Outcomes from salvage esophagectomy post definitive chemoradiotherapy compared with resection following preoperative neoadjuvant chemoradiotherapy

Chemoradiotherapy (CRT) as a definitive treatment for esophageal cancer, is being used with increasing frequency and as a result, surgeons will be required to assess more patients who have residual or recurrent local malignancy. This article aimed to assess outcomes after esophagectomy following definitive CRT (dCRT) and compare any difference between them and patients who had preoperative neoadjuvant CRT (nCRT) using a similar regimen of chemotherapy. From a prospective database the details of patients who had a resection following nCRT and dCRT were analyzed. The main therapeutic difference between the groups was the dose of radiotherapy (35 vs 60 Gy) and the timing of the resection following completion of the CRT (median 4 vs 28 weeks). Fourteen patients had an esophagectomy following a dCRT and 53 had one following a nCRT. Preoperatively, the dCRT group had worse respiratory function and more ECG abnormalities. Preoperative tumor length, pathological TNM staging and R0 resection rates were the same in both groups. Post resection, the dCRT group had greater morbidity than the nCRT group, spending longer in the intensive care unit (median 48 vs 24 h), more days in hospital (median 31 vs 13) and having more severe respiratory complications (37%vs 6%). The operative mortality was higher in the dCRT group (7%vs 0%). The three-year survival was 24% after dCRT. Patients selected for salvage esophagectomy following dCRT are a major challenge in postoperative care. However, some patients survive for a reasonable period of time, making resection a worthwhile option.     

Carcinosarcoma of the esophagus treated with chemoradiotherapy: report of four cases

Esophageal carcinosarcoma is a rare neoplasm. Esophagectomy with lymph node dissection has often been performed, although the efficacy of chemotherapy or radiotherapy is not yet confirmed. Four cases of esophageal carcinosarcoma who underwent chemoradiotherapy are presented. Complete response of the primary tumor was observed in one case; tumor size decreased in three cases. Two patients have been observed to be disease free, another patient died of metastatic disease, and the other had recurrence. Six cases of carcinosarcoma treated with chemoradiotherapy were retrieved from the literature and analyzed with the four cases in the current study. Reduction of the tumor was observed in seven of the ten cases. Disease progression or local recurrence was observed in three cases, and another two cases died of metastatic disease. Although chemoradiotherapy seems to be capable of local control, whether it is beneficial in terms of prolonging survival of patients with this disease remains unknown.     

Effective treatment of locally advanced endocrine tumors of the pancreas with chemoradiotherapy

BACKGROUND/AIMS: The use of chemoradiation in the management of locally advanced pancreatic endocrine tumors has not been reported in the medical literature. Patients with unresectable tumors are often included in trials of systemic chemotherapy, and use of external beam radiation has been only described in few case reports. Given the sensitivity of pancreatic endocrine tumors to cytotoxic agents including streptozocin, doxorubicin and 5-FU, we have hypothesized that the combination of concurrent and sequential chemotherapy and radiation will yield higher response rates than acheivable with chemotherapy alone. METHODS: Six patients with locally advanced pancreatic endocrine tumors were treated with a protocol consisting of radiation concurrent with infusional 5-FU (or capecitabine) along with induction and consolidation chemotherapy (streptozocin and doxorubicin). We retrospectively determined the objective radiographic response rate. RESULTS: The objective response rate was 80%. With a median follow-up of 29 months, all six patients in the study have had continued reduction in tumor size from the time of the first posttreatment scan to the most recent scan. None of the patients have experienced local or metastatic disease progression. Treatment was well tolerated with minimal toxicity. CONCLUSION: The combination of concurrent and sequential chemoradiotherapy appears to be a highly effective treatment for locally advanced pancreatic endocrine tumors.     

Salvage pharyngolaryngectomy with total esophagectomy following definitive chemoradiotherapy

Historically, total pharyngolaryngectomy with total esophagectomy has been the standard radical surgical treatment for synchronous cancer of the thoracoabdominal esophagus and pharyngolaryngeal region, and for cancer of the cervical esophagus that has invaded as far as the thoracic esophagus. Although definitive chemoradiotherapy that enables preservation of the larynx has often been the first choice of treatment for cancers involving the cervical esophagus, total pharyngolaryngectomy with total esophagectomy is required as a salvage therapy for cases involving failure of complete remission or locoregional recurrence after chemoradiotherapy. However, salvage esophageal surgery after definitive high‐dose chemoradiotherapy is generally associated with high morbidity and mortality. The aim of this study was to examine the short‐term outcome of salvage total pharyngolaryngectomy with total esophagectomy. From 2001 to 2014, nine patients underwent salvage total pharyngolaryngectomy with total esophagectomy at the Department of Gastroenterological Surgery, Nagoya University. The mortality and morbidity rates were high at 22% and 89%, respectively. Four patients (44%) developed tracheal necrosis, which in two patients eventually led to lethal hemorrhage. Salvage total pharyngolaryngectomy with total esophagectomy is an uncommon and highly demanding surgical procedure that should be carefully planned and conducted in selected centers of excellence. Measures must be taken to preserve the tracheal blood supply, thus avoiding fatal complications.     

Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas

To examine the histopathologic effect of neoadjuvant therapy and its impact on survival in patients with carcinoma of the pancreas, we retrospectively reviewed the records of 116 patients who underwent resections for pancreatic cancer from 1987 to 2000. Median follow-up of surviving patients was 19 mo (range 4–150 mo). Preoperative chemotherapy was administered in 61 patients (53%) and consisted of 5-fluorouracil/mitomycin C in 35 patients and gemcitabine in 26 patients, given concurrently with external beam radiation (5040 cGy). All resections were performed with curative intent (98 Whipples, 11 total, 6 distal, and 1 central pancreatectomy). Histopathologic examination included an estimation of the amount of fibrosis present in the tumor specimen (expressed as the percentage of fibrosis identified relative to the amount of neoplastic cells present). The mean fibrosis level for the series was 56% (range 5% to 100%). The administration of neoadjuvant therapy resulted in greater fibrosis (73%) than no preoperative treatment (38%) (p=0.0001). Higher mean fibrosis levels were observed in patients with negative lymph nodes (p=0.0006) and negative margins (p=0.05). Factors associated with improved survival (log rank test) included: negative margins (p=0.001), negative lymph nodes (p=0.03), and use of neoadjuvant therapy (p=0.03). Median survival in the neoadjuvant group was 23 mo vs 16 mo without preoperative therapy (p=0.03). In conclusion, the use of neoadjuvant therapy resulted in a greater degree of fibrosis in the specimen. Patients with negative margins and negative lymph nodes had a greater amount of fibrosis present, and these were significant predictors of improved outcome. Although retrospective, this series suggests an improvement in survival in patients treated with neoadjuvant therapy.     

Outcomes from chemoradiotherapy for patients with esophageal cancer

Chemoradiotherapy is a widely used alternative treatment to surgical resection in certain patient groups with early esophageal cancer. The aim of this study was to retrospectively assess toxicity and outcome of patients treated with definitive chemoradiotherapy for early esophageal cancer at one institution. A retrospective analysis of all patients treated with chemoradiotherapy between February 2000 and December 2008 at a single tertiary center was performed with documentation of treatment given, toxicities recorded, and follow‐up and outcome data. Sixty‐two patients received chemoradiotherapy for esophageal cancer. There were 20 males and 42 female patients with an average age of 68 years. Histology revealed adenocarcinoma in 28 patients and squamous cell carcinoma in 34 patients. All patients were staged with a computerized tomography scan, endoscopic ultrasound and positron emission tomography scan. Selection criteria for chemoradiotherapy were unfit for surgery, upper esophageal squamous carcinoma, unresectable primary tumor, or patient choice. The majority of the patients received a combination of cisplatin and 5‐fluorouracil chemotherapy with 55 Gy in 25 fractions of radiotherapy. Grade 3 toxicities were recorded in 11% of the patients. Eleven patients suffered from local recurrence and a stent was required in nine patients. Radiation strictures occurred in 10 patients requiring dilation in four. Five patients required a radiologically inserted feeding gastrostomy. The median overall survival was 21 months. Patients with adenocarcinomas and those with squamous cell carcinoma had a similar median survival. Overall survival was 70% at 1 year, 48% at 2 years, and 26% at 3 years. This case series of patients treated with chemoradiation for localized esophageal cancer suggest a generally well‐tolerated treatment with survival rates after chemoradiotherapy comparable with those seen with surgery.     

Pancreatic cancer chemoradiotherapy

Pancreatic cancer is the most lethal gastrointestinal tumour. Chemotherapy is the mainstay of therapy in the majority of the patients whereas resection is the only chance of cure but only possible in 15–20% of all patients. The integration of radiotherapy into multimodal treatment concepts is heavily investigated. It is now commonly accepted that induction chemotherapy should precede radiotherapy. When fractionated conventionally it should be given as chemoradiotherapy. Recently, stereotactic body radiotherapy emerged as an alternative, but will have to be carefully investigated in clinical trials. This review aims to give an overview of radiotherapeutic strategies with a focus on the latest developments in the field in the context of chemotherapy and surgery.     

恶性肿瘤化疗与联合放化疗动态心电图对比分析

目的了解化疗及放化疗期间恶性肿瘤患者出现心慌、心悸等症状时心电图的改变。方法对尚未治疗组（A组）、化疗组（B组）及放化疗组（C组）恶性肿瘤患者在治疗期间出现心慌、心悸等症状时作24h动态心电图（DCG）,对其心率、期前收缩、异位心动过速及ST—T改变等进行对比分析。结果24h最高心率、最低心率、平均心率及24h总心率,B、c组与A组比较具有非常显著性差异（P〈0．01及O．001）。B与C组间平均心率、24h总心率有显著性差异（P〈0．05）,但最高心率、最低心率无显著性差异（P〉0．05）。〉100次／24h房性及室性期前收缩,A与B组间具有显著性差异（P〈0．05）,A与C组间具有非常显著性差异（P〈0．01）。B与C组间房性期前收缩具有显著性差异（P〈0．05）,但室性期前收缩无显著性差异（P〉0．05）。A与B及A与C组间短阵性房性心动过速具有非常显著性差异（P〈0．01）,但B与C组间无显著性差异（P〉0．05）。室性心动过速三组间无显著性差异（P〉0．05）。A与C组间ST—T改变具有非常显著性差异（P〈0．01）,但A与B及B与C间无显著性差异（P〉0．05）。结论化疗、放疗对心脏具有一定毒性作用,联合放化疗可加重二者的毒性作用。动态心电图可作为在化疗、放化疗时,对有症状性肿瘤患者的心脏毒性作用最简捷的监测方法,有利于临床医生及时调整方案。     

Preoperative chemoradiotherapy in patients with locally advanced rectal cancer

BACKGROUND/AIMS: To determine the percentage of responders and the resectability rate for patients with locally advanced carcinoma of the rectum treated by infusional 5-fluorouracil chemotherapy and pelvic radiation. METHODOLOGY: Twenty-four patients with a diagnosis of locally advanced unresectable rectal cancer received preoperative 5-fluorouracil by intravenous infusion at the dose of 250-300mg/m2/day concurrent with pelvic radiation (median 50.4 Gy/28 fractions). Surgery was performed with a mean delay of 15 days after completion of irradiation and included 11 abdominoperineal resections and five anal sphincter-preserving procedures. RESULTS: The median follow-up was 22 months. Complete histological response occurred in 6%, and tumor down-staging in 58% of cases. There was a significant difference in the rate of local control based on the distance of the tumor from the anal verge (>5.4cm; p=0.046). Our results have suggested the importance of the total dose on the local control (p=0.061). Higher local failure rate has been observed with prolonged treatment time (p=0.018). With metastasis-free survival as the endpoint, only stage (p=0.027) was a statistically significant prognostic factor. CONCLUSIONS: The favorable influence of higher doses of preoperative radiotherapy on pathologic stage has been observed. Even after preoperative radiotherapy, postoperative staging remained a prognostic factor.     

Intensive chemoradiotherapy with autologous marrow transplantation for small cell carcinoma of the lung

Ten patients with small cell carcinoma of the lung (seven with extensive and three with limited disease) underwent several courses of conventional therapy. The patients were then referred for autologous marrow transplantation, three during a complete response, six during a partial response, and one following no response. The pretransplantation regimen consisted of 120 mg/kg of cyclophosphamide followed by 800-1000 rad of total-body irradiation. In addition, six of the seven patients with extensive disease received high-dose nitrosourea. Following the infusion of cryopreserved autologous marrow, all patients achieved engraftment. Of the three patients without detectable tumor at the time of transplant, two died with tumor present and one survives without recurrence 27 months after transplantation. Of the other seven patients, two had a complete tumor response; both died of interstitial pneumonitis, one without detectable tumor and one with microscopic tumor at autopsy. One of the other five patients had a partial response, but all died of tumor progression. The median survival from initial therapy in patients with extensive disease was 9 months and with limited disease was 18.5 months.     

Perianal Paget's disease: Successful treatment with combined chemoradiotherapy

A case of locally extensive perianal Paget's disease is presented. Initial wide local excision, guided by frozen sections, was inadequate. Multiple punch biopsies subsequently revealed extensive circumferential involvement of the anoderm by Paget's disease, making wide local excision difficult. Therefore, the patient was treated with combined chemoradiotherapy (5000 cGy, 5-fluorouracil, and mitomycin C). Fourteen months after treatment, the patient had a complete response.     

Preoperative chemoradiotherapy in cancer of the thoracic esophagus

Surgery with or without adjuvant radiotherapy (RT) is the standard treatment of esophageal cancer. Preoperative radio- and chemotherapy (CT) have been introduced to improve prognosis. We report a phase II prospective non-randomized trial of preoperative RT (42 Gy/25) plus CT (cisplatin 20 mg/mq/day plus 5-fluorouracil 600 mg/mq/day, 1-5 weeks) for the treatment of thoracic esophageal cancer. From 1993, 50 patients were enrolled (40 men and 10 women, mean age 57 years, range 30-75 years). Squamous cell carcinoma accounted for 90% of cases; 10% were adenocarcinoma. Downstaging of the disease was obtained in 77.3% of cases; there were 13 (29.5%) complete responses (CR) and 21 (47.7%) partial responses (PR). Median survival was 28 and 25 months, respectively, for CR and partial response (PR) plus stable disease (SD) and progressive disease (PD) (P = 0.05). Progressive-free median survival was 22 and 17 months, respectively, for CR and PR + SD + PD (P = 0.08). Multimodal treatment of esophageal cancer showed promising results, although not significant, in terms of survival and disease progression for patients achieving a complete pathologic response.     

Impact of comorbidity and age on the outcome of patients with inoperable NSCLC treated with concurrent chemoradiotherapy

BACKGROUND: The value of concurrent chemoradiotherapy (CRT) for treatment of locally advanced non-small cell lung cancer (NSCLC) in elderly and multimorbid patients is generally disputed due to the assumed lack of toxicity compensation or the limited prognosis of the accompanying morbidity. AIM: We investigated correlation between impaired organ function, age, tumor-associated symptoms, social factors and acute toxicity as well as survival following CRT. PATIENTS AND METHODS: Retrospective data collection and analysis were performed on the variables age, functional parameters: FEV1, VC, DLCO, LVEF, creatinine clearance, age, several categories of comorbidities, WHO performance status, alcohol and nicotine habits, toxicity according CTC-criteria and survival of all patients (n=66) with inoperable NSCLC suffering substantial comorbidities or advanced age (>70 years) treated with an CRT consisting of two cycles cisplatin or carboplatin plus vinorelbine and a conventionally fractionated radiotherapy up to 63Gy. RESULTS: Median survival of all patients was 13 months (10.6-15.4 months, 95% confidence interval). Univariate analyses showed significantly poorer survival (12 months vs. 15 months) in patients with LVEF<50% compared with LVEF> or = 50% (P=0.022, in log-rank test). All other variables did not exhibit any significant correlation to survival. Multivariate analyses revealed significantly inferior survival in patients suffering from cardiac or pulmonary dysfunction (P=0.039, hazard ratio [HR]: 2.18; 95% CI of HR [1.04-4.59]). Elderly patients (>70 years) had a higher prevalence of hematotoxicity of higher degree than younger patients (< or = 70 years), but without significant impact on the feasibility of both treatment modalities. CONCLUSION: Our results suggest that cardiac and pulmonary dysfunction may be associated with a reduced survival in elderly or poor-risk patients with inoperable NSCLC after CRT.     

Intraoperative radiotherapy vs concurrent chemoradiotherapy in the treatment of patients with locally advanced pancreatic cancer

PurposeThe purpose of the multi-institutional retrospective study was to evaluate whether intraoperative radiotherapy (IORT) has advantages in the treatment of patients with locally advanced pancreatic cancer (LAPC) compared with concurrent chemoradiotherapy (CCRT).Patients and methodsA total of 103 patients with LAPC whom was treated with IORT (Arm A; n = 50) or CCRT (Arm B; n = 53) from 2015.6 to 2016.7 were retrospectively identified. Data on feasibility, toxicity, and overall survival (OS) were evaluated.ResultsMost factors of the two cohorts were similar. The severe adverse events (grade 3 and 4) patients in Arm B were higher than patients in Arm A (34% vs 0%). Disease progression was noted in 38 patients (76%) in Arm A and 37 patients (69.8%) in Arm B. The median survival of patients in Arm A and B were 15.3 months (95% CI, 13.0–17.6 months) and 13.8 months (95% CI, 11.0–16.6 months), respectively. The 1-year survival rate were 66.3% in Arm A (95% CI, 52.3%–80.2%) and 60.9% in Arm B (95% CI, 46.4%–75.4%). There was no significant difference in OS between patients treated with IORT and with CCRT (p = 0.458).ConclusionOur results demonstrated that patients with LAPC treated with IORT showed fewer adverse events, less treatment time, and high feasibility compared to CCRT. Although, IORT has no advantages in survival and tumor control compared with CCRT.     

Impact of preoperative chemoradiotherapy on survival in patients with resectable pancreatic cancer

AIM:To explore whether preoperative chemoradiation therapy improves survival of patients with pancreatic cancer undergoing resectional surgery. METHODS:Forty-seven patients with a malignant pancreatic tumor localized in the head or uncinate process of the pancreas underwent radical pancreaticoduodenectomy. Twenty-two received chemoradiation therapy (gemcitabine and radiation dose 50.4 Gy) before surgery (CRR) and 25 patients underwent surgery only (RO). The study was non-randomised. Patients were identified from a prospective database. RESULTS:The median survival time was 30.2 mo in the CRR group and 35.9 mo in the RO group. No statistically significant differences were found in subclasses according to lymph node involvement,TNM stages,tumor size,or perineural invasion. The one,three and five year survival rates were 81%,33% and 33%,respectively,in the CRR group and 72%,47% and 23%,respectively,in the RO group. In ductal adenocarcinoma,the median survival time was 27 mo in the CRR group and 20 mo in the RO group. No statistically significant differences were found in the above subclasses. The one,three and five year survival rates were 79%,21% and 21%,respectively,in the CRR group and 64%,50% and 14%,respectively,in the RO group. The overall hospital mortality rate was 2%. The morbidity rate was 45% in the CRR group and 32% (NS) in the RO group. CONCLUSION:Major multicenter randomized studies are needed to conclusively assess the impact of neoadjuvant treatment in the management of pancreatic cancer.     

Modeling the risk of radiation pneumonitis in esophageal squamous cell carcinoma treated with definitive chemoradiotherapy

Esophagus - To develop and validate a nomogram for the prediction of symptomatic radiation pneumonitis (RP) in patients with esophageal squamous cell carcinoma (ESCC) who received definitive...     

Resection surgery with neoadjuvant chemoradiotherapy improves outcomes of patients with T4 esophageal carcinoma

The prognosis of patients with T4 esophageal carcinoma is poor, and thus an effective treatment needs to be established. The present study assessed the effect of chemoradiotherapy (CRT), postoperative morbidity and mortality, and survival time in 41 patients with T4 esophageal carcinoma. Of these, 24 received CRT followed by surgery (group A) and the remaining 17 were treated with CRT alone (group B). Postoperative complications in group A were compared with 251 patients (group C) who underwent surgery without CRT during the same period. Postoperative complications were more frequent in group A than group C (29.2% vs 8.4%, P < 0.05). The overall median survival of group A was statistically longer than that of group B (13.8 months and 3.3 months respectively, P < 0.001). Complete histologic response (grade 3) was documented in 4 group A patients (16.7%). The overall median survival of grade 3 patients was statistically longer than the rest of group A (38.9 months vs 8.8 months, P < 0.05). The data confirm that chemoradiotherapy creates tumor regression in some patients and allows resection surgery in T4 esophageal carcinoma. Moreover, surgery with CRT confers a survival advantage in T4 esophageal carcinoma.     

Obesity and outcomes in patients treated with chemoradiotherapy for esophageal carcinoma

Body mass index (BMI) is a risk factor for comorbid illnesses and cancer development. It was hypothesized that obesity status affects disease outcomes and treatment‐related toxicities in esophageal cancer patients treated with chemoradiotherapy (CRT). From March 2002 to April 2010, 405 patients with non‐metastatic esophageal carcinoma at MD Anderson Cancer Center treated with either definitive or neoadjuvant CRT were retrospectively analyzed. Patients were categorized as either obese (BMI ≥ 25 kg/m²) or nonobese (BMI < 25 kg/m²). Progression‐free survival and overall survival times were examined using the Kaplan–Meier method and Cox proportional hazards regression analysis. One hundred fifteen (28.4%) patients were classified as nonobese and 290 (71.6%) as obese. Obese patients were more likely than others to have several comorbid diseases (P < 0.001), adenocarcinoma located distally (P < 0.001), and have undergone surgery (P = 0.004). Obesity was not associated with either worse operative morbidity/mortality (P > 0.05) or worse positron emission tomography tumor response (P = 0.46) on univariate analysis, nor with worse pathologic complete response (P = 0.98) on multivariate analysis. There was also no difference in overall survival, locoregional control, or metastasis‐free survival between obese and nonobese patients (P = 0.86). However, higher BMI was associated with reduced risk of chemoradiation‐induced high‐grade esophagitis (P = 0.021), esophageal stricture (P < 0.001), and high‐grade hematologic toxicity (P < 0.001). In esophageal cancer patients treated with CRT, obesity is not predictive of poorer disease outcomes or operative morbidities; instead, data suggest it may be associated with decreased risk of acute chemotherapy‐ and radiotherapy‐related treatment toxicities.     

Rectal cancer: Neoadjuvant chemoradiotherapy

The monolithic approach to apply the same schedule of preoperative 5-fluorouracil (5-FU)- or capecitabine-based chemoradiotherapy (CRT) to all patients with clinically staged TNM stage II/III rectal cancer need to be questioned. Five randomized trials have been completed to determine if the addition of oxaliplatin to preoperative 5-FU/capecitabine-based CRT offers an advantage compared with single-agent CRT. In contrast to the German CAO/ARO/AIO-04 trial, results from the ACCORD 12, STAR-01, PETACC-6 and NSAPB R-04 trials failed to demonstrate a significant improvement of early or late efficacy endpoints with the addition of oxaliplatin. Most of the phase II trials incorporating cetuximab into CRT reported disappointingly low rates of pCR; the combination of CRT with VEGF inhibition showed encouraging pCR rates but at the cost of increased surgical complications. Novel clinical trials currently address (1) the role of induction and consolidation chemotherapy before or after CRT, (2) minimal or omitted surgery following complete response to CRT, or (3) the omission of radiotherapy for selected patients with response to neoadjuvant chemotherapy. The notion of different multimodal treatment concepts according to tumor stage, location, mesorectal fascia margin status, molecular profiles, tumor response, and patients' preferences becomes increasingly popular and will render the multimodal treatment approach of rectal cancer more risk-adapted.