Systematic review and meta‐analysis on the significance of salvage esophagectomy for persistent or recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy

The therapeutic strategy to be recommended in case of recurrent or persistent squamous cell esophageal cancer after completed definitive chemoradiotherapy (dCRT) has to be documented. Salvage esophagectomy has traditionally been recognized as a viable option, but many clinicians oppose the use of surgery due to the associated excessive morbidity and mortality. ‘Second‐line’ chemoradiotherapy (CRT) without surgery may offer a treatment alternative in these difficult and demanding clinical situations. Until now, no comprehensive attempt has been carried out to compare the respective therapeutic options. A systematic literature search was performed focusing on studies comparing survival and treatment‐related mortality in patients submitted to salvage esophagectomy or second‐line CRT for recurrent or persistent esophageal squamous cell carcinoma after dCRT. Hazard ratios and risk ratios were calculated to compare the effect of these therapeutic strategies on overall survival and treatment‐related mortality, respectively. Four studies containing 219 patients, with persistent or recurrent esophageal squamous cell carcinoma after dCRT, were included in the meta‐analysis. The analysis revealed an overall survival benefit following salvage esophagectomy with a pooled hazard ratio for death of 0.42 (95% confidence interval 0.21–0.86, P = 0.017) compared with second‐line CRT. A treatment‐related mortality of 10.3% was recorded in the 36 patients who were submitted to salvage esophagectomy, while it was impossible to perform a meta‐analysis comparing treatment‐related mortality between the groups. Salvage esophagectomy offers significant gain in long‐term survival compared with second‐line CRT, although the surgery is potentially at a price of a high treatment‐related mortality.     

Neoadjuvant chemoradiotherapy followed by esophagectomy versus definitive chemoradiotherapy in resectable stage II/III (T1-3N0, 1M0) esophageal squamous cell carcinoma

Background There are two intensive modalities for the treatment of resectable esophageal carcinoma: esophagectomy and definitive chemoradiotherapy (CRT). Esophagectomy with preoperative CRT was retrospectively compared with CRT alone in resectable stage II/III esophageal squamous cell carcinoma. Methods Seventy-four patients with resectable stage II/III (T1-3N0, 1M0) esophageal squamous cell carcinoma were treated with preoperative CRT by 5-fluorouracil (5-FU) 700 mg/m² on days 1 to 5, nedaplatin 80 mg/m² on day 1, and concurrent radiation for a total of 30 Gy in 3 weeks. If patients decided to undergo surgery, esophagectomy from the thoracoabdominal approach was carried out 6 weeks after the completion of CRT (CRT + Surg group, n = 51). If patients decided not to undergo surgery, they were treated with one more course of CRT (CRT-alone group, n = 23). Results There was no significant difference in overall survival between the two groups (P = 0.1006), whereas the disease-free survival in the CRT + Surg group was improved compared with the CRT-alone group (P = 0.0186). In the patients with clinical stage III carcinoma or with regional lymph node metastasis, the overall survival rate was significantly improved in the CRT + Surg group compared with the CRT-alone group. The rate of local failures in the CRT + Surg group was significantly lower compared with the CRT-alone group (P = 0.0011). Conclusions Preoperative CRT followed by esophagectomy provides better local control, but does not prolong overall survival, compared with definitive CRT. However, in clinical stage III or N1, esophagectomy with preoperative CRT could contribute to the improvement of survival in esophageal squamous cell carcinoma.     

Comparison of salvage chemoradiation versus salvage surgery for recurrent esophageal squamous cell carcinoma after definitive radiochemotherapy or radiotherapy alone

A consensus treatment strategy for esophageal squamous cell carcinoma (ESCC) patients who recur after definitive radiochemotherapy/radiotherapy has not been established. This study compared the outcomes in ESCC patients who underwent salvage surgery, salvage chemoradiation (CRT) or best supportive care (BSC) for local recurrence. Ninety‐five patients with clinical stage I to III ESCC who had completely responded to the initial definitive radiochemotherapy or radiotherapy alone and developed local recurrence were enrolled in this study. Fifty‐one of them received salvage esophagectomy, and R0 resection was performed in 41 patients, 36 underwent salvage CRT, and the remaining eight patients received BSC only. The 5‐year overall survival was 4.6% for the 87 patients receiving salvage surgery or CRT, while all patients in the BSC group died within 12.0 months, the difference was statistically significant (P = 0.018). The 1‐, 3‐, 5‐year survival rates in the salvage surgery and salvage CRT groups were 45.1%, 20.0%, 6.9% and 51.7%, 12.2%, 3.1%, respectively, there was no difference of overall survival between the two groups (P = 0.697). Patients also presented with lymph node relapse had inferior survival compared to those with isolated local tumor recurrence after salvage therapy. In the salvage surgery group, infections occurred in eight patients, and three developed anastomotic leakage. In the salvage CRT group, grade 2–4 esophagitis and radiation pneumonitis was observed in 19 and 3 patients, respectively. Seven patients (19.4%) developed esophagotracheal fistula or esophageal perforation. This study of salvage CRT versus salvage surgery for recurrent ESCC after definitive radiochemotherapy or radiotherapy alone did not demonstrate a statistically significant survival difference, but the frequency of complications including esophagotracheal fistula and esophageal perforation following salvage CRT was high.     

A single institutional non-randomized retrospective comparison between definitive chemoradiotherapy and radical surgery in 82 Japanese patients with resectable esophageal squamous cell carcinoma

SUMMARY.  This retrospective study was conducted to compare the treatment results between radical surgery and definitive chemoradiotherapy for resectable squamous cell carcinoma of the esophagus. Between June 2000 and May 2005, 82 consecutive patients were selected for this study in which 33 were treated with chemoradiotherapy and 49 with surgery. The patients in the chemoradiotherapy (CRT) group received 2–4 cycles of 5-fluorouracil (1000 mg/m²/day, day 1–4, continuous) combined with cisplatin (75 mg/m², day 1, bolus) plus 50.4 Gy of radiation, while those in the surgery group were treated by an esophagectomy with radical node dissection. Eighteen surgical patients received postoperative chemotherapy. The baseline clinical TNM stage was similar between the two groups. With a median follow-up period of 36 months (range: 23–84 months) with 47 survivors (57%), the 3-year overall survival rates ( P = 0.22) and disease-free survival rates ( P = 0.16) were 48% and 44% in the chemoradiotherapy group versus 65% and 59% in the surgery group, and lacked statistical significance. This non-randomized study on patients with resectable squamous cell carcinoma of the esophagus showed that chemoradiotherapy could result in survival comparable with conventional surgery in spite of selection bias of patients. There is a trend toward improved survival with surgery versus definitive CRT.     

Long-term outcomes following neoadjuvant chemoradiotherapy in patients with clinical T2N0 esophageal squamous cell carcinoma

The optimal treatment for patients with local esophageal cancer (cT2N0 disease) has not yet been defined. We sought to determine whether neoadjuvant chemoradiotherapy (CRT) can improve prognosis compared with direct esophagectomy in this patient group. Between 1994 and 2005, patients with cT2N0 esophageal squamous cell carcinoma who underwent either neoadjuvant CRT or surgery as first-line treatment were retrospectively reviewed. We collected information on their demographic characteristics, staging modality, clinical and pathological stages, perioperative course, and survival. The study endpoints included tumor recurrence, disease-specific survival (DSS), and overall survival rate. Of the 71 eligible patients, 14 received an esophagectomy first, whereas the remaining 57 received neoadjuvant CRT first. Despite the high pathological complete response (pCR) rate of 37% after neoadjuvant CRT, routine neoadjuvant CRT did not translate into better survival compared to direct surgery (5-year DSS: 39% vs. 68%, P= 0.17). The dramatic survival difference between pCR and non-pCR patients (5-year DSS: 85% vs. 4%, P < 0.001) accounts for these unsatisfactory results. In our series, the administration of neoadjuvant CRT to patients with clinical stage T2N0 esophageal squamous cell carcinoma did not significantly improve outcomes compared with direct esophagectomy.     

EMR as salvage treatment for patients with locoregional failure of definitive chemoradiotherapy for esophageal cancer

BACKGROUND: Definitive chemoradiotherapy is recognized as a standard treatment for esophageal cancer. Although most failures of this combined modality are locoregional, without distant metastasis, there are few curative treatment options available in such cases except salvage esophagectomy. METHODS: Experience with 16 patients with squamous cell carcinoma of the esophagus who underwent EMR as a salvage treatment after locoregional failure of definitive chemoradiotherapy was reviewed retrospectively. EMR was performed by using the mucosal strip technique. Eight patients had local recurrence at the primary site after a complete response to chemoradiotherapy, 5 had metachronous multiple cancers, and 3 had residual tumor after completing chemoradiotherapy. RESULTS: In all patients, the EMR-treated tumors were histopathologic stage T1 and were clinical stage N0M0 as defined by EUS and CT. No serious complication was observed in any patient. At a median follow-up of 33 months (range 11-73 months) from the initiation of chemoradiotherapy, 3 patients (38%) with local recurrence at the primary site, 3 (40%) with metachronous multiple cancers, and two (67%) with residual cancer were still alive and disease-free after salvage EMR, for periods of 30 to 63 months. The 3-year survival rate from the initiation of salvage EMR for all patients was 56%. CONCLUSIONS: Long-term survival can be achieved with salvage EMR for locoregional failure after definitive chemoradiotherapy for esophageal cancer without serious complications. EMR may be a salvage treatment option when a recurrent or residual tumor is superficial or local.     

Is surgery always necessary in esophageal cancer?

Two randomized trials showed that survival was similar after definitive chemoradiation (CRT) or after CRT and surgery in locally advanced esophageal squamous cell cancer, despite more frequent local recurrences. In one trial randomization was done at inclusion, whereas in the other trial a workup was performed after initial CRT; only clinical responders were randomized between surgery and additional CRT. Therefore, clinical non-responders could be operated on without delay. Indeed, randomized patients and nonrandomized operated patients had a similar survival, even if no response was seen on the specimen. However, evidence of benefit is poor in cases of delayed recurrence. Only small nonrandomized studies have considered this issue. R0 resection rates ranged from 50 to 87%, 5-year survival rates from 0 to 33%, and operative mortality from 12.5 to 25%; only R0 resection was associated with long survival. Therefore, the benefit of delayed salvage resection should be assessed in a prospective strategic randomized trial, after a CRT intensive enough to eradicate a sensitive tumor without increasing the risk of eventual surgery. The FFCD (Fédération Francophone de Cancérologie Digestive) is working on such a trial in locally advanced operable esophageal carcinoma: CRT and systematic surgery compared with CRT followed by surgery in case of proven persistent tumor or resectable local recurrence. CRT will be improved with induction chemotherapy, new drugs, and up-to-date protracted radiotherapy.     

Neoadjuvant chemoradiotherapy followed by esophagectomy for initially resectable squamous cell carcinoma of the esophagus with multiple lymph node metastasis

Neoadjuvant chemoradiotherapy (CRT) was expected to improve surgical curability and prognosis for advanced esophageal cancer. However, the clinical efficacy of neoadjuvant CRT followed by esophagectomy with three-field lymphadenectomy (3FL) for initially resectable esophageal squamous cell carcinoma (SCC) remains unclear. Since 1998, we have defined the status of metastases to five or more nodes, or nodal metastases present in all three fields as multiple lymph node metastasis, which was previously shown to be associated with poor prognosis. Between 1998 and 2002, 83 patients with initially resectable esophageal SCC were prospectively allocated into two groups, according to the clinical status of nodal metastasis. Nineteen patients clinically accompanied by multiple lymph node metastasis initially underwent neoadjuvant CRT followed by curative esophagectomy with 3FL (CRT group). The other 64 patients clinically without multiple lymph node metastasis immediately received curative esophagectomy with 3FL (control group). Although the overall morbidity rate was significantly higher in the CRT group, no in-hospital death occurred in either group. Patients without pathologic multiple lymph node metastasis in the CRT group showed a significantly better disease-free survival rate than either patients pathologically with multiple lymph node metastasis in the control group or those in the CRT group. However, the differences in the overall survival rate among the groups were not significant. Thus, the significant survival benefit by neoadjuvant CRT in addition to esophagectomy with 3FL was not confirmed, although it may have been advantageous, without increase in mortality, to at least some patients who responded well to neoadjuvant CRT. Therefore, neoadjuvant CRT can be an initial treatment of choice for resectable esophageal SCC clinically with multiple lymph node metastasis. The prediction of response to CRT and the development of alternative treatment for hematogenous recurrence could achieve a further survival benefit of this trimodality treatment.     

Salvage radiation therapy and chemoradiation therapy for postoperative locoregional recurrence of esophageal cancer

The purpose of this retrospective study was to assess the efficacy of salvage radiation therapy (RT) or chemoradiation therapy (CRT) for locoregional recurrence (LR) of esophageal cancer after curative surgery. Forty‐two patients who received salvage RT or CRT for LR of esophageal cancer after curative surgery between November 2000 and May 2012 were reviewed. The intended RT regimen was 60 Gy in 30 fractions combined with concurrent platinum‐based chemotherapy. Median follow‐up periods were 17.9 months for all evaluable patients and 28.2 months for patients still alive (19 patients) at analysis time. The 1‐, 2‐, and 3‐year survival rates were 81.2 ± 6.4%, 51.3 ± 8.6%, and 41.1 ± 8.7%, respectively, with a median survival time of 24.3 ± 4.1 months. Out of 41 evaluable patients, 16 patients (39%) were alive beyond 2 years from salvage therapy. However, univariate analyses for overall survival showed no significant prognostic factor. Grade 3 or higher leukocytopenia was observed in 46% of the patients. Salvage RT or CRT for LR after surgery for esophageal cancer was safe and effective. These therapies may offer long‐term survival to some patients. RT or CRT should be considered for LR.     

Lymph node dissection with cervical approach as a salvage surgery for locoregional failure after definitive chemoradiotherapy in a patient with recurrent esophageal carcinoma: report of a case

Salvage surgery is one important therapeutic option after locoregional failure of definitive chemoradiotherapy (dCRT) in patients with advanced or recurrent esophageal carcinoma. We have performed cervical lymph node dissection as a salvage surgery after chemoradiotherapy in a patient with recurrent esophageal carcinoma. A 54-year-old Japanese man was admitted to our hospital because of multiple lymph node metastases after endoscopic submucosal dissection (ESD) for early-stage esophageal carcinoma. The patient underwent a circumferential ESD of early-stage esophageal carcinoma in another hospital. The esophageal carcinoma, measuring 75 × 60 mm in size, was a superficial spreading type located in the middle portion of the thoracic esophagus. Histology of the resected specimen revealed a moderately to poorly differentiated squamous cell carcinoma, and the depth of invasion was limited within the mucosal layer associated with a small area being attached to the muscularis mucosae. Five months after ESD, lymph node metastases in the regions of right recurrent nerve and the left tracheobronchus were found, for which dCRT was performed. These metastatic lymph nodes disappeared in the chest CT scan images. Lymph node metastasis in the region of the right recurrent nerve then reappeared 8 months after the completion of CRT. Considering the solitary lymph node metastasis and surgical invasiveness, lymph node dissection using a cervical approach was selected as a salvage surgery. Cervical approach for the lymph node dissection in the region of right recurrent nerve may be one feasible option as a minimally invasive salvage surgery for patients with recurrent esophageal carcinoma after dCRT.     

Chemoradiotherapy with and without esophagectomy for advanced esophageal cancer

BACKGROUND/AIMS: To evaluate the impact of surgery on survival after chemoradiotherapy, we analyzed the long-term outcome of patients with advanced esophageal cancer. METHODOLOGY: Data on 92 consecutive patients with T3 or T4 esophageal cancer who were initially treated by chemoradiotherapy were reviewed retrospectively. Of 82 patients who completed the planned schedule, 35 patients underwent esophagectomy (CRT+E Group) and 47 patients received definitive chemoradiotherapy (CRT Group). RESULTS: A response to chemoradiotherapy was obtained in 71% of all 92 patients. The 1- and 3-year survival rates in the patients with T3M0 were 87 and 44 percent respectively, while these in the patients with T4 and/or M1(Lymph) disease were 47 and 20 percent. Although there was no difference in overall survival between the CRT+E Group and the CRT Group, the survival of responders in the CRT+E Group was significantly higher than that of those in the CRT Group (P=0.0448). The locoregional recurrence rate of responders in the CRT Group was higher than that in the CRT+E Group. Multivariate analysis showed that the independent prognostic factors were response, M(Lymph), and esophagectomy. CONCLUSIONS: Although this study was retrospective and nonrandomized, esophagectomy after chemoradiotherapy might improve the survival of responders for locoregional control.     

Locoregional chemotherapy in pancreatic cancer

BACKGROUND/AIMS: Investigating whether or not locoregional chemotherapy has an effect on survival among patients with pancreatic cancer. The possibility of radical surgical interventions for treatment of cancer of the pancreas is very low. Locoregional chemotherapy is one of the modalities advocated to increase survival of such patients. METHODOLOGY: Twenty-nine patients with cancer of the pancreas underwent surgery in our clinic. Eleven patients were female and 18 were male. Surgical procedures and adjuvant locoregional chemotherapy applied to these patients as well as survival obtained are evaluated and compared to those reported in the literature. RESULTS: Eight of the 9 patients that received curative surgery and adjuvant locoregional chemotherapy are still alive after 5, 6, 7, 7, 9, 12, 13, and 17 months. Seventeen patients with advanced stage pancreatic cancer had palliative diversion procedures. Mean survival was 10.5 months for the seven that received locoregional chemotherapy, but 6.2 months for the 10 patients that did not receive locoregional chemotherapy. Mean survival of 3 patients that had only laparotomy was 2.3 months. CONCLUSIONS: Neoadjuvant or adjuvant locoregional chemotherapy has a beneficial effect on the survival of patients that undergo curative or palliative surgery for pancreatic cancer. However further multicenter trials are necessary.     

Radiation therapy alone for stage I (UICC T1N0M0) squamous cell carcinoma of the esophagus: indications for surgery or combined chemoradiotherapy

BACKGROUND AND AIM: The aim of this study was to clarify the efficacy and limitations of radiation therapy (RT) for superficial esophageal carcinoma, and to explore the indications for more aggressive therapy, such as combined chemo-radiotherapy. METHODS: Sixty-eight patients with stage I (UICC T1N0M0) esophageal squamous cell carcinoma treated by definitive RT alone were analyzed. Brachytherapy was administered in 36 patients as a boost, and the prescribed doses were 10 Gy (5 Gy x 2 times) at a low dose rate (19 patients) and 9 Gy (3 Gy x 3 times) at a high dose rate (17 patients). Recurrence patterns and survival rates were assessed and the factors predisposing to recurrences after RT were statistically investigated by univariate analysis. RESULTS: The 5-year cause-specific survival rate and the locoregional control rate were 79.9% and 82.1%, respectively. No case of recurrence or disease-related death was observed in any of the patients with mucosal cancer. Among the cases with the cancer invading the submucosa, there were 12 cases with locoregional recurrence and two cases with distant metastases. In cases of submucosal esophageal cancer, the tumor length was the only statistically significant factor predicting locoregional control. The 5-year locoregional control rate in cases with a short length of the tumor (5 cm in length was 57.8% (P = 0.036). Patients treated by additional brachytherapy exhibited better cause-specific survival and locoregional control rates than those receiving external RT alone, however, the addition had no statistically significant influence on the outcome. CONCLUSIONS: RT was a successful treatment for stage I esophageal cancer, and the treatment outcome using RT was nearly comparable to that of surgery. However, it is suggested that chemo-radiation should be considered in inoperable cases of submucosal cancer when the tumor is more than 5 cm in length.     

Utility of weekly docetaxel combined with preoperative radiotherapy for locally advanced esophageal cancer from pathological analysis

Esophageal squamous cell cancer (ESCC) is a high‐grade carcinoma that is treated with multidisciplinary approaches, including chemoradiotherapy (CRT) followed by surgery. Despite some success with these therapies, overall survival remains poor. In order to investigate a newer CRT regimen, we designed a comparative study to evaluate preoperative CRT using docetaxel (DOC) or 5‐Fluorouracil and cisplatin (FU+CDDP [FP] therapy) for treatment of resectable ESCC. In a retrospective review of patients with resectable, locally advanced ESCC, 95 patients received preoperative CRT between 2001 and 2007. CRT was administered using either FP (n = 40) or DOC (n = 55). Pathological response and clinical outcomes were compared between the two groups. Hazard ratios and time‐to‐event analyses were used to assess outcomes; the ratios were controlled by multivariate logistic regression analysis of potential prognostic factors, and survival was presented with Kaplan–Meier curves. In the FP group, a significant curative effect was observed on the basis of pathological examination of postoperative lesions. However, the DOC group presented a significantly better prognosis on the basis of cumulative survival rates. Logistic regression analysis revealed that the presence of five or more lymph node metastases was an independent predictor of reduced survival. Patients with lymph node metastasis exhibited a better prognosis in the DOC group than those in the FP group. Preoperative CRT for locally advanced esophageal cancer using DOC results in similar or better long‐term outcomes compared with FP‐based CRT. Therefore, CRT using DOC is a promising therapy option for esophageal cancer.     

Submucosal tumor appearance is a useful endoscopic predictor of early primary‐site recurrence after definitive chemoradiotherapy for esophageal squamous cell carcinoma

Chemoradiotherapy (CRT) for esophageal cancer is disadvantageous because of a high locoregional failure rate. Detecting early small recurrent cancers at the primary site is necessary for potential salvage treatment. However, most endoscopists are inexperienced and therefore, a role for surveillance endoscopy after complete remission (CR) has not been established. We retrospectively evaluated serial surveillance endoscopic images from patients eventually proved to have primary‐site recurrence in order to identify useful endoscopic features for early diagnosis. From January 2000 to December 2004, 303 patients with esophageal squamous cell carcinoma underwent definitive CRT, and 133 of them achieved CR. The surveillance endoscopic images stored at intervals of 1–3 months for the 16 patients with recurrence only at the primary tumor site and the 61 patients with no recurrence were collected for reexamination. Among 133 patients who achieved CR, 16 (12%) developed only local recurrence at the primary site. Thirteen of the 16 primary‐site recurrent tumors (81%) appeared as submucosal tumors (SMT), with the remaining appearing as erosions or mild strictures. Of biopsy‐proven recurrences, 81% were preceded by newly developed lesions such as SMT, erosions, or mild strictures detected by earlier surveillance endoscopies. For all 77 patients achieving CR with no metastasis, 86% of the evolving SMT with negative biopsies were eventually confirmed as cancer at later endoscopies. Thirteen of the 21 evolving lesions were subsequently confirmed as recurrent cancer. Early primary‐site recurrence of esophageal cancer after a complete response to CRT is detectable with frequent endoscopic surveillance. SMT appearance is a useful endoscopic sign of early recurrence, as well as a predictor of subsequent diagnosis of recurrence.     

Predictive factors of survival in patients treated with definitive chemoradiotherapy for squamous cell esophageal carcinoma

AIM: The aim of the study was to evaluate the predictive factors of survival in patients with locally advanced squamous cell esophageal carcinoma (LASCOC) treated with definitive chemoradiotherapy (CRT) regimen based on the 5FU/CDDP combination. METHODS: All patients with LASCOC treated with a definitive CRT using the 5FU/CDDP combination between 1994 and 2000 were retrospectively included. Clinical complete response (CCR) to CRT was assessed by esophageal endoscopy and CT-scan 2 mo after CRT completion. Prognostic factors of survival were assessed using univariate and multivariate analysis by the Cox regression model. RESULTS: A total of 116 patients were included in the study. A CCR to CRT was observed in 86/116 (74.1%). The median survival was 20 mo (range 2-114) and the 5-year survival was 9.4%. Median survival of responder patients to CRT was 25 mo (range 3-114) as compared to 9 mo (range 2-81) in non-responder patients (P < 0.001). In univariate analysis, survival was associated with CCR (P < 0.001), WHO performance status < 2 (P = 0.01), tumour length < 6 cm (P = 0.045) and weight loss < 10% was in limit of significance (P = 0.053). In multivariate analysis, survival was dependant to CCR (P < 0.0001), weight loss < 10% (P = 0.034) and WHO performance <2(P = 0.046). CONCLUSION: Our results suggest that survival in patients with LASCOC treated with definitive CRT was correlated to CCR, weight loss and WHO performance status.     

Large cell carcinoma of the lung: a contribution on prognosis after potentially curative resection.

Between 1976 and 1989, 53 out of 60 patients with large cell carcinoma of the lung underwent potentially curative surgery, i.e. macroscopically and microscopically complete resection. For better comparison, all tumors were classified according to the TNM staging system of the UICC 4th edition of 1987. Following potentially curative surgery, in stage I the mean survival time was 19 months and the five-year survival rate 30.1%, in stage II 8 months and 10%, and in stage IIIa 6.5 months and 0%, respectively. The differences in the long term prognosis between the tumor stages are significant. No significant differences could be demonstrated between II and IIIa in terms of the mean survival times. The prognosis for patients with potentially curatively resected squamous cell carcinoma is significantly better than that for patients with large cell carcinoma.     

The Prognostic Impact of Preoperative and Postoperative Chemoradiation in Clinical Stage II and III Esophageal Squamous Cell Carcinomas: A Population Based Study in Taiwan

While preoperative chemoradiation followed by surgery (pre-OP CRT) has been widely applied in the treatment of patients with esophageal cancer, some studies have shown a survival benefit of postoperative chemoradiation (post-OP CRT). The optimal combination of multimodality therapy and the sequence of surgery and chemoradiation for esophageal cancer remain to be investigated.A total of 1385 patients with clinical stage II and III esophageal squamous cell carcinoma (ESCC) were included. On the basis of the sequence of surgery and chemoradiation, the patients were grouped as follows: preoperative chemoradiation followed by surgery (pre-OP CRT+S), surgery alone (S), and surgery followed by postoperative chemoradiation (S+post-OP CRT). Propensity score matching analysis was used to identify 78 well-balanced patients in each group for outcome comparison.In all, 753, 339, and 293 patients were in the pre-OP CRT+S, S, and S+post-OP CRT groups, respectively. Before matching, no differences were observed in the overall survival among the patients in these 3 groups (P = 0.422). After matching, both the pre-OP CRT+S and S+post-OP CRT groups were significantly associated with a better survival compared with the S group (pre-OP CRT+S vs. S: P < 0.001; S+post-OP CRT vs. S: P = 0.005). In contrast, the survival was similar between the pre-OP CRT+S and S+post-OP CRT groups (P = 0.544). In the subgroup analysis, patients with clinical T3/4 stage tumors or those with a tumor size greater than 5 cm were more likely to demonstrate an overall survival benefit from pre-OP CRT compared with post-OP CRT.Both pre-OP CRT and post-OP CRT demonstrated a survival benefit compared with surgery alone, which indicates the importance of trimodality therapy in patients with clinical stage II/III ESCC. However, no survival difference was observed among patients in the pre-OP CRT+S and S+post-OP CRT groups, which suggests that the sequence of surgery and chemoradiation may be irrelevant to the outcome.     

The rates and CT patterns of locoregional recurrence after resection surgery of lung cancer: correlation with histopathology and tumor staging

The purpose of our study was to assess the rates and CT patterns of locoregional recurrence after resection surgery of lung cancers according to histopathology and tumor staging. Three hundred and seventy nine patients who underwent lung resection surgery due to lung cancer in a recent 6 year period were followed up with CT (at 3, 6, 12, 18, 24 months, and then annually after surgery) for evaluation of locoregional tumor recurrence (analysis of hilar or mediastinal lymph nodes and surgical margin including bronchial stump, pleura, and chest wall). The recurrence rates and CT patterns were compared in terms of underlying histopathology and tumor staging. Of 379 patients, 75 (20%) patients had locoregional recurrences. The recurrence rates were higher in squamous cell carcinoma (39/190, 21%) than adenocarcinoma (24/140, 17%) (P = 0.012). The patterns of recurrence in 75 patients were hilar-mediastinal lymph node enlargement (n = 39, 52%), ipsilateral pleural lesion (n = 24, 32%), chest wall lesion (n = 13, 17%), bronchial stump lesion (n = 8, 11%), and bronchial extension including the trachea (n = 3, 4%). Bronchial stump recurrence was seen only in squamous cell carcinoma. Bronchioloalveolar carcinoma did not show any evidence of locoregional recurrence. Pleural (P = 0.0016) and mediastinal nodal (P = 0.001) recurrence, respectively, were more common in N2 than N0 cancers. Chest wall recurrence rates were higher with higher T staging (P < 0.001). The locoregional recurrence of lung cancer occurs in about one fifth of patients who undergo curative resection and is more common in squamous cell carcinoma than in adenocarcinoma. Recurrent patterns are diverse and different according to histopathologic type and pathologic staging of lung cancer.     

Definitive concomitant chemoradiotherapy with docetaxel and cisplatin in squamous esopheageal carcinoma

Chemoradiotherapy is a standard treatment for esophageal carcinoma. This study evaluated the docetaxel‐based definitive concomitant chemoradiotherapy in patients with esophageal squamous cell carcinoma to determine its clinical response and overall survival. In this unicenter trail, we enrolled 59 patients with histologically proven squamous cell carcinoma in the esophagus between March 2004 and December 2007. All patients were staged II to IV and treated with definitive concomitant chemoradiotherapy. Radiotherapy was delivered with conventional fraction, 50–64 Gy in 25–35 fractions. Patients received two cycles of a 1‐day regimen containing docetaxel (60 mg/m²) and cisplatin (80 mg/m²) every 3 weeks during the period of radiotherapy. The chemoradiotherapy was applied as planned in all patients and the median chemotherapy delay time was 6 days (ranging from 2 to 8 days). The overall response rate for 59 evaluable patients was 98.3%, with 42 complete responses and 26 partial responses. During the follow‐up time (median 18 months, 4～53 months), the median overall survival time was 22.6 months. The rate of locoregional progression‐free survival, progression‐free survival, and overall survival in 3 years was 59.6%, 29.2%, and 36.7%, respectively. Hematologic toxicity Grade 3 and Grade 4 were observed in 39.0% and 20.3% of patients respectively, with severe non‐hemotologic acute toxicity being infrequent. Eleven patients had pleural effusion after chemoradiotherapy and four of them required therapeutic thoracentesis. Definitive concomitant chemoradiotherapy with docetaxel and cisplatin in squamous cell esophageal carcinoma was associated with a satisfactory outcome and manageable toxicity.