This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Temple, L. K.F. Articles by Schrag, D. Search for Related Content PubMed PubMed Citation Articles by Temple, L. K.F. Articles by Schrag, D. Social Bookmarking                            What's this?

Use of Surgery Among Elderly Patients With Stage IV Colorectal Cancer

From the Departments of Surgery, Medicine, Epidemiology, and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY

Address reprint requests to Deborah Schrag, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room Box 221, New York, NY 10021; e-mail: schragd{at}mskcc.org

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
PURPOSE: The role of surgery to remove the primary tumor among patients with stage IV colorectal cancer (CRC) is controversial. The purpose of this study was to evaluate surgical practice patterns for patients 65 years of age with stage IV CRC in a US population-based cohort.

PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results-Medicare–linked database to evaluate the patterns of cancer treatment for 9,011 Medicare beneficiaries presenting with stage IV CRC from 1991 to 1999. Patients were categorized according to whether they had primary–cancer-directed surgery (CDS) or no CDS within 4 months of diagnosis. The use of other treatment modalities, including metastasectomy, chemotherapy, and radiation, was evaluated in relationship to whether patients belonged to the CDS or no CDS group.

RESULTS: Seventy-two percent (6,469 of 9,011) of patients received CDS, and their 30-day postoperative mortality was 10%. Patients with left-sided or rectal lesions, patients older than age 75 years, blacks, and those of lower socioeconomic status were less likely to undergo CDS; but even among those older than age 75, the CDS rate was 69% (3,378 of 4,909). In contrast, chemotherapy use was less common (47% for patients who had CDS and 31% for those who did not). Metastasectomy was rare; only 3.9% of patients underwent these operations at any point from diagnosis to death.

CONCLUSION: Palliative resection of the primary tumor is often performed for elderly US patients with stage IV colorectal cancer. This practice pattern merits re-evaluation, given the improvement in the efficacy of systemic chemotherapy.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
For patients with stage IV colorectal cancer, the role of surgery directed toward removal of the primary tumor is controversial, and data to guide treatment decision making are limited. Retrospective case series suggest that surgical outcomes in stage IV disease are related to factors such as the extent of liver disease,^1-5 peritoneal disease,² primary tumor resection,³ tumor differentiation,¹ age older than 75 years,⁴ and cardiovascular disease.⁵ Small retrospective series have evaluated the role of surgical resection of the primary tumor in the setting of unresectable metastatic disease^5,6; however, it is difficult to draw conclusions about the utility of surgery from these analyses because the studies are all small, nonrandomized, and represent selected cohorts often from referral centers with dedicated colorectal surgical teams.

Although palliative surgery is indicated for most patients with bowel obstruction or uncontrollable bleeding, the benefit of surgery directed toward removal of the primary tumor for the management of asymptomatic patients with stage IV colorectal cancer and unresectable metastases is uncertain. Recent practice guidelines from the National Comprehensive Cancer Network recommend that patients with stage IV colorectal cancer undergo surgery only if they are symptomatic, at risk of impending obstruction, or have metastatic sites amenable to potentially curative resection.⁷ Surgical resection of the primary tumor at diagnosis may delay or even preclude systemic chemotherapy.

The rationale for up-front surgical resection of the primary tumor is the prevention of acute bowel obstruction later during the treatment course because surgery in the setting of bowel obstruction is associated with higher postoperative mortality. Some patients who do not undergo immediate resection will require surgical intervention at a later date; however, most will never develop bowel obstruction. Prospective studies evaluating immediate versus deferred surgical strategies for managing an asymptomatic primary colorectal cancer in the setting of unresectable metastatic disease have not been conducted.

To understand national practice patterns for stage IV colorectal cancer patients, we used Medicare claims and registry data detailing surgery performed for individuals diagnosed within the areas covered by the Surveillance, Epidemiology, and End Results (SEER) Program between 1991 and 1999. We sought to measure how often surgery directed toward removal of the primary tumor is performed in patients with stage IV colorectal cancer, and how often these operations are accompanied (either synchronously or metachronously) by attempts to resect metastatic disease foci.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
Data Sources
We used the linkage of the SEER with the Center for Medicare and Medicaid Services claims database to identify a cohort of patients diagnosed with stage IV colon or rectal cancer at age 65 years or older. The SEER registries, sponsored by the National Cancer Institute, ascertain all incident cancer cases diagnosed in five states and six US metropolitan areas, representing approximately 14% of the US population.⁸ The SEER program collects information on each incident cancer, including the primary site and histology (classified according to the International Classification of Diseases [ICD] for Oncology, second edition⁹), the tumor stage at diagnosis, and patient demographics.

The Medicare program provides health insurance for 97% of the US population aged 65 and older. The Medicare Provider Analysis and Review files give details of all hospitalizations for persons eligible for Medicare Part A. To receive payment, hospitals submit medical claims coding up to 10 diagnoses and 10 procedures using the ICD 9th revision, clinical modification (ICD9-CM) classification. For the 96% of Medicare beneficiaries who opt for Part B coverage, claims for care delivered in hospital outpatient departments and physicians' offices are also recorded. Medicare also documents date of death for beneficiaries on the basis of information provided by the Social Security Administration. The SEER and Medicare data have been linked to facilitate population-based studies of cancer treatment. Ninety-four percent of patients in SEER aged 65 or older have been linked successfully to their Medicare records.¹⁰

Cohort Definition
Medicare-enrolled patients aged 65 and older, initially diagnosed with stage IV colon or rectal cancer in a SEER area during the years 1991 to 1999, were potentially eligible for inclusion in our study. SEER codes were used to define colon cancer (18.0 to 18.9) and rectal cancer (19.9, 20.9). We restricted our cohort to those with a histologic diagnosis consistent with adenocarcinoma (SEER histology codes 8140, 8210 to 8211, 8220 to 8221, 8260 to 8263, 8470, 8480 to 8481, and 8490). Diagnoses noted exclusively on death certificates or at autopsy were excluded, as were those in which the month of diagnosis was unknown.

Under capitation, claims detailing the specific procedures and noncancer diagnoses are not reported to the Health Care Financing Administration by risk-contract health maintenance organizations. Therefore, patients enrolled in these plans were excluded from our cohort. During the study years, 20% of the patients in SEER regions were enrolled in a health maintenance organization at time of diagnosis.

Identification of Surgery and Procedure
The primary outcome was surgery directed at the primary tumor within 4 months of a diagnosis of stage IV colorectal cancer. To identify surgical procedures, we reviewed Medicare claims for the first 4 months after diagnosis, and reviewed SEER data using the site-specific surgery variable for 1991 to 1997 and the surgery of primary site variable for 1998 to 1999. Patients were categorized as having had primary–cancer-directed surgery (CDS) or no primary CDS. Assignment to the primary CDS group was made on the basis of a Medicare claim indicating bowel resection (ICD9 codes 45.7, 45.8, 48.4, 48.5, 48.6; CPT codes 44140 to 44160, 45110 to 45119) or evidence of primary tumor resection in SEER (site-specific surgery codes [1991 to 1997], 30 to 70; surgery of primary site codes [1998 to 1999], 30 to 80) within the first 4 months after diagnosis. Inclusion in the no CDS group was predicated on lack of evidence of primary tumor resection within the first 4 months, and these patients were further subdivided into three groups: (1) diversion, which included patients who underwent a bowel bypass (CPT code 44130; ICD9 code 45.9x; SEER site-specific surgery codes 6, 10, or 20) or the creation of a surgical stoma (CPT codes 44130, 44300, 44310, 44320, 44322; ICD9 code 46.0x; SEER site-specific surgery) without resection of the primary tumor; (2) late CDS, which included patients who underwent CDS more than 4 months after diagnosis; or (3) no surgery, which included patients who had had none of these operations. The specific billing codes used in this classification are shown in the Appendix.

Romano's modification of the Charlson comorbidity index^11,12 was used to adjust for potential confounding based on the severity of noncancer medical illness. The diagnoses included in the Romano-Charlson comorbidity index capture many of the absolute or relative contraindications to surgery. We examined all available inpatient Medicare claims for the 12 months preceding the month before diagnosis, and assigned patients the maximal comorbidity observed (0, 1, or 2).

Other Treatment
We evaluated rates of chemotherapy use among all patients. Stage IV patients who had claims indicating chemotherapy use in either the inpatient (Medicare Provider Analysis and Review), outpatient (standard analytical file), or physician or supplier (National Claims Histories) Medicare files, at any point subsequent to diagnosis, were considered chemotherapy recipients; the absence of such claims indicated lack of treatment. Medicare claims for medical evaluation for chemotherapy (ICD9 codes V58.1, V66.2, and V67.2), chemotherapy administration (ICD9 code 99.25; CPT codes 96400 to 96549; Health Care Financing Administration Common Procedure Coding System codes Q0083 to Q0085; or revenue center codes 0331, 0332, and 0335), and intravenous chemotherapy agents (Health Care Financing Administration Common Procedure Coding System codes J9000 to J9999, and J0640: leucovorin) identified usage. Capecitabine, an oral form of fluorouracil (FU), was introduced in the late 1990s and may have been used by a few physicians as primary treatment. However, use of this outpatient prescription medication was not assessed because Medicare did not consistently record it.

Metastasectomy
An important reason for surgical removal of the primary tumor in the setting of metastatic disease is the possibility that curative resection of isolated metastases may be feasible. To determine how often primary surgery was accompanied by or followed by metastasectomy, we evaluated rates of liver resection (ICD9 codes 50.22, 50.3; CPT codes 47120, 47122, 47125, 47130), pelvic exenteration (men, ICD9 code 57.71; women, ICD9 code 68.8; CPT code 45126, 58240, 51597), and pulmonary resection (ICD9 code 32.3, 32.4, 32.5, 132.9; CPT codes 32440, 32442, 32445, 32480, 32482, 32484, 32500, 32520) performed between diagnosis and death.

Statistical Analysis
Patients were dichotomized into primary CDS and no CDS groups for statistical analyses. We performed univariate logistic regression analysis to identify potential associations between patient characteristics and receipt of primary CDS versus no CDS. Patient characteristics were entered as indicator variables according to the categories listed in Table 1. Those categories that were statistically significant at the .05 level were entered into the multiple logistic regression to examine their simultaneous effects on surgical treatment. P values in Table 2 were calculated using the likelihood ratio test. All reported P values are two sided, and SAS software (version 8.0; SAS Institute, Cary, NC) was used for all analyses.

View this table: [in this window] [in a new window]   Table 1. Characteristics According to Treatment Within 4 Months of Diagnosis in 9,011 Medicare Beneficiaries With Stage IV Colorectal Cancer Age 65 Years

View this table: [in this window] [in a new window]   Table 2. Univariate and Multivariate Predictors of Primary–Cancer-Directed Surgery Among 9,011 Medicare Beneficiaries Diagnosed From 1991 to 1999 With Stage IV Colorectal Cancer at Age 65 Years

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

View larger version (16K): [in this window] [in a new window]   Fig 1. Breakdown of cohort by cancer-directed surgery (CDS) and no CDS. Dx, diagnosis.

To determine primary management strategies, and whether CDS is used alone or in conjunction with other therapeutic modalities, we characterized cohort members on the basis of all treatments they received (CDS, chemotherapy, radiation alone, and/or any combination) within 4 months of diagnosis (Fig 2). Of the cohort members, 32% had CDS followed by chemotherapy, and 40% had CDS without chemotherapy. Overall, only 44% of cohort members had chemotherapy administered within 4 months of diagnosis. Palliative radiotherapy was administered to only 12% of cohort members within the first 4 months of treatment; these were primarily patients with rectal cancer. Of note, 18% of cohort members did not receive treatment with any of the major therapeutic modalities within 4 months of diagnosis.

View larger version (82K): [in this window] [in a new window]   Fig 2. Treatment patterns in stage IV colorectal cancer Medicare beneficiaries diagnosed with stage IV colorectal cancer in a Surveillance, Epidemiology, and End Results region 1991 to 1999. Treatment received within 4 months of diagnosis. CDS, primary–cancer-directed surgery; XRT, radiation; Chem, chemotherapy.

The indications for surgery and operation types for the 6,469 (72%) cohort members who had CDS and the 816 (9%) who had surgical diversion or late CDS are listed in Table 3. An ostomy was more common in the no CDS group when compared with the CDS patients (32% [805 of 2,542] v 24% [1,574 of 6,469], respectively; P < .001). Among patients undergoing CDS for colon cancer, 86% had resection with anastomosis and 14% had resection requiring an ostomy. For rectal cancer patients undergoing CDS, these rates were inverted: 31% underwent resection with anastomosis and 69% had resection with ostomy (Table 3). Among the no CDS group, the majority of patients had an ostomy rather than a bypass. Table 3 also indicates that few patients (0.2%) underwent primary resection of their tumor more than 4 months after diagnosis (ie, late CDS).

Surgical Mortality and Overall Survival
An exact surgical date could be identified from the Medicare claims for 6,077 of the 6,469 patients (94%) who underwent CDS and 677 of the 816 (83%) who had diversion or delayed resections. The 30-day surgical mortality was significantly greater in the no CDS group among patients who underwent a surgical procedure, when compared with the primary CDS group (26% [173 of 677] v 9% [576 of 6,077], respectively; P = .001). The overall median survival for the entire cohort was 7 months. Although differences in survival between patients treated with CDS and no CDS exist (median, 10 v 3 months, respectively) as shown in Figures 3 and 4, inferences about the efficacy of surgery cannot be drawn reliably because of patient selection in the nonrandomized setting.

View larger version (16K): [in this window] [in a new window]   Fig 3. Survival of 9,011 stage IV colorectal cancer patients, by primary–cancer-directed surgery (CDS) treatment. CDS, primary CDS with 4 months of diagnosis; no CDS, no CDS within 4 months of diagnosis.

View larger version (20K): [in this window] [in a new window]   Fig 4. Survival of 9,011 stage IV colorectal cancer patients, by treatment of primary–cancer-directed surgery (CDS) and chemotherapy. CDS, primary CDS within 4 months of diagnosis; no CDS, no CDS within 4 months of diagnosis; Chemo, chemotherapy at some point during life span of patient; no Chemo, no chemotherapy during life span of patient.

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

Our analysis demonstrates that the majority of elderly patients with stage IV colorectal cancer undergo resection of the primary tumor, and that nearly all such operations are performed with noncurative intent. SEER-Medicare data do not enable us to determine what percentage of these procedures is being performed for palliation of active symptoms, and what percentage is being performed with prophylactic intent.

Case series from specialty centers report favorable outcomes in patients who undergo surgery for their local and metastatic disease.^13,15 In contrast, our analysis describes what happens in the population as a whole. The data from our current analysis cannot be used to suggest that metastasectomy should be performed more frequently or to define the role of CDS in the stage IV patient. Rather, our analysis of national patterns of care indicates that patients with advanced disease are frequently taken to the operating room, and therefore the role of surgery in this setting merits more systematic evaluation than it has previously received. We hope that the evaluation of practice patterns will promote a dialogue between both surgical and medical oncologists to establish a rationale for determining the conditions and timing of surgical and/or medical intervention.

One of the most significant limitations of our analysis is the fact that SEER-Medicare data do not reliably indicate whether patients were symptomatic at presentation. Because screening in the elderly is underused, elderly patients may present with more advanced-stage disease. However, it is unlikely that all cohort members who had surgical resection were symptomatic. We found that patients with right-sided colon cancers were more likely to undergo initial surgery, despite the fact that left-sided and rectal cancers are more likely to obstruct than right-sided lesions. The data also demonstrate that many of the patients with left colon cancers did not have a stoma, which suggests that patients were not completely obstructed because they were able to tolerate a primary anastomosis. This provides indirect evidence that a significant proportion of patients were asymptomatic at the time of surgical resection.

Although we cannot reliably distinguish patients who were and were not symptomatic, the 72% surgical resection rate is high, particularly when juxtaposed with the fact that 44% of patients had chemotherapy administered within 4 months of diagnosis (Fig 2). A recently published study of patients in randomized chemotherapy trials who had metastatic disease demonstrated that there were no differences in gastrointestinal complications (fistulas, peritonitis, obstruction) in patients who did not have CDS (n = 82) and patients who had CDS (n = 280),¹⁶ lending support to the argument that asymptomatic patients with stage IV colorectal cancer can tolerate chemotherapy without requiring surgery to remove the primary tumor. The opportunity to initiate chemotherapy rapidly is made more important with advances in chemotherapy, in which combinations of infusional FU and oxaliplatin or infusional FU and irinotecan each have response rates that exceed 50%, and have been associated with median survival of 20 months in prospective clinical trials.^17,18 Although experience with these combination regimens in the elderly has just begun to emerge and no population-based series are as yet available, preliminary evidence suggests that elderly patients are capable of tolerating these regimens. Pooled analyses of elderly patients who have participated in cooperative group trials suggest that performance status is more powerful than age as a predictor of outcomes.¹⁹ In an era in which the efficacy of chemotherapy has so dramatically improved, the threshold for primary surgical management requires re-evaluation.

Another limitation of our retrospective cohort study is that we were not able to determine how frequently advanced disease was appreciated preoperatively. Given the widespread availability of imaging modalities throughout the 1990s, many patients would have had preoperative staging (ie, computed tomography [CT], magnetic resonance imaging, and/or ultrasound). If a significant proportion of patients were diagnosed with stage IV disease at surgical exploration, then our results suggest that more intensive preoperative diagnostic evaluation is warranted.

The comorbidity algorithm we used did not discriminate well between patients who did or did not receive CDS. On the one hand, patients who have complications related to their cancer diagnosis (eg, bleeding, abscess, perforation) are more likely to undergo primary CDS; on the other hand, debilitated patients are also more likely to be deemed inappropriate surgical candidates.

This analysis provokes additional questions that cannot be answered using retrospective registry data and claims histories. Given that surgery is used for palliation, its role in the management of stage IV colorectal cancer needs to be evaluated in terms of symptom control, impact on quality of life, and the extent to which it prolongs survival. Prospective measurement of parameters such as quality of life, number of hospital days, and interval from surgery to initiation of chemotherapy would provide additional insights into the rationale for surgery.

Although our observational study design precludes meaningful comparisons of survival differences between groups, we describe outcomes for cohort members to emphasize the fact that survival in the setting of stage IV colorectal cancer remained poor throughout the early 1990s when fluorouracil was the only efficacious chemotherapy available. Since the availability of irinotecan²⁰ in 1996, oxaliplatin in 2002,¹⁷ and the monoclonal antibodies cetuximab²¹ and bevacizumab,²² systemic therapy and the ability to palliate patients medically has improved. Simultaneously, techniques for endoluminal stenting provide an alternative to the need for colonic resection to alleviate obstruction. Conversely, better chemotherapy and longer survival may increase the number of patients who ultimately develop symptoms for their primary tumor, necessitating resection. Better chemotherapy may also render stage IV patients who were unresectable into candidates for potentially curative operations that remove all sites of visible disease. Thus, the role of surgery in this setting merits reevaluation, as it may shift from that of a first-line management strategy to treatment for those patients who obtain a favorable response to first-line systemic chemotherapy.

There were other limitations to our analysis. First, claims-based analyses can be subject to inaccuracies because of variations in coding practices.^24-26 However, the outcomes measured in our analyses are major surgical procedures, constituting a large source of revenue for both the physician and hospital, and are therefore likely to be reliably reported to Medicare for payment. Second, these findings are specific to patients older than age 65 years enrolled in fee-for-service Medicare, and may not be generalizable to younger patients or those enrolled in managed care. However, our data set is typical of US colorectal cancer patients, given that the vast majority (> 80%) are insured by fee-for-service Medicare, and more than 55% are older than age 65 at diagnosis. Finally, no meaningful comparisons about the efficacy of various treatment strategies can be inferred from this observational analysis because of the strong selection bias for particular treatment strategies on the basis of both measurable and unmeasured factors.

Although evidence-based guidelines on surgical issues in colorectal cancer were developed recently,²⁷ the role of surgery for patients with stage IV colorectal cancer was not addressed. Because of the availability of several efficacious combination chemotherapy regimens, our practice is to perform resection of the primary tumor only for patients who are clearly symptomatic or are undergoing resection of metastatic sites of disease with curative intent. Asymptomatic stage IV patients at our institution are currently treated with combination chemotherapy. The recent availability of endoluminal colorectal stenting has also created a new alternative that may obviate the need for surgery in some circumstances. We suggest that before stage IV colorectal cancer patients undergo surgical resection, they should receive careful preoperative staging to evaluate the extent of disease with imaging, such as a contrast-enhanced CT scan of the abdomen and pelvis, and consultation with a multidisciplinary clinical team to inform their treatment decision making.

It will be important to revisit surgical practice patterns in the 2000s, in light of recent advances in both chemotherapy and endoluminal stenting. Data from recent randomized controlled trials evaluating systemic chemotherapy may effect significant changes in practice patterns.^17,23 The appropriate role of palliative surgery for stage IV colorectal cancer, including its impact on symptom control and quality of life, remains to be fully evaluated.

	Authors' Disclosures of Potential Conflicts of Interest

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
The authors indicated no potential conflicts of interest.

	NOTES

 
Authors' disclosures of potential conflicts of interest are found at the end of this article.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
1. Liu SK, Church JM, Lavery IC, et al: Operation in patients with incurable colon cancer: Is it worthwhile? Dis Colon Rectum 40:11-14, 1997[CrossRef][Medline]

2. Rosen SA, Buell JF, Toshida A, et al: Initial presentation with stage IV colorectal cancer: How aggressive should we be? Arch Surg 135:530-535, 2000[Abstract/Free Full Text]

3. Makela J, Haukipuro K, Laitinen S, et al: Palliative operations for colorectal cancer. Dis Colon Rectum 33:846-850, 1990[CrossRef][Medline]

4. Joffe J, Gordon PH: Palliative resection for colorectal carcinoma. Dis Colon Rectum 24:355-360, 1981[Medline]

5. Ruo L, Gougoutas C, Paty PB, et al: Elective bowel resection for incurable stage IV colorectal cancer: Prognostic variables for asymptomatic patients. J Am Coll Surg 196:772-778, 2003

6. Scoggins CR, Meszoely IM, Blanke CD, et al: Nonoperative management of primary colorectal cancer in patients with stage IV disease. Ann Surg Oncol 6:651-657, 1999[CrossRef][Medline]

7. National Comprehensive Cancer Network: Clinical Practice Guidelines. http://www.nccn.org/physician_gls/f_guidelines.html

8. National Cancer Institute: Surveillance, Epidemiology, and End Results. http://www.seer.cancer.gov

9. Percy C, Holton VV, Muir C: International Classification of Diseases for Oncology (ed 2). Geneva, Switzerland, World Health Organization, 1990

10. Potosky AL, Riley GF, Lubitz JD, et al: Potential for cancer related health services research using a linked Medicare-tumor registry database. Med Care 31:732-748, 1993[Medline]

11. Romano PS, Roos LL, Jollis JG: Adapting a clinical comorbidity index for use with ICD-9-CM administrative data: Differing perspectives. J Clin Epidemiol 46:1075-1090, 1993[CrossRef][Medline]

12. Charlson ME, Pompei P, Ales KL, et al: A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis 40:373-383, 1987[CrossRef][Medline]

13. Fong Y, Fortner J, Sun RL, et al: Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: Analysis of 1001 consecutive cases. Ann Surg 230:309-321, 1999[CrossRef][Medline]

14. Jarnagin WR, Gonen M, Fong Y, et al: Improvement in perioperative outcome after hepatic resection: Analysis of 1,803 consecutive cases over the past decade. Ann Surg 236:397-407, 2002[CrossRef][Medline]

15. de Gramont A, Figer A, Seymour M, et al: Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18:2938-2947, 2000[Abstract/Free Full Text]

16. Tebbutt NC, Norman AR, Cunningham D, et al: Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases. Gut 52:568-573, 2003[Abstract/Free Full Text]

17. Goldberg RM, Sargent DJ, Morton RF, et al: A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 22:23-30, 2004[Abstract/Free Full Text]

18. Tournigand C, Andre T, Achille E, et al: FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: A randomized GERCOR study. J Clin Oncol 22:229-237, 2004[Abstract/Free Full Text]

19. Sargent DG, Goldberg RM, Jacobson SD, et al: A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med 345:1091-1097, 2001[Abstract/Free Full Text]

20. Saltz LB, Cox JV, Blanke C, et al: Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 343:905-914, 2000[Abstract/Free Full Text]

21. Saltz LB, Meropol NJ, Loehrer PJ Sr, et al: Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22:1201-1208, 2004[Abstract/Free Full Text]

22. Hurwitz H, Fenvenbacher L, Novotny W, et al: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335-2342, 2004[Abstract/Free Full Text]

23. Camunez F, Echenagusia A, Simo G, et al: Malignant colorectal obstruction treated by means of self-expanding metallic stents: Effectiveness before surgery and in palliation. Radiology 216:492-497, 2000[Abstract/Free Full Text]

24. Iezzoni LI: Assessing quality using administrative data. Ann Intern Med 127:666-674, 1997 (8 pt 2)[Abstract/Free Full Text]

25. Lloyd SS, Rissing JP: Physician and coding errors in patient records. JAMA 254:1330-1336, 1985[Abstract/Free Full Text]

26. McCarthy EP, Iezzoni LI, Davis RB, et al: Does clinical evidence support ICD-9-CM diagnosis coding of complications? Med Care 38:868-876, 2000[CrossRef][Medline]

27. Nelson H, Petrelli N, Carlin A, et al: Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst 93:583-596, 2001[Abstract/Free Full Text]

Submitted October 31, 2003; accepted May 20, 2004.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				G. A. Poultsides, E. L. Servais, L. B. Saltz, S. Patil, N. E. Kemeny, J. G. Guillem, M. Weiser, L. K.F. Temple, W. D. Wong, and P. B. Paty Outcome of Primary Tumor in Patients With Synchronous Stage IV Colorectal Cancer Receiving Combination Chemotherapy Without Surgery As Initial Treatment J. Clin. Oncol., July 10, 2009; 27(20): 3379 - 3384. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Temple, L. K.F. Articles by Schrag, D. Search for Related Content PubMed PubMed Citation Articles by Temple, L. K.F. Articles by Schrag, D. Social Bookmarking                            What's this?