A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer

Urschel, John D.; Vasan, Hari

doi:10.1016/s0002-9610(03)00066-7

Cited by 603 publications

(372 citation statements)

References 29 publications

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“…Preoperative RT has the theoretical advantages of tumor downstaging and smaller treatment volumes. 5 In the current study, it was not possible to ascertain whether the survival benefits observed with preoperative RT were attributable to tumor downstaging because the tumor staging information in the SEER database reported only pathologic staging data. Because preoperative treatment fields in patients with esophageal cancer (5 cm superiorly and inferiorly from macroscopic tumor disease) are classically smaller than postoperative treatment fields (coverage of the entire postoperative esophagectomy surgical bed), 20 they should result in less radiation dose to the heart and lungs (Fig.…”

Section: Discussionmentioning

confidence: 90%

“…However, the sensitivity analysis as performed in the current study suggests that the survival advantages of preoperative RT remained clinically Second, an important caveat of the current study is that the SEER database does not provide data regarding chemotherapy. However, both preoperative and postoperative RT are almost always administered concurrently with chemotherapy, [1][2][3][4][5]7,26,28 and therefore it is less likely that the lack of chemotherapy data is a source of bias in the concurrent setting. In addition, chemotherapy itself can be a possible cause of cardiopulmonary mortality.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6] In the subset of patients with tumors of the gastroesophageal junction, CRT delivered postoperatively has also demonstrated a survival benefit. 7 To the best of our knowledge, no randomized controlled trials currently exist that compare the outcomes of the sequencing of CRT in relation to surgery in patients with esophageal cancer.…”

Section: Introductionmentioning

confidence: 99%

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The impact of radiation therapy sequencing on survival and cardiopulmonary mortality in the combined modality treatment of patients with esophageal cancer

Wojcieszynski

Berman²,

Wan³

et al. 2013

Cancer

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BACKGROUND: The addition of chemoradiation (CRT) to surgery has been shown to improve survival in patients with esophageal cancer. In the current study, the authors determined whether the sequencing of CRT has an effect on survival and cardiopulmonary mortality in patients with esophageal cancer. METHODS: Patients with the following inclusion criteria were identified within 17 Surveillance, Epidemiology, and End Results registries from 1988 through 2007: adenocarcinoma or squamous cell carcinoma of the esophagus and having undergone esophagectomy. Patients who died within 90 days of surgery were excluded. Demographic, tumor, and survival data were compared between patients receiving preoperative and postoperative RT. Cox proportional hazards regression models were calculated to identify parameters associated with cause-specific survival and overall survival. A competing risk analysis was performed to account for death due to esophageal cancer in the calculation of cardiopulmonary mortality. RESULTS: Of 5512 patients, 1881 received preoperative RT, 901 received postoperative RT, and 2730 did not receive RT. Patients receiving preoperative RT had improved 5-year cause-specific survival (41% vs 31%; P < .0001) and overall survival (33% vs 23%; P < .0001) compared with those receiving postoperative RT. No differences in adjusted cardiopulmonary mortality were found between patients who received RT versus those who did not (8% vs 10% at 10 years; hazards ratio [HR] KEYWORDS: esophageal neoplasms, combined modality therapy, radiation oncology, survival, heart diseases, lung diseases. INTRODUCTIONIn patients with locally advanced esophageal cancer, the addition of chemoradiation (CRT) to surgery has shown improvements in overall survival (OS) when given preoperatively. [1][2][3][4][5][6] In the subset of patients with tumors of the gastroesophageal junction, CRT delivered postoperatively has also demonstrated a survival benefit. 7 To the best of our knowledge, no randomized controlled trials currently exist that compare the outcomes of the sequencing of CRT in relation to surgery in patients with esophageal cancer.Preoperative CRT is preferred over postoperative treatment in patients with other gastrointestinal malignancies such as rectal cancer, in whom preoperative CRT has been demonstrated to have a superior locoregional control rate, toxicity profile, and survival rate. 8,9 It is postulated that preoperative treatment is favored because of tumor downstaging and smaller radiation treatment fields. We hypothesized that preoperative RT is associated with decreased cardiopulmonary mortality from lower RT doses to the heart and lungs as well as improved survival outcomes compared with postoperative RT in patients with esophageal cancer.Using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, we assessed differences in survival outcomes between patients treated with preoperative RT and those treated with postoperative RT and analyzed the effect of RT on heart and lung morbidity a...

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The impact of radiation therapy sequencing on survival and cardiopulmonary mortality in the combined modality treatment of patients with esophageal cancer

Wojcieszynski

Berman²,

Wan³

et al. 2013

Cancer

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“…However, when applied to patients with very early disease, the latest chemotherapy regimes offer excellent results, and 5-year survival for T1 -2N0 disease is now greater than 80% (Urschel and Vasan, 2003). Therefore, at present, the key to successful treatment of oesophageal cancer is early diagnosis and there is consequently great interest in the development of a screening test that will identify patients with asymptomatic oesophageal malignant or premalignant disease.…”

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confidence: 99%

Diagnosis of oesophageal cancer by detection of minichromosome maintenance 5 protein in gastric aspirates

et al. 2004

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Symptomatic oesophageal cancer is usually advanced and the prognosis poor. Lethality of symptomatic oesophageal cancer has motivated screening for these diseases earlier in their evolution, but reliable methods for early diagnosis remain elusive. We have demonstrated that dysregulated expression of minichromosome maintenance (MCM) proteins 2 -7 is characteristic of early epithelial carcinogenesis, and that these key DNA replication initiation factors can be used as diagnostic markers for cervical and genito-urinary tract cancer. In this study, we investigated whether minichromosome maintenance protein 5 (Mcm5) can be used to detect oesophageal cancer cells in gastric aspirates. Two monoclonal antibodies raised against His-tagged human Mcm5 were used in a timeresolved immunofluorometric assay to measure Mcm5 levels in cells isolated from gastric aspirates of 40 patients undergoing gastroscopy for suspected or known oesophageal carcinoma or symptoms of dyspepsia. The test discriminated with high specificity and sensitivity between patients with and without oesophageal cancer (85% sensitivity (95% confidence interval (CI) ¼ 62 -97%), 85% specificity (CI ¼ 66 -96%)), as demonstrated by the large area under the receiver operating characteristics curve (0.93 (95% CI ¼ 0.85 -0.99)). Elevated levels of Mcm5 in gastric aspirates are highly predictive of oesophageal cancer. This simple test for oesophageal cancer is readily automated with potential applications in primary diagnosis, surveillance and screening.

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“…In the Fig. 1 Comparison of OS and DFS in group A and B meta-analysis by Florica et al [13], increase in survival was offset by double postoperative mortality while Urshel and Vasant [14] suggested an increase in mortality, with benefit of preoperative therapy seen only after 3 years of treatment. In a study by Bossetet al [15] there was improvement in disease free survival with induction therapy in stage I and II, but low overall survival due to increase in postoperative mortality from 3.6 to 12.3 %.…”

Section: Discussionmentioning

confidence: 98%

Radical Esophagectomy After Neoadjuvant Chemoradiation: Single Institutional Experience from Tertiary Cancer Centre in India

Goel

Shah

Selvakumar

et al. 2015

Indian J Surg Oncol

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Although preoperative chemoradiation has shown to improve surgical outcomes in both loco-regional control and long term survival; it has still not become the standard of care in many centers. There is reluctance in accepting preoperative chemoradiation primarily due to fear of increased perioperative morbidity/mortality or non-availability of infrastructure and expertise. We present a retrospective analysis of our results of radical esophagectomy after neoadjuvant chemoradiation. All patients who underwent Radical Esophagectomy from January 2009 to December 2013 by a single surgical team at our institute were included in the series (n=118). Patients undergoing surgery after chemo-radiation (group A= 66) were compared with those under going upfront surgery (group B=52) in terms of patient variables (age, sex, comorbidities, tumor location, staging, histology) and postoperative surgical outcomes and complications using Chi square test. Overall and disease free survival was analyzed using Kaplan Meir curve. There was no difference in duration of surgery, postoperative stay and overall morbidity and mortality in both groups. Although group A patients had more of advanced cases clinically, but histopathology showed complete pathological response (pCR) in nearly 40 % patients and negative nodes (pN0) in 62.5 % patients. OS and DFS showed a trend towards better survival with preoperative chemoradiation. We conclude that radical esophagectomy after preoperative chemoradiation is feasible and safe in developing countries. Moreover pathological complete response correlates well with improved survival. Randomized control trials may be required to further substantiate the results.

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A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer

Cited by 603 publications

References 29 publications

The impact of radiation therapy sequencing on survival and cardiopulmonary mortality in the combined modality treatment of patients with esophageal cancer

The impact of radiation therapy sequencing on survival and cardiopulmonary mortality in the combined modality treatment of patients with esophageal cancer

Diagnosis of oesophageal cancer by detection of minichromosome maintenance 5 protein in gastric aspirates

Radical Esophagectomy After Neoadjuvant Chemoradiation: Single Institutional Experience from Tertiary Cancer Centre in India

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