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Keywords:

  • esophageal cancer;
  • poor prognostic group;
  • surgery;
  • chemoradiation;
  • positron emission tomography evaluation

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

BACKGROUND:

The prognosis of patients with localized gastroesophageal carcinoma (LGC) can be defined after chemoradiation by the standardized uptake value (SUV) of positron emission tomography (PET). High SUV (HSUV) after chemoradiation portends a poor prognosis. The authors retrospectively examined the role of surgery in patients with HSUV after chemoradiation.

METHODS:

The authors analyzed the postchemoradiation PET scans of 204 LGC patients. One hundred twenty-nine patients had HSUV. Two postchemoradiation variables were evaluated: SUV and surgery and their association with overall survival (OS) and event-free survival (EFS). The log-rank test, multivariate Cox proportional hazards model, and Kaplan-Meier survival plots were used to assess the association between OS or EFS and the dichotomized SUV (using the median SUV as the cutoff) and surgery.

RESULTS:

The median SUV was 4.6. The OS of the 52 patients who had an SUV above the median and did not undergo surgery (HSUV-NS) (median OS, 1.22 years; 95% confidence interval [95% CI], 1.02-2.16 years) was much shorter than that of the 77 patients with an SUV above the median who underwent surgery (HSUV-S) (median OS, 2.7 years; 95% CI, 2.43 years to not reached [P <.0001]). Similarly, the EFS for patients with HSUV-NS was significantly shorter than that for patients with HSUV-S (P = .001). In the multivariate analyses, patients who underwent surgery (irrespective of SUV) had a lower risk of death (P = .0001) and disease progression (P = .002).

CONCLUSIONS:

The data from the current study suggest that surgery may prolong OS and EFS in patients with a poor prognosis after chemoradiation as defined by PET. However, these data need confirmation. Cancer 2010. © 2010 American Cancer Society.

Esophageal carcinoma imposes a significant health burden worldwide. The incidence of squamous cell carcinoma of the esophagus is declining in the West, but that of adenocarcinoma of the esophagus and gastroesophageal junction has increased over the past 25 years1, 2 Adenocarcinoma is diagnosed in late stages when patients have substantial symptoms; therefore, the mortality rate from it continues to increase.2 Nevertheless, localized gastroesophageal carcinoma (LGC) is a potentially curable condition. Patients with LGC are often offered chemoradiation3, 4 in a definitive manner or preoperatively,5, 6 but the results from the published randomized trials on preoperative chemoradiation do not support its benefit.7-11 Surgery remains an important component of therapy in physiologically fit patients.12, 13

When treated with a similar therapeutic strategy, the outcome of patients with LGC remains unpredictable. To the best of our knowledge, the reasons for this unpredictability in clinical outcome are not entirely clear but could be attributed to the differences in molecular compositions of cancers14-18 and/or patient genetics.19, 20 However, the imaging techniques with [F-18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) are able to provide some discrimination with regard to the prognosis of patients with LGC.21-32 We have reported that the standardized uptake value (SUV) after chemoradiation can divide the LGC patients into 2 groups: 1) a better prognostic group if the postchemoradiation SUV is low and 2) a poor prognostic group if the postchemoradiation SUV is high.30, 33 The overall survival (OS) and event-free survival (EFS) are significantly different in these 2 groups, and in the multivariate analyses, the postchemoradiation SUV was found to be an independent prognosticator of OS and EFS.33 It would be important to address the role of surgery to improve outcomes in the patient population with high SUV (HSUV) after chemoradiation. We believe all patients with LGC who can withstand surgery should be offered surgery, but to our knowledge it is not known whether surgical resection improves the outcome of patients whose tumors demonstrate aggressive clinical behavior as defined by postchemoradiation PET results. The other consideration is in patients who are initially believed to be unsuitable for a trimodality approach (TM, or preoperative chemoradiation followed by an attempted surgical resection), but have HSUV after chemoradiation; should they be reconsidered for surgery?

The objective of the current study was to retrospectively assess whether the outcome of patients with postchemoradiation HSUV is different in patients who underwent surgery compared with those who did not undergo surgery. To reduce bias in this analysis, we also added a third cohort of patients who had low SUV (LSUV) (less than the median of 4.6, the median value in this study) after chemoradiation and underwent surgery (LSUV-S). It is not known whether surgery provides any clinical benefit to patients who have a poor prognosis as determined by postchemoradiation PET. We analyzed 204 patients and focused on 129 patients who had HSUV after chemoradiation to assess the impact of surgery on OS and EFS.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

Patient Selection

LGC patients who presented to the University of Texas M. D. Anderson Cancer Center from 2002 through 2008 and had a PET-computed tomography (CT) scan after chemoradiation were eligible for this retrospective study. The primary disease site was assigned using the Siewert classification,34 and patients with anatomic type 1 (esophageal) or type 2 (gastroesophageal) disease were included, whereas those with T1N0 disease were excluded. Pretreatment investigations included a complete blood count, measurement of serum electrolytes, chest radiograph, CT scan of chest and abdomen, barium swallow radiography, upper gastroesophageal endoscopy with endoscopic ultrasound, and a PET. A multidisciplinary team (medical oncologists, gastroenterologists, radiation oncologists, and thoracic surgeons) evaluated every patient and assigned an appropriate initial treatment strategy. All patients had a PET-CT scan performed approximately 5 to 6 weeks after the end of chemoradiation. The Institutional Review Board approved this project.

Study Objectives

The objective of the current study was to assess whether the outcome of patients with postchemoradiation HSUV is different in patients who underwent surgery compared with those who did not undergo surgery. Our hypothesis was that surgery after chemoradiation would benefit some patients with postchemoradiation HSUV.

Chemoradiotherapy

All patients received a fluoropyrimidine and a taxane or platinum compound concurrently with radiation. The median radiation dose delivered was 45 grays (Gy) (range, 45-50.4 Gy). Since 2005, patients at our institution have received a radiation dose of 50.4 Gy in 28 fractions regardless of whether surgery is planned.

Surgery

Approximately 5 to 6 weeks after the completion of chemoradiation, all patients were evaluated (preoperative evaluation for TM patients) with CT scans, esophagoscopy, and a PET-CT scan. All patients had complete blood work, including serum chemistry.

Surgical procedures performed included a 3-field esophagectomy, transhiatal esophagectomy, transthoracic esophagectomy, or minimally invasive esophagectomy. The type of surgery was left to the discrimination of the individual surgeon. Extensive lymph node dissection is routinely performed. Proximal and distal resection margins of ≥5 cm are the goal. Information regarding OS and EFS were collected from the hospital records, patient follow-up records, death records (social security database), and the University of Texas M. D. Anderson Cancer Center tumor registry.

PET-CT

FDG-PET-CT scans were performed on a dedicated PET-CT system (Discovery ST, STe, or RX; General Electric Medical Systems, Milwaukee, WI). Scan coverage was generally from the orbits to the proximal thighs, although coverage was altered to answer specific clinical questions and also occasionally included the entire head and/or the lower extremities. Scans were acquired 60 to 90 minutes after intravenous (iv) administration of FDG with a dose range of 15 to 20 millicuries (mCi) (555-740 megabecquerel [MBq]). PET studies were acquired in either 2-dimensional or 3-dimensional (3D) acquisition mode at 3 to 5 minutes per bed position (depending on the patient's body mass index). Images were reconstructed using ordered subset expectation maximization (OSEM) with 128 × 128 matrix size and a field of view of 70 cm (5.47-mm pixels). CT was acquired without oral or iv contrast material and was used for attenuation correction of the PET scan. The CT acquisition parameters were 120 kilovolt peaks, 300 millieAmperes (mAs), and 0.50-second rotation, with a pitch of 1.375. The CT images were reconstructed using a 3.75-mm slice thickness with a slice interval of 3.27 mm to match the PET data. PET-CT images were reviewed on a workstation (Advantage Workstation; General Electric Medical Systems). PET, CT, and PET-CT fusion datasets were reviewed in multiple imaging planes.

SUV Calculations

The maximum SUV (SUVmax) was based on body weight and was calculated using a volume of interest that was drawn to encompass the entire 3D extent of the lesion. The SUVmax was then calculated using the following equation: SUVmax = A/(ID/BW), in which A is the maximum decay-corrected activity concentration in tissue/volume of interest (measured in mCi per mL), ID is the injected dose of FDG (measured in mCi), and BW is the patient's body weight (measured in g). This gives an SUVmax unit of g/mL. At our institution, we follow the National Cancer Institute guidelines for image preparation, acquisition, and analyses.35-37 We used the SUVmax because it is reproducible, unlike mean SUV, and reporting of SUVmax is the standard at our institution. We recognize that the consensus on optimum SUV assessment is currently lacking and a subject of debate. Various institutional preferences exist, but for LGC patients, we have chosen SUVmax for reporting our analyses and are willing to consider another method when compelling data by others investigators are reported.

Statistical Analysis

The log-rank test,38 univariate and multivariate Cox39 proportional hazards regression analyses, and Kaplan-Meier40 survival plot were used to evaluate the association of the dichotomized PET SUV with OS and EFS. The OS was computed as the time period from the initiation of chemoradiation to either the date of death or date of last follow-up, whichever occurred first. Patients alive at the last follow-up date were censored. The EFS was computed as the time period from the date of chemoradiotherapy to the date of last follow-up, the date of disease recurrence, or date of death, whichever occurred first. Patients who were alive without disease recurrence at the last follow-up date were censored. All statistical tests were 2-sided and performed at a .05 significance level. The SAS software package (version 9.01) was used for computations (SAS Institute, Cary, NC).

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

Patient Characteristics

Relevant patient characteristics of the 204 patients with postchemoradiation HSUV (n = 129) plus LSUV-S (n = 75) are shown in Table 1. As anticipated, most patients were white men and most patients had adenocarcinoma.

Table 1. Patient Characteristics
CovariatesSubgroupsHSUV-NSHSUV-SLSUV-SPa
  • HSUV-NS indicates patients with a high postchemoradiation standardized uptake value (SUV) who did not undergo surgery; HSUV-S, patients with a high postchemoradiation SUV who underwent surgery; LSUV-S, patients with a low postchemoradiation SUV who underwent surgery.

  • a

    P values were calculated using the Fisher exact test.

  • b

    Only 7 patients with localized stage IVB were included.

EthnicityNon-white13 (50%)6 (23.1%)7 (26.9%).015
 White39 (21.9%)71 (39.9%)68 (38.2%) 
GenderFemale6 (28.6%)8 (38.1%)7 (33.3%).96
 Male46 (25.1%)69 (37.7%)68 (37.2%) 
Baseline stageIIA and IIB”10 (18.9%)28 (38.9%)34 (47.2%).008
 III and IV (A and Bb)42 (36.1%)49 (27.4%)40 (30.5%) 
HistologyAdenocarcinoma38 (21.6%)72 (40.9%)66 (37.5%).003
 Adenosquamous0 (0%)0 (0%)2 (100%) 
 Squamous cell carcinoma14 (53.9%)5 (19.2%)7 (26.9%) 
Tumor gradeWell differentiated0 (0%)2 (100%)0 (0%).15
 Moderate differentiation22 (20%)44 (40%)44 (40%) 
 Poor differentiation29 (34.1%)27 (31.8%)29 (34.1%) 
 Not designated1 (14.3%)4 (57.1%)2 (28.6%) 

PET SUV and OS and EFS

The median survival and the 1-year, 3-year, and 5-year OS rates are shown in Table 2. The median survival of all 204 patients was 2.85 years (95% confidence interval [95% CI], 2.43-4.24 years). The median survival of patients with HSUV who did not undergo surgery (HSUV-NS) was 1.22 years (95% CI, 1.02-2.16 years) whereas that of patients with HSUV who did undergo surgery (HSUV-S) was 2.70 years (95% CI, 2.43 to not estimable). The median survival of patients with LSUV-S was 4.24 years (95% CI, 3.6 to not estimable). Figure 1 shows the Kaplan-Meier OS plots comparing patients with HSUV-S and HSUV-NS (P <.0001), and Figure 2 shows the Kaplan-Meier OS plots when the third cohort of LSUV-S is added (P <.0001). At least for the first 27 months, the survival curves for patients with HSUV-S were found to be similar to those of patients with LSUV-S (suggesting the impact of surgery), but the curves then separated (suggesting the true metastatic potential of cancer in the HSUV-S group). It is intriguing to note that the shapes of the curves of the HSUV-S and HSUV-NS groups were very similar after approximately 15 months.

Table 2. Median OS and OS Rates at 1, 3, and 5 Years
 TypeNo.EventMedian OS (95% CI), YearsOS Rate at 1 Year (95% CI)OS Rate at 3 Years (95% CI)OS Rate at 5 Years (95% CI)P
  1. OS indicates overall survival; 95% CI, 95% confidence interval; HSUV-NS, patients with high postchemoradiation standardized uptake value (SUV) who did not undergo surgery; HSUV-S, patients with high postchemoradiation SUV who underwent surgery; NA, not applicable; LSUV-S, patients who had low postchemoradiation SUV and underwent surgery.

GroupsAll patients204832.85 (2.43-4.24)0.791 (0.735-0.851)0.48 (0.395-0.584)0.282 (0.17-0.466) 
 HSUV-NS52301.22 (1.02-2.16)0.638 (0.513-0.792)0.123 (0.026-0.574)<.0001
 HSUV-S77262.70 (2.43 to NA)0.845 (0.764-0.934)0.482 (0.333-0.696) 
 LSUV-S75274.24 (3.60 to NA)0.835 (0.754-0.925)0.632 (0.513-0.777)0.383 (0.227-0.647) 
thumbnail image

Figure 1. Kaplan-Meier plots estimating probability of overall survival (OS) by surgery are shown in patients who had a postchemoradiation standardized uptake value (SUV) of ≥4.6 (n = 129). E indicates the number of deaths; N, number of patients at risk.

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thumbnail image

Figure 2. Kaplan-Meier plots estimating probability of overall survival (OS) by the combined effect of standardized uptake value (SUV) and surgery are shown in all patients (n = 204). pCTRT indicates postchemoradiation; E, number of deaths; N, number of patients at risk.

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The EFS (Table 3) (Figs. 3 and 4) followed the same patterns for all 3 groups (HSUV-S, HSUV-NS, and LSUV-S) as was noted for OS.

Table 3. Median EFS and EFS Rates at 1, 3, and 5 Years
 TypeNo.EventMedian EFS (95% CI) YearsEFS Rate at 1 Year (95% CI)EFS Rate at 3 Years (95% CI)EFS Rate at 5 Years (95% CI)P
  1. EFS indicates event-free survival; 95% CI, 95% confidence interval; HSUV-NS, patients with high postchemoradiation standardized uptake value (SUV) who did not undergo surgery; HSUV-S, patients with high postchemoradiation SUV who underwent surgery; NA, not applicable; LSUV-S, patients who had low postchemoradiation SUV and underwent surgery.

 All patients2041061.69 (1.32-2.55)0.657 (0.593-0.727)0.376 (0.299-0.474)0.264 (0.164-0.424) 
GroupsHSUV-NS52340.84 (0.65-1.70)0.419 (0.299-0.588)0.136 (0.031-0.598)<.0001
 HSUV-S77381.69 (1.51-NA)0.712 (0.615-0.825)0.348 (0.222-0.545) 
 LSUV-S75343.54 (1.67-NA)0.755 (0.663-0.86)0.508 (0.392-0.659)0.36 (0.218-0.594) 
thumbnail image

Figure 3. Kaplan-Meier plots estimating probability of event-free survival (EFS) by surgery are shown in patients who had a postchemoradiation standardized uptake value (SUV) of ≥4.6 (n = 129). E indicates the number of disease recurrences or deaths; N, number of patients at risk.

Download figure to PowerPoint

thumbnail image

Figure 4. Kaplan-Meier plots estimating probability of event-free survival (EFS) by the combined effect of standardized uptake value (SUV) and surgery is shown in all patients (n = 204). pCTRT indicates postchemoradiation; E, number of disease recurrences or deaths; N, number of patients at risk.

Download figure to PowerPoint

Age and the HSUV-S, HSUV-NS, and LSUV-S Groups

Table 4 shows that age was statistically significantly related in the 3 groups (P = .0001). The median age of the patients with HSUV-NS was 70 years (range, 34-82 years) compared with 63 years for patients with HSUV-S, and 61 years for patients with LSUV-S.

Table 4. Age by Surgery and Postchemoradiation SUV Status
 Median (Range)Pa
  • SUV indicates standardized uptake value; HSUV-NS, patients with high postchemoradiation SUV who did not undergo surgery; HSUV-S, patients with high postchemoradiation SUV who underwent surgery; LSUV-S, patients who had low postchemoradiation SUV who underwent surgery.

  • a

    P values were calculated using the Kruskal-Wallis test. Shown is the P value when all 3 groups were compared.

  • b

    Patients with LSUV-S were the youngest group.

HSUV-NS70 (34-82)<.0001
HSUV-S63 (31-78) 
LSUV-Sb61 (34-78) 

Multivariate Analysis

Table 5 shows the multivariate analyses to evaluate the association between surgery and OS and EFS after adjusting for the age effect. Surgery, irrespective of high or low SUV, appears to play an independent role for OS and EFS, whereas SUV itself has an independent prognostic value (translating into a higher rate of events at a later stage). In this circumstance, the best outcome is noted for patients with LSUV-S followed by those with HSUV-S, and the worst outcome is noted for patients with HSUV-NS. The most intriguing finding in Table 5 is that, when surgery was possible, it superseded the impact of SUV on OS (P = .37) and EFS (P = .2).

Table 5. Cox Proportional Hazards Model to Establish the Association Between the Combination of Postchemoradiation SUV and Surgery With OS and EFS After Adjusting for Age Effecta
 HR (95% CI)P
OS
  • SUV indicates standardized uptake value; OS, overall survival; EFS, event-free survival; HR, hazards ratio; 95% CI, 95% confidence interval; HSUV-S, patients with high postchemoradiation SUV who underwent surgery; HSUV-NS, patients with high postchemoradiation SUV who did not undergo surgery; LSUV-S, patients who had low postchemoradiation SUV and underwent surgery.

  • a

    Patients who underwent surgery remained at a significantly lower risk of death or an event.

Age 1.01 (0.98-1.03).62
Surgery and SUV status   
 HSUV-S vs HSUV-NS0.39 (0.22-0.69).001
 LSUV-S vs HSUV-NS0.3 (0.17-0.55).0001
EFS
Age 0.99 (0.97-1.01).46
Surgery and SUV status   
 HSUV-S vs HSUV-NS0.45 (0.27-0.74).002
 LSUV-S vs HSUV-NS0.33 (0.19-0.57)<.0001

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

Surgery plays an important role in the management of patients with LGC; however, surgery as primary therapy is reported to result in poor OS rates for patients with >ypT1 tumors, as demonstrated by Rice et al41 in >4000 patients worldwide who were treated with surgery as their primary therapy and by Siewert at al,42 who reported on their own vast experience. Preoperative chemoradiation is practiced frequently in the United States,5, 6, 43 even though, its benefit on OS has not been documented by any of the trials conducted to date and questions have been raised regarding the approach.7-11

When patients are congregated into a certain clinical stage (particularly, stage II or stage III), they are offered similar therapy (surgery first or multimodality therapy, depending on the practice culture). This empiric approach assumes that all patients' tumors are similar in their responsiveness to therapy and clinical aggressiveness, but after therapy is delivered, we notice variable and unpredictable outcomes. Currently, we do not have any validated tools with which to optimize therapy for our patients. However, during therapy, PET studies can discriminate between patients with good and poor prognosis.21-32 We chose to retrospectively examine whether surgery plays a beneficial role in the group of patients who are designated to have a poor OS or EFS based on PET SUV.

The data from the current study are unique because, by using the combination of postchemoradiation PET SUV and surgery, we are able to define 3 subgroups among 204 patients. In these patients, we included 75 patients with LSUV-S to reduce bias in our analysis and to provide further evidence of the importance of surgery, even in a group of patients who are designated, by postchemoradiation PET SUV, as having poor survival. We did not include the fourth group of patients (LSUV-NS) in this report because an analysis of these patients is presented in another report.33 At our institution, we offer surgery for patients with LGC after chemoradiation, when feasible. The long-term strategy for patients with LGC is often established through a multidisciplinary interaction. Thus, usually at the outset, we designate a patient for a bimodality approach (definitive chemoradiation) or a TM approach. However, such decisions are revisited at various time points and particularly after recovery from chemoradiation (when a full staging is performed).

A few years ago, one would not have been able to reliably subgroup patient prognosis based solely on endoscopy and CT scans after chemoradiation, but now, with the advent of PET evaluations, one can group patients into 2 subgroups. The data from the current study are in agreement with the literature in that patients can be separated in 2 groups after chemoradiation: those with good prognosis having a low SUV and those with poor prognosis having a high SUV. However, by adding surgery as a variable, we were able to create a third subgroup (HSUV-S). Our hypothesis is that some patients with HSUV after chemoradiation (which portends poor prognosis) would benefit from surgery. This observation emphasizes that surgery should be revisited in patients with HSUV who are initially considered borderline for a TM approach and for those patients with HSUV who are not inclined to undergo surgery. However, it is unclear and not possible to determine which patients with HSUV after chemoradiation are likely to have prolonged survival. Perhaps the use of biomarkers in conjunction with imaging techniques may sort this out in the future, but it is a challenge.

We also noted that, once the surgery is accomplished in patients with HSUV or LSUV, the OS curves travel together for approximately 27 months but after that, survival events are more common in the HSUV-S group compared with the LSUV-S group and the shapes of the curves for the HSUV-S and HSUV-NS groups are very similar for events. A similar pattern is noted in the EFS curves. This suggests that tumors in HSUV patients have high metastatic potential manifesting later (irrespective of surgery) compared with those in patients with with LSUV. In our data, the LSUV-S group did not have a preponderance of pathologic complete responses (pathCRs), suggesting the inability of PET to correlate with pathCR. Patients with LSUV represents an interesting group of patients and demonstrate that the tumor biology as represented by the SUV after chemoradiation has considerable effect on their prognosis. Such analyses, when combined with tumor biology and patient genetics, may allow us in the future to optimize therapy much more effectively than using a single parameter such as imaging.

The data in the current study suffer from several shortcomings: 1) the current study is a retrospective review of events; 2) HSUV patients who did not undergo surgery were most likely patients who were treated with a bimodality approach from the outset, but additional biases incorporated in their management are not known and therefore were not incorporated in this analysis; and 3) even though the current study is the largest series in the literature to date, considerable patient heterogeneity exists and a larger series is desirable. Because these data were retrospective, they provide no guidance in the management of any patient. We believe data from the current study need to be confirmed by another group and, more importantly, in a prospective setting.

In conclusion, data from the current study indicate that, after chemoradiation, LGC patients can be divided into 3 subgroups and that the poor prognostic group of patients with HSUV after chemoradiation could be salvaged by surgery. Continued evaluation of PET during treatment of patients with LGC might provide some insights as to how to optimize complex and morbid treatments for these individuals.

Acknowledgements

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

We acknowledge the invaluable contributions of Drs. Alexandria Phan, Ritsuko Komaki, Alexander Dekovich, Jeremy Erasmus, David C. Rice, William A. Ross, Dipen M. Maru, and Ara A. Vaporciyan.

CONFLICT OF INTEREST DISCLOSURES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

Supported in part by grants from The University of Texas M. D. Anderson Cancer Center; the Dallas, Cantu, Smith, and Park Families; and the Rivercreek Foundation.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES
  • 1
    Cancer Research UK. Oesophageal cancer - UK incidence statistics. Available at: http://info.cancerresearchuk.org/cancerstats/types/oesophagus/incidence/. Accessed October 14, 2008.
  • 2
    Brown LM, Devesa SS, Chow WH. Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age. J Natl Cancer Inst. 2008; 100: 1184-1187.
  • 3
    Ajani JA, Winter K, Komaki R, et al. Phase II randomized trial of two nonoperative regimens of induction chemotherapy followed by chemoradiation in patients with localized carcinoma of the esophagus: RTOG 0113. J Clin Oncol. 2008; 26: 4551-4556.
  • 4
    Cooper JS, Guo MD, Herskovic A, et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999; 281: 1623-1627.
  • 5
    Suntharalingam M, Moughan J, Coia LR, et al. Outcome results of the 1996-1999 patterns of care survey of the national practice for patients receiving radiation therapy for carcinoma of the esophagus. J Clin Oncol. 2005; 23: 2325-2331.
  • 6
    Suntharalingam M, Moughan J, Coia LR, et al. The national practice for patients receiving radiation therapy for carcinoma of the esophagus: results of the 1996-1999 Patterns of Care Study. Int J Radiat Oncol Biol Phys. 2003; 56: 981-987.
  • 7
    Pereira B, Gourgou-Bourgade S, Azria D, Ychou M. Neoadjuvant chemoradiotherapy in esophageal cancer: is it still the question? J Clin Oncol. 2008; 26: 5133-5134.
  • 8
    Tepper J, Krasna MJ, Niedzwiecki D, et al. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008; 26: 1086-1092.
  • 9
    Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol. 2001; 19: 305-313.
  • 10
    Bosset JF, Gignoux M, Triboulet JP, et al. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med. 1997; 337: 161-167.
  • 11
    Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996; 335: 462-467.
  • 12
    Rice TW, Blackstone EH, Rybicki LA, et al. Refining esophageal cancer staging. J Thorac Cardiovasc Surg. 2003; 125: 1103-1113.
  • 13
    Sasako M, Sano T, Yamamoto S, et al. Left thoracoabdominal approach versus abdominal-transhiatal approach for gastric cancer of the cardia or subcardia: a randomised controlled trial. Lancet Oncol. 2006; 7: 644-651.
  • 14
    Chin L, Gray JW. Translating insights from the cancer genome into clinical practice. Nature. 2008; 452: 553-563.
  • 15
    Sawyers CL. The cancer biomarker problem. Nature. 2008; 452: 548-552.
  • 16
    van't Veer LJ, Bernards R. Enabling personalized cancer medicine through analysis of gene-expression patterns. Nature. 2008; 452: 564-570.
  • 17
    Luthra MG, Ajani JA, Izzo J, et al. Decreased expression of gene cluster at chromosome 1q21 defines molecular subgroups of chemoradiotherapy response in esophageal cancers. Clin Cancer Res. 2007; 13: 912-919.
  • 18
    Luthra R, Wu TT, Luthra MG, et al. Gene expression profiling of localized esophageal carcinomas: association with pathologic response to preoperative chemoradiation. J Clin Oncol. 2006; 24: 259-267.
  • 19
    Hildebrandt MAT, Yang H, Hung MC, et al. Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcome in esophageal cancer patients treated with chemoradiotherapy. J Clin Oncol. 2009; 27: 857-871.
  • 20
    Wu X, Gu J, Wu TT, et al. Genetic variations in radiation and chemotherapy drug action pathways predict clinical outcomes in esophageal cancer. J Clin Oncol. 2006; 24: 3789-3798.
  • 21
    Ott K, Herrmann K, Lordick F, et al. Early metabolic response evaluation by fluorine-18 fluorodeoxyglucose positron emission tomography allows in vivo testing of chemosensitivity in gastric cancer: long-term results of a prospective study. Clin Cancer Res. 2008; 14: 2012-2018.
  • 22
    Ott K, Weber W, Siewert JR. The importance of PET in the diagnosis and response evaluation of esophageal cancer. Dis Esophagus. 2006; 19: 433-442.
  • 23
    Wieder HA, Geinitz H, Rosenberg R, et al. PET imaging with [18F]3′-deoxy-3′-fluorothymidine for prediction of response to neoadjuvant treatment in patients with rectal cancer. Eur J Nucl Med Mol Imaging. 2007; 34: 878-883.
  • 24
    Flamen P, Lerut A, Van Cutsem E, et al. Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma. J Clin Oncol. 2000; 18: 3202-3210.
  • 25
    Ott K, Weber WA, Lordick F, et al. Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. J Clin Oncol. 2006; 24: 4692-4698.
  • 26
    Weber WA, Ott K, Becker K, et al. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol. 2001; 19: 3058-3065.
  • 27
    Wieder HA, Brucher BL, Zimmermann F, et al. Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment. J Clin Oncol. 2004; 22: 900-908.
  • 28
    Erasmus JJ, Munden RF, Truong MT, et al. Preoperative chemo-radiation-induced ulceration in patients with esophageal cancer: a confounding factor in tumor response assessment in integrated computed tomographic-positron emission tomographic imaging. J Thorac Oncol. 2006; 1: 478-486.
  • 29
    Lordick F, Ott K, Krause BJ, et al. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 2007; 8: 797-805.
  • 30
    Swisher SG, Erasmus J, Maish M, et al. 2-Fluoro-2-deoxy-D-glucose positron emission tomography imaging is predictive of pathologic response and survival after preoperative chemoradiation in patients with esophageal carcinoma. Cancer. 2004; 101: 1776-1785.
  • 31
    Brucher BL, Weber W, Bauer M, et al. Neoadjuvant therapy of esophageal squamous cell carcinoma: response evaluation by positron emission tomography. Ann Surg. 2001; 233: 300-309.
  • 32
    Brucher BL, Swisher SG, Königsrainer I, et al. Response to preoperative therapy in upper gastrointestinal cancers. Ann Surg Oncol. 2009; 16: 878-886.
  • 33
    Murthy SB, Patnana SV, Xiao L, et al. The standardized uptake value of 18-fluoro-deoxy glucose positron emission tomography after chemoradiation and clinical outcome in patients with localized gastroesophageal carcinoma. Oncology. In press.
  • 34
    Siewert JR, Stein HJ. Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg. 1998; 85: 1457-1459.
  • 35
    Kelloff GJ, Sullivan DM, Wilson W, et al. FDG-PET lymphoma demonstration project invitational workshop. Acad Radiol. 2007; 14: 330-339.
  • 36
    Shankar LK, Sullivan DC. PET/CT in cancer patient management. Commentary. J Nucl Med. 2007; 48( suppl 1): 1S.
  • 37
    Shankar LK, Hoffman JM, Bacharach S, et al. Consensus recommendations for the use of 18F-FDG PET as an indicator of therapeutic response in patients in National Cancer Institute Trials. J Nucl Med. 2006; 47: 1059-1066.
  • 38
    Mantel N. Evaluation of survival data and two new rank order statistics arising in ints consideration. Cancer Chemother Rep. 1996; 60: 163-170.
  • 39
    Cox DR. Regression models and life tables (with discussion). J R Stat Soc B. 1972; 34: 187-220.
  • 40
    Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958; 53: 457-481.
  • 41
    Rice TW, Rusch VW, Apperson-Hansen C, et al. Worldwide esophageal cancer collaboration. Dis Esophagus. 2009; 22: 1-8.
  • 42
    Siewert JR, Sendler A, Stein HJ. Esophageal cancer: surgical approach. In: MarkmanM, ed. Atlas of Cancer. Philadelphia: Current Medicine Group of Springer Science; 2007: 211-220.
  • 43
    Ajani JA, Barthel JS, Bekaii-Saab T, et al. Esophageal cancer. J Natl Compr Canc Netw. 2008; 6: 818-849.