Downstaging of esophageal cancer after preoperative radiation and chemotherapy.

OBJECTIVE: This retrospective, nonrandomized review evaluates 125 patients with esophageal carcinoma (adenocarcinoma and squamous cell) who underwent either surgery only or preoperative chemotherapy and/or radiation therapy followed by surgery. Major end points were survival and postchemoradiation downstaging. METHODS: Forty-four patients underwent radiation therapy of 4500 cGy over 5 weeks. Fluorouracil and cisplatin were administered on the first and fifth week of radiotherapy. Ninety-eight patients underwent "potentially curative" resections-transhiatal esophagectomy (70), Lewis esophagogastrectomy (25), and left esophagogastrectomy (3). All patients with preoperative adjuvant therapy underwent endoscopy and biopsy before surgery. RESULTS: There were no differences in overall mortality (5%) or surgical complications in either group. Fourteen of 44 patients (32%) downstaged to complete pathologic response, with 5-year survival of 57%. Fifteen of 44 patients (34%) downstaged to microscopic residual tumor, with 1- and 3-year survival of 77% and 31%, respectively. Twenty-eight of 29 patients in the two downstaged groups were lymph node negative. Overall, 5-year survival in the adjuvant therapy plus surgery group versus surgery only was 36% and 11% (p = 0.04). Five-year survival in lymph node-negative adjuvant therapy and surgery patients was 49% (p = 0.005). Positive nodes in the surgery only group was 48% versus 23% in the adjuvant therapy and surgery group (p = 0.02). CONCLUSION: Although retrospective and nonrandomized, these results suggest that preoperative chemoradiation results in significant clinical and pathologic downstaging, increases survival, and may sterilize local and regional lymph nodes, accounting for both downstaging and survival statistics.     

Neoadjuvant therapy for esophageal cancer: standard of care or elusive myth?

Although surgical resection as the sole treatment modality for esophageal carcinoma has historically been associated with poor survival rates, improvements have recently been reported using varied neoadjuvant chemo-radiation protocols. This study evaluates the outcome of patients undergoing surgery for esophageal carcinoma at the University of Miami/Jackson Memorial Hospital between July 1991 and June 1996. Seventy-two patients underwent esophageal resection; 51 males and 21 females with a median age of 62.5 years (range = 42-82). Histology was equally distributed between adenocarcinoma (36 patients; 50%) and squamous cell carcinoma (36 patients; 50%). Pathological stage distribution consisted of 6 stage 0 (8%), 10 stage I (14%), 23 stage II (32%), 31 stage III (43%), and 2 stage IV (3%) lesions. Patients were divided into three groups according to the type of preoperative treatment; Group 1 (n = 44); surgery alone; Group 2 (n = 18); neoadjuvant 5-fluorouracil based chemotherapy, and Group 3 (n = 9); neoadjuvant 5-fluorouracil based chemotherapy in conjunction with external beam radiation (XRT). One patient received preoperative XRT alone. All survivors were followed for a minimum of 1 year and statistical analysis was performed using Kaplan-Meier curves, log-rank, and chi-square tests. In the 28 patients receiving any form of neoadjuvant therapy only one patient had a pathological complete response (CR) (3.5%). The overall 5 year and median survival rates were 18 per cent and 20.5 months (range = 0-73), respectively. Individual treatment group survival rates at 5 years were 28% for Group 1; 21% for Group 2; and 0% for Group 3, showing no survival difference between Groups 1 and 2; Group 3 fared significantly worse than the other two, probably as a result of the high operative mortality in this group. These results indicate that surgical resection continues to be an important treatment modality for esophageal carcinoma. Neoadjuvant chemotherapy in our experience failed to improve these survival rates and pre-operative chemoradiation was associated with a high perioperative mortality rate. Chemotherapy regimens with higher CRs may further improve these survival rates.     

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.     

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.     

Cancer of the esophagus. The Cleveland Clinic experience.

The therapy and survival rates of patients with esophageal carcinoma at the Cleveland Clinic over the 12-year period 1969-1980 are reviewed. Data on 238 patients were analyzed. Seventy-one per cent of the patients underwent surgery, with esophagogastrectomy being performed in half of these. One or more early postoperative complications occurred in 72.6% of these patients. Most of these complications were pulmonary and related to the patients' chronic obstructive pulmonary disease. The mortality rate for esophagogastrectomy at the Cleveland Clinic has decreased over the past 15 years to 7.1%. The 5-year survival rate after "curative" esophagogastrectomy was 15.4% with a mean survival time of 34.4 months. Invasion of the tumor through or beyond the serosa in this group of patients was associated with an increased relative risk of death of 3.3 compared to those with lesser degrees of invasion. The cell type, degree of differentiation, stage of disease, and presence of tumor at the lines of resection were all prognostically significant for all patients.     

Adenocarcinoma of the head of the pancreas: effects of surgical and nonsurgical therapy on survival--a ten-year experience

A retrospective analysis of all patients treated for adenocarcinoma of the head of the pancreas from 1989 to 1998 was performed. Excluded were cancers in the body and tail, cystic neoplasms, ampullary tumors, and cancers of the duodenum and bile ducts. One hundred forty-five patients were reviewed, and 43 patients underwent pancreaticoduodenectomy. Data collected included the stage, lymph node status, surgical margins, adjuvant therapies, and survival. Statistical analysis was performed with Cox's Proportional Hazards Analysis and Log-Rank Life Table Analysis. The surgical population had a 21 per cent 3-year survival rate and a 7 per cent operative mortality rate. Median survival was: 1) the resection group versus no resection was 13.5 versus 3.1 months; 2) adjuvant therapy versus no therapy after resection was 16.1 versus 5.1 months; and 3) chemoradiation therapy versus no therapy for unresectable disease was 5.3 versus 1.8 months. The presence of positive surgical margins was found in 33 per cent of the surgical specimens and carried an increased mortality hazard ratio of 3.1. Patients with negative lymph nodes had a 15 per cent 5-year survival, versus 0 per cent with positive nodes. Seventy-three per cent of those resected had a T2 lesion, and 46 per cent of patients presented with metastatic disease. Surgical resection and adjuvant therapy significantly improves survival in patients with adenocarcinoma of the head of the pancreas. All patients who underwent resection as part of their therapy showed extended survival compared with chemoradiation therapy alone. Adjuvant chemoradiation improved survival when compared with surgery alone. Multimodality treatment in carcinoma of the head of the pancreas provides the best treatment option. However, better adjuvant therapies are needed.     

Neoadjuvant chemotherapy in stage III breast cancer

Neoadjuvant chemotherapy in advanced breast cancer can potentially downstage disease prior to definitive surgery. In this study, a doxorubicin-based neoadjuvant regimen was administered to stage III breast cancer patients to assess 1) primary tumor response, 2) tumor involvement of resection margins, and 3) predictive value in cancer outcome. Eighty-two patients with stage IIIA and IIIB breast cancer diagnosed between 1990 and 2003 were studied. All patients received similar chemotherapy regimens, consisting of doxorubicin, cisplatin, and 5-fluorouracil, plus surgery and radiation therapy. End points measured include primary tumor response [complete response (CR) = 100%, partial response (PR) > 50%, or no response (NR) < or = 50%], resection margins for tumor, disease-free, and overall survival. Kaplan-Meier and log-rank tests were performed. Of the 82 patients studied, 34 received neoadjuvant therapy, 48 received conventional postoperative treatment. Seventy-two per cent of the stage IIIB and 22 per cent of the stage IIIA patients received neoadjuvant therapy. In the neoadjuvant group, 29 (85%) patients demonstrated tumor response, 9 (26%) of which were CR. Tumor-free resection margins were achieved in 94 per cent of the neoadjuvant group. Survival analysis demonstrated no benefit comparing neoadjuvant versus postoperative adjuvant therapy but hints at improved disease-free survival in neoadjuvant CR patients (log-rank test, P = 0.07). Eighty-five per cent of patients with stage III breast cancer treated with neoadjuvant chemotherapy experienced clinical response, with 26 per cent CR, and 97 per cent tumor-free resection margins. CR may portend a better cancer outcome.     

Ivor Lewis esophagogastrectomy for esophageal cancer

Background. To examine the efficacy of the Ivor Lewis esophagogastrectomy for esophageal carcinoma prior to the widespread use of preoperative chemotherapy and irradiation, we reviewed our experience.

Methods. We reexamined the cases of 220 consecutive patients who underwent an Ivor Lewis esophagogastrectomy for esophageal cancer from January 1992 through December 1995.

Results. There were 196 men (89.1%) and 24 women. Median age was 65 years (range, 29 to 85 years). The results of pathological study showed adenocarcinoma in 188 patients (85.5%), squamous cell carcinoma in 31 (14.1%), and leiomyosarcoma in 1 patient (0.5%). Postsurgical staging was as follows: stage 0 in 10 patients, stage I in 19, stage IIa in 38, stage IIb in 28, stage III in 111, and stage IV in 14. The operative mortality rate was 1.4% (3 patients), and complications occurred in 83 patients (37.7%). Follow-up was 98.6% complete. Median survival for operative survivors was 1.9 years (range, 32 days to 8.7 years). The overall 5-year survival rate was 25.2%; it was 80% for patients in stage 0, 94.4% for those in stage I, 36.0% for those in stage IIa, 14.3% for patients in stage IIb, 10% for those in stage III and 0% for patients in stage IV.

Conclusions. Ivor Lewis esophagogastrectomy for esophageal cancer is a safe operation. Long-term survival is stage dependent. The low survival associated with advanced cancers should stimulate the search for effective neoadjuvant therapy.     

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

BACKGROUND: Esophagectomy is often considered the standard treatment for resectable esophageal cancer but the rate of cure is low. Combining neoadjuvant chemotherapy with surgery has theoretical appeal and some clinical evidence suggests a benefit. We performed a meta-analysis of randomized controlled trials (RCTs) that compared neoadjuvant chemotherapy and surgery with surgery alone for esophageal cancer. METHODS: Medline and manual searches were done to identify all published RCTs that compared neoadjuvant chemotherapy and surgery to surgery alone for esophageal cancer. The selection process was inclusive; no trials were excluded. Trial validity assessment was done and a trial quality score was assigned. Outcomes assessed by meta-analysis included 1-, 2-, and 3-year survival, rate of resection, rate of complete resection, operative mortality, anastomotic leaks, postoperative pulmonary complications, all treatment mortality, local-regional cancer recurrence, distant cancer recurrence, and all cancer recurrence. A random-effects model was used and odds ratio was the principal measure of effect. Systematic quantitative review was done for outcomes unique to the neoadjuvant chemotherapy treatment group (clinical response, pathological complete response, and chemotherapy mortality). RESULTS: Eleven RCTs, which included 1,976 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 chemotherapy and surgery versus surgery alone (treatment versus control; values <1 favor chemotherapy-surgery arm), was 1.00 (0.76, 1.30; P = 0.98) for 1-year survival, 0.88 (0.62, 1.24; P = 0.45) for 2-year survival, 0.77 (0.37, 1.59; P = 0.48) for 3-year survival, 1.71 (1.22, 2.40; P = 0.002) for rate of resection, 0.71 (0.58, 0.87; P = 0.001) for rate of complete resection, 0.94 (0.66, 1.35; P = 0.76) for operative mortality, 1.08 (0.45, 2.60; P = 0.87) for anastomotic leaks, 1.31 (0.77, 2.23; P = 0.32) for postoperative pulmonary complications, 1.36 (0.83, 2.25; P = 0.22) for all treatment mortality, 0.71 (0.36, 1.42; P = 0.33) for local-regional cancer recurrence, 0.79 (0.57, 1.10; P = 0.16) for distant cancer recurrence, and 0.63 (0.28, 1.41; P = 0.26) for all cancer recurrence. A clinical response to chemotherapy was observed in 31% of patients and 5% had a complete pathological response. Chemotherapy mortality (before surgery) was 1.6%. CONCLUSIONS: Compared with surgery alone, neoadjuvant chemotherapy and surgery is associated with a lower rate of esophageal resection but a higher rate of complete (R0) resection. It does not increase treatment related mortality. This meta-analysis did not demonstrate a survival benefit for the combination of neoadjuvant chemotherapy and surgery.     

Treatment of gastric lymphoma.

A review of 52 patients with gastric lymphoma at the Texas A&M University College of Medicine Affiliated Scott and White Memorial Hospital (Temple, TX). was performed to determine the influence of different treatment modalities. Thirty-one patients had a potentially curative resection, while 21 underwent a palliative procedure or biopsy alone. Overall 5-year survival was 73.4 per cent after curative resection and 38.3 per cent for lesser operative procedures (P less than .005). Adjuvant radiation was given to 14 patients after curative resection with a 5-year survival rate of 71.5 per cent compared to 82.4 per cent in the 17 patients treated by curative resection alone (nonsignificant). Patients who underwent palliative surgery or biopsy who received postoperative radiation therapy had a 38.0 per cent 5-year survival rate compared to a 0.0 per cent 5-year survival rate in patients who received no therapy (P = .18). The authors conclude that curative resection is the treatment of choice for gastric lymphoma, but radiation therapy may offer some benefit when complete resection is not feasible.     

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.     

Long-term survival of resectable subset after induction chemotherapy in patients with locally advanced head and neck cancer

BACKGROUND: Although meta-analysis showed that survival improved with concurrent chemoradiation in locally advanced head and neck cancer, neoadjuvant chemotherapy is still unique, because it renders curative surgery feasible for marginally resectable head and neck cancer patients. METHODS: We reviewed patients with locally advanced head and neck cancer, who had been treated with neoadjuvant chemotherapy between June 1984 and February 2001 at the Seoul National University Hospital. RESULTS: A total of 167 patients were included. After 2 to 3 chemotherapy cycles, either surgery (38 patients) or radiation (104 patients) was conducted. Those who received surgery exhibited better survival than those who received radiation [median survival: not reached vs 33.6 months (95% CI: 22.6-44.7), p = .006]. The 5-year and 10-year survival rates of surgery group were 63.2% and 59.8%. CONCLUSION: The potential benefit of neoadjuvant chemotherapy with surgery in patients with locally advanced head and neck cancers merits further evaluation in future clinical trials.     

Impact of neoadjuvant therapy on postoperative complications in patients undergoing resection for rectal adenocarcinoma

Surgical resection continues to be the mainstay of treatment for rectal cancer. Neoadjuvant therapy (chemotherapy and radiation) has also been shown to be efficacious. The impact of preoperative chemotherapy and radiation on postoperative complications is unclear. The purpose of this study is to evaluate the relationship of neoadjuvant therapy on postoperative complications in patients undergoing a resection of rectal cancer. A total of 325 patients who underwent curative resection for rectal cancer from 1984 to 2001 were retrospectively reviewed. Only cases with complete data sets who had undergone surgery at this institution were evaluable (257). The patients were divided into groups based on the operative procedure performed; abdominoperineal resection (APR) versus sphincter-sparing (SS) procedures (LAR/Transanal) and whether or not preoperative chemotherapy or radiation was administered. There was no significant difference between complication rates for APR and SS with 19 per cent and 14 per cent, respectively. The preoperative therapy had no effect on complications after APR. However, the SS group showed 21 per cent of the patients who received radiation had complications compared to 11 per cent in those who did not (P = 0.087). Complications in the SS group included leaks, wound infections, abscess, embolism, cardiac dysrhythmias, and myocardial infarctions. The 30-day mortality was 1.9 per cent for the entire cohort with no clear difference between groups. There was no significant difference in complication rate between APR and SS. In the APR group, neoadjuvant therapy had no impact on the incidence of complications. However, the SS group did show a trend between preoperative chemotherapy and radiation and complication rate. However, this may not outweigh the advantages of preoperative therapy in this setting.     

食管癌辅助化疗期间并发症对预后的影响

目的探讨食管癌患者术后辅助化疗器件发生并发症对预后的影响。 方法回顾分析2003—2011年南京鼓楼医院接受食管癌手术治疗并采用辅助化疗的738例患者的临床资料,并随访至2017年12月。采用多变量Cox比例风险模型分析辅助化疗期间发生血液系统和非血液系统并发症与短期和长期病死率之间的联系。 结果在738例患者中,73例(9.9% )患者因辅助化疗产生并发症需要急诊住院治疗,血液系统并发症可导致术后90 d病死率升高(HR＝5.63,95% CI：1.26～24.81),在肿瘤分期为0～Ⅱ期的腺癌、无论切缘是否有残留的患者中尤为明显,食管腺癌术后5年疾病相关病死率显著升高(HR＝3.21,95% CI：1.05～10.33)。在预计预后较差组(肿瘤分期Ⅲ～Ⅳ期)发生非血液系统并发症术后5年病死率较高(HR＝2.34,95% CI：1.17～4.89)。其他亚组患者发生血液系统或非血液系统并发症并不影响5年病死率。 结论食管癌患者接受食管切除术后行辅助化疗,发生相关并发症可能对患者近期及远期病死率产生不利影响。     

Use of oesophagogastroscopy to assess the response of oesophageal carcinoma to neoadjuvant therapy

BACKGROUND: Approximately 25 per cent of patients with oesophageal cancer who undergo neoadjuvant chemoradiotherapy have no evidence of tumour in the resected specimen (complete pathological response). Those who do not respond have a poor 5-year survival compared with complete responders, regardless of whether or not they undergo surgery. Selecting for surgery only those who have a response to neoadjuvant therapy has the potential to improve overall survival as well as to rationalize the management of non-responders. This study assessed the accuracy of oesophagogastroscopy in this setting. METHODS: A prospective database of 804 patients undergoing oesophageal resection for carcinoma was reviewed. Endoscopic assessment of the response to neoadjuvant therapy in 100 consecutive patients was compared with the pathological assessment of response. The survival for each level of response was compared. RESULTS: At endoscopy 30 patients were considered to have had a complete response. This was confirmed pathologically in 15 patients. Survival was improved in those with a pathologically confirmed complete response (3-year survival rate 62.4 (s.e. 12.9) per cent) compared with non-responders (16.3 (s.e. 6.6) per cent). Those with microscopic residual disease also had an improved 3-year survival rate (46.3 (s.e. 12.2) per cent); however, oesophagogastroscopy failed to identify this subset. CONCLUSION: Oesophagogastroscopy may be useful in the assessment of tumour response to neoadjuvant therapy. However, owing to its poor accuracy patients should not be excluded from further therapeutic intervention on the basis of this assessment alone.     

Results of pulmonary resection following neoadjuvant therapy for locally advanced (IIIA-IIIB) lung cancer.

OBJECTIVE: We performed this study to determine the role and prognostic factors of neoadjuvant therapy followed by surgery for locally advanced non-small cell cancer. METHODS: One hundred patients with clinical stage III non-small cell lung cancer (79 IIIA, 21 IIIB; 78 males, 22 females; average age 60.5 years) received neoadjuvant therapy, of whom 84 received two cycles of platinum chemotherapy combined with an average radiation dose of 41.5Gy, and 16 patients underwent chemotherapy alone. The mean follow-up duration was 80.9 months. Survival rate was estimated by the Kaplan-Meier method, and a Cox proportional hazards model was applied to determine the prognostic factors. RESULTS: The operative procedures included 74 lobectomies, 7 bi-lobectomies, and 19 pneumonectomies. Two patients died within 30 days due to adult respiratory distress syndrome and acute pulmonary embolism, respectively. The overall 5-year survival rate was 39.7% with a median survival time (MST) of 39.6 months. The 5-year survival rate for downstaged (pN1,2) patients was 53.5% while it was 16.3% for patients with residual N2. There was no difference in survival between lobectomy and pneumonectomy (MST 38 months vs 42 months). Univariate and multivariate analyses revealed that nodal status and tumor size after neoadjuvant therapy were independent prognostic factors. CONCLUSIONS: Neoadjuvant therapy was shown to deliver the optimal effect for surgery for cIIIA/IIIB NSCLC with acceptable mortality. Re-staging to exclude the residual multiple nodal metastasis can lead to the proper patient selection. A pneumonectomy, as a last option, following neoadjuvant therapy did not affect the mortality.     

Effects of Neoadjuvant Therapy on Perioperative Morbidity in Elderly Patients Undergoing Esophagectomy for Esophageal Cancer

Background The use of cytoreductive therapy followed by surgery is preferred by many centers dealing with locally advanced esophageal cancer. However, the potential for increase in mortality and morbidity rates has raised concerns on the use of chemoradiation therapy, especially in elderly patients. The aim of this study was to assess the effects of induction therapy on postoperative mortality and morbidity in elderly patients undergoing esophagectomy for locally advanced esophageal cancer at a single institution. Methods Postoperative mortality and morbidity of patients ≥70 years old undergoing esophagectomy after neoadjuvant therapy, between January 1992 and October 2005 for cancer of the esophagus or esophagogastric junction, were compared with findings in younger patients also receiving preoperative cytoreductive treatments. Results 818 patients underwent esophagectomy during the study period. The study population included 238 patients <70 years and 31 ≥70 years old undergoing esophageal resection after neoadjuvant treatment. Despite a significant difference in comorbidities (pulmonary, cardiological and vascular), postoperative mortality and morbidity were similar irrespective of age. Conclusions Elderly patients receiving neoadjuvant therapies for cancer of the esophagus or esophagogastric junction do not have a significantly increased prevalence of mortality and major postoperative complications, although cardiovascular complications are more likely to occur. Advanced age should no longer be considered a contraindication to preoperative chemoradiation therapy preceding esophageal resection in carefully selected fit patients.     

The Cost-Effectiveness of Neoadjuvant Chemoradiation is Superior to a Surgery-First Approach in the Treatment of Pancreatic Head Adenocarcinoma

Background

In treating pancreatic cancer, there is no clearly defined optimal sequence of chemotherapy, radiation therapy and surgery. Therefore, cost-effectiveness should be considered. The objective of this study was to compare cost and outcomes between a surgery-first approach versus neoadjuvant chemoradiation followed by surgery for resectable pancreatic head cancer.

Methods

A decision analytic model was constructed to compare the 2 approaches. Data from the National Cancer Database, National Surgical Quality Improvement Program, and literature populated the surgery-first arm. Data from our prospectively maintained institutional pancreatic cancer database populated the neoadjuvant arm. Costs were estimated by Medicare payment (2011 U.S. dollars). Survival was reported in quality-adjusted life-months (QALMs).

Results

The neoadjuvant chemoradiation arm consisted of 164 patients who completed preoperative therapy. Of these, 36 (22 %) did not proceed to surgery; 12 (7 %) underwent laparotomy but had unresectable disease; and 116 (71 %) underwent definitive resection. The surgery-first approach cost $46,830 and yielded survival of 8.7 QALMs; the neoadjuvant chemoradiation approach cost $36,583 and yielded survival of 18.8 QALMs. In the neoadjuvant arm, costs and survival times for patients not undergoing surgery, those with unresectable disease at laparotomy, and those completing surgery were $12,401 and 7.7 QALMs, $20,380 and 7.1 QALMs, and $45,673 and 23.4 QALMs, respectively.

Conclusions

Neoadjuvant chemoradiation for pancreatic cancer identifies patients with early metastases or poor performance status, who can be spared an ineffective or prohibitively morbid operation, and is associated with improved survival at significantly lower cost than a surgery-first approach. Neoadjuvant chemoradiation followed by surgery is a strategy that provides more cost-effective care than a surgery-first approach.

     

First-line chemotherapy improves the resection rate and long-term survival of locally advanced (T4, any N, M0) squamous cell carcinoma of the thoracic esophagus: final report on 163 consecutive patients with 5-year follow-up.

OBJECTIVE: The objective of this prospective, nonrandomized study was to evaluate the immediate and long-term results of first-line chemotherapy and possible surgery in locally advanced, presumably T4 squamous cell esophageal cancer. SUMMARY BACKGROUND DATA: Locally advanced esophageal cancer is rarely operable and has a dismal prognosis. For this reason, neoadjuvant cytoreductive treatments are more and more frequently used with the aim of downstaging the tumor, increasing the resection rate, and possibly improving survival. Methods: From January 1983 to December 1991, 163 consecutive patients with a presumedly T4 squamous cell carcinoma of the thoracic esophagus (group A) received on average 2.5 cycles (range, 1-6) of first-line chemotherapy with cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 per day, in continuous infusion from day 1 through day 5). Chemotherapy was followed by surgery when adequate downstaging of the tumor was obtained. RESULTS: Chemotherapy toxicity was WHO grade 0 to 2 in 80% of cases, but 3 toxic deaths (1.9%) occurred. Restaging suggested a downstaging of the tumor in 101 of 163 patients (62%), but only 85 patients (52%) underwent resection surgery; it was complete or R0 in 52 (32%) and incomplete or R1-2 in 33. Overall postoperative mortality was 11.7% (10 of 85), morbidity 41% (35 of 85). Complete pathologic response was documented in 6 patients, and significant downstaging to pStage I, IIA, or IIB occurred in 25 more patients. The overall 5-year survival was 11 % (median, 11 months). After resection surgery, the 5-year survival was 20% (median, 16 months); none of the nonresponders survived 4 years after palliative treatments without resection (median survival, 5 months). The 5-year survival rate of the 52 patients undergoing an R0 resection was 29% (median, 23 months). Stratifying patients according to the R, pT, pN, and pStage classifications, the survival curves were comparable to the corresponding data obtained in the 587 group B patients with "potentially resectable" esophageal cancer who underwent surgery alone during the same period. Furthermore, the results were improved in comparison with 136 previous or subsequent patients with a locally advanced tumor who did not undergo neoadjuvant treatments (group C). In these patients, the R0 resection rate was 7%, and the overall 5-year survival was 3% (median, 5 months). CONCLUSION: Although nonrandomized, these results suggest that in locally advanced esophageal carcinoma, first-line chemotherapy increases the resection rate and improves the overall long-term survival. In responding patients who undergo R0 resection surgery, the prognosis depends on the final pathologic stage and not on the initial pretreatment stage.     

Improved survival following complete excision of retroperitoneal sarcomas.

Charts and slides of 47 patients with primary retroperitoneal sarcomas (excluding pediatric rhabdomyosarcoma) were reviewed to determine clinical presentation, histologic features, extent of surgical resection, operative morbidity and mortality, use of radiation and/or chemotherapy, and survival data. Most patients presented with pain and a palpable mass. Leiomyosarcomas and liposarcomas were the most common tumors. Eighteen of the 47 patients (38%) had complete tumor excision; 68% required resection of adjacent organs. Operative morbidity was 33% with no mortality. After complete resection, the disease-free 5-year survival was 50% and the overall survival was 70% at 5 years; 10-year disease-free survival was 25% with an overall 58% survival at 10 years. Eleven patients (61%) developed recurrent disease with a median interval of 5 years following complete excision. Six patients received adjuvant radiation and/or chemotherapy with four remaining disease-free from 46 to 61 months. Eighteen patients underwent partial excision of tumor and 11 patients underwent biopsy only; these groups had similar survival curves with only 4% alive at 5 years. Their operative morbidity was 18% and mortality was 7%; median time to clinical evidence of tumor progression was 12 months. Sixty per cent of these patients received therapeutic radiation and/or chemotherapy, but their survival was the same as those undergoing surgery alone. These data emphasize the importance of an aggressive surgical approach in the treatment of retroperitoneal sarcomas. Complete tumor resection and total excision of recurrences will allow many patients long-term survival.