06; P = 0.12) for 1-year survival, 0.77 (0.56, 1.05; P = 0.10) for 2-year survival, 0.66 (0.47, 0.92; P = 0.016) for 3-year survival, 2.50 (1.05, 5.96; P = 0.038) for rate of resection, 0.53 (0.33, 0.84; P = 0.007) for rate of complete resection, 1.72 (0.96, 3.07; P = 0.07) for operative mortality, 1.63 (0.99, 2.68; P = 0.053) for all treatment mortality, 0.38 (0.23, 0.63; P = 0.0002) for local-regional cancer recurrence, 0.88 (0.55, 1.41; P = 0.60) for distant cancer recurrence, and 0.47 (0.16, 1.45; P = 0.19) for all cancer recurrence. A complete pathological response to chemoradiation occurred in 21% of patients. The 3-year survival benefit was most pronounced when chemotherapy and radiotherapy were given concurrently (OR 0.45, 95% CI 0.26 to 0.79, P = 0.005) instead of sequentially (OR 0.82, 95% CI 0.54 to 1.25, P = 0.36). CONCLUSIONS: Compared with surgery alone, neoadjuvant chemoradiation and surgery improved 3-year survival and reduced local-regional cancer recurrence. It was associated with a lower rate of esophageal resection, but a higher rate of complete (R0) resection. There was a nonsignificant trend toward increased treatment mortality with neoadjuvant chemoradiation. Concurrent administration of neoadjuvant chemotherapy and radiotherapy was superior to sequential chemoradiation treatment scheduling.     

Are patients with esophageal cancer who become PET negative after neoadjuvant chemoradiation free of cancer?

BACKGROUND: Esophageal cancer continues to increase in incidence. Many patients are presenting with stage II or greater disease and proceeding to neoadjuvant chemoradiation therapy before resection. Approximately 30% of patients will achieve a complete response and might not benefit from proceeding to resection. This study will examine the ability of PET to predict patients with a complete pathologic response. STUDY DESIGN: A query of our IRB-approved esophageal database revealed 81 patients who underwent a pre- and postchemoradiation PET scan and then proceeded to esophageal resection. Statistical analysis was performed to determine the ability of PET to predict a complete pathologic response. RESULTS: When comparing posttherapy PET with final pathology, it was determined that PET could not consistently differentiate a complete pathologic response from patients who still had persistent disease. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 61.8%, 43.8%, 70%, 35%, and 56%, respectively, for patients with a complete PET response after neoadjuvant therapy. CONCLUSIONS: A complete PET response after neoadjuvant chemoradiation is not substantially predictive of a complete pathologic response. Patients should still be referred for resection unless distant metastases are identified.     

胰腺癌新辅助化疗进展

胰腺癌目前仍然是临床非常棘手的问题,但在一些胰腺外科中心通过手术切除改善了胰腺癌的预后.目前已有结果提示新辅助治疗对胰腺癌患者安全,且能够显著提高手术切除率.但新辅助治疗与手术治疗、术后辅助治疗及姑息治疗相比较其疗效如何,到目前为止,尚缺少高质量的循证医学证据,也没有关于胰腺癌新辅助化疗或放化疗与外科手术后系统化疗间比较的随机对照研究.需要设计完善的随机对照研究对比新辅助化疗和手术治疗,以此来评价新辅助化疗在胰腺癌多种治疗方案中的价值.     

Accuracy of endorectal ultrasonography and computed tomography for restaging rectal cancer after preoperative chemoradiation

BACKGROUND: Preoperative restaging of irradiated rectal cancer is essential for the planning of optimal therapy. The aim of this study was to compare the accuracy of endorectal ultrasonography (ERUS) and CT in restaging rectal cancer after preoperative chemoradiation and to evaluate the factors affecting the accuracy of ERUS. STUDY DESIGN: Eighty-three patients with initial, locally advanced rectal cancer were prospectively evaluated by ERUS (n=60) and CT (n=80) after preoperative chemoradiation and just before surgery. All patients then underwent subsequent surgical resection and complete pathologic staging. RESULTS: In restaging the depth of invasion, the overall accuracy was 38.3% (23 of 60) by ERUS and 46.3% (37 of 80) by CT. Overstaging was more common than understaging with both imaging modalities. Accuracy for restaging lymph node metastasis was 72.6% (37 of 51) by ERUS and 70.4% (50 of 71) by CT. The predictive value of node-negative cases by ERUS was somewhat lower than that of CT (81.1% versus 85.4%, respectively). Complete pathology-proved remission was not correctly predicted in any of the 11 patients by any imaging modalities. Pathologic T and N staging correlated with the staging accuracy of ERUS (p=0.028 and p=0.001, respectively). CONCLUSIONS: ERUS and CT may allow good prediction of node-negative rectal cancers, although they are inaccurate modalities for predicting treatment response on the rectal wall. New methods of interpretation and diagnostic criteria for ERUS and CT are essential for increasing the accuracy of cancer prediction in at-risk patients.     

Endoscopic ultrasound predicts outcomes for patients with adenocarcinoma of the gastroesophageal junction

BACKGROUND: Endoscopic ultrasound (EUS) is the most accurate locoregional staging tool for gastroesophageal junction (GEJ) adenocarcinoma, and it may allow pretreatment risk stratification. The purpose of this study was to compare preoperative EUS staging with postoperative pathologic staging and to assess the ability of EUS to predict survival after resection for GEJ adenocarcinoma. STUDY DESIGN: Patients with GEJ adenocarcinoma, who had preoperative staging with EUS followed by resection, were identified from a prospectively maintained database. Patients receiving neoadjuvant therapy were excluded. EUS stage was compared with pathologic stage. Survival analyses were performed in patients who underwent complete gross resection. RESULTS: From 1985 through 2003, 209 patients underwent preoperative EUS followed by surgery without neoadjuvant therapy for GEJ adenocarcinoma. EUS correlated with pathologic T stage in 128 of 209 (61%) patients and with pathologic nodal stage in 154 of 206 (75%) patients. EUS accurately stratified patients into "early" (T0-2 N0) or "advanced" (T3-4 or N1) disease categories in 173 (83%) patients. Curative (R0) resection was performed in 184 patients: EUS "early" (n=84) and "advanced" (n=122) stages were associated with R0 rates of 100% and 82%, respectively (p=0.001). EUS "early" versus "advanced" stage was highly predictive of outcomes (p < 0.0001). The 5-year disease-specific survival for EUS "early" patients was 65% compared with 34% for EUS "advanced" stage. CONCLUSIONS: EUS accurately predicts pathologic stage. In addition, EUS is predictive of outcomes after complete gross resection without neoadjuvant treatment for GEJ adenocarcinoma and identifies a high-risk population that might benefit from preoperative therapy.     

可能切除的胰腺癌外科治疗争议与共识

“可能切除（borderline resectable）”胰腺癌的临床研究为目前热点课题。由于其合并周围大血管受累,多需行联合血管切除并重建的胰腺切除术式。直接手术切除致切缘阳性的可能较大,提倡对此类病人开展新辅助治疗,以提高R0切除率。较多回顾性研究表明新辅助治疗可提高R0切除率,改善病人预后。前瞻性研究数量有限,样本量也普遍偏小,一些多中心、大样本量的前瞻性研究正在进行之中,目前尚缺乏有高级别证据的研究结果。手术、新辅助化疗、放疗在可能切除的胰腺癌中的地位和作用,尚须进一步评价。     

Response to neoadjuvant chemotherapy best predicts survival after curative resection of gastric cancer

OBJECTIVE: In Western populations, long-term survival rates after curative resection of gastric cancer remain extremely poor. The lack of effective adjuvant therapy has prompted the evaluation of neoadjuvant approaches. Since 1988, we have conducted three separate phase II trials using neoadjuvant chemotherapy to treat patients with potentially resectable gastric cancer. The present study was conducted to evaluate whether response to neoadjuvant chemotherapy is predictive of survival in patients with resectable gastric cancer. METHODS: Eighty-three patients with pathologically confirmed gastric adenocarcinoma were treated with neoadjuvant chemotherapy before planned surgical resection. Response was assessed by upper gastrointestinal series, endoscopy, computed tomography scan, and pathologic examination. RESULTS: For the three phase II trials, clinical response rates ranged from 24% to 38%. Three patients (4%) had a complete pathologic response. Sixty-one patients (73%) underwent a curative resection. Median follow-up was 26 months. Univariate analysis revealed T stage, number of positive nodes, and response to chemotherapy to be significant predictors of overall survival. However, on multivariate analysis, response to chemotherapy was found to be the only independent prognostic factor. CONCLUSIONS: Response to neoadjuvant chemotherapy is the single most important predictor of overall survival after neoadjuvant chemotherapy for gastric cancer. These findings support further evaluation of neoadjuvant approaches in the treatment of this disease.     

Serum CA 19-9 as a Marker of Resectability and Survival in Patients with Potentially Resectable Pancreatic Cancer Treated with Neoadjuvant Chemoradiation

Purpose

The role of carbohydrate antigen (CA) 19-9 in the evaluation of patients with resectable pancreatic cancer treated with neoadjuvant therapy prior to planned surgical resection is unknown. We evaluated CA 19-9 as a marker of therapeutic response, completion of therapy, and survival in patients enrolled on two recently reported clinical trials.

Patients and Methods

We analyzed patients with radiographically resectable adenocarcinoma of the head/uncinate process treated on two phase II trials of neoadjuvant chemoradiation. Patients without evidence of disease progression following chemoradiation underwent pancreaticoduodenectomy (PD). CA 19-9 was evaluated in patients with a normal bilirubin level.

Results

We enrolled 174 patients, and 119 (68%) completed all therapy including PD. Pretreatment CA 19-9 <37 U/ml had a positive predictive value (PPV) for completing PD of 86% but a negative predictive value (NPV) of 33%. Among patients without evidence of disease at last follow-up, the highest pretreatment CA 19-9 was 1,125 U/ml. Restaging CA 19-9 <61 U/ml had a PPV of 93% and a NPV of 28% for completing PD among resectable patients. The area under the receiver-operating characteristics curve of pretreatment and restaging CA 19-9 levels for completing PD was 0.59 and 0.74, respectively. We identified no association between change in CA 19-9 and histopathologic response (P = 0.74).

Conclusions

Although the PPV of CA 19-9 for completing neoadjuvant therapy and undergoing PD was high, its clinical utility was compromised by a low NPV. Decision-making for patients with resectable PC should remain based on clinical assessment and radiographic staging.     

Neoadjuvant treatments in digestive cancer

Neoadjuvant chemotherapy or chemoradiotherapy is an important concept in the treatment of colorectal liver metastasis, gastric cancer, and esophageal or rectal tumors. This treatment strategy improves disease-free survival and sometimes overall survival. It allows surgical resection of lesions that where not resectable at diagnosis. The new standards of neoadjuvant treatments in gastrointestinal oncology are described in this article.     

Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas

Only 10% to 20% of patients with pancreatic cancer are considered candidates for curative resection at the time of diagnosis. We postulated that preoperative chemoradiation therapy might promote tumor regression, eradicate nodal metastases, and allow for definitive surgical resection in marginally resectable patients. The objective of this study was to evaluate the effect of a preoperative chemoradiation therapy regimen on tumor response, resectability, and local control among patients with marginally resectable adenocarcinoma of the pancreas and to report potential treatment-related toxicity. Patients with marginally resectable adenocarcinoma of the pancreas (defined as portal vein, superior mesenteric vein, or artery involvement) were eligible for this protocol. Patients received 50.4 to 56 Gy in 1.8 to 2.0 Gy/day fractions with concurrent protracted venous infusion of S-fluorouracil (250 mg/m²/day). Reevaluation for surgical resection occurred 4 to 6 weeks after therapy. Fifteen patients (9 men and 6 women) completed preoperative chemoradiation without interruption. One patient required a reduction in the dosage of S-fluorouracil because of stomatitis. Acute toxicity from chemoradiation consisted of grade 1 or 2 nausea, vomiting, diarrhea, stomatitis, palmar and plantar erythrodysesthesia, and hematologic suppression. CA 19-9 levels declined in all nine of the patients with elevated pretreatment levels. Nine of the 1.5 patients underwent a pancreaticoduodenectomy, and all had uninvolved surgical margins. Two of these patients had a complete pathologic response, and two had microscopic involvement of a single lymph node. With a median follow-up of 30 months, the median survival for resected patients was 30 months, whereas in the unresected group median survival was 8 months. Six of the nine patients who underwent resection remain alive and disease free with follow-up of 12, 30, 30, 34, 39, and 72 months, respectively. Preoperative chemoradiation therapy is well tolerated. It may downstage tumors, sterilize regional lymph nodes, and improve resectability in patients with marginally resectable pancreatic cancer. Greater patient accrual and longer follow-up are needed to more accurately assess its future role in therapy. Presented at the Eighty-Second Annual Meeting of the American Radium Society, London, England, April l–5, 2000.     

Controversies in the Multimodality Management of Locally Advanced Esophageal Cancer: Evidence-Based Review of Surgery Alone and Combined-Modality Therapy

Most patients with esophageal cancer present with locoregional disease, and the optimal initial management is controversial. The current National Comprehensive Cancer Network (NCCN) practice guidelines support diverse treatment options for locoregional disease, including surgical resection alone, definitive chemoradiation therapy, and preoperative combined-modality (neoadjuvant/trimodality) therapy. Many cancer centers worldwide favor a neoadjuvant approach, although the evidence supporting this practice is inconsistent. A concise review of the literature is presented. The topics discussed do not necessarily reflect each authors opinions or clinical practices.     

A Highly Active and Tolerable Neoadjuvant Regimen Combining Paclitaxel,Carboplatin, 5-FU,and Radiation Therapy in Patients with Stage II and III Esophageal Cancer

BACKGROUND: The present phase II study aimed to assess the feasibility and efficacy of a new paclitaxel-based neoadjuvant chemoradiation regimen followed by surgery in patients with stage II-III esophageal cancer. METHODS: From January 2002 to November 2004, 50 patients with a potentially resectable stage II-III esophageal cancer received chemotherapy with paclitaxel, carboplatin, and 5-FU in combination with radiotherapy 45 Gy in 25 fractions. Surgery followed 6-8 weeks after completion of neoadjuvant treatment. RESULTS: Patient characteristics: male/female: 44/6, median age 60 years (34-75), median WHO 1 (0-2), adenocarcinoma (n = 42), squamous cell carcinoma (n = 8). Toxicity was mild, and 84 % of the patients completed the whole regimen. Forty-seven patients underwent surgery with a curative intention (transhiatal n = 44, transthoracic n = 3). Pathologic complete tumor regression was achieved in 18 of 47 operated patients (38%). R0 resection was achieved in 45 of 47 operated patients (96%). There were four postoperative deaths (8.5). Postoperative complications were comparable with other studies. After a median follow-up of 41.5 months (21-59) estimated 3- and 5-year survival on an intention-to-treat basis was 56 and 48%. Estimated 3-year survival in responders was 61%, in nonresponders 33%. CONCLUSION: This novel neoadjuvant chemoradiation regimen for treatment of patients with stage II-III esophageal cancer is feasible. Results are encouraging with a high pathologic complete tumor regression and R0 resection rate and an acceptable morbidity and mortality. Preliminary survival data are very promising.     

Early response evaluation and prediction in neoadjuvant-treated patients with esophageal cancer

Since the introduction of multimodal therapy regimens, the prognosis of esophageal cancer has improved. There is undoubtedly true for patients with surgically resected tumors in the case of a response to neoadjuvant chemotherapy or chemoradiation. Important conclusions can be drawn from this regarding the indication for perioperative therapies, the radicality of surgery, or the surgical indications. Thus, most of the current research in this field is aimed at the early identification of this subset of patients, at the beginning of, or even before, neoadjuvant treatment. Conventional staging tools have failed to predict responses to neoadjuvant therapy. However, molecular imaging methods, e.g. positron emission tomography (PET)-scans, have shown promising results in the early selection of responders and non-responders during the course of neoadjuvant therapy, allowing physicians to alter the treatment plan accordingly. Even more desirable is the identification of potential responders before the start of neoadjuvant therapy. Preliminary molecular data on biopsy specimens demonstrate the possibility of early response prediction in these patients. We present the current knowledge on response evaluation and prediction in esophageal cancer and draw conclusions for future clinical practice and studies in this review.