Salvage surgery after failed chemoradiotherapy in squamous cell carcinoma of the esophagus

Aims

To investigate the survival benefit and preoperative risk factors for hospital mortality of salvage surgery in esophageal cancer patients who had locoregional residual/recurrent tumor after definitive chemoradiotherapy.

Methods

We retrospectively reviewed the esophageal cancer patients who presented at our hospital from 1997 to 2004. Forty-seven patients who had squamous cell cancer and developed locoregional recurrent/persistent disease after primary definitive chemoradiotherapy were elected. Twenty-seven of them received salvage esophagectomy (group 1) and the other 20 underwent non-operative treatment only (group 2). In order to assess the surgery-related mobility and mortality in group 1, 191 patients who received neoadjuvant chemoradiotherapy followed by operation during the same time period were also enrolled (group 3).

Results

The 5-year overall survival of group 1 patients was 25.4%. In contrast, all of the patients in the group 2 died within 16.7 months. The difference was statistically significant (p = 0.0029). In comparison with group 3, group 1 patients had significantly more surgery-related complications and hospital mortality. In univariate analysis for preoperative risk factors, a low albumin or hemoglobulin level was associated with high hospital mortality in group 1 (p = 0.004 and 0.003, respectively). After multivariate analysis, only the low albumin level remained borderline significance. As for disease specific survival after salvage surgery, R0 resection was the only independent prognosticator (p = 0.049).

Conclusion

Salvage surgery provides survival benefit in esophageal cancer patients with locoregional persistent or recurrent disease after primary definitive chemoradiotherapy. Preoperative albumin and hemoglobulin levels are associated with hospital mortality and may aid in selecting suitable patient for salvage surgery.     

Overall survival analysis of neoadjuvant chemoradiotherapy and esophagectomy for esophageal cancer

Background

Patients treated with neoadjuvant chemoradiotherapy (NAC) followed by esophagectomy are more likely to have negative margins at resection, be downstaged, and have improved overall survival (OS). The specific aim of this study was to analyze OS outcomes using NAC followed by esophagectomy at a single, tertiary care academic medical center.

Methods

We retrospectively analyzed 106 patients that underwent NAC with platinum-based chemotherapy plus 5-fluorouracil (5-FU) or capecitabine followed by esophagectomy from September 1996 to May 2011. OS was analyzed by the Kaplan Meier method.

Results

Initial staging determined that of 106 patients, 62% had stage III (n=66), 31% stage II (n=33), and 7% had stage I disease (n=7). Following NAC, 92.5% (n=98) were resected with negative (R0) margins and pathologic staging revealed 59% (n=62) were downstaged, 9% (n=10) were upstaged, and 32% (n=34) remained at the same stage. A pathologic complete response (pCR) was achieved in 29% (n=31) of the cohort. Median OS was 35.2 months for all patients, 42 months for downstaged patients, 13 months when upstaged, and 17 months for those who remained at the same stage (P=0.08). OS by histological type was 30 months for adenocarcinoma and 71 months for squamous cell carcinoma (P=0.06).

Conclusions

NAC was effective in downstaging 59% of patients and effectively increased the chance for an R0 resection. These patients, in turn, had improved OS compared to the median OS. Patients with squamous cell carcinoma showed a trend towards more favorable OS.     

食管鳞癌全量放化疗后复发补救手术患者的生存期分析

目的　评价食管鳞癌全量放化疗后复发补救性食管切除手术的临床价值及安全性,并分析影响预后的因素。方法　收集５８例食管鳞癌根治性放化疗后复发补救性食管切除手术患者的临床资料,回顾性分析手术方式、术后并发症、术后ｐＴＮＭ分期等参数对预后的影响。结果　５８例患者均予右胸入路,经后纵隔食管床胃代食管重建消化道,行颈胸腹三切口颈部吻合术式４３例,胸腹二切口胸内吻合１５例。Ｒ０切除５０例,Ｒ１切除８例。术后并发症发生率和住院死亡率分别为２２.４％和３.４％。术后中位总生存期为５９.９个月,５年生存率为４９.３％。单因素及多因素分析显示,术后ｐＴ、ｐＮ分期为影响术后远期生存的危险因素。结论　食管鳞癌全量放化疗后复发予以补救性食管切除手术的风险较高,但可延长生存。术后ｐＴ分期、ｐＮ分期可以为术后的生存预测提供参考。     

食管癌放化疗后复发再程放疗的Meta分析

目的 Meta分析食管癌放化疗后复发再程放疗与其他疗法疗效和不良反应。方法 通过计算机检索PubMed、Embase、Cochrane Library、CNKI、万方等数据库,搜集有关食管癌放化疗后复发再程放疗与其他治疗方法比较的临床对照研究。检索时间为建库至 2020年4月。采用RevMan 5.1软件进行分析,组间差异采用RR及 95%CI描述。结果 根据纳入排除标准最终纳入11篇文献,包括 842例患者。Meta分析结果显示再程放疗组与手术组相比总生存率略低(RR=0.40,95%CI为 0.27~0.61,P<0.001),与单纯化疗组相比则得到了提高(RR=2.91,95%CI为 1.43~5.95,P=0.003)。再程放疗组与手术组治疗相关死亡率相近(RR=0.53,95%CI为 0.14~1.98,P=0.350),但手术组发生率较高(1.7%~11.4%∶1.9%~2.8%)。结论 再程放疗是放化疗后复发食管癌的有效治疗手段,可作为临床患者的选择方案。     

The role of adjuvant chemotherapy after neoadjuvant chemotherapy or chemoradiotherapy plus esophagectomy in patients with esophageal cancer: a retrospective cohort study

BackgroundThe 5-year survival rate of patients with locally advanced esophageal cancer is still low after neoadjuvant therapy plus esophagectomy, and additional adjuvant treatment may be required. Some studies have shown that patients can still benefit from adjuvant chemotherapy (AC) despite its toxic and side effects. This study was designed to explore which patients could benefit from AC.MethodsA retrospective cohort study based on patients who received neoadjuvant therapy plus esophagectomy with complete survival information between December 2014 and November 2020 was conducted. The inclusion criteria were as follows: esophageal cancer was diagnosed by pathological biopsy; neoadjuvant chemotherapy; neoadjuvant chemoradiotherapy; R0 resection. The exclusion criteria were as follows: neoadjuvant chemotherapy combined with targeted therapy or immunotherapy; adjuvant radiotherapy, adjuvant chemoradiotherapy, immunotherapy, or targeted therapy; dead within 90 days of surgery; nonradical (R1/R2) resection; one cycle of postoperative chemotherapy. Patients were divided into AC group (AC) and non-AC group [AC(−)] according to whether AC was performed. We obtained the tumor recurrence and survival status of the patients through inpatient medical records, outpatient electronic medical records, and telephone follow-up of the First Affiliated Hospital of Zhengzhou University. Overall survival (OS) and recurrence-free survival (RFS) were investigated as the outcome measures via Kaplan-Meier curves and Cox analyses.ResultsIn total, 318 patients were enrolled, among which 214 patients received AC while the other 104 patients did not [AC(−)]. There were significant differences in age and lymph nodes dissected between patients who received AC and those who did not receive AC (P<0.05). Survival curves were plotted using the Kaplan-Meier method, and in the overall group and subgroup, AC was beneficial for OS but not for RFS. In the overall group, sex (P=0.027) and age (P=0.027) were independent prognostic factors for OS. Subgroup multivariate Cox proportional hazards analysis showed that age (P=0.026) and AC (P=0.023) were independent prognostic factors for patients.ConclusionsFor patients with locally advanced esophageal cancer who have residual disease after surgery, adjuvant therapy after neoadjuvant chemoradiotherapy and surgery may be a better treatment.     

食管癌同步放化疗的疗效及预后因素分析

目的 探讨食管癌同步放化疗的疗效及影响预后的因素。方法 2008—2015年符合入组条件的食管鳞癌患者135例。采用2DRT (56例)或3DRT (79例)技术60~64 Gy (1.8~2.0 Gy/次),同步化疗采用氟尿嘧啶+顺铂或紫杉醇+顺铂方案,分别在放疗的第1、5周给予。采用Kaplan-Meier法计算OS、PFS率并Logrank检验及单因素分析,Cox模型行多因素分析。结果 1、3、5年样本数分别为96、31、16例,OS率分别为74.0%、39.0%、28.6%,中位OS期为25个月;PFS率分别为57.3%、27.3%、16.6%,中位PFS期为15个月。单因素分析结果显示临床分期、放疗方式、M分期是影响OS和PFS的因素(P=0.006、0.000、0.032和0.017、0.004、0.000)。多因素结果显示临床分期、放疗方式是影响OS和PFS的因素(P=0.006、0.000和0.033、0.023)。结论 对于非手术治疗的食管癌患者,根治性同步放化疗应作为首选治疗方案,疗效和耐受性可。     

同期放化疗对侵犯气管的局部晚期食管癌的疗效观察

目的　探讨同期放化疗对晚期食管癌侵及气管的临床疗效。方法　收集经病理检查确诊的１６８例食管癌侵及气管病例,其中７３例采取单纯放射治疗（单放组）,以６／１５ＭＶＸ线常规外照射,１.８Ｇｙ／次,５次／周,照射总剂量６１.２～６４.８Ｇｙ;９５例患者行化放疗治疗（化放组）,予顺铂（ＤＤＰ）联合氟尿嘧啶（５-ＦＵ）方案化疗（ＤＤＰ２０ｍｇｄ１～ｄ５,５-ＦＵ５００ｍｇ／ｍ２ｄ１～ｄ５）４个周期,２８天为１周期,于第２周期化疗开始时行同期放疗,放疗方案同单放组。观察两组的近期疗效、毒副反应和远期疗效。结果　化放组的有效率（ＲＲ）为６５.３％,高于单放组的４５.２％（Ｐ＝０.００９）;化放组较单放组ＫＰＳ评分提高更显著（Ｐ＝０.００４）。化放组的３年生存率为１７.９％,高于单放组的６.９％（Ｐ＝０.０３５）。两组主要毒副反应包括急性放射性食管炎、放射性气管炎和白细胞减少,化放组的白细胞减少发生率高于单放组（Ｐ＝０.０２２）。结论　同期放化疗对晚期食管癌侵及气管患者较单纯放射治疗的近期疗效好,明显改善患者的生活质量,生存时间延长,且相对安全。     

Frequency of surgical resection after starting neoadjuvant chemoradiotherapy in patients with esophageal cancer: A population-based cohort study

BackgroundNeoadjuvant chemoradiotherapy (nCRT) for resectable esophageal cancer is accompanied by the risk of treatment-related toxicity. The aim of this population-based cohort study was to provide insight in patients who do not proceed to surgical resection after starting nCRT.MethodsPatients who started nCRT for primary esophageal cancer diagnosed in 2015 and 2016 were selected from the nationwide population-based cancer registry. Outcome measurements included omission from surgical resection, reasons for omission of surgical resection, mortality during nCRT (≤90 days after ending nCRT) and 1-year overall survival. Multivariable logistic regression analyses were performed to identify predictive factors for omission of surgical resection.ResultsA total of 1521 patients were included, of whom 215 (14.1%) did not undergo surgical resection after starting nCRT. Age (OR:1.04, 95%CI:1.01–1.06), BMI (OR:0.95, 95%CI:0.90–0.99), WHO performance status (WHO 1: OR:1.62, 95%CI:1.16–2.62 and WHO 2: OR:3.53, 95%CI:1.68–7.41) and clinical N status (cN2: OR:1.57, 95% CI:1.04–2.37 and cN3: OR:2.52, 95%CI:1.14–5.55) were significantly associated with omission from surgery. The most frequently reported reasons for omission from surgery were disease progression (44.3%) and physical functioning (22.8%). During nCRT or within the subsequent waiting period to surgery, 38 patients (2.5%) deceased. One year overall survival of the patients who underwent nCRT followed by surgical resection was 94.9%, and 73.5% in the patients who did not undergo surgical resection following nCRT.ConclusionsOne in 7 patients who started nCRT for esophageal cancer do not proceed to surgical resection and have a decreased one year overall survival compared to patients who do proceed to surgical resection. Mortality during nCRT is considerable.     

Photodynamic therapy as salvage treatment for local failure after chemoradiotherapy in patients with esophageal squamous cell carcinoma: a phase II study

Local failure at the primary site is a major problem after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC). Salvage surgery is the only treatment option with curative intent, but it is associated with high morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of salvage photodynamic therapy (PDT) after CRT. Patients with histologically proven local failure limited to the submucosal layer, and without any metastasis after definitive CRT (≥50 Gy) for ESCC were enrolled in the study. PDT began with intravenous administration of 2 mg/kg of porfimer sodium followed 48-72 hr later by excimer dye laser irradiation with a fluence of 75 J/cm2. The primary endpoint was a complete response (CR) to treatment with PDT, and the secondary endpoints were toxicity related to PDT, progression-free survival (PFS) and overall survival (OS). Twenty-five patients were enrolled in the study. A CR was attained in 19 of 25 patients treated with PDT (CR rate, 76%; 95% CI, 55-91%). One treatment-related death (4%) caused by gastrointestinal hemorrhage at the irradiated site occurred 33 days after PDT. No adverse events greater than grade 3 were related to PDT in the other patients. After a median follow-up of 48 months after PDT, the PFS and OS at 3 years were 40% (95% CI, 21-59%) and 38% (95% CI, 17-60%), respectively. PDT is a potentially curative and tolerable salvage treatment after CRT for carefully selected patients with local failure without any metastasis.     

Factors affecting the prognosis of patients with esophageal cancer undergoing salvage surgery after definitive chemoradiotherapy

BACKGROUND AND OBJECTIVES: Although salvage surgery after definitive chemoradiotherapy (CRT) is common, the safety and indication has not yet been established. METHODS: We retrospectively compared the mortality and morbidity of 24 patients who underwent salvage surgery with those of historical controls treated with neoadjuvant CRT followed by planned esophagectomy during the same period, and analyzed the prognostic factor of salvage surgery. RESULTS: Preoperative serum albumin (3.7 vs. 4.1 g/dl, P = 0.0157) and lymphocyte count (763 vs. 964/mm(3), P = 0.0111) in the salvage group were significantly lower than those in the neoadjuvant group. A significant difference was also observed in operation time (567 vs. 474 min, P = 0.0381), C-reactive protein (CRP) on postoperative day 1 (11.2 vs. 8.7 mg/dl, P = 0.0021), and postoperative systemic inflammatory response syndrome (SIRS) duration (3.5 vs. 2.9 days, P = 0.0486). There were three hospital deaths in the salvage group, whereas no patient died in the neoadjuvant group. Multivariate analysis showed curability (R0 vs. R1 + R2) to be the strongest prognostic factor of salvage surgery (P = 0.0064). R1 + R2 operation was more frequently performed in the salvage group (33% vs. 13%), and the reason for all cases was unresectable T4, which had been underestimated preoperatively. CONCLUSIONS: Salvage surgery is a highly invasive and morbid operation, which is performed on immunocompromised hosts. The indication must be carefully considered, with care taken to avoid non-curative surgery.     

同步放化疗治疗不能手术的食管癌疗效分析

目的 :不能手术的食管癌同步放化疗的疗效观察。方法 :88例食管癌患者根据入选标准随机分组 ,4 3例进入化疗 +放射治疗组 (放化组 ) ,4 5例进入单纯放射治疗组 (单放组 )。放化组 :化疗为DF方案 ,即 5 Fu 5 0 0mg/m2 d1～d4 ,DDP2 0mg/m2 d1 d4 ;放射治疗从第 1天即开始 ,6MV x射线照射 ,三野等中心照射DT 6 0GY 6 5GY/30 33Fr/6 6 5W。单放组 :放射治疗方案同综合组。结果 :放化组的 12个月、2 4个月生存率分别为 76 7%、5 8 1% ,单放组的 12个月、2 4个月生存率分别为 6 6 7%、4 2 2 % ,但二组间的生存率统计学上未显示出统计学差异 (χ2 =2 2 7,P =0 132 )。放化组的 2年远处转移发生率为 16 3% ,低于单放组的 2 8 9% (P <0 0 5 )。放化组的毒性反应大于单放组 ,但患者均能耐受。结论 :以DF方案化疗配合放射治疗不能手术的食管癌降低了远处转移发生率 ,同时有提高远期生存率的可能性 ,虽毒性反应增加 ,但患者均能耐受 ,有进一步研究的价值     

Wait-and-see or radical surgery for rectal cancer patients with a clinical complete response after neoadjuvant chemoradiotherapy: a cohort study

A wait-and-see policy might be considered instead of surgery for rectal cancer patients with no residual tumor or involved lymph nodes on imaging or endoscopy after neoadjuvant chemoradiotherapy (clinical complete response, cCR). In this cohort study, we compared the oncologic outcomes of rectal cancer patients with a cCR who were managed according to a wait-and-see policy (observation group) or with surgery (surgery group). In the observation group, follow-up was performed every 3 months for the first year and consisted of MRI, endoscopy with biopsy, computed tomography and transrectal ultrasonography. In the surgery group, patients received radical surgery. Long-term oncologic outcomes were estimated using Kaplan-Meier curves. Thirty patients were enrolled in the observation group (median follow-up, 60 months; range, 18-100 months), and 92 patients were enrolled in the surgery group (median follow-up, 58 months; range, 18-109 months). The 5-year disease free survival and overall survival rates were similar in the two groups: 90.0% vs. 94.3% (P = 0.932) and 100.0% vs. 95.6% (P = 0.912), respectively. We conclude that for rectal cancer patients with a cCR after neoadjuvant chemoradiotherapy, a wait-and-see policy with strict selection criteria, follow-up and salvage treatments achieves outcomes at least as good as radical surgery. Additionally, we declare that the pCR (pathologic complete regression) and non-pCR subgroups of patients with a cCR have similar long-term failure (local recurrence and/or distant metastasis) rate.     

Management and outcomes of anastomotic leakage after McKeown esophagectomy: A retrospective analysis of 749 consecutive patients with esophageal cancer

PurposeCervical anastomotic leakages may manifest either cervically or intrathoracically. We retrospectively investigated the management strategies and clinical outcomes of patients who developed anastomotic leakages after McKeown esophagectomy and the spectrum of its clinical manifestations.MethodsPatients with esophageal cancer who underwent McKeown esophagectomy with cervical anastomosis (n = 749) between January 2015 and December 2018 were included.ResultsCervical anastomosis leakage was diagnosed in 53/749 (7.3%) patients. The leakage was primarily limited to cervical region in 16 (30.2%) patients, whereas intrathoracic spread was present in 37 (69.8%) patients. Intrathoracic manifestations were more commonly accompanied by fever (75.7% vs. 18.8%, P < 0.001) and leukocytosis than cervical manifestations (81.1% vs. 25.0%, P < 0.001). Compared to patients with cervical manifestations, those with intrathoracic manifestations had a longer duration of hospital stay (median; 58 vs. 40 days, P = 0.006) and higher incidence of tracheal fistula (21.6% vs. 0%, P = 0.045). Drainage through the neck wound was effective in all patients with cervical manifestations. Patients with intrathoracic manifestations who had transnasal inner drain or mediastinal drain placed intraoperatively achieved satisfactory drainage (27/37, 73.0%). Subsequent healing of anastomotic leaks was observed in 50 (94.3%) patients. There was no mortality associated with complications related to anastomotic leakage.ConclusionIntrathoracic manifestations of cervical anastomotic leakage are common in patients after McKeown esophagectomy. However, they are diagnosed later and are associated with more severe clinical consequences than cervical manifestations. Thus, a high index of suspicion and an early intervention policy for such anastomotic leaks should be adopted and strengthened to decrease the incidence of adverse clinical outcomes.     

Impact of curative treatment on the physical fitness of patients with esophageal cancer: A systematic review and meta-analysis

BackgroundEsophageal cancer and curative treatment have a significant impact on the physical fitness of patients. Knowledge about the course of physical fitness during neoadjuvant therapy and esophagectomy is helpful to determine the needs for interventions during and after curative treatment. This study aims to review the current evidence on the impact of curative treatment on the physical fitness of patients with esophageal cancer.MethodsA systematic literature search of PubMed, Embase, Cinahl and the Cochrane Library was conducted up to March 29, 2021. We included observational studies investigating the change of physical fitness (including exercise capacity, muscle strength, physical activity and activities of daily living) from pre-to post-neoadjuvant therapy and/or from pre-to post-esophagectomy. Quality of the studies was assessed and a meta-analysis was performed using standardized mean differences.ResultsTwenty-seven articles were included. After neoadjuvant therapy, physical fitness decreased significantly. In the first three months after surgery, physical fitness was also significantly decreased compared to preoperative values. Subgroup analysis showed a restore in exercise capacity three months after surgery in patients who followed an exercise program. Six months after surgery, there was limited evidence that exercise capacity restored to preoperative values.ConclusionCurative treatment seems to result in a decrease of physical fitness in patients with esophageal cancer, up to three months postoperatively. Six months postoperatively, results were conflicting. In patients who followed a pre- or postoperative exercise program, the postoperative impact of curative treatment seems to be less.