Postoperative pulmonary complications after preoperative chemoradiation for esophageal carcinoma: correlation with pulmonary dose-volume histogram parameters.
Lee HK, Vaporciyan AA, Cox JD, Tucker SL, Putnam JB Jr, Ajani JA, Liao Z, Swisher SG, Roth JA, Smythe WR, Walsh GL, Mohan R, Liu HH, Mooring D, Komaki R.
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
PURPOSE: To clarify the relationship between the percentage of lung receiving low radiation doses with concurrent chemotherapy and the occurrence of postoperative pulmonary complications in the treatment of esophageal carcinoma. METHODS: From 117 patients who underwent preoperative chemoradiation for esophageal cancer at our institution between 1998 and 2002, we selected 61 patients for whom complete pulmonary dose-volume histogram (DVH) data were available and analyzed the incidence of pneumonia and acute respiratory distress syndrome (ARDS) in this group. All patients received concurrent chemoradiation therapy, and 39 patients also received induction chemotherapy before concurrent chemoradiation. The median age was 62 years, and the median radiotherapy dose was 45 Gy. The percentage of lung volume receiving at least 10 Gy (V10), 15 Gy (V15), and 20 Gy (V20) were recorded from each pulmonary DVH. RESULTS: Eleven (18%) of the 61 patients had pulmonary complications, 2 of whom died after progression of pneumonia. Pulmonary complications were noted more often (35% vs. 8%, p = 0.014) when the pulmonary V10 was > or =40% vs. <40% and when the V15 was > or /=30% vs. < 30% (33% vs. 10%, p = 0.036). An apparent increase in pulmonary complication rate when V20 was > or =20% vs. <20% (32% vs. 10%, p = 0.079) was not significant. None of the other factors analyzed (surgical procedure, tumor location, use of induction chemotherapy, use of concurrent taxane-based chemoradiation, or smoking history) was associated with the occurrence of pulmonary complications. The median hospital stay was 17 days for patients who had pulmonary complications vs. 12 days for patients who did not (p = 0.08). CONCLUSIONS: The use of multimodality therapy may require minimization of lung volume irradiation to levels lower than previously expected. Radiotherapy techniques that decrease the volume of lung receiving low radiation doses may significantly reduce the risk of this potentially life-threatening complication.
PMID: 14630268 [PubMed - indexed for MEDLINE]
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Outcome of chemoradiation in treating carcinoma esophagus.
Gilani JA, Hameed K, Asghar AH, Zaman N, Jawad S, K A.
Department of Radiation Division, IRNUM, Peshawar.
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OBJECTIVE: To observe the role of chemoradiation in treating carcinoma of esophagus, its complications and outcome of disease. DESIGN: Analytical descriptive study. PLACE AND DURATION OF STUDY: Conducted at IRNUM in collaboration with Hayatabad Medical Complex (HMC), Peshawar, for one year. PATIENTS AND METHODS: A total of 47 males and 53 females with an average age of 53 +/- 13 years were inducted in this study. Patients having upper end carcinoma or esophageal surgery were excluded from this study. They were treated with radio as well as chemotherapy. Those patients who had completed radiation six months before were planned for repeat endoscopies. Response evaluation was categorized as no evidence of disease, residual disease or stricture formation simulating carcinoma. Seventy percent of endoscoped patients were disease free and 30% were having residual disease. Of these 30%, 10% were having growth while rest of the 20% showed stricture formation due to radiation. RESULTS: Out of 100 patients, 70% were palliated maximally and no evidence of disease was found on endoscopy done after 1-6 months. Only 30% came up again with dysphagia. Out of these 30%, 20% were having esophageal stricture, which on dilatation improved the quality of life. Rest of the 10% were having stricture hiding the residual disease. Giving 1-2 cycles of chemotherapy before the start of radiation reduced the disease burden and predicted response to radiation by improving dysphagia. CONCLUSION: In spite of certain complications like neutropenia, emesis and stricture formation, chemoradiation is still the best treatment option available. It is because of its safety, well-tolerability and cost effectiveness. It is equally good for patients who refuse surgery and those with advanced disease.
PMID: 14588168 [PubMed - indexed for MEDLINE]
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Long-term outcome of phase II trial evaluating chemotherapy, chemoradiotherapy, and surgery for locoregionally advanced esophageal cancer.
Swisher SG, Ajani JA, Komaki R, Nesbitt JC, Correa AM, Cox JD, Lahoti S, Martin F, Putnam JB, Smythe WR, Vaporciyan AA, Walsh GL, Roth JA.
Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
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PURPOSE: To evaluate the long-term outcome of chemotherapy, chemoradiotherapy, and surgery for patients with locoregionally advanced esophageal cancer. METHODS AND MATERIALS: Thirty-eight patients with locoregionally advanced esophageal cancer were entered into a Phase II study between November 1996 and October 1998 at the University of Texas M. D. Anderson Cancer Center. Patients initially received two cycles of chemotherapy with paclitaxel (200 mg/m(2)), 5-fluorouracil (750 mg/m(2)/d for 5 days), and cisplatin (15 mg/m(2)/d for 5 days), followed by chemoradiotherapy, consisting of radiation (45 Gy during 5 weeks) with 5-fluorouracil (300 mg/m(2)/d during radiation) and cisplatin (15 mg/m(2)/d for 5 days). Surgical resection was performed 4-6 weeks after the completion of the chemoradiotherapy. RESULTS: Most patients had adenocarcinoma (n = 32; 84%). Pretreatment endoscopic ultrasonography revealed T3 tumors in 33 patients (87%) and N1 disease in 25 patients (66%). Thirty-seven patients (97%) completed the planned chemotherapy and chemoradiotherapy, and 35 patients (92%) underwent surgery, with a 30-day mortality rate of 6% (2 of 35 patients). A pathologic complete response or microscopic residual carcinoma (<10% viable) was found in 25 (71%) of 35 patients and was associated with a disease-free survival rate of 72% at 3 years and 51% at 5 years. On the basis of an intention-to-treat analysis and a median potential follow-up of 58 months, the 3- and 5-year overall survival rate for all 38 patients was 63% and 39%, respectively. CONCLUSION: The long-term results of this study suggest that the strategy of induction chemotherapy followed by chemoradiotherapy and surgery is safe and warrants further evaluation in the treatment of patients with locoregionally advanced esophageal cancer.
Publication Types:
- Clinical Trial
- Clinical Trial, Phase II
PMID: 12909224 [PubMed - indexed for MEDLINE]
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Multimodality treatment for esophageal cancer: the role of surgery and neoadjuvant therapy.
Makary MA, Kiernan PD, Sheridan MJ, Tonnesen G, Hetrick V, Vaughan B, Graling P, Elster E.
Department of Surgery, Georgetown University Hospital, Washington, DC, USA.
Treatment of esophageal cancer has traditionally included surgery as the initial modality. Neoadjuvant chemoradiation therapy has been introduced with the goal of downstaging tumors before surgical resection; however, its role in esophageal cancer remains controversial. We report 116 patients who underwent esophagogastrectomy with reconstruction for carcinoma of the esophagus or esophagogastric junction over a 10-year period (January 1, 1990 to June 1, 2001). Forty patients underwent neoadjuvant radiation and chemotherapy followed by surgery. Hospital mortality in this group was 7.5 per cent, complete pathologic response (CPR) was 37.5 per cent, and overall 3- and 5-year survival rates were 47 and 38 per cent. Five-year survival in the 15 patients with CPR was 85 per cent. Five patients underwent neoadjuvant single-agent therapy (four chemotherapy and one radiation) followed by surgery, and none survived to 3 years. Seventy-one patients underwent surgery without neoadjuvant therapy. Hospital mortality in this group was 1.4 per cent, with 3- and 5-year survival of 21 and 17 per cent--a decreased long-term survival compared with the neoadjuvant therapy group despite the observation that patients who underwent neoadjuvant therapy had a larger tumor size on presentation (5.5 +/- 0.4 cm vs 3.8 +/- 0.2 cm; P = 0.002). Squamous cell carcinomas seemed to be more responsive to neoadjuvant radiation and chemotherapy followed by surgery than were adenocarcinomas, with a CPR of 44.4 versus 35.5 per cent; however, 5-year survival rates in these complete responders were not significantly different (100% and 78%, respectively; P = 0.97). We report that esophagogastrectomy in conjunction with neoadjuvant therapy results in increased survival compared with surgery without neoadjuvant therapy (P < 0.01), although there may be an increased perioperative mortality associated with neoadjuvant therapy. Further studies are needed to evaluate the role of preoperative chemoradiation and to better identify the pretreatment characteristics of patients with a complete pathological response.
PMID: 12953828 [PubMed - indexed for MEDLINE]
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The national practice for patients receiving radiation therapy for carcinoma of the esophagus: results of the 1996-1999 Patterns of Care Study.
Suntharalingam M, Moughan J, Coia LR, Krasna MJ, Kachnic L, Haller DG, Willett CG, John MJ, Minsky BD, Owen JB; 1996-1999 Patterns of Care Study.
Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
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PURPOSE: A Patterns of Care Study (PCS) was conducted to evaluate the standards of practice for patients receiving radiation therapy for esophageal cancer from 1996 to 1999. This study examined the evaluation and treatment schemes used during this time and compared these results to the PCS data obtained between 1992 and 1994 to identify any fundamental changes in national practice. METHODS: A national survey was conducted using a two-stage cluster sampling technique. Specific information was collected on 414 patients with esophageal cancer who received radiotherapy (RT) as part of definitive or adjuvant management at 59 institutions. Patients were staged according to the 1983 AJCC. Eligibility criteria for case review included RT between 1996 and 1999, no evidence of distant metastasis (including CT evidence of either supraclavicular or celiac nodes >1 cm), squamous cell or adenocarcinoma histology, Karnofsky performance status >60, tumors in the thoracic esophagus with <2 cm extension into the stomach, and no prior malignancies within the last 5 years. Statistical analysis was performed on the database using SUDAAN software to accurately reflect the type of sampling technique used by PCS. For the purpose of this analysis, institutions were stratified as either large or small based on the number of new cases seen each year. For the purposes of comparison, the 1992-1994 PCS esophageal survey results were subjected to the same statistical procedures and tests. RESULTS: The median age of patients was 64 years. Seventy-seven percent were male, and 23% were female. Karnofsky performance status was >or=80% in 85% of patients. The racial profile mirrors the previous survey with 75% Caucasian, 21% African-American, 3% Asian, and <1% Hispanic. A review of the histology revealed a nearly 50:50 split between squamous cell and adenocarcinoma. Sixteen percent were clinical Stage I, 39% clinical Stage II, and 33% clinical Stage III according to the 1983 AJCC system. Workup included endoscopy (96%), CT of the chest (87%), CT of the abdomen (75%), and esophagram (64%). Endoscopic ultrasound (EUS) was used in 18% of cases as compared to <2% in the original survey (p < 0.0001). Patients treated at large centers were more likely to undergo EUS than those treated at small centers (23% vs. 12%, p = 0.047). Fifty-six percent of patients received concurrent chemoradiation as definitive treatment. There was a significant increase in the use of concurrent chemoradiation before planned surgical resection as compared to the original survey (27% vs. 10%, p = 0.007). Other schemes included RT alone (10%), postoperative RT (1%), and postoperative chemoradiation (5%). Forty-six percent of patients with adenocarcinoma underwent trimodality therapy as compared to 19% with squamous cell carcinomas (p = 0.0002). Patients undergoing preoperative chemoradiation were more likely to have had an EUS. The median total dose of external RT was 50.4 Gy, and the median dose per fraction was 1.8 Gy. Brachytherapy was used in 6% of cases. The chemotherapy agents most commonly used included 5-fluorouracil (82%), cisplatin (67%), and paclitaxel (22%). Paclitaxel was more commonly employed as part of a preoperative chemoradiation regimen than in the setting of definitive chemoradiation (46% vs. 12%, p = 0.03). Compared to the original survey, paclitaxel use significantly increased between 1996 and 1999 (0.2% vs. 22%, p = 0.001). CONCLUSIONS: The Patterns of Care Survey confirms the use of concurrent chemoradiation as part of the national standards of practice for the management of esophageal cancer patients. A comparison with the previous study documents the significant rise in the use of EUS, preoperative chemoradiation followed by surgery, and the increasing use of paclitaxel as part of a combined modality regimen.
PMID: 12829133 [PubMed - indexed for MEDLINE]
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Comment in:
Preoperative therapy with concurrent paclitaxel/carboplatin/infusional 5-FU and radiation therapy in locoregional esophageal cancer: final results of a Minnie Pearl Cancer Research Network phase II trial.
Meluch AA, Greco FA, Gray JR, Thomas M, Sutton VM, Davis JL, Kalman LA, Shaffer DW, Yost K, Rinaldi DA, Hainsworth JD.
Sarah Cannon Cancer Center, Nashville, Tennessee 37203, USA.
PURPOSE: This phase II study was designed to determine the feasibility, toxicity, and therapeutic efficacy of a novel outpatient combined-modality preoperative regimen in patients with localized esophageal cancer. PATIENTS AND METHODS: One hundred twenty-nine eligible patients with previously untreated, potentially resectable, clinical stage I-III carcinoma of the esophagus were treated between July 1995 and July 1999. Combined-modality treatment included: paclitaxel, 200 mg/m2, 1-hour i.v. infusion, days 1 and 22; carboplatin, an area under the concentration time curve 6.0 i.v., days 1 and 22; 5-fluorouracil, 225 mg/m2/day, continuous i.v. infusion, days 1-42; and radiation therapy, 45 Gy, 1.8-Gy single daily fractions 5 days weekly, beginning day 1. All patients underwent surgical resection 4-8 weeks after completion of the preoperative therapy. RESULTS: One hundred twenty-three patients (95%) completed preoperative therapy, 105 patients (81%) underwent attempted resection, and 96 patients (74%) had definitive resection. A pathological complete response was achieved in 47 of 123 evaluable patients (38%); an additional 30 patients (24%) had only microscopic residual tumor. With a median follow-up of 45 months, the median survival is 22 months (95% CI = 15-32 months), with actuarial 1-, 2-, and 3-year survivals of 71%, 47%, and 41%, respectively. The most frequent grade 3/4 toxicities of the neoadjuvant program were leukopenia (73%) and esophagitis (43%). Although 73 patients (57%) required brief hospitalizations during preoperative therapy, there were no treatment-related deaths, and 94% of patients remained candidates for resection after the completion of treatment. Six patients (6%) died after surgery. CONCLUSIONS: This novel combined-modality regimen is highly active in the treatment of locoregional esophageal cancer, producing an actuarial 3-year survival of 41%. Although this preoperative regimen produced moderate acute toxicity, there were no treatment-related deaths and the large majority of patients were able to undergo subsequent esophageal resection. These results, obtained in a community-based setting and involving multiple surgeons, radiation oncologists, and medical oncologists, compare favorably with those of previous single-center and multicenter results. Further evaluation of novel combined-modality programs is warranted, as is the incorporation of epidermal growth factor receptor antagonists or other targeted agents.
Publication Types:
- Clinical Trial
- Clinical Trial, Phase II
- Multicenter Study
PMID: 12967135 [PubMed - indexed for MEDLINE]
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Influence of celiac axis lymph nodes in the definitive treatment of esophageal cancer.
Frizzell B, Sinha D, Williams T, Reed CE, Sherman CA, Turrisi A.
Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina, USA.
The management of patients with cancer of the distal thoracic esophagus is often made difficult by the presence of disease in the celiac axis lymph nodes. We investigated the outcome of such patients treated for cure in an attempt to better define the best treatment. The charts of all patients with esophageal cancer treated at the Department of Radiation Oncology at the Medical University of South Carolina between 1990 and 1998 were reviewed. Three groups of patients were analyzed: NoMo, N1Mo, and patients with positive celiac axis lymph nodes (M1a). Among 217 patients, 56 patients received radiotherapy with intent to cure, along with surgery, chemotherapy, or some combination of these modalities. Of these, 14 had disease of the distal esophagus with the celiac axis as their only site of distant disease. Comparison of survival curves in the three analyzed groups revealed no statistically significant differences in terms of overall survival (p = 0.3458 by the log-rank test) or disease-free survival (p = 0.5509 by the log-rank test). Patients with positive celiac axis lymph nodes as their only site of "M1" disease experienced a 2-year survival rate similar to "Mo" patients when treated with curative intent.
PMID: 12796587 [PubMed - indexed for MEDLINE]
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The significance of cardiac doses received during chemoradiation of oesophageal and gastro-oesophageal junctional cancers.
Mukherjee S, Aston D, Minett M, Brewster AE, Crosby TD.
Velindre Hospital, Whitchurch, Cardiff, Wales, UK.
AIM: Although radiation-induced cardiotoxicity has been described in patients with breast cancer and Hodgkin's disease, the effect of oesophageal radiotherapy on the heart has not been evaluated. This study was designed to evaluate the dose received by the heart during chemoradiotherapy (CT-RT) for oesophageal cancer, to assess its impact on cardiac function, and explore methods of reducing this dose. METHODS: Cardiac doses were calculated from dose-volume histograms in 15 patients with carcinoma of mid and lower oesophagus undergoing combined technique treatment, in whom pre- and post-treatment multigated acquisition scans were available. Chemotherapy consisted of cisplatin and 5-fluorouracil with or without paclitaxel. The radiotherapy was delivered in two phases to a total dose of 45-50 Gy in 25 fractions. RESULTS: There was a significant reduction in median ejection fraction after CT-RT (63% to 58%, P = 0.003). The median dose received by the heart using three-dimensional conformal technique was 27.4 Gy (interquartile range 25.8-34.2 Gy). If shielding blocks were not used, as would be the case with conventional planning, the median dose would have been 35 Gy (interquartile range 28.2-37.7 Gy), which is significantly higher (P = 0.002). The use of a three-field technique throughout treatment also reduced the median cardiac dose from 27.4 Gy to 22.7 Gy (P = 0.001) and the volume of heart receiving 70% of total dose from 63.8% to 25% (P = 0.001). CONCLUSION: This study highlights the significant dose of radiation received by the heart during oesophageal CT-RT, with consequent reduction in cardiac ejection fraction. Conformal radiotherapy reduces cardiac doses received. The cardiac, as well as the pulmonary, side effects of CT-RT needs to be borne in mind, especially when using this treatment before radical surgery.
PMID: 12801047 [PubMed - indexed for MEDLINE]
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Comment in:
Value of radiotherapy after radical surgery for esophageal carcinoma: a report of 495 patients.
Xiao ZF, Yang ZY, Liang J, Miao YJ, Wang M, Yin WB, Gu XZ, Zhang de C, Zhang RG, Wang LJ.
Department of Radiation Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
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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.
Publication Types:
- Clinical Trial
- Randomized Controlled Trial
PMID: 12607634 [PubMed - indexed for MEDLINE]
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Definitive chemoradiotherapy for patients with malignant stricture due to T3 or T4 squamous cell carcinoma of the oesophagus.
Kaneko K, Ito H, Konishi K, Kurahashi T, Ito T, Katagiri A, Yamamoto T, Kitahara T, Mizutani Y, Ohtsu A, Mitamura K.
Second Department of Internal Medicine, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
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We retrospectively investigated the efficacy and feasibility of concurrent chemoradiotherapy for patients with severe dysphagia caused by oesophageal squamous cell carcinoma. Concurrent chemoradiotherapy was performed in 57 patients with T3 or T4 disease containing M1 lymph node (LYM) disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil (5-FU) 400 mg m(-2) 24 h(-1) on days 1-5 and 8-12, combined with 2-h infusion of cisplatin (CDDP) 40 mg m(-2) on days 1 and 8. Radiation treatment at a dose of 30 Gy in 15 fractions of the mediastinum was administered concomitantly with chemotherapy. A course schedule with 3-week treatment and a 1 to 2-week break was applied twice, with a total radiation dose of 60 Gy, followed by two or more courses of 5-FU and CDDP. In all, 24 patients (42%) achieved a complete response, and the 3-year survival rate was 19%. Major toxicities were leukocytopenia and oesophagitis, and there were two (4%) treatment-related deaths. In contrast, 22 patients with T3 disease survived longer than 35 patients with T4 disease (P=0.001); however, the survival rate in 15 patients with M1 LYM disease did not differ significantly from that in 42 patients without M1 LYM disease (P=0.3545). Our results indicate that definitive chemoradiotherapy is potentially curative for locally advanced oesophageal carcinoma with malignant stricture. The efficacy and survival of patients treated with this regimen are related to the T factor.
PMID: 12556953 [PubMed - indexed for MEDLINE]
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A systematic overview of radiation therapy effects in oesophageal cancer.
Ask A, Albertsson M, Jarhult J, Cavallin-Stahl E.
Department of Oncology, University Hospital, Lund, Sweden.
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A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for oesophageal cancer is based on data from 42 randomized trials and 2 meta-analyses. A total of 44 scientific articles are included, involving 5 772 patients. The conclusions reached can be summarized as follows: There is fairly strong evidence that preoperative radiotherapy does not improve the survival in patients with potentially resectable oesophageal cancer. There is moderate evidence that preoperative chemo-radiotherapy has no beneficial impact on the survival of patients with potentially resectable oesophageal cancer. There is no scientific evidence that postoperative radiotherapy improves survival in patients with resectable oesophageal cancer. The documentation is, however, poor, consisting of only three randomized trials. There is fairly strong evidence that concomitant (but not sequential) chemo-radiotherapy gives significantly better survival rate than radiotherapy alone in inoperable oesophageal cancer. The results of the reported clinical trials are, however, conflicting, and no solid conclusion can be drawn. Hyperfractionated radiotherapy has been compared with conventionally fractionated radiotherapy in two randomized studies with conflicting results and no firm conclusion can be drawn.
Publication Types:
PMID: 14596507 [PubMed - indexed for MEDLINE]
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Second primary oesophageal cancer following radiation for breast cancer.
Matheson JB, Burmeister BH, Smithers BM, Gotley D, Harvey JA, Doyle L.
Upper Gastrointestinal Oncology Clinic, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Qld. 4102, Australia.
The management of 12 women who presented with a second primary oesophageal cancer following radiotherapy for breast cancer was reviewed. It was concluded that nine cases fitted the classical description of a radiation-induced malignancy. Most cases were successfully managed with combined modality therapy in spite of their previous radiotherapy.
PMID: 12464444 [PubMed - indexed for MEDLINE]
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Improving the consistency in cervical esophageal target volume definition by special training.
Tai P, Van Dyk J, Battista J, Yu E, Stitt L, Tonita J, Agboola O, Brierley J, Dar R, Leighton C, Malone S, Strang B, Truong P, Videtic G, Wong CS, Wong R, Youssef Y.
Department of Oncology, London Regional Cancer Center, London, Ontario, Canada.
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PURPOSE: Three-dimensional conformal radiation therapy requires the precise definition of the target volume. Its potential benefits could be offset by the inconsistency in target definition by radiation oncologists. In a previous survey of radiation oncologists, a large degree of variation in target volume definition of cervical esophageal cancer was noted for the boost phase of radiotherapy. The present study evaluated whether special training could improve the consistency in target volume definitions. METHODS AND MATERIALS: A pre-training survey was performed to establish baseline values. This was followed by a special one-on-one training session on treatment planning based on the RTOG 94-05 protocol to 12 radiation oncologists. Target volumes were redrawn immediately and at 1-2 months later. Post-training vs. pre-training target volumes were compared. RESULTS: There was less variability in the longitudinal positions of the target volumes post-training compared to pre-training (p < 0.05 in 5 of 6 comparisons). One case had more variability due to the lack of a visible gross tumor on CT scans. Transverse contours of target volumes did not show any significant difference pre- or post-training. CONCLUSION: For cervical esophageal cancer, this study suggests that special training on protocol guidelines may improve consistency in target volume definition. Explicit protocol directions are required for situations where the gross tumor is not easily visible on CT scans. This may be particularly important for multicenter clinical trials, to reduce the occurrences of protocol violations.
Publication Types:
PMID: 12062623 [PubMed - indexed for MEDLINE]
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Influence of staging thoracic computed tomography on radiation therapy planning for esophageal carcinoma.
Leung SF, Griffith JF, Ahuja A, Chan AC.
Department of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
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Radiation therapy with concurrent chemotherapy is frequently used as definitive treatment for esophageal carcinoma. Although thoracic computed tomography (CT) is widely used in staging esophageal carcinoma, its application to radiation therapy planning has been regarded as optional rather than mandatory. Conventional radiation therapy planning is esophagogram-based rather than CT-based. The treatment port is generated by adding 5 cm to the proximal and distal margins of the tumor-involved segment as seen on esophagogram performed in the treatment position. Historically, a maximum port length of 15 cm was recommended to avoid excessive treatment morbidity. The authors examined the limitations of such a planning protocol by projecting conventional treatment ports onto the thoracic CT of 75 consecutive newly diagnosed cases of nondisseminated esophageal squamous cell carcinoma. The authors assessed the adequacy of coverage of the primary tumor and metastatic nodes, with respect to data from thoracic CT and neck ultrasonography. It was found that up to 38% of T2-T3 tumors and 30% of short-length (< or =5 cm) tumors had metastatic nodes outside the port. The addition of neck ultrasonography led to identification of an additional 5% of patients with nonpalpable nodes outside the port. It is concluded that the frequency of inadequate tumor coverage using an esophagogram-based planning protocol, with a maximum port length of 15 cm, is unacceptably high. Thoracic CT should be a mandatory rather than optional imaging investigation in guiding radiation therapy planning for esophageal cancer.
PMID: 11956364 [PubMed - indexed for MEDLINE]
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Combined modality therapy of esophageal cancer--standard of care?
Urba S.
Division of Hematology/Oncology, University of Michigan Medical Center, 1500 E. Medical Center Drive, 1364 Cancer Center, Ann Arbor, MI 48109, USA.
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Because of the controversies and conflicting data described above, it is very difficult to provide strict guidelines for the treatment of patients with locoregional esophageal carcinoma. It is necessary, however, to try to put current knowledge in perspective. Surgery remains a standard of care for potentially resectable disease. Definitive chemoradiation is a standard of care for locoregional disease, particularly if a patient is medically unfit for surgery, if a surgeon experienced in esophagectomies is unavailable, or if the patient has cervical disease, which would require very extensive surgery. Chemoradiation is superior to radiation alone for these patients. Some frail patients may only be able to tolerate palliative radiation. Preoperative chemotherapy is controversial, with two large randomized studies resulting in two different conclusions regarding survival benefit. NCCN guidelines do not suggest this modality as a standard of care. After assessment of the patient's tumor stage, performance status, and personal wishes for aggressive treatment, it is possible that some physicians may consider offering this option to patients. The patient should have advanced disease, an excellent performance status, and understand the controversies and lack of consensus about this option. Preoperative chemoradiation is controversial. Only one of three randomized trials showed a clear survival benefit; however, the patients treated with surgery alone in that trial had an unusually poor outcome. The second trial showed no benefit, and the third trial was negative but statistically powered only to reveal a large survival difference and in multivariate analysis showed a possible trend to improved outcome. The NCCN guidelines do not advocate preoperative chemoradiation as a standard of care. As stated above, however, some physicians may consider offering this option to patients with advanced disease, excellent performance status, and who understand the controversies and lack of consensus about this option. Patients with adenocarcinoma of the GE junction treated with surgery alone should have postoperative chemoradiation, particularly if there is tumor involvement in the lymph nodes. No definitive trial has been performed to determine whether chemoradiation plus surgery is superior to chemoradiation alone.
Publication Types:
PMID: 12424857 [PubMed - indexed for MEDLINE]
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Comment in:
INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy.
Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, Okawara G, Rosenthal SA, Kelsen DP.
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
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PURPOSE: To compare the local/regional control, survival, and toxicity of combined-modality therapy using high-dose (64.8 Gy) versus standard-dose (50.4 Gy) radiation therapy for the treatment of patients with esophageal cancer. PATIENTS AND METHODS: A total of 236 patients with clinical stage T1 to T4, N0/1, M0 squamous cell carcinoma or adenocarcinoma selected for a nonsurgical approach, after stratification by weight loss, primary tumor size, and histology, were randomized to receive combined-modality therapy consisting of four monthly cycles of fluorouracil (5-FU) (1,000 mg/m(2)/24 hours for 4 days) and cisplatin (75 mg/m(2) bolus day 1) with concurrent 64.8 Gy versus the same chemotherapy schedule but with concurrent 50.4 Gy. The trial was stopped after an interim analysis. The median follow-up was 16.4 months for all patients and 29.5 months for patients still alive. RESULTS: For the 218 eligible patients, there was no significant difference in median survival (13.0 v 18.1 months), 2-year survival (31% v 40%), or local/regional failure and local/regional persistence of disease (56% v 52%) between the high-dose and standard-dose arms. Although 11 treatment-related deaths occurred in the high-dose arm compared with two in the standard-dose arm, seven of the 11 deaths occurred in patients who had received 50.4 Gy or less. CONCLUSION: The higher radiation dose did not increase survival or local/regional control. Although there was a higher treatment-related mortality rate in the patients assigned to the high-dose radiation arm, it did not seem to be related to the higher radiation dose. The standard radiation dose for patients treated with concurrent 5-FU and cisplatin chemotherapy is 50.4 Gy.
Publication Types:
- Clinical Trial
- Clinical Trial, Phase III
- Randomized Controlled Trial
PMID: 11870157 [PubMed - indexed for MEDLINE]
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Salvage esophagectomy for recurrent tumors after definitive chemotherapy and radiotherapy.
Swisher SG, Wynn P, Putnam JB, Mosheim MB, Correa AM, Komaki RR, Ajani JA, Smythe WR, Vaporciyan AA, Roth JA, Walsh GL.
Department of Thoracic and Cardiovascular Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
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OBJECTIVES: Some patients and oncologists choose to treat localized esophageal cancer with definitive chemotherapy and radiation therapy rather than surgery. A subset of these patients have local relapse without distant metastases and therefore have no other curative intent treatment option but salvage esophagectomy. METHODS: We reviewed our experience with salvage esophagectomy from 1987 to 2000 at M.D. Anderson Cancer Center (n = 13, salvage after chemotherapy and radiotherapy group) and compared the data with those of patients receiving esophagectomy in a planned fashion 4 to 6 weeks after preoperative chemotherapy and radiation therapy (n = 99, preoperative chemotherapy and radiotherapy group). RESULTS: Increases in morbidity were seen after resection in the salvage after chemotherapy and radiotherapy group relative to the preoperative chemotherapy and radiotherapy group: mechanical ventilation (9.0 days vs 3.3 days, P =.08), intensive care unit stay (11.2 days vs 5.1 days, P =.07), hospital stay (29.4 days vs 18.4 days, P =.03), and anastomotic leak rates (5/13 [39%] vs 7/99 [7%], P =.005). Operative mortality (within 30 days) also tended to be increased statistically nonsignificantly (2/13 [15%] vs 6/99 [6%], P =.2). Salvage esophagectomy resulted in long-term survival (25% 5-year survival) in a subset of patients. Improved survival after salvage esophagectomy was associated with early pathologic stage (T1 N0, T2 N0), prolonged time to relapse, and R0 surgical resection. CONCLUSION: Patients who undergo salvage esophagectomy for relapse of tumor after definitive chemoradiation therapy have increased morbidity, mortality, and hospital use relative to patients undergoing planned esophagectomy after preoperative chemoradiation. Nevertheless, long-term survival can be achieved in this group, and such treatment should be considered for carefully selected patients at an experienced center.
PMID: 11782772 [PubMed - indexed for MEDLINE]
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Comment in:
Swallowing function and weight change observed in a phase I/II study of external-beam radiation, brachytherapy and concurrent chemotherapy in localized cancer of the esophagus (RTOG 9207).
Gaspar LE, Winter K, Kocha WI, Pinover WH, Herskovic, Graham M, Gunderson L.
University of Colorado, Denver, USA.
BACKGROUND: A multi-institutional, prospective study was designed to determine the feasibility and tolerance of combined-modality chemotherapy, external-beam irradiation, and esophageal brachytherapy in a potentially curable group of patients with adenocarcinoma or squamous cell carcinoma of the esophagus. Swallowing function and weight were assessed before and after treatment. MATERIALS AND METHODS: Planned treatment was with 50 Gy of external-beam irradiation (25 fractions/5 weeks) followed 2 weeks later by esophageal brachytherapy (either a high dose rate of 5 Gy at weeks 8, 9, and 10 for a total of 15 Gy or a low dose rate of 20 Gy at week 8). Chemotherapy was given weeks 1, 5, 8, and 11 with cisplatinum, 75 mg/m2, and 5-fluorouracil, 1,000 mg/m2/24 hours in a 96-hour infusion. Swallowing was graded from 0 (no dysphagia) to 4 (complete obstruction for solids and liquids). Weight "loss" or weight gain was defined as a change in 3-month post- to pretherapy weight of < or = 5% or > 5%, respectively. RESULTS: The estimated survival rate at 1 and 2 years was 49% and 31%, respectively, and the estimated median survival was 11 months. Swallowing before treatment was graded as grade 1 in 14 patients, grade 2 in 22 patients, grade 3 in nine patients, and grade 4 in four patients. Swallowing grade after treatment was reported as improved in 29 patients (59%), unchanged in 12 patients (24.5%), and worse in eight patients (16.5%). The bestimproved dysphagia score after treatment in the 29 patients reporting improvement was grade 0 in 19 patients, grade 1 in five patients, grade 2 in four patients, and grade 3 in one patient. A posttreatment weight in 42 evaluable patients was categorized as a loss in 29 patients (69%), a gain in four patients (9.5%), and stable in nine patients (21.5%). Weight loss was significantly correlated with high swallowing grade, low performance status, and absence of a feeding tube. CONCLUSIONS: Swallowing function after brachytherapy and concurrent chemoradiation therapy is satisfactory in most surviving patients. Ninety-two percent of patients were able to swallow at least liquids at some point after therapy. Future plans are to compare this with other cooperative group studies that utilized chemoradiation or surgery, without brachytherapy.
Publication Types:
- Clinical Trial
- Clinical Trial, Phase I
- Clinical Trial, Phase II
- Multicenter Study
PMID: 11693897 [PubMed - indexed for MEDLINE]
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Multifocal squamous cell carcinoma of the oesophagus following radiotherapy for bilateral breast carcinoma.
Shousha S, Fawcett A, Luqmani YA, Theodorou N.
Department of Histopathology, Imperial College School of Medicine and Charing Cross Hospital, London W6 8RF, UK.
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A 60 year old woman who presented with dysphagia and weight loss was found to have multiple foci of dysplasia and in situ and invasive squamous cell carcinoma scattered along the whole length of the oesophagus, with intervening areas of normal mucosa. The patient had a history of two breast carcinomas 19 and one year previously for which she had repeated radiotherapy. Several members of the patient's close family had histories of malignant disease. All oesophageal lesions and the more recent breast cancer showed positive immunostaining for p53 protein. p53 mutations, some involving different exons, were also detected in these lesions. No p53 immunostaining or mutations were detected in the normal oesophageal mucosa. The findings suggest an independent origin of the multiple dysplastic and neoplastic foci, which might have developed in a background of a field change, possibly related to the previous radiotherapy. The strong family history of malignant diseases raises the possibility that, in addition, genetic factors might have played a role in the development of the oesophageal disease.
Publication Types:
PMID: 11533082 [PubMed - indexed for MEDLINE]
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