REG Iα is a Reliable Marker of Chemoradiosensitivity in Squamous Cell Esophageal Cancer Patients

Background A reliable marker of chemoradiosensitivity that would enable appropriate and individualized treatment of thoracic squamous cell esophageal cancer has long been sought. We investigated whether regenerating gene (REG) Iα is such a marker. Methods We assessed expression of REG Iα in untreated endoscopic biopsy specimens and examined the correlation between REG Iα expression and the clinical responses to definitive chemoradiotherapy and prognosis. We also examined the relationship between REG Iα expression in the resected tumor and the prognosis of patients who received esophagectomy for thoracic squamous cell esophageal cancer. Results Among the 42 patients treated with definitive chemoradiotherapy, 8 of the 23 REG I-positive patients (35%) showed complete responses to chemoradiotherapy, while only one of the 19 REG I-negative patients did so. The survival rate among the REG I-positive patients was significantly better than among the REG I-negative patients. For the 76 patients treated surgically, there was no significant difference in the survival rates among the REG I-positive and REG I-negative patients. Conclusions REG Iα expression in squamous cell esophageal carcinoma may be a reliable marker of chemoradiosensitivity. We anticipate that it will enable us to provide more appropriate and individualized treatment to patients of advanced esophageal squamous cell carcinoma.     

Treatments for esophageal cancer: a review

Esophageal cancer is the eighth most common form of cancer worldwide. The treatments for esophageal cancer depend on its etiology. For mucosal cancer, endoscopic mucosal resection and endoscopic submucosal dissection are standard, while for locally advanced cancer, esophagectomy remains the mainstay. The three most common techniques for thoracic esophagectomy are the transhiatal approach, the Ivor Lewis esophagectomy (right thoracotomy and laparotomy), and the McKeown technique (right thoracotomy followed by laparotomy and neck incision with cervical anastomosis). Surgery for carcinoma of the cervical esophagus requires an extensive procedure with laryngectomy in many cases. When the tumor is more advanced, neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy is added. The theoretical advantages of adding chemotherapy to the treatment of esophageal cancer are potential tumor down-staging prior to surgery, as well as targeting micrometastases and, thus, decreasing the risk of distant metastasis. Cisplatin- and 5-fluorouracil-based regimes are used worldwide. Chemoradiotherapy is the standard for unresectable esophageal cancer and could also be considered as an option for resectable tumors. For patients who are medically or technically inoperable, concurrent chemoradiotherapy should be the standard of care. Although neoadjuvant chemoradiotherapy followed by surgery or salvage surgery after definitive chemoradiotherapy is a practical treatment; judicious patient selection is crucial. It is important to have a thorough understanding of these therapeutic modalities to assist in this endeavor.     

Salvage esophagectomy after definitive chemotherapy and radiotherapy for advanced esophageal cancer

BACKGROUND: Although local recurrence of advanced esophageal cancer is frequent after definitive chemoradiotherapy (CRT), the clinical benefit of salvage esophagectomy has not been elucidated. METHODS: We reviewed 27 patients with squamous-cell cancer who underwent esophagectomy after definitive CRT (> or = 50 Gy) (salvage group) and 28 patients who underwent planned esophagectomy after neoadjuvant CRT (30 to 45 Gy) (neoadjuvant group). RESULTS: The preoperative albumin level and vital capacity were significantly lower in the salvage group than in the neoadjuvant group. Two patients (7.4%) from the salvage group who underwent extended esophagectomy with three-field lymphadenectomy died of postoperative complications, but no deaths occurred after less-invasive surgery. There was no difference of overall postoperative survival between the salvage and neoadjuvant groups. CONCLUSIONS: The outcome of salvage esophagectomy after definitive CRT was similar to that of planned esophagectomy after neoadjuvant CRT. Less-invasive procedures might be better for salvage esophagectomy because of the high operative risk.     

Factors Influencing the Long-Term Survival in Patients with Esophageal Cancer Who Underwent Esophagectomy After Chemoradiotherapy

Background

Salvage esophagectomy is potentially the only treatment available that can offer a chance of long-term survival when definitive chemoradiotherapy (CRT) fails to achieve local control for patients with esophageal squamous cell carcinoma (ESCC). However, salvage esophagectomy is a highly invasive procedure with various postoperative complications compared to planned esophagectomy after neoadjuvant chemoradiotherapy (CRT). We hypothesize that severe postoperative complications may affect not only surgical mortality but also tumor recurrence and long-term survival for patients with salvage esophagectomy after definitive CRT.

Methods

For the present study we reviewed the surgical procedures, postoperative complications, and the prognosis of 65 consecutive patients with thoracic ESCC who underwent the esophagectomy after neoadjuvant (neoadjuvant group: n = 40) or definitive (salvage group: n = 25) CRT.

Results

Most patients underwent right-transthoracic extended esophagectomy and reconstruction using gastric conduit by way of subcutaneous route with left cervical anastomosis. The incidence of postoperative pneumonia was found to be higher in the salvage group than in the neoadjuvant group. In both groups, the survival of patients with R0 resection was significantly better than those with R1/R2 resection. Moreover, in the salvage group, the postoperative survival rate of patients with pneumonia or bacteremia/sepsis was significantly lower than that for patients who did not suffer the same complications. In the neoadjuvant group, R0 resection was selected to be the only independent prognostic factor in univariate and multivariate analysis. In contrast, in the salvage group, R0 resection and bacteremia/sepsis remained significant and were independent of the other factors in multivariate analysis.

Conclusions

This study reveals that postoperative morbidity affects not only the perioperative mortality but also the long-term survival of patients with ESCC who undergo salvage esophagectomy after definitive CRT.     

Cell-Cycle Regulators and the Ki-67 Labeling Index Can Predict the Response to Chemoradiotherapy and the Survival of Patients With Locally Advanced Squamous Cell Carcinoma of the Esophagus

Background: We investigated whether aberrant p53 and p16 expression, the Ki-67 labeling index (LI), and int-2/cyclin D1 gene amplification predict the response to chemoradiotherapy (CRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC).Methods: p53 and p16 expression status, the Ki-67 LI, and int-2/cyclin D1 amplification were assessed by immunohistochemical staining and slot blot analysis in pretreatment endoscopic biopsy specimens of 41 patients with T4 or M1 Lym (distant lymph node metastasis) ESCC. All patients received a course of chemotherapy (5-fluorouracil and cisplatin) with radiotherapy.Results: The CRT therapeutic response rate was 71%, and resection after CRT was successful in 15 of the cases in which the CRT effect was significant. The cumulative survival rate after CRT in the p53-negative patients was significantly higher than in the p53-positive patients (P = .037). The mean Ki-67 LI in the CRT response cases was significantly higher than in the CRT no-response cases (P = .023). Multivariate regression analysis revealed high Ki-67 LI to be an independent variable linked to a pathologic complete response to CRT (P = .033). The cumulative survival rate after CRT in the group that was p53-negative and int-2/cyclin D1 amplification-positive was significantly higher than in the other groups (P = .008).Conclusions: Evaluating predictive factors in pretreatment endoscopic biopsy specimens may allow selection of more suitable multimodal treatment for ESCC patients and improve their quality of life.     

REG1A Expression Status Suggests Chemosensitivity Among Advanced Thoracic Esophageal Squamous Cell Carcinoma Patients Treated with Esophagectomy Followed by Adjuvant Chemotherapy

Background

Regenerating gene 1A (REG1A) plays an important role in tissue regeneration and in cell proliferation in the mucous membrane of the gastrointestinal tract. We previously reported that the positive expression status of REG1A was predictive of chemoradiosensitivity in patients treated with preoperative chemoradiotherapy before esophagectomy or with definitive chemoradiotherapy. To further confirm the utility of REG1A as a chemosensitivity marker, we carried out an additional retrospective clinical study aimed at determining whether REG1A is a reliable chemosensitivity marker in patients treated with esophagectomy followed by adjuvant chemotherapy.

Method

A total of 177 patients with T2–4 thoracic esophageal squamous cell carcinoma received curative surgery without preoperative treatment at Akita University Hospital between 2001 and 2011. A tissue microarray was constructed, and REG1A expression status was analyzed immunohistochemically. We then statistically analyzed the relationships between REG1A expression status and 5-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS).

Results

In the adjuvant group (n = 105), REG1A-positive patients showed significantly better prognoses than REG1A-negative patients. (5-year OS, p = .0022; DSS, p = .0004; and DFS, p = .0040). However, there were no significant differences between REG1A-positive and REG1A-negative patients in the surgery group (n = 72). Univariate and multivariate analyses showed REG1A expression status to be a significant prognostic factor affecting 5-year DSS, comparable to lymph node metastatic status.

Conclusion

The present study suggests REG1A expression status has the potential to be a highly reliable and clinically useful chemosensitivity marker in patients treated with advanced thoracic esophageal squamous cell carcinoma. REG1A expression status will provide a good indication of treatment strategy and enable more individualized treatment for patients.     

Concurrent Chemoradiotherapy or Endoscopic Stenting for Advanced Squamous Cell Carcinoma of Esophagus: A Case-Control Study

Background We evaluated the role of chemoradiotherapy (CRT) for patients with inoperable squamous esophageal cancer. Methods Patients with locally advanced or metastatic squamous esophageal carcinoma who received CRT were recruited. The CRT consists of continuous infusion of 5-fluorouracil at 200 mg/m²/day, and cisplatin at 60 mg/m² on days 1 and 22, with concurrent radiotherapy for a total of 50 to 60 Gy in 25 to 30 fractions over 6 weeks. Efficacy was assessed by endoscopy and computed tomographic scan before and 8 weeks after completion of the treatment program. Median survival and the need for palliative esophageal stenting were compared with another group of patients who received endoscopic stenting. Results From 1996 to 2003, a total of 36 consecutive patients (33 male, mean ± SD age 63.2 ± 9.5 years) with T4 disease (81%) with or without cervical nodal metastasis (50%) received CRT, while 36 patients treated with endoscopic stenting alone were recruited as controls. Both groups were comparable in demographics, pretreatment dysphagia score, comorbidities, and tumor characteristics. CRT was completed in 32 patients (89%). There was no treatment-related mortality. Tumor volume was greatly reduced after CRT in 19 patients. Four patients (11%) received salvage esophagectomy 9 to 42 months after CRT. Compared with the stenting group, CRT statistically significantly improved 5-year survival (15% vs. 0%, P = .01), median survival (10.8 months vs. 4.0 months, P < .005), and need for stenting (22% vs. 100%, P = .005). Conclusions Palliative CRT can effectively improve the symptoms of dysphagia in patients with inoperable squamous esophageal carcinoma. It results in better survival compared with endoscopic stenting in these patients.     

Standard radical esophagectomy in thoracic esophageal cancer

In Japan, the standard radical surgical procedure in patients with thoracic esophageal cancer is right thoracoabdominal esophagectomy with lymphadenectomy. However, with the development of endoscopic surgery and improvements in chemotherapy and chemoradiotherapy, the role of radical surgery has been changing. The indications for radical surgery are stage I disease without indications for endoscopic resection (endoscopic mucosal resection or endoscopic submucosal dissection), stage II disease, or stage III disease without T 4 tumors. Because of the favorable results of chemoradiotherapy in the treatment of stage I disease, the Japan Clinical Oncology Group (JCOG) started a randomized, controlled trial comparing surgery and chemoradiotherapy in the treatment of stage I thoracic esophageal cancer. The 5-year overall survival rates in patients who underwent surgery alone for thoracic esophageal cancer were 88% with stage I and 52% with stage II + III disease in Japan. The most important area in lymphadenectomy is the region from the neck to superior mediastinum, and three-field dissection is widely performed in Japan. However, there is no evidence that three-field dissection is necessary or that two-field dissection is sufficient. The efficacy of postoperative adjuvant chemotherapy for the treatment of thoracic esophageal cancer was confirmed in a Japanese randomized, controlled trial and it is expected that the timing of adjuvant chemotherapy will change from post- to pre-surgery (neoadjuvant chemotherapy).     

Salvage esophagectomy for local recurrent esophageal cancer after definitive chemoradiotherapy followed by photodynamic therapy: A case report

IntroductionPhotodynamic therapy (PDT) is performed as a salvage treatment for patients with residual or recurrent esophageal cancer after chemoradiotherapy (CRT). Although PDT is considered less invasive than salvage surgery, it is unclear how deep its effects are and whether it causes damage to adjacent tissues. Herein, we report a case of esophageal cancer treated with PDT followed by esophagectomy. In this case, we evaluated the effect of PDT on adjacent tissues based on surgical and pathological examination.Presentation of caseA 58-year-old man with dysphagia was diagnosed with esophageal squamous cell carcinoma (SqCC; T1N0M0, Stage I) in the upper thoracic esophagus. He underwent definitive CRT with two courses of 5-fluorouracil and cisplatin every 4 weeks with 60 Gy of radiation. Twelve months after CRT, endoscopic examination revealed local recurrence, and PDT using talaporfin sodium was performed. The tumor recurred again 6 months after PDT, and robot-assisted thoracoscopic esophagectomy was performed as a definitive treatment. Tissues around the left side of the esophagus and thoracic duct were tightly adherent with severe fibrosis and were successfully removed by extended resection. Histopathological examinations showed that the esophageal wall and peri-esophageal tissue were replaced by fibrous tissue and this extended even beyond the tumor.DiscussionThe primary tumor was limited to the submucosal layer, and the target for irradiation had some longitudinal margins. Therefore, PDT can cause intense inflammation in tissues adjacent to the tumor.ConclusionsIt is necessary to consider the location when performing salvage esophagectomy after PDT.     

Comparison Between Radical Esophagectomy and Definitive Chemoradiotherapy in Patients with Clinical T1bN0M0 Esophageal Cancer

Background

Esophagectomy remains the mainstay treatment for clinical T1bN0M0 esophageal cancer because pathologic lymph node metastases in these patients are not negligible. Recently, chemoradiotherapy (CRT), which can preserve the esophagus, has been reported to be a promising therapeutic alternative to esophagectomy. However, to our knowledge, no comparative studies of esophagectomy and CRT have been reported in clinical T1bN0M0 esophageal cancer.

Methods

A total of 173 patients with clinical T1bN0M0 squamous cell carcinoma of the thoracic esophagus were enrolled in this study, 102 of whom were treated with radical esophagectomy (S group) and 71 with definitive CRT (CRT group). Treatment results of both groups were retrospectively compared.

Results

No statistically significant difference was found in overall survival, but the S group displayed significantly better progression-free survival than the CRT group. Disease recurrence was observed in 12 S group patients and 20 CRT group patients. The incidence of distant recurrence was similar, while local recurrence and lymph node recurrence were significantly more frequent in the CRT group. In the S group, 20 patients had pathologic lymph node metastasis. The progression-free survival of patients with pathologic lymph node metastasis did not differ from those without nodal metastasis. In the CRT group, local recurrence could be controlled by salvage esophagectomy, but treatment results of lymph node recurrence were poor; only 4 of 12 patients with lymph node recurrences were cured.

Conclusions

Selection of patients at high risk of pathologic lymph node metastasis is essential when formulating treatment decisions for clinical T1bN0M0 esophageal cancers.     

Survival Impact of Total Resected Lymph Nodes in Esophageal Cancer Patients With and Without Neoadjuvant Chemoradiation

Background

Current esophageal treatment guidelines suggest that, when more than 15 lymph nodes are detected, dissection should be done as the minimum requirement for staging in esophageal squamous cell carcinoma (ESCC) patients undergoing esophagectomy without induction chemoradiotherapy (CRT). However, for neoadjuvant CRT, there is limited information. We sought to clarify the role of lymphadenectomy in ESCC patients with and without neoadjuvant CRT.

Patients and Methods

Data on 3156 ESCC patients receiving esophagectomy with (group 1, n?=?1399) and without (group 2, n?=?1757) neoadjuvant CRT between 2008 and 2014 were collected from a national cancer registry in Taiwan. The impact of the resected lymph nodes on overall survival was assessed according to pathologic stages. A Cox regression model was used to identify prognostic factors for overall survival.

Results

Five-year overall survival rates were 35.6% for the entire group, 30.32% for group 1, and 39.55% for group 2 (p?<?0.0001 for group 1 vs group 2). The best cutoff value was 21 lymph nodes in both group 1 and group 2. In group 1, the independent prognostic factors included age?≥?54 years, clinical N status, y-pathologic T, y-pathologic N, y-pathologic stage, grade, location, margin status, esophagectomy (thoracoscopic vs open), and number of total resected lymph nodes (≤?21 vs?>?21). For group 2, the independent prognostic factors were gender, clinical stage, pathologic T, pathologic N, tumor length, grade, and margin status.

Conclusions

Extent of lymphadenectomy was associated with survival in patients with neoadjuvant CRT followed by esophagectomy. The optimum lymphadenectomy should be modulated by pathologic stage.

     

MiRNAs and Their Association with Locoregional Staging and Survival Following Surgery for Esophageal Carcinoma

Background

Prognostic and staging information for esophageal cancer impacts clinical decision making. miRNAs, a newly discovered class of biomarkers and their expression might add additional information relevant to this. In this study we evaluated the expression of selected miRNAs and their relationship to tumor stage and survival in patients with locally advanced tumors following esophagectomy.

Materials and Methods

A total of 43 individuals undergoing esophagectomy (without neoadjuvant therapy) for locally advanced but not metastatic (pT2/3; pN0/1) disease (22 adenocarcinoma [EAC], 21 squamous cell carcinoma [SCC]) were included in this study. Perioperative clinical and survival data were collected and managed on a database. The expression of miR-21, miR-106a, miR-148a, miR-205 in formalin-fixed paraffin-embedded specimens was evaluated by TaqMan qPCR assays. Expression was compared with clinicopathological features of the cancers and outcome.

Results

In EAC, miR-148a expression levels were inversely associated with cancer differentiation. miR-21 expression levels were higher in SCC if distant lymph node metastases were present. miR-148a levels were lower when EAC was more proximally located, and miR-21 levels were lower when SCC was more proximal. miR-106a and miR-148a were lower in patients with SCC who developed recurrent disease or had a tumor-related death.

Conclusions

In patients with locally advanced esophageal squamous cell carcinoma, but not adenocarcinoma, alterations in the expression of miR-21 correlate with tumor location and lymph node status. Furthermore, miR-106a and miR-148a expression correlates with disease recurrence and tumor-related mortality. miRNA markers might inform the initial assessment of these patients, and predict those at higher risk of postsurgical recurrence.     

Postoperative Pneumonia is Associated with Long-Term Oncologic Outcomes of Definitive Chemoradiotherapy Followed by Salvage Esophagectomy for Esophageal Cancer

Background or Purpose

As we previously indicated, postoperative pneumonia has a negative impact on the overall survival after planned esophagectomy. However, the impact of postoperative pneumonia after salvage esophagectomy on long-term oncologic outcomes still remains unclear. This study aimed to indicate the association between postoperative pneumonia and long-term outcomes of definitive chemoradiotherapy followed by salvage esophagectomy. Furthermore, we determined a prediction model for overall survival (OS) and disease-free survival (DFS) using a survival classification and regression tree (CART).

Methods

Ninety-three patients who underwent CRT followed by esophagectomy for thoracic esophageal cancer were identified for this study. Forty-nine patients and 44 patients were included in the salvage and neoadjuvant groups, respectively. We investigated the association between postoperative pneumonia and long-term oncologic outcomes following salvage esophagectomy.

Results

Patients from the salvage group tended to have a lower OS compared to neoadjuvant group (median survival: salvage, 24 months vs neoadjuvant, 43 months, p?=?0.117). Multivariate analyses revealed that postoperative pneumonia adversely affected both OS (p?<?0.001) and DFS (p?=?0.044) after salvage esophagectomy. We generated the prediction model for OS and DFS in the salvage group using survival CART. Postoperative pneumonia was the most important parameter for predicting the OS.

Discussion

The present study demonstrates the long-term outcomes and risk factors for mortality of salvage esophagectomy. To improve OS after salvage surgery, the development of a means of decreasing pulmonary complications is needed.

     

Pretreatment Gene Expression Profiles Can Be Used to Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

BACKGROUND: The use of neoadjuvant therapy, in particular chemoradiotherapy (CRT), in the treatment of esophageal cancer (EC) remains controversial. The ability to predict treatment response in an individual EC patient would greatly aid therapeutic planning. Gene expression profiles of EC were measured and relationship to therapeutic response assessed. METHODS: Tumor biopsy samples taken from 46 EC patients before neoadjuvant CRT were analyzed on 10.5K cDNA microarrays. Response to treatment was assessed and correlated to gene expression patterns by using a support vector machine learning algorithm. RESULTS: Complete clinical response at conclusion of CRT was achieved in 6 of 21 squamous cell carcinoma (SCC) and 11 of 25 adenocarcinoma (AC) patients. CRT response was an independent prognostic factor for survival (P < .001). A range of support vector machine models incorporating 10 to 1000 genes produced a predictive performance of tumor response to CRT peaking at 87% in SCC, but a distinct positive prediction profile was unobtainable for AC. A 32-gene classifier was produced, and by means of this classifier, 10 of 21 SCC patients could be accurately identified as having disease with an incomplete response to therapy, and thus unlikely to benefit from neoadjuvant CRT. CONCLUSIONS: Our study identifies a 32-gene classifier that can be used to predict response to neoadjuvant CRT in SCC. However, because of the molecular diversity between the two histological subtypes of EC, when considering the AC and SCC samples as a single cohort, a predictive profile could not be resolved, and a negative predictive profile was observed for AC.     

Salvage esophagectomy under bilateral thoracotomy after definitive chemoradiotherapy for aorta T4 thoracic esophageal squamous cell carcinoma: Report of a case

IntroductionThe surgical technique for esophagectomy to treat esophageal malignancies has been improved over the past several decades. Nevertheless, it remains extremely difficult to surgically treat patients with locally advanced T4b tumors invading the aorta or respiratory tract.Presentaion of caseA 37-year-old Japanese man was diagnosed with T4b (descending aorta) N2M0, Stage IIIC middle thoracic esophageal squamous cell carcinoma. He was initially treated with definitive CRT followed by 3 courses of DCF. After the DCF, CT showed that the main tumor had shrunk and appeared to have separated from the descending aorta. Therefore we decided to perform a salvage esophagectomy. Because we needed the ability to closely observe the site of invasion to determine whether aortic invasion was still present, half the esophageal resection was performed under right thoracotomy, but the final resection at the invasion site was performed under left thoracotomy. Consequently, the thoracic esophagus was safely removed and aortic replacement was avoided. The patient has now survived more than 30 months after the salvage esophagectomy with no additional treatment for esophageal cancer and no evidence of recurrent disease.DiscussionBecause this and the previously reported procedures, each have particular advantages and disadvantages, one must contemplate and select an approach based on the situation for each individual patient.ConclusionSalvage esophagectomy through a right thoracotomy followed by careful observation of the invasion site for possible aortic replacement through a left thoracotomy is an optional procedure for these patients.     

The role of endoscopic resection in early-stage esophageal adenocarcinoma: Esophagectomy is associated with improved survival in patients presenting with clinical stage T1bN0 disease

BackgroundStudies evaluating endoscopic resection for early-stage (cT1N0M0) esophageal adenocarcinoma include small numbers of patients with T1b tumors. The role of endoscopic resection in esophageal adenocarcinoma remains incompletely defined.MethodsWe queried the National Cancer Database to identify patients presenting with esophageal adenocarcinoma between 2010 and 2017. Those treated with neoadjuvant chemoradiotherapy and endoscopic ablation were excluded. Patients undergoing endoscopic resection for cT1a and cT1b tumors were separately 1:1 propensity matched for relevant demographic and tumor factors to those undergoing esophagectomy for disease of like clinical stage. The Kaplan-Meier method was used to compare 5-year overall survival for matched cohorts.ResultsA total of 3,157 patients met the inclusion criteria. Of these patients, 2,024 (64.1%) had cT1a and 1133 (35.9%) had cT1b disease. Among those with cT1a tumors, 461 (22.8%) underwent esophagectomy, 1,357 (67.0%) endoscopic resection, and 206 (10.2%) treatment with chemoradiotherapy alone. Among those with cT1b tumors, 649 (57.3%) underwent esophagectomy, 293 (25.9%) endoscopic resection, and 191 (16.8%) chemoradiotherapy. On unadjusted comparison, patients treated for esophageal adenocarcinoma with chemoradiotherapy had a lower rate of overall survival than those treated with endoscopic resection or esophagectomy (26.1% vs 73.1% vs 75.5%, P < .001). On comparison of matched cohorts, patients undergoing endoscopic resection for cT1b tumors demonstrated lower rates of overall survival than those undergoing esophagectomy (60.6% vs 74.1%, P = .0013), whereas those undergoing endoscopic resection for cT1a tumors demonstrated rates of overall survival statistically similar to those undergoing esophagectomy (77.8% vs 80.2%, P = .75).ConclusionEsophagectomy is associated with improved overall survival relative to endoscopic resection in patients presenting with cT1bN0M0 but not in those with cT1a esophageal adenocarcinoma.     

Correlation Between Biomarker Candidate Proteins with the Effect of Neoadjuvant Chemoradiation Therapy on Esophageal Squamous Cell Carcinoma

Background

While chemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC), it is important to predict response prior to treatment by using markers because some patients respond well and others do not.

Methods

Fifty-nine patients with ESCC were treated with neoadjuvant CRT at the Kagoshima University Hospital. The expression of seven types of biomarker candidate proteins in biopsy specimens of untreated primary tumors was evaluated to determine whether it correlated with response and prognosis.

Results

The positive expression rates were 47% for p53, 83% for CDC25B, 68% for 14-3-3sigma, 76% for p53R2, 75% for ERCC1, 32% for Gli-1, and 54% for Nrf2. In terms of histological response, tumor grade of the 59 patients was 48.8% for grade 1 as the non-responder, 29.2% for grade 2, and 22.0% for grade 3 as the responder. CRT was significantly effective in p53(?), p53R2(?), ERCC1(?), and Nrf2(?) tumors, while p53(?), p53R2(?), and ERCC1(?) were factors independently correlated with effective histological response. Their combined expression of two or three negative expressions had 100% effective response and was a significant prognostic factor.

Conclusion

Our results suggest that two or three negative expressions of p53, p53R2, and ERCC1 in biopsy specimens of primary tumors were associated with a favorable response to CRT for ESCC. Assessment of tumor suppressor and DNA repair protein expressions in biopsy specimens may be useful for the potential utility of CRT therapy for patients with ESCC prior to treatment.

     

Neoadjuvant Chemoradiation Versus Hyperfractionated Accelerated Radiotherapy in Locally Advanced Rectal Cancer

Background Neoadjuvant therapy is increasingly used in resectable locally advanced rectal cancer. The exact role of the addition of chemotherapy is not established. We compared neoadjuvant therapy using chemoradiation (CRT) or hyperfractionated accelerated radiotherapy (HART). Methods Clinical, pathological, and survival data were obtained from patients with resectable stage II or III rectal cancer within 7 cm from the anal verge. A group of 50 patients was treated with a preoperative dose of 41.6 Gy of radiotherapy (RT) in two daily fractions of 1.6 Gy over 13 days immediately followed by surgery (HART). A second group of 96 patients received 45 Gy of conventionally fractionated RT in 25 daily fractions of 1.8 Gy combined with 5-fluorouracil–based chemotherapy followed by surgery within 4 to 6 weeks (CRT). Both groups were compared in terms of morbidity, pathological downstaging, local recurrence, and survival. Results Both groups were comparable in terms of preoperative clinicopathological variables. The mean distance from the anal verge was 5.8 cm (HART) versus 4.9 cm (CRT). Sphincter preservation was possible in 74% (HART) versus 83.5% (CRT) of patients (P = .013). The clinical anastomotic leak rate was 2% (HART) versus 2.2% (CRT). Pathological complete response was observed in 4% (HART) versus 18% (CRT) of the resected specimens (P = .002). A pelvic recurrence developed in 6% (HART) versus 4.4% (CRT) of patients (P = .98). Overall 5-year survival was 58% (HART) versus 66% (CRT) (P = .19); disease-free 5-year survival was 51% (HART) versus 62% (CRT) (P = .037). Conclusions Compared with preoperative HART followed by immediate surgery, preoperative CRT followed by a 6-week waiting period enhances pathological response and increases sphincter preservation rate. This could be explained by the addition of chemotherapy or the longer interval between neoadjuvant therapy and surgery. No statistically significant difference was observed in local control or overall survival.     

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.