Temporal Trends in Survival Outcomes for Patients with Esophageal Cancer Following Neoadjuvant Chemoradiotherapy: A 14-Year Analysis.

BACKGROUND: The prognosis for patients with esophageal cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery has shown improvement in recent years. We sought to identify the critical factors contributing to enhanced survival outcomes. PATIENTS AND METHODS: We retrospectively examined 427 patients with esophageal cancer treated with nCRT and esophagectomy across two periods: P1 (from 1 January 2004 to 31 December 2011) and P2 (from 1 January 2012 to 31 December 2017). The introduction of the CROSS regimen and total meso-esophagectomy in P2 prompted an evaluation of their effects on perioperative outcomes and overall survival (OS). RESULTS: During P2, the occurrence of recurrent laryngeal nerve palsy increased significantly from 3.9 to 16.8% (p < 0.001), while pneumonia and in-hospital mortality rates remained unchanged. The median OS improved from 19.2 to 29.2 months (p < 0.001) between P1 and P2. Multivariable analysis identified higher nodal yields and the achievement of major response as favorable prognostic factors. Conversely, an involved circumferential resection margin (CRM), an advanced ypN stage, and pneumonia were independently associated with poor outcomes. Patients treated during P2 had a lower prevalence of involved CRM (10% vs. 25.1%, p < 0.001), a higher rate of major response (52.7% vs. 34.8%, p < 0.01), and a greater nodal yield (27.8 vs. 10.9, p < 0.001). CONCLUSIONS: The clinical outcomes following nCRT and surgery have improved significantly over time. This progress can be attributed to multiple factors, with the primary drivers being the refinement of nCRT protocols and the application of radical surgery.

Focused ultrasound combined with radiotherapy for malignant brain tumor: a preclinical and clinical study.

INTRODUCTION: Blood-brain barrier (BBB) remains to be the major obstacle to conquer in treating patients with malignant brain tumors. Radiation therapy (RT), despite being the mainstay adjuvant modality regardless of BBB, the effect of radiation induced cell death is hindered by the hypoxic microenvironment. Focused ultrasound (FUS) combined with systemic microbubbles has been shown not only to open BBB but also potentially increased regional perfusion. However, no clinical study has investigated the combination of RT with FUS-BBB opening (RT-FUS). METHODS: We aimed to provide preclinical evidence of RT-FUS combination in GBM animal model, and to report an interim analysis of an ongoing single arm, prospective, pilot study (NCT01628406) of combining RT-FUS for recurrent malignant high grade glioma patients, of whom re-RT was considered for disease control. In both preclinical and clinical studies, FUS-BBB opening was conducted within 2 h before RT. Treatment responses were evaluated by objective response rate (ORR) using magnetic resonance imaging, progression free survival, and overall survival, and adverse events (AE) in clinical study. Survival analysis was performed in preclinical study and descriptive analysis was performed in clinical study. RESULTS: In mouse GBM model, the survival analysis showed RT-FUS (2 Gy) group was significantly longer than RT (2 Gy) group and control, but not RT (5 Gy) group. In the pilot clinical trial, an interim analysis of six recurrent malignant high grade glioma patients underwent a total of 24 RT-FUS treatments was presented. Three patients had rapid disease progression at a mean of 33 days after RT-FUS, while another three patients had at least stable disease (mean 323 days) after RT-FUS with or without salvage chemotherapy or target therapy. One patient had partial response after RT-FUS, making the ORR of 16.7%. There was no FUS-related AEs, but one (16.7%) re-RT-related grade three radiation necrosis. CONCLUSION: Reirradiation is becoming an option after disease recurrence for both primary and secondary malignant brain tumors since systemic therapy significantly prolongs survival in cancer patients. The mechanism behind the synergistic effect of RT-FUS in preclinical model needs further study. The clinical evidence from the interim analysis of an ongoing clinical trial (NCT01628406) showed a combination of RT-FUS was safe (no FUS-related adverse effect). A comprehensive analysis of radiation dosimetry and FUS energy distribution is expected after completing the final recruitment.

Treatment of Primary Central Nervous System Germinomas With Short-course Induction Chemotherapy Followed by Low-dose Radiotherapy Without a Tumor Bed Boost: Prognostic Impact of Human Chorionic Gonadotropin.

OBJECTIVE: To investigate the clinical utility of short-course induction chemotherapy followed by low-dose radiotherapy without a tumor bed boost in patients with primary central nervous system (CNS) germinomas. METHODS: We retrospectively reviewed the clinical records of patients with primary CNS germinomas who received short-course induction chemotherapy (2 cycles of cisplatin 20 mg/m2 plus etoposide 40 or 100 mg/m2 for 5 days) followed by low-dose radiotherapy (dose: 2340 cGy) without a tumor bed boost. Disease-free survival and overall survival served as the main outcome measures. RESULTS: Between February 2002 and June 2018, 24 patients (20 males and 4 females; median age: 14.1 y; age range: 7.9 to 21.2 y) with pathology-proven CNS germinomas were included. The median follow-up time was 106 months (range: 17 to 169 mo). Isolated and multifocal lesions were identified in 13 and 11 patients, respectively. Tumor location was as follows: pineal gland (n=17), suprasellar region (n=13), periventricular region (n=7), and basal ganglia (n=2). Five patients had increased levels (>5 mIU/mL) of beta-human chorionic gonadotropin (ß-hCG), whereas alpha-fetoprotein concentrations were within the reference range in all participants. A total of 16 patients achieved remission after induction chemotherapy. The complete response rates of patients with increased and normal ß-hCG levels were 40.0% and 72.2%, respectively (P=0.208). Low-dose radiotherapy without a tumor bed boost was subsequently delivered to either the whole ventricle (n=16) or the whole brain (n=8), resulting in complete remission in all participants. Compared with patients without increased ß-hCG levels, those with ß-hCG-secreting germinomas had less favorable 5-year disease-free survival rates (100% vs. 60%, respectively, P=0.000115). CONCLUSIONS: Some children with primary CNS germinoma may benefit from short-course induction chemotherapy followed by low-dose radiotherapy to the whole ventricle without a tumor bed boost. The validity of our findings needs to be confirmed in a randomized phase II study for children with ß-hCG levels <5 mIU/mL.

Prognostic value of lymph node to primary tumor standardized uptake value ratio in unresectable esophageal cancer.

BACKGROUND: Unresectable esophageal cancer harbors high mortality despite chemoradiotherapy. Better patient selection for more personalized management may result in better treatment outcomes. We presume the ratio of maximum standardized uptake value (SUV) of metastatic lymph nodes to primary tumor (NTR) in 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (FDG PET/CT) may provide prognostic information and further stratification of these patients. METHODS: The patients with non-metastatic and unresectable esophageal squamous cell carcinoma (SCC) receiving FDG PET/CT staging and treated by chemoradiotherapy were retrospectively reviewed. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cut-off value for NTR. Kaplan-Meier method and Cox regression model were used for survival analyses and multivariable analyses, respectively. RESULTS: From 2010 to 2016, 96 eligible patients were analyzed. The median follow-up time was 10.2 months (range 1.6 to 83.6 months). Using ROC analysis, the best NTR cut-off value was 0.46 for prediction of distant metastasis. The median distant metastasis-free survival (DMFS) was significantly lower in the high-NTR group (9.5 vs. 22.2 months, p = 0.002) and median overall survival (OS) (9.5 vs. 11.6 months, p = 0.013) was also significantly worse. Multivariable analysis revealed that NTR was an independent prognostic factor for DMFS (hazard ratio [HR] 1.81, p = 0.023) and OS (HR 1.77, p = 0.014). CONCLUSIONS: High pretreatment NTR predicts worse treatment outcomes and could be an easy-to-use and helpful prognostic factor to provide more personalized treatment for patients with non-metastatic and unresectable esophageal SCC.

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.

Oligodendrogliomas in Children: Clinical Experiences With 20 Patients.

Oligodendrogliomas occurring rarely in children are incompletely characterized. The purpose of this study was to identify prognostic factors affecting the local control and survival in the management of children with oligodendrogliomas. We retrospectively analyzed clinical data on 20 pediatric patients with oligodendrogliomas treated at Chang Gung Children's Hospital between 1994 and 2014. There were 12 males and 8 females with a median age of 9.2 years at diagnosis (range, 3 mo to 18 y). Eighteen (90%) tumors were located in the cerebral hemispheres, 10 cases were located on the right, 8 on the left. One was located in the third ventricle and 1 in the thoracic spine. Presenting symptoms included seizures (n=7), headache (n=5), visual field defects (n=3), limb weakness (n=2), vomiting (n =1), back pain (n=1), and increased head circumference (n=1). All patients underwent craniotomy: 8 gross total resections, 8 subtotal resections, and 4 biopsies. Nine of the patients had pure oligodendroglioma and 11 had anaplastic oligodendroglioma (WHO grade III or IV). Ten children had adjuvant therapy including radiation (n=7), chemotherapy (n=1) or both (n=2). With the median follow-up of 5.3 years (range, 1.2 to 14.7 y), the 5-year overall survival and disease-free survival rates were 78.9% with 65.0%, respectively. Total tumor resection offers better overall survival regardless of the histologic grading. Our data demonstrate that patients with less than gross total resections are at increased risk for progression and may benefit from more aggressive therapy.

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.

Corpus callosum involvement and postoperative outcomes of patients with gliomas.

Corpus callosum involvement is associated with poorer survival in high grade glioma (HGG), but the prognostic value in low grade glioma (LGG) is unclear. To determine the prognostic impact of corpus callosum involvement on progression free survival (PFS) and overall survival (OS) in HGG and LGG, the records of 233 glioma patients treated from 2008 to 2011 were retrospectively reviewed. Preoperative magnetic resonance (MR) images were used to identify corpus callosum involvement. Age, sex, preoperative Karnofsky performance scale, postoperative Eastern Cooperative Oncology Group (ECOG) score and extent of resection (EOR) were evaluated with respect to PFS and OS. The incidence of corpus callosum involvement was similar among HGG (14 %) and LGG (14.5 %). Univariate analysis revealed that PFS and OS were significantly shorter in both WHO grade II and grade IV glioma with corpus callosum involvement (both, p < 0.05). Multivariate analysis showed that grade II glioma with corpus callosum involvement have shorter PFS (p = 0.03), while EOR, instead of corpus callosum involvement (p = 0.16), was an independent factor associated with PFS in grade IV glioma (p < 0.05). Corpus callosum involvement was no longer significantly associated with OS after adjusting age, gender, EOR, preoperative and postoperative performance status (p = 0.16, 0.17 and 0.56 in grade II, III and IV gliomas, respectively). Corpus callosum involvement happened in both LGG and HGG, and is associated with lower EOR and higher postoperative ECOG score both in LGG and HGG. Corpus callosum involvement tends to be an independent prognostic factor for PFS in LGG, but not for OS in LGG or in HGG.

Linear accelerator stereotactic radiosurgery in the management of intracranial arteriovenous malformations: long-term outcome.

BACKGROUND: Arteriovenous malformation (AVM) is one of the cerebrovascular diseases that bear a high risk of hemorrhage. The treatment modalities include microsurgical resection, endovascular embolization, stereotactic radiosurgery, or combinations that vary widely. Several large series have been reported, while data from Asian populations were few. The aim of this study was to examine the efficacy of linear accelerator stereotactic radiosurgery (LINAC SRS) for the treatment of intracranial AVMs, to evaluate the hemorrhage rate and to analyze associated factors. METHODS: One hundred and sixteen patients with AVM were treated with LINAC SRS in a single institute between September 1994 and May 2005 and were retrospectively evaluated. The demographics of patients, clinical characteristics of AVM, the treatment modalities, and the parameters of the LINAC SRS were analyzed. Delayed toxicity and hemorrhage rate after treatment were also evaluated. The AVM obliteration and bleed rates were calculated using the Kaplan-Meier method and Cox regression analyses. RESULTS: The efficacy rate with total obliteration after treatment was 81.9% (95 of 116 patients). The median interval to achieve total obliteration was 49 months. Microsurgical resection combined with SRS for residual AVMs achieved better obliteration rates compared to SRS alone (statistically significant, p = 0.001), while no significant difference was found between the embolization group and the group with no prior treatment (p = 0.895). The Spetzler-Martin grade of AVM is a relative factor of obliteration, higher grades resulting in a worse outcome (p = 0.009). Obliteration was significantly influenced by AVM volume in univariate analysis (p = 0.034), and volume <5 cm(3) contributed to improved obliteration (p = 0.01). There was no statistically significant difference in the hemorrhagic rate and the complication rate between ruptured and unruptured AVMs, while the unruptured group had a higher obliteration rate (p = 0.024). The annual hemorrhage rate after LINAC SRS treatment was 1.9%. The bleeding rate was 3.3% in the first year after radiosurgery, 2.1% in the second year, 1.9% between the second and fifth year, and 1.5% between the fifth and tenth year. Patients with hemorrhagic events before radiosurgery appeared to have a higher rebleeding risk during the latency period. Twenty-three patients (19.8%) had late adverse effects with regard to posttreatment radiological follow-up, but only 1 (0.8%) had newly developed neurological deficits. CONCLUSION: LINAC SRS achieved a high obliteration rate and reduced the risk of hemorrhage effectively in ruptured and unruptured intracranial AVMs. Prior microsurgical resection provided better outcome, while embolization showed no benefit. Adverse effects after treatment are acceptable and require long-term follow-up.

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.

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.

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.

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.

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.

Rescue by hematopoietic progenitor cells derived from engrafted cord blood unit in a child with brain tumor after transplantation for T-cell acute lymphoblastic leukemia.

An 8-year-old boy with T-cell acute lymphoblastic leukemia received unrelated cord blood transplantation in April 2006. His course was uneventful until February 2007, when a hyperintense lesion was noted in the pons. A subsequent bone marrow examination confirmed that he was in remission with full donor chimerism. He was therefore diagnosed with an inoperable brain tumor after cord blood transplantation. Despite radiotherapy for the brain lesion, his neurological status worsened. High-dose chemotherapy with "autologous" progenitor cell rescue was adopted, although the fact that these cells were originally derived from engrafted umbilical cord unit. He was in apparent remission of his brain tumor for 3 years.