Unexpected Microscopically Positive Proximal Resection Margins in Esophageal Squamous Cell Carcinoma After Chemoradiotherapy: Predictors and Prognostic Significance.

BACKGROUND: Esophageal cancer has the propensity to spread in a longitudinal manner (either proximally or distally), potentially resulting in the unexpected presence of microscopic disease at grossly tumor-free margins. The clinical significance of this phenomenon in patients treated with chemoradiotherapy (CRT) remains unclear. The purpose of this study was to investigate the prevalence, predictors, and prognostic impact of microscopically positive proximal resection margins (PPRMs) in patients with esophageal squamous cell carcinoma (ESCC) who received CRT. METHODS: Between 2000 and 2014, we identified 332 ESCC patients who underwent complete gross resection (R0/R1) following CRT. Patients were divided into two groups according to the status of the proximal resection margins on microscopic examination [negative proximal resection margins (NPRMs) vs PPRMs]. The occurrence of anastomotic leakage (AL) and anastomotic recurrence (AR) served as outcome measures. RESULTS: Sixteen (4.8 %) patients had PPRM. The presence of PPRM was not associated with AL but was a strong predictor of AR (PPRM vs NPRM, 23.1 vs 7 %, respectively, P = 0.033). Multivariate analysis identified a resection margin length <3.5 cm [odds ratio (OR) 4.473, P = 0.022] and salvage resection (OR 3.171, P = 0.045) as independent predictors of PPRM. The estimated PPRM rates were 16.7, 6.3, and 1.3 % for patients with 2, 1, and 0 predictors, respectively. CONCLUSIONS: PPRM occurred in 4.8 % of ESCC patients following CRT and was associated with AR. An intraoperative frozen section margin analysis should be performed in patients carrying risk factors to avoid unexpected PPRM.

Development of a nomogram for the prediction of pathological complete response after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma.

Nomograms incorporating multiple prognostic factors are useful for individualized estimation of survival in cancer patients. However, nomograms for the prediction of pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal cancer are scarce. Here, we describe the development of a nomogram for predicting pCR after nCRT in patients with esophageal squamous cell carcinoma (ESCC). We retrospectively reviewed the records of 392 ESCC patients who underwent nCRT followed by esophagectomy. Seventy percent of the participants (n = 274) were randomly assigned to a training cohort, whereas the remaining 30% were included in a validation cohort (n = 118). Data from the training cohort were subjected to multivariate logistic regression analyses for selecting variables to be included in the nomogram. The performance of the resulting nomogram was internally and externally validated by calculating the bias-corrected concordance statistic (c-statistic) and the area under the receiver operating characteristics curve (AUROC) in the training and validation cohorts, respectively. After surgery, 25.77% of the study patients achieved pCR. The following variables were included in the nomogram: (i) age, (ii) pretreatment tumor length, (iii) history of head and neck cancer, (iv) post-nCRT albumin levels, and (v) post-nCRT endoscopic findings coupled with endoscopic biopsy results. The bias-corrected c-statistic and AUROC of the internal and external validation sets were 0.77 and 0.747, respectively. Our nomogram showed a good performance for predicting pCR after nCRT in ESCC patients.

Survival outcomes of consolidation chemoradiotherapy in esophageal cancer patients who achieve clinical complete response but refuse surgery after neoadjuvant chemoradiotherapy.

Some esophageal cancer patients may be reluctant to accept the scheduled resection after neoadjuvant chemoradiotherapy (nCRT) because of its potential negative impact on quality of life as a result of high morbidity. This study was performed to investigate the survival outcomes of these patients. Between 2000 and 2012, we identified 190 patients with resectable esophageal squamous cell carcinoma (ESCC) who did not proceed to surgery following nCRT. Subjects who had a clinical complete response (cCR) and were medically fit for surgery were deemed eligible. Survival rates, recurrence patterns, and risk factors for recurrence served as the main outcome measures. The study cohort consisted of 73 patients (67 males and 6 females; mean age: 61.3 years). The 5-year overall survival was 39.6% (median survival time: 46.77 months). Cancer recurrences were observed in 44 patients (60.2%), with locoregional recurrence (LR) being the most common failure pattern (n = 35). Endoscopic findings after nCRT were the most important independent predictor of LR identified in multivariate analysis. Compared with the 'normal findings' subgroup, the odds ratios for LR in cCR patients who refused surgery were 4.774 (P = 0.026) and 2.844 (P = 0.16) in the 'scar' and 'other findings' subgroups, respectively. Patients with 'normal findings' had the lowest rate of LR (22.2%), with no recurrences occurring within the first 6 months. Sixty percent of ESCC patients who achieve cCR following nCRT but refuse esophagectomy develop disease recurrence, with LR being the most common pattern. Post-nCRT endoscopic findings may serve as a predictor for LR.

Identification of patients with hormone receptor-positive breast cancer who need adjuvant tamoxifen therapy for more than 5 years.

BACKGROUND/PURPOSE: Extended hormonal therapy with tamoxifen for > 5 years has improved disease-free survival (DFS) and overall survival (OS) in hormone receptor (HR)-positive breast cancer patients. The aim of this study was to identify the HR-positive breast cancer women who need adjuvant tamoxifen for > 5 years. METHODS: Between 1990 and 2004, 1104 HR-positive breast cancer patients who had received tamoxifen treatment at our institution and had been disease free for at least 6 years were included in this analysis. Univariate and multivariate analyses of prognostic factors for late recurrence were performed using the binary logistic regression model. RESULTS: During a median follow-up period of 10.9 years after surgery, 70 patients died and 99 showed recurrence. In multivariate analysis, age < 40 years (p < 0.001) and lymph node metastasis (p < 0.001) were associated with higher rates of recurrence. We stratified patients into high-risk (age < 40 years or positive lymph node status, 536 patients) and low-risk (age > 40 years and negative lymph node status, 566 patients) groups. The recurrence rates were 14.6% and 3.5% in the high-risk and low-risk groups, respectively. Patients in the high-risk group had poorer disease-free survival (p < 0.001) and overall survival (p = 0.010) than those in the low-risk group. CONCLUSION: Our findings suggest that HR-positive breast cancer women either aged < 40 years or with positive lymph node status were justified in continuing with tamoxifen therapy for > 5 years.

A Pathological Study of Residual Cancer in the Esophageal Wall Following Neoadjuvant Chemoradiotherapy: Focus on Esophageal Squamous Cell Carcinoma Patients with False Negative Preoperative Endoscopic Biopsies.

BACKGROUND: Endoscopic biopsy examinations after neoadjuvant chemoradiotherapy (nCRT) are of limited value in patients with esophageal cancer due to the high rates of false negative (FN) findings. We sought to investigate the anatomical locations of residual tumors in esophageal squamous cell carcinoma (ESCC) patients with FN endoscopic biopsies with the ultimate goal of improving their clinical management. METHODS: ESCC patients with residual cancers after nCRT which were not identified by preoperative endoscopic biopsy were deemed eligible. All of the surgical specimens were re-reviewed with a special focus on (1) distribution of residual cancer in each esophageal layer; (2) tumor regression grade (TRG); and (3) shortest distance between the lumen and the residual tumor. RESULTS: Among the 49 ESCC patients with FN biopsy results, a strong 'layer-dependent' tumor regression was observed. There was a preferential clearing of esophageal cancer cells located in the adventitia, followed by muscle and the submucosal (SM) and mucosal (M) layers (p < 0.001). Residual malignancies located in the muscle layer or the adventitia without simultaneous involvement of the M/SM layers were rare (n = 3; 6.1 %). TRG following nCRT did not affect the rate of M/SM involvement (p = 0.55) but was inversely associated with the distance between the lumen and residual cancer (mean distance in patients with TRG of 2, 3, and 4 was 1.1, 0.82, and 0.37 mm, respectively; p = 0.041). CONCLUSION: Most ESCC patients who show FN endoscopic biopsies following nCRT still have detectable lesions in the M/SM layers. Aggressive biopsy protocols may potentially improve detection rates.

Prognostic significance of lymphovascular invasion in patients with esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy.

OBJECTIVE: To investigate the prognostic significance of lymphovascular invasion (LVI) in patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (nCRT). METHODS: We retrospectively reviewed the charts of 416 consecutive patients with ESCC who underwent surgical resection following nCRT at the Chang Gung Memorial Hospital between 1998 and 2008. After exclusion of patients with non-R0 resection or showing no residual tumor (ypT0Nx), the histological tumor sections of 231 patients were reviewed for LVI. Univariate and multivariate analyses were used to identify the independent predictors of overall survival (OS). RESULTS: LVI was observed in 85 patients (36.8 %). The presence of LVI was related to close circumferential resection margins (CRMs), a greater depth of invasion, poor tumor differentiation, and an increased occurrence of lymph node metastases (LNM). The 5 year OS was significantly lower (10 %) in patients with LVI than in those without (31 %; p < 0.001). By multivariate Cox regression analyses, LVI (hazard ratio [HR] 1.5; p = 0.002) and LNM (HR 1.6; p = 0.007) were identified as independent adverse prognostic factors for OS. The 5 year OS rates according to the number of risk factors present were 35, 21, 20, and 5 for LVI(-)LNM(-), LVI(+)LNM(-), LVI(-)LNM(+), and LVI(+)LNM(+) patients, respectively (p < 0.001). CONCLUSIONS: The presence of LVI is independently associated with shorter OS in ESCC patients receiving nCRT. Links between LVI and LNM may provide new clues for the prognostic stratification of esophageal cancer.

Pegylated liposomal doxorubicin (Lipo-Dox®) combined with cyclophosphamide and 5-fluorouracil is effective and safe as salvage chemotherapy in taxane-treated metastatic breast cancer: an open-label, multi-center, non-comparative phase II study.

BACKGROUND: Anthracycline and taxane are classes of drugs that are frequently used in the adjuvant and palliative settings of metastatic breast cancer (MBC); however, treatment failure occurs in most cases. Limited data demonstrated favorable response in MBC after previous taxane-based treatment. The aim of this study was to evaluate the efficacy and safety of pegylated liposomal doxorubicin (Lipo-Dox®) used as part of a combination salvage therapy for patients with MBC whose tumors progressed during or after taxane-based treatment. METHODS: Patients with MBC who failed to respond to previous taxane-based treatments were recruited. Treatment with pegylated liposomal doxorubicin (40 mg/m(2)), cyclophosphamide (500 mg/m(2)), and 5-fluorouracil (500 mg/m(2)) was administered every 3 weeks. Tumor response to treatment was determined by using the Response Evaluation Criteria in Solid Tumor criteria version 1.0, and left ventricular ejection fraction was measured before and after treatment using echocardiography. Each patient was followed for 30 days after the last dose of study medication or until resolution/stabilization of any drug-related adverse event. RESULTS: Forty-five patients were recruited. As of December 2012, the median follow-up duration was 29.8 months, the overall response rate was 41.9 %, the median progression-free survival was 8.2 months, and the median overall survival was 36.6 months for all treated patients. Grade 3/4 neutropenia, leucopenia, and neutropenic fever were observed in 14 %, 9 %, and 1 % of the cycles, respectively. Other non-hematologic adverse effects were mild to moderate and were manageable. No decrease in left ventricular ejection function was noted. CONCLUSION: This regimen of combined of pegylated liposomal doxorubicin, cyclophosphamide, and 5-fluorouracil exhibited a promising overall response rate, progression-free survival rate, and overall survival rate, with a safe cardiac toxicity profile and manageable adverse effects. This regimen could be considered as a treatment option for patients with MBC whose tumors progressed during or after taxane-based treatment.

Adherence to prescribed exercise time and intensity declines as the exercise program proceeds: findings from women under treatment for breast cancer.

PURPOSE: Adherence to prescribed exercise is a challenge for cancer patients undergoing treatment. The changing pattern of exercise adherence over time cannot be fully understood by an overall measure of adherence. This study was aimed to identify the trajectory of exercise adherence and its predictors for women with breast cancer during their chemotherapy. METHODS: Participants were 78 women with breast cancer assigned to the exercise arm of a randomized control trial. Based on the weekly adherence rates in time and intensity, patients were classified as good (>100%), acceptable (80-100%), and poor (<80%) adherents. Data were analyzed using ordinal logistic hierarchical linear modeling. RESULTS: The trajectories for both time and intensity adherence declined significantly. The decline in exercise-time adherence was significantly slower in women who reported higher interest in exercise. Women with higher perceived importance of exercise, early disease stage, and employed were more likely to be classified as good intensity adherents. Poorer weekly adherence for both exercise time and intensity was associated with higher fatigue level for that week. CONCLUSIONS: Adherence to exercise adherence in breast cancer patients declined as the dose of exercise prescription increased. Factors influencing overall adherence and adherence trend were identified.

Bronchoscopic finding determined outcome after chemoradiotherapy in esophageal cancer patients with airway invasion.

BACKGROUND: We studied whether the bronchoscopic findings could be help to predict outcome after chemoradiotherapy (CRT) in patients with airway invasion by esophageal cancer. METHOD: Between 2000 and 2010, we retrospectively investigated esophageal cancer patients with T4 disease due to airway invasion who had received CRT as first line treatment. Airway invasion is defined as infiltration of the tracheobronchial wall or protruded intraluminal growth on bronchoscopy. The total radiation dose of CRT was 60 Gy and divided into two cycles. Bronchoscopic findings were evaluated together with other clinical parameters and correlated with overall survival (OS). RESULT: There were 68 patients with a mean age of 54.5 years. After the first cycle of CRT, bronchoscopic examination showed complete regression of endobronchial lesion in 16 patients. OS was 26% at 1 year and 5% at 3 years with the median survival time (MST) of 7 months. Multivariate analysis revealed vocal cord palsy (unfavorable, OR [95% CI]:2 [1.07-3.84], P = 0.03), carina involvement (unfavorable, OR [95% CI]:2.6 [1.12-6], P = 0.025) and intraluminal tumor growth (unfavorable, OR [95% CI]:1.9 [1.1-3.3], P = 0.023) as independent factors for survival. The MST after CRT was 12.1, 6.1, 5.7 months in patients with 0, 1, 2 factors, respectively (P < 0.001). CONCLUSION: Bronchoscopic finding determined outcome after CRT in esophageal cancer patients with airway invasion.

Predictors of pathological complete response to neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma.

BACKGROUNDS: In this study, we evaluated the factors associated with a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal squamous cell carcinoma (ESCC). METHODS: Pre-nCRT parameters in ESCC patients treated between 1999 and 2006 were analyzed to identify predictors of pCR. All patients received 5-fluorouracil/cisplatin-based chemotherapy and external beam radiation followed by scheduled esophagectomy. Variables were analyzed using univariate and multivariate analyses with pCR as the dependent variable. Estimated pCR rate was calculated with a regression model. RESULTS: Fifty-nine (20.9%) of 282 patients achieved pCR. Univariate analysis identified four patient factors (age, smoking status, drinking history and hypertension), one pre-nCRT parameter (tumor length) as significant predictors of pCR (all P <0.05). On multivariate analysis, tumor length ≤3 cm (favorable, odds ratio (OR): 4.85, P = 0.001), patient age >55 years (favorable, OR: 1.95, P = 0.035), and being a non-smoker (favorable, OR: 3.6, P = 0.003) were independent predictors of pCR. The estimated pCR rates based on a logistic regression including those three predictors were 71%, 35 to approximately 58%, 19 to approximately 38%, and 12% for patients with 3, 2, 1 and 0 predictors, respectively. CONCLUSION: Age, smoking habit and tumor length were important pCR predictors. These factors may be used to predict outcomes for ESCC patients receiving nCRT, to develop risk-adapted treatment strategies, and to select patients who could participate in trials on new therapies.

Using pretreatment tumor depth and length to select esophageal squamous cell carcinoma patients for nonoperative treatment after neoadjuvant chemoradiotherapy.

BACKGROUND: Two randomized trials have shown that in patients with good response to neoadjuvant chemoradiotherapy (nCRT), a nonoperative approach (additional CRT) had equal survival to scheduled esophagectomy. However, controversy exists because of the high locoregional recurrence (LR) following a nonoperative approach. Endoscopic complete response (e-CR) determined by endoscopic finding is a good criterion for predicting local control after definitive CRT. We evaluated whether e-CR could also be used to select patients for nonoperative treatment after nCRT. METHODS: We retrospectively analyzed esophageal squamous cell carcinoma (SCC) patients with e-CR after nCRT between 1999 and 2006. Patients were divided into two groups by the type of treatment given after e-CR (group A, scheduled esophagectomy; group B, no scheduled surgery and continued CRT). RESULTS: There were 71 and 79 patients in groups A and B, respectively with similar pre/post-nCRT characteristics. Despite similarity in survival and recurrence between groups, the recurrence site differed significantly. LR occurred more frequently in group B, whereas systemic recurrence was the predominant failure pattern in group A (P<.001). With use of multivariate analysis on group B, we determined that pretreatment depth of tumor invasion≥T3 [odds ratio (OR), 11.19; 95% CI, 1.4-89; unfavorable, P=.023] and tumor length≥6 cm (OR, 3.069; 95% CI, 1.17-8.1; unfavorable, P=.023) were predictors for LR. Patients with initial clinical T2 and <6 cm tumor had comparable LR (5%) to the surgery group; these patients were candidates for nonoperative treatment after nCRT. CONCLUSION: In esophageal SCC patients who achieved e-CR after nCRT, pretreatment tumor depth and length were good indicators to select candidates for nonoperative treatment.

Interval between neoadjuvant chemoradiotherapy and surgery for esophageal squamous cell carcinoma: does delayed surgery impact outcome?

BACKGROUND: Although esophagectomy traditionally is recommended to perform within 8 weeks after neoadjuvant chemoradiotherapy (nCRT), data from neoadjuvantly treated rectal cancer patients demonstrate that delayed surgery ([8 weeks) can maximize the effect of CRT. Despite these promising data, investigators are concerned that delayed surgery may lead to tumor repopulation. We report the impact of delayed surgery in patients with esophageal cancer who were treated with nCRT. METHODS: We retrospectively studied 276 esophageal cancer patients treated with nCRT and surgery between 2002 and 2008. We compared perioperative complication, rate of pathological complete response (pCR), distribution of tumor regression grade (TRG), and overall survival (OS) in patients who underwent surgery within 8 weeks (group A) and after 8 weeks (group B) after nCRT. RESULTS: There were 138 patients in each group with similar pre/post-nCRT characteristics. Delayed surgery did not result in lower surgical risk or higher pCR rate. Survival outcome also did not improve following a longer surgery interval (5-year OS: group A vs. group B, 29 vs. 23 %; P = 0.3). On the contrary, a subgroup analysis showed that delayed surgery might be hazardous, especially in patients who demonstrate a good response after nCRT. The amount of residual cancer, as measured by TRG, increased significantly after a longer surgical interval (P = 0.024). Survival also decreased after a longer surgical interval (5-year OS B8 vs. [8 weeks, 50 vs. 35 %; P = 0.038). CONCLUSIONS: After nCRT, esophagectomy should be performed within 8 weeks, especially in patients with good response.

Lymph node dissection after chemoradiation in esophageal cancer: a subgroup analysis of patients with and without pathological response.

BACKGROUND: Extensive lymph node dissection (LND) is beneficial in primarily resected esophageal cancer patients. Such benefit was believed to be seen in neoadjuvant chemoradiotherapy (CRT)-treated patients, but evidence was inconsistent. We hypothesized that CRT might offset the benefit of LND in certain subgroup of patients, especially in major responders. METHODS: The clinical pathological data and survival of esophageal squamous cell carcinoma patients who received curative resection after CRT between 1996 and 2007 were analyzed. On the basis of the mean LND number of the cohort, patients were divided into two groups: group 1, lower LND, and group 2, higher LND. RESULTS: The cohort comprised 303 patients (295 men and 8 women) with a mean age of 55.4 years. There were 179 patients in group 1 and 124 patients in group 2. One hundred one patients had pathological complete response (pCR). There were more pCR in group 1 (38 vs. 26.6%, P = 0.039) and more lymph node positive cases in group 2 (16 vs. 27.4%, P = 0.018). Extent of LND had no survival difference in the entire cohort (overall survival 32 vs. 38%, P = 0.31). With the stratification analysis according to tumor response, inadequate LND exhibited negative impact in patients who did not experience pCR (P = 0.027). Without adequate LND, the survival of ypTxN0 was equally poor as ypN-positive cases (overall survival 15 vs. 16%, P = 0.791). In the pCR group, the extent of LND had an impact on survival. CONCLUSIONS: The effect of LND was influenced by tumor response after CRT. There is a strong survival benefit for extensive LND after CRT in esophageal squamous cell carcinoma, especially in non-pCR patients.

Favorable outcome of secondary axillary dissection in breast cancer patients with axillary nodal relapse.

PURPOSE: Little evidence can be found about the long-term outcome of breast cancer patients after axillary lymph node recurrence (ALNR) and its survival benefit after different kinds of management. The present study intends to evaluate the risk factors associated with axillary recurrence after definite surgery for primary breast cancer. The prognosis after ALNR and particularly outcome of different management methods also were studied. METHODS: We retrospectively reviewed data from 4,473 patients who were diagnosed with primary breast cancer and received surgical intervention in a single institute from January 1990 to December 2002. Medical files were reviewed and data on survival were updated annually. Risk factors and prognosis of patients with axillary recurrence were analyzed. Breast-cancer-specific survival of patients with ALNR and outcomes after different management methods also were studied. RESULTS: After a median follow-up of 70.2 months, axillary recurrence developed in 0.8% of patients. Factors associated with ALNR included: age younger than 40 years, medial tumor location, no initial standard level I & II axillary dissection, and not receiving hormonal therapy. The 5-year breast-cancer-specific survival after ALNR was 57.9%. For patients who received further axillary dissection, the 5-year survival rate was 82.5% compared with 44.9% for patients who did not receive further dissection. CONCLUSIONS: ALNR is a rare event in treating breast cancer. Young age at diagnosis and medially located tumor are associated with higher risk, but standardized initial axillary dissection to level II and adjuvant hormonal therapy is protective against ALNR. In patients with ALNR, the outcome is not dismal and survival may be improved if further axillary dissection is given.

Impact of the number of lymph nodes sampled on outcome in ypT0N0 esophageal squamous cell carcinoma patients.

BACKGROUND: Higher extent of lymph node dissection (LND) is beneficial in primarily resected esophageal cancer patients by providing accurate staging and better tumor control. Achieving pathological complete response (pCR) after chemoradiotherapy (CRT) also represents better outcome. We studied the controversial question whether higher LND could further improve survival after pCR. METHOD: Between 1996 and 2007, Esophageal squamous cell carcinoma (ESCC) patients with pCR after CRT were included. Based on the median number of dissected lymph node, patients were divided into two groups (Group 1: Lower LND; Group 2: Higher LND). We compared the demographic features, perioperative outcomes, recurrence, and survival between groups. RESULTS: The cohort comprised 101 patients (100 males and one female) with a mean age of 58 years. There were 56 and 45 patients in Group 1 and 2, respectively. Clinical features and perioperative outcome were similar between groups. During a mean follow-up of 78.8 months, 32 (33.7%) patients died of the disease and 35.8% of patients developed recurrence. There was no difference in locoregional (11.3% vs. 9.5%, P=0.78) or distant recurrence (22.6% vs. 33.3%, P=0.18) between the two groups. Patients with lowest LND also had similar outcomes as those with the highest LND. The 5-year disease specific survival rate was 65 and 64% in Group 1 and 2, respectively. CONCLUSION: In ESCC patients, the number of negative lymph nodes had no prognostic impact after pCR.

Impact of circumferential resection margin distance on locoregional recurrence and survival after chemoradiotherapy in esophageal squamous cell carcinoma.

BACKGROUND: Close circumferential resection margin (CRM) is an established predictor for locoregional recurrence (LR) in rectal cancer but remains controversial in esophageal malignancy. As yet, little is known about the significance of CRM after chemoradiotherapy (CRT), especially in squamous cell carcinoma (SCC). This study investigated the relationship between CRM distance and recurrence after neoadjuvant CRT in esophageal SCC patients. METHODS: Between 1997 and 2005, esophageal SCC patients who underwent surgery after neoadjuvant CRT and with pathology stage T3N0M0 and T3N1M0 (metastatic lymph nodes <2) were selected. CRM distance was reassessed and divided into three groups (group 1: CRM >1 mm, group 2: uninvolved CRM but <1 mm, group 3: CRM involved). RESULTS: The cohort comprised 145 male and 6 female patients with mean age of 57 years. There were 74, 51, and 26 patients in group 1, 2, and 3, respectively. With median follow-up period of 50 months, LR developed in 30.5% of patients. Both group 2 and group 3 had significantly higher LR than group 1 (37 and 42% vs. 21%, P < 0.05). Meanwhile, mean time from operation to recurrence was also significantly shorter in group 2 and group 3 than in group 1 (267 and 269 days versus 402 days, P < 0.05). Five-year disease-specific survival (DSS) was highest in group 1 (40%). Despite the similarity in LR, 5-year DSS significantly differed between group 2 and group 3 (22 vs. 7%, P < 0.05). The higher rate of distant recurrence (DR) and concomitant LR + DR in group 3 accounted for the survival difference. CONCLUSION: In ypT3 esophageal SCC patients, CRM distance provides useful information for risk stratification in cancer recurrence and survival.

Definitive concurrent chemoradiotherapy with paclitaxel plus carboplatin is superior to cisplatin plus 5-fluorouracil in patients with inoperable esophageal squamous cell carcinoma using retrospective, real-world evidence.

BACKGROUND: The optimal definitive chemotherapy regimen during concurrent chemoradiotherapy (CRT) for patients with advanced esophageal squamous cell carcinoma (ESCC) remains unclear because of conflicting evidence. This study aimed to compare the effectiveness of taxane-based chemotherapy with that of conventional cisplatin plus 5-fluorouracil (PF) as the chemotherapy regimen in definitive CRT for ESCC. PATIENTS AND METHODS: This retrospective study included patients with ESCC who received paclitaxel plus carboplatin (PC) or PF during definitive CRT between May 2012 and February 2015 in a medical center in Taiwan. Survival outcomes were compared after adjustment for risk factors. RESULTS: Overall, 229 patients were evaluated. Patients in the PC group had an objective response rate of 71.1% compared with the 51.4% of the PF group (p = 0.016). The PC group showed a significantly longer progression-free survival (PFS, p = 0.002) and overall survival (OS, p = 0.019) than the PF group. Salvage surgery also helped prolong both the PFS and OS (p < 0001). Sex (male vs. female, HR, 1.831; 95% CI, 1.016-3.303), clinical stage (HR, 1.282; 95% CI, 1.069-1.537), accumulative radiation dose (≥41.4 Gy vs. <41.4 Gy; HR, 0.640; 95% CI, 0.413-0.993), salvage surgery (yes vs. no, HR: 0.412, 95% CI: 0.298-0.570), and regimen (PF vs. PC; HR, 1.514; 95% CI, 1.109-2.067) were independent prognostic factors for cancer mortality. CONCLUSION: Compared with the PF regimen, the PC regimen for definitive CRT yielded significantly increased response rates and longer survival times; therefore, the PC regimen may be preferable for chemotherapy for definitive CRT in patients with advanced ESCC.

Long-Term Outcomes of Breast Cancer Patients Who Underwent Selective Neck Dissection for Metachronous Isolated Supraclavicular Nodal Metastasis.

We retrospectively enrolled 139 patients who developed metachronous isolated supraclavicular lymph node metastasis (miSLNM) from 8129 consecutive patients who underwent primary surgery between 1990 and 2008 at a single medical center. The median age was 47 years. The median follow-up time from date of primary tumor surgery was 73.1 months, and the median time to the date of neck relapse was 43.9 months in this study. Sixty-one (43.9%) patients underwent selective neck dissection (SND). The 5-year distant metastasis-free survival (DMFS), post-recurrence survival, and overall survival (OS) rates in the SND group were 31.1%, 40.3%, and 68.9%, respectively, whereas those of the no-SND group were 9.7%, 32.9%, and 57.7%, respectively (p = 0.001). No SND and time interval from primary tumor surgery to neck relapse ≤24 months were the only significant risk factors in the multivariate analysis of DMFS (hazard ratio (HR), 1.77; 95% confidence interval (CI), 1.23-2.56; p = 0.002 and HR, 1.76, 95% CI, 1.23-2.52; p = 0.002, respectively) and OS (HR, 1.77; 95% CI, 1.22-2.55; p = 0.003 and HR, 3.54, 95% CI, 2.44-5.16; p < 0.0001, respectively). Multimodal therapy, including neck dissection, significantly improved the DMFS and OS of miSLNM. Survival improvement after miSLNM control by intensive surgical treatment suggests that miSLNM is not distant metastasis.

Discrepancy of Breast and Axillary Pathologic Complete Response and Outcomes in Different Subtypes of Node-positive Breast Cancer after Neoadjuvant Chemotherapy.

Few studies have analyzed the discrepancy between breast pathologic complete response (B-pCR) and axillary node pCR (N-pCR) rates and their impact on survival outcomes in different intrinsic subtypes of early breast cancer after neoadjuvant chemotherapy (NAC). We retrospectively reviewed B-pCR, N-pCR, and total (breast and axillary node) pCR (T-pCR) after NAC to assess the discrepancy and outcomes between 2005 and 2017. A total of 968 patients diagnosed with cT1-4c, N1-2, and M0 breast cancer were enrolled in the study. The median age was 49 years and the median follow-up time was 45 months. Of these patients, 213 achieved T-pCR, 31 achieved B-pCR with axillary node pathologic non-complete response (N-non pCR), 245 achieved N-pCR with breast pathologic non-complete response (B-non pCR), and 479 achieved total (breast and axillary node) pathologic non-complete response (T-non pCR) after NAC. The highest B-pCR and N-pCR rates were found in the hormone receptor-negative, human epidermal growth factor receptor 2-positive HR(-)HER2(+) subtype, while the lowest B-pCR rate was found in the HR(+)HER2(-) subtype. The N-pCR rate was correlated to the B-pCR rate (P<0.001), but was higher than the B-pCR rate in all subtypes. The 5-year overall survival (OS) rates for patients with T-pCR, B-pCR, and N-pCR were 91.2%, 91.7%, and 91.9%, respectively. For non-pCR, non-pCR, and non-pCR, the 5-year OS rates were 73.6%, 78.9%, and 74.7%, respectively (P<0.0001). B-non pCR patients had a lower risk of recurrence than T-non pCR or N-non-pCR patients, although there were no differences in OS among them. In conclusion, the N-pCR rate was higher than the B-pCR rate after NAC in all intrinsic subtypes, and N-non pCR or T-non pCR patients had the worst outcomes.

Distant nodal metastases from intrathoracic esophageal squamous cell carcinoma: characteristics of long-term survivors after chemoradiotherapy.

BACKGROUND: Non-regional lymph node metastasis in intrathoracic esophageal cancer is classified as M1 lesion with poor prognosis following surgery alone. We studied the controversial question of whether chemoradiotherapy (CRT) improves survival of these patients. METHODS: A cohort of patients with clinically overt nodal M1 disease, which could be encompassed by a tolerable radiation therapy port, was selected from the database of the Chang Gung Memorial Hospital. RESULTS: From 1994 to 2005, 54 nodal stage IV intrathoracic esophageal squamous cell carcinoma (SCC) patients received neoadjuvant CRT. Significant response occurred in 24 patients. Scheduled esophagectomy was performed in 26 patients. The 3-year overall survival (OS) and disease-free survival (DFS) for the whole group were 27% (median: 14.2 months) and 22% (median: 14.7 months), respectively. Multivariate analysis identified pretherapy lymph nodes classified as M1a and R0 resection after CRT as independent favorable prognosticators. Median survival reached 36.9 months in the pretherapy M1a subgroup as opposed to 12.5 months in the M1b subgroup (3-year-DFS: 40% vs. 10%, P = 0.0117). Scheduled surgery after CRT benefits only after R0 resection (3-year-DFS: 36%, median survival: 45 months). The group with incomplete resection had a high surgical risk and dismal survival compared to the non-surgery group (3-year-DFS: 0% vs. 9%, 9.5 vs. 10.5 months). CONCLUSIONS: Pretherapy M1a disease had a significantly better survival than nodal M1b disease after CRT in SCC. Aggressive surgical treatment after CRT is reserved for cases when complete resection is anticipated.