Preface
Contributors
Site Wise Working Groups
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The
oesophagus is one of the common sites of malignancy in the gastro-intestinal
tract. World-over, the incidence of esophageal cancer, particularly
adenocarcinoma, is on the rise. In the US, the incidence has increased
five fold. At the Tata Memorial hospital, between 800 and 1000 patients
of cancer oesophagus are registered every year. Unlike in the west,
the majority of these are squamous carcinoma. The standard treatment
of operable oesophageal cancer in the absence of medical contraindications
is surgery. Radiation, chemo-radiation for definitive treatment
and combination of radiation and chemotherapy with surgery are other
treatment options. However, the overall survival continues to remain
far from satisfactory. The reported five year survival ranges from
5% to 30%.
N-stage (regional lymph nodes)
M-stage (distant metastases)
For tumours of mid thoracic oesophagus use only M1b, since these tumours with metastasis in non regional lymph nodes have an equally poor prognosis as those with metastasis in other distant sites. Stage Grouping
The
current staging system for esophageal cancer is most applicable
to patients with squamous cell carcinomas of the upper- and middle-thirds
of the oesophagus, as opposed to distal esophageal and gastroesophageal
junction adenocarcinomas. The present system of classifying coeliac
lymph node metastases as M1 seems to be unreasonable. The prognosis
of patients with positive abdominal lymph nodes is not the same
as with metastases to distant organs. Patients with regional and/or
celiac axis lymphadenopathy should not necessarily be considered
to have unresectable disease due to metastases. Complete resection
of the primary tumour and appropriate lymphadenectomy should be
attempted when possible.
Stage
0 (TisN0M0)
Dose
: 60 - 64.8Gy / 33 - 36 fractions, with reducing fields
When
feasible, external Radiotherapy can be combined with Intraluminal
radiotherapy (ILRT) as a boost. Concomitant chemo-radiation regimen
Principles of Chemotherapy
Palliative
treatment |
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| Management algorithm for Carcinoma Esophagus | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Workup
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Disseminated disease with good performance status
Poor performance status and / or nutritional status
Recurrent disease
Best supportive care
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| Ideal
Pathology Report Gross Description Measurement of length - The esophagus tends to contract after resection and may lose upto 25% if its length immediately after resection and upto 60% after fixation without being pinned out on a fixing board. Measurement of the main tumor and its location with respect to the gastro-esophageal junction. Macroscopic description - whether ulcerated growth, stricturous lesion, or polypoid tumor Microscopic features – Histological type of tumor. – Differentiation : well, moderate, poor. – Depth of invasion High grade dysplasia Invasion of lamina propria / submucosa Invasion of muscularis propria Invasion beyond muscularis propria Invasion of adjacent structures. Involvement of serosa – Margins Proximal - Normal, involved, dysplasia. Distal - Normal, involved, dysplasia. Circumferential margins >1mm - uninvolved. <1mm - involved. – Vascular invasion – Perineural invasion – Lymph nodes Number examined… Number positive (N1) – Distant metastasis Coeliac axis nodes, other distant metastases. Final diagnosis and pathological staging |
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| Extended
transthoracic resection compared with limited transhiatal resection
for adenocarcinoma of the esophagus. Hulscher JB, van Sandick JW, de Boer AG et al. N Engl J Med. 2002 Nov 21;347(21):1662-9. BACKGROUND : Controversy exists about the best surgical treatment for esophageal carcinoma. METHODS : We randomly assigned 220 patients with adenocarcinoma of the mid-to-distal esophagus or adenocarcinoma of the gastric cardia involving the distal esophagus either to transhiatal esophagectomy or to transthoracic esophagectomy with extended en bloc lymphadenectomy. Principal end points were overall survival and disease-free survival. Early morbidity and mortality, the number of quality-adjusted life-years gained, and cost effectiveness were also determined. RESULTS: A total of 106 patients were assigned to undergo transhiatal esophagectomy, and 114 to undergo transthoracic esophagectomy. Demographic characteristics and characteristics of the tumor were similar in the two groups. Perioperative morbidity was higher after transthoracic esophagectomy, but there was no significant difference in in-hospital mortality (P=0.45). After a median follow-up of 4.7 years, 142 patients had died—74 (70 percent) after transhiatal resection and 68 (60 percent) after transthoracic resection (P=0.12). Although the difference in survival was not statistically significant, there was a trend toward a survival benefit with the extended approach at five years: disease-free survival was 27 percent in the transhiatal-esophagectomy group, as compared with 39 percent in the transthoracic-esophagectomy group (95 percent confidence interval for the difference, -1 to 24 percent [the negative value indicates better survival with transhiatal resection]), whereas overall survival was 29 percent as compared with 39 percent (95 percent confidence interval for the difference, -3 to 23 percent). CONCLUSIONS : Transhiatal esophagectomy was associated with lower morbidity than transthoracic esophagectomy with extended en bloc lymphadenectomy. Although median overall, disease-free, and quality-adjusted survival did not differ statistically between the groups, there was a trend toward improved long-term survival at five years with the extended transthoracic approach. Transthoracic versus transhiatal esophagectomy : a prospective study of 945 patients. Rentz J, Bull D, Harpole D et al. J Thorac Cardiovasc Surg. 2003 May;125(5):1114-20. OBJECTIVE : Debate continues as to whether transhiatal esophagectomy results in lower morbidity and mortality than transthoracic esophagectomy. Most data addressing this issue are derived from single-institution studies. To investigate this question from a nationwide multicenter perspective, we used the Veterans Administration National Surgical Quality Improvement Program to prospectively analyze risk factors for morbidity and mortality in patients undergoing transthoracic esophagectomy or transhiatal esophagectomy from 1991 to 2000. METHODS : Univariate and multivariate analyses were performed on 945 patients (mean age, 63 +/- 10 years). There were 562 transthoracic esophagectomies and 383 transhiatal esophagectomies in 105 hospitals, with complete 30-day outcomes recorded. RESULTS : There were no differences in recorded preoperative variables between the groups that might bias any comparisons. Overall mortality was 10.0% (56/562) for transthoracic esophagectomy and 9.9% (38/383) for transhiatal esophagectomy (P =.983). Morbidity occurred in 47% (266/562) of patients after transthoracic esophagectomy and in 49% (188/383) of patients after transhiatal esophagectomy (P =.596). Risk factors for mortality common to both groups included a serum albumin value of less than 3.5 g/dL, age greater than 65 years, and blood transfusion of greater than 4 units (P <.05). When comparing transthoracic esophagectomy with transhiatal esophagectomy, there was no difference in the incidence of respiratory failure, renal failure, bleeding, infection, sepsis, anastomotic complications, or mediastinitis. Wound dehiscence occurred in 5% (18/383) of patients undergoing transhiatal esophagectomy and only 2% (12/562) of patients undergoing transthoracic esophagectomy (P =.036). CONCLUSIONS : These data demonstrate no significant differences in preoperative variables and postoperative mortality or morbidity between transthoracic esophagectomy and transhiatal esophagectomy on the basis of a 10-year, prospective, multi-institutional, nationwide study. Transthoracic versus transhiatal resection for carcinoma of the esophagus: a meta-analysis. Hulscher JB, Tijssen JG, Obertop H et al. Ann Thorac Surg. 2001 Jul;72(1):306-13 There is much controversy about the surgical approach to esophageal carcinoma: should an extensive resection be done to optimize long-term survival or should the extent of the operation be limited to obtain lower perioperative morbidity and mortality rates? We systematically reviewed the English-language literature published during the past decade, with emphasis on the differences between transthoracic and transhiatal resections regarding early morbidity, in-hospital mortality rates, and 3- and 5-year survival. Although transthoracic resections had significantly higher early (pulmonary) morbidity and mortality rates, 5-year survival was approximately 20% after both transthoracic and transhiatal resections. CARCINOMA OESOPHAGUS : EXTENT OF LYMPH NODE DISSECTION A prospective randomized trial of extended cervical and superior mediastinal lymphadenectomy for carcinoma of the thoracic esophagus. Nishihira T, Hirayama K, Mori S. Am J Surg. 1998 Jan;175(1):47-51 BACKGROUND : Recurrence of thoracic esophageal carcinoma in the cervical and superior mediastinal lymph nodes occurs frequently and contributes to a poor prognosis. Extensive lymphadenectomy has been advocated. Findings in support of this to date, however, have been based on a comparison with historical controls. We herein report a prospective randomized trial of extended and conventional lymphadenectomy. METHODS : Cases of thoracic esophageal carcinoma meeting criteria predictive of complete resection were randomized into conventional and extended cervical and superior mediastinal lymphadenectomy groups. RESULTS : In the extended and conventional lymphadenectomy groups, respectively, mean operative time was 487 +/- 47 and 396 +/- 43 minutes, blood loss was 850 +/- 429 and 576 +/- 261 mL, node count was 82 +/- 22 and 43 +/- 15, hospital deaths occurred in 3% and 7%, 2-year survival was 83.3% and 64.8%, 5-year survival was 66.2% and 48.0%, and recurrence rate was 19.9% and 24.1%. CONCLUSION : Extended lymphadenectomy may prevent recurrence and prolong survival after resection of thoracic esophageal carcinoma. Extended esophagectomy with 3-field lymph node dissection for esophageal cancer. Tachibana M, Kinugasa S, Yoshimura H et al. Arch Surg. 2003 Dec;138(12):1383-9; OBJECTIVE : To review the surgical outcomes of extended esophagectomy with 3-field lymph node dissection (3FLND) for esophageal cancer. DATA SOURCES : Only articles written in English and written after 1980 were selected from MEDLINE. The following terms were identified : 3FLND, extensive or extended lymph node dissection (lymphadenectomy), radical lymph node dissection, cervical lymph node dissection, and extended or radical esophagectomy in esophageal cancer. STUDY SELECTION : There were no exclusion criteria for published information relevant to the topic. The most representative articles were selected when there were several articles from the same institution. Case reports were excluded. DATA EXTRACTION : Twenty-six articles were finally collected from MEDLINE. Eleven articles were also selected from reference lists of the pertinent literature. DATA SYNTHESIS : The collected information was organized. CONCLUSIONS : The conclusions drawn from those articles showed that extended esophagectomy with 3FLND would be a safe procedure in experienced hands, with low morbidity and acceptable mortality rates. When strict patient selection criteria were maintained, this procedure reduced locoregional recurrence and improved long-term survival rates. Although the therapeutic value of 3FLND is unproved in a randomized trial, extended esophagectomy with 3FLND would be the treatment of choice in selected patients. Optimal lymphadenectomy for squamous cell carcinoma in the thoracic esophagus : comparing the short-and long-term outcome among the four types of lymphadenectomy. Fujita H, Sueyoshi S, Tanaka T et al. World J Surg. 2003 May;27(5):571-9. Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume City, Fukuoka 830-0011, Japan. fujita@med.kurume-u.ac.jp Controversy continues over the optimal extent of lymphadenectomy (regional versus three-field) for a potentially resectable squamous cell carcinoma in the thoracic esophagus. In the Consensus Conference of the International Society for Diseases of the Esophagus (ISDE), held in Munich in 1994, the types of lymphadenectomy were classified as standard, extended, total, or three-field lymphadenectomy. The objective of the present study was to determine the optimal procedure among these four types of lymphadenectomy. The mortality and morbidity rates, postoperative course, and survival rates were compared among 302 patients who underwent curative (R0) transthoracic esophagectomy with one of these four types of lymphadenectomy at Kurume University Hospital, Fukuoka, Japan, from 1986 to 1998. Three-field lymphadenectomy resulted in better survival than any other type of lymphadenectomy for patients with positive lymph node metastasis from a cancer in the upper or middle thoracic esophagus. A postoperative complication, such as recurrent laryngeal nerve paralysis, anastomotic leakage, and tracheal ischemic lesion, was significantly more common after three-field lymphadenectomy. However, the mortality rate was the same among the four procedures. Three-field lymphadenectomy was optimal for an upper or middle thoracic esophageal cancer with metastasis in the lymph node(s) based on improved long-term survival, whereas there was not a large difference in short-term and long-term outcomes after the four types of lymphadenectomy for a lower thoracic esophageal cancer. |
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Esophageal
cancer - Definitive Radiation Therapy
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| Combined
chemotherapy and radiotherapy (without surgery) compared with radiotherapy
alone in localized carcinoma of the esophagus (Cochrane Review). Rebecca Wong, Richard Malthaner In : The Cochrane Library, Issue 4, 2003. Chichester, UK. Background : Esophageal carcinoma can be managed primarily with either a surgical or radiotherapeutic (non surgical) approach. Strategies to improve the outcome of either modality alone include the use of combined modalities. Combination chemotherapy radiotherapy is one approach that has been explored over the years with increasing application in clinical practice especially in North America. Objectives : To evaluate the effectiveness of combined chemotherapy and radiotherapy versus radiotherapy alone in the outcome of patients with localized esophageal carcinoma. Outcomes of interest include overall survival, cause specific survival, local recurrence, dysphagia relief, quality of life, acute and chronic toxicities. Search Strategy : The Cochrane strategy for identifying randomized trials was combined with MeSH headings including esophageal neoplasms, radiotherapy, chemotherapy combined modality, drug therapy combination. MEDLINE, CancerLIT and EMBASE were searched using this strategy. In addition, the Cochrane library was also searched. References from relevant articles and personal files were included. Selection Criteria : Randomized controlled trials in patients with localized esophageal cancer, with one arm employing radiotherapy alone, and one arm employing combination radiotherapy chemotherapy were included. Studies comparing non chemotherapy agents such as pure radiotherapy sensitisers, immunostimulants, planned esophagectomy, were excluded. Data collection and analysis : Data were extracted by two independent reviewers, and the trial quality was assessed using both the Jadad scoring and Detsky checklist. Sensitivity analysis was planned to explore sources of heterogeneity where heterogeneity existed. The factors hypothesized a priori included combination versus sequential treatment, quality of study, biological effective radiotherapy dose (i.e. Radiotherapy dose) cisplatin versus non cisplatin containing trials, and 5FU versus non 5FU containing trials. Odds Ratio (OR) and 95% confidence limits were used to assess the significance of the difference between the treatment arms. Absolute risk difference and number needed to treat (NNT) were used to express the magnitude of difference where appropriate. Main Results : Thirteen randomized trials were included in the analysis. There were eight concomitant and five sequential radiotherapy and chemotherapy (RTCT) studies. The studies were analyzed separately due to observed heterogeneity across all the studies and biological considerations. Concomitant RTCT provided significant overall reduction in mortality at 1 and 2 years. The mortality in the control arms was 62% and 83% respectively. Combined RTCT provided an absolute reduction of mortality by 7% (95% CI 1-15%) and 7% (95% CI 0-15%) respectively. Expressed as NNT, this is 12 and 12 respectively. At longer follow up, the results were heterogeneous, cautioning against pooling of the data. There was a reduction in the overall local recurrence rate. The local recurrence rate for the control arms was in the order of 68%. Combined RTCT provided an absolute reduction of local recurrence rate of 12% (95% CI 3-22%) with a NNT of 9. There was significant increase of severe and life threatening toxicities with a NNH of 6, with this approach. The sensitivity analysis did not identify any factor that interacted with the results, or subgroup in which the benefit appear to be limited to. The results from the sequential RTCT studies were heterogeneous and could not be pooled. Factors hypothesized a priori did not identify any single source that could account for a significant component of the heterogeneity. Examining the results individually, there was no data to support clinical benefit. This approach was also accompanied by significant toxicities. Reviewers’ conclusions : When a non-operative approach is selected, then concomitant RTCT is superior to the RT alone. This approach is accompanied by significant toxicities. In patients who are in good general condition, and the risk benefit has been thoroughly discussed with the patient, concomitant RTCT should be considered for the management of esophageal cancer compared with radiotherapy alone. The quality of swallowing for patients with operable esophageal carcinoma : a randomized trial comparing surgery with radiotherapy. Badwe RA, Sharma V, Bhansali MS et al. Cancer. 1999 Feb 15;85(4):763-8 BACKGROUND : Surgery is considered the standard treatment for operable esophageal carcinoma, although there is no compelling evidence that surgery can achieve better results than radiotherapy. There has previously been no direct randomized comparison of these two modalities with survival or disease specific outcome end points. METHODS : Ninety-nine patients with operable squamous cell carcinoma of the esophagus were randomly allocated to surgery or radiotherapy after stratification for tumor length (< or = or >5 cm). Those randomized to surgery underwent transthoracic esophagectomy with limited lymphadenectomy, whereas those in the radiotherapy arm received 50 gray in 28 fractions followed by a 15-gray boost to the primary tumor. Disease specific outcome was assessed for 4 subgroups: 1) disease specific symptoms, 2) physical symptoms, 3) ability to work, and 4) social/family interaction and global perception of disease specific outcome. The questionnaire was given prior to treatment and posttreatment at 3-month intervals for 1 year. Death was a secondary end point. RESULTS : There was an overall improvement in the quality of swallowing in both treatment arms after treatment and with the passage of time. The swallowing status was better in the surgery arm than in the radiotherapy arm at 6 months after treatment (P = 0.03, Fisher’s exact test). Logistic regression analysis showed randomization arm (P = 0.035), time since treatment (P = 0.003), and pretreatment swallowing status to be significant determinants of posttreatment swallowing status. Surgery was twice as likely to result in improvement in swallowing than radiotherapy after correction for time and pretreatment swallowing status. Overall survival was better in the surgery arm than in the radiotherapy arm (P = 0.002, log rank test) (OR = 2.74 with 95% confidence intervals 1.51-4.98; P < 0.009, Cox proportional hazards model). CONCLUSIONS : Both surgery and radiotherapy can improve the quality of swallowing significantly for patients with operable esophageal carcinoma. Surgery is marginally superior to radiotherapy in improving the quality of swallowing. In this trial, survival in the surgery arm was significantly better than in the radiotherapy arm, although the small number of patients is a limitation. |
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Esophageal
cancer - Neoadjuvant Treatment
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| Preoperative
radiotherapy for esophageal carcinoma (Cochrane Review). Arnott SJ, Duncan W, Gignoux M, Girling DJ et al. In : The Cochrane Library, Issue 4, 2003. Chichester, UK Background : The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. Objectives : This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery and whether or not any pre-defined patient subgroups benefit more or less from preoperative radiotherapy. Search Strategy : Medline and CancerLit searches were supplemented by information from trial registers and by hand searching relevant meeting proceedings and by discussion with relevant trialists, organisations and industry. The search strategy was run again in Medline, Embase and the Cochrane Library on 30th April 2001, two years after original publication. No new trials were found. In August 2002 and 2003 the original search strategy was re-run in Medline, CancerLit, Embase and the Cochrane Library, and again no new trials were identified. Selection Criteria : Trials were eligible for inclusion in this meta-analysis provided they randomized patients with potentially resectable carcinoma of the esophagus (of any histological type) to receive radiotherapy or no radiotherapy prior to surgery. Trials must have used a randomization method which precluded prior knowledge of treatment assignment and completed accrual by December 1993, to ensure sufficient follow-up by the time of the first analysis (September 1995). Data collection and analysis : A quantitative meta-analysis using updated data from individual patients from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. This approach was used to assess whether preoperative radiotherapy improves overall survival and whether it is differentially effective in patients defined by age, sex and tumour location. Main Results : With a median follow-up of 9 years, in a group patients with mostly squamous carcinomas, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p=0.062). No clear differences in the size of the effect by sex, age or tumor location were apparent. Reviewers’ conclusions : Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients (90% power, 5% significance level) would be needed to reliably detect such an improvement (from 15 to 20%). Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. Kelsen DP, Ginsberg R, Pajak TF et al. N Engl J Med. 1998 Dec 31;339(27):1979-84 BACKGROUND : We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer. METHODS: Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival. RESULTS : Of the 440 eligible patients with adequate data , 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who underwent immediate surgery (P=0.53). At one year, the survival rate was 59 percent for those who received chemotherapy and 60 percent for those who had surgery alone; at two years, survival was 35 percent and 37 percent, respectively. The toxic effects of chemotherapy were tolerable, and the addition of chemotherapy did not appear to increase the morbidity or mortality associated with surgery. There were no differences in survival between patients with squamous-cell carcinoma and those with adenocarcinoma. Weight loss was a significant predictor of poor outcome (P=0.03). With the addition of chemotherapy, there was no change in the rate of recurrence at locoregional or distant sites. CONCLUSIONS : Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Medical Research Council Oesophageal Cancer Working Group. BACKGROUND : The outlook for patients with oesophageal cancer undergoing surgical resection with curative intent is poor. We aimed to assess the effects of preoperative chemotherapy on survival, dysphagia, and performance status in this group of patients. METHODS : 802 previously untreated patients with resectable oesophageal cancer of any cell type were randomly allocated either two 4-day cycles, 3 weeks apart, of cisplatin 80 mg/m(2) by infusion over 4 h plus fluorouracil 1000 mg/m(2) daily by continuous infusion for 4 days followed by surgical resection (CS group, n=400), or resection alone (S group, 402). Clinicians could choose to give preoperative radiotherapy to all their patients irrespective of randomisation. Primary outcome measure was survival time. Analysis was by intention to treat. FINDINGS : No patients dropped out of the study. Resection was microscopically complete in 233 (60%) of 390 assessable CS patients and 215 (54%) of 397 S patients (p<0.0001). Postoperative complications were reported in 146 (41%) CS and 161 (42%) S patients. Overall survival was better in the CS group (hazard ratio 0.79; 95% CI 0.67-0.93; p=0.004). Median survival was 512 days (16.8 months) in the CS group compared with 405 days (13.3 months) in the S group (difference 107 days; 95% CI 30-196), and 2-year survival rates were 43% and 34% (difference 9%; 3-14). INTERPRETATION : Two cycles of preoperative cisplatin and fluorouracil improve survival without additional serious adverse events in the treatment of patients with resectable oesophageal cancer. Preoperative chemotherapy for resectable thoracic esophageal cancer (Cochrane Review). Malthaner R, Fenlon D. In : The Cochrane Library, Issue 4, 2003. Chichester, UK Background : Surgery has been the treatment of choice for localized esophageal cancer. A number of studies have investigated whether preoperative chemotherapy followed by surgery leads to an improvement in cure rates, but the individual reports have been conflicting. An explicit systematic update of the role of preoperative chemotherapy in the treatment of resectable thoracic esophageal cancer is therefore warranted. Objectives : The objective of this review is to determine the role of preoperative chemotherapy on patients with resectable thoracic esophageal carcinomas. Search Strategy : Trials were identified by searching the Cochrane Controlled Trials Register, MEDLINE (1966 - 2003), EMBASE (1988 - 2003) and CancerLit (1993 - 2003). There were no language restrictions. Selection Criteria : Types of studies Studies that randomised patients with potentially resectable carcinomas of the esophagus (of any histologic type) to chemotherapy or no chemotherapy before surgeries were included in this review. Types of participants The participants consisted of patients with localized potentially resectable thoracic esophageal carcinomas. Trials involving patients with carcinomas of the cervical esophagus were excluded. Types of interventions Trials that compared chemotherapy before surgery (esophagectomy) with surgical resections alone (esophagectomy) were included. Types of outcome measures The primary outcome was overall survival at yearly intervals after randomisation. Secondary outcomes of interest included rates of resections, response to chemotherapy, rates of local and distant recurrences, quality-of-life, and treatment morbidity and mortality. Data collection and analysis : All analyses were carried out on intention-to-treat. Survival at 1, 2, 3, 4 and five years were used as endpoints of clinical relevance along with the median survival. The risk ratio (relative risk; RR) was the primary measure of effect for survival, rates of resections, and tumour recurrences. The risk difference (RD) was used to describe differences in response to chemotherapy, treatment morbidity and mortality. Main Results : There were 11 randomised trials involving 2051 patients. At 1- year and 2-year the risk ratios showed no difference in survival between preoperative chemotherapy and surgery alone. The 3-year risk ratios found a 21% increase in survival (RR = 1.21; 95% CI 0.88 to 1.68; p = 0.25) and a 24% increase in survival with preoperative chemotherapy at 4 years (RR = 1.24; 95% CI 0.92 to 1.68; p = 0.15) but they did not reach statistical significance. Only at 5 years did the results become significant (RR = 1.44; 95% CI 1.05 to 1.97; p = 0.02). The overall rate of resections and the rate of complete resections (R0) did not differ between the preoperative chemotherapy arm and surgery alone. The pooled clinical response to chemotherapy was about 36% (RD = 0.36; 95% CI 0.26 to 0.47) but the complete pathologic response was a disappointing 3% (RD = 0.03; 95% CI 0.01 to 0.04). No single agent or combination of chemotherapeutic agents was found to be superior to the others. There was a 19% reduction in local recurrence with preoperative chemotherapy, but this was not significant (RR = 0.81; 95% CI 0.54 to 1.22; p = 0.3). Preoperative chemotherapy was somewhat more harmful to patients than surgery alone. Reviewers’ conclusions : In summary, preoperative chemotherapy plus surgery appears to offer a survival advantage at 3, 4, and 5 years, which reached significance only at 5 years compared to surgery alone for resectable thoracic esophageal cancer of any histologic type. The number needed to treat for one extra survivor at five years is eleven patients. The results are tempered by the increased toxicity and mortality associated with chemotherapy. The most beneficial chemotherapy combination appears to be cisplatin and 5-flurouracil based, however, the dosing is unclear. A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer. Urschel JD, Vasan H. Am J Surg. 2003 Jun;185(6):538-43 BACKGROUND : Esophagectomy is a standard treatment for resectable esophageal cancer but relatively few patients are cured. Combining neoadjuvant chemoradiation with surgery may improve survival but treatment morbidity is a concern. We performed a meta-analysis of randomized controlled trials (RCTs) that compared the use of neoadjuvant chemoradiation and surgery with the use of surgery alone for esophageal cancer. METHODS : Medline and manual searches were done to identify all published RCTs that compared neoadjuvant chemoradiation and surgery with surgery alone for esophageal cancer. A random-effects model was used and the odds ratio (OR) was the principal measure of effect. Systematic quantitative review was done for outcomes unique to the neoadjuvant chemoradiation treatment group, such as pathological complete response. RESULTS : Nine RCTs that included 1,116 patients were selected with quality scores ranging from 1 to 3 (5-point Jadad scale). Odds ratio (95% confidence interval [CI]; P value), expressed as chemoradiation and surgery versus surgery alone (treatment versus control; values <1 favor chemoradiation-surgery arm), was 0.79 (0.59, 1.06; P=0.12) for 1-year survival, 0.77 (0.56, 1.05; P=0.10) for 2-year survival, 0.66 (0.47, 0.92; P=0.016) for 3-year survival, 2.50 (1.05, 5.96; P=0.038) for rate of resection, 0.53 (0.33, 0.84; P=0.007) for rate of complete resection, 1.72 (0.96, 3.07; P=0.07) for operative mortality, 1.63 (0.99, 2.68; P=0.053) for all treatment mortality, 0.38 (0.23, 0.63; P=0.0002) for local-regional cancer recurrence, 0.88 (0.55, 1.41; P=0.60) for distant cancer recurrence, and 0.47 (0.16, 1.45; P=0.19) for all cancer recurrence. A complete pathological response to chemoradiation occurred in 21% of patients. The 3-year survival benefit was most pronounced when chemotherapy and radiotherapy were given concurrently (OR 0.45, 95% CI 0.26 to 0.79, P=0.005) instead of sequentially (OR 0.82, 95% CI 0.54 to 1.25, P=0.36). CONCLUSIONS : Compared with surgery alone, neoadjuvant chemoradiation and surgery improved 3-year survival and reduced local-regional cancer recurrence. It was associated with a lower rate of esophageal resection, but a higher rate of complete (R0) resection. There was a nonsignificant trend toward increased treatment mortality with neoadjuvant chemoradiation. Concurrent administration of neoadjuvant chemotherapy and radiotherapy was superior to sequential chemoradiation treatment scheduling. |
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Esophageal
cancer - Adjuvant Treatment
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| Value
of radiotherapy after radical surgery for esophageal carcinoma: a
report of 495 patients. Xiao ZF, Yang ZY, Liang J et al. Ann Thorac Surg. 2003 Feb;75(2):331-6. BACKGROUND : Despite three decades of debate, no conclusion has been reached concerning the effectiveness of postoperative radiotherapy for resected esophageal carcinoma. From 1986 through 1997, a prospective randomized study was carried out with 495 patients in an attempt to define the value of this therapeutic modality. METHODS : A total of 495 patients with esophageal cancer who had undergone radical resection were randomized by the envelope method into a surgery-alone group (S) of 275 patients and a surgery plus radiotherapy group (S + R) of 220 patients. Radiation treatment was started 3 to 4 weeks after the operation. The portals encompassed the entire mediastinum and bilateral supraclavicular areas. A midplane dose of 50 to 60 Gy in 25 to 30 fractions was delivered over 5 to 6 weeks. RESULTS : The overall 5-year survival rate was 31.7% for the S group and 41.3% (p=0.4474) for the S + R group. The 5-year survival rates of patients who were lymph node positive were 14.7% and 29.2% (p=0.0698), respectively. Five-year survival rates of stage III patients were 13.1% and 35.1% (p=0.0027), respectively. CONCLUSIONS : Postoperative prophylactic radiotherapy improved the 5-year survival rate in esophageal cancer patients with positive lymph node metastases and in patients with stage III disease compared with similar patients who did not receive radiation therapy. These results were almost significant for patients with positive lymph node metastases and highly significant for patients with stage III disease. Surgery Plus Chemotherapy Compared With Surgery Alone for Localized Squamous Cell Carcinoma of the Thoracic Esophagus : A Japan Clinical Oncology Group Study—JCOG9204. Ando N, Iizuka T, Ide H et al. J Clin Oncol. 2003 Dec 15;21(24):4592-6. PURPOSE : We performed a multicenter randomized controlled trial to determine whether postoperative adjuvant chemotherapy improves outcome in patients with esophageal squamous cell carcinoma undergoing radical surgery. PATIENTS AND METHODS : Patients undergoing transthoracic esophagectomy with lymphadenectomy between July 1992 and January 1997 at 17 institutions were randomly assigned to receive surgery alone or surgery plus chemotherapy including two courses of cisplatin (80 mg/m2 of body-surface area x 1 day) and fluorouracil (800 mg/m2 x 5 days) within 2 months after surgery. Adaptive stratification factors were institution and lymph node status (pN0 versus pN1). The primary end point was disease-free survival. RESULTS : Of the 242 patients, 122 were assigned to surgery alone, and 120 to surgery plus chemotherapy. In the surgery plus chemotherapy group, 91 patients (75%) received both full courses of chemotherapy; grade 3 or 4 hematologic or nonhematologic toxicities were limited. The 5-year disease-free survival rate was 45% with surgery alone, and 55% with surgery plus chemotherapy (one-sided log-rank, P=.037). The 5-year overall survival rate was 52% and 61%, respectively (P=.13). Risk reduction by postoperative chemotherapy was remarkable in the subgroup with lymph node metastasis. CONCLUSION : Postoperative adjuvant chemotherapy with cisplatin and fluorouracil is better able to prevent relapse in patients with esophageal cancer than surgery alone. Benefit of postoperative adjuvant chemoradiotherapy in locoregionally advanced esophageal carcinoma. Rice TW, Adelstein DJ, Chidel MA et al. J Thorac Cardiovasc Surg. 2003 Nov;126(5):1590-6. OBJECTIVE : We sought to determine whether chemoradiotherapy after esophagectomy improves survival. METHODS : From 1994 to 2000, 31 patients with locoregionally advanced esophageal carcinoma (90% pT3, 81% pN1, and 13% pM1a) received postoperative adjuvant chemoradiotherapy. Concurrently, 52 patients with advanced carcinoma underwent esophagectomy alone and survived at least 10 weeks, the time frame for adjuvant therapy. A propensity score based on demographic, tumor, and surgical factors was used to identify matched pairs to determine the association of adjuvant therapy with outcomes. RESULTS : For patients receiving adjuvant therapy versus esophagectomy alone, risk-unadjusted median, 1-year, and 4-year survivals were 28 versus 14 months, 68% +/- 8.4% versus 60% +/- 6.8%, and 44% +/- 9.0% versus 17% +/- 5.6%, respectively (P=.05). Similarly, risk-unadjusted median time to recurrence was 25 versus 13 months (P=.15), and median recurrence-free survival was 22 versus 11 months (P=.04). Among propensity-matched patients, median, 1-year, and 4-year survivals for those receiving adjuvant therapy versus esophagectomy were 28 versus 15 months, 60% +/- 11.0% versus 65% +/- 10.7%, and 44% +/- 11.3% versus 0% (P=.05). Median time to recurrence was 25 versus 13 months (P=.04), and recurrence-free survival was 22 versus 10 months (P=.02). CONCLUSION : In patients with locoregionally advanced esophageal carcinoma, addition of postoperative adjuvant chemoradiotherapy to esophagectomy alone doubled survival time, time to recurrence, and recurrence-free survival. Patients with locoregionally advanced carcinoma after esophagectomy should be considered for adjuvant therapy. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. Macdonald JS, Smalley SR, Benedetti J et al. N Engl J Med. 2001 Sep 6;345(10):725-30. BACKGROUND : Surgical resection of adenocarcinoma of the stomach is curative in less than 40 percent of cases. We investigated the effect of surgery plus postoperative (adjuvant) chemoradiotherapy on the survival of patients with resectable adenocarcinoma of the stomach or gastroesophageal junction. METHODS : A total of 556 patients with resected adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to surgery plus postoperative chemoradiotherapy or surgery alone. The adjuvant treatment consisted of 425 mg of fluorouracil per square meter of body-surface area per day, plus 20 mg of leucovorin per square meter per day, for five days, followed by 4500 cGy of radiation at 180 cGy per day, given five days per week for five weeks, with modified doses of fluorouracil and leucovorin on the first four and the last three days of radiotherapy. One month after the completion of radiotherapy, two five-day cycles of fluorouracil (425 mg per square meter per day) plus leucovorin (20 mg per square meter per day) were given one month apart. RESULTS : The median overall survival in the surgery-only group was 27 months, as compared with 36 months in the chemoradiotherapy group; the hazard ratio for death was 1.35 (95 percent confidence interval, 1.09 to 1.66; P=0.005). The hazard ratio for relapse was 1.52 (95 percent confidence interval, 1.23 to 1.86; P<0.001). Three patients (1 percent) died from toxic effects of the chemoradiotherapy; grade 3 toxic effects occurred in 41 percent of the patients in the chemoradiotherapy group, and grade 4 toxic effects occurred in 32 percent. CONCLUSIONS : Postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach or gastroesophageal junction who have undergone curative resection. |
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Introduction Lung
cancer is a major problem in both developed and developing countries
in the world. It is the leading type of cancer (more than a million
new cases; 12.8% of all cancers) and the leading cause of cancer
mortality (921,000 deaths; 17.8% of all cancer deaths) worldwide.
It is expected that lung cancer will remain a major health problem
at least for the next 30-40 years, even if there is a reduction
in incidence as a result of smoking cessation interventions. In
India, Untreated, it has a high mortality with 95% patients dying
within one year.
Management
of NSCLC Surgery
is the treatment of choice in patients with localized disease with
no involvement of mediastinal lymph nodes.
* Single
most important test is the predicted postoperative FEV1 (Ppo FEV
1) |
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Preoperative
Management
VATS lung resections
II. Patients with positive mediastinal lymph nodes (T1-3, N2) A. Preoperatively diagnosed N2 disease
B. Surgically discovered N2 disease
Adjuvant therapy
III. Patients with locoregionally advanced disease (T4 and N3)
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