Definitive Chemoradiotherapy In Patients Research Articles

Long-term outcomes of combined endoscopic resection and chemoradiotherapy for esophageal squamous cell carcinoma with submucosal invasion

BackgroundFor esophageal squamous cell carcinoma (ESCC) with submucosal (SM) invasion, surgery is the standard treatment. Definitive chemoradiotherapy (D-CRT) is a less invasive alternative option, but sometimes results in locoregional failure. AimTo examine whether endoscopic resection for primary lesion removal combined with chemoradiotherapy (ER-CRT) reduces locoregional failure rates in cases of ESCC with SM invasion. MethodsWe retrospectively compared clinical outcomes between ER-CRT and D-CRT in patients diagnosed with ESCC with SM invasion between 2003 and 2014. Twenty-one patients underwent ER-CRT based on a pathological diagnosis, and 43 patients underwent D-CRT based on a clinical diagnosis. ResultsLocoregional failure developed in 26% of patients in the D-CRT group, and in no patients in the ER-CRT group (p < 0.01). Thus, the 5-year relapse-free survival in the ER-CRT group was significantly more favorable than that in the D-CRT group (85.1% vs 59.2%; p < 0.05), although there was no difference in overall survival (85.1% vs 79.1%) nor in cause-specific survival (90.5% vs 87.2%) between the groups. There were no instances of perforation or hemorrhage associated with ER. ConclusionER-CRT is a safe and effective treatment strategy and can be considered as a new minimally invasive treatment option for patients with ESCC with SM invasion.

Prognostic significance of residual lymph node status after definitive chemoradiotherapy in patients with node-positive cervical cancer

ObjectiveLymph node involvement is an important prognostic factor in patients with cervical cancer. However, the prognostic significance of lymph node response to chemoradiotherapy remains unclear. We retrospectively analyzed the relationship between residual lymph node status after definitive chemoradiotherapy and survival. MethodsWe enrolled 117 patients with node-positive cervical cancer. All patients were treated with definitive chemoradiotherapy in our institution, from 2006 to 2016. The median follow-up period was 41months (range, 6–128months). The criterion for a positive lymph node was defined as a maximum short axis diameter of ≥8mm on pretreatment magnetic resonance imaging (MRI)/computed tomography (CT) scans. Posttreatment pelvic MRI was obtained 3months after the completion of chemoradiotherapy. Residual primary tumor was defined as any residual lesion identified upon clinical examination and/or MRI. Residual lymph node was defined as any lymph node with a short axis diameter of ≥8mm posttreatment, according to MRI/CT. ResultsAt follow-up, 3months after chemoradiotherapy, we observed residual primary tumor in 30 patients (25.6%), and residual lymph node in 31 patients (26.5%). The presence of residual lymph node was associated with worse overall survival according to multivariate analysis (hazard ratio, 3.04; 95% confidence interval, 1.43–6.44; p=0.004). In the 5-year time-dependent ROC analysis of survival prediction, the presence of residual lymph node showed an AUC value of 0.72. ConclusionsThe presence of residual lymph node after chemoradiotherapy was associated with worse survival in patients with node-positive cervical cancer.

Effect of consolidation chemotherapy following definitive chemoradiotherapy in patients with esophageal squamous cell cancer

Definitive chemoradiotherapy (dCRT) is a treatment option for patients with localized esophageal squamous cell carcinoma (ESCC). We investigated consolidation chemotherapy (CCT) in patients with ESCC who attained clinical complete response after dCRT. Between January 2009 and December 2012, medical records of ESCC patients treated with dCRT were retrospectively reviewed, and those who attained CCR were identified. Progression-free survival and overall survival rates were estimated by the Kaplan-Meier method. The Cox regression model was used to determine prognostic factors. Of the 522 patients treated with dCRT, 209 patients achieved CCR, with 67 receiving consolidation chemotherapy (the CCT group) and 142 receiving dCRT alone (the control group). CCT did not prolong progression-free survival (33.0 vs 18.0 months, P = 0.07, HR = 0.70, 95% CI, 0.48–1.04); however, CCT improved the median overall survival (53.4 vs 27.0 months, P = 0.04, HR = 0.67, 95% CI, 0.44–0.99) compared with dCRT alone. CCT remained a favorable prognostic factor for overall survival in a multivariate analysis (HR = 0.59, P = 0.02); however, a propensity score analysis failed to show an additional overall survival benefit with CCT. In the present analysis, CCT did not improve progression-free survival but may have extended overall survival in ESCC patients who achieved complete clinical response after dCRT.

Prognostic value of supraclavicular nodes and upper abdominal nodes metastasis after definitive chemoradiotherapy for patients with thoracic esophageal squamous cell carcinoma.

The purpose of this study is to assess the prognostic value of supraclavicular nodes, left gastric nodes, celiac nodes and common hepatic nodes metastasis in esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. A total of 293 ESCC patients treated with radiotherapy or chemoradiotherapy entered the study. The results showed that the presence of supraclavicular nodes (χ2 = 0.075, P = 0.785) and left gastric nodes (χ2 = 3.603, P = 0.058) metastasis had no significant influence on survival, while celiac nodes (χ2 = 33.775, P < 0.001) and common hepatic nodes (χ2 = 42.350, P < 0.001) metastasis were associated with significantly shorter survival, regardless of the sites of primary tumor. Multivariate analysis showed that celiac nodes (HR: 0.457, 95% CI: 0.256-0.816; P = 0.008) and common hepatic nodes (HR: 0.241, 95% CI: 0.092-0.630; P = 0.004) metastasis were independently adverse indicator of survival in upper ESCC. While in the middle and lower ESCC, only the common hepatic nodes (middle ESCC: HR: 0.345, 95% CI: 0.161-0.738, P = 0.006; lower ESCC: HR: 0.377, 95% CI: 0.160-0.890, P = 0.026) metastasis was an independently adverse indicator of survival. In conclusion, our study demonstrated that in ESCC treated with definitive radiotherapy, both of celiac nodes and common hepatic nodes metastasis were adverse indicator of survival in upper ESCC, and common hepatic nodes metastasis were adverse indicator of survival in middle and lower ESCC. Supraclavicular nodes an left gastric nodes metastasis is not associated with patients survival in ESCC.

Long-term Outcomes and Late Effects of Definitive Chemoradiotherapy in Patients with Cervical Cancer in Nova Scotia.

Purpose: To determine the long-term oncologic outcomes and toxicity of patients treated with definitive chemo-radiotherapy for cervical cancer. Methods and Materials: The study period was January 1, 2000 to December 31, 2009. All patients diagnosed with cervical cancer who received curative-intent chemoradiotherapy were included. Patients were excluded if they resided out of the province, received surgery as an initial treatment, or were treated with palliative intent. A retrospective chart review was performed.Results: Four hundred and eighty-six patients were diagnosed with cervical cancer; 190 met eligibility criteria. Median follow-up for all patients was 3.2 years (interquartile range 1.1—5.6 years). Clinical stage was FIGO IIB or higher in 139 of 190 patients (73.2%). One hundred and fifty-eight (82.7%) received concurrent cisplatin chemotherapy (mean # cycles = 4.8). The most common external beam radiotherapy (EBRT) dose/fractionation schedule was 45 Gray (Gy) in 25 fractions (149 pts, 78.0%). One hundred and thirty-six (71.2%) received low-dose-rate (LDR) brachytherapy (BT: most common dose = 35 Gy). High-dose-rate (HDR) BT was implemented in 2008; the most common HDR dose was 24 Gy in 8 fractions over five days. Five-year overall survival (OS) and progression-free survival (PFS) were 69.4% and 61.4%, respectively. OS and PFS were significantly higher in patients who received chemotherapy vs. radiotherapy alone. For those receiving HDR-BT, there was a significantly higher OS, but not PFS. The rate of late RTOG Grade 3/4 toxicity at five years was 23.3% (gastrointestinal - 26 events, 13% of patients; genitourinary - 13 events, 8% of patients). Fourteen patients had Grade 3 radiation proctitis as the only late toxicity. EBRT dose above 45 Gy was the only factor associated with late toxicity on multivariate analysis.Conclusion: Outcomes of patients treated with chemoradiotherapy for cervical cancer are in keeping with those reported in other series. Chemotherapy improved OS and PFS. External beam radiotherapy dose above 45 Gy was the only predictor of late toxicity.

Salvage Esophagectomy After Definitive Chemoradiotherapy for Patients with Esophageal Squamous Cell Carcinoma: Who Really Benefits from this High-Risk Surgery?

The aim of this study was to identify good candidates for salvage esophagectomy after definitive chemoradiotherapy (dCRT), based on safety and survival. Sixty-three patients who underwent salvage esophagectomy, after dCRT, at the Cancer Institute Hospital, Tokyo, Japan, between 1988 and 2013, were retrospectively analyzed. Short-term outcomes were evaluated by reviewing postoperative complications, length of postoperative hospital stay, and mortality. Survival rates were calculated using the Kaplan-Meier method, and statistical significance was determined using the log-rank test. The Cox proportional hazards model was used for univariate and multivariate analyses of overall survival. Univariate logistic regression analysis was used to identify factors related to R0 resection. Postoperative complications occurred in 41 patients (65.1 %), and the mortality rate was 7.9 %. In-hospital deaths did not occur among patients with less advanced tumors prior to dCRT (cT1-2 and cN0), or among those who had previously achieved a complete response (CR); the 3- and 5-year overall survival rates were 29.8 % and 15.0 %, respectively. Univariate analysis revealed that residual disease, tumor depth, dCRT response, lymph node metastasis, and time to relapse were significant factors affecting overall survival. Multivariate analysis demonstrated that R0 resection and ypT0-2 tumors were significant, favorable prognostic factors in patients undergoing salvage esophagectomy. In addition, cT1-2 tumors, initially resectable tumors, ycT1-2 tumors, and relapse after CR were factors predicting R0 resection. Based on both short- and long-term outcomes, patients with pretreatment or preoperative T1-2 tumors and those with relapse after CR are good candidates for salvage esophagectomy.

N2切除可能非小細胞肺癌に対する化学放射線療法の可能性（WJOG5008Lより）

N2切除可能非小細胞肺癌に対する化学放射線療法の可能性（WJOG5008Lより）

Epidermal Growth Factor Receptor Mutation Is Associated With Longer Local Control After Definitive Chemoradiotherapy in Patients With Stage III Nonsquamous Non–Small-Cell Lung Cancer

To determine the frequency and clinical significance of epidermal growth factor receptor (EGFR) mutations in patients with potentially curable stage III non-small-cell lung cancer (NSCLC) who are eligible for definitive chemoradiotherapy (CRT). Between January 2001 and December 2010, we analyzed the EGFR mutational status in consecutive NSCLC patients who were treated by CRT. The response rate, relapse-free survival, 2-year relapse-free rate, initial relapse sites, and overall survival of the patients were investigated. A total of 528 patients received CRT at our hospital during the study period. Of these, 274 were diagnosed as having nonsquamous NSCLC. Sufficient specimens for mutational analyses could be obtained from 198 of these patients. The proportion of patients with EGFR activating mutations was 17%. In addition to the well-known characteristics of patients carrying EGFR mutations (female, adenocarcinoma, and never/light smoker), the proportion of cases with smaller primary lesions (T1/2) was found to be higher in patients with EGFR mutations than in those with wild-type EGFR. Patients with EGFR mutations showed similar response rate, relapse-free survival, and 2-year relapse-free rates as compared to patients with wild-type EGFR. Local relapses as the site of initial relapse occurred significantly less frequently in patients with EGFR mutation (4% vs 21%; P=.045). Patients with EGFR mutations showed longer local control (adjusted hazard ratio 0.49; P=.043). After disease progression, a majority of the patients with EGFR mutations received EGFR tyrosine kinase inhibitors (62%), and these patients showed longer postprogression survival than those with wild-type EGFR. Our study is the first to show radiosensitive biology of EGFR-mutated tumors in definitive CRT with curative intent. This finding could serve as a credible baseline estimate of EGFR-mutated population in stage III nonsquamous NSCLC.

FDG volumetric parameters and survival outcomes after definitive chemoradiotherapy in patients with recurrent head and neck squamous cell carcinoma.

The purpose of this study was to establish the predictive value of (18)F-FDG parameters for overall survival in biopsy-proven recurrent head and neck squamous cell cancer (HNSCC) patients after definitive chemoradiotherapy. We conducted a retrospective study including 34 patients with HNSCC who had biopsy-proven recurrence between April 2004 and March 2012 and underwent FDG PET/CT at our institution at the time of recurrence. Maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. The primary outcome measure was overall survival. ROC analysis, univariate and multivariate Cox regression models, and Kaplan-Meir survival curves were performed. In univariate analyses, human papillomavirus (HPV) status (p = 0.04), primary site recurrence of MTV (p = 0.03), metastasis of MTV (p = 0.02), metastasis of TLG (p = 0.02), total MTV (p = 0.002), and total TLG (p = 0.04) were significantly associated with overall survival outcome. Total MTV remained as significant independent prognostic factor when adjusted for all other covariates except for primary site recurrence SUVmax and SUVpeak and lymph node SUVmax and SUVpeak. There was a significant difference in time to survival between patients with total MTV above and below the 50th percentile (Mantel-Cox log-rank test, p = 0.05 and Gehan-Breslow-Wilcoxon test, p = 0.03) and the optimum threshold of 16.8 mL (Mantel-Cox log-rank test, p = 0.01 and Gehan-Breslow-Wilcoxon test, p = 0.01; hazard ratio [HR], 0.25). FDG PET/CT-based total MTV and clinical HPV status may be significant prognostic markers for overall survival of patients with recurrent HNSCC after definitive chemoradiotherapy.

Treatment outcomes after intraluminal brachytherapy following definitive chemoradiotherapy in patients with esophageal cancer.

To report the results of treatment with intraluminal brachytherapy (ILRT) after concurrent chemoradiotherapy for esophageal carcinoma with respect to disease free survival (DFS), dysphagia free interval (DFI), and complications of treatment. The study retrospectively analyzed the records of 26 eligible patients with nonmetastatic carcinoma of the esophagus treated with definitive chemoradiotherapy followed by ILRT between 2008 and 2011. The DFS and DFI were estimated and factors likely to influence them were analyzed. Nineteen (73%) patients were males. The mean age at presentation was 60 years (range: 47-90 years). All the patients had squamous cell carcinomas. Following treatment, the median DFS was 12.7 months (range: 0-27 months). Sixteen patients (61.5%) had local control of their disease, while one had residual disease at completion of treatment. Other than three patients who were not evaluated for recurrent dysphagia, six (23.1%) had proven local recurrence on follow-up. The estimated mean DFI was 13.8 months (range: 0-27 months). One patient died of tracheoesophageal fistula following treatment. On statistical analysis, only the location of tumor was prognostically significant, with lower third tumors performing worse. Other probable predictors of poor outcome included large volume (> 40 cc), tumor length (> 6 cm), and eccentric location. ILRT boost following concurrent chemoradiotherapy is well tolerated and potentially improves outcomes. It might be beneficial in selected patients with esophageal carcinoma. Further studies are required to identify its role in definitive treatment.

Short- and long-term outcomes of definitive chemoradiotherapy in patients with esophageal carcinoma aged ≥75 years

The most relevant treatment modalities in elderly patients with esophageal carcinoma (EC) remain a subject of debate. Combined definitive chemoradiotherapy (CRT) is currently widely accepted as a non-surgical treatment for esophageal cancer. However, elderly patients were excluded from the majority of studies on CRT, or the proportion of elderly patients was relatively low in those studies and the number of available studies on the treatment of EC patients aged ≥75 years is limited. The aim of the present retrospective study was to analyze the safety and efficacy of CRT in patients aged ≥75 years in order to assess the short- and long-term outcomes of CRT for elderly patients with EC. In this study, based on further refinement of patient age groups and analysis of the Charlson comorbidity score, we performed a statistical analysis of factors such as short-term response, long-term survival and toxicity reactions. The results of the analysis indicated that the treatment of patients with EC aged ≥75 years with radiotherapy (RT) and chemotherapy was effective. However, we recommend that customized treatment is based on the stratification of patients into different age groups and the Charlson score, as for patients aged ≥80 years a lower-dose therapy may be more beneficial and for patients aged ≥85 years definitive CRT should be administered with greater caution.

Impact of the presence of EGFR mutation on definitive chemoradiotherapy in patients with locally advanced non-small cell lung cancer: Pattern of relapses and survival analyses in 145 patients.

7540 Background: EGFR mutational status is an important biomarker in advanced NSCLC patients. However, little is known about the frequency and clinical significance of the presence of EGFR mutation in patients with potentially curable locally advanced NSCLC (LA-NSCLC) eligible for definitive chemoradiotherapy (CRT). Methods: Between Jan 2001 and Dec 2010, we conducted analysis for the presence of EGFR mutations, in consecutive NSCLC patients who were eligible for CRT. The response rate (RR), progression-free survival (PFS), 2-year relapse-free rate, first relapse sites, and overall survival were investigated according to the EGFR mutational status. Results: A total of 528 patients received CRT at the National Cancer Center Hospital during the study period. Of these, 274 were diagnosed as having non-squamous NSCLC, and sufficient specimens for mutational analyses could be obtained from 145 patients. EGFR mutants (EGFR-mt) were found at a frequency of 18% in these patients. In addition to the well-known characteristics of NSCLC patients carrying EGFR mutations (female, adenocarcinoma, and never/ light smoker), the proportion of cases with smaller (T1/2) primary lesions was higher in patients with EGFR-mt than in those carrying wild-type EGFR (EGFR-wt). EGFR-mt showed a slightly better RR (85.7% vs. 72.9%), but similar median PFS (12.2 m vs. 10.6 m) and 2-year relapse free rates (23.8% vs. 29.2%) as compared to EGFR-wt. Local recurrence as first relapse occurred less frequently in EGFR-mt than in EGFR-wt (6% vs. 20%). After disease progression, a majority of EGFR-mt received EGFR-TKIs (62%), and these patients showed longer post-progression survival and a higher 5 year survival rate (60% vs. 40%) than EGFR-wt. Conclusions: Among the LA-NSCLC patients eligible for definitive CRT analyzed, 18% had EGFR- activating mutations. Although definitive CRT was similarly effective in both EGFR-mt and EGFR-wt, slightly better local control rate was noted in EGFR-mt. Treatment with EGFR-TKIs contributed to longer post-progression survival and overall survival in LA-NSCLC patients harboring EGFR mutations.

Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial

Definitive chemoradiotherapy (CRT) is an alternative to surgery for the curative treatment of oesophageal carcinoma. The SCOPE1 trial aimed to investigate the addition of cetuximab to cisplatin and fluoropyrimidine-based definitive CRT in patients with localised oesophageal squamous-cell cancer and adenocarcinomas to assess activity, safety, and feasibility of use. In this multicentre, randomised, open-label, phase 2/3 trial, we recruited patients aged 18 years and older from UK radiotherapy centres who had non-metastatic, histologically confirmed carcinoma of the oesophagus (adenocarcinoma, squamous-cell, or undifferentiated; WHO status 0-1; stage I-III disease) and been selected to receive definitive CRT. Patients were randomly assigned (1:1) via a central computerised system using stratified minimisation (with an 80:20 random element) to receive CRT alone or CRT with cetuximab (400 mg/m(2) on day 1 followed by 250 mg/m(2) weekly), stratified by recruiting hospital, primary reason for not having surgery, tumour histology, and tumour stage. CRT consisted of cisplatin 60 mg/m(2) (day 1) and capecitabine 625 mg/m(2) twice daily (days 1-21) for four cycles; cycles three and four were given concurrently with 50 Gy in 25 fractions of radiotherapy. The primary endpoint was the proportion of patients who were treatment failure free at week 24 for the phase 2 trial and overall survival for the phase 3 trial, both measured from randomisation. We analysed data by intention to treat. This trial is an International Standard Randomised Controlled Trial, number 47718479. 258 patients (129 assigned to each treatment group) from 36 UK centres were recruited between Feb 7, 2008, and Feb 22, 2012. Recruitment was stopped without continuation to phase 3 because the trial met criteria for futility, but we continued to follow-up recruited patients until all had reached at least 24-week follow-up (median follow-up of patients who survived was 16.8 months [IQR 11.2-24.5]). Fewer patients were treatment failure free at 24 weeks in the CRT plus cetuximab group (79 of 119 patients [66·4%, 90% CI 58·6-73·6]) than in the CRT only group (93 of 121 patients [76.9%, 69.7-83.0]). The CRT plus cetuximab group also had shorter median overall survival (22.1 months [95% CI 15.1-24.5] vs 25.4 months [20.5-37.9]; adjusted HR 1.53 [95% CI 1.03-2.27]; p=0.035). Patients who received CRT plus cetuximab had more non-haematological grade 3 or 4 toxicities (102 [79%] of 129 patients vs 81 [63%] of 129 patients; p=0.004). The most common grade 3 or 4 toxicities were low white blood cell count (14 [11%] in the CRT plus cetuximab group vs 21 [16%] in the CRT only group), low absolute neutrophil count (15 [12%] vs 24 [19%]), fatigue (26 [20%] vs 25 [19%]), and dysphagia (35 [27%] vs 37 [29%]). The addition of cetuximab to standard chemotherapy and radiotherapy cannot be recommended for patients with oesophageal cancer suitable for definitive CRT. Cancer Research UK.

18F-fluorodeoxyglucose positron emission tomography after definitive chemoradiotherapy in patients with oesophageal carcinoma

BackgroundThe purpose of the study was to investigate the value of 18F-fluorodeoxyglucose-positron emission tomography performed after definitive chemoradiotherapy in patients with locally advanced oesophageal carcinoma. MethodsForty consecutive patients underwent 18F-fluorodeoxyglucose-positron emission tomography at baseline and after chemoradiotherapy completion. Assessment of the clinical complete response to chemoradiotherapy included oesophagoscopy plus biopsies and computed tomography scan. Cox regression analysis was used to develop the univariate and multivariate models describing the association of the independent variables with survival and local control. ResultsA clinical complete response and 18F-fluorodeoxyglucose-positron emission tomography response were present in 29 patients (72.5%) and 13 patients (32.5%), respectively. A combined response was observed in 11 patients (27.5%). During follow-up, a local failure was detected in 27.2% of patients with 18F-fluorodeoxyglucose-positron emission tomography response versus 33.3% in non-responders (p=.9). In multivariate analysis, clinical complete response (HR 5.77, p=.009) and 18F-fluorodeoxyglucose-positron emission tomography response (HR 6.27, p=.031) were identified as independent prognostic factors of overall survival. ConclusionIn patients treated for an esophageal cancer, the present study suggested that 18F-fluorodeoxyglucose-positron emission tomography after chemoradiotherapy completion was an independent prognostic factor of overall survival without significant impact on local recurrence prediction.

Sa1212 Interaction Between Esophageal Cancer (EC) Total Length of Disease and Treatment With Either Surgery or Definitive Chemoradiotherapy for Patients With EC

Introduction EC primary tumour length has long been considered important when planning surgical treatment. More recently, the total length of oesophageal disease (including the most distal and most proximal tumour extent or lymph node metastasis) as measured at endoscopic ultrasound (ELoD) has emerged as a strong prognostic indicator. This study aimed to investigate the prognostic importance of the ELoD treatment interaction (ELoD*RxI) with surgery or definitive chemoradiotherapy (dCRT). Methods Six hundred and forty-five (430 male, 215 female) consecutive patients (median age 65 (31-85) yr, 430 male) with esophageal cancer were studied. Three hundred and twenty-three patients underwent surgical resection (155 neoadjuvant chemo, 53 neoadjuvant CRT) and 322 received dCRT. Cox regressionmultivariate analysis was employed in order to identify the independent, significant prognostic indicators. The final model from the multivariate analysis included the variables ELoD and Treatment, thereby allowing the calculation of the relative hazard of death for those receiving surgery and those receiving dCRT according to the ELoD. The hazard ratio of death following surgery versus dCRT was subsequently plotted in relation to increasing ELoD in order to identify a hypothetical ELoD crossover point at which the hazard of death following surgery would become greater than the hazard of death following dCRT. Results Median, 2 year and 5 year survival was 28 months, 57.1% & 34.5% following surgery compared with 22 months, 47.5% & 24.4% following dCRT (Chi2 11.202, df 1, p=0.001). On multivariate analysis the ELoD (HR 1.624, 95%CI 1.146-2.301, p=0.006), Treatment (HR 1.617, 95%CI 1.098-2.380, p=0.015) and the ELoD*Treatment interaction (HR 0.667, 95%CI 0.433-1.027, p=0.066) were included in the final model. The hazard ratios for surgery versus dCRT were calculated according to the ELoD and are shown below (Fig.1) Conclusions EC patients with shorter EloDs are better treated with surgery. Patients with EloDs approaching 12cm may still benefit from surgery or dCRT. However, patients with EloDs over 12cm are arguably better treated with dCRT.

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

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

Palifermin in Prevention of Head and Neck Cancer Radiation-Induced Mucositis: Not Yet a Definitive Word on Safety and Efficacy Profile

TO THE EDITOR: We read with great interest the two reports on palifermin in the prevention of mucositis induced by postoperative or definitive chemoradiotherapy in patients with head and neck cancer. They address the unmet need of prevention of this debilitating adverse effect. However, in our opinion, there are some limitations of the studies that should be stressed. The authors correctly underlined that safety data regarding palifermin on patient outcome should be interpreted with caution, because the sample sizes were chosen only to address the primary end points. We would emphasize this lack of safety data by adding two more considerations. First, erythropoiesis stimulating agents were allowed to deal with severe anemia, although their role can be detrimental to outcome in patients with head and neck cancer. A possible imbalance in the use of erythropoiesis stimulating agents between the two arms could have had an impact on outcome. Second, half of the patients included in both trials had oropharyngeal tumors without stratifying for human papillomavirus positivity. This could have severely biased outcome analysis because of the favorable prognosis of human papillomavirus– positive patients. Interestingly, the benefit of palifermin in physician-assessed mucositis in both trials was not paralleled by a better patient-reported outcome (PRO), assessed through the mouth and throat soreness score. Generally, adverse events reported by physicians are less accurate than those reported by PRO instruments. Indeed, for mucositis, some clinicians have proposed replacing physician scales with patientassessed mucositis reporting. Although mouth and throat soreness scores have been shown to be comparable to clinician assessment of mucositis, the same PRO in a randomized trial with palifermin in hematopoietic stem-cell transplantation anticipated the onset, peak, and resolution of mucositis assessed by clinicians. These data would imply that for the present studies, the most sensitive instrument was not able to detect any difference. Thus, we fully share the same conclusions of the authors. The role of palifermin in mucositis prevention, along with its safety profile, must be further elucidated in future trials.

THRB Genetic Polymorphisms Can Predict Severe Myelotoxicity after Definitive Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma

Objective: Chemotherapy-related toxicities are difficult to predict before treatment. In this study, we investigated whether thyroid hormone receptor beta (THRB) genetic polymorphisms can serve as a potential biomarker in patients with esophageal squamous cell carcinoma (ESCC).Methods: Forty-nine Japanese patients with ESCC who received a definitive chemoradiotherapy (CRT) with 5-fluorouracil and cisplatin in conjunction with concurrent irradiation were retrospectively analyzed. Severe acute toxicities, including leukopenia, stomatitis, and cheilitis, were evaluated according to 6 single nucleotide polymorphisms (SNPs) in the gene; the intronic SNPs of rs7635707 G/T, rs6787255 A/C, rs9812034 G/T, and rs9310738 C/T and the SNPs in the 3′-untranslated region (3′-UTR) of rs844107 C/T and rs1349265 G/A.Results: Distribution of the 4 intronic SNPs, but not the 2 SNPs in the 3′-UTR, showed a significant difference between patients with and without severe acute leukopenia. Stomatitis and cheilitis were not associated with any of the 6 analyzed SNPs. Frequency of haplotype of the 4 intronic SNPs reached approximately 97% with the 2 major haplotypes G-A-G-C (73.4%) and T-C-T-T (23.5%).Conclusions: THRB intronic SNPs can provide useful information on CRT-related severe myelotoxicity in patients with ESCC. Future studies will be needed to confirm these findings.

Definitive chemoradiotherapy in patients with esophageal adenocarcinoma: An alternative to surgery?

Definitive chemoradiotherapy (CRT) is considered curative intent treatment for locally advanced esophageal squamous cell carcinoma. Data concerning the usefulness of definitive CRT in patients with esophageal adenocarcinoma (ADC) are lacking. The aim of the study was to compare the results of definitive CRT versus surgery in patients with an ADC. All consecutive patients with a non-metastatic ADC treated between 1994 and 2008 were retrospectively assessed. Patients were divided into two groups: surgery group (±pre-operative treatment) versus definitive CRT group. In surgery and definitive CRT groups, 67 and 79 patients were evaluated, respectively. A complete resection was achieved in 92.5% of patients in surgery group and a clinical complete response was observed in 49.4% of patients in definitive CRT group. Overall survival was 36.2 ± 2.0 months in surgery group versus 16.5 ± 0.8 months in definitive CRT group (P = 0.02). The predictive factors of survival were age (P < 0.01), stage (P = 0.04), WHO performance status (P < 0.01), initial weight loss (P < 0.01), and the treatment group (P < 0.01). The results of the study do not support definitive CRT as an alternative to surgery in esophageal ADC treatment. Definitive CRT should be reserved for patients with a major operative risk.

Retrospective Review of Surgery and Definitive Chemoradiotherapy in Patients with Squamous Cell Carcinoma of the Thoracic Esophagus Aged 75 Years or Older

The aim of this study was to review the treatment outcomes of surgery and definitive chemoradiotherapy (CRT) in elderly patients with squamous cell carcinoma of the thoracic esophagus. A total of 64 patients aged 75 or older were retrospectively reviewed; 40 were treated with surgery and 24 with CRT. The CRT group included eight patients with unresectable disease and four patients medically unfit for surgery. Surgery included esophagectomy with lymphadenectomy and CRT consisted of 60-70 Gy of radiation concurrent with 5-fluorouracil alone or combined with cisplatin. Short- and long-term outcomes and survival of each modality were assessed. In the surgery group, 33 patients (82.5%) had co-morbid conditions. Complete resection rate was 90.0%. An overall post-operative complication rate was 65.0% and in-hospital mortality was seen in three patients (7.5%). In the CRT group, complete response rate was 41.7%. Leukopenia was most common Grade 3 hematological toxicity. Treatment-related deaths caused by acute toxicities occurred in three patients (12.5%), whereas those caused by late toxicities in four (16.7%). For cStage I disease in the surgery group, the overall 1-, 3- and 5-year survival rate were 90.9%, 63.6% and 54.5%, respectively, with a median survival time of 78.7 months. For cStages II-IV, the median survival time of the surgery and the CRT group was 18.7 and 12.8 months, respectively. The short- and long-term outcomes of surgery for the elderly seemed acceptable; however, definitive CRT may be a promising treatment modality. Further investigation may alter the sphere of influence in the field of esophageal cancer treatment in the elderly.